Global tuberculosis report

Transcription

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2 215 Globl tuberculosis report

3 WHO Librry Ctloguing-in-Publiction Dt Globl tuberculosis report Tuberculosis epidemiology. 2.Tuberculosis, Pulmonry prevention nd control. 3.Tuberculosis economics. 4.Tuberculosis, Multidrug-Resistnt. 5.Annul Reports. I.World Helth Orgniztion. ISBN (NLM clssifiction: WF 3) World Helth Orgniztion 215 All rights reserved. Publictions of the World Helth Orgniztion re vilble on the WHO website ( or cn be purchsed from WHO Press, World Helth Orgniztion, 2 Avenue Appi, 1211 Genev 27, Switzerlnd (tel.: ; fx: ; e-mil: bookorders@who.int). Requests for permission to reproduce or trnslte WHO publictions whether for sle or for non-commercil distribution should be ddressed to WHO Press through the WHO website ( The designtions employed nd the presenttion of the mteril in this publiction do not imply the expression of ny opinion whtsoever on the prt of the World Helth Orgniztion concerning the legl sttus of ny country, territory, city or re or of its uthorities, or concerning the delimittion of its frontiers or boundries. Dotted nd dshed lines on mps represent pproximte border lines for which there my not yet be full greement. The mention of specific compnies or of certin mnufcturers products does not imply tht they re endorsed or recommended by the World Helth Orgniztion in preference to others of similr nture tht re not mentioned. Errors nd omissions excepted, the nmes of proprietry products re distinguished by initil cpitl letters. All resonble precutions hve been tken by the World Helth Orgniztion to verify the informtion contined in this publiction. However, the published mteril is being distributed without wrrnty of ny kind, either expressed or implied. The responsibility for the interprettion nd use of the mteril lies with the reder. In no event shll the World Helth Orgniztion be lible for dmges rising from its use. Designed by minimum grphics Cover designed by Irwin Lw Printed in Frnce WHO/HTM/TB/ ii n GLOBAL TUBERCULOSIS REPORT 215

4 Contents Abbrevitions Acknowledgements Prefce Executive summry 1 Chpter 1. Introduction 5 Chpter 2. Disese burden nd 215 trgets ssessment 8 Chpter 3. TB cse notifictions nd tretment outcomes 36 Chpter 4. Drug-resistnt TB 54 Chpter 5. Dignostics nd lbortory strengthening 69 Chpter 6. Addressing the co-epidemics of TB nd HIV 78 Chpter 7. Finncing 87 Chpter 8. Reserch nd development 15 Annexes 1. Access to the WHO globl TB dtbse Country profiles for 22 high-burden countries Regionl profiles for 6 WHO regions Key TB indictors for individul countries nd territories, WHO regions nd the world 155 iv v ix GLOBAL TUBERCULOSIS REPORT 215 n iii

5 Abbrevitions ART ARV BCG BRICS CDR CHMP CI CPT CTD CROI CRS DST EMA EQA FDA FIND GDP GHE HBC HIV HVTN IDRI IGRA IMPAACT IPT LED LF-LAM LPA LTBI MDGs MDR-TB NAAT ntiretrovirl therpy ntiretrovirl (drug) Bcille-Clmette-Guérin Brzil, Russin Federtion, Indi, Chin, South Afric cse detection rtio Committee for Medicinl Products for Humn Use confidence intervl co-trimoxzole preventive therpy Centrl TB Division (Indi) Conference on Retroviruses nd Opportunistic Infections creditor reporting system drug susceptibility testing Europen Medicines Agency externl qulity ssessment US Food nd Drug Administrtion Foundtion for Innovtive New Dignostics gross domestic product government helth expenditures high-burden country humn immune-deficiency virus HIV Vccine Trils Network Infectious Disese Reserch Institute interferon gmm relese ssys Interntionl Mternl Peditric Adolescent AIDS Clinicl Trils Group isonizid preventive therpy light-emitting diode microscopy urine lterl flow liporbinomnnn line probe ssy ltent TB infection Millennium Development Gols multidrug-resistnt TB nucleic cid mplifiction test NHA NHI NIAID NRL NTP OBR OECD OOP PK PMDT PPM RNTCP RR-TB SDGs SMS SRL SRL-CE TAG TB TBTC TBVI TPP TST UHC UNAIDS USAID VR WHA WHO XDR-TB ZN Ntionl Helth Account ntionl helth insurnce US Ntionl Institute of Allergy nd Infectious Diseses ntionl reference lbortory ntionl TB progrmme optimized bckground regimen Orgniztion for Economic Coopertion nd Development out-of-pocket phrmcokinetic progrmmtic mngement of drugresistnt TB public-privte mix Revised Ntionl Tuberculosis Control Progrmme (Indi) rifmpicin-resistnt TB Sustinble Development Gols short messging services Suprntionl Reference Lbortory SRL Ntionl Centres of Excellence Tretment Action Group tuberculosis TB Tril Consortium Tuberculosis Vccine Inititive trget product profile tuberculin skin test universl helth coverge Joint United Ntions Progrmme on HIV/ AIDS US Agency for Interntionl Development vitl registrtion World Helth Assembly World Helth Orgniztion extensively drug-resistnt TB Ziehl-Neelsen iv n GLOBAL TUBERCULOSIS REPORT 215

6 Acknowledgements This globl TB report ws produced by core tem of 19 people: Lur Anderson, Ann Den, Dennis Flzon, Ktherine Floyd, Inés Grci Ben, Christopher Gilpin, Philippe Glziou, Yohhei Hmd, Tom Hitt, Avinsh Knchr, Irwin Lw, Christin Lienhrdt, Linh Nguyen, Andrew Sirok, Chrlmbos Sismnidis, Ln Syed, Hzim Timimi, Wyne vn Gemert nd Mtteo Zignol. The tem ws led by Ktherine Floyd. Overll guidnce ws provided by the Director of the Globl TB Progrmme, Mrio Rviglione. The dt collection forms (long nd short versions) were developed by Philippe Glziou nd Hzim Timimi, with input from stf f throughout the WHO Globl TB Progrmme. Hzim Timimi led nd orgnized ll spects of dt mngement. The review nd follow-up of dt ws done by tem of reviewers tht included Lur Anderson, Annemieke Brnds, Andre Brz, Dennis Flzon, Inés Grci Ben, Giulino Grgioni, Mede Gegi, Yohhei Hmd, Avinsh Knchr, Soleil Lbelle, Irwin Lw, Fud Mirzyev, Linh Nguyen, Andrew Sirok, Ln Syed, Hzim Timimi, Mukund Uplekr, Wyne vn Gemert nd Mtteo Zignol t WHO hedqurters; Tom Hitt from the Western Pcific Regionl Office; Ann Scrdigli, Ymil Silv Cbrer, Ezr Tesser, Eliud Wndwlo nd Mohmmed Yssin from the Globl Fund; nd Andre Pntoj (consultnt). Dt for the Europen Region were collected nd vlidted jointly by the WHO Regionl Of fice for Europe nd the Europen Centre for Disese Prevention nd Control (ECDC); we thnk in prticulr Encrn Gimenez, Vhur Hollo nd Csb Ködmön from ECDC for providing vlidted dt files nd Andrei Ddu from the WHO Regionl Of fice for Europe for his substntil contribution to follow-up nd vlidtion of dt for ll Europen countries. UNAIDS mnged the process of dt collection from ntionl AIDS progrmmes nd provided ccess to their TB/HIV dtset. Review nd vlidtion of TB/HIV dt ws undertken in collbortion with Theres Bbovic nd Michel Beusenberg from the WHO HIV deprtment, long with UNAIDS hedqurters, regionl nd country strtegic informtion dvisers. Mny people contributed to the nlyses, preprtion of figures nd tbles, nd writing required for the min chpters of the report. Chpter 2 (TB disese burden nd 215 trgets ssessment) ws prepred by Ktherine Floyd, Philippe Glziou nd Chrlmbos Sismnidis, with contributions from Lur Anderson, Tom Hitt, Irwin Lw nd Ikushi Onozki. Chpter 3, on TB notifictions nd tretment outcomes s well s the tretment of ltent TB infection, ws prepred by Ktherine Floyd, Hileyesus Gethun, Yohhei Hmd, Tom Hitt, Alberto Mtteelli, Aniss Sidibe, Ln Syed nd Mukund Uplekr, with contributions from Hnnh Monic Dis, Dennis Flzon, Achutn Sreenivs nd Hzim Timimi. Chpter 4, on drug-resistnt TB, ws prepred by Ann Den, Dennis Flzon, Linh Nguyen nd Mtteo Zignol, with input from Ktherine Floyd, Chrlmbos Sismnidis nd Krin Weyer. Chpter 5, on TB dignostics nd lbortory strengthening, ws prepred by Wyne vn Gemert, with input from Christopher Gilpin, Fud Mirzyev nd Krin Weyer. Chpter 6, on the co-epidemics of TB nd HIV, ws prepred by Ktherine Floyd, Hileyesus Gethun, Yohhei Hmd, Tom Hitt nd Avinsh Knchr, who re lso grteful to Bhrt Rewri for his contribution to Box 6.1. Chpter 7, on TB finncing, ws prepred by Ktherine Floyd, Inés Grci Ben nd Andrew Sirok. Chpter 8, on TB reserch nd development, ws prepred by Christin Lienhrdt (new TB drugs nd new TB vccines) nd Christopher Gilpin (new TB dignostics), with input from Krin Weyer nd Ktherine Floyd. Tom Hitt coordinted the finliztion of figures nd tbles for ll chpters nd ws the focl point for communictions with the grphic designer. Irwin Lw designed the report cover nd lso coordinted the review nd correction of proofs. The report tem is grteful to vrious internl nd externl reviewers for their useful comments nd suggestions on dvnced drfts of the min chpters of the report. Prticulr thnks re due to Michel Beusenberg, Theres Bbovic nd Jesus Mri Grci Cllej from the HIV deprtment in WHO nd collegues from UNAIDS for their creful review of Chpter 6; nd to Dniell Cirillo nd Tom Shinnick (new TB dignostics), Cherise Scott nd Mel Spigelmn (new TB drugs) nd Jonthn Dniels, Jennifer Woolley nd Tom Evns (new TB vccines) for their reviews of nd input to Chpter 8. Annex 1, which explins how to use the online globl TB dtbse, ws written by Hzim Timimi. The country profiles tht pper in Annex 2, the regionl profiles tht pper in Annex 3 nd the detiled tbles showing dt for key indictors for ll countries in the ltest yer for which informtion is vilble (Annex 4) were lso prepred by Hzim Timimi. The online technicl ppendix tht explins the methods used to estimte the burden of disese cused by TB (incidence, prevlence, mortlity) ws prepred by Philippe Glziou, with input from Ann Den, Crel Pretorius, Chrlmbos Sismnidis nd Mtteo Zignol. We thnk Colin Mthers of the WHO Mortlity nd Burden of Disese tem for his creful review. We thnk Pmel Billie in the Globl TB Progrmme s monitoring nd evlution unit for impeccble dministr- GLOBAL TUBERCULOSIS REPORT 215 n v

7 tive support, Doris M Ft from the WHO Mortlity nd Burden of Disese tem for providing TB mortlity dt extrcted from the WHO Mortlity Dtbse, nd UNAIDS for providing epidemiologicl dt tht were used to estimte HIV-ssocited TB mortlity. The entire report ws edited by Srh Glbrith-Emmi, who we thnk for her excellent work. We lso thnk, s usul, Sue Hobbs for her excellent work on the design nd lyout of this report. Her contribution, s lwys, ws very highly pprecited. The principl source of finncil support for WHO s work on globl TB monitoring nd evlution is the United Sttes Agency for Interntionl Development (USAID), without which it would be impossible to produce the Globl Tuberculosis Report. Production of the report ws lso supported by the governments of Jpn nd the Republic of Kore. We cknowledge with grtitude their support. In ddition to the core report tem nd those mentioned bove, the report benefited from the input of mny stf f working in WHO regionl nd country of fices nd hundreds of people working for ntionl TB progrmmes or within ntionl surveillnce systems who contributed to the reporting of dt nd to the review of report mteril prior to publiction. These people re listed below, orgnized by WHO region. We thnk them ll for their invluble contribution nd collbortion, without which this report could not hve been produced. Among the WHO stf f not lredy mentioned bove, we thnk in prticulr Ann Volz, Mirth Del Grndo, Khurshid Alm Hyder, Rfel López Olrte, Nobu Nishikiori, André Ndongosieme, Kefs Smson, Krm Shh, nd Henriette Wembnym for their mjor contribution to fcilittion of dt collection, vlidtion nd review. WHO stf f in regionl nd country of fices WHO Africn Region Boubcr Abdel Aziz, Abdoulye Mrim Bïss, Esther Aceng-Dokotum, Hrur Admu, Incio Alvreng, Smuel Herms Andrinriso, Jvier Armburu, Cludin Augusto d Cruz, Ayodele Awe, Nyé Bh, Mrie Ctherine Broun, Bbou Bzie, Sirimn Cmr, Mlng Coly, Dvi Kokou Mwule, Ev De Crvlho, Noel Djemdji, Sithembile Dlmini-Nqeketo, Ismel Hssen Endris, Louis Gnd, Boingotlo Gsennelwe, Crolin Crdoso d Silv Gomes, Ptrick Hzngwe, Télesphore Hounsou, Jeuronlon Moses Kerkul, Michel Jose, Joel Kngngi, Nzuzi Ktondi, Kss Hilu Ketem, Khelifi Houri, Dniel Kibug, Hillry Kipruto, Aristide Désiré Komngoy Nzonzo, Ktherine Lo, Shrmil Lreef-Jh, Mwendweli Mboshe, Leonrd Mbemb, Mbumb Ngimbi Richrd, Julie Mugbekzi, Christine Musnhu, Ahmd NssuriI, Andre Ndongosieme, Denise Nkezimn, Wilfred Nkhom, Nicols Nkiere, Abel Nkolo, Ghisline Nkone Asseko, Ishmel Nysulu, Lurence Nyirmsrbwe, Smuel Ogiri, Dniel Olusoti, Amos Omoniyi, Hermnn Ongouo, Chijioke Oskwe, Felici Owusu-Antwi, Philip Ptrobs, Klpesh Rhevr, Hrill Nirin Rzkso, Richrd Oleko Rehn, Kefs Smson, Bbtunde Snni, Neem Gideon Simkoko, Susn Zimb-Tembo, Trore Tieble, Dest Tiruneh, Hubert Wng, Henriette Wembnym, Addislem Yilm, Assefsh Zehie. WHO Region of the Americs Jen Seme Alexndre, Monic Alonso Gonzlez, Pedro Avedillo, Crlos Ayl, Jen Seme Fils Alexndre, Angel Mnuel Alvrez, Miguel Angel Argón, Denise Arkki, Pedro Avedillo, Eldonn Boisson, Gustvo Brets, Mrgrette Bury, Dvid Chvrri, Betriz Cohenc, Mirth del Grndo, This dos Sntos, Mrcos Espinl, Ingrid Grcí, Yitdes Gebre, Mssimo Ghidinelli, Guillermo Gonzlvez, Percy Hlkyer, Kthryn Johnston, Sndr Jones, Frncisco Leon Brvo, Rfel Lopez Olrte, Roberto Montoy, Romeo Montoy, Enrique Perez, Soledd Pérez, Giovnni Rvsi, Jen Mrie Rwngbwob, Hns Sls, Alfonso Tenorio, Jorge Victori, Mrcelo Vil, Ann Volz. WHO Estern Mediterrnen Region Mohmed Abdel Aziz, Rehb Abdelhi, Ali Akbr, Smih Bghddi, Mi Eltigny Mohmmed, Kkr Qutubuddin, Ali Rez Aloudel, Sindni Ireneus Sebit, Syed Krm Shh, Bshir Suleimn, Rhim Tghizdeh. WHO Europen Region Andrei Ddu, Msoud Dr, Jmshid Gdoev, Dmitriy Pshkevich, Bogdn Shcherbk-Verln, Szbolcs Szigeti, Gzmend Zhuri. WHO South-Est Asi Region Mohmmd Akhtr, Vikrunnes Begum, Mri Regin Christin, Erwin Cooremn, Mrtin Dwihrdini, Md Khurshid Alm Hyder, Nvrtnsingm Jnkn, Kim Kwng Jin, Prth Prtim Mndl, Gimpolo Mezzbott, O Hyng Song, Mlik Prmr, Poknevych Igor, Rnjni Rmchndrn, Rim Kwng Il, Mukt Shrm, Achuthn Nir Sreenivs, Sber Sultn, Nmgy Tshering, Lungten Wngchuck. vi n GLOBAL TUBERCULOSIS REPORT 215

8 WHO Western Pcific Region Ahmdov Shll, Lur Gillini, Lepiti Hnsell, Corneli Hennig, Tom Hitt, Tuhid Islm, Nrntuy Jdmb, Ridh Jebenini, Woo-Jin Lew, Nobuyuki Nishikiori, Ktsunori Osug, Khnh Phm, Fbio Scno, Jcques Sebert, Mthid Thongseng, Ynni Sun, Rjendr-Prsd Ydv. Ntionl respondents who contributed to reporting nd verifiction of dt WHO Africn Region Mohmed Khirou Abdllhi Troré, Oumr Abdelhdi, Abderrmne Abdelrhim, Aben Foe Jen Louis, Kwmi Afutu, Gbriel Akng, Sofine Alihlss, Arlindo Tomás do Amrl, Rosmunde Amuteny, Angonou Séverin, Andrinsolo Lzso Rdonirin, Assoumni Younouss, Georges Bksw Ntmbwe, Bllé Boubkr, Adm Mrie Bngour, Jorge Brreto, Wilfried Bekou, Serge Bisut Fuez, Frnk Ade Bonsu, Miguel Cmrá, Evngelist Chiskitw, Amdou Cissé, Abdoul Krim Coulibly, António Rmos d Silv, Isis Dmbe, Dikite Aïch, Aw Helene Diop, Mrie Srr Diouf, Themb Dlmini, Sicelo Smuel Dlmini, Antoine Etoundi Evoun, Jun Eyene Acuresil, Lynd Fory, Gilberto Frot, Gsn Evriste, Michel Gsn, Abu George, Belineh Girm, Amnuel Hdegu Mebrhtu, Boukoulmé Hing, Hinikoye Aou Him Oumrou, Adm Jllow, Sf f Kmr, Mdou Kne, Knyerere Henry Shdreck, Nthn Kpt, Kesselly Deddeh, Botshelo Tebogo Kgwdir, Fnnie Khumlo, Désiré Aristide Komngoy Nzonzo, Ptrick Konwloh, Koukou Jcquemin, Andrgchew Kums, Kuye Joseph Oluwtoyin, Joseph Lsu, Gertrude Ly Ofli, Thoms Dougls Lere, Joseph Lou, Llng Mm-Mime, Jocelyn Mhoumbou, Lerole Dvid Mmetj, Ivn Mnhiç, Tseliso Mrt, Enos Msini, Fri Mvhung, Agnès Mezene, Slem Mohmeden, Louine Morel, Youwog Isidore Moyeng, Mpung Jmes Upile, Mry Mudiope, Frnk Mugbe Rwbinumi, Clif ford Munyndi, Betrice Mutyob, Lindiwe Mvusi, Aboubcr Mzembb, Fulgence Ndyikengurukiye, Thddée Ndikumn, Fith Ngri, Ngoulou Antoine, Lourenço Nhocun, Emmnuel Nkiligi, Adolphe Nkou Bikoe, Nii Nortey, Gérrd Nthizniye, Frnck Hrdin Okemb-Okombi, Emile Rkotondrmnn, Mrtin Rkotonjnhry, Thto Rleting, Rnivomhef Myrienne Bkoliriso Znjohry, Mohmmed Fezul Rujeedw, Agbenyegn Smey, Chrles Sndy, Kebb Snneh, Tndogo Soudogo, Emilie Srr Seck, Nichols Sizib, Kte Schnippel, Celestino Frncisco Teixeir, Gebreyesus Rhw Tekle, Kssim Trore, Eucher Dieudonné Yzipo, Eric Ismël Zoungrn. WHO Region of the Americs Rosmond Adms, Srit Aguirre Grcí, Shluddin Ahmed, Vlentin Antoniet Alrcon Guizdo, Xochil Alemán de Cruz, Kirn Kumr All, Mirin Alvrez, Aish Andrewin, Alister Antoine, Chris Archibld, Crlos Ayl Lun, Wiedjipreksh Blesr, Drurio Brreir, Ptrici Brtholomy, Beltrme Soledd, Dorothe Bergen Weichselberger, Mrí del Crmen Bermúdez Perez, Mrt Isbel Clon de Abrego, Mrtín Cstellnos Joy, Jorge Cstillo Crbjl, Annbell Cedeño Uglde, Krolyn Chong Cstillo, Eric Commiesie, Crlos Cruz, Ofeli Cuevs, Cecili de Arngo, Nild de Romero, Cmille Deleveux, Dy-Jun DeRoz, Khn Din, Luz Mrin Duque, Mercedes Espñ Cedeño, Alish Eugene, Sntigo Fdul, Fernndez Hugo, Cecili Figuero Benites, Gret Frnco, Victor Gllnt, Julio Gry Rmos, Izzy Gerstenbluth, Normn Gil, Mrgrit Godoy, Roscio Gomez, Betriz Gutierrez, Yskr Hlbi, Dorothe Hzel, Mri Henry, Tni Herrer, Crl Jeffries, Olg Joglr Jusino, Trcy- Ann Kernnet-Huggins, Athelene Linton, Cludi Lleren, Eugène Mduro, Andre Mldondo Svedr, Mrvin Mnznero, Belkys Mrcelino, Mrrero Figuero Antonio, Mrí de Lourdes Mrtínez, Zeidy Mt Azofeif, Timothy McLughlin-Munroe, Angelic Medin, Monic Mez, Roque Mirmontes, Leilwti Mohmmed, Jeetendr Mohnlll, Ernesto Moreno, Frncis Morey, Willy Morose, Denis Dnny Mosqueir Sls, Alice Neymour, Andres Oyol, Cheryl Peek-Bll, Toms Portillo, Ird Potter, Robert Prtt, Edwin Antonio Quiñonez Villtoro, Mnohr Singh Rjmnickm, Dottin Rmoutr, Ann Esther Reyes Godoy, Pul Ricketts, Rincon Andres, Cielo Rios, Dvid Rodriguez, Jorge Rodriguez De Mrco, Mrcel Rojs, Myrin Román, Monic Rondon, Arelisbel Ruiz, Wilmer Slzr, Hild Mrí Slzr Bolños, Mritz Smyo Peláez, Jon Simon, Nicol Skyers, Ntli Sos, Din Sotto, Stijnberg Deborh, Jckurlyn Sutton, Ariel Antonio Torres Rodríguez, Mribelle Tromp, Willim Turner, Meliss Vldez, Din Vrgs, Dniel Vázquez, Nestor Ver, Jun Jose Victori, An Mrí Vinuez, Michel Willims, Oritt Zchrih. WHO Estern Mediterrnen Region Njib Abdulziz Abdullh, Mohmmd Abouzeid, Khled Abu Rummn, Abu Sbrh Ndi, Ahmdi Shhnz, Abdul Ltif Al Khl, Mohmmed Redh Al Lwti, Al Sidi Khlood, Rshid Alhddry, Abdulbri Al-Hmmdi, Reem Alsifi, Kifh ALshqeldi, Wgdy Amin, Ngi Awd, Bhnsy Smir, Bennni Kenz, Molk Bouin, Swsen Boussett, Wlid Doud, Rchid Fourti, Mohmed Furjni, Aml Gll, Dhikryet Gmr, Assi Hissm, Klthoom Hssn, Abu Bkr Ahmd Hssn, Hw Hsssn Guessod, Slm Hudi, Bshrt Khn, Syed Doud Mhmoodi, Slh Ben Mnsour, Mulhm Mustf, Nsehi Mhshid, Ejz Qdeer, Mohmmd Khlid Seddiq, Sghir Mohmmed, Tmr Tyeb, Mohemmed Tben, Ycoub Him, Ammr Zidn. GLOBAL TUBERCULOSIS REPORT 215 n vii

9 WHO Europen Region Tleukhn Abildev, Ibrhim Abubkr, Alikhnov Ntvn, Ekkehrdt Altpeter, Elen Andrds Argonés, Delphine Antoine, Trude Mrgrete Arnesen, Andrei Astrovko, Zz Avlini, Avzbek Jlolov, Velimir Bereš, Yn Besstrschnov, Thorsteinn Blöndl, Oktm Bobokhojev, Bojovic Oliver, Snježn Brcklo, Bonit Brodhun, Ann Crgli, Aysoltn Chryev, Dniel Chemtob, Domnic Ion Chiotn, An Ciobnu, Nico Ciorn, Thierry Comolet, Rdmil Curcic, Edit Dvidvicene, Hyk Dvtyn, Gerrd de Vries, Irène Demuth, Antonio Diniz, Rquel Durte, Mlden Duronjic, Lnfrnco Fttorini, Lyly Gbbsov, Gsimov Viktor, Mjlind Gjocj, Lrus Jon Gudmundsson, Genndy Gurevich, Wlter Hs, Armen Hyrpetyn, Peter Helbling, Ilievsk-Poposk Biljn, Srh Jckson, Jkelj Andrz, Jonsson Jerker, Erhn Kbskl, Abdullt Kdyrov, Dmitriy Klimuk, Mri Korzeniewsk-Kosel, Kosnik Mitj, Kovcs Gbor, Meve Llor, Yn Levin, Irin Lucenko, Ekterin Mliukov, Donik Mem, Violet Mihilovic-Vucinic, Usmon Mihmnov, Vldimir Milnov, Uch Nnv, Anne Negre, Ntli Nizov, Zdenk Novkov, Jon O Donnell, Anlit Pce Ascik, Clr Plm Jordn, Olg Pvlov, Sbine Pfeiffer, Mri Grzi Pomp, Georget Gild Popescu, Kte Pulmne, Bozidrk Rkocevic, Vij Riekstin, Jerome Robert, Elen Rodríguez-Vlín, Krin Rønning, Kzimierz Roszkowski-Sliz, Gerrd Scheiden, Firuze Shripov, Aleksndr Simunovic, Cthrine Slorbk, Erik Slump, Hnn Soini, Ivn Solovic, Petr Svetin Sorli, Sergey Sterlikov, Jn Svecov, Tillyshykhov Mirzgleb, Shhnoz Usmonov, Tonk Vrlev, Piret Viiklepp, Kte Vulne, Jiri Wllenfels, Wnlin Mryse, Pierre Weicherding, Aysegul Yildirim, Zkosk Mj, Zsrnoczy Istvn, Hsn Žutic. WHO South-Est Asi Region Shin Ahmed, Aminth Aroosh, Si Thu Aung, Rtn Bhttri, Choe Tong Chol, Lurindo d Silv, Triy Novit Dinihri, Sulistyo Epid, Emddul Hque, Jittimnee Sirinph, Nirj Kulshresth, Myo Su Kyi, Biksh Lmichhne, Prmil Liynge, Consttino Lopes, Md. Mojibur Rhmn, Md. Mozzmel Hque, Nmwt Chwetsn, Nirup Pllewtt, Kirnkumr Rde, Chewng Rinzin, Sudth Smrweer, Gmini Senevirtne, Jnk Thilkrtne, Christin Widningrum, Biml Ydv. WHO Western Pcific Region Mohd Rotpi Abdullh, Pul Ai, Cecili Teres Arcig, Zirwtul Adilh Aziz, Mhfuzh Mohmd Azrnyi, Puntsg Bnzrgch, Christin Brej, Cheng Shiming, Phonenly Chittmny, Chou Kuok Hei, Nese Ituso Conwy, Jne Dowbobo, Myleen Ekiek, Fni Sen, Florence Flment, Ludovic Floury, Jiloris Frederick Dony, Ann Mrie Celin Grfin, Donn Me Gviol, Go Un-Yeong, Shkti Gounder, Neti Hermn, Anie Hryni Hj Abdul Rhmn, Dniel Houillon, Hjime Inoue, Noel Itogo, Tom Jck, Kng He-Young, Seiy Kto, Khin Mr Kyi Win, Dniel Lmr, Leo Lim, Liz Lopez, Skius Minwll, Henri-Pierre Mllet, Mo Tn Eng, Andre McNeill, Serfi Mo, Grizeld Mokoi, Nguyen Viet Nhung, Nguyen Binh Ho, Nou Chnly, Connie Olikong, Dorj Otgontsetseg, Sosi Penitni, Nukutu Pokur, Mrcelin Rbulimn, Asmh Rzli, Berek Reiher, Ris Bukbuk, Bernrd Rouchon, Temilo Seono, Hidekzu Shimd, Vit Skilling, Grnt Storey, Phnnsinh Sylvnh, Tgro Mrkleen, Tm Cheuk Ming, Silivi Tvite, Kyw Thu, Tieng Sivnn, Toms Cindy, Tong K Io, Alfred Tongnibei, Kzuhiro Uchimur, Kzunori Umeki, Lixi Wng, Yee Tng Wng, Du Xin. viii n GLOBAL TUBERCULOSIS REPORT 215

10 Prefce Dr Mrio Rviglione At meeting of stkeholders nd donors to the Globl TB Progrmme held in Oslo in September 1995, key discussion point relted to the need to monitor progress towrds globl trgets set in 1991 by the World Helth Assembly. The trgets the populr 7% cse detection rte nd 85% cure rte for new cses of smer-positive pulmonry TB were to be reched by 2. At the time of the meeting, no stndrdized globl monitoring system existed. While cler definitions of TB cses nd tretment outcomes were key components of WHO s then-new globl TB strtegy DOTS the only dt vilble to ssess trends in the disese cme from the epidemiologicl bulletins of better-of f countries nd occsionl d-hoc reports from low-income countries following reviews nd monitoring missions. Since TB is primrily disese of poor countries, this ws not good enough for the influentil people meeting in Oslo. Their request cme loud nd cler: WHO should strt immeditely to develop system tht would request ll Member Sttes to report essentil informtion on TB notifictions nd tretment outcomes, so tht progress or lck of progress could be monitored nd discussed t their next meeting. Though globl trgets hd been set in 1991, it nevertheless took four yers before such system ws recognized s necessity: this ws not yet the er of precision, ccountbility, nd evidence-bsed evlution. Since only couple of other progrmmes hd developed such systems by then, the field of TB ws mong the pioneers in this endevour. As result of the discussions in Oslo, Dr Art Kochi, then the Director of the Globl TB Progrmme, sked me to move quickly to crete globl monitoring nd evlution system tht would stisfy the request. Exctly 2 yers go, in October 1995, I strted setting up tem composed of hndful of people chrged with globlizing the locl recording nd reporting system recommended within the DOTS strtegy. Tht strtegy ws bsed on the model progrmmes tht Dr Krel Styblo hd developed in severl countries where the KNCV Tuberculosis Foundtion nd the Union were implementing modern TB control efforts. During severl months of intensive work, we creted dtbse nd stndrd dt collection form (in pper nd electronic formts) tht ws distributed to ll Member Sttes. By the summer of 1996, most countries hd provided informtion to WHO Hedqurters using stndrdized definitions so tht dt from one country could be compred esily with dt from nother. For the first time, we could ssess globl progress towrd the 2 trgets. The results were presented t the September 1996 meeting of donors nd other stkeholders. They showed tht fewer thn 2% of ll cses estimted worldwide were being detected nd tht the globl cure rte ws less thn 8%. In the following yers, our globl monitoring nd evlution system for TB evolved further, with the inclusion of dditionl informtion nd more sophisticted nlyses. For exmple, our tem led first by Dr Christopher Dye nd lter by Dr Ktherine Floyd GLOBAL TUBERCULOSIS REPORT 215 n ix

11 begn to monitor the finncing of TB control to ssess whether Member Sttes were investing s required. Lter, we integrted dt from the drug resistnce surveillnce system to enble us to ssess comprehensively ll the key indictors needed to monitor progress nd to identify nd correct problems. Our tem, under the guidnce of Dr Philippe Glziou, developed more precise estimtes of the burden of TB, improving the methodology to mesure incidence, prevlence nd mortlity. In prticulr, since 26, concerted ef forts hve been guided by the WHO Globl Tsk Force on TB Impct Mesurement, resulting in substntilly incresed dt from ntionl TB prevlence surveys nd much greter use of mortlity dt from vitl registrtion systems. As result of these ef forts, 2 yers lter, we re ble to judge firly precisely the sttus of the epidemic nd the response of Member Sttes. We cn ssess where people with TB re missing from notifiction systems; where cure rtes remin low nd filure rtes re high; where multidrug- resistnt TB is serious issue; nd where domestic funding must be complemented by interntionl finncing. None of this ws possible in We re now entering the er of the Sustinble Development Gols, in which prdigm shif ts re expected in ll sectors, including helth. TB is n infectious disese tht, despite ll progress, clims number of deths prlleled only by those from HIV/ AIDS. To end the epidemic (defined s n incidence of fewer thn 1 cses per million people) by 235 will require rpid upgrde of cre nd mngeril stndrds. During the next 2 yers, we will need to chnge our mentlity nd dopt ll ef fective innovtions, including those exploiting digitl technology, especilly in the relm of informtion mngement. Novel wys of dignosing nd reporting lredy exist nd their doption will help us evolve further towrds interventions tht re more userfriendly, cheper nd more sustinble. If fully dopted, these technologies will not only trnsform the wy we hndle cre nd surveillnce, but will increse the ef fectiveness of mngeril nd trining efforts for the benefit of those who suffer from TB. On the occsion of the publiction of this 2th WHO globl TB report, which coincides with the ssessment of the 215 globl TB trgets set s prt of the Millennium Development Gols, I m humbled by the progress in terms of impct nd opertions tht we hve witnessed in mny countries over two decdes. The Globl Report is testimony to the tireless ef forts of mny people worldwide, from Ntionl TB Progrmme stf f to community members, from clinicins nd nurses to those working for non-governmentl orgniztions who hve devoted themselves to the noble fight ginst clssic exmple of disese of poverty. Mrio Rviglione Director of the Globl TB Progrmme x n GLOBAL TUBERCULOSIS REPORT 215

12 Executive summry Bckground The yer 215 is wtershed moment in the bttle ginst tuberculosis (TB). It mrks the dedline for globl TB trgets set in the context of the Millennium Development Gols (MDGs), nd is yer of trnsitions: from the MDGs to new er of Sustinble Development Gols (SDGs), nd from the Stop TB Strtegy to the End TB Strtegy. It is lso two decdes since WHO estblished globl TB monitoring system; since tht time, 2 nnul rounds of dt collection hve been completed. Using dt from 25 countries nd territories, which ccount for more thn 99% of the world s popultion, this globl TB report documents dvnces in prevention, dignosis nd tretment of the disese. It lso identifies res where ef forts cn be strengthened. Min findings nd messges The dvnces re mjor: TB mortlity hs fllen 47% since 199, with nerly ll of tht improvement tking plce since 2, when the MDGs were set. In ll, ef fective dignosis nd tretment of TB sved n estimted 43 million lives between 2 nd 214. The MDG trget to hlt nd reverse TB incidence hs been chieved on worldwide bsis, in ech of the six WHO regions nd in 16 of the 22 high-burden countries tht collectively ccount for 8% of TB cses. Globlly, TB incidence hs fllen by n verge of 1.5% per yer since 2 nd is now 18% lower thn the level of 2. This yer s report describes higher globl totls for new TB cses thn in previous yers, but these reflect incresed nd improved ntionl dt rther thn ny increse in the spred of the disese. Despite these dvnces nd despite the fct tht nerly ll cses cn be cured, TB remins one of the world s biggest threts. In 214, TB killed 1.5 million people (1.1 million HIV-negtive nd.4 million HIV-positive). The toll comprised 89 men, 48 women nd 14 children. TB now rnks longside HIV s leding cuse of deth worldwide. HIV s deth toll in 214 ws estimted t 1.2 million, which included the.4 million TB deths mong HIVpositive people. 1 Worldwide, 9.6 million people re estimted to hve fllen ill with TB in 214: 5.4 million men, 3.2 million women nd 1. million children. Globlly, 12% of the 9.6 million new TB cses in 214 were HIV-positive. To reduce this burden, detection nd tretment gps must be ddressed, funding gps closed nd new tools developed. In 214, 6 million new cses of TB were reported to WHO, fewer thn two-thirds (63%) of the 9.6 million people estimted to hve fllen sick with the disese. This mens tht worldwide, 37% of new cses went undignosed or were not reported. The qulity of cre for people in the ltter ctegory is unknown. Of the 48 cses of multidrug-resistnt TB (MDR-TB) estimted to hve occurred in 214, only bout qurter of these 123 were detected nd reported. Although the number of HIV-positive TB ptients on ntiretrovirl therpy (ART) improved in 214 to 392 people (equivlent to 77% of notified TB ptients known to be co-infected with HIV), this number ws only one third of the estimted 1.2 million people living with HIV who developed TB in 214. All HIV-positive TB cses re eligible for ART. Funding gps mounted to US$ 1.4 billion for implementtion of existing interventions in 215. The most recent estimte of the nnul funding gp for reserch nd development is similr, t bout US$ 1.3 billion. From 216, the gol is to end the globl TB epidemic by implementing the End TB Strtegy. Adopted by the World Helth Assembly in My 214 nd with trgets linked to the newly dopted SDGs, the strtegy serves s blueprint for countries to reduce the number of TB deths by 9% by 23 (compred with 215 levels), cut new cses by 8% nd ensure tht no fmily is burdened with ctstrophic costs due to TB. 1 The cuse of TB deths mong HIV-positive people is clssified s HIV in the Interntionl clssifiction of diseses system. GLOBAL TUBERCULOSIS REPORT 215 n 1

13 Additionl highlights from the report Disese burden nd 215 trgets ssessment "" The quntity nd qulity of dt vilble to estimte TB disese burden continue to improve. These include direct mesurements of mortlity in 129 countries nd finl results from 18 ntionl TB prevlence surveys completed since 29, six of them in the pst yer (Ghn, Indonesi, Mlwi, Sudn, Zmbi nd Zimbbwe). "" Revised estimtes for Indonesi (1 million new cses per yer, double the previous estimte) explin the upwrd revision to WHO s globl estimtes of incident cses compred with those published in 214. Importntly, however, revisions lso f fect estimtes for previous yers nd the trend in TB incidence globlly s well s in Indonesi is still downwrd since round 2. "" Of the 9.6 million new TB cses in 214, 58% were in the South-Est Asi nd Western Pcific regions. "" The Africn Region hd 28% of the world s cses in 214, but the most severe burden reltive to popultion: 281 cses for every 1 people, more thn double the globl verge of 133. "" Indi, Indonesi nd Chin hd the lrgest number of cses: 23%, 1% nd 1% of the globl totl, respectively. "" Globlly, TB prevlence in 215 ws 42% lower thn in 199. The trget of hlving the rte compred with 199 ws chieved in three WHO regions the Region of the Americs, the South-Est Asi Region nd the Western Pcific Region nd in nine high-burden countries (Brzil, Cmbodi, Chin, Ethiopi, Indi, Mynmr, the Philippines, Ugnd nd Viet Nm). "" The trget of hlving the TB mortlity rte by 215 compred with 199 ws met in four WHO regions the Region of the Americs, the Estern Mediterrnen Region, the South-Est Asi Region nd the Western Pcific Region nd in 11 high-burden countries (Brzil, Cmbodi, Chin, Ethiopi, Indi, Mynmr, Pkistn, the Philippines, Ugnd, Viet Nm nd Zimbbwe). "" All three of the 215 trgets (for incidence, prevlence nd mortlity) were met in nine high-burden countries Brzil, Cmbodi, Chin, Ethiopi, Indi, Mynmr, the Philippines, Ugnd nd Viet Nm. TB cse notifictions nd tretment outcomes "" In the 2 yers since WHO estblished globl reporting system in 1995, it hs received reports of 78 million TB cses, 66 million of which were treted successfully. "" In 214, tht system mesured mrked increse in globl TB notifictions for the first time since 27. The nnul totl of new TB cses, which hd been bout 5.7 million until 213, rose to slightly more thn 6 million in 214 (n increse of 6%). This ws mostly due to 29% increse in notifictions in Indi, which followed the introduction of policy of mndtory notifiction in My 212, cretion of ntionl web-bsed reporting system in June 212 nd intensified ef forts to engge the privte helth sector. Indi ccounted for 27% of globl TB notifictions in 214. "" Globlly, the tretment success rte for people newly dignosed with TB ws 86% in 213, level tht hs been sustined since 25. Tretment success rtes require improvement in the Region of the Americs nd the Europen Region (75% in both regions in 213). Drug-resistnt TB "" Globlly, n estimted 3.3% of new TB cses nd 2% of previously treted cses hve MDR-TB, level tht hs chnged little in recent yers. "" In 214, n estimted 19 people died of MDR-TB. "" More TB ptients were tested for drug resistnce in 214 thn ever before. Worldwide, 58% of previously treted ptients nd 12% of new cses were tested, up from 17% nd 8.5% respectively in 213. This improvement is prtly due to the doption of rpid moleculr tests. "" If ll of the TB cses notified in 214 hd been tested for drug resistnce, n estimted 3 would hve been found to hve MDR-TB, with more thn hlf of them (54%) occurring in Indi, Chin nd the Russin Federtion. "" The number of cses detected (123 ) worldwide represented just 41% of this globl estimte, nd only 26% of the 48 incident cses of MDR-TB estimted to hve occurred in 214. Detection gps were worst in the Western Pcific Region, where the number of cses detected ws only 19% of the number of notified cses estimted to hve MDR-TB (the figure for Chin ws 11%). "" A totl of 111 people strted MDR-TB tretment in 214, n increse of 14% compred with 213. "" The rtio of ptients enrolled in tretment to ptients newly notified s hving MDR-TB or rifmpicin-resistnt TB ws 9% globlly. The rtio ws bove 9% in 15 of the 27 high MDR-TB burden countries s well s in the Europen Region nd the Region of the Americs. "" Globlly, only 5% of MDR-TB ptients were successfully treted. However, the 215 tretment success trget of 75% for MDR-TB ptients ws reched by 43 of the 127 countries nd territories tht reported outcomes for the 212 cohort, including three high MDR-TB burden countries (Estoni, Ethiopi nd Mynmr). "" Extensively drug-resistnt TB (XDR-TB) hd been reported by 15 countries by 215. An estimted 9.7% of people with MDR-TB hve XDR-TB. Dignostics nd lbortory strengthening "" The use of the rpid test Xpert MTB/RIF hs expnded substntilly since 21, when WHO first recommended its use. In ll, 4.8 million test crtridges were procured in 214 by 116 low- nd middle-income countries t concessionl prices, up from 55 in 211. "" By 215, 69% of countries recommended using Xpert MTB/RIF s the initil dignostic test for people t risk of 2 n GLOBAL TUBERCULOSIS REPORT 215

14 drug-resistnt TB, nd 6% recommended it s the initil dignostic test for people living with HIV. Addressing the co-epidemics of TB nd HIV "" In 214, n estimted 1.2 million (12%) of the 9.6 million people who developed TB worldwide were HIV-positive. The Africn Region ccounted for 74% of these cses. "" The number of people dying from HIV-ssocited TB peked t 57 in 24 nd hd fllen to 39 in 214 ( 32% decrese). "" Globlly, 51% of notified TB ptients hd documented HIV test result in 214, smll increse from 49% in 213. The figure ws highest in the Africn Region, t 79%. "" The number of people living with HIV who were treted with isonizid preventive therpy reched 933 in 214, n increse of bout 6% compred with 213. A lrge proportion of these people (59%) were in South Afric. Finncing "" The funding required for full response to the globl TB epidemic in low- nd middle-income countries is estimted t US$ 8 billion per yer in 215, excluding reserch nd development. Projections mde in 213 suggested tht, by 215, bout US$ 6 billion could be mobilized from domestic sources, leving blnce of US$ 2 billion needed from interntionl donors. "" Bsed on self-reporting by countries, funding for TB prevention, dignosis nd tretment reched US$ 6.6 billion in 215, up from US$ 6.2 billion in 214 nd more thn double the level of 26 (US$ 3.2 billion). "" Overll, 87% (US$ 5.8 billion) of the US$ 6.6 billion vilble in 215 is from domestic sources. "" Interntionl donor funding reported by countries to WHO hs incresed since 26, reching US$.8 billion in 215. "" The totl mount of interntionl donor funding recorded in the creditor reporting system of the Orgniztion for Economic Coopertion nd Development (OECD) is higher: the ltest dt show totl contributions of US$ 1 billion in 213. Of this mount, 77% ws from the Globl Fund. The lrgest country donor ws the government of the United Sttes of Americ, which contributed bout one third of the TB funding chnnelled vi the Globl Fund s well s bilterl funds of US$ 362 million for TB nd TB/ HIV in "" Domestic funding ccounts for more thn 9% of the totl funding in 215 in three country groups: Brzil, the Russin Federtion, Indi, Chin nd South Afric (BRICS); upper-middle-income countries; nd regions outside Afric nd Asi. "" Interntionl donor funding domintes in the group of 17 high-burden countries outside BRICS (72% of the totl funding vilble in 215) nd in low-income countries (81% of the totl funding vilble in 215). "" The cost per ptient treted for drug-susceptible TB in 214 rnged from US$ 1 5 in most countries with high burden of TB. The cost per ptient treted for MDR- TB ws typiclly US$ 5 1. Reserch nd development "" In the dignostics pipeline, tests bsed on moleculr technologies re the most dvnced. "" A dignostic pltform clled the GeneXpert Omni is in development. It is intended for point-of-cre testing for TB nd rifmpicin-resistnt TB using Xpert MTB/RIF crtridges. The device is expected to be smller, lighter nd less expensive thn currently vilble pltforms for point-of-cre nucleic cid detection nd will come with built-in, 4-hour bttery. WHO expects to evlute the pltform in 216. "" A next-genertion crtridge clled Xpert Ultr is lso in development. It is intended to replce the Xpert MTB/RIF crtridge nd could potentilly replce conventionl culture s the primry dignostic tool for TB. "" Eight new or repurposed nti-tb drugs re in dvnced phses of clinicl development. For the first time in six yers, n nti-tb drug cndidte (TBA-354) is in Phse I testing. "" Severl new TB tretment regimens for drug-susceptible nd/or drug-resistnt TB re being tested in Phse II or Phse III trils; t lest two more trils re scheduled to strt towrds the end of 215 or in erly 216. "" WHO hs issued interim guidnce on the use of bedquiline (in 213) nd delmnid (in 214). "" By the end of 214, 43 countries reported hving used bedquiline to tret ptients s prt of ef forts to expnd ccess to tretment for MDR-TB. "" Recent observtionl studies of the ef fectiveness of short tretment regimens for MDR-TB in Niger nd Cmeroon found tht 12-month regimen ws effective nd well-tolerted in ptients not previously exposed to second-line drugs. At lest 16 countries in Afric nd Asi hve introduced shorter regimens s prt of trils or observtionl studies under opertionl reserch conditions, nd WHO will ressess current guidnce on their use in 216. "" Fif teen vccine cndidtes re in clinicl trils. Their emphsis hs shif ted from children to dolescents nd dults. "" New dignostics, drugs nd vccines will be needed to chieve the trgets set in the End TB Strtegy. 1 Not ll of these bilterl funds re cptured in the OECD dtbse. For exmple, this does not record flows of funds between OECD countries, nd funding for TB/HIV my be coded s funding for HIV. GLOBAL TUBERCULOSIS REPORT 215 n 3

15 Box 1.1 Bsic fcts bout TB TB is n infectious disese cused by the bcillus Mycobcterium tuberculosis. It typiclly f fects the lungs (pulmonry TB) but cn f fect other sites s well (extrpulmonry TB). The disese is spred in the ir when people who re sick with pulmonry TB expel bcteri, for exmple by coughing. Overll, reltively smll proportion (5 15%) of the estimted 2 3 billion people infected with M. tuberculosis will develop TB disese during their lifetime. However, the probbility of developing TB is much higher mong people infected with HIV. The most common method for dignosing TB worldwide remins sputum smer microscopy (developed more thn 1 yers go), in which bcteri re observed in sputum smples exmined under microscope. However, developments in TB dignostics in the lst few yers men tht the use of rpid moleculr tests to dignose TB nd drug-resistnt TB is incresing, nd some countries re phsing out use of smer microscopy for dignostic (s opposed to tretment monitoring) purposes. In countries with more developed lbortory cpcity, cses of TB re lso dignosed vi culture methods (the current reference stndrd). Without tretment, the deth rte is high. Studies from the pre-chemotherpy er found tht bout 7% of people with sputum smerpositive pulmonry TB died within 1 yers, nd tht this figure ws 2% mong culture-positive (but smer-negtive) cses of pulmonry TB. Ef fective drug tretments were first developed in the 194s. The most ef fective first-line nti-tb drug, rifmpicin, becme vilble in the 196s. The currently recommended tretment for new cses of drug-susceptible TB is six-month regimen of four first-line drugs: isonizid, rifmpicin, ethmbutol nd pyrzinmide. Tretment success rtes of 85% or more for new cses re regulrly reported to WHO by its Member Sttes. Tretment for multidrug-resistnt TB (MDR-TB), defined s resistnce to isonizid nd rifmpicin (the two most powerful nti-tb drugs) is longer, nd requires more expensive nd more toxic drugs. For most ptients with MDR-TB, the current regimens recommended by WHO lst 2 months, nd tretment success rtes re much lower. New TB drugs re now emerging from the pipeline, nd combintion regimens tht include new compounds re being tested in clinicl trils. There re severl TB vccines in Phse I or Phse II trils. For the time being, however, vccine tht is ef fective in preventing TB in dults remins elusive. Tiemersm EW et l. Nturl history of tuberculosis: durtion nd ftlity of untreted pulmonry tuberculosis in HIV-negtive ptients: A systemtic review. PLoS ONE, 211, 6(4): e n GLOBAL TUBERCULOSIS REPORT 215

16 CHAPTER 1 Introduction Tuberculosis (TB) is mjor globl helth problem. It cuses ill-helth mong millions of people ech yer nd rnks longside the humn immunodeficiency virus (HIV) s leding cuse of deth worldwide. 1 In 214, there were n estimted 9.6 million new TB cses: 5.4 million mong men, 3.2 million mong women nd 1. million mong children. There were lso 1.5 million TB deths (1.1 million mong HIV-negtive people nd.4 million mong HIV-positive people), of which pproximtely 89 were men, 48 were women nd 14 were children. The number of TB deths is uncceptbly high: with timely dignosis nd correct tretment, lmost ll people with TB cn be cured. Bsic fcts bout TB re summrized in Box 1.1. The World Helth Orgniztion (WHO) hs published globl TB report every yer since The min im of these reports is to provide comprehensive nd up-to-dte ssessment of the TB epidemic nd progress in prevention, dignosis nd tretment of the disese t globl, regionl nd country levels, in the context of recommended globl TB strtegies nd trgets endorsed by WHO s Member Sttes. For the pst decde, the focus hs been on progress towrds 215 globl trgets for reductions in TB disese burden set in the context of the Millennium Development Gols (MDGs). The trgets re tht TB incidence should be flling (MDG Trget 6.c) nd tht TB prevlence nd mortlity rtes should be hlved compred with their 199 levels. The Stop TB Strtegy, 2 developed for the period , hs been WHO s recommended pproch to chieving these trgets (Box 1.2). With 215 mrking the MDG nd globl TB trget dedline, the specil emphsis nd most importnt topic of this 215 globl TB report is n ssessment of whether the 215 trgets hve been chieved. This ssessment is mde for the world, for the six WHO regions nd for the 22 high-burden countries tht collectively ccount for 8% of TB cses. The topics covered in the remining six chpters of the report re: TB cse notifictions nd tretment outcomes; drugresistnt TB; dignostics nd lbortory strengthening; ddressing the co-epidemics of TB nd HIV; finncing; nd reserch nd development. Since the end of 215 lso mrks the end of the MDG nd Stop TB Strtegy ers nd the strt of post-215 development frmework (216 23) of Sustinble Development Gols (SDGs) 3 nd n ssocited post-215 globl TB strtegy, 4 ech chpter of the report fetures content relted to the trnsition to the new End TB Strtegy (Box 1.3). As usul, the 215 globl TB report is bsed on dt collected in nnul rounds of globl TB dt collection from countries nd territories, including 194 Member Sttes. This is done using web-bsed system ( tme), which ws opened for reporting in mid-mrch. In 215, 25 countries nd territories tht ccount for more thn 99% of the world s popultion nd estimted TB cses reported dt; this included 183 of WHO s 194 Member Sttes. Dt bout the provision of isonizid preventive therpy (IPT) to people living with HIV nd ntiretrovirl therpy (ART) for HIV-positive TB ptients, which were collected by the HIV deprtment in WHO nd the Joint United Ntions Progrmme on HIV/AIDS (UNAIDS), were lso used. Following review nd follow-up with countries, the results presented in the min prt of this report re bsed on dt vilble on 6 August 215. The report hs four nnexes. Annex 1 describes the contents of the globl TB dtbse, how dt were collected nd how to ccess the dt. Annex 2 contins country profiles for the 22 high-burden countries (profiles for other countries re vilble online 5 ) nd Annex 3 contins regionl profiles. Annex 4 provides detiled dt tbles for key indictors for the most recent yer for which dt or estimtes re vilble, for ll countries. As the 2th in the series, this 215 globl TB report mrks n importnt lndmrk in globl TB monitoring by WHO. 1 In 214, there were n estimted 1.2 million deths due to HIV; this includes.4 million deths from TB mong HIV-positive people. See unids.org. 2 Rviglione M, Uplekr M. WHO s new Stop TB strtegy. The Lncet, 26; 367: Uplekr M, Weil D, Lonnroth K, Jrmillo E, Lienhrdt C, Dis HM, et l. WHO s new End TB Strtegy. The Lncet. 215;385: GLOBAL TUBERCULOSIS REPORT 215 n 5

17 Box 1.2 The Stop TB Strtegy t glnce (26 215) VISION GOAL OBJECTIVES TARGETS A TB-free world To drmticlly reduce the globl burden of TB by 215 in line with the Millennium Development Gols (MDGs) nd the Stop TB Prtnership trgets n Achieve universl ccess to high-qulity cre for ll people with TB n Reduce the humn suffering nd socioeconomic burden ssocited with TB n Protect vulnerble popultions from TB, TB/HIV nd drug-resistnt TB n Support development of new tools nd enble their timely nd effective use n Protect nd promote humn rights in TB prevention, cre nd control n MDG 6, Trget 6.c: Hlt nd begin to reverse the incidence of TB by 215 n Trgets linked to the MDGs nd endorsed by the Stop TB Prtnership: 215: reduce prevlence of nd deths due to TB by 5% compred with bseline of : eliminte TB s public helth problem (defined s <1 cse per 1 million popultion per yer) COMPONENTS 1. Pursue high-qulity DOTS expnsion nd enhncement. Secure politicl commitment, with dequte nd sustined finncing b. Ensure erly cse detection, nd dignosis through qulity-ssured bcteriology c. Provide stndrdized tretment with supervision, nd ptient support d. Ensure ef fective drug supply nd mngement e. Monitor nd evlute performnce nd impct 2. Address TB/HIV, MDR-TB, nd the needs of poor nd vulnerble popultions. Scle up collbortive TB/HIV ctivities b. Scle up prevention nd mngement of MDR-TB c. Address the needs of TB contcts, nd of poor nd vulnerble popultions 3. Contribute to helth system strengthening bsed on primry helth cre. Help improve helth policies, humn resource development, finncing, supplies, service delivery nd informtion b. Strengthen infection control in helth services, other congregte settings nd households c. Upgrde lbortory networks, nd implement the Prcticl Approch to Lung Helth d. Adpt successful pproches from other fields nd sectors, nd foster ction on the socil determinnts of helth 4. Engge ll cre providers. Involve ll public, voluntry, corporte nd privte providers through public privte mix pproches b. Promote use of the Interntionl Stndrds for Tuberculosis Cre 5. Empower people with TB, nd communities through prtnership. Pursue dvoccy, communiction nd socil mobiliztion b. Foster community prticiption in TB cre, prevention nd helth promotion c. Promote use of the Ptients Chrter for Tuberculosis Cre 6. Enble nd promote reserch. Conduct progrmme-bsed opertionl reserch b. Advocte for nd prticipte in reserch to develop new dignostics, drugs nd vccines. 6 n GLOBAL TUBERCULOSIS REPORT 215

18 Box 1.3 The End TB Strtegy t glnce ( ) VISION GOAL INDICATORS Reduction in number of TB deths compred with 215 (%) A WORLD FREE OF TB zero deths, disese nd suffering due to TB END THE GLOBAL TB EPIDEMIC MILESTONES TARGETS SDG 23 End TB % 75% 9% 95% Reduction in TB incidence rte compred with 215 (%) 2% (<85/1 ) 5% (<55/1 ) 8% (<2/1 ) 9% (<1/1 ) TB-f fected fmilies fcing ctstrophic costs due to TB (%) PRINCIPLES 1. Government stewrdship nd ccountbility, with monitoring nd evlution 2. Strong colition with civil society orgniztions nd communities 3. Protection nd promotion of humn rights, ethics nd equity 4. Adpttion of the strtegy nd trgets t country level, with globl collbortion PILLARS AND COMPONENTS 1. INTEGRATED, PATIENT-CENTRED CARE AND PREVENTION A. Erly dignosis of TB including universl drug-susceptibility testing, nd systemtic screening of contcts nd high-risk groups B. Tretment of ll people with TB including drug-resistnt TB, nd ptient support C. Collbortive TB/HIV ctivities, nd mngement of co-morbidities D. Preventive tretment of persons t high risk, nd vccintion ginst TB 2. BOLD POLICIES AND SUPPORTIVE SYSTEMS A. Politicl commitment with dequte resources for TB cre nd prevention B. Enggement of communities, civil society orgniztions, nd public nd privte cre providers C. Universl helth coverge policy, nd regultory frmeworks for cse notifiction, vitl registrtion, qulity nd rtionl use of medicines, nd infection control D. Socil protection, poverty llevition nd ctions on other determinnts of TB 3. INTENSIFIED RESEARCH AND INNOVATION A. Discovery, development nd rpid uptke of new tools, interventions nd strtegies B. Reserch to optimize implementtion nd impct, nd promote innovtions Trgets linked to the Sustinble Development Gols (SDGs). GLOBAL TUBERCULOSIS REPORT 215 n 7

19 CHAPTER 2 Disese burden nd 215 trgets ssessment Key fcts nd messges The dt vilble to estimte TB disese burden (incidence, prevlence, mortlity) continue to improve. In 214, dt from vitl registrtion (VR) systems nd/or mortlity surveys were used to estimte TB mortlity in 129 countries (up from three countries in 28). There hs been substntil progress in the implementtion of ntionl popultion-bsed surveys of the prevlence of TB disese since 28, with 18 surveys (of which 12 were first-ever ntionl surveys) completed between 29 nd August 215. Of these, results from six surveys were finlized in the pst yer (Ghn, Indonesi, Mlwi, Sudn, Zmbi, Zimbbwe), nd dditionl survey results becme vilble for the United Republic of Tnzni. Three dditionl surveys were begun in lte 214 or 215. Notifiction dt for 214 were reported by 25 countries nd territories. This chpter presents the ltest WHO estimtes of TB disese burden between 199 nd 215. Specil emphsis is given to ssessment of whether 215 trgets set in the context of the Millennium Development Gols (MDGs) were chieved. The trgets were tht incidence should be flling by 215 (MDG trget 6c) nd tht prevlence nd mortlity rtes should be hlved compred with 199 levels. Globlly in 214, there were n estimted 9.6 million incident cses of TB: 5.4 million mong men, 3.2 million mong women nd 1. million mong children. The globl totl is considerble upwrd revision compred with estimtes published in 214, following results from the ntionl prevlence survey in Indonesi. It is now estimted tht there re bout 1 million new TB cses per yer in Indonesi, twice the previously estimted level. Globlly in 214, there were n estimted 1.2 million new HIVpositive TB cses (12% of ll TB cses). Almost three-qurters of these cses were in the Africn Region. Globlly in 214, there were n estimted 1.5 million deths from TB: 1.1 million deths mong people who were HIVnegtive nd 39 deths mong people who were HIVpositive.* TB rnks longside HIV (1.2 million deths in 214, including the 39 TB deths mong HIV-positive people) s leding cuse of deth worldwide. The South-Est Asi nd Western Pcific Regions collectively ccounted for 58% of the world s TB cses in 214. The Africn Region hd 28% of the world s cses, but the most severe burden reltive to popultion (281 incident cses per 1 popultion on verge, more thn double the globl verge of 133). Indi, Indonesi nd Chin hd the lrgest numbers of cses (23%, 1% nd 1% of the globl totl, respectively). The MDG trget of hlting nd reversing TB incidence by 215 ws chieved globlly, in ll six WHO regions nd in 16 of the 22 high TB burden countries (HBCs). The TB incidence rte hs fllen t n verge rte of 1.5% per yer since 2. Globlly, the TB mortlity rte in 215 ws 47% lower thn in 199: the trget of 5% reduction ws lmost met. The trget ws chieved in four WHO Regions (the exceptions were the Africn nd Europen regions), nd in 11 HBCs. Globlly, the TB prevlence rte in 215 ws 42% lower thn in 199. The trget of 5% reduction ws met in three WHO regions nd in nine HBCs. All three 215 trgets were met in the Region of the Americs, the South-Est Asi Region nd the Western Pcific Region, nd in nine HBCs: Brzil, Cmbodi, Chin, Ethiopi, Indi, Mynmr, the Philippines, Ugnd nd Viet Nm. Between 2 nd 214, TB tretment lone sved 35 million lives mong HIV-negtive people; TB tretment nd ntiretrovirl therpy sved n dditionl 8 million lives mong HIV-positive people. * The underlying cuse of TB deths mong HIV-positive people is clssified s HIV in the interntionl clssifiction of diseses system. The burden of TB disese cn be mesured in terms of incidence (defined s the number of new nd relpse cses of TB rising in given time period, usully one yer), prevlence (defined s the number of cses of TB t given point in time) nd mortlity (defined s the number of deths cused by TB in given time period, usully one yer). This chpter presents the ltest WHO estimtes of TB incidence, prevlence nd mortlity between 199 nd 215. Specil emphsis is given to ssessment of whether 215 tr- gets set in the context of the Millennium Development Gols (MDGs) were chieved t globl level, in the six WHO regions nd in the 22 high TB burden countries (HBCs) tht collectively ccount for bout 8% of the world s TB cses. The trgets were tht incidence should be flling by 215 (MDG trget 6c) nd tht prevlence nd mortlity rtes should be hlved compred with their levels in 199 (Box 2.1). WHO updtes estimtes of the burden of disese cused by TB nnully, using the ltest vilble dt nd nlyticl 8 n GLOBAL TUBERCULOSIS REPORT 215

20 methods. 1,2 Since 26, concerted ef forts hve been mde to improve the vilble dt nd methods used, under the umbrell of the WHO Globl Tsk Force on TB Impct Mesurement (Box 2.1). Notifiction dt re consistently reported by bout 2 countries nd territories ech yer (25 in 214). For this report, direct mesurements of TB mortlity from ntionl or smple vitl registrtion (VR) systems were vilble for 127 countries (up from three countries in 28) nd dt from mortlity surveys were vilble for two countries. Between 29 nd August 215, 18 popultion-bsed surveys of the prevlence of TB disese (of which 12 were first-ever ntionl surveys) were completed. Of these, results from six surveys were finlized in the pst yer (Ghn, Indonesi, Mlwi, Sudn, Zmbi, Zimbbwe), nd dditionl survey results becme vilble for the United Republic of Tnzni. These results re reflected in prevlence estimtes published in this report, nd hve lso llowed improvements to estimtes of TB incidence nd mortlity. Those for Indonesi in prticulr hve hd mjor impct on globl estimtes of TB incidence nd prevlence. A summry of the min updtes to vilble dt nd methods is provided in Box 2.2. The chpter hs five mjor sections. The first three cover estimtes of TB incidence, prevlence nd mortlity in turn, including ssessment of whether the 215 trget ws met. The section on TB mortlity includes estimtes of the lives sved through TB tretment (including the dditionl benefit from ntiretrovirl therpy for HIV-positive TB ptients) between 2 nd 214. The fourth section presents estimtes disggregted by ge nd sex. The fif th nd finl section explins how WHO will updte the current lists of HBCs for the post-215 er. 2.1 TB incidence TB incidence hs never been mesured t ntionl level becuse this would require long-term studies mong lrge cohorts of people (hundreds of thousnds), involving high costs nd chllenging logistics. Notifictions of TB cses provide good proxy indiction of TB incidence in countries tht hve both high-performnce surveillnce systems (for exmple, there is little under-reporting of dignosed cses) nd where the qulity of nd ccess to helth cre mens tht few cses re not dignosed. In the lrge number of countries where these criteri re not yet met, better estimtes of TB incidence cn be obtined from n inventory study (n inventory study is survey to quntify the level of underreporting of detected TB cses; if certin conditions re met, cpture-recpture methods cn lso be used to estimte TB 1 The online technicl ppendix is vilble t 2 It should be highlighted tht these updtes f fect the entire time-series bck to 199. For this reson, estimtes presented in this chpter for supersede those of previous reports nd direct comprisons (for exmple, 213 estimtes in this report nd 213 estimtes in the lst report) re not pproprite. incidence). 3 To dte, such studies hve been undertken in only few countries: exmples include Egypt, Irq, Pkistn nd Yemen. A recent exmple, from the Republic of Kore, is profiled in Box 2.3. The ultimte gol is to directly mesure TB incidence from TB notifictions in ll countries. This requires combintion of strengthened surveillnce, better quntifiction of under-reporting (i.e. the number of cses tht re missed by surveillnce systems) nd universl ccess to helth cre. A TB surveillnce checklist developed by the WHO Globl Tsk Force on TB Impct Mesurement defines the stndrds tht need to be met for notifiction dt to provide direct mesure of TB incidence (Box 2.1). By August 215, totl of 38 countries including 16 HBCs hd completed the checklist (Figure 2.1). Methods currently used by WHO to estimte TB incidence cn be grouped into four mjor ctegories (Figure 2.2). These re: 1. Cse notifiction dt combined with expert opinion bout cse detection gps. Expert opinion, elicited in regionl workshops or country missions, is used to estimte levels of under-reporting nd under-dignosis. Trends re estimted using either mortlity dt, surveys of the nnul risk of infection or exponentil interpoltion using estimtes of cse detection gps for three yers. In this report, this method is used for 12 countries tht ccounted for 51% of the estimted globl number of incident cses in Results from ntionl TB prevlence surveys. Incidence is estimted using prevlence survey results combined with either dynmic model or estimtes of the durtion of disese. This method is used for 19 countries tht ccounted for 46% of the estimted globl number of incident cses in Notifictions in high-income countries djusted by stndrd fctor to ccount for under-reporting nd under-dignosis. This method is used for 73 countries (ll high-income countries except the Netherlnds nd the United Kingdom), which ccounted for 3% of the estimted globl number of incident cses in Results from inventory/cpture-recpture studies. This method is used for 5 countries: Egypt, Irq, the Netherlnds, the United Kingdom nd Yemen. They ccounted for.5% of the estimted globl number of incident cses in 214. Further detils bout these methods re provided in the online technicl ppendix 1 nd in bckground documents prepred for the globl review of methods used to produce TB burden 3 Inventory studies cn be used to mesure the number of cses tht re dignosed but not reported. A guide on inventory studies is vilble t: GLOBAL TUBERCULOSIS REPORT 215 n 9

21 Box globl TB trgets ssessment Bckground Globl trgets for reductions in TB disese burden by 215 were set within the context of the United Ntions Millennium Development Gols (MDGs). The trgets were tht TB incidence should be flling, nd tht TB mortlity nd prevlence rtes should be hlved by 215 compred with their level in 199. The trgets were dopted t regionl nd country levels. The Stop TB Strtegy (26 215) developed by WHO hd the overll gol of chieving these trgets (Chpter 1). Since 25, WHO hs published estimtes of TB incidence, prevlence nd mortlity nd n ssessment of progress towrds 215 trgets in its nnul globl TB report. With 215 mrking the MDG nd globl TB trget dedline, the specil emphsis nd most importnt topic of this 215 globl TB report is n ssessment of whether the 215 trgets were chieved. This ssessment is mde for the world, for the six WHO regions nd for the 22 high-burden countries (HBCs) tht collectively ccount for 8% of TB cses. It is built on the work of the WHO Globl Tsk Force on TB Impct Mesurement. The WHO Globl Tsk Force on TB Impct Mesurement The WHO Globl Tsk Force on TB Impct Mesurement ws estblished in 26, with the im of ensuring tht ssessment of whether 215 trgets were met should be s rigorous, robust nd consensus-bsed s possible. To fulfil this mndte, the Tsk Force greed upon three strtegic res of work: 1. Strengthened surveillnce in ll countries, towrds the ultimte gol of direct mesurement of TB incidence nd TB mortlity using notifiction nd vitl registrtion dt, respectively; 2. Ntionl TB prevlence surveys in 22 globl focus countries; 3. Periodic review nd updting of methods used to trnslte surveillnce nd survey dt into TB disese burden estimtes. A wide rnge of technicl, finncil nd development gencies, countries nd individul experts hve been engged in the work of the Tsk Force, nd full detils cn be found on the Tsk Force website. The Tsk Force s work on strengthened surveillnce hs covered four min topics. These re: " Development of TB surveillnce checklist of stndrds nd benchmrks (with ten core nd three supplementry stndrds). b This cn be used to systemticlly ssess the extent to which surveillnce system meets the stndrds required for notifiction nd vitl registrtion dt to provide direct mesurement of TB incidence nd mortlity, respectively. By August 215, 38 countries including 16 HBCs hd used the checklist (Figure 2.1). " Electronic recording nd reporting. Cse-bsed electronic dtbses re the reference stndrd for recording nd reporting TB surveillnce dt. A guide ws produced in 211, c nd ef forts to introduce such systems hve been supported. " Development of guide on inventory studies to mesure underreporting of detected TB cses, d nd support to such studies in priority countries. One of the min resons for uncertinty in estimtes of TB incidence is tht in mny countries, especilly those with lrge privte sector, cses my be detected but not reported. An inventory study cn be used to quntify the number of cses tht re detected but not reported to ntionl surveillnce systems, nd serve s bsis for ddressing gps in reporting. " Expnded use of dt from vitl registrtion (VR) systems nd mortlity surveys to produce estimtes of the number of TB deths, nd contributions to wider ef forts to promote VR systems. In this report, estimtes of TB mortlity re bsed on such dt sources for 129 countries (Figure 2.15). There hs been substntil success in the implementtion of ntionl TB prevlence surveys. Between 29 nd 215, 18 countries including 15/22 globl focus countries completed survey nd more re scheduled to do so by 216 (Figure 2.11, Figure 2.12). Results from these surveys hve provided lrge body of new evidence bout the burden of TB disese (Box 2.2) nd lso hve importnt policy, progrmmtic nd funding implictions (Box 2.4). A Tsk Force subgroup undertook mjor review nd updte of methods between June 28 nd October 29. Recommendtions were endorsed t full meeting of the Tsk Force in Mrch 21. A second thorough nd comprehensive review of these methods s well s possible lterntives ws undertken in 215, with the purpose of reching consensus on methods to be used for reporting in the 215 globl TB report on whether 215 trgets were met. The key recommendtion from the group of experts ws tht existing methods should be used the consensus ws to finish the cycle with estblished methods. e Looking forwrd: TB burden estimtes post-215 The End TB Strtegy includes mbitious trgets for reductions in TB incidence nd TB mortlity (Chpter 1). During the expert review of current methods used to estimte these indictors, there ws strong greement tht the min gol is to strengthen TB surveillnce so tht TB cses nd TB deths cn be directly mesured using notifiction nd vitl registrtion systems. e Therefore, the Tsk Force strtegic re of work relted to strengthened surveillnce needs to be continued. In the interim, for countries without high-performnce surveillnce systems, options for improving current methods tht were identified included the use of new sttisticl models, use of dynmic models (especilly for estimtion of TB incidence in countries with recent prevlence survey dt), nd implementtion of more inventory studies to mesure under-reporting. It ws lso greed tht strtegic selection of priority countries in which repet prevlence surveys should be done to mesure trends is importnt. b c d e Electronic recording nd reporting for TB cre nd control. Genev, World Helth Orgniztion, 211 (WHO/HTM/TB/211.22). Avilble t Assessing tuberculosis underreporting through inventory studies. Genev, World Helth Orgniztion, 213 (WHO/HTM/TB/212.12). Avilble t: vvv tskforce/meetings/globl_consulttion_meeting_report.pdf 1 n GLOBAL TUBERCULOSIS REPORT 215

22 Box 2.2 Updtes to estimtes of TB disese burden in this report nd updtes tht re nticipted in the ner future UPDATES IN THIS REPORT 1. New dt from ntionl TB prevlence surveys Between October 214 nd August 215, finl results from surveys in Ghn, Indonesi, Mlwi, Sudn, the United Republic of Tnzni, Zmbi nd Zimbbwe becme vilble. The size of Indonesi s popultion nd TB burden mens tht upwrd revisions to estimtes bsed on the prevlence survey f fect globl estimtes of the bsolute number of incident cses (lthough importntly, globl trends in TB incidence re not f fected nd the impct on estimtes of globl TB deths is smll given reltively low cse ftlity rtio in Indonesi). In the other countries, updted estimtes re either higher (Ghn, Mlwi, United Republic of Tnzni, Zmbi) or lower (Sudn, Zimbbwe) thn previous estimtes. Post-survey estimtes re lmost lwys more precise thn erlier estimtes tht were indirectly derived from incidence (Figure B2.2.1). 2. Newly reported dt nd updted estimtes from other gencies New VR dt were reported to WHO between mid-214 nd mid-215 nd some countries mde corrections to historicl dt. UNAIDS published updted HIV estimtes in August 214. The United Ntions Popultion Division published new estimtes in July 215. In most instnces, ny resulting chnges to TB burden estimtes re well within the uncertinty intervls of previously published estimtes, nd trends re generlly consistent. For the first time, estimtes of TB mortlity (HIV-negtive) in Indonesi could be produced using dt from smple vitl registrtion system, f ter djustment for incomplete coverge nd ill-defined cuses of deth. For South Afric, estimtes of TB mortlity (HIV-negtive) were obtined from the Institute of Helth Metrics nd Evlution; these estimtes use dt from the ntionl vitl registrtion system, djusted for widespred miscoding of deths cused by HIV nd TB,,b nd replce previous indirect estimtes derived from TB incidence nd the cse ftlity rtio. FIGURE B2.2.1 Estimtes of TB prevlence (ll ges, ll forms of TB) for 17 countries, before (in blue) nd f ter (in red) results from ntionl prevlence surveys becme vilble. Pnels re ordered ccording to the before-f ter dif ference. Lo PDR Indonesi Cmbodi Thilnd Chin Pkistn Mynmr Asi UR Tnzni Mlwi Ghn Nigeri Zmbi Rwnd Sudn Ethiopi Zimbbwe Gmbi Prevlence per 1 popultion (log scle) Prevlence per 1 popultion (log scle) The wide uncertinty intervl of the post-survey estimte for the United Republic of Tnzni is becuse lbortory chllenges ment tht it ws only possible to directly estimte the prevlence of smer-positive (s opposed to bcteriologiclly confirmed) TB. Afric 3. Updted methods for estimting TB burden In Mrch 215, the WHO Globl Tsk Force on TB Impct Mesurement convened n expert group to review methods for estimting TB disese burden (see Box 2.1). In generl, the meeting recommended tht current methods should be retined, especilly for the purposes of reporting on whether 215 trgets were met. An exception ws methods used to estimte the burden of TB disese mong children, which hve been published by WHO since 213 nd which re not relevnt to reporting on 215 trgets. It ws recommended tht WHO should updte methods used to estimte TB incidence mong children by implementing n ensemble pproch in which estimtes derived from cse notifictions djusted for under-detection nd under-reporting c re combined with estimtes derived from dynmic modelling. d An dditionl recommendtion ws tht HIV-positive TB mortlity in children should be estimted using similr pproch to tht used for disggregting TB/HIV mortlity by sex. Estimtes of childhood TB incidence nd mortlity presented in this report re bsed on these recommendtions. 4. In-depth epidemiologicl reviews t country level Estimtes for Angol were revised bsed on discussions with experts from the NTP nd prtners. They should however be considered preliminry, pending the findings of n ongoing epidemiologicl review. Estimtes for Kzkhstn were updted in Februry 215 following n in-depth review conducted by WHO stf f (hedqurters nd the Regionl Of fice for Europe) in close collbortion with the Ministry of Helth. UPDATES ANTICIPATED IN THE NEAR FUTURE Updtes to estimtes of disese burden re expected within the next yer for three countries in which ntionl TB prevlence survey hs been recently completed (Ugnd, July 215) or is scheduled for completion round the end of 215 (Bngldesh, Mongoli). Estimtes of TB incidence my be updted following the implementtion of inventory studies to mesure underreporting of detected TB in Chin, Indonesi, the Philippines, Thilnd nd Viet Nm. An expert review of methods used to estimte the burden of MDR-TB is scheduled for 216. b c d Murry C, Ortbld K, Guinovrt C et l. Globl, regionl, nd ntionl incidence nd mortlity for HIV, tuberculosis, nd mlri during : systemtic nlysis for the Globl Burden of Disese Study 213. Lncet 214; 384: Groenewld P, Nnnn N, Bourne D et l. Identifying deths from AIDS in South Afric. AIDS 25; 19: Jenkins H, Tolmn A, Yuen C et l. Incidence of multidrug-resistnt tuberculosis disese in children: systemtic review nd globl estimtes. Lncet 214; 383: Dodd P, Grdiner E, Coghln R et l. Burden of childhood tuberculosis in 22 high-burden countries: mthemticl modelling study. Lncet Glob Helth 214; 2: e GLOBAL TUBERCULOSIS REPORT 215 n 11

23 n FIGURE 2.1 Countries tht hd completed systemtic ssessment of TB surveillnce using the WHO TB surveillnce checklist of stndrds nd benchmrks by August 215 High-burden countries (16) Other countries (22) n FIGURE 2.2 Min method used to estimte TB incidence Min method Cse notifictions, expert opinion Prevlence survey Cse notifictions, stndrd djustment Cpture recpture No dt Not pplicble In the first method, cse notifiction dt re combined with expert opinion bout cse detection gps (under-reporting nd under-dignosis), nd trends re estimted using either mortlity dt, repet surveys of the nnul risk of infection or exponentil interpoltion using estimtes of cse detection gps for three yers. For ll high-income countries except the Netherlnds nd the United Kingdom, notifictions re djusted by stndrd mount or mesure of under-reporting from inventory studies, to ccount for cse detection gps. For further detils bout ll four methods, see text. 12 n GLOBAL TUBERCULOSIS REPORT 215

24 Box 2.3 Low level of under-reporting of detected TB cses in the Republic of Kore A ntionl cse-bsed nd internet-bsed TB notifiction system is key element of the NTP in the Republic of Kore, linked to the initition of response mesures including outbrek investigtions, evlution of contcts nd TB cse mngement. The online TB reporting system ws estblished in 2. All TB ptients who re treted in public helth centres re notified to the Kore Ntionl TB Surveillnce System (KNTSS). In 26, ntionl survey found tht only 67.6% of ptients dignosed nd treted in the privte sector were notified, despite legl frmework mking notifiction of TB cses mndtory. Since 28, the coverge of routine TB surveillnce hs been systemticlly ssessed using record-linkge of medicl records from the Ntionl Helth Insurnce (NHI) system nd records from the KNTSS dtbse. b Ntionl identifiction numbers re used for record-linkge. Dt on levels of under-reporting of TB cse notifictions in 212 nd 213 re presented in Tble B Under-reporting ws defined s filing to report detected cse within 6 months. TABLE B2.3.1 Under-reporting of detected TB cses in the Republic of Kore Ntionl helth insurnce system Ntionl TB surveillnce system Under-reporting 11.5% 6.7% Under-reporting to the ntionl TB surveillnce system ws found to be lower when cses were dignosed in generl hospitls (8%, ) compred with privte clinics (24%). A regultion is being put in plce tht mkes reimbursement from the ntionl helth insurnce system conditionl upon notifiction of cses by prescribing physicins, s prt of 5-yer pln for TB elimintion ( ). In 211, the ntionl helth insurnce system covered 9% of medicl expenses relted to TB, nd reimbursement coverge is plnned to rech 1% for TB ptients in 216. The new regultion regrding conditionl reimbursement nd the plnned increse in coverge of helth insurnce to 1% for TB ptients should ensure close to zero level of under-reporting of detected cses in the ner future. b WJ Lew, EG Lee, JY Bi et l. An Internet-bsed surveillnce system for tuberculosis in Kore. Int J Tuberc Lung Dis, 26; 1: YS Prk, SJ Hong, YK Boo et l. The ntionl sttus of tuberculosis using ntionwide medicl records survey of ptients with tuberculosis in Kore. Tuberc Respir Dis (Seoul), 212; 73: estimtes tht ws held 31 Mrch 2 April 215 (Box 2.1). 1,2 In 214, there were n estimted 9.6 million incident cses of TB (rnge, 9.1 million 1. million) 3 globlly, equivlent to 133 cses per 1 popultion (Tble 2.1, Tble 2.2). The bsolute number of incident cses is flling slowly (Figure 2.3), t n verge rte of 1.5% per yer nd 2.1% between 213 nd 214. The cumultive reduction in the TB incidence rte ws 18%. Most of the estimted number of cses in 214 occurred in Asi (58%) nd the Africn Region (28%); 4 smller proportions of cses occurred in the Estern Mediterrnen Region (8%), the Europen Region (3%) nd the Region of the Americs (3%). The 22 HBCs tht hve been given highest priority t the globl level since 2 (listed in Tble 2.1 nd Tble 2.2) ccounted for 83% of ll estimted incident cses worldwide. The six countries tht stnd out s hving the lrgest number of incident cses in 214 were Indi, Indonesi, Chin, Nigeri, Pkistn nd South Afric; these nd the other five countries tht mke up the top ten in terms of numbers of cses re highlighted in Figure 2.4. Indi, Indonesi nd Chin lone ccounted for combined totl of 43% of globl cses in 214. The 9.6 million incident TB cses in 214 included 1.1 million 1.3 million (11 13%) mong people living with HIV, with best estimte of 1.2 million (12%) (Tble 2.1, Tble 2.2). The proportion of TB cses co-infected with HIV ws highest in countries in the Africn Region (Figure 2.5). Overll, 32% of TB cses were estimted to be co-infected with HIV in this region, which ccounted for 74% of TB cses mong people living with HIV worldwide. In prts of southern Afric, more thn 5% of TB cses were co-infected with HIV (Figure 2.5). Following systemtic review of evidence bout mortlity cused by MDR-TB undertken in 213 nd consensus bout wht indictors to use for reporting on the burden of MDR-TB, 5 this report includes updted globl estimtes of MDR-TB incidence nd mortlity. The best estimte is tht there were 48 (rnge, 36 6 ) new cses of MDR-TB worldwide in 214 (see lso Chpter 4). This totl includes cses of primry nd cquired MDR-TB. The number of incident TB cses reltive to popultion size (the incidence rte) vries widely mong countries (Figure 2.6, Figure 2.7). The lowest rtes re found predominntly in high-income countries including most countries in western Europe, Cnd, the United Sttes of Americ, Austrli nd New Zelnd. In these countries, the incidence rte is less thn 1 cses per 1 popultion per yer. Most countries in the Region of the Americs hve rtes below 5 per 1 popultion per yer nd this is the region with 1 The online technicl ppendix is vilble t 2 All bckground documents re vilble t dvisory_bodies/impct_mesurement_tskforce/meetings/ consulttion_pril_215_tb_estimtes_subgroup/en/ 3 Rnge refers here nd elsewhere to the 95% uncertinty intervl. 4 Asi refers to the WHO Regions of South-Est Asi nd the Western Pcific. 5 See Box 5.3, Chpter 5 in the 214 globl TB report. GLOBAL TUBERCULOSIS REPORT 215 n 13

25 n TABLE 2.1 Estimted epidemiologicl burden of TB, 214. Best estimtes re followed by the lower nd upper bounds of the 95% uncertinty intervl. Numbers in thousnds. b c POPULATION MORTALITY b HIV-POSITIVE TB MORTALITY PREVALENCE INCIDENCE HIV-POSITIVE INCIDENT TB CASES Afghnistn < Bngldesh c Brzil Cmbodi Chin DR Congo Ethiopi Indi Indonesi Keny Mozmbique Mynmr Nigeri Pkistn Philippines < Russin Federtion South Afric Thilnd Ugnd UR Tnzni Viet Nm Zimbbwe High-burden countries AFR AMR EMR EUR SEAR WPR Globl Numbers for mortlity, prevlence nd incidence shown to two significnt figures. Totls (HBCs, regionl nd globl) re computed prior to rounding. Mortlity excludes deths mong HIV-positive TB cses. Deths mong HIV-positive TB cses re clssified s HIV deths ccording to ICD-1 nd re shown seprtely in this tble. For Bngldesh, joint ressessment of estimtes of TB disese burden will be undertken following completion of the ntionl TB prevlence survey. 14 n GLOBAL TUBERCULOSIS REPORT 215

26 n TABLE 2.2 Estimted epidemiologicl burden of TB, 214. Best estimtes re followed by the lower nd upper bounds of the 95% uncertinty intervl. Rtes per 1 popultion except where indicted. POPULATION (THOUSANDS) MORTALITY HIV-POSITIVE TB MORTALITY PREVALENCE INCIDENCE HIV PREVALENCE IN INCIDENT TB CASES (%) Afghnistn Bngldesh b Brzil Cmbodi Chin < DR Congo Ethiopi Indi Indonesi Keny Mozmbique Mynmr Nigeri Pkistn Philippines < Russin Federtion South Afric Thilnd Ugnd UR Tnzni Viet Nm Zimbbwe High-burden countries b AFR AMR EMR EUR SEAR WPR Globl Mortlity excludes deths mong HIV-positive TB cses. Deths mong HIV-positive TB cses re clssified s HIV deths ccording to ICD-1 nd re shown seprtely in this tble. For Bngldesh, joint ressessment of estimtes of TB disese burden will be undertken following completion of the ntionl TB prevlence survey. GLOBAL TUBERCULOSIS REPORT 215 n 15

27 n FIGURE 2.3 Estimted bsolute numbers of TB cses nd deths (in millions per yer), TB incidence 2 TB deths Millions All TB cses Millions TB deths mong HIV-negtive people 2 HIV-positive TB cses TB deths mong HIV-positive people HIV-ssocited deths re clssified s HIV deths ccording to ICD-1. n FIGURE 2.4 Estimted TB incidence: top-ten countries, 214. The rnge shows the lower nd upper bounds of the 95% uncertinty intervl. The bullet mrks the best estimte. Incidence: bsolute numbers Incidence: rtes Indi Lesotho Indonesi South Afric Chin Swzilnd Nigeri Djibouti Pkistn Nmibi South Afric Mozmbique Bngldesh Timor Leste Philippines Gbon DR Congo DPR Kore Ethiopi Ppu New Guine Millions Rte per 1 popultion per yer the lowest burden of TB on verge. Most of the HBCs hve rtes of round 15 3 cses per 1 popultion per yer (Tble 2.2, Figure 2.7); HBCs with mrkedly lower rtes in 214 were Brzil, Chin nd the Russin Federtion, while rtes were bove 5 per 1 popultion in Mozmbique nd South Afric. Other countries in the top ten worldwide in terms of incidence rtes in 214 re shown in Figure 2.4. Globlly, the incidence rte ws reltively stble from 199 up until round 2, nd then strted to fll (Figure 2.8), chieving the MDG trget fr hed of the 215 dedline. The MDG trget hs lso been met in ll six WHO regions nd in 16 of the 22 HBCs (Figure 2.9, Figure 2.1, Tble 2.3). 2.2 TB prevlence In countries with reltively high burden of TB (round 1 cses per 1 popultion or more), the prevlence of bcteriologiclly-confirmed pulmonry TB cn be directly mesured in ntionwide popultion-bsed surveys using smple sizes of round 5 people. Survey results cn be used to produce ntionl estimte of TB prevlence tht includes ll forms of TB. The cost of survey usully rnges from US$ 1 to 4 million, nd comprehensive theoreticl nd prcticl guidnce on survey design, implementtion, 16 n GLOBAL TUBERCULOSIS REPORT 215

28 n TABLE trgets ssessment: globl, WHO regions nd 22 high-burden countries b GLOBAL INDICATORS AND 215 TARGETS INDICATOR TB INCIDENCE RATE TB PREVALENCE RATE TB MORTALITY RATE TARGET INCIDENCE RATE FALLING 5% REDUCTION IN PREVALENCE RATE BY 215 COMPARED WITH 199 5% REDUCTION IN MORTALITY RATE BY 215 COMPARED WITH 199 Globl Met Almost met Almost met WHO REGION Africn (AFR) Met Not met Not met Americs (AMR) Met Met Met Estern Mediterrnen (EMR) Met Not met Met Europen (EUR) Met Not met Not met South-Est Asi (SEAR) Met Met Met Western Pcific (WPR) Met Met Met 22 HIGH-BURDEN COUNTRIES AFR DR Congo Not met Not met Not met Ethiopi Met Met Met Keny Met Not met Not met Mozmbique Not met Not met Almost met Nigeri Not met Not met Not met South Afric Met Not met Not met Ugnd Met Met Met UR Tnzni Met Not met Not met Zimbbwe Met Not met Met AMR Brzil Met Met Met EMR Afghnistn Not met Not met Not met Pkistn Not met Not met Met EUR Russin Federtion Met Not met Not met SEAR Bngldesh b Not met Not met Not met Indi Met Met Met Indonesi Met Not met Not met Mynmr Met Met Met Thilnd Met Not met Almost met WPR Cmbodi Met Met Met Chin Met Met Met Philippines Met Met Met Viet Nm Met Met Met Met (green) mens tht the trget ws chieved before or by the end of 215. Not met (ornge) mens tht the trget will not be chieved by the end of 215. Almost met (light green) mens tht the reduction ws in the rnge 4 49%, ccording to the best estimte. Vlues for 215 were bsed on n lgorithm tht selects the best performing mong fmily of exponentil smoothing vi stte-spce models of the time-series. For Bngldesh, joint ressessment of estimtes of TB disese burden will be undertken following completion of the ntionl TB prevlence survey. GLOBAL TUBERCULOSIS REPORT 215 n 17

29 n FIGURE 2.5 Estimted HIV prevlence in new nd relpse TB cses, 214 HIV prevlence in new TB cses, ll ges (%) No dt Not pplicble n FIGURE 2.6 Estimted TB incidence rtes, 214 Estimted new TB cses (ll forms) per 1 popultion per yer No dt Not pplicble 18 n GLOBAL TUBERCULOSIS REPORT 215

30 n FIGURE 2.7 Globl distribution of estimted TB incidence by rte nd bsolute number, 214. The size of ech bubble is proportionl to the size of the country s popultion. High-burden countries re shown in red. 2 Indi 4 WHO region SEAR Cses per yer (thousnds) 15 1 Chin Indonesi Cses per yer (thousnds) EUR AMR WPR EMR 1 2 Rte per 1 popultion per yer AFR 5 Russin Viet Federtion Nm Nigeri Pkistn Bngldesh South Afric Philippines Democrtic DR Congo Ethiopi People's UR Tnzni Republic Mozmbique Mynmr of Kore Thilnd Keny Cmbodi Afghnistn Zimbbwe Timor-Leste Nmibi Djibouti Swzilnd Lesotho Brzil Ugnd Kiribti Rte per 1 popultion per yer nlysis nd reporting of results is vilble. 1 Repet surveys conducted bout every ten yers llow trends in disese burden to be ssessed. HBCs tht hve completed repet surveys in the lst ten yers include Cmbodi, Chin, the Philippines nd Thilnd. Repet surveys re plnned in Mynmr nd Viet Nm round ; fourth survey is lso plnned in the Philippines in 216. Countries in which surveys hve been implemented or re plnned in the ner future re shown in Figure 2.11 nd Figure In the 199s nd erly 2s, there ws typiclly no or one survey per yer, nd ll the surveys tht were done were in Asi. Between 29 nd 216, n unprecedented number of ntionl TB prevlence surveys hve been or will be conducted, in both Afric nd Asi (Figure 2.12, Box 2.1, Box 2.2). The results nd lessons lerned from one of the most recent surveys, in Indonesi, re highlighted in Box TB prevlence surveys: hndbook. Genev, World Helth Orgniztion, 211 (WHO/HTM/TB/21.17). Avilble t bodies/impct_mesurement_tskforce/resources_documents/ thelimebook/ In low- nd medium-burden countries, smple sizes nd costs for surveys become prohibitively lrge. If survey dt re not vilble, prevlence cn be indirectly estimted s the product of incidence nd the verge durtion of disese, but with considerble uncertinty. Detils bout the methods used to produce estimtes of TB prevlence re provided in the online technicl ppendix nd in bckground documents prepred for the globl review of methods used to produce TB burden estimtes tht ws held 31 Mrch 2 April 215 (Box 2.1). 2,3 There were n estimted 13 million prevlent cses (rnge, 11 million 14 million) of TB in 214 (Tble 2.1), equivlent to 174 cses per 1 popultion (Tble 2.2). By the end of 215, it is estimted tht the prevlence rte will hve fllen 42% globlly since 199, missing the trget (Figure 2.8, Tble 2.3). However, two regions met the trget before 215 (the Region of the Americs nd the Western Pcific Region) nd the South-Est Asi Region reched the trget (ccord- 2 The online technicl ppendix is vilble t 3 All bckground documents re vilble t dvisory_bodies/impct_mesurement_tskforce/meetings/ consulttion_pril_215_tb_estimtes_subgroup/en/ GLOBAL TUBERCULOSIS REPORT 215 n 19

31 Box 2.4 The 213/214 ntionl TB prevlence survey in Indonesi: min results, nd policy, progrmmtic nd funding implictions A ntionl survey of the prevlence of TB disese in Indonesi ws successfully implemented in 213/214 under the ledership of the Ntionl TB Progrmme nd the Ntionl Institute of Helth Reserch nd Development. The min objective of the survey ws to estimte the prevlence of pulmonry TB (bcteriologicllyconfirmed) mong the generl popultion ged 15 yers old. Methods nd min results Survey methods from design through implementtion, nlysis nd reporting of results followed the interntionl recommendtions of the WHO Globl Tsk Force on TB Impct Mesurement. All survey prticipnts were screened for symptoms by interview nd chest X-ry exmintion. Prticipnts with ny current symptom suggestive of TB or rdiologicl lesion(s) in the lung were requested to submit two sputum specimens (one spot nd one erly-morning) tht were exmined by microscopy (AFB) nd culture (LJ solid medi). A totl of people of ll ges were enumerted, from 156 clusters round the country. Of these, there were eligible individuls ged 15 yers old. All eligible individuls were invited to prticipte in the survey, of whom (89%) did so. Of those who prticipted, (23%) screened positive nd were eligible for sputum exmintion. A totl of 426 TB cses were identified by the survey (Figure B2.4.1). The excellent prticiption rte s well s other survey indictors (for exmple, very low levels of missing dt) show tht the survey ws implemented to high stndrd. The TB prevlence rte per 1 popultion ged 15 yers old ws estimted to be 257 (95% CI: 21 33) for smer-positive TB, nd 759 (95% CI: ) for bcteriologiclly-confirmed TB. Cler nd consistent ge nd sex dif ferentils were observed for both smer-positive nd bcteriologiclly-confirmed TB, with higher rtes mong men nd older ge groups (Figure B2.4.2). The finl survey results were used in combintion with other sources of informtion (such s notifiction dt, mortlity dt from smple vitl registrtion system nd previous ntionl TB prevlence surveys) to updte estimtes of the burden of TB disese in Indonesi (Figure B2.4.3). Both survey results nd these updted estimtes were discussed nd greed upon in ntionl consensus meetings involving ll key stkeholders tht were held in September nd October 214. Lessons lerned The key lessons lerned from the survey were: 1. The burden of TB disese in Indonesi is much higher thn previously thought. b Revised figures for 213 re n estimted TB incidence rte of 43 (rnge, ) per 1 popultion nd n estimted prevlence (ll forms of TB, nd including children s well s dults) of 66 (rnge, ) per 1 popultion. The 213/214 survey hs provided more ccurte mesurement of TB disese burden compred with erlier surveys, since unlike previous surveys it included systemtic chest X-ry screening of the entire survey popultion nd bcteriologicl testing for ll those with signs or symptoms suggestive of TB. 2. When nlysed longside results from previous surveys, TB incidence is flling, in line with the MDG trget for TB. TB prevlence nd mortlity re lso flling. In ddition, the cse ftlity rtio (the proportion of incident cses tht die from TB) is estimted t 11%, considerbly better thn the globl verge of 16%. 3. Overll, only bout one third of the estimted 1 million incident cses tht occur ech yer re being detected nd reported to ntionl uthorities. 4. The number of TB ptients receiving tretment in public nd privte hospitls, without linkge or reporting to the ntionl TB progrmme, ws much lrger thn expected. A high proportion of detected cses (bout 5%) hd not been reported. 5. A high proportion of people with TB hd not been detected t the time of the survey, showing serious delys in TB dignosis nd tretment. Policy, progrmmtic nd funding implictions The mjor implictions of survey results, some of which require high-level policy ction, include: 1. TB wrrnts being one of the top helth priorities in Indonesi. 2. Funding needs for TB prevention, dignosis nd tretment re considerbly lrger thn previously thought. Additionl resources will need to be mobilized t ntionl, provincil nd district levels. 3. Expnsion of helth insurnce coverge is crucil to support high qulity TB dignosis nd tretment in public nd privte hospitls (nd in the privte sector in generl), to ensure tht TB disese does not impose finncil burden on ptients nd their households, nd to ensure pproprite cost-recovery for cre providers. 4. The current policy of mndtory cse notifiction needs to be strongly enforced to reduce under-reporting of detected cses. This could be fcilitted by systems tht mke it esier for cre providers to notify cses, such s user-friendly electronic surveillnce system, nd by incentives for reporting (or penlties for not reporting). 5. Screening nd dignostic tools tht hve higher sensitivity thn current symptom screening nd smer microscopy need to be introduced or expnded to help reduce the number of undetected cses in the community, s well s to reduce the possibility of over-dignosis. Exmples include much wider use of chest X-ry screening nd rpid moleculr dignostics. 6. Referrl mechnisms between helth centres nd hospitls in both the public nd privte sectors need to be strengthened nd wreness of TB incresed throughout the popultion nd mong helth cre workers. These mesures will lso help to reduce the number of undetected cses in the community. Conclusions nd next steps The 213/214 ntionl survey of the prevlence of TB disese in Indonesi is one of the highest qulity ntionl TB prevlence surveys conducted to dte, nd the importnce of the evidence it 2 n GLOBAL TUBERCULOSIS REPORT 215

32 FIGURE B2.4.1 Consort digrm of the ntionl TB prevlence survey in Indonesi Enumerted popultion: Not eligible to prticipte: (31.8%) were less thn 15 yers old were resident for less thn 1 month Eligible to prticipte: 76,576 (68.2%) Did not prticipte: (11.3%) Prticipted: (88.7%) Negtively screened: (77.3%) Positively screened, eligible for sputum exmintion: (22.7%) Symptom nd chest X-ry positive: (28.9%) Symptom positive only: (24.9%) Chest X-ry positive only: (43.7%) Other: 4 (2.6%) Did not submit sputum: 35 (2.%): 174 refused, 131 could not produce sputum Submitted t lest one sputum specimen: (98.%) Submitted two sputum specimens: Submitted only one specimen: 573 of which 557 were spot specimens nd 16 were morning specimens No lbortory result: 14 (.1%) Lbortory results were vilble: (99.9%) All lbortory results were norml: At lest one smer ws positive Culture results: MTB: 141 NTM: 14 Negtive: 129 Contmintion: 6 NA: 1 Both smers were negtive Culture results: MTB: 259 NTM: 386 Contmintion: 333 NA: 22 Pnel review Not TB cses 14 7 TB cses: 426 Definite cse: 419 Probble cse: 7 Smer positive TB Bcteriologiclly confirmed TB FIGURE B Overll, nd ge nd sex-specific TB prevlence rtes s mesured in the ntionl TB prevlence survey in Indonesi, with 95% confidence intervls Mle Femle All Mle Femle All Rte per 1 popultion GLOBAL TUBERCULOSIS REPORT 215 n 21

33 FIGURE B2.4.3 Trends in estimted rtes of incidence, prevlence nd mortlity in Indonesi, Lef t pnel: the incidence rte (green) is shown longside notifictions of TB cses (blck). Centre nd right pnels: The horizontl dshed lines represent the Stop TB Prtnership trgets of 5% reduction in prevlence nd mortlity rtes by 215 compred with 199. Shded res represent uncertinty bnds. Incidence Prevlence Mortlity (HIV-negtive) Rte per 1 popultion per yer Rte per 1 popultion 1 5 Rte per 1 popultion per yer hs produced is cler. Following wide dissemintion of findings, results hve been used to help develop the ntionl strtegic pln nd the preprtion of Concept Note required for finncing from the Globl Fund. A survey report hs been finlized nd results will be summrized in pper for peer-reviewed journl. b Tuberculosis prevlence surveys: hndbook. Genev: World Helth Orgniztion; 21 (WHO/HTM/TB/21.17). Avilble t: resources_documents/thelimebook/en/ Other exmples of countries where survey hs shown tht the burden of TB ws higher thn previously include Los PDR (211), Nigeri (212), Ghn (213), Mlwi (213) nd Zmbi (214). ing to the best estimte) in 215 (Figure 2.13). 1 TB prevlence is flling in ll of the other three regions. Among the 22 HBCs, nine re ssessed to hve met the trget of 5% reduction from 199 levels (Figure 2.14, Tble 2.3). 2.3 TB mortlity TB mortlity mong HIV-negtive people cn be directly mesured using dt from ntionl VR systems, provided tht these systems hve high coverge nd cuses of deth re ccurtely coded ccording to the ltest revision of the Interntionl clssifiction of diseses (ICD-1). Smple VR systems covering representtive res of the country (e.g. s in Chin) provide n interim solution. Mortlity surveys cn lso be used to estimte deths cused by TB. In 214, most countries with high burden of TB lcked ntionl or smple VR systems nd few hd conducted mortlity surveys. In the bsence of VR systems or mortlity surveys, TB mortlity cn be estimted s the product of TB incidence nd the cse ftlity rte, or from ecologicl modelling bsed on mortlity dt from countries with VR systems. TB mortlity mong 1 Vlues for 215 were estimted using n lgorithm tht selects the best performing mong fmily of exponentil smoothing vi stte-spce models of the time-series. HIV-positive people is hrd to mesure even when VR systems re in plce becuse deths mong HIV-positive people re coded s HIV deths nd contributory cuses (such s TB) re of ten not relibly recorded. For this 215 report, countryspecific estimtes of TB deths mong HIV-positive people were produced using the Spectrum sof twre tht hs been used for HIV burden estimtes for over decde. Until 28, WHO estimtes of TB mortlity used VR dt for only three countries. This ws substntilly improved to 89 countries in 29; however, most of the dt were from countries in the Europen Region nd the Region of the Americs, which ccounted for less thn 1% of the world s TB cses. In 211, the first use of smple VR dt from Chin nd survey dt from Indi enbled further mjor improvement to estimtes of TB mortlity. For the current report, VR dt of suf ficient coverge nd qulity were vilble for 127 countries (Figure 2.15) including Indonesi nd South Afric for the first time (Box 2.2), nd survey dt were vilble for two countries (Indi nd Viet Nm). The combined totl of 129 countries ccounted for 43% of the estimted number of TB deths globlly in 214. The Africn Region is the prt of the world in which there is the gretest need to introduce or strengthen vitl registrtion system in which cuses of deth re clssified ccording to the ICD system. 22 n GLOBAL TUBERCULOSIS REPORT 215

34 n FIGURE 2.8 Globl trends in estimted rtes of TB incidence ( ), nd prevlence nd mortlity rtes ( ). Lef t: Estimted incidence rte including HIV-positive TB (green) nd estimted incidence rte of HIV-positive TB (red). Centre nd right: The horizontl dshed lines represent the Stop TB Prtnership trgets of 5% reduction in prevlence nd mortlity rtes by 215 compred with 199. Shded res represent uncertinty bnds. Mortlity excludes TB deths mong HIV-positive people. Incidence Prevlence Mortlity Rte per 1 popultion per yer Rte per 1 popultion Rte per 1 popultion per yer n FIGURE 2.9 Estimted TB incidence rtes by WHO region, Estimted TB incidence rtes (green) nd estimted incidence rtes of HIV-positive TB (red). Shded res represent uncertinty bnds. 4 Afric 6 The Americs 15 Estern Mediterrnen Rte per 1 popultion per yer Europe South Est Asi Western Pcific GLOBAL TUBERCULOSIS REPORT 215 n 23

35 Approximtely 9% of totl TB deths (mong HIV-negtive nd HIV-positive people) nd 8% of TB deths mong HIV-negtive people occurred in the Africn nd South-Est Asi Regions in 214. Indi nd Nigeri ccounted for bout one third of globl TB deths (both including nd excluding those mong HIV-positive people). The number of TB deths (mong HIV-negtive people) per 1 popultion verged 16 globlly in 214 (Tble 2.2) nd 21 when TB deths mong HIV-positive people re included. There is considerble vrition mong countries (Figure 2.17), rnging from <1 TB deth per 1 popultion (exmples include most countries in western Europe, Cnd, the United Sttes of Americ, Austrli nd New Zelnd) to more thn 4 deths per 1 popultion in much of the Africn Region s well s five HBCs (Afghnistn, Bngldesh, Cmbodi, Indonesi nd Mynmr). Globlly, the mortlity rte (excluding deths mong HIVn FIGURE 2.1 Estimted TB incidence rtes, 22 high burden countries, Estimted TB incidence rtes (green) nd estimted incidence rtes of HIV positive TB (red). Shded res represent uncertinty bnds. Afghnistn Bngldesh Brzil Cmbodi Chin Rte per 1 popultion per yer DR Congo Ethiopi Indi Indonesi Keny Mozmbique Mynmr Nigeri Pkistn Philippines Russin Federtion South Afric Thilnd Ugnd UR Tnzni Viet Nm Zimbbwe For Bngldesh, joint ressessment of estimtes of TB disese burden will be undertken following completion of the ntionl TB prevlence survey. Detils bout the methods used to produce estimtes of TB mortlity re provided in the online technicl ppendix nd in bckground documents prepred for the globl review of methods used to produce TB burden estimtes tht ws held 31 Mrch 2 April 215 (Box 2.1). 1,2 There were n estimted 1.5 million TB deths in 214 (Tble 2.1, Figure 2.2): 1.1 million mong HIV-negtive people nd 39 mong HIV-positive people (TB deths mong HIV-positive people re clssified s HIV deths in ICD-1). 3 TB rnks longside HIV s leding cuse of deth from n infectious disese (Figure 2.16, Figure 2.16b). 4 1 The online technicl ppendix is vilble t 2 All bckground documents re vilble t dvisory_bodies/impct_mesurement_tskforce/meetings/ consulttion_pril_215_tb_estimtes_subgroup/en/ 3 Interntionl sttisticl clssifiction of diseses nd relted helth problems, 1th revision (ICD-1), 2nd ed. Genev: World Helth Orgniztion; WHO Globl Helth Observtory dt repository, vilble t pps.who.int/gho/dt/node.min.ghecod?lng=en (ccessed 27 August 215). 24 n GLOBAL TUBERCULOSIS REPORT 215

36 n FIGURE 2.11 Countries in which ntionl popultion-bsed surveys of the prevlence of TB disese hve been implemented using currently recommended screening nd dignostic methods since 199 or re plnned in the ner future: sttus in August 215 No ntionl survey plnned Ntionl survey plnned b Ntionl survey ongoing c One ntionl survey completed d Repet ntionl survey plnned 1 repet ntionl survey completed e Not pplicble b c d e Screening methods include field chest X-ry; culture is used to confirm dignosis. A country hs submitted t lest drf t survey protocol nd budget pln to the WHO Globl Tsk Force for TB Impct Mesurement. Countries were implementing field opertions in August 215 or were undertking dt clening nd nlysis. A survey ws conducted in ccordnce with WHO recommendtions s outlined in Tuberculosis prevlence surveys: hndbook (211) nd t lest preliminry report hs been published. A repet ntionl survey is one in which prticipnts were screened with chest X-ry, nd culture exmintion ws used to dignose TB cses. In the Philippines, repet survey is plnned in 216. n FIGURE 2.12 Globl progress in implementing ntionl surveys of the prevlence of TB disese, ctul (22 215) nd expected ( ) Number of surveys Asi GFC Afric GFC Non GFC Globl focus countries (GFC) selected by WHO Globl Tsk Force on TB Impct Mesurement Gmbi DPR Kore Nepl Lo PDR Nigeri Mongoli Mozmbique Ethiopi Rwnd Sudn Zimbbwe Keny South Afric Philippines Cmbodi UR Tnzni Ghn Zmbi Ugnd Philippines Cmbodi Mlysi Indonesi Eritre Thilnd Viet Nm Bngldesh Mynmr Chin Pkistn Thilnd Mlwi Indonesi Bngldesh Viet Nm Mynmr GLOBAL TUBERCULOSIS REPORT 215 n 25

37 n FIGURE 2.13 Estimted TB prevlence rtes , by WHO region. Shded res represent uncertinty bnds. The horizontl dshed lines represent the Stop TB Prtnership trget of 5% reduction in the prevlence rte by 215 compred with 199. Rte per 1 popultion Afric The Americs Estern Mediterrnen Europe South Est Asi Western Pcific n FIGURE 2.14 Estimted TB prevlence rtes , 22 high burden countries. Shded res represent uncertinty bnds. The horizontl dshed lines represent the Stop TB Prtnership trget of 5% reduction in the prevlence rte by 215 compred with 199. Rte per 1 popultion Afghnistn Bngldesh Brzil Cmbodi Chin DR Congo Ethiopi Indi Indonesi Keny Mozmbique Mynmr Nigeri Pkistn Philippines Russin Federtion South Afric Thilnd Ugnd UR Tnzni Viet Nm Zimbbwe For Bngldesh, joint ressessment of estimtes of TB disese burden will be undertken following completion of the ntionl TB prevlence survey. 26 n GLOBAL TUBERCULOSIS REPORT 215

38 n FIGURE 2.15 Countries (in red) for which TB mortlity is estimted using mesurements from vitl registrtion systems (n=127) nd/or mortlity surveys (n=2) n TABLE 2.4 Estimted cse ftlity rtios (CFRs) in the bsence of tretment CATEGORY OF TB CASE CFR (95% UNCERTAINTY INTERVAL) HIV-negtive, not on TB tretment.43 (.28.53) HIV-positive, not on TB tretment or ART.78 (.65.94) positive people) 1 fell 47% between 199 nd 215, nrrowly missing the trget of 5% reduction (Figure 2.8, Tble 2.3). However, two WHO regions met the trget bout ten yers in dvnce of the dedline (the Region of the Americs nd the Western Pcific Region), nd the Estern Mediterrnen nd South-Est Asi Regions reched the trget (ccording to the best estimte) by 215 (Figure 2.18). 2 TB mortlity hs been flling rpidly in the Europen Region since round 25, but not fst enough to rech the trget given the increse in mortlity levels tht occurred during the 199s. In the Africn Region, mortlity is flling but only slowly. Among the 22 HBCs, 11 re ssessed to hve met the 5% reduction trget (Figure 2.19, Tble 2.3). 1 Trends in TB mortlity rtes re restricted to TB deths mong HIV-negtive people, given tht TB deths mong HIV-positive people re clssified s HIV deths in ICD-1. 2 Vlues for 215 were estimted using n lgorithm tht selects the best performing mong fmily of exponentil smoothing vi stte-spce models of the time-series Estimted number of lives sved by TB tretment, The ctul numbers of TB deths (presented bove) cn be compred with the number of TB deths tht would hve occurred in the bsence of TB tretment, to give n estimte of the lives sved by TB interventions. The number of deths tht would hve occurred ech yer in the bsence of TB tretment (nd without ART provided longside TB tretment for HIV-positive cses) cn be conservtively estimted s the number of estimted incident cses (section 2.1) multiplied by the relevnt cse ftlity rtio (Tble 2.4). 3 Estimtes re conservtive becuse they do not ccount for the impct of TB control or ART on the level of TB incidence, or the indirect, downstrem impct of these interventions on future levels of infections, cses nd deths. Between 2 nd 214, TB tretment lone sved n estimted 35 million lives mong HIV-negtive people (Tble 2.5). Among HIV-positive people, TB tretment supported by ART sved n dditionl 8.4 million lives. 2.4 Estimtes disggregted by ge nd sex This section presents estimtes of TB incidence nd TB mortlity disggregted by ge nd sex. Specificlly, estimtes re shown for men (defined s mles ged 15 yers), women 3 Further detils bout methods used to estimte lives sved, including CFRs for dif ferent ctegories of TB cse, re provided in the online technicl ppendix, vilble t GLOBAL TUBERCULOSIS REPORT 215 n 27

39 n TABLE 2.5 Cumultive number of lives sved by TB nd TB/HIV interventions (in millions), globlly nd by WHO region. Best estimtes re followed by 95% uncertinty intervls. HIV-NEGATIVE PEOPLE HIV-POSITIVE PEOPLE TOTAL WHO REGION BEST ESTIMATE UNCERTAINTY INTERVAL BEST ESTIMATE UNCERTAINTY INTERVAL BEST ESTIMATE UNCERTAINTY INTERVAL AFR AMR EMR EUR SEA WPR Globl n FIGURE 2.16 Top cuses of deth worldwide in 212.,b Deths from TB mong HIV-positive people re shown in grey. c Ischemic hert disese Stroke Lower respirtory infections Chronic obstructive pulmonry disese TB Trchel, bronchus, lung cncers Dirrhel diseses n FIGURE 2.16b Estimted number of deths from HIV/AIDS nd TB in 214. Deths from TB mong HIV-positive people re shown in grey.,b TB HIV/AIDS Millions For HIV/AIDS, the ltest estimtes of the number of deths in 214 tht hve been published by UNAIDS re vilble t org/en/resources/documents/215/hiv_estimtes_with_uncertinty_ bounds_ For TB, the estimtes for 214 re those published in this report. b Deths from TB mong HIV-positive people re of ficilly clssified s deths cused by HIV/AIDS in the Interntionl clssifiction of diseses. Dibetes mellitus HIV/AIDS Rod injury Millions This is the ltest yer for which estimtes for ll cuses re currently vilble. See WHO Globl Helth Observtory dt repository, vilble t (ccessed 27 August 215). b For HIV/AIDS, the ltest estimtes of the number of deths in 212 tht hve been published by UNAIDS re vilble t org/en/resources/documents/215/hiv_estimtes_with_uncertinty_ bounds_ For TB, the estimtes for 212 re those published in this report. c Deths from TB mong HIV-positive people re of ficilly clssified s deths cused by HIV/AIDS in the Interntionl clssifiction of diseses. 28 n GLOBAL TUBERCULOSIS REPORT 215

40 n FIGURE 2.17 Estimted TB mortlity rtes excluding TB deths mong HIV positive people, 214 Estimted TB deths per 1 popultion Not pplicble n FIGURE 2.18 Estimted TB mortlity rtes , by WHO region. Estimted TB mortlity excludes TB deths mong HIV-positive people. Shded res represent uncertinty bnds. The horizontl dshed lines represent the Stop TB Prtnership trget of 5% reduction in the mortlity rte by 215 compred with Afric 6 The Americs 4 Estern Mediterrnen Rte per 1 popultion per yer Europe South Est Asi Western Pcific The width of n uncertinty bnd nrrows s the proportion of regionl mortlity estimted using vitl registrtion dt increses or the qulity nd completeness of the vitl registrtion dt improves. GLOBAL TUBERCULOSIS REPORT 215 n 29

41 n FIGURE 2.19 Estimted TB mortlity rtes , 22 high burden countries. Estimted TB mortlity excludes TB deths mong HIV-positive people. The horizontl dshed lines represent the Stop TB Prtnership trget of 5% reduction in the mortlity rte by 215 compred with 199. Uncertinty is due to djustments mde to the mortlity dt from vitl registrtion systems tht were reported by countries (mortlity dt from vitl registrtion systems re represented by the x symbol) Afghnistn Bngldesh b Brzil Cmbodi Chin Rte per 1 popultion per yer DR Congo Ethiopi Indi Indonesi Keny Russin Federtion South Afric Thilnd Ugnd UR Tnzni Viet Nm Mozmbique Mynmr Nigeri Pkistn Philippines Zimbbwe b The width of n uncertinty bnd nrrows s the proportion of regionl mortlity estimted using vitl registrtion dt increses or the qulity nd completeness of the vitl registrtion dt improves. For Bngldesh, joint ressessment of estimtes of TB disese burden will be undertken following completion of the ntionl TB prevlence survey. (defined s femles ged 15 yers) nd children (defined s people ged <15 yers). The cut-of f of 15 yers is used becuse it is consistent with the ge ctegories for which notifiction dt re reported nd with the cut-of f used in current guidelines to define people eligible to prticipte in TB prevlence survey. 1 Detils of the methods used to produce disggregted estimtes re provided in the online technicl ppendix. 2 1 TB prevlence surveys: hndbook. Genev: World Helth Orgniztion; 211 (WHO/HTM/TB/21.17). Avilble t bodies/impct_mesurement_tskforce/resources_documents/ thelimebook 2 The online technicl ppendix is vilble t TB incidence Estimtes of TB incidence mong men nd women were produced by using notifiction dt combined with the ssumption tht the men:women rtio of notified cses (1.7 globlly) 3 ws the sme s the rtio for incident cses. 4 In 214, there were n estimted 5.4 million (rnge, million) incident cses mong men nd 3.2 million (rnge, million) mong women. 3 See lso Tble 3.2 in Chpter 3. 4 Evidence from ntionl prevlence surveys of bcteriologiclly-positive TB consistently show bigger rtios of prevlence to notifictions in men thn women. This mens tht the implicit ssumption mde here, tht there is no sex dif ferentil in the detection of incident cses, my not be correct. With currently vilble dt, it is not possible to estimte mle nd femle cse detection rtios for ll countries, but if nything the estimtes presented in this chpter re underestimting the shre of totl TB incidence tht is ccounted for by men. 3 n GLOBAL TUBERCULOSIS REPORT 215

42 n FIGURE 2.2 Globl progress in reporting of TB cses mong children, Lef t pnel: Number of notifictions of cses mong children reported to WHO. Right pnel: Percentge of cse notifictions reported to WHO tht re ge-disggregted. 4 3 Cse notifictions 14 ge group 4 ge group 5 14 ge group 1 8 Completeness of reporting Number (thousnds) 2 1 Percentge new smer-positive new smer-negtive nd smer not done new extrpulmonry new nd relpse, ll forms Before 213 childhood cse notifictions included smer-positive, smer-negtive, smer not done nd extrpulmonry TB for ll new ptients. Af ter 213 (shown s gp in the grph) childhood cse notifiction include ll new nd relpse cses irrespective of cse type. n FIGURE 2.21 Reporting of new nd relpse TB cse notifictions disggregted by ge, 214 Age disggregtion (new) Age disggregtion (new nd relpse) No ge disggregtion No dt reported Not pplicble GLOBAL TUBERCULOSIS REPORT 215 n 31

43 Box 2.5 Estimting TB incidence mong children: chllenges, progress to dte nd next steps It is well recognized tht estimting the incidence of TB in children is dif ficult nd tht published estimtes vry.,b There re t lest four mjor resons for this: 1. TB in children is rrely bcteriologiclly confirmed. Direct exmintion of sputum smers nd tuberculin skin testing both suf fer from very poor dignostic performnce. TB in children is thus condition tht is usully cliniclly dignosed bsed on combintion of signs nd symptoms tht re not specific to TB. Cse definitions re inconsistent mong countries nd within countries over time (s result of chnges in medicl prctice). 2. Peditricins who dignose TB do not lwys report cses to public helth uthorities. Childhood TB is not usully public helth priority nd ef fective linkges between NTPs nd the hospitls nd clinics where children re usully dignosed re lcking. Reporting of cses is therefore of ten incomplete nd not supported by legl frmework. 3. TB cses mong children re less likely to be dignosed in countries with high burden of TB compred with dults. Sick children my be evluted in fcilities with little to no cpcity to dignose childhood TB, nd dignostic chllenges (the low specificity of clinicl signs nd symptoms) trnslte into low ccess to qulity dignosis nd cre services. 4. Dif ferent methods hve been used to produce estimtes. These include dynmic model nd sttisticl pproches. The estimtes included in this report re bsed on combining results from dynmic model, c sttisticl pproch bsed on recent study, d nd methods previously used by WHO b in sttisticl ensemble model. e Estimtes from the dynmic model nd sttisticl pproches using the most updted dt for 214 were found to be similr. This hs contributed to more robust combined estimte compred with those produced using the dynmic model or sttisticl pproches on their own. In turn, this mens tht the uncertinty intervl from the ensemble pproch is nrrower thn those of estimtes produced from ech pproch used on its own. Nonetheless, the uncertinty intervl reltive to the best estimte is bout twice s lrge s the reltive uncertinty of the overll TB incidence estimte for ll ges. The lck of overlp between the estimte of childhood TB incidence in this report nd the one published in the 214 edition b illustrtes the dif ficulties in producing such estimtes (explined bove) nd limittions in the documenttion of uncertinty. The estimtes in this report use n updted methodologicl pproch recommended by the WHO Globl Tsk Force on TB Impct Mesurement (Box 2.1, Box 2.2). However, even using this pproch does not llow ll sources of uncertinty, such s uncertinty due to model specifiction, to be fully quntified in prctice. The vribility nd lck of stbility in recently published estimtes of TB incidence mong children is concerning. Addressing this chllenge requires much greter commitment from ntionl public helth uthorities to the definition nd ppliction of consistent cse definitions, to ensuring reporting of cses bsed on legl frmework nd ensuring tht children who re close contcts of people with TB re thoroughly investigted using up-to-dte ntionl recommendtions. JA Seddon nd D Shingdi. Epidemiology nd disese burden of tuberculosis in children: globl perspective. Infect Drug Resist, 7:153 65, null 214. World Helth Orgniztion. Globl tuberuclosis report 214. World Helth Orgniztion, Genev; 214. (WHO/HTM/TB/214.8). See prticulrly Box 2.5 in Chpter 2. PJ Dodd, E Grdiner, R Coghln, nd JA Seddon. Burden of childhood tuberculosis in 22 high-burden countries: mthemticl modelling study. Lncet Glob Helth 214; 2:e HE Jenkins, AW Tolmn, CM Yuen et l. Incidence of multidrugresistnt tuberculosis disese in children: systemtic review nd globl estimtes. Lncet, 214; 383: For detils, see the online technicl ppendix to this report t www. who.int/tb/dt. b c d e Globl progress in reporting of cses mong children since 1995 (the first yer in which such dt were requested for the 14 ge group) nd since 25 (when further disggregtion for those ged 4 nd 5 14 ws requested) is shown in Figure 2.2. By 214, reporting of ge-disggregted notifiction dt ws lmost universl (Figure 2.21). In 214, 359 new nd relpse cses mong children were reported, n increse of bout 3% compred with 213. The lrgest increses were in Indi (bout 3 ) nd the Philippines (bout 1 ). Cmbodi nd Mynmr reported ge-disggregted dt for the first time. Producing estimtes of TB incidence mong children is chllenging (Box 2.5). However, progress is being mde, bsed on collbortions estblished in 213 between WHO nd cdemic groups working on the estimtion of TB disese burden mong children, s well s recommendtions from globl consulttion held erlier in 215 (Box 2.1, Box 2.2). Methods to estimte TB incidence in children were updted for this report compred with those used to produce estimtes published in 213 nd 214. The updted methods involve use of n ensemble pproch in which results from two independent methods re combined. The first method is bsed on the WHO pproch used since 212, with the modifiction tht child-specific cse detection rtios (s opposed to one rtio for ll ges) re used ccording to previously published methods 1 tht were updted to use more recent notifiction dt. 2 The second method is 1 HE Jenkins, AW Tolmn, CM Yuen et l. Incidence of multidrug-resistnt tuberculosis disese in children: systemtic review nd globl estimtes. Lncet, 214; 383: This is in line with WHO suggestions documented in 214. See Sismnidis C, Lw I, Glziou P,et l. The burden of tuberculosis disese in children. Lncet. 214; 384(9951):1343. doi: 1.116/S (14) n GLOBAL TUBERCULOSIS REPORT 215

44 n FIGURE 2.22 The mle:femle rtios of TB deths mong dults (ged 15 yers), globlly nd by WHO region HIV-negtive HIV-positive AFR AMR EMR EUR SEAR WPR Globl Sex Rtio (M:F) Sex Rtio (M:F) dynmic model tht uses dult TB prevlence estimtes nd prmeters relted to the nturl history of TB in children. Globl nd regionl estimtes of TB incidence mong children using this ensemble pproch re shown in Tble 2.6. The totl estimted number of incident cses in 214 ws 1 million, with CDR of 36%. The Africn nd South-Est Asi Regions ccount for bout one third of globl cses ech TB mortlity To produce estimtes of TB deths mong HIV-negtive dults, mortlity dt from VR systems disggregted by ge nd sex were used. Dt were vilble for 113 countries (ll middle or high-income countries). For countries without VR dt, estimtes were produced using n imputtion model tht included risk fctors known to be ssocited with TB mortlity. This model ws used to estimte the rtios of the mle to femle nd child to dult number of TB deths. TB deths mong HIV-positive people were disggregted by sex nd ge using the ssumption tht the mle to femle nd children to dult rtios re similr to the corresponding rtios of AIDS deths estimted by UNAIDS. TB deths mong HIV-negtive people There were n estimted 7 TB deths mong HIVnegtive men nd 34 mong HIV-negtive women in 214 (Tble 2.7). The mle: femle rtio ws lso bove two in ll six WHO regions (lef t pnel of Figure 2.22). There were n dditionl 81 (rnge, ) TB deths mong HIV-negtive children, equivlent to 7% of the totl number of HIV-negtive TB deths. n TABLE 2.6 Estimted number of incident cses of TB mong children in 214, globlly nd by WHO region WHO REGION NUMBER OF TB CASE NOTIFICATIONS BEST ESTIMATE ESTIMATED TB INCIDENCE UNCERTAINTY INTERVAL AFR AMR EMR EUR SEAR WPR Globl n TABLE 2.7 Estimted number of TB deths mong HIV-negtive dults disggregted by sex, globlly nd by WHO region WHO REGION BEST ESTIMATE WOMEN UNCERTAINTY INTERVAL BEST ESTIMATE MEN UNCERTAINTY INTERVAL AFR AMR EMR EUR SEAR WPR Globl TB deths mong HIV-positive people There were n estimted 19 TB deths mong HIV-positive men nd 14 mong HIV-positive women in 214 GLOBAL TUBERCULOSIS REPORT 215 n 33

45 n TABLE 2.8 Estimted number of TB deths mong HIV-positive dults disggregted by sex, globlly nd by WHO region WHO REGION BEST ESTIMATE WOMEN UNCERTAINTY INTERVAL BEST ESTIMATE MEN UNCERTAINTY INTERVAL AFR AMR EMR EUR SEA WPR World (Tble 2.8). Most of these deths were in the Africn Region, where the mle:femle rtio ws close to one (right pnel of Figure 2.22). The mle:femle rtio in other regions vried from round 2 4, with best estimtes of There were n dditionl 55 (rnge, 5 6 ) TB deths mong HIV-positive children, equivlent to 14% of the totl number of HIV-positive TB deths. The totl number of TB deths mong children (136, rnge ) corresponds to CFR of 13.6% (compred with 15.5% in dults). 2.5 HBC lists to be used by WHO in the post-215 er Bckground nd brief history The concept of high burden country hs become very fmilir nd widely used in the context of TB. The initil definition of HBCs in 1998 ws bsed on the burden of TB in bsolute terms. Its purpose ws to llow focused interventions in the countries responsible for 8% of the globl burden (mesured in terms of the estimted number of incident cses), since progress in these countries would trnslte into globl impct. The concept ws subsequently pplied to TB/HIV (in 25) nd MDR-TB (in 28). The current list of 22 HBCs (fetured throughout this chpter) hs not chnged since 22, nd the HBC lists for TB/HIV nd MDR-TB hve not been updted since 29 nd 28, respectively. 1 With the end of the MDGs nd Stop TB Strtegy in 215 nd the trnsition to new er of Sustinble Development Gols (SDGs) nd the End TB Strtegy (Chpter 1), 215 ws the idel yer in which to revisit ll three HBC lists nd consider their future. 1 For the TB/HIV list, see Tble 6.1 in Chpter 6. For the MDR-TB list, see Tble 4.1 in Chpter Process used to revisit HBC lists nd their use post-215 The process of revisiting HBC lists strted with the development of discussion pper by the Globl TB Progrmme in WHO. This provided brief history of the current HBC lists, nd identified their potentil dvntges nd disdvntges, drwing on input provided from cross the WHO TB network, by mjor globl technicl nd finncil gencies, nd by individuls who plyed leding role in the originl estblishment nd definition of ech list. An online survey ws then conducted in My 215, focused on elicittion of feedbck bout the dvntges nd disdvntges of the lists, principles nd design chrcteristics relted to their use post-215, nd which of four high-level options for the use of lists f ter 215 ws preferred. 2 Bsed on feedbck received on the discussion pper nd the results of the online survey, proposl ws then presented for considertion by WHO s Strtegic nd Technicl Advisory Group for TB (STAG-TB) in June 215. Full detils re vilble in the discussion pper prepred for the STAG-TB meeting Proposl presented to STAG-TB, June 215 The proposl presented t the June 215 meeting of STAG-TB cn be summrized s follows: "" Three updted lists, for ech of TB, MDR-TB nd TB/HIV. "" Ech list includes 3 countries, defined s the top 2 in terms of bsolute numbers of cses, plus the 1 countries with the most severe burden in reltive terms tht do not lredy pper in the top 2 ( 2+1 ). "" Two options for defining the dditionl top ten tht hve severe burden in reltive terms were presented for considertion. The first ws to use rtes per cpit for the TB list, nd the proportion of TB cses with MDR-TB nd TB/ HIV for the other two lists. The second ws to use rtes per cpit for ll three lists. It ws lso recognized tht for the dditionl top ten, threshold in terms of minimum number of cses ws relevnt. The TB list with nd without threshold of 1 cses ws presented. "" A lifetime of five yers for ll three lists, The STAG-TB recognized the vlue of HBC lists nd endorsed the proposl for three 2+1 lists tht would hve lifetime of five yers. It ws recommended to use rtes per cpit to define the dditionl top-ten countries, nd to lso use 2 These were: 1) Discontinue the use of HBC lists; 2) Continue to use three HBC lists (TB, MDR-TB, TB/HIV) but updte them using the originl criteri; 3) Continue to use three HBC lists (TB, MDR-TB, TB/HIV) but define them using new criteri; 4) Define one HBC list only. 3 World Helth Orgniztion. Use of high TB burden country lists in the post-215 er. Genev: World Helth Orgniztion; 215. (Discussion pper). Avilble t: This document ws updted in August 215 to reflect the recommendtions provided during the STAG-TB meeting nd to use the ltest estimtes of disese burden prepred for this report. 34 n GLOBAL TUBERCULOSIS REPORT 215

46 threshold for minimum number of cses. It ws noted tht countries with high rtes but smll numbers of cses re best included s prt of regionl HBC lists (if such lists re considered useful t tht level) Definition of HBC lists to be used by WHO post-215, nd ssocited next steps Following the STAG-TB meeting, the Globl TB Progrmme finlized the definition of the HBC lists to be used by WHO post-215, s follows: "" Three HBC lists, one for ech of TB, MDR-TB nd TB/HIV. "" Ech list includes 3 countries, defined s the top 2 in terms of bsolute numbers nd n dditionl ten tht hve the highest rtes per cpit nd tht re not lredy prt of the top 2. 1 For inclusion in the lists on the bsis of rtes, countries must lso hve minimum of 1 incident cses per yer (for the TB list) or 1 cses per yer (for the TB/HIV nd MDR-TB lists). "" The estimtes of TB disese burden used to define the lists re the most up-to-dte estimtes vilble in 215 i.e. those published in this 215 globl TB report. "" The lists will hve lifetime of five yers, In ech list, the resulting list ccounts for 86 9% of the globl number of cses. There re two mjor next steps in 215. The first is further communiction by the Globl TB Progrmme to WHO Member Sttes, technicl prtners nd funding gencies bout the finl definition of the lists. The second is meeting to be held on 3 November in ssocition with the interntionl conference on TB nd lung diseses (orgnized by the Union in Cpe Town, South Afric). This will focus on implementtion of the End TB Strtegy (Chpter 1) with prticulr ttention to the 3 countries in the new HBC list for TB. Strting in 216, the new lists of 3 HBCs for TB, TB/HIV nd MDR-TB will be used by WHO, including in the next edition of the globl TB report. 1 Some countries with the highest numbers in bsolute terms lso rnk in the top ten in terms of rtes. GLOBAL TUBERCULOSIS REPORT 215 n 35

47 CHAPTER 3 TB cse notifictions nd tretment outcomes Key fcts nd messges 215 is lndmrk yer in globl monitoring of TB cse notifictions nd tretment outcomes by WHO: it is twenty yers since system for nnul collection of these dt from ll countries ws estblished in Between 1995 nd 214, dt compiled vi this system show tht cumultive totl of 78 million cses of TB were notified to WHO nd 66 million TB ptients were successfully treted. In 214, 6.3 million cses of TB were notified by ntionl tuberculosis progrmmes (NTPs) nd reported to WHO: just over 6 million individuls were newly dignosed in 214 nd 261 were previously dignosed TB ptients whose tretment regimen ws chnged. In 214, most notified TB cses were dults. Children (ged <15 yers) ccounted for 6.5% of notified cses, rnging from 3.4% in the Western Pcific Region to 9.5% in the Estern Mediterrnen Region. The mle:femle rtio of notified cses cross ll ge groups ws 1.7 globlly, rnging from 1. in the Estern Mediterrnen Region to 2.1 in the Western Pcific Region. Among pulmonry TB cses, 58% were bcteriologiclly confirmed (s opposed to cliniclly dignosed) in 214; this ws unchnged from 213. For the first time since 27, there ws noticeble increse in globl TB notifictions in 214 (these hd stbilized t round million new nd relpse cses for ). The increse is explined by 29% increse in notifictions in Indi, linked to the introduction of policy of mndtory notifiction, new web-bsed nd cse-bsed reporting system tht hs been rolled out ntionwide nd greter enggement of the country s lrge privte helth sector. Indi ccounted for 27% of globl TB notifictions in 214, followed by Chin (14%). The privte helth sector, providers of helth services in the public sector tht re not directly linked to NTPs nd community workers or volunteers cn mke importnt contributions to the notifiction nd tretment of TB cses. For exmple, 12% of notifictions in Indi were from the privte sector in 214, nd 55% of notifictions in Chin were from public hospitls outside the NTP network. In six of 41 countries tht reported dt, more thn 5% of notifictions were from community referrls in res where community enggement ctivities were in plce. Globlly, notifictions of newly dignosed TB cses in 214 represented 63% (95% uncertinty intervl, 6 66%) of estimted incident cses. The best estimte of the gp between notifictions of new episodes of TB (new nd relpse cses) nd incident cses ws 3.6 million cses. Two fctors explin gps between notifictions nd estimted incidence. The first is under-reporting of dignosed TB cses: for exmple, of cses detected nd treted in the privte sector. The second is under-dignosis. Resons for under-dignosis include poor ccess to helth cre nd filure to detect cses when people with TB visit helth cre fcilities. Intensified ef forts, such s those lredy being mde in Indi, re needed to ensure tht ll cses re detected, notified to ntionl surveillnce systems, nd treted ccording to interntionl stndrds. Globlly in 213, the tretment success rte for new cses of TB ws 86%. Improvement in tretment outcomes is needed in the Region of the Americs nd the Europen Region, where tretment success rtes in 213 were 75% nd 76%, respectively. The mngement of ltent TB infection (LTBI) is criticl component of the new post-215 End TB Strtegy, nd WHO issued guidnce for upper-middle nd high-income countries with n incidence rte of less thn 1 per 1 popultion in 215. In mny of these countries, LTBI policies re in plce nd detection nd tretment is being provided. However, there re lso policy-prctice gps tht need to be ddressed nd systems for routine recording nd reporting of dt need to be improved. Routine recording nd reporting of the numbers of TB cses dignosed nd treted by ntionl TB progrmmes (NTPs) nd monitoring of tretment outcomes ws one of the five components of the globl TB strtegy (DOTS) lunched by WHO in the mid-199s; this remined core element of its successor, the Stop TB Strtegy (26 215), nd is prt of the new End TB Strtegy (Chpter 1). With the stndrd definitions of cses nd tretment outcomes recommended by WHO nd ssocited recording nd reporting frmework s foundtion, the number of people dignosed nd treted for TB nd ssocited tretment outcomes is routinely monitored by NTPs in lmost ll countries, which in turn report these dt to WHO in nnul rounds of globl TB dt collection (Chpter 1). 215 is lndmrk yer in globl monitoring of TB cse notifictions nd tretment outcomes by WHO: it is twenty yers since system for nnul collection of these 36 n GLOBAL TUBERCULOSIS REPORT 215

48 dt from ll countries ws estblished in Between 1995 nd 214, dt compiled vi this system show tht cumultive totl of 78 million cses of TB were notified to WHO nd 66 million TB ptients were successfully treted. 1 This chpter hs six prts. Section 3.1 summrizes the totl number of people dignosed with TB nd notified by NTPs in 214; these numbers re lso disggregted by cse type, ge nd sex. Section 3.2 presents nd discusses the specific contribution to totl cse notifictions of public public nd public privte mix (PPM) inititives. Section 3.3 highlights the role of community enggement in TB detection nd tretment. Section 3.4 presents trends in notifictions between 199 nd 214 nd compres these with trends in estimted TB incidence. The rtios of notified to estimted incident cses (n indictor known s the cse detection rte or CDR) re provided for selected yers. Section 3.5 describes the ltest dt on tretment outcomes (for cses registered for tretment in 213) s well s tretment outcomes chieved in selected yers since Section 3.6, the finl prt of the chpter, introduces new topic to the globl TB report: policy nd prctices relted to tretment of ltent TB infection (LTBI). This is core component of the End TB Strtegy, which covers the period (Chpter 1). 3.1 Cse notifictions in 214 by type of disese, ge nd sex Box 3.1 lists the definitions of TB cses recommended by WHO s prt of n updted recording nd reporting frmework issued in Mrch 213, 2 nd tht were used in the 214 nd 215 rounds of globl TB dt collection. These updted definitions were necessry to ccommodte dignosis using Xpert MTB/RIF nd other WHO-endorsed moleculr tests (Chpter 5), s well s of fering n opportunity to improve spects of the previous (26) frmework, such s inclusion of more comprehensive reporting of TB cses mong children. Notifictions of TB cses in 214 re summrized globlly, for the six WHO regions nd for the 22 high TB-burden countries (HBCs) in Tble 3.1. In 214, 6.3 million people with TB were notified to NTPs nd reported to WHO. Of these, just over 6 million hd new episode of TB (shown s the totl of new nd relpse cses) nd 261 hd lredy been dignosed with TB but their tretment ws chnged to retretment regimen. For the first time since 27, there ws noticeble increse in globl TB notifictions in 214, which hd previously stbilized t million new nd relpse cses for the seven yers from (Figure 3.1). The increse is mostly explined by 29% increse in notifictions in Indi, linked to the introduction of policy of mndtory notifiction, new web-bsed nd cse-bsed reporting system tht 1 These figures re for new nd relpse cses. See Box 3.1 for cse definitions. 2 Definitions nd reporting frmework for tuberculosis 213 revision. Genev, World Helth Orgniztion; 213 (WHO/HTM/TB/213.2). Avilble t: hs been rolled out ntionwide, nd greter enggement of the country s lrge privte helth sector. Indi ccounted for 27% of globl TB notifictions in 214 (Box 3.2, Figure 3.3), up from 22% in 213. The South-Est Asi nd Western Pcific Regions (which include Indi nd Chin, respectively) together ccounted for 63% of notifictions of new nd relpse cses globlly, nd the Africn Region for 21%. The other three regions ccounted for reltively smll proportions of cses. Among pulmonry TB cses, 58% were bcteriologiclly confirmed (s opposed to cliniclly dignosed) in 214; this ws unchnged from 213. In both the Estern Mediterrnen nd Western Pcific regions, the TB epidemic is mrkedly geing one, with progressive increse in the notifiction rte with ge nd pek mong those ged 65 yers old (Figure 3.4). A similr pttern is evident in the South-Est Asi Region. Elsewhere, nd most noticebly in the Africn Region, notifiction rtes in 214 peked in younger dults. Most countries re now ble to report notifictions disggregted by both ge nd sex (Tble 3.2). In 214, dults ccounted for most of the notified cses. Children (ged <15 yers) ccounted for only 6.5% of notifictions, lthough this rnged from 3.4% in the Western Pcific Region to 9.5% in the Estern Mediterrnen Region. The globl mle:femle sex rtio ws 1.7, but mong HBCs this rtio vried from.7 in Afghnistn to 3. in Viet Nm. Vrition mong countries in the child:dult nd mle:femle rtios of cses my reflect rel dif ferences in epidemiology, dif ferentil ccess to or use of helth cre services linked to the NTP, nd/or differentil reporting prctices. Evidence from recent ntionl TB prevlence surveys shows tht the mle:femle rtio for bcteriologiclly-confirmed TB mong dults is typiclly round 2 3 in Asin countries nd 1 2 in Afric, nd tht the rtio of prevlent to notified cses is systemticlly higher mong men thn women (suggesting tht women with TB hve higher chnce of being notified). 3,4 3.2 Contribution of public public nd public privte mix inititives to TB cse notifictions nd tretment support in 214 Ensuring proper dignosis, stndrdized tretment nd prompt notifiction of ll TB cses to NTPs requires collbortion with the full rnge of helth cre providers. Engging ll cre providers in TB cre nd control is component four of the Stop TB Strtegy nd prt of pillr two (of three) of the post-215 End TB Strtegy (Chpter 1). In recent yers, mny countries hve mde con siderble progress in scling up PPM inititives. However, demon- 3 Onozki I, Lw I, Sismnidis C et l. Ntionl tuberculosis prevlence surveys in Asi : n overview of results nd lessons lerned. Trop Med Int Helth 215; 2(9): doi: /tmi Epub 215 Jun 7. 4 WHO nd prtners re prepring pper summrizing results from recent prevlence surveys in Afric. It is nticipted tht this will be published in 216. GLOBAL TUBERCULOSIS REPORT 215 n 37

49 Box 3.1 WHO definitions of TB cses recommended for use since Mrch 213 nd tht were used in the 214 nd 215 rounds of globl TB dt collection Bcteriologiclly confirmed cse of TB A ptient from whom biologicl specimen is positive by smer microscopy, culture or WHO-pproved rpid dignostic test (such s Xpert MTB/RIF). All such cses should be notified, regrdless of whether TB tretment is strted. Cliniclly dignosed cse of TB A ptient who does not fulfil the criteri for bcteriologiclly confirmed TB but hs been dignosed with ctive TB by clinicin or other medicl prctitioner who hs decided to give the ptient full course of TB tretment. This definition includes cses dignosed on the bsis of X-ry bnormlities or suggestive histology nd extrpulmonry cses without lbortory confirmtion. Cliniclly dignosed cses subsequently found to be bcteriologiclly positive (before or f ter strting tretment) should be reclssified s bcteriologiclly confirmed. Cse of pulmonry TB Any bcteriologiclly confirmed or cliniclly dignosed cse of TB involving the lung prenchym or the trcheobronchil tree. Miliry TB is clssified s pulmonry TB becuse there re lesions in the lungs. Tuberculous intr-thorcic lymphdenopthy (medistinl nd/or hilr) or tuberculous pleurl ef fusion, without rdiogrphic bnormlities in the lungs, constitute cse of extrpulmonry TB. A ptient with both pulmonry nd extrpulmonry TB should be clssified s cse of pulmonry TB. Cse of extrpulmonry TB Any bcteriologiclly confirmed or cliniclly dignosed cse of TB involving orgns other thn the lungs, e.g. bdomen, genitourinry trct, joints nd bones, lymph nodes, meninges, pleur, skin. New cse of TB A ptient who hs never been treted for TB or hs tken nti-tb drugs for less thn one month. Retretment cse of TB A ptient who hs been treted for one month or more with nti-tb drugs in the pst. Retretment cses re further clssified by the outcome of their most recent course of tretment into four ctegories. 1. Relpse ptients hve previously been treted for TB, were declred cured or tretment completed t the end of their most recent course of tretment, nd re now dignosed with recurrent episode of TB (either true relpse or new episode of TB cused by reinfection). 2. Tretment f ter filure ptients hve previously been treted for TB nd their most recent course of tretment filed i.e. they hd positive sputum smer or culture result t month 5 or lter during tretment. 3. Tretment f ter loss to follow-up ptients hve previously been treted for TB nd were declred lost to follow-up t the end of their most recent course of tretment. 4. Other previously treted ptients re those who hve previously been treted for TB but whose outcome f ter their most recent course of tretment is unknown or undocumented. Cse of multidrug-resistnt TB (MDR-TB) TB tht is resistnt to two first-line drugs: isonizid nd rifmpicin. For most ptients dignosed with MDR-TB, WHO recommends tretment for 2 months with regimen tht includes second-line nti-tb drugs. Cse of rifmpicin-resistnt TB (RR-TB) A ptient with TB tht is resistnt to rifmpicin detected using phenotypic or genotypic methods, with or without resistnce to other nti-tb drugs. It includes ny resistnce to rifmpicin, whether mono-resistnce, multidrug resistnce, polydrug resistnce or extensive drug resistnce. Definitions nd reporting frmework for tuberculosis 213 revision. Genev, World Helth Orgniztion, 213 (WHO/HTM/TB/213.2). Avilble t n FIGURE 3.1 Globl trends in bsolute number of notified TB cses (blck) nd estimted TB incidence (green), Cse notifictions include new nd relpse cses (ll forms). Cses per yer (millions) Rte per 1 popultion per yer n GLOBAL TUBERCULOSIS REPORT 215

50 n TABLE 3.1 Cse notifictions, 214 TOTAL NOTIFIED NEW AND RELAPSE RETREAT- MENT EXCLUDING RELAPSE PULMONARY BACTERI O- LOGICALLY CONFIRMED NEW OR PREVIOUS TREATMENT HISTORY UNKNOWN PULMONARY CLINICALLY DIAGNOSED EXTRA- PULMONARY PULMONARY BACTERIO- LOGICALLY CONFIRMED RELAPSE PULMONARY CLINICALLY DIAGNOSED EXTRA- PULMONARY PERCENTAGE OF PULMO- NARY CASES BACTERIO- LOGICALLY CONFIRMED Afghnistn Bngldesh Brzil Cmbodi Chin DR Congo Ethiopi Indi Indonesi Keny Mozmbique Mynmr Nigeri Pkistn Philippines Russin Federtion South Afric Thilnd Ugnd UR Tnzni Viet Nm Zimbbwe High-burden countries AFR AMR EMR EUR SEAR WPR Globl Blnk cells indicte dt not reported. New nd relpse includes cses for which the tretment history is unknown. strting progress in terms of the contribution of non-ntp public nd privte sector providers to totl cse notifictions requires systemtic recording of the source of referrl nd plce of TB tretment loclly, nd reporting nd nlysis of ggregted dt ntionlly. In mny countries, dt relted to the contribution of privte sector providers re still not collected or reported through routine monitoring systems, lthough there re excellent exmples of how this cn be done (Box 3.2). The vilble dt show tht the pproch to nd contribution of PPM vries cross countries, nd is relted to the number nd type of helth cre providers. Tble 3.3 shows ten prominent exmples of countries (including HBCs) where public-public mix interventions contributed between 11% nd 55% of totl notifictions in 214. Tble 3.3b presents ten prominent exmples of countries (including HBCs) where public-privte mix interventions contributed between 12% nd 46% of totl cse notifictions. GLOBAL TUBERCULOSIS REPORT 215 n 39

51 Box 3.2 Substntil increses in TB notifictions in Indi the role of mndtory notifiction nd e-helth interventions The number of new nd relpse TB cses notified in Indi reched 1.61 million in 214, 29% increse compred with 1.24 million in 213 (Figure B3.2). This substntil increse is due to better reporting of detected cses to ntionl uthorities (s opposed to n increse in the underlying TB incidence), which cn be explined by three mjor fctors: " The introduction of policy of mndtory notifiction of TB cses in My 212; " The lunch of new web-bsed system (Nikshy) for csebsed notifiction by the Centrl TB Division (CTD) nd the Ntionl Informtics Centre in June 212; b " Incresed nd intensified ef forts to engge with the privte sector by the Revised Ntionl Tuberculosis Control Progrmme (RNTCP), which hve been fcilitted by Nikshy. FIGURE B3.2 Cse notifictions in Indi, Cses per yer (millions) Mndtory notifiction ws introduced in recognition of the fct tht while the privte sector provides tretment for pproximtely 5% of TB ptients, c most of these cses were not being reported to the RNTCP. Nikshy ws introduced s prt of ef forts to fcilitte reporting of TB cses, including those treted in the privte sector. The system is vilble for reporting of cses by both public nd privte helth cre fcilities. It is ccessible vi ndroid-bsed smrtphones nd web-portl, both of which fcilitte the process of notifying cses. Since its rollout ntionwide by the end of 212, reporting from the privte sector hs grown nd dt qulity hs improved. By June 215, more thn 4.6 million TB ptients hd been reported by over 4 public nd over 9 privte helth cre fcilities, with bout 5 TB cses being dded to the system ech dy. Nikshy hs lso eliminted the time previously tken to trnsmit lbortory results to tretment sites nd peripherl units. Nikshy cptures dt tht re importnt for both progrmme mngement nd clinicl cre. These include detils of who notified TB cse, who provides direct observtion of tretment (DOT), ptient trnsfers, nd contct trcing, s well s demogrphic nd clinicl detils of the individul TB ptient such s ge, sex, HIV sttus, bcteriology nd drug-susceptibility test results, nd tretment outcomes. This hs llowed the RNTCP to generte reports consistent with updted definitions of cse definitions nd tretment outcomes recommended by WHO since 213 (Box 3.1). This includes ge nd sex-disggregted dt for ll new nd relpse cses, which could not be produced using the old reporting system. The CTD uses five vribles to void entry of duplicte records in Nikshy. The greter grnulrity of the dt being recorded in Nikshy is lso llowing better forecsting of TB drug requirements for children nd dults, nd provides informtion on the nutritionl sttus of ptients. To support the introduction nd implementtion of Nikshy, online videos in English nd Hindi were used to trin frontline workers, nd mobile-phone short messging services (SMS) were used to ensure regulr contct of users with progrmme mngers t ll levels. Mngers cn now receive reports on cse-finding, sputum conversion nd tretment outcome vi SMS. Ptients hlf of whom hve mobile number entered in the system lso benefit from SMS reminders for visits relted to follow-up of tretment. Trditionl pper-bsed nd ggregted qurterly reporting will be phsed out in 216, nd reporting will be entirely through Nikshy. In the next phse of Nikshy s development, the im is to cpture geosptil dt to enble sptil surveillnce, nd to use nd record br-codes on mediction boxes for drug supply chin nd inventory mngement. Linking up with other electronic services my lso llow electronic pyments to ptients nd providers, nd ccess to the ntionl unique identifiction number (Adhr) d nd relted socil support schemes for TB ptients. The cities of Mumbi, Ptn nd Mehsn lredy provide good exmples of how digitl technologies re helping the RNTCP to rech out to providers who re involved in TB cre but who hve previously been outside the rech of ntionl surveillnce. In these settings, privte providers cn phone cll centres free of chrge to ensure free nti-tb medictions for their ptients. Ptients receive e-vouchers for stndrdized medictions, which they cn redeem t no chrge t privte chemists. Cll centres lso issue reminders to ptients for follow-up visits vi telephone clls nd SMS. This digitl system is linked with the RNTCP, so tht progrmme stf f receive lerts nd cn tke ctions s necessry. Incentives for notifiction re pid to providers electroniclly, s re pyments for lbortory tests. e-lerning tools hve lso been introduced to fcilitte the dissemintion of the Stndrds for TB Cre in Indi, nd e-lerning techniques hve lso been useful for rpid, lrgescle trining of stf f on the use of the cll centres. b c d Stynryn S, Nir SA, Chdh SS, et l. From where re tuberculosis ptients ccessing tretment in Indi? Results from cross-sectionl community bsed survey of 3 districts. PLoS One 211; 6: e n GLOBAL TUBERCULOSIS REPORT 215

52 n FIGURE 3.2 Cse notifiction nd estimted TB incidence rtes by WHO region, Regionl trends in cse notifiction rtes (new nd relpse cses, ll forms) (blck) nd estimted TB incidence rtes (green). Shded res represent uncertinty bnds. 4 Afric 6 The Americs 15 Estern Mediterrnen Rte per 1 popultion per yer Europe 2 2 South Est Asi Western Pcific In Chin, lrge proportion of people with TB seek cre from public hospitls, nd vrious models of hospitl engge ment exist. In 214, public hospitls contributed 55% of ll notified TB cses. A web-bsed system for reporting of communicble diseses hs plyed key role in ensuring tht TB cses detected in public hospitls outside the NTP network re notified. Medicl college hospitls in Indi, specility lung hospitls nd generl hospitls in Indonesi, hospitls owned by socil security orgniztions in Peru nd other Ltin Americn countries, nd the hospitls of helth insurnce orgniztions in Egypt re other exmples of public helth cre providers tht re mking importnt contributions to TB cse notifictions. In 214, public sector medicl college hospitls in Indi lone reported 176 TB cses. Given tht helth centres nd hospitls re of ten mnged by dif ferent deprtments within ministries of helth nd tht ministries such s those for eduction, socil welfre, defence or justice cn lso be involved in providing helth services, implementing public-public mix pproches is essentil in mny prts of the world. Public-privte mix pproches re necessry in countries with lrge privte sector, including most HBCs in the South-Est Asi nd Western Pcific regions nd n incresing number of countries in the Africn Region, where the privte medicl sector is growing rpidly. The steep rise in TB cse notifictions from privte sector cre providers in Indi between 213 nd 214 (from 85 to 195 in 214) is prticulrly impressive. Further detils re provided in Box 3.2. A lrge increse of more thn 3% in notifictions from the privte sector in Pkistn between 213 nd 214 is lso notble chievement. Both countries hve mde concerted ef forts to increse notifictions of detected cses by the privte sector, nd these re now pying of f. The privte helth sector in Afric is of ten considered insignificnt in terms of its contribution to provision of TB cre. Dt from Keny, Mlwi nd Nigeri show tht this is not lwys the cse. In 214 s in 213, lmost one in five cses notified in Mlwi ws reported by privte cre provider, even though TB drugs re generlly not vilble in privte phrmcies (unlike in Keny nd Nigeri). Most of the contributions to TB cse notifictions in Mlwi re referrls of people with TB signs nd symptoms to the public sector by the front-line, community-bsed privte helth cre providers. These of ten include clinicl of ficers, nurses nd trditionl helers. Engging such front-line cre providers, including drug shops nd phrmcies, fcilittes erly cse detection. The Mlwi exmple should prompt other countries tht hve not previously considered PPM to be of importnce to revisit their strtegies. In ll settings, PPM interventions should lso be designed to help not only detection of TB cses, but lso erly detection by providers where cre is of ten sought first. GLOBAL TUBERCULOSIS REPORT 215 n 41

53 n FIGURE 3.3 Cse notifiction nd estimted TB incidence rtes, 22 high-burden countries, Trends in cse notifiction rtes (new nd relpse cses, ll forms) (blck) nd estimted TB incidence rtes (green). Shded res represent uncertinty bnds Afghnistn Bngldesh Brzil Cmbodi Chin DR Congo Ethiopi Indi Indonesi Keny Rtes per 1 popultion per yer Mozmbique Mynmr Nigeri Pkistn Philippines Russin Federtion South Afric Thilnd Ugnd UR Tnzni Viet Nm 3 Zimbbwe For Bngldesh, joint ressessment of estimtes of TB disese burden will be undertken following completion of the ntionl TB prevlence survey. n FIGURE 3.4 Regionl TB notifiction rtes by ge, Rte per 1 popultion per yer 2 1 AFR AMR SEAR EMR EUR WPR Age group (yers) Countries not reporting cses in these ctegories re excluded. Cses included mke up 87% of reported cses nd exclude the following high burden countries: Afghnistn, Ethiopi, Mozmbique nd Thilnd. 3.3 Community contributions to TB notifictions nd tretment support Despite the best ef forts of helth systems, bout one third of people who develop TB globlly re still either not dignosed, or their cses re not reported (see section 3.5). Dif ficulty in ccessing helth fcilities is one of the resons why people with TB my not be dignosed, nd cn lso hve negtive impct on tretment dherence. Access to helth cre cn be f fected by socil nd politicl fctors (such s stigm nd discrimintion, nd the vilbility of cross-border services for migrnts), nd economic brriers (for exmple, the cost of trnsport). The role of community enggement in contributing to TB prevention, dignosis nd tretment, especilly where people with TB hve poor ccess to forml helth services, is therefore well-recognized. Fostering such community prticiption hs been n explicit component of the Stop TB Strtegy nd strong colition with civil society 42 n GLOBAL TUBERCULOSIS REPORT 215

54 n TABLE 3.2 Notifictions of new nd relpse TB cses by ge nd sex, YEARS 15 YEARS AGE UNKNOWN % AGED < 15 YEARS MALE/ FEMALE RATIO Afghnistn* Bngldesh* Brzil Cmbodi Chin DR Congo* Ethiopi* Indi Indonesi Keny Mozmbique Mynmr Nigeri Pkistn Philippines Russin Federtion South Afric Thilnd* Ugnd UR Tnzni Viet Nm* Zimbbwe High-burden countries AFR AMR EMR EUR SEAR WPR Globl Blnk cells indicte dt tht could not be reported for the ge ctegories shown. indictes vlues tht cnnot be clculted. * New cses only. TABLE 3.3 Contribution of public-public mix to notifictions of TB cses in selected countries, 214 COUNTRY NUMBER OF TB CASES NOTIFIED BY NON-NTP PUBLIC SECTOR CARE PROVIDERS TOTAL NUMBER OF TB CASES NOTIFIED CONTRIBUTION OF NON-NTP PUBLIC SECTOR CARE PROVIDERS TO TOTAL CASE NOTIFICATIONS (%) Chin Côte d Ivoire Egypt El Slvdor Indi Indonesi Irq Peru Sri Lnk Yemen Includes ll contributions from non-ntp providers of cre in the public sector, including public hospitls, public medicl colleges, prisons/ detention centres, militry fcilities, rilwys nd public helth insurnce orgniztions. TABLE 3.3b Contribution of public-privte mix to notifictions of TB cses in selected countries, 214 COUNTRY NUMBER OF TB CASES NOTIFIED BY PRIVATE SECTOR CARE PROVIDERS TOTAL NUMBER OF TB CASES NOTIFIED CONTRIBUTION OF PRIVATE SECTOR CARE PROVIDERS TO TOTAL NOTIFICATIONS (%) Bngldesh Ethiopi Indi Irn Irq Keny Mlwi Mynmr Nigeri Pkistn Privte sector providers include privte individul nd institutionl providers, corporte/business sector providers, mission hospitls, nongovernmentl orgniztions nd fith-bsed orgniztions. GLOBAL TUBERCULOSIS REPORT 215 n 43

55 Box 3.3 Definitions of key terms nd indictors used to monitor community enggement Community-bsed TB ctivities. These cover wide rnge of ctivities tht contribute to the detection, referrl nd tretment of people with drug-susceptible, drug-resistnt nd HIV-ssocited TB. They re conducted outside the premises of forml helth fcilities (e.g. hospitls, helth centres nd clinics) in community-bsed structures (e.g. schools, plces of worship, congregte settings, mrkets) nd homesteds. Community helth workers nd community volunteers crry out communitybsed TB ctivities, depending on the ntionl nd locl context. Community helth workers. These re people with some forml eduction who hve been given trining to contribute to community-bsed helth services, including TB prevention nd ptient cre nd support. Their profile, roles nd responsibilities vry gretly mong countries, nd their time is of ten compensted by incentives in kind or in csh. Community volunteers. These re people who hve been systemticlly sensitized bout TB prevention nd cre, either through short, specific trining scheme or through repeted, regulr contct sessions with professionl helth workers. Core indictors for routine monitoring of community-bsed TB ctivities In 213, three core indictors were defined nd greed by WHO nd prtners. These re: 1. Percentge of TB notifictions from community referrls. This indictor mesures the proportion of notified TB ptients (ll forms of TB) who were referred by community helth worker or community volunteer. 2. Percentge of registered TB ptients who received tretment support in the community. This indictor mesures the proportion of TB ptients who were supported during tretment by community helth worker or community volunteer. 3. Percentge of registered TB ptients who received tretment support in the community who were successfully treted. This indictor mesures the proportion of TB ptients who received tretment support from community helth worker or community volunteer during their TB tretment nd who were successfully treted. orgniztions nd communities is one of the four principles underpinning the End TB Strtegy (Chpter 1). Estblishing nd strengthening collbortion with nongovernmentl nd other civil society orgniztions to scle up communitybsed TB ctivities, nd enhncing their role in the design nd implementtion of ntionl TB strtegic plns, re importnt. Accurte monitoring of the contributions of communities to TB notifictions nd tretment support requires stndrd definitions of key concepts nd indictors, nd stndrdized systems for recording nd reporting of dt. These were developed in 213 nd re shown in Box 3.3. Dt for the three core indictors were collected for the first time in 213, with focus on 13 countries in the Africn nd South-Est Asi regions tht were known to be recording nd reporting such informtion. In 214, dt collection ws expnded nd 22 countries from the sme two regions reported dt. Bsed on these two yers of experience, dt collection ws expnded in the 215 round of globl TB dt collection to cover the Europen, Estern Mediterrnen nd Western Pcific regions. Following consulttions with WHO stf f in Regionl nd Country Of fices, totl of 69 countries were trgeted for reporting of dt. Of these, 41 reported dt for t lest one of the three core indictors; 34 (83%) reported dt on the percentge of TB ptients who received tretment support in the community, nd 3 (73%) reported dt on the percentge of TB notifictions tht originted from community referrls. A summry of the contribution of communities to TB notifictions nd tretment support is provided in Tble 3.4. About one third (14/41) of countries reported ntionwide coverge of community enggement in cse notifiction, nd 41% (17/41) reported ntionwide coverge of communitybsed tretment support. In res where community-bsed referrl ctivities were in plce, the percentge of notified TB ptients ccounted for by community referrls rnged from 2% in Mynmr nd Sri Lnk to 73% in Cmbodi. The proportion of TB ptients receiving community-bsed tretment support rnged from 2% in Mlysi, Romni nd Sierr Leone to 1% in Keny, Pkistn nd Tjikistn. Reporting of the tretment success rte mong TB ptients who received tretment support in the community hs continued to be chllenge. Among the 41 countries tht reported dt relted to community enggement, only 26 (41%) reported informtion for this indictor. Even in these countries, there re concerns with the ccurcy of the reported dt. For exmple, while the generl tendency ws for tretment outcomes to improve between 213 nd 214 mong ptients receiving tretment support from community volunteer or community helth worker, there were lrge yer-to-yer chnges in some countries tht ppered implusible. Intensified ef forts re needed to improve the ccurcy of dt for this indictor, nd/or to revisit its sttus s core indictor. For exmple, it my be more pproprite to ssess this indictor s prt of periodic evlution, rther thn through routine reporting. This is being considered by WHO s prt of wider ef forts to develop expnded guidnce on community enggement. It is lso importnt to note tht there re countries in which community-bsed TB ctivities re routine com- 44 n GLOBAL TUBERCULOSIS REPORT 215

56 Box 3.4 The ENGAGE-TB pproch: progress nd highlights to dte The ENGAGE-TB pproch ims to integrte community-bsed TB ctivities into the work of nongovernmentl orgniztions nd other civil society orgniztions tht were previously not engged in TB prevention, dignosis nd tretment. Pilot projects were strted in 212 with funding from the Bristol-Myers Squibb Foundtion Secure the Future in five countries: the Democrtic Republic of the Congo, Ethiopi, Keny, South Afric nd the United Republic of Tnzni. In Ethiopi, TB ctivities were integrted into mternl nd child helth ctivities nd cervicl cncer screening. In Keny, they were integrted into mternl nd child helth ctivities nd livelihood inititives. In the other three countries, they were integrted into HIV progrmmes. By the end of 214, the totl popultion covered by the pilot projects hd reched 8 million nd 24 previously unengged nongovernmentl orgniztions hd strted to implement community-bsed TB ctivities. In pilot res, community referrls of people with signs nd symptoms suggestive of TB contributed 5 68% of notified TB ptients in 213 nd 214, nd 2 89% of ll TB ptients hd benefited from community-bsed tretment support during the sme period. ponent of TB services, but where it is not yet possible to quntify this contribution. For exmple, Zimbbwe hs recently finlized revisions to its ntionl monitoring nd evlution system nd will be ble to report dt on community contributions strting in 216. In the ner future, it is lso nticipted tht Mlwi will incorporte routine reporting of community contributions within the existing monitoring nd evlution system. In ddition to improving the documenttion nd reporting of community-bsed TB ctivities, ef forts to engge nongovernmentl orgniztions tht hve previously not been involved in TB prevention, dignosis nd tretment hve continued using the ENGAGE-TB pproch. 1 In ddition to five focus countries (the Democrtic Republic of the Congo, Ethiopi, Keny, South Afric nd the United Republic of Tnzni), five dditionl countries hve now integrted the ENGAGE-TB pproch into their ntionl strtegies nd mobilized funding for its implementtion. These re Burkin Fso, Côte d Ivoire, Mlwi, Nmibi nd Zimbbwe. Progress mde to dte in the originl five countries is described in Box Trends in cse notifictions nd estimtes of the cse detection rte Globlly, the number of TB cses newly dignosed nd notified per 1 popultion remined reltively stble between 199 nd 2, rose shrply between 2 nd 28, nd then fell slowly from 29 to 213 (Figure 3.1). In terms of bsolute numbers, there ws n increse from 1995 to 2, more pronounced increse from 2 to 28 nd then very little chnge from 28 to 213 (Figure 3.1). Between 213 nd 214, these ptterns chnged, with cler upwrd increse in terms of rtes nd bsolute numbers. This chnge is driven by n increse in the South-Est Asi Region (Figure 3.2), which itself reflects the lrge increse in notifictions (of 366 cses) in Indi between 213 nd 214 (Figure 3.3, Box 3.2). 1 Globlly nd in ll WHO regions, cler gp exists between the numbers of notified cses nd the estimted numbers of incident cses. However, this gp hs nrrowed in the lst 15 yers, especilly in the Estern Mediterrnen nd Western Pcific regions nd to lesser extent in the South-Est Asi Region (Figure 3.2). Trends in the 22 HBCs re shown in Figure 3.3; for other countries these trends re illustrted in country profiles tht re vilble online. 2 The cse detection rte (CDR) 3 for TB is n indictor tht is included within the Millennium Development Gols (MDG) frmework. For given country nd yer, the CDR is clculted s the number of new nd relpse TB cses (see Box 3.1 for definitions) tht were notified by NTPs (Tble 3.1), divided by the estimted number of incident cses of TB tht yer. The CDR is expressed s percentge; it gives n pproximte 4 indiction of the proportion of ll incident TB cses tht re ctully dignosed nd reported to NTPs or ntionl surveillnce systems. The best estimte of the CDR for ll forms of TB globlly in 214 ws 63% (rnge, 6 66%), up from 48 52% in 25 nd 36 4% in 1995 the yer in which the DOTS strtegy begn to be introduced nd expnded (Tble 3.5). 5 The best estimte of the globl gp between notifictions (of new episodes of TB i.e. new nd relpse cses) nd incident cses in 214 ws 3.6 million cses. At regionl level, the highest CDRs in 214 were estimted to be in the Region of the Americs (best estimte 77%; rnge, 75 81%), the Western Pcific Region (best estimte 85%; rnge, 81 9%) nd the Europen Region (best estimte 79%; rnge, 75 83%). The other regions hd estimted CDRs of 43 75%, with best estimtes in the rnge 48 62% The CDR is ctully rtio rther thn rte, but the term rte hs become stndrd terminology in the context of this indictor. 4 It is pproximte becuse of uncertinty in the underlying incidence of TB nd becuse notified cses re not necessrily subset of incident cses tht occurred in the sme yer; see Chpter 2 for further discussion. 5 The rnges represent 95% uncertinty intervls. There is uncertinty in estimtes of the CDR becuse of uncertinty in estimtes of TB incidence (the denomintor). GLOBAL TUBERCULOSIS REPORT 215 n 45

57 TABLE 3.4 Community contributions to TB cse notifictions nd tretment support for TB ptients (ll forms) in 41 countries, Dt re for the bsic mngement units (BMUs) tht reported dt. b c COUNTRIES CONTRIBUTION TO TB NOTIFICATIONS, 214 CONTRIBUTION TO TREATMENT ADHERENCE SUPPORT, 213 TB PATIENTS (ALL FORMS) WHO RECEIVED TOTAL TB NOTIFICATIONS (ALL FORMS) FROM COMMUNITY REFERRALS IN 214 TREATMENT ADHERENCE SUPPORT IN THE COMMUNITY IN 213 GEOGRAPHIC NUMBER % OF BMU NOTIFICATIONS COVERAGE OF DATA REPORTING BY BMUs NUMBER % OF ALL TB PATIENTS GEOGRAPHIC COVERAGE OF DATA REPORTING BY BMUs Afghnistn / /722 Bngldesh /88 Not vilble Botswn Not vilble /27 Bulgri /22 Not vilble Burkin Fso / /86 Burundi / /17 Cmbodi /93 Not vilble Côte d Ivoire / /184 DR Congo / /516 Eritre /69 Not vilble Ethiopi / /957 Georgi /77 Not vilble Ghn / /216 Guine b / /465 Indi / /3 394 Indonesi / /511 Keny / /3 32 Lesotho Not vilble /34 Mdgscr / /215 Mlysi Not vilble /146 Mongoli / /32 Mozmbique b / /323 Mynmr / /354 Nmibi Not vilble /34 Nepl / /75 Nigeri Not vilble /774 Pkistn Not vilble /1 36 Republic of Moldov Not vilble /57 Romni Not vilble /177 Rwnd / /515 So Tome nd Principe /1 Not vilble Senegl / /76 Sierr Leone / /17 South Afric c Not vilble Not vilble Sri Lnk / /26 Tjikistn / /19 Timor-Leste Not vilble /18 Ugnd Not vilble /117 UR Tnzni / /168 Uzbekistn b / /4 516 Viet Nm Not vilble /815 Twenty-eight countries did not submit dt for either indictor: Algeri, Angol, Armeni, Azerbijn, Benin, Bhutn, Cmeroon, Cpe Verde, Centrl Africn Republic, Chd, Congo, Gbon, Gmbi, Guine-Bissu, Kiribti, Liberi, Mlwi, Mli, Muritni, Niger, Philippines, Sudn, Swzilnd, Thilnd, Togo, Turkey, Zmbi nd Zimbbwe. The proportion of ptients receiving tretment support in the community ws clculted using the totl cohort (ll BMUs) of TB ptients strting tretment in 213 s the denomintor. Dt disggregted by BMU were not reported. The proportion of notifictions tht cme from community referrls ws clculted using the totl cohort (ll BMUs) of TB ptients notified in 214 s the denomintor. Dt disggregted by BMU were not reported. 46 n GLOBAL TUBERCULOSIS REPORT 215

58 n TABLE 3.5 Estimtes of the cse detection rte for new nd relpse cses %, Best estimtes re followed by the lower nd upper bounds of the 95% uncertinty intervl Afghnistn Bngldesh Brzil Cmbodi Chin DR Congo Ethiopi Indi Indonesi Keny Mozmbique Mynmr Nigeri Pkistn Philippines Russin Federtion South Afric Thilnd Ugnd UR Tnzni Viet Nm Zimbbwe High-burden countries AFR AMR EMR EUR SEAR WPR Globl indictes vlues tht cnnot be clculted. Estimtes for ll yers re reclculted s new informtion becomes vilble nd techniques re refined, so they my dif fer from those published previously. The lower nd upper bounds re defined s the 2.5th nd 97.5th centiles of outcome distributions produced in simultions. All regions hve improved their estimted CDRs since the mid-199s, with improvements prticulrly evident since 2. Among the 22 HBCs, the highest rtes of cse detection in 214 (>8%) were estimted to be in Brzil, Chin, the Philippines nd the Russin Federtion. The lowest rtes, with best estimtes of 5% or less, were in the Democrtic Republic of the Congo, Indonesi, Mozmbique, Nigeri nd the United Republic of Tnzni. There re two mjor resons for gp between notifictions nd estimted incidence. The first is underreporting of dignosed TB cses, for exmple becuse privte sector providers fil to notify cses. This is one of the resons for reltively low CDR in Indonesi (see lso Box 2.4, Chpter 2). The second is under-dignosis of people with TB for resons such s poor ccess to helth cre nd filure to recognize TB signs nd symptoms nd test for TB when people do present to helth cre fcilities. A good exmple is Nigeri, where the 212 ntionl TB prevlence survey suggested tht this is mjor reson for the low CDR. 1 It should lso be cknowledged tht the estimtes of TB incidence re uncertin, nd the gp between the estimted number of incident cses nd 1 World Helth Orgniztion. Globl tuberculosis report 214. Genev: World Helth Orgniztion; 214 (WHO/HTM/TB/214.8). See pp1 11. GLOBAL TUBERCULOSIS REPORT 215 n 47

59 Box 3.5 Definitions of tretment outcomes for new nd relpse cses recommended for use since Mrch 213 nd tht were used in the 214 nd 215 rounds of globl TB dt collection Cured A pulmonry TB ptient with bcteriologiclly-confirmed TB t the beginning of tretment who ws smer- or culturenegtive in the lst month of tretment nd on t lest one previous occsion. Completed tretment A TB ptient who completed tretment without evidence of filure but with no record to show tht sputum smer or culture results in the lst month of tretment nd on t lest one previous occsion were negtive, either becuse tests were not done or becuse results re unvilble. Died A TB ptient who died from ny cuse during tretment. Filed A TB ptient whose sputum smer or culture is positive t month five or lter during tretment. Lost to follow-up A TB ptient who did not strt tretment or whose tretment ws interrupted for two consecutive months or more. Not evluted A TB ptient for whom no tretment outcome is ssigned. This includes cses trnsferred out to nother tretment unit s well s cses for whom the tretment outcome is unknown to the reporting unit. Successfully treted A ptient who ws cured or who completed tretment. Cohort A group of ptients in whom TB hs been dignosed, nd who were registered for tretment during specified time period (e.g. the cohort of new cses registered in the clendr yer 212). This group forms the denomintor for clculting tretment outcomes. The sum of the ptients included in the bove tretment outcome ctegories should equl the number of cses registered. It should be highlighted tht in the new definitions recommended since Mrch 213 ny ptient found to hve drug-resistnt TB nd plced on second-line tretment should be removed from the drug-susceptible TB outcome cohort. This mens tht mngement of the stndrd TB register nd of the second-line TB tretment register needs to be coordinted to ensure proper ccounting of the outcomes of tretment (see lso Chpter 4). Definitions nd reporting frmework for tuberculosis 213 revision. Genev, World Helth Orgniztion, 213 (WHO/HTM/TB/213.2). Avilble t the number of notifictions could be under- or over-stted. Intensified ef forts re needed to ensure tht ll cses re detected, notified to ntionl surveillnce systems, nd treted ccording to interntionl stndrds. Progress towrds the gol of universl helth coverge, implementtion of PPM inititives such s those described in section 3.2, nd ensuring tht there is n ef fective regultory frmework tht includes mndtory notifiction of cses re ll essentil to reduce underreporting nd under-dignosis, nd constitute prt of the End TB Strtegy (Chpter 1). The current sttus of progress towrds universl helth coverge from finncing perspective is discussed further in Chpter Tretment outcomes The definitions of TB tretment outcomes for new nd relpse cses of TB tht re recommended by WHO s prt of n updted recording nd reporting frmework issued in Mrch 213, nd used in the 215 round of globl TB dt collection, re shown in Box Most of these cses (97% globlly) hve drug-susceptible TB, but in some prts of the world, especilly countries of the former Soviet Union, more thn 2% of new nd relpse cses hve MDR-TB (Chpter 4). Universl ccess to drug susceptibility testing, s clled for in the End TB Strtegy (Chpter 1), is required to ensure tht ll people with TB receive pproprite tretment. Dt on tretment outcomes for new nd relpse cses of 1 Tretment outcomes for people dignosed with rifmpicin-resistnt nd MDR-TB re presented in Chpter 4. TB re shown for the world, the six WHO regions nd the 22 HBCs in Tble 3.6 nd Figure 3.5. Globlly, the tretment success rte for the 5.4 million new nd relpse cses tht were treted in the 213 cohort ws 86%. It is impressive tht s the size of the globl tretment cohort grew from 1. million in 1995 to 4.2 million in 25 nd 5.4 million in 213, the tretment success rte first improved nd hs subsequently been sustined t high level. Among the six WHO regions, the highest tretment success rtes were in the Western Pcific Region, the South- Est Asi Region nd the Estern Mediterrnen Region. The tretment success rte ws 79% in the Africn Region. The lowest tretment success rtes were in the Region of the Americs nd the Europen Region (both 75%). In the Region of the Americs, tretment outcomes would probbly be considerbly improved if the number of ptients in the not evluted ctegory could be reduced. In the Europen Region, rtes of tretment filure, deth nd loss to follow-up, s well s the proportion of ptients without documented tretment outcome, ll need to be reduced. One explntion for the poor outcomes in this region my be tht the proportion of new nd relpse cses tht hve drugresistnt TB is high (Chpter 4). All cses need to be tested for susceptibility to first-line drugs, nd those with rifmpicin-resistnt nd MDR-TB enrolled on second-line rther thn first-line regimens. Most of the 22 HBCs hve reched or exceeded tretment success rte of 85%. Improvements re still needed in 48 n GLOBAL TUBERCULOSIS REPORT 215

60 n TABLE 3.6 Tretment success for ll new nd relpse cses (%) nd cohort size (thousnds), Tretment success (%) Afghnistn Bngldesh Brzil Cmbodi Chin DR Congo Ethiopi Indi Indonesi Keny Mozmbique b Mynmr Nigeri Pkistn Philippines Russin Federtion South Afric Thilnd Ugnd UR Tnzni Viet Nm Zimbbwe High-burden countries AFR AMR EMR EUR SEAR WPR Globl b. Cohort size (thousnds) Afghnistn Bngldesh Brzil Cmbodi Chin DR Congo Ethiopi Indi Indonesi Keny Mozmbique Mynmr Nigeri Pkistn Philippines Russin Federtion South Afric Thilnd Ugnd UR Tnzni Viet Nm Zimbbwe High-burden countries AFR AMR EMR EUR SEAR WPR Globl Blnk cells indicte dt not reported. indictes vlues tht cnnot be clculted. Cohorts before 212 include new cses only. For the 212 nd 213 cohorts, 14 nd 16 high-burden countries respectively included both new nd relpse cses, s recommended in the revised recording nd reporting frmework issued by WHO in 213 (see Definitions nd reporting frmework for tuberculosis 213 revision. Genev, World Helth Orgniztion, 213 (WHO/HTM/TB/213.2). Avilble t b Tretment outcomes in Mozmbique re for new pulmonry bcteriologiclly-confirmed cses only. Introduction of monitoring of outcomes for other cses ws strted in 215. GLOBAL TUBERCULOSIS REPORT 215 n 49

61 Box 3.6 Outcomes of TB tretment by HIV sttus In the 215 round of globl TB dt collection, 14 countries reported tretment outcomes for the 213 ptient cohort tht were disggregted by HIV sttus. This ws n increse from 133 countries tht reported such dt for 212. These 14 countries included 22 of the 41 high TB/HIV burden countries (listed in Tble 6.1 of Chpter 6) nd collectively ccounted for 71% (n= 397 ) of the HIV-positive TB ptients reported by NTPs in 213, similr to the level of 212 (7%). Overll, the tretment success rte in 213 ws worse for HIVpositive TB ptients (73%) compred with HIV-negtive TB ptients (88%), similr to levels in 212 (Figure B3.6). The dif ference ws smller in the Africn region (75% nd 84%, respectively). There were lrge dif ferences in the Europen nd Estern Mediterrnen Regions, where the tretment success rtes mong HIV-positive TB ptients were only 47% nd 6% respectively, compred with 8% nd 91% mong HIV-negtive ptients. The tretment success rte in the Europen Region were much worse thn in 212 (47% versus 57%), minly reflecting dt for Ukrine. This country ccounted for 8% of the HIV-positive TB ptients for whom tretment outcomes in 213 were reported, but did not report dt in 212. More encourgingly, the tretment success rte for HIV-positive TB ptients in the Western Pcific Region ws substntilly better in 213 compred with 212 (73% vs 57%). Globlly, the proportion of TB ptients who died during tretment remined more thn three times higher mong HIV-positive TB ptients (11% versus 3.5%). In the Africn Region, HIV-positive TB ptients were lmost twice s likely to die compred with HIV-negtive TB ptients (9.8% versus 5.1%). Dif ferentils were lrger in the Europen Region (21% versus 6.6%) nd the Estern FIGURE B3.6 Outcomes of TB tretment by HIV sttus, Percentge of cohort Mediterrnen Region (17% versus 1.8%). The proportion of ptients ctegorized s lost to follow-up, who my lso hve died of TB, ws lso higher for those who were HIV-positive (6.5% versus 4.6%), similr to levels in 212. The proportion of HIV-positive TB ptients for whom the tretment outcome ws not evluted ws reltively similr globlly (8.1% compred with 7.6% of HIVnegtive TB ptients), lthough there ws noticeble drop in the Western Pcific Region (from 3% of ptients in 212 to 12% in 213). This is the min explntion for the lrge improvement in the tretment success rte for HIV-positive TB ptients in this region Tretment success Filed Died HIV+ Lost to follow-up HIV Not evluted Countries with no tretment outcome dt for HIV-positive TB ptients were excluded from the nlysis. Brzil, the Russin Federtion, South Afric, Thilnd, Ugnd nd Zimbbwe. Tretment outcomes in 213 were worse mong HIVpositive TB ptients compred with HIV-negtive TB ptients (Box 3.6). Further ef forts re needed to nrrow this gp. 3.6 Detection nd tretment of ltent TB infection Ltent TB infection (LTBI) is defined s the presence of immune responses to Mycobcterium tuberculosis ntigens without clinicl evidence of ctive TB. Most people with LTBI hve no signs or symptoms of TB disese nd re not infectious. However, they re t risk of developing ctive TB disese nd becoming infectious. The lifetime risk of TB disese for person with documented LTBI is estimted t 5 15%, with the mjority of cses occurring within the first five yers f ter initil infection. 1 The risk of LTBI rectivtion cn be reduced by preventive tretment. WHO hs issued globl recommendtions on the tretment of LTBI for people living with HIV nd for 1 Gethun H, Mtteelli A, Chisson RE, Rviglione M. Ltent Mycobcterium tuberculosis infection. New Engl J Med. 215;372(22): children ged less thn 5 yers old who re close contcts of TB cse. 2,3 Most recently, WHO hs issued guidelines on the mngement of LTBI tht re trgeted t upper-middle nd high-income countries with n estimted incidence rte of less thn 1 per 1 popultion. 4 In these countries, systemtic testing nd tretment of LTBI is recommended for wider rnge of risk groups: people living with HIV, dult s well s child contcts of pulmonry TB cses, ptients with silicosis, ptients inititing nti-tumour necrosis fctor (TNF) tretment, ptients on dilysis, nd trnsplnt ptients (Tble 3.7). The mngement of LTBI is criticl component of the new post-215 End TB Strtegy (Chpter 1), nd is one of the interventions tht cn help countries to chieve the mbi- 2 World Helth Orgniztion. Guidelines for intensified tuberculosis cse-finding nd isonizid preventive therpy for people living with HIV in resource-constrined settings. Genev: World Helth Orgniztion; World Helth Orgniztion. Recommendtions for investigting contcts of persons with infectious tuberculosis in low- nd middle income countries. Genev: World Helth Orgniztion; World Helth Orgniztion. Guidelines on the mngement of ltent tuberculosis infection. Genev: World Helth Orgniztion; 215. Avilble t: en/ 5 n GLOBAL TUBERCULOSIS REPORT 215

62 n TABLE 3.7 WHO recommendtions for the mngement of ltent TB infection, by country group COUNTRY GROUP AT RISK POPULATIONS TESTING ALGORITHM TREATMENT OPTIONS High-income nd upper middleincome countries with n estimted TB incidence rte of less thn 1 per 1 popultion Strongly recommended for the following risk groups: 1) People living with HIV; 2) Adults nd children who re household or close contcts of pulmonry TB cses; 3) Clinicl indictions ptients with silicosis; ptients inititing nti-tnf tretment; ptients on dilysis; trnsplnt ptients. Exclude ctive TB using TB investigtions. A positive IGRA or TST test result is required to dignose LTBI. 6 months dily isonizid 9 months dily isonizid 3 months weekly rifpentine plus isonizid 3 to 4 months dily isonizid plus rifmpicin 3 to 4 months dily rifmpicin Resource-limited nd other middleincome countries with n estimted TB incidence rte of more thn 1 per 1 popultion 1) People living with HIV; 2) Children under 5 yers of ge who re household contcts of TB cse. Exclude ctive TB using TB investigtions. An LTBI test is not required prior to LTBI tretment, but is encourged for people living with HIV. IGRA should not replce TST. 6 months dily isonizid n FIGURE 3.5 Tretment outcomes for new nd relpse cses, 213, globlly, for the six WHO regions nd 22 high-burden countries Afghnistn Bngldesh Brzil Cmbodi Chin DR Congo Ethiopi Indi Indonesi Keny Mozmbique b Mynmr Nigeri Pkistn Philippines Russin Federtion South Afric Thilnd Ugnd UR Tnzni Viet Nm Zimbbwe High-burden countries AFR AMR EMR EUR SEAR WPR Globl tious trgets of 9% reduction in the TB incidence rte nd 95% reduction in TB deths by 235, compred with 215 levels. LTBI mngement cn lso contribute to TB elimintion, especilly in low TB incidence settings. In this context, country prepredness for the progrmmtic implementtion of LTBI mngement (including ddressing well-recognized chllenges such s tretment dherence) is of growing priority nd importnce. A two-pronged pproch is required, in which: (1) tretment for LTBI is provided in ll countries to people living with HIV nd children ged less thn 5 yers old who re household or close contcts of TB cse; nd (2) tretment for LTBI is provided to dditionl risk groups in upper-middle nd high-income countries with n incidence rte of less thn 1 per 1 popultion. Dt on the tretment of LTBI mong people living with HIV re lredy collected routinely, with dt presented in this report (Chpter 6). In 214 nd 215, WHO expnded dt collection relted to LTBI through discussions during regionl meetings of NTP mngers (or their equivlent) nd other ntionl stkeholders in four WHO regions, nd by conducting specil survey of existing policy nd prctices in upper-middle income nd high-income countries with n incidence rte of less thn 1 per 1 popultion (shown in Figure 3.6). The min results re summrized below Percentge of cohort (%) Tretment success Filure Died Lost to follow-up Not evluted b Tretment outcomes re for new cses only. Tretment outcomes in Mozmbique re for new pulmonry bcteriologiclly-confirmed cses only. Introduction of monitoring of outcomes for other cses ws strted in 215. GLOBAL TUBERCULOSIS REPORT 215 n 51

63 n FIGURE 3.6 The 113 upper-middle-income nd high-income countries with n estimted incidence rte of less thn 1 per 1 popultion tht re the primry udience for 215 WHO guidelines on the mngement of ltent TB infection n FIGURE 3.7 Reported policies nd prctices for ltent TB infection (LTBI) in upper-middle-income nd high-income countries with n estimted incidence rte of less thn 1 per 1 popultion, four WHO regions Number of countries AMR EMR EUR WPR WHO region Ntionl policy on LTBI exists Testing nd tretment for LTBI being provided for people living with HIV, nd/or children who re close contcts of TB cses. Two countries in the Africn Region (Algeri nd Seychelles) were included in the survey, both of which reported tht they hd ntionl policies on LTBI nd were providing LTBI testing nd tretment for people living with HIV nd/or children who re close contcts of TB cses. One country in the South-Est Asi Region (Mldives) ws invited to prticipte in the survey but no response ws received Results from survey of LTBI policy nd prctice in upper-middle nd high-income countries with n incidence rte of less thn 1 per 1 popultion Dt were reported by 74 (69%) of the 18 countries invited to prticipte in the survey. 1 Among these countries, 76% (56/74) hd ntionl policy on LTBI but higher number (68/74, 92%) were providing testing for LTBI nd preventive tretment for people living with HIV nd/or children who were contcts of TB cses. This demonstrtes gp between policy nd prctice, which existed in three of four WHO regions (Figure 3.7). Systemtic testing nd tretment for LTBI in other risk groups for whom it is recommended ws reported by only few countries. Testing for LTBI nd exclusion of ctive TB Of the 68 countries implementing systemtic testing nd tretment of LTBI in t lest one t-risk popultion, 3 (44%) relied only on the tuberculin skin test (TST); the other 38 countries used both TST nd interferon-gmm relese ssys (IGRAs) to test for LTBI. 2 TST ws the only test used in most countries in the Estern Mediterrnen Region (7%, 7/1) nd the Americs (73%, 11/15). Both tests were common- 1 Five countries or territories with very smll popultions nd numbers of TB cses were not included in the survey: Bermud, Monco, Sn Mrino, Turks nd Cicos Islnds, US Virgin Islnds. 2 In the remining six countries, specific t-risk popultions were not identified. 52 n GLOBAL TUBERCULOSIS REPORT 215

64 ly used in the Europen Region (81%, 25/31). Shortges of TST were reported by 34 countries. To exclude ctive TB prior to strting tretment for LTBI, most countries (62%, 42/68) used combintion of clinicl screening for TB symptoms nd chest X-ry; this is consistent with WHO recommendtions. A further 24 countries used these methods but supplemented them with dditionl dignostic tests including smer microscopy, culture, nd moleculr testing. The remining country used only clinicl symptoms to exclude ctive TB. Tretment regimens In just over hlf of the 68 countries (35/68, 51%), the only option for LTBI tretment ws dily regimen of isonizid for six or nine months. Rifmycin-contining regimens were used in other countries, but to dte the shortest nd simplest regimen ( weekly dose of rifpentine plus isonizid for 12 weeks) hd been dopted by only five of these countries. Recording nd reporting Recording nd reporting gps were evident in mny countries. Of the 4 countries providing testing nd tretment for LTBI for people living with HIV, only 21 hd system for recording nd reporting dt. Of the 53 countries providing LTBI to children ged less thn five who were household or close contcts of TB cses, 33 hd system for recording or reporting dt. A monitoring nd evlution frmework for LTBI is being developed by WHO nd is expected to be vilble in 216. Key messges nd conclusions Overll, the survey shows tht intensified efforts re needed to ensure tht ntionl LTBI policies re in plce, s foundtion for progrmmtic mngement of LTBI using stndrdised pproches. Such policies should prioritize nd trget popultion groups with the highest risk of progression to ctive disese in whom the benefits of preventive tretment outweigh the potentil risks. Ef forts re needed to promote the use of short tretment regimens, such s weekly rifpentine plus isonizid for 12 weeks, which would hve potentil benefits in terms of cceptbility, dherence, nd tolerbility compred to the stndrd isonizid regimen. Systems for routine collection nd nlysis of dt re required in ll countries nd shortges in the supply of TST must be ddressed. GLOBAL TUBERCULOSIS REPORT 215 n 53

65 CHAPTER 4 Drug-resistnt TB Key fcts nd messges Drug-resistnt TB poses mjor thret to control of TB worldwide. By the end of 214, dt on nti-tb drug resistnce were vilble for 153 countries, ccounting for more thn 95% of the world s popultion nd estimted TB cses. Eighty of these countries hve continuous surveillnce systems, while the others rely on epidemiologicl surveys. In 214, the first-ever drug resistnce surveys were completed in the Democrtic People s Republic of Kore (North Hwnghe Province), Irq, Ppu New Guine (four provinces), Turkmenistn nd Ukrine; repet surveys were completed in Irn, Lesotho, Morocco nd Senegl. In mid-215, drug resistnce surveys were ongoing in 13 countries. These included the first ntionwide surveys in the Democrtic Republic of the Congo, Indi nd Sudn. Globlly, n estimted 3.3% (95% CI: %) of new cses nd 2% (95%CI: 14 27%) of previously treted cses hve MDR-TB; these levels hve remined virtully unchnged in recent yers. In 214, there were n estimted 48 (rnge: 36 6 ) new cses of MDR-TB worldwide, nd pproximtely 19 (rnge: ) deths from MDR-TB. Among ptients with pulmonry TB who were notified in 214, n estimted 3 (rnge: ) hd MDR-TB. More thn hlf of these ptients were in Indi, Chin nd the Russin Federtion. Extensively drug-resistnt TB (XDR-TB) hs been reported by 15 countries. On verge, n estimted 9.7% (95% CI: %) of people with MDR-TB hve XDR-TB. There ws mjor progress in coverge of drug susceptibility testing (DST) between 213 nd 214. Worldwide, 12% of new bcteriologiclly-confirmed TB cses nd 58% of previously treted TB ptients were tested for drug resistnce in 214, up from 8.5% nd 17% respectively in 213 (representing proportionl increses of 43% nd 223%, respectively). Coverge ws highest in the Europen Region (97% of new cses). In the South-Est Asi nd Western Pcific regions combined, two-thirds of previously treted cses underwent testing. Globlly in 214, 123 ptients with MDR -TB or rifmpicinresistnt tuberculosis (RR-TB) were notified, of whom bout 75% lived in the Europen Region, Indi, South Afric or Chin. This ws equivlent to 41% of the 3 notified TB ptients who were estimted to hve MDR-TB in 214. The number of notified MDR/RR-TB cses in 214 ws lmost the sme s in 213. A mjor dignostic gp hs therefore persisted, nd ws worst in the Western Pcific Region where detected cses represented 19% of estimted cses. The figure for Chin ws 11%. People with MDR-TB or RR-TB re eligible for second-line tretment with MDR-TB regimens. A totl of 111 people were strted on MDR-TB tretment in 214, n increse of 14% compred with 213. The rtio of enrolled to notified MDR/ RR-TB cses ws 9% globlly, nd >9% in 15 high MDR-TB burden countries s well s the Europen Region nd the Region of Americs. The rtio ws <6% in 3 high MDR-TB burden countries: Chin (49%), Mynmr (44%) nd Nigeri (53%). The 215 tretment success trget of 75% for MDR-TB ptients ws reched by 43 of the 127 countries nd territories tht reported outcomes for the 212 cohort. Only three high MDR-TB burden countries (Estoni, Ethiopi, nd Mynmr) chieved tretment success rte of 75%. Globlly, only 5% of ptients on MDR-TB tretment were successfully treted, lrgely due to high rtes of mortlity nd loss to follow-up. Despite progress in responding to the chllenge of drugresistnt TB, serious detection nd tretment gps remin. Intensified efforts to close these gps re urgently required. Drug-resistnt TB continues to threten globl TB control nd remins mjor public helth concern in mny countries. The first prt of this chpter (section 4.1) summrizes the progress mde in the globl coverge of surveillnce of nti-tb drug resistnce, using the most recent dt gthered from epidemiologicl surveys nd continuous surveillnce systems, with focus on multidrug-resistnt TB (MDR-TB) 1 nd extensively drug-resistnt TB (XDR-TB). 2 The second prt 1 Defined s resistnce to t lest rifmpicin nd isonizid, the two most powerful first-line nti-tb drugs. 2 XDR-TB is defined s MDR-TB plus resistnce to t lest one fluoroquinolone nd second-line injectble. of this chpter presents n ssessment of globl nd ntionl progress in dignosing nd treting rifmpicin-resistnt (RR- TB) nd MDR-TB (section 4.2). 4.1 Surveillnce of drug-resistnt TB Progress in the coverge of drug resistnce surveillnce Since the lunch of the Globl Project on Anti-tuberculosis Drug Resistnce Surveillnce in 1994, dt on drug resistnce hve been systemticlly collected nd nlysed from 153 countries worldwide (79% of 194 WHO Member Sttes). 54 n GLOBAL TUBERCULOSIS REPORT 215

66 This number includes 8 countries tht hve continuous surveillnce systems bsed on routine dignostic drug susceptibility testing (DST) of ll TB ptients, nd 73 countries tht rely on epidemiologicl surveys of representtive smples of ptients. Over the pst two decdes, ll 22 high TB nd/or 27 high MDR-TB burden countries (for totl of 36 countries) hve either estblished continuous surveillnce system or conducted t lest one survey to monitor drug resistnce. Progress towrds chieving globl coverge of drug resistnce surveillnce dt is shown in Figure 4.1. Continuous surveillnce for MDR-TB, bsed on routine DST of TB ptients nd systemtic collection nd nlysis of dt, is the most ef fective pproch to monitor trends in drug resistnce. The number of countries tht cn rely on dt generted by continuous surveillnce systems is incresing, following mjor ef forts to scle up the vilbility of culture nd DST services. In the pst two yers, n dditionl 1 countries estblished high qulity continuous surveillnce systems to monitor drug resistnce in new nd previously treted TB cses. Severl countries of the estern Europen nd centrl Asin regions, where proportions of MDR-TB mong TB cses re the highest, hve estblished high qulity surveillnce systems to monitor drug resistnce. These re Belrus, Estoni, Georgi, Kzkhstn, Ltvi, Lithuni, the Russin Federtion (t subntionl level) nd Tjikistn. Surveys conducted every five yers represent the most common pproch to investigting the burden of drug resistnce in resource-limited settings where routine DST is not ccessible to ll TB ptients, due to lck of lbortory cpcity or resources. In 214, the first-ever drug resistnce surveys were completed in the Democrtic People s Republic of Kore (North Hwnghe Province), Irq, Ppu New Guine (four provinces), Turkmenistn nd Ukrine; repet surveys were completed in Irn, Lesotho, Morocco nd Senegl. Of the 36 high TB nd/or MDR-TB burden countries, 26 hve generted drug resistnce dt through epidemiologicl surveys. Nerly hlf of these (14 countries) hve conducted surveys recently, between 21 nd 214. These re Afghnistn (Centrl region), Azerbijn, Bngldesh, Kyrgyzstn, Mynmr, Nigeri, Pkistn, the Philippines, Tjikistn, Thilnd, Ugnd, Ukrine, Uzbekistn nd Viet Nm. Three countries hve not completed survey since the mid-199s: the Democrtic Republic of the Congo, Keny nd Zimbbwe. However, ntionl survey is currently being implemented in ll three of these countries. Six high TB nd/or MDR-TB burden countries (Afghnistn, Brzil, the Democrtic Republic of the Congo, Indi, Indonesi nd the Russin Federtion) still rely on drug resistnce surveillnce dt gthered from sub-ntionl res only. This sitution will improve in the ner future. In 214, Brzil lunched lrge ntionwide sentinel system to monitor drug resistnce. The Democrtic Republic of the Congo nd Indi re currently conducting ntionl surveys, nd in Indonesi the first-ever ntionwide drug resistnce survey is n FIGURE 4.1 Globl coverge of surveillnce dt on drug resistnce, Yer of most recent dt Ongoing survey in 215 No dt Subntionl dt only Not pplicble GLOBAL TUBERCULOSIS REPORT 215 n 55

67 n TABLE 4.1 Estimted proportion of TB cses tht hve MDR-TB, globlly nd for 27 high MDR-TB burden countries nd WHO regions b ESTIMATED % OF NEW TB CASES 95% WITH CONFIDENCE MDR-TB INTERVAL ESTIMATED % OF RE- TREATMENT TB CASES 95% WITH CONFIDENCE MDR-TB INTERVAL Armeni Azerbijn Bngldesh Belrus Bulgri Chin DR Congo b Estoni Ethiopi Georgi Indi Indonesi Kzkhstn Kyrgyzstn Ltvi Lithuni Mynmr Nigeri Pkistn Philippines Republic of Moldov Russin Federtion South Afric Tjikistn Ukrine Uzbekistn Viet Nm High MDR-TB burden countries AFR AMR EMR EUR SEAR WPR Globl Best estimtes re for the ltest vilble yer. The estimtes for DR Congo re indirect estimtes bsed on dt from countries in the sme epidemiologicl region. scheduled for implementtion in 216. The remining countries should consider conducting ntionwide drug resistnce surveys in the short term to better understnd the burden of MDR-TB nd to guide the plnning of dignostic, tretment nd cre services. In mid-215, drug resistnce surveys were ongoing in 13 countries. These included the first-ever ntionwide surveys in the Democrtic Republic of the Congo, Indi nd Sudn; nd repet surveys in Bolivi, Chin, Côte d Ivoire, Keny, Nmibi, Romni, Rwnd, Venezuel, South Afric nd Zimbbwe. Centrl nd Frncophone Afric remin the prts of the world where drug resistnce surveillnce dt re most lcking, lrgely s result of wek lbortory infrstructure. These countries should consider conducting drug resistnce surveys using Xpert MTB/RIF to t lest obtin ntionlly representtive estimte of the proportion of TB ptients with rifmpicin resistnce Percentge of new nd previously treted TB cses tht hve MDR-TB Globlly in 214, there were n estimted 3.3% (95% CI: %) of new cses nd 2% (95%CI: 14 27%) of previously treted cses with MDR-TB (Tble 4.1). These estimtes re essentilly unchnged from those published in recent globl TB reports. The proportions of new nd previously treted TB cses with MDR-TB t the country level re shown in Figure 4.2 nd Figure 4.3, nd for the 27 high MDR-TB burden countries lso in Tble 4.1. Estern Europen nd centrl Asin countries continue to hve the highest levels of MDR-TB. Among new cses, the proportions with MDR-TB were highest in Belrus, Estoni, Kzkhstn, Kyrgyzstn, the Republic of Moldov, the Russin Federtion, Ukrine nd Uzbekistn. Among previously treted TB cses, the proportions with MDR-TB were highest in Belrus, Estoni, Kzkhstn, Kyrgyzstn, the Republic of Moldov, Tjikistn, Ukrine nd Uzbekistn. In the Russin Federtion, even though the verge proportion of previously treted cses with MDR-TB does not exceed 5%, the proportion is well bove 5% in severl Federl Subjects. Levels of drug resistnce mong new cses remin low (<3%) in mny prts of the world, including in lmost ll countries in the Region of the Americs; most Africn countries where drug resistnce surveys hve been conducted; most of the South-Est Asi Region; most of western Europe; nd severl countries in the Western Pcific Region Estimted globl incidence of MDR-TB nd estimted number of MDR-TB cses mong notified TB ptients in 214 Dt compiled from surveys nd continuous surveillnce of drug resistnce mong TB ptients cn be used to estimte the totl number of incident cses of MDR-TB worldwide nd the totl number of deths from MDR-TB in 214. Methods 56 n GLOBAL TUBERCULOSIS REPORT 215

68 n FIGURE 4.2 Percentge of new TB cses with MDR-TB Percentge of cses No dt Subntionl dt only Not pplicble Figures re bsed on the most recent yer for which dt hve been reported, which vries mong countries. Dt reported before the yer 2 re not shown. n FIGURE 4.3 Percentge of previously treted TB cses with MDR-TB Percentge of cses No dt Subntionl dt only Not pplicble Figures re bsed on the most recent yer for which dt hve been reported, which vries mong countries. Dt reported before the yer 2 re not shown. In six countries or territories, the high percentges of previously treted cses with MDR-TB refer to only smll number (1 8) of notified TB cses. These re: Bhrin; Belize; Bonire, Sint Eusttius nd Sb; Cyprus; Isrel; nd So Tomé nd Principe. GLOBAL TUBERCULOSIS REPORT 215 n 57

69 used to produce these estimtes re described in detil in n online technicl ppendix (vilble t dt). The number of incident cses includes cses mong notified TB ptients, cses mong people dignosed with TB tht were not notified to ntionl TB progrmmes (NTPs) in whom dignosis of MDR-TB ws missed, nd cses mong people not dignosed with TB t ll. Globlly in 214, there were n estimted 48 (rnge: 36 6 ) incident cses of MDR-TB. This number is essentilly unchnged from those published in recent globl TB reports, despite n upwrd revision to globl estimtes of the burden of TB following results from the 213/214 ntionl TB prevlence survey in Indonesi (which indicted tht there re bout 1 million rther thn.5 million incident TB cses per yer in this country; see Chpter 2). The explntion is tht the upwrd revision to the estimted number of incident cses of MDR-TB in Indonesi (equivlent to pproximtely 12 extr cses) hs been compensted for by reductions in the reported numbers of previously treted cses in severl high MDR-TB burden countries (for exmple, Indi); this ctegory of cse (especilly those not defined s relpse cses) hs n importnt influence on estimtes of the totl number of incident cses of MDR-TB. 1 There were pproximtely 19 (rnge: ) deths from MDR-TB in 214, comprble to estimtes published in recent globl TB reports. Dt compiled from surveys nd continuous surveillnce of drug resistnce mong TB ptients lso llow the production of globl s well s country-specific estimtes of the number of MDR-TB cses mong notified TB ptients with pulmonry TB. These re the MDR-TB cses tht could be detected if ll notified ptients were tested for drug resistnce to rifmpicin nd isonizid using WHO-recommended dignostic tests. Globlly, in 214 there were n estimted 3 (rnge: ) MDR-TB cses mong notified TB ptients; this is unchnged from the estimte for Of the 3 cses, 53% were mong new cses nd 47% were mong previously treted cses. Of note, the incresed number of TB cses notified in Indi between 213 nd 214 (Chpter 3) nd the higher proportions of MDR-TB detected in Ukrine in the ltest survey of drug resistnce were counter-blnced by lower numbers of new TB cses notified in Chin, the Russin Federtion nd Ukrine nd lower numbers of previously treted TB cses notified in Indi nd 1 The number of incident cses of MDR-TB is estimted s the sum of the number of cses in three distinct groups. These re (i) new cses of TB; (ii) relpse cses nd (iii) ll previously treted cses of TB, excluding those in the relpse ctegory. A review of methods used by WHO to estimte MDR-TB incidence nd mortlity is scheduled for 216. In line with retining current methods for the 215 trgets ssessment, methods to estimte the burden of MDR-TB hve not been chnged this yer (see lso Chpter 2, prticulrly Box 2.1 nd Box 2.2). Further detils bout the methods used to estimte the burden of MDR-TB re provided in the online technicl ppendix, vilble t tb/dt 2 WHO. Globl tuberculosis report 214. Genev: World Helth Orgniztion; 214 (WHO/HTM/TB/214.8). severl Estern Europen countries. Country-specific estimtes re discussed in section 4.2. Given the incresing use of moleculr dignostics tht detect RR-TB (Chpter 5), their growing importnce in detection of TB ptients with RR-TB (section 4.2) nd the fct tht the recommended tretment for people with RR-TB is the sme s for those with MDR-TB, monitoring nd evlution of the response to drug-resistnt TB requires more ttention to nd emphsis on the underlying burden of RR-TB. The burden of rifmpicin resistnce is presented in Box 4.1 nd compred with tht of MDR-TB Resistnce to second-line drugs XDR-TB, defined s MDR-TB plus resistnce to t lest one fluoroquinolone nd second-line injectble, hd been reported by 15 countries globlly by the end of 214. A totl of 83 countries nd five territories reported representtive dt from continuous surveillnce or surveys regrding the proportion of MDR-TB cses tht hd XDR-TB. Combining their dt, the verge proportion of MDR-TB cses with XDR-TB ws 9.7% (95% CI: %), similr to estimtes for previous yers (9.% in 213 nd 9.6% in 212). Fourteen of these countries reported 1 XDR-TB cses in the most recent yer for which dt were vilble. Among those countries, the proportion of MDR-TB cses with XDR-TB ws highest in Belrus (29% in 214), Georgi (15% in 214), Ltvi (19% in 214) nd Lithuni (25% in 213). Among the 36 high TB nd/ or MDR-TB burden countries, 23 hve surveillnce dt on second-line drug resistnce but only eight hve estblished ntionl continuous surveillnce system for second-line drug resistnce mong ptients with MDR-TB. Incresed ef forts should be mde to ensure tht ll ptients dignosed with MDR-TB undergo testing for susceptibility to fluoroquinolones nd injectble gents, nd tht results re recorded nd reported. The proportion of MDR-TB cses with resistnce to ny fluoroquinolone for which testing ws done, including ofloxcin, levofloxcin nd moxifloxcin, ws 21% (95% CI: %). 4.2 Mngement of drug-resistnt TB Coverge of drug susceptibility testing (DST) Trgets included in the Globl Pln to Stop TB cll for 2% of ll new bcteriologiclly-confirmed TB cses (i.e. those considered to be t high risk for MDR-TB) s well s ll previously treted cses to undergo DST to first-line TB drugs. 3 According to WHO recommendtions, ll ptients with MDR-TB should undergo testing for susceptibility to fluoroquinolones nd second-line injectble gents, to determine if they hve XDR-TB. There ws mjor progress in DST coverge between The Globl Pln to Stop TB : trnsforming the fight towrds elimintion of tuberculosis. Genev: World Helth Orgniztion; 21 (WHO/HTM/STB/21.2). 58 n GLOBAL TUBERCULOSIS REPORT 215

70 Box 4.1 Monitoring nd evlution of progress in the response to drug-resistnt TB: the incresing importnce of rifmpicin-resistnt TB (RR-TB) Following the rollout of moleculr tests for the detection of M. tuberculosis nd rifmpicin resistnce (line probe ssys nd Xpert MTB/RIF) (Chpter 5), the Globl TB Progrmme in WHO hs collected nd reported notifictions of drug-resistnt TB tht combine rifmpicin-resistnt TB (RR-TB) nd MDR-TB since 213. All RR-TB nd/or MDR-TB cses detected by either rpid moleculr dignostics or conventionl DST re reported s cses of drug-resistnt TB. Furthermore, in ccordnce with WHO recommendtions to enrol ll ptients dignosed with RR-TB on n MDR-TB drug regimen, tretment enrolment nd tretment outcomes of ptients receiving MDR-TB tretment hve been reported for ll ptients dignosed with RR-TB, including those tht did not hve MDR-TB. To dte, estimtes of the burden of drug-resistnt TB t globl, regionl nd country levels hve focused on MDR-TB. The number of cses with MDR-TB will be slightly lower thn the combined number of cses with MDR-TB or RR-TB (tht is not MDR-TB). This mens tht when the burden of MDR-TB is used s the denomintor for estimting detection nd tretment coverge, the vlues for both indictors will be slightly overstted. For these resons, it is becoming incresingly importnt to estimte the combined burden of MDR-TB nd RR-TB. In 214, the globl proportion of TB cses with MDR-TB, irrespective of tretment history, ws 7.7% (95%CI: %), with n estimted number of MDR-TB cses mong notified pulmonry TB ptients of 3. In the sme yer, the globl proportion of TB cses with RR-TB ws 8.8% (95%CI: %), mening tht there were pproximtely 4 dditionl cses of RR-TB tht were not MDR-TB. In future globl TB reports, greter emphsis will be given to estimtes of the combined burden of MDR-TB nd RR-TB when ssessing globl, regionl nd ntionl progress in the detection nd tretment of drug-resistnt TB. Compnion Hndbook to the WHO Guidelines for the Progrmmtic Mngement of Drug-Resistnt Tuberculosis. Genev: World Helth Orgniztion; 214 (WHO/HTM/TB/214.11). iris/bitstrem/1665/13918/1/ _eng.pdf. nd 214 (Figure 4.4, Figure 4.5). Globlly in 214, 12% of the 2.7 million new bcteriologiclly-confirmed TB cses nd 58% of the.7 million previously treted TB ptients were tested for drug resistnce in 214, up from 8.9% nd 17% respectively in 213. This represents proportionl increses in DST coverge of 43% nd 223% mong new nd previously treted cses, respectively. 1 Coverge ws highest in the Europen Region, where 97% of new cses were tested in 214 (Tble 4.2). In the South- Est Asi nd Western Pcific regions combined, two-thirds of previously treted cses underwent testing, reflecting reltively better ccess to DST in these regions. Levels of testing remined below 5% mong new cses in the South-Est Asi nd Estern Mediterrnen regions, while there ws substntil increse in testing coverge mong new bcteriologiclly confirmed cses in the Africn Region (from.9% in 213 to 6.4% in 214). Testing coverge mong previously treted cses lso improved considerbly in most regions, notbly from 5.8% to 67% in the South-Est Asi Region (driven lrgely by improved reporting from Indi) nd from 9.6% to 33% in the Africn Region. Among the 27 high MDR-TB burden countries which ccount for >85% of estimted MDR-TB cses in the world the proportion of TB ptients who were tested for drug susceptibility in 214 vried mrkedly (Tble 4.2). In nine of the 12 Europen countries tht reported dt, testing ws done for 95% of new cses; three of these countries reported universl coverge mong previously treted cses. Among 1 These figures re bsed on dt reported by 16 (73%) countries nd territories for new TB cses nd by 157 (72%) countries nd territories for previously treted cses. n FIGURE 4.4 DST coverge mong new cses nd enrolment on MDR-TB tretment, compred with the trgets in the Globl Pln to Stop TB, Lines indicte the plnned trgets, blue circles show the ctul sitution in Percentge of cses (%) Number of ptients DST coverge mong new bcteriologicllyconfirmed cses b. Enrolment on MDR-TB tretment GLOBAL TUBERCULOSIS REPORT 215 n 59

71 n FIGURE 4.5 DST coverge in previously treted TB cses, globlly nd for WHO regions, Numbers of cses tested re shown for ech br. Percentge of retretment cses (%) Afric 7 The Americs Estern Mediterrnen Europe South-Est Asi Western Pcific Globl DST is for rifmpicin only or for both rifmpicin nd isonizid. the high MDR-TB burden countries outside Europe, testing mong new cses ws highest in Mynmr (24%) nd Chin (19%). Among previously treted cses, testing coverge ws higher overll, nd reched 96% in Viet Nm, 88% in Indonesi nd 75% in the Democrtic Republic of the Congo. In South Afric, the equivlent of 69% of ll notified TB cses were tested, lthough DST dt were not vilble seprtely for new nd previously treted cses. Among MDR-TB ptients notified in 214, only 24% hd DST performed for both fluoroquinolones nd second-line injectble drugs. Coverge ws lowest in the Europen Region, likely s result of incomplete reporting of DST results from lbortories. Evidence of progress in DST coverge notwithstnding, dignostic DST must be further expnded, especilly given the cll for universl DST in the post-215 End TB Strtegy (Chpter 1). This requires continued strengthening of lbortory cpcity nd wider uptke of new rpid dignostics (see Chpter 5), s well s incresed deployment of informtion nd communiction technologies (ICT) to improve the completeness of reporting from lbortory nd tretment centres Notifiction of RR-TB nd MDR-TB cses Globlly, 123 cses of MDR-TB or RR-TB, who re eligible for tretment with MDR-TB regimens, were notified to WHO in 214. Indi, the Russin Federtion nd South Afric ccounted for lmost hlf of the totl (Tble 4.3). These 123 cses represented 41% of the estimted 3 (rnge, ) MDR-TB cses mong pulmonry TB ptients tht were notified in 214 (Figure 4.6), 1 nd 26% of the estimted 48 (rnge: 36 6 ) incident MDR-TB cses in the world in 214. The number of MDR/RR-TB cses reported for 214 ws nerly identicl to the ltest figure for 213. In this context, it should be highlighted tht the dt vilble t the time of preprtion of this report show tht the number of MDR/RR- TB cses detected globlly in 213 ws lower thn previously published, 2 following downwrd correction to numbers originlly reported for Indi. Increses in the number of detected cses did however occur between 213 nd 214 in Indi ( to ), Chin (4 183 to 5 87), the Russin Federtion ( to ), nd Mynmr (1 984 to 3 495). There were reductions between 213 nd 214 in the Philippines, South Afric, Ukrine, Uzbekistn nd severl other countries (Figure 4.7). The resons for the pprent stgntion in detection, given incresing DST coverge, re not cler nd should be investigted s mtter of priority. A comprison of the number of Xpert MTB/RIF crtridges procured nd the number of MDR/RR-TB cses detected in eight countries is provided in Box 4.2. The number of notified MDR/RR-TB cses s proportion of the estimted number of MDR-TB cses mong pulmonry TB ptients rnged from 19% in the Western Pcific Region to 8% in the Africn Region. In Kzkhstn, South 1 When compred with the estimte of ll MDR/RR-TB cses (not just the MDR-TB cses), this vlue would decrese to 36% (see lso Box 4.1). 2 The number published in the 214 globl TB report ws 136 in n GLOBAL TUBERCULOSIS REPORT 215

72 n TABLE 4.2 DST coverge mong TB nd MDR-TB cses, globlly nd for 27 high MDR-TB burden countries nd WHO regions, 214 NEW BACTERIOLOGICALLY CONFIRMED CASES RETREATMENT CASES CONFIRMED MDR TB CASES NUMBER WITH DST RESULTS % OF CASES WITH DST RESULT NUMBER WITH DST RESULTS % OF CASES WITH DST RESULT NUMBER WITH DST b RESULTS % OF CASES WITH DST RESULT Armeni Azerbijn 2 59 > > Bngldesh Belrus Bulgri Chin DR Congo Estoni 175 > Ethiopi Georgi Indi Indonesi Kzkhstn > >1 Kyrgyzstn Ltvi Lithuni 968 > Mynmr >1 Nigeri Pkistn Philippines Republic of Moldov Russin Federtion South Afric Tjikistn Ukrine Uzbekistn > Viet Nm High MDR TB burden countries AFR AMR EMR EUR SEAR WPR Globl Blnk cells indicte dt not reported. indictes vlues tht cnnot be clculted. The percentges my exceed 1% s result of the inclusion of extrpulmonry ptients mong cses tested or indequte linkges between lbortory nd clinicl registers. DST is for rifmpicin only or for both rifmpicin nd isonizid. b DST for fluoroquinolone nd second-line injectble drug. GLOBAL TUBERCULOSIS REPORT 215 n 61

73 TABLE 4.3 Estimted MDR-TB cses in 214, notified cses of rifmpicin-resistnt TB nd MDR-TB nd enrolments on MDR-TB tretment in 214, nd tretment outcome reporting for 212 cohort, globlly nd for 27 high MDR-TB burden countries nd WHO regions ESTIMATED MDR-TB AMONG NOTIFIED PULMONARY TB CASES, 214 NOTIFIED MDR/RR-TB CASES, 214 CASES ENROLLED ON MDR- TB TREATMENT, 214 MDR-TB CASES REPORTED WITH TREATMENT OUTCOME DATA, 212 COHORT b BEST ESTIMATE UNCERTAINTY INTERVAL NUMBER NOTIFIED/ ESTIMATED MDR-TB (%) NUMBER ENROLLED/ NOTIFIED MDR/RR TB (%) NUMBER % b Armeni >1 115 >1 Azerbijn Bngldesh Belrus > >1 Bulgri Chin DR Congo >1 Estoni Ethiopi > Georgi >1 623 >1 Indi Indonesi >1 Kzkhstn > > Kyrgyzstn Ltvi Lithuni Mynmr Nigeri >1 Pkistn Philippines >1 Republic of Moldov > Russin Federtion > >1 South Afric > Tjikistn > Ukrine > Uzbekistn Viet Nm >1 High MDR-TB burden countries AFR AMR EMR EUR > >1 SEAR WPR >1 Globl Notified cses of MDR/RR-TB in 214 s percentge of the best estimte of MDR-TB cses mong ll cses of pulmonry TB in the sme yer. The percentge my exceed 1% if estimtes of the number of MDR-TB re too conservtive nd if linkge between the clinicl nd lbortory registers is indequte. Percentges shown re slightly higher thn wht would be expected if n estimte for ll RR-TB cses (rther thn MDR-TB) ws used s denomintor (see lso Box 4.1). The percentge of MDR-TB cses originlly notified in 212 with outcomes reported. The percentge my exceed 1% s result of updted informtion bout MDR-TB cses in 212, indequte linkges between notifiction systems for TB nd MDR-TB, the inclusion of RR-TB cses in the numertor who were not confirmed MDR-TB, nd the inclusion in the tretment cohort of cses of MDR-TB from yer prior to n GLOBAL TUBERCULOSIS REPORT 215

74 Box 4.2 The roll-out of rpid TB dignostics compred with chnges in the number of cses of MDR/RR-TB notified by ntionl TB progrmmes Globl progress in the detection of drug-resistnt TB should be relted to the roll-out of moleculr dignostics such s Xpert MTB/RIF nd line probe ssys (LPAs). However, s use of these technologies expnds, the number of tests required to detect one cse my increse. This is becuse initil use of the test is likely to focus on groups with higher risk of hving MDR/ RR-TB (such s previously treted TB ptients), in line with policy recommendtions, b nd then broden to cover people t lower risk for drug-resistnce (such s ptients being evluted for TB). Vrition mong countries is lso expected given dif ferences in the prevlence of MDR/RR-TB (for exmple, the prevlence of MDR-TB is much higher in Ukrine compred with Bngldesh). The reltionship between nnul procurements of Xpert MTB/RIF crtridges nd notifictions of MDR/RR-TB cses for 8 high MDR-TB burden countries is shown in Figure B These countries re mong the mjor users of Xpert globlly (ech hving procured crtridges in 214) nd Xpert is of ten the leding dignostic test for drug resistnce tht is in use. Although there ws substntil vrition in the number of MDR/RR-TB cses reported for every 1 Xpert crtridges procured, the rtio tended to decrese over time in ll countries. It ws striking tht shrp flls in the number of MDR/RR-TB cses detected for every 1 Xpert crtridges procured in Ethiopi nd the Philippines between 213 nd 214 occurred longside n bsolute reduction in the totl number of reported MDR/RR-TB cses. The resons for this re not well understood. Possible explntions include issues with reporting of cses, s opposed to ctul levels of testing or lbortory results, nd lg times between orders nd ctul use of tests. For further detils bout these technologies, see Chpter 5. b Xpert MTB/RIF implementtion mnul: technicl nd opertionl how-to ; prcticl considertions. Genev: World Helth Orgniztion; 214 (WHO/HTM/TB/214.1). bitstrem/1665/112469/1/ _eng.pdf. FIGURE B4.2.1 The number of MDR/RR-TB cses reported for every 1 Xpert crtridges procured in selected high MDR-TB burden countries, Bngldesh Ethiopi Indonesi Nigeri Number (log scle) Pkistn Philippines Ukrine Viet Nm Afric, nd Tjikistn the figure ws bove 1% (Tble 4.3), indicting either repeted reporting of cses when informtion systems re bsed on lbortory results without linkge to ptient registers, nd/or tht estimtes of MDR-TB re too conservtive (for exmple, becuse drug resistnce surveillnce dt hve become outdted) Enrolment of notified RR-TB nd MDR-TB cses on tretment The number of ptients enrolled globlly on MDR-TB tretment ws 111 in 214, up from 97 in 213. There ws 13% increse in enrolments between 213 nd 214 in the 27 high MDR-TB burden countries, with increments exceeding 1 ptients in Indi, Pkistn, the Russin Federtion nd Uzbekistn. Globlly, the number of ptients strting second-line GLOBAL TUBERCULOSIS REPORT 215 n 63

75 n FIGURE 4.6 Number of MDR TB cses estimted to occur mong notified pulmonry TB cses, 214 Estimted MDR-TB cses No dt Not pplicble MDR-TB tretment ws 9% of those notified with MDR/ RR-TB in 214 (Tble 4.3). The rtio ws over 9% in 15 high MDR-TB burden countries, the Europen Region nd the Region of Americs. The rtio ws lowest in the Western Pcific (66%) nd Africn (68%) regions. In eight high MDR-TB burden countries, enrolments outstripped notifictions of MDR/RR-TB (Figure 4.7). This my be cused by empiricl tretment of TB ptients considered t risk of hving MDR-TB but for whom lbortory-confirmed dignosis ws missing, incomplete reporting of lbortory dt, or enrolment of witing lists of people with MDR- TB who were detected before 214. In contrst, the rtio of enrolled to dignosed cses ws under 6% in 3 high MDR-TB burden countries in 214, nd below 5% in Chin (49%) nd Mynmr (44%). These low rtios show tht progress in detection is fr outstripping cpcity to provide tretment but my lso reflect weknesses in dt collection systems. Overll, while the number of ptients being enrolled on tretment for MDR-TB continues to increse, progress flls fr short of Globl Pln trgets (Figure 4.4b, Tble 4.3). Getting closer to the Globl Pln trgets requires intensifiction of ef forts in mny countries, but prticulrly Chin nd the Russin Federtion. These two countries rnk second nd third globlly in terms of estimted numbers of cses, while levels of detection nd tretment coverge remin reltively low. Continued support to NTPs through updted guidnce, s well s direct technicl ssistnce provided through the mechnisms of the Regionl Green Light Committees nd the Globl Drug-resistnt TB Inititive ( mdrtb/), is expected to improve globl detection nd tretment of drug-resistnt TB. In 214, 49 countries nd territories reported treting people with XDR TB (Figure 4.8). Globlly, 4 44 ptients with XDR-TB were enrolled on tretment (higher thn the level of in 213). Most of the cses in 214 were notified from Indi (1 262, up from 392 in 213), Ukrine (657), South Afric (562), Belrus (431), nd Kzkhstn (318) Accelerting the scle-up of detection nd enrolment on tretment for people with drug-resistnt TB: the role of models of cre nd non-ntp providers In mny countries, one of the resons for indequte ccess to dignosis nd tretment of drug-resistnt TB is tht the network for the progrmmtic mngement of drugresistnt TB (PMDT) is too centrlized. Hospitl-bsed models of cre, which re still dominnt in mny countries, re brrier to the expnsion of PMDT becuse they depend on hospitls or referrl centres. Greter use of mbultory cre s prt of decentrlized PMDT services is necessry to expnd ccess. However, ntionl policies nd prctices vry nd hospitliztion is still the predominnt model of cre in mny countries. Among the 27 high MDR-TB burden countries, the Democrtic Republic of the Congo reported the lowest level of 64 n GLOBAL TUBERCULOSIS REPORT 215

76 n FIGURE 4.7 MDR TB cses nd dditionl rifmpicin resistnt TB cses detected (red) compred with TB cses enrolled on MDR TB tretment (blue), globl trend nd trend in 27 high MDR TB burden countries, Globl Armeni Azerbijn Bngldesh Belrus Bulgri Chin DR Congo Number of cses Estoni 9 Ethiopi 6 Georgi 8 Indi Indonesi 2 Kzkhstn 9 Kyrgyzstn Ltvi Lithuni 6 Mynmr 4 Nigeri 8 Pkistn Philippines Republic of Moldov Russin Federtion South Afric Tjikistn Ukrine Uzbekistn Viet Nm The globl totl of MDR/RR-TB cses detected in 213 (123 1) is lower thn previously published in the 214 Globl TB Report ( ) following revisions to dt reported by Indi GLOBAL TUBERCULOSIS REPORT 215 n 65

77 n FIGURE 4.8 Number of ptients with lbortory confirmed XDR TB strted on tretment in 214 Number of ptients No dt Not pplicble hospitliztion (5% of MDR-TB ptients), followed by Mynmr (1%). In contrst, hospitliztion for 1% of MDR-TB ptients in 214 (t lest for prt of their tretment) ws reported by 1 high MDR-TB countries, including two of the top three MDR-TB burden countries: Chin nd the Russin Federtion. In further six high MDR-TB burden countries, t lest 9% of MDR-TB ptients were hospitlized. When MDR-TB ptients re hospitlized the durtion of sty ws reltively short in Indonesi, t five dys, nd rnged from 3 6 dys in five other countries (Bngldesh, Chin, Estoni, Ethiopi, Mynmr). In the other 15 countries tht reported dt, the verge length of sty ws 16 dys. The number of visits to helth fcility f ter dignosis of MDR-TB lso vried mrkedly, from less thn 3 (Bngldesh, Estoni, Mynmr, nd South Afric) to over 7 (Armeni, Georgi, Indonesi, Russin Federtion nd Ukrine). The involvement of ll relevnt non-ntp helth cre providers is importnt to scle up PMDT nd improve ccess to services. Unfortuntely, relible dt on these ctivities re of ten not collected by NTPs. In 214, only nine high MDR-TB burden countries provided informtion on the numbers of ptients strted on MDR-TB tretment by non-ntp helth cre providers. The Philippines, Ltvi nd Kyrgyzstn reported tht 22%, 14% nd 11% respectively of MDR-TB cses were treted by non-ntp providers, while figures of 1 5% were reported to be treted in the privte sector in Mynmr, Viet Nm nd four Estern Europen countries: Armeni, Republic of Moldov, Ukrine nd Uzbekistn. In 214, only 39 countries (including 13 of the 27 high MDR-TB burden countries) reported tht pllitive nd endof-life cre were provided within the scope of their NTPs. This finding ttests to the huge unmet need for such services, which should be delivered longside proper infection control mesures (since most of these ptients remin source of infection) Tretment outcomes for ptients with MDR-TB nd XDR-TB The Globl Pln included trget tht ll countries should report outcomes for ll notified MDR-TB cses by 215. A totl of 127 countries nd territories reported tretment outcomes for cses strted on MDR-TB tretment in 212. The country cohort size rnged from 1 to 16 cses. The number of cses reported in nnul cohorts hs stedily incresed in ll six WHO regions over time (with the exception of smll decrese in the Region of the Americs between the 211 nd the 212 cohorts). The totl reched 7 cses globlly in 212, 33% more thn in 211 (Tble 4.3 nd Figure 4.9). The use of electronic systems to mnge MDR-TB ptient dt could help to improve the completeness of reporting on tretment outcomes. One of the Globl Pln trgets is for ll 27 high MDR-TB countries to mnge their dt on tretment of MDR-TB ptients electroniclly by 215. By 214, 15 of these countries reported tht ntionl electronic dtbses were in plce for TB ptients nd nother six hd systems for MDR- TB ptients only. 66 n GLOBAL TUBERCULOSIS REPORT 215

78 n FIGURE 4.9 Tretment outcomes for ptients dignosed with MDR TB by WHO Region, cohorts. The totl number of cses with outcome dt is shown beside ech br Afric The Americs Estern Mediterrnen Europe South-Est Asi Western Pcific Globl Percentge of cohort Tretment success Filure Died Lost to follow-up Not evluted Percentge of cohort Overll, the proportion of MDR-TB ptients in the 212 cohort who successfully completed tretment (i.e. cured or tretment completed) ws 5%; 16% died, 16% were lost to follow-up, tretment filed for 1% nd 8% hd no outcome informtion (Figure 4.9). The tretment success rte ws highest in the Estern Mediterrnen Region (65%), nd lowest in the Europen nd South-Est Asi regions (49%). In the 212 cohort, tretment filure ws highest in the Europen Region (13%), nd the deth rte ws highest in the South- Est Asi Region (21%). The Globl Pln trget of chieving tretment success rte of 75% by 215 hd lredy been reched in 4 of the 122 countries tht reported outcome dt for the 212 cohort, including three of the 27 high MDR-TB burden countries (Estoni, Ethiopi, nd Mynmr). Between 27 nd 212, more thn 1 people who strted MDR-TB tret- GLOBAL TUBERCULOSIS REPORT 215 n 67

79 ment were reported to hve hd successful outcome nd numbers hve incresed over time (dt not shown). Among XDR-TB ptients in the 212 cohorts of 41 countries for whom outcomes were reported, 682 (26%) completed tretment successfully; 89 (3%) died; tretment filed for 51 (19%); nd 684 (25%) were lost to follow-up or their tretment outcome ws not evluted. The Russin Federtion ccounted for 51% of the XDR-TB ptients for whom outcomes were reported in 212. The high mortlity of XDR-TB ptients in South Afric (47%) is likely to be ssocited with high level of HIV co-infection in TB ptients (see Chpter 6). The introduction of new drugs nd novel regimens could potentilly improve the tretment outcomes of ptients with MDR- nd XDR-TB. By the end of 214, t lest 43 countries reported hving used bedquiline to tret ptients s prt of ef forts to expnd ccess to tretment for MDR-TB, either for compssionte use or under norml progrmmtic conn FIGURE 4.1 Countries tht hd used bedquiline for the tretment of M/XDR-TB s prt of expnded ccess, compssionte use or under norml progrmmtic conditions by the end of 214 Yes No No dt Not pplicble ditions in the public or privte sectors (Figure 4.1). Most (75%) of these ptients were from two countries: the Russin Federtion nd South Afric. In ddition, t lest 16 countries in Afric nd Asi hve introduced shorter regimens s prt of trils or observtionl studies under opertionl reserch conditions, nd severl hve strted to include repurposed drugs in tretment regimens, to try to improve the tretment outcomes of MDR-TB nd XDR-TB ptients. Since the strt of globl monitoring, tretment success rtes mong ptients with MDR-TB nd XDR-TB hve remined consistently nd uncceptbly low. Mjor ef forts re required to ddress this sitution, using mesures tht re prt of the End TB Strtegy. These include dequte resources for detection nd tretment nd building cpcity mong helth cre workers to provide high qulity cre. Reserch nd development is lso crucil. Without new TB drugs nd regimens, it will be very dif ficult to improve tretment outcomes in the ner future. 68 n GLOBAL TUBERCULOSIS REPORT 215

80 CHAPTER 5 Dignostics nd lbortory strengthening Key fcts nd messges The End TB Strtegy clls for the erly dignosis of TB nd universl drug susceptibility testing (DST), highlighting the criticl role of lbortories in the post-215 er for rpidly nd ccurtely detecting TB nd drug resistnce. Lbortory confirmtion of TB nd drug resistnce is essentil to ensure tht individuls with TB re correctly dignosed nd hve ccess to the pproprite tret ment s soon s possible. Of the 5.2 million incident (new nd relpse) pulmonry TB ptients notified globlly in 214, 3. million (58%) were bcteriologiclly confirmed, i.e., were smer- or culturepositive or positive ccording to WHO-recommended rpid dignostic such s Xpert MTB/RIF. Among new (previously untreted) cses of bcteriologiclly confirmed TB, 12% hd ccess to DST; mong previously treted cses, 58% hd ccess to DST. A new WHO Policy frmework for implementing tuberculosis dignostics ws published in April 215. This provides n overview of ll current WHO policy recommendtions on TB dignostics nd the role of ech test within ef fective dignostic lgorithms cross lbortory network. The document lso describes the mngeril, technicl nd opertionl processes required for developing nd implementing comprehensive ntionl strtegy for TB lbortories. WHO hs recently issued policy recommendtions on the use of the urine lterl flow liporbinomnnn (LF-LAM) ssy (Alere Determine TM TB LAM Ag test). The test is not recommended for TB screening or dignosis of TB in most popultion groups. However, it is recommended to help with the dignosis of TB in two popultion groups: HIV-positive people who re inptients with signs or symptoms of TB nd who hve CD4 cell count less thn or equl to 1 cells/µl, nd HIV-positive people who re seriously ill (both inptients nd outptients) with dnger signs, regrdless of CD4 count or if the CD4 count is unknown. The use of the rpid moleculr test Xpert MTB/RIF continues to expnd in line with WHO recommendtions for its use since December 21. By the end of 214, 69% of countries reported tht ntionl policy by the end of 214 indicted the use of Xpert MTB/RIF s the initil dignostic test for people t risk of drug-resistnt TB, nd 6% reported tht ntionl policy indicted its use s the initil dignostic test for people living with HIV. In 116 of the 145 countries eligible for concessionl pricing tht hve purchsed the technology, totl of GeneXpert mchines hd been procured for use in the public sector by the end of 214. In 214 lone, 4.8 million Xpert MTB/ RIF test crtridges were procured, up from 55 in 211. Ensuring the qulity of microscopy networks is criticl, given tht smer microscopy remins the most widely used tool for TB dignosis in low- nd middle-income countries. Among the 22 HBCs, only four reported n externl qulity ssessment scheme tht encompssed ll microscopy centres in 214, nd five more reported progrmme tht included t lest 9% of centres. Severl sources of guidnce nd trining pltforms hve been developed to ssist TB reference lbortories to implement qulity mngement system tht meets interntionl ccredittion stndrds. In 214, 123 of 173 responding countries nd territories (71%) indicted tht forml qulity mngement system towrds chieving lbortory ccredittion hd t lest been strted t the ntionl reference lbortory (NRL). In 215, the WHO TB Suprntionl Reference Lbortory Network expnded to include three newly designted Ntionl Centres of Excellence in the Russin Federtion. The three lbortories re of prticulr vlue for estblishing nd mintining high-qulity lbortory services within the country for the progrmmtic mngement of drug-resistnt TB, including through the coordintion of technicl ssistnce, provision of monitoring nd supervision, nd orgniztion of trining for lbortory stf f involved in dignostic testing for drug resistnce nd monitoring of tretment for ptients with drug-resistnt TB. The microbiologicl detection of TB nd drug susceptibility using rpid WHO-recommended dignostics, together with n ef ficient system for trnsfer of specimens nd results, llows ptients to be correctly dignosed nd strted on the most ef fective tretment regimen s erly s possible. One of the core components of the first pillr of the post-215 End TB Strtegy (Chpter 1) is the erly dignosis of TB, including universl drug susceptibility testing (DST). Opertionl guidnce on the implementtion of the strtegy clls for ll ptients to receive DST t lest for rifmpicin, with further tests for drug susceptibility to first nd second-line drugs for ny TB ptients found to hve rifmpicin resistnce. A wellequipped nd stf fed, qulity-ssured lbortory network with n ef ficient referrl system is therefore n essentil requirement for ny ntionl TB progrmme (NTP) in the post-215 er. For decdes, resource-constrined countries hve relied on sputum smer microscopy s the primry method for detect- GLOBAL TUBERCULOSIS REPORT 215 n 69

81 ing TB. While inexpensive nd requiring miniml biosfety stndrds, microscopy is not sensitive test (prticulrly for people living with HIV nd children) nd it provides no informtion on the resistnce profile of the bcilli. Furthermore, microscopy is not ble to distinguish between Mycobcterium tuberculosis complex nd non-tuberculosis mycobcteri. Bcteriologicl culture is considered the reference stndrd for detecting TB, but suf fers from the disdvntges tht results tke weeks to obtin nd tht testing requires well-equipped lbortory, highly trined stff, nd n efficient trnsport system to ensure the vibility of specimens. Phenotypic DST on cultured specimens is the conventionl method used to detect resistnce to first- nd second-line TB drugs, nd fster commercil liquid culture systems re now vilble. Building dequte culture cpcity in mny countries with high burden of TB hs been slow, given the cost nd infrstructure requirements. In recent yers, limited but growing number of rpid nd more sensitive tests for TB nd drug-resistnt TB bsed on moleculr methods, including Xpert MTB/RIF (Cepheid, USA) nd line probe ssys (LPAs), hve become vilble to replce or complement existing conventionl tests. Despite the dvntges of moleculr tests, conventionl microscopy nd culture remin necessry for monitoring ptients response to tretment. Furthermore culture-bsed DST methods re currently the only methods vilble for ccurte testing of susceptibility to second-line drugs. Of the 5.2 million incident pulmonry TB ptients notified globlly in 214, only 3. million (58%) were bcteriologiclly confirmed, i.e., were smer- or culture-positive or positive ccording to WHO-recommended rpid dignostic such s Xpert MTB/RIF (Chpter 3). The remining 42% of ptients who were not bcteriologiclly confirmed were dignosed cliniclly, i.e. bsed on symptoms, chest X-ry bnormlities or suggestive histology. The common symptoms of TB combined with the poor specificity of X-ry screening my result in flse dignoses nd people without TB being enrolled on TB tretment when it is not needed. Furthermore, low rte of lbortory confirmtion reflects under-dignosis of true TB cses nd contributes in prt to the continuing globl gp between notified nd estimted incident TB cses: 6 million nd 9.6 million in 214, respectively (Chpter 3). The proportion of new nd previously treted cses receiving DST hs stedily incresed but much remins to be done. Globlly, 12% of new bcteriologiclly-confirmed TB cses nd 58% of those previously treted for TB were tested for drug resistnce in 214 (Chpter 4). Lbortory strengthening nd new dignostics re crucil to improve the proportion of notified TB cses with definitive (bcteriologiclly confirmed) dignosis of TB, nd to close detection nd tretment gps for TB nd drug-resistnt TB. This chpter summrizes the sttus of progress in 214. Section 5.1 highlights key developments in WHO guidnce on TB dignostics nd lbortory strengthening during Section 5.2 presents the sttus of lbortory cpcity globlly, regionlly nd ntionlly in 214, bsed on dt reported to WHO by countries in 215. Here, the focus is on the 36 countries in the combined list of 22 high burden countries (HBCs) nd 27 high MDR-TB burden countries. Section 5.3 describes recent ctivities to strengthen TB lbortories, including qulity mngement systems, externl qulity ssessment nd the WHO TB Suprntionl Reference Lbortory (SRL) Network. 5.1 Developments in WHO policy guidnce on TB dignostics nd lbortory strengthening, The WHO Globl TB Progrmme follows systemtic process for development of policy recommendtions on TB dignostics, involving synthesis of the vilble evidence on performnce nd cost ef fectiveness through systemtic reviews, met-nlyses nd modelling s pproprite, ssessment of the evidence by n externl Guideline Development Group using the GRADE pproch, 1 nd development of policy guidnce 2 for dissemintion to Member Sttes nd other stkeholders. Policy documents re reviewed periodiclly, nd revised s necessry when new evidence becomes vilble. In June 215, WHO convened Guideline Development Group to review the evidence on the use of the urine lterl flow liporbinomnnn (LF-LAM) ssy (Alere Determine TM TB LAM Ag test, Alere Inc, USA) for detection of TB in people living with HIV. A liporbinomnnn (LAM) ntigen is lipopolyscchride present in mycobcteril cell wlls, which is relesed from metboliclly ctive or degenerting bcteril cells nd ppers to be present only in people with ctive TB disese. Tests bsed on the detection of LAM in urine hve the potentil to be point-of-cre tests for TB. Further dvntges over sputum-bsed testing re tht urine is esy to collect nd store, nd lcks the infection control risks ssocited with sputum collection. The urinry LAM ssys currently vilble re unsuitble s generl dignostic or screening tests for TB, due to suboptiml sensitivity. However, unlike trditionl dignostic methods for TB, they demonstrte improved sensitivity mong people living with HIV, which further increses s CD4 counts fll. Following the Guideline Development Group s evlution of the LF-LAM ssy, the resulting 215 WHO policy recommendtions on its use re summrized in Box 5.1. In the coming yer, evlutions nd updted reviews re plnned for severl other technologies. These include LPAs for detection of resistnce to first- nd second-line drugs (Hin LifeScience, Germny; nd Nipro Corp., Jpn); the use of sequencing for detection of resistnce-conferring muttions; nd the Xpert Ultr ssy nd GeneXpert Omni (Cepheid, USA). Further potentil technologies on the evlu WHO hndbook for guideline development, 2nd ed. Genev, World Helth Orgniztion; 214. Avilble t: hndbook_2nd_ed.pdf. 7 n GLOBAL TUBERCULOSIS REPORT 215

82 Box 5.1 WHO recommendtions on urine lterl flow liporbinomnnn (LF-LAM) ssy (Alere Determine TM TB LAM Ag test, Alere Inc, USA) The 215 WHO recommendtions on LF-LAM ssy re: 1. LF-LAM should not be used for the dignosis of TB, except s specificlly described below for persons with HIV with low CD4 counts or who re seriously ill (strong recommendtion; low qulity of evidence). 2. LF-LAM my be used to ssist in the dignosis of TB in HIV-positive dult inptients with signs or symptoms of TB (pulmonry nd/or extrpulmonry) who hve CD4 cell count less thn or equl to 1 cells/µl, or HIV-positive ptients who re seriously ill regrdless of CD4 count or with unknown CD4 count (conditionl recommendtion; low qulity of evidence). Remrks " This recommendtion lso pplies to HIV-positive dult outptients with signs nd symptoms of TB (pulmonry nd/or extrpulmonry) who hve CD4 cell count less thn or equl to 1 cells/µl, or HIV-positive ptients who re seriously ill regrdless of CD4 count or with unknown CD4 count, bsed on the generlistion of dt from inptients. " This recommendtion lso pplies to children, bsed on the generlistion of dt from dults while cknowledging very limited dt nd concern regrding the low specificity of the LF-LAM ssy in children. 3. LF-LAM should not be used s screening test for TB (strong recommendtion; low qulity of evidence). seriously ill is defined bsed on four dnger signs: respirtory rte > 3/min, temperture >39 C, hert rte >12/min nd unble to wlk unided. tion horizon include severl rpid nd sensitive dignostic tests tht re expected to be vilble for use t reference lbortory level s well s closer to or t the point of ptient cre (Chpter 8). In April 215, new WHO Policy frmework for implementing tuberculosis dignostics ws published. 1 This document provides comprehensive guidnce on the mngeril, technicl nd opertionl processes required for developing nd implementing comprehensive ntionl strtegy for TB lbortories, which encompss erly dignosis of TB nd universl ccess to DST s well s systemtic screening of contcts of people with TB nd high-risk groups. The positioning of WHO-recommended dignostics t dif ferent levels of lbortory network is described, nd templtes of dignostic lgorithms re presented. This generic policy frmework 1 WHO Policy frmework for implementing tuberculosis dignostics. Genev, World Helth Orgniztion; 215. Avilble t: who.int/tb/publictions/implementing_tb_dignostics/en/ cn be dpted nd customized t country level to ccount for the wide vrition in country resources nd needs, s well s dif ferences in the epidemiology of TB, HIV-ssocited TB nd drug-resistnt TB. A comprehensive list of existing WHO policy documents, including on the use of microscopy, culture, DST nd non-commercil nd moleculr dignostic methods, is vilble t: Sttus of lbortory cpcity globlly, regionlly nd ntionlly Smer microscopy continues to be the most widely used tool for TB dignosis in low- nd middle-income countries, despite its shortcomings. A microscopy network with dequte popultion coverge nd high qulity performnce (see Section 5.3) is therefore criticl. The Globl Pln to Stop TB includes the trget tht countries mintin t lest one smer microscopy centre per 1 popultion. 2 Globlly, the trget hs been met (1.1 centres per 1 popultion in 214), but significnt disprities remin t regionl nd country levels (Tble 5.1). For exmple, the Western Pcific nd Estern Mediterrnen regions hd less thn one centre per 1 popultion in 214. The trget now requires country-specific dpttion given the incresed use of Xpert MTB/RIF s n initil dignostic test, especilly in settings with high burdens of HIV nd MDR-TB. In ddition, it is importnt to emphsize tht geogrphic vritions in the TB epidemic within country s well s differences in ccess between urbn nd rurl settings require tht the number nd plcement of microscopy centres re strtegiclly considered within countries. Fluorescent light-emitting diode (LED) microscopy is more sensitive thn conventionl Ziehl Neelsen (ZN) light microscopy nd hs further qulittive, opertionl nd cost dvntges. In 29, WHO recommended tht LED microscopy be phsed in s n lterntive for ZN microscopy. Globlly, the switch to LED microscopes hs been grdul: the technology ws reported to hve been present in only 7% of microscopy centres in 214, up from 2% in 212. Nonetheless, mjor progress is evident in certin countries. Among HBCs, mjor dopters of LED microscopy include South Afric (1% of microscopy sites in 214), Chin (38%), Mynmr (31%), Bngldesh (22%), Keny (21%) nd Mozmbique (21%). Adoption of LED microscopy remins prticulrly low in Indonesi (%), Afghnistn (<1%), Brzil (<1%), Philippines (<1%), the Democrtic Republic of the Congo (1%), Indi (2%), nd Viet Nm (2%). The current trget in the Globl Pln to Stop TB for both culture nd DST (to t lest rifmpicin nd isonizid) 2 The Globl Pln to Stop TB, Genev, World Helth Orgniztion; 21 (WHO/HTM/STB/21.2). GLOBAL TUBERCULOSIS REPORT 215 n 71

83 n TABLE 5.1 Lbortory cpcity, 214 SMEAR MICROSCOPY CULTURE DRUG SUSCEPTIBILITY TESTING LINE PROBE ASSAY XPERT MTB/RIF HIGH TB BURDEN HIGH MDR-TB BURDEN NUMBER OF LABORATORIES LABORATORIES PER 1 POPULATION PERCENTAGE OF LABORATORIES USING LED MICROSCOPES YES NO Afghnistn < Armeni Azerbijn Bngldesh <.1 3 <.1 1 <.1 38 Belrus Brzil < <.1 48 Bulgri Cmbodi Chin DR Congo <.1 39 Estoni Ethiopi Georgi Indi Indonesi <.1 41 Kzkhstn Keny Kyrgyzstn Ltvi Lithuni Mozmbique Mynmr Nigeri Pkistn Philippines < <.1 84 Republic of Moldov Russin Federtion South Afric Tjikistn Thilnd Ugnd Ukrine UR Tnzni < Uzbekistn < Viet Nm Zimbbwe High-burden countries High MDR-TB burden countries AFR AMR EMR EUR SEAR WPR Globl indictes vlues tht cnnot be clculted. The regionl nd globl figures re ggregtes of dt reported by low- nd middle-income countries nd territories. Dt for the vribles shown in the tble re not requested from high-income countries in the WHO dt collection form. NUMBER OF LABORATORIES LABORATORIES PER 5 MILLION POPULATION NUMBER OF LABORATORIES LABORATORIES PER 5 MILLION POPULATION NUMBER OF LABORATORIES LABORATORIES PER 5 MILLION POPULATION NUMBER OF SITES 72 n GLOBAL TUBERCULOSIS REPORT 215

84 cpcity is one lbortory per 5 million popultion. In 214, 12 of the 27 high MDR-TB burden countries did not rech the trget (Tble 5.1), nd severl countries with lrge TB cselods continue to completely lck in-country cpcity for phenotypic DST (Figure 5.1). In 214, 12 countries reported more thn 1 notified TB cses but no cpcity to perform phenotypic DST: Afghnistn, Burkin Fso, Chd, Congo, Equtoril Guine, Gbon, Guine-Bissu, Ppu New Guine, Sierr Leone, Somli, South Sudn nd Timor Leste. Among these, Equtoril Guine nd Sierr Leone lso reported lcking ny cpcity for Xpert MTB/RIF testing, which would t lest llow for detection of rifmpicin resistnce. Ptients with MDR-TB require DST for second-line drugs to refine nd optimize their tretment regimen. Some countries with smll cselods of MDR-TB ptients hve resonbly opted to rely on prtner lbortories (including WHO Suprntionl Reference Lbortories) for such testing, insted of building in-country cpcity. However, 28 countries with reported RR/MDR-TB cses indicted tht they hd neither in-country cpcity nor linkge with prtner lbortory for second-line DST: Albni, Cmbodi, Centrl Africn Republic, Chd, Congo, Djibouti, Eritre, Gbon, Ghn, Guine, Guine-Bissu, Guyn, Jordn, Keny, Kuwit, Mlwi, Mli, Muritni, Muritius, Morocco, Pnm, Prguy, So Tome nd Principe, Sudi Arbi, Syrin Arb Republic, Togo, Turkmenistn nd Yemen. Countries with sizeble TB nd MDR-TB cselods should im s priority to build sustinble in-country cpcity to undertke DST to t lest rifmpicin, to llow the timely dignosis of drug-resistnt strins. As high-throughput moleculr tool for use t centrl nd regionl levels, LPAs hve been dopted by mny countries for rpid first-line DST (to rifmpicin nd isonizid) on smer-positive specimens or cultures. In 214, 92 countries nd territories reported t lest one fcility with cpcity to perform LPA tests. Of the 27 high MDR-TB burden countries, 13 reported LPA cpcity in more thn one lbortory per 5 million popultion. Following initil WHO recommendtions issued in December 21, Xpert MTB/RIF hs been quickly dopted by countries s n ef fective tool for the rpid detection of TB nd rifmpicin resistnce t lower levels of the helth system. By the end of December 214, totl of GeneXpert instruments comprising modules hd been procured in the public sector in 116 of the 145 countries eligible for concessionl pricing. In 214, 4.8 million test crtridges were procured by eligible countries (Figure 5.2), up from 55 in 211. Of these, 51% (2.4 million) went to South Afric. The originl WHO policy guidnce on Xpert MTB/RIF issued in 21 recommends its use s the initil dignostic test in individuls suspected of hving MDR-TB or HIV-ssocited TB (strong recommendtions). A policy updte in 213 expnded its recommended uses, including for the dignosis of TB in children, on selected specimens for the dignosis n FIGURE 5.1 Globl cpcity for drug-susceptibility testing (DST), 214 1st- nd 2nd-line DST 1st-line DST only Xpert MTB/RIF only No cpcity No dt Not pplicble Dt for 213 were used if dt for 214 were not reported (n=6). GLOBAL TUBERCULOSIS REPORT 215 n 73

85 n FIGURE 5.2 Xpert MTB/RIF crtridge procurements in 214 t concessionl prices Xpert MTB/RIF crtridges procured in 214 (thousnds) Not eligible for preferentil pricing Not pplicble of extrpulmonry TB, nd for ll individuls suspected of hving pulmonry TB (conditionl recommendtions). High-burden countries hve lrgely dopted the strong recommendtions on its use s the initil dignostic test for individuls suspected of hving MDR-TB or HIV-ssocited TB (Tble 5.2). While 19 of the 22 high TB burden countries hve indicted policies on the use of Xpert MTB/RIF for individuls suspected of hving HIV-ssocited TB, not ll of the 41 TB/HIV priority countries reported hving such policy: by the end of 214, Centrl Africn Republic, Chd, Chin, Cote d Ivoire, Mlwi, Mynmr, Nmibi, Sierr Leone nd Sudn indicted tht Xpert MTB/RIF ws not yet the initil dignostic test for people suspected of hving HIV-ssocited TB (see lso Box 6.2 in Chpter 6). Incresingly, countries re lso updting their policies to include the use of Xpert MTB/RIF for children nd for detection of extrpulmonry TB (5% nd 41% of ll reporting countries, respectively). A smll number of countries with suf ficient resources, including South Afric, Swzilnd nd Moldov, re lso plcing Xpert MTB/RIF s the initil dignostic test for ll people suspected of hving TB. Some countries tht cnnot f ford the use of Xpert MTB/RIF s the initil dignostic test for ll people with suspected TB hve introduced dignostic lgorithms in which chest X-ry is used s n initil screening tool, with those with X-ry bnormlities then eligible for testing using Xpert MTB/ RIF. As countries continue to scle-up coverge of Xpert MTB/RIF testing, lgorithms should be widened to increse ptient ccess to the test s sensitive nd rpid tool both for detection of rifmpicin resistnce nd for TB cse-finding. The growing number of drug-resistnt cses being detected by Xpert MTB/RIF nd LPAs requires djustment of country culture nd phenotypic DST cpcities. The introduction of Xpert MTB/RIF nd LPAs reduces the need for culture s the initil dignostic test, but t the sme time the growing detection of drug-resistnt TB cses requires culture cpcity for monitoring of tretment nd DST of other nti-tb drugs to guide tretment djustments. It is lso impertive tht the incresing cpcity of countries to dignose drug-resistnt TB is mtched by incresed cpcity to provide pproprite tretment to ll dignosed cses (see lso Chpter 4). One of the min resons for low TB nd drug-resistnt TB cse detection rtes in mny prts of the world (Chpter 3) is the existence of significnt privte sector, in which cre providers frequently dignose people with TB nd drug-resistnt TB but fil to notify these to ntionl uthorities. The qulity of dignostic services in the privte sector is highly vrible or unknown. Furthermore, in some settings, lbortories in the public sector tht re not under the uspices of the NTP lso dignose TB nd drug-resistnt TB without necessrily following recommended guidelines nd qulity ssurnce procedures. Collbortion between NTPs nd ll lbortories of fering TB nd drug-resistnt TB dignosis is criticl to ensure tht ntionl guidelines re followed, tht pproprite dignostic tests re used, nd tht ptients dignosed 74 n GLOBAL TUBERCULOSIS REPORT 215

86 n TABLE 5.2 Incorportion of WHO policy guidnce on Xpert MTB/RIF, 214 YES NO HIGH TB BURDEN HIGH MDR-TB BURDEN PEOPLE LIVING WITH HIV XPERT MTB/RIF AS THE INITIAL DIAGNOSTIC TEST PEOPLE AT RISK OF DRUG-RESISTANT TB CHILDREN SUSPECTED OF HAVING TB EXTRAPULMONARY TB USING SELECTED SPECIMENS Afghnistn Armeni Azerbijn Bngldesh Belrus Brzil Bulgri Cmbodi Chin DR Congo Estoni Ethiopi Georgi Indi Indonesi Kzkhstn Keny Kyrgyzstn Ltvi Lithuni Mozmbique Mynmr Nigeri Pkistn Philippines Republic of Moldov Russin Federtion South Afric Tjikistn Thilnd Ugnd Ukrine UR Tnzni Uzbekistn Viet Nm Zimbbwe High-burden countries 86% 1% 77% 64% High MDR-TB burden countries 85% 93% 81% 7% AFR 72% 84% 67% 4% AMR 52% 48% 35% 3% EMR 56% 62% 38% 44% EUR 5% 57% 45% 44% SEAR 55% 82% 36% 45% WPR 72% 83% 56% 5% Globl 6% 69% 5% 41% The regionl nd globl figures re ggregtes of dt reported by low- nd middle-income countries nd territories. Dt for the vribles shown in the tble re not requested from high-income countries in the WHO dt collection form. GLOBAL TUBERCULOSIS REPORT 215 n 75

87 with TB nd drug-resistnt TB re notified to the NTP nd receive proper cre. In 214, 17 of 36 high TB nd MDR-TB burden countries reported some level of collbortion with lbortories in the privte sector, nd 23 reported collbortion with non-ntp lbortories in the public sector. 5.3 Strengthening TB lbortories globlly, regionlly nd ntionlly Strengthening TB lbortories involves not only equipping them with modern dignostics suitble to the vrious levels of the network (Section 5.2), but lso ensuring the qulity of every step in the dignostic process, from the collection nd testing of smples, to the recording nd reporting of results. Implementing system of qulity mngement should be priority cross ll TB lbortories in network. A comprehensive qulity mngement system llows for the necessry ctivities to be crried out t the right time nd by the ppropritely trined people, for the necessry equipment nd consumbles to be in stock, nd for ll mnuls, guidelines, forms nd stndrd operting procedures to be in plce so tht processes re crried out correctly. Severl sources of guidnce nd trining pltforms hve been developed to ssist TB reference lbortories to implement qulity mngement system tht meets interntionl ccredittion stndrds. The GLI stepwise process towrds TB lbortory ccredittion is n online interctive guide 1 divided into four phses, developed by the Royl Tropicl Institute (KIT), the Union, the United Sttes Centers for Disese Control nd Prevention, the United Sttes Agency for Interntionl Development (USAID) nd WHO. The frmework known s the WHO guide for the stepwise lbortory improvement process towrd ccredittion in the Africn Region (SLIPTA) is bsed on 12 qulity-system essentils, nd it is pplicble to ll lbortory settings nd disciplines. The United Sttes Centers for Disese Control nd Prevention hs developed tsk-bsed mentoring progrmme known s Strengthening lbortory mngement towrds ccredittion (SLMTA). The Foundtion for Innovtive New Dignostics (FIND) hs modified both the SLMTA progrmme nd the SLIPTA frmework to include TB-specific guidnce, to form TB-SLMTA nd TB-SLIPTA. In 214, 123 of 173 responding countries nd territories (71%) indicted tht forml qulity mngement system towrds chieving lbortory ccredittion hd t lest been strted t the ntionl reference lbortory (NRL). Qulity ssurnce of microscopy remins criticl ctivity of ll lbortory networks, nd comprehensive externl qulity ssessment (EQA) progrmme should be implemented tht includes on-site evlution, rndom blinded rechecking, nd pnel testing. Of the 14 countries nd territories tht reported dt on the number of smer microscopy centres undergoing EQA in 213, only 34% indicted the existence of scheme tht covered ll centres in the country, with further 16% covering t lest 9% of cen- 1 tres. Among the 22 HBCs, only four reported scheme tht encompssed ll centres in 214 (Bngldesh, Indi, Ugnd nd Zimbbwe) nd five more reported progrmme tht included t lest 9% of centres (Cmbodi, Chin, Pkistn, South Afric nd Viet Nm). Qulity-ssured DST is criticl to ensure ccurte detection of drug resistnce to inform tretment decisions nd to void flse dignoses. Of the high TB nd MDR-TB burden countries tht reported on EQA coverge of DST lbortories in 214 (34 of 36), 24 (71%) reported hving scheme tht encompssed ll DST lbortories. Of the 116 reporting countries globlly, 78 (67%) indicted scheme tht encompssed ll lbortories. Ensuring qulity needs to be priority for ll levels of lbortory network. As key prtner in strengthening the cpcity nd qulity of TB lbortories globlly, the WHO TB Suprntionl Reference Lbortory (SRL) Network comprises 36 lbortories tht provide long-term technicl ssistnce to low- nd middle-income countries under the frmework of collbortive greements. The network ws formed in 1994 to ensure the qulity of drug resistnce surveys, but tody SRLs provide wide rnge of technicl ssistnce services, including trining, on-site supervisory missions, guidnce to the development of ntionl lbortory strtegic plns, nd proficiency testing. 156 countries nd territories reported hving forml link with prtner SRL in 214. The SRL Network lso includes Ntionl Centres of Excellence (SRL-CEs), which re well-performing ntionl nd regionl TB reference lbortories in lrge, middle-income countries. These SRL-CEs hve similr terms of reference (nd ntionl sttus) to tht of n SRL but with n in-country focus for its lbortory strengthening ctivities. To meet its objectives, SRL-CE commits to provide minimum service requirements including estblishing forml links with t lest two intermedite level lbortories within the country nd undertking t lest one nnul technicl ssistnce visit to ech lbortory. A SRL-CE needs to be nominted by its NTP to the WHO country office, estblish collbortive greement with n existing SRL, undergo lbortory ssessment by WHO, nd ctively implement qulity mngement system towrds ccredittion. In 214, the Ministry of Helth of the Russin Federtion nominted TB lbortories of three Federl Institutes to undergo evlutions to ssess their suitbility for designtion s SRL-CEs: Centrl Tuberculosis Reserch Institute, Moscow; Novosibirsk Tuberculosis Reserch Institute, Novosibirsk; nd Url Reserch Institute for Phthisiopulmonology, Yekterinburg. Following ssessment missions, ll three of the lbortories were recognized s performing well, with high-qulity infrstructure nd high clibre of suitbly-qulified technicl stf f. They were ll subsequently designted s SRL-CEs in April 215. These lbortories hve prticulr vlue for estblishing nd mintining high-qulity lbortory services within the country for the 76 n GLOBAL TUBERCULOSIS REPORT 215

88 n FIGURE 5.3 The WHO TB Suprntionl Reference Lbortory Network Boston, USA Atlnt, USA Mexico City, Mexico Gudeloupe, Frnce Copenhgen, Denmrk Rig, Ltvi Moscow, Russi Antwerp, Belgium Yekterinburg, Russi Novosibirsk, Russi London, UK Borstel, Germny Guting, Germny Prgue, Czech Republic Miln, Itly Zgreb, Croti Porto, Portugl Rome, Itly Seoul, Republic of Kore Brcelon, Spin Le Hmm, Algeri Ciro, Egypt New Delhi, Indi Cotonou, Benin Stockholm, Sweden Chenni, Indi Kmpl, Ugnd Krchi, Pkistn Hong Kong, Chin SAR Bngkok, Thilnd Tokyo, Jpn Sntigo, Chile Johnnesburg, South Afric Buenos Aires, Argentin Adelide, Austrli Suprntionl Reference Lbortory Suprntionl Reference Lbortory Coordinting Centre Cndidte Suprntionl Reference Lbortory Ntionl Centre of Excellence Brisbne, Austrli progrmmtic mngement of drug-resistnt TB, including through the coordintion of technicl ssistnce, provision of monitoring nd supervision, nd orgniztion of trinings to lbortory stf f involved in dignostic testing for drug resistnce nd monitoring of tretment for ptients with drug-resistnt TB. The SRL network s of July 215 is shown in Figure 5.3. GLOBAL TUBERCULOSIS REPORT 215 n 77

89 CHAPTER 6 Addressing the co-epidemics of TB nd HIV Key fcts nd messges In 214, n estimted 1.2 million (12%) of the 9.6 million people who developed TB worldwide were HIV-positive. The Africn Region ccounted for 74% of the estimted number of HIVpositive incident TB cses. The number of people dying from HIV-ssocited TB peked t 57 in 24 nd hs since fllen to 39 in 214 ( reduction of 32%). In 214, HIV-ssocited TB deths ccounted for 25% of ll TB deths (mong HIV-negtive nd HIV-positive people) nd one third of the estimted 1.2 million deths from HIV/AIDS. In 24, WHO recommended the implementtion of 12 collbortive TB/HIV ctivities. Between 25 nd 214, n estimted 5.8 million lives were sved by TB/HIV interventions. Globlly, 51% of notified TB ptients hd documented HIV test result in 214, smll increse from 49% in 213. The figure ws highest in the Africn Region, t 79%, nd 9% in 18 of the 41 high TB/HIV burden countries. The prevlence of HIV co-infection mong TB ptients is highest in the Africn Region. Of the 1.1 million TB ptients with known HIV sttus in 44 countries, 39% were HIV-positive in 214, slight decline compred with 41% in 213. The proportion of TB ptients who were known to be HIV-positive in the Africn Region rnged from 6% in Eritre to 73% in Swzilnd. In 214, coverge of ntiretrovirl therpy (ART) for notified TB ptients who were known to be co-infected with HIV reched 77% globlly. Further ef forts re needed to rech the trget of 1%. This is especilly the cse given tht the number of HIVpositive TB ptients on ART in 214 represented only 33% of the estimted number of people living with HIV who developed TB in 214. Coverge of co-trimoxzole preventive therpy (CPT) mong HIV-positive TB ptients remins high, nd incresed slightly to 87% globlly nd 89% in the Africn Region in 214. The number of people living with HIV who were treted with isonizid preventive therpy (IPT) reched 933 in 214, n increse of bout 6% compred with 213. However, provision of IPT ws reported by just 23% of countries globlly, including only 13 of the 41 high TB/HIV burden countries. As in previous yers, lrge proportion of the people living with HIV who were initited on IPT were in South Afric (59%), lthough in most countries tht reported dt in 213 nd 214, coverge levels grew. Preventing TB deths mong HIV-positive people requires intensified scle-up of TB prevention, dignosis nd tretment interventions, including erlier initition of ART mong people living with HIV nd those with HIV-ssocited TB. Incresed ef forts in joint TB nd HIV progrmming could fcilitte further scle-up nd consolidtion of collbortive TB/HIV ctivities. Globlly, people living with HIV re 26 times more likely to develop TB disese thn those who re HIV-negtive. 1 Beginning in the 198s, the HIV epidemic led to mjor upsurge in TB cses nd TB mortlity in mny countries, especilly in southern nd estern Afric (Chpter 2). In 214, 1.2 million (12%) of the 9.6 million people who developed TB worldwide were HIV-positive (Chpter 2, Tble 2.1); 74% of these HIV-positive TB cses were in the Africn Region. The number of people dying from HIV-ssocited TB peked t 57 in 24 nd hs since fllen to 39 in 214 ( reduction of 32%). 2 However, this still represents n enormous burden of preventble deths nd ill-helth. In 214, TB deths mong HIV-positive people ccounted for 25% of ll TB deths (mong HIV-negtive nd HIV-positive people) nd one third of the estimted 1.2 million deths from HIV/AIDS. 3 Current trends indicte tht the trget set by WHO, UNAIDS nd the Stop TB Prtnership to hlve the number of HIV-ssocited TB deths by 215 (compred with 24) will not be met globlly (Chpter 2). 4 WHO recommendtions on the interventions needed to 1 The probbility of developing TB mong people living with HIV divided by the probbility of developing TB mong HIV-negtive people is the incidence rte rtio (IRR). The men estimted globl IRR (ll ges) in 214 ws 26 (rnge 24 28). However, there is considerble vrition mong countries: in 214, the medin IRR ws 23 (interqurtile rnge 14-36). Further detils re provided in the online technicl ppendix. 2 Estimtes of the totl burden of TB disese nd of the number of TB cses nd deths mong HIV-positive people re updted nnully by WHO. For further detils, see Chpter 2 nd the online technicl ppendix ( 3 with_uncertinty_bounds_ Of the 41 countries with the highest burden of HIV ssocited TB, 17 re estimted to hve met the trget by the end of n GLOBAL TUBERCULOSIS REPORT 215

90 prevent TB in HIV-positive people nd to reduce the impct of HIV mong TB ptients were first issued in 24, nd re collectively known s collbortive TB/HIV ctivities. 1 They include: estblishing nd strengthening coordintion mechnisms for delivering integrted TB nd HIV services; HIV testing for ll TB ptients s well s people with TB signs or symptoms; providing ntiretrovirl therpy (ART) nd cotrimoxzole preventive therpy (CPT) to ll HIV-positive TB ptients; providing HIV prevention services for TB ptients; intensifying TB cse-finding mong people living with HIV; of fering isonizid preventive therpy (IPT) to people living with HIV who do not hve ctive TB; nd preventing the trnsmission of TB infection in helth cre nd congregte settings. The ltter three ctivities re referred to s the Three Is for HIV/TB nd, together with erlier ART, re the principl interventions for preventing TB mong people living with HIV. Between 25 nd 214, TB/HIV interventions sved n estimted 5.8 million lives. 2 In ddition, use of the rpid moleculr test, Xpert MTB/RIF nd erly ART mong HIV positive TB ptients re incresingly considered criticl components of collbortive TB/ HIV ctivities. WHO recommends the use of Xpert MTB/RIF s the primry dignostic test for TB mong people living with HIV who hve TB signs nd symptoms, nd ART for ll HIV-positive TB ptients within the first eight weeks of strting TB tretment (irrespective of their CD4 cell count). Erly initition of ART (within two weeks of strting TB tretment) is lso importnt, prticulrly for TB ptients with profound immunosuppression (e.g. CD4 cell count less thn 5) mong whom it hs been shown to significntly improve survivl. WHO begn monitoring the implementtion of collbortive TB/HIV ctivities in 24. This chpter presents the ltest sttus of progress, using dt for ech yer from 24 through HIV testing nd documenttion of HIV sttus mong TB ptients WHO recommends tht routine HIV testing should be of fered to ll TB ptients, to ll those with TB signs nd symptoms, nd to prtners of known HIV-positive TB ptients. 3 In the WHO online dt collection system, dt re reported for TB ptients only. In 214, 3.2 million notified TB ptients hd documented HIV test result, equivlent to 51% of notified TB cses (Tble 6.1, Figure 6.1). This represented n increse from 3 million nd 49% respectively in 213, nd more thn 17 times the cov- 1 An updte ws issued in 212. See WHO policy on collbortive TB/HIV ctivities: guidelines for ntionl progrmmes nd other stkeholders. Genev, World Helth Orgniztion, 212 (WHO/ HTM/TB/212.1). Avilble t publictions/212/ _eng.pdf 2 Estimtes of lives sved by TB nd HIV interventions re covered in more detil in Chpter 2. 3 WHO policy on collbortive TB/HIV ctivities: guidelines for ntionl progrmmes nd other stkeholders. Genev: World Helth Orgniztion; 212 (WHO/ HTM/TB/212.1). Avilble t publictions/212/ _eng.pdf erge reported in 24 (Figure 6.1). There were 89 countries in which 75% of TB ptients hd documented HIV test result in 214 (Figure 6.2); this ws unchnged from 213. Overll, mong the 41 countries identified s priorities for the globl TB/HIV response (listed in Tble 6.1), 6% of notified TB ptients hd documented HIV test result in 214, up from 58% in 213. There hs been stedy increse in these 41 countries since 27. However, levels of coverge vry significntly, rnging from 5% in Indonesi to 99% in Rwnd in Eighteen of the 41 countries reported tht 9% of TB ptients knew their HIV sttus in 214, of which five (Botswn, Keny, Mozmbique, Rwnd nd Swzilnd) hve mnged to mintin this level since 211. A further 14 countries (Burkin Fso, Cmbodi, Cmeroon, Côte d Ivoire, Lesotho, Mlwi, Nmibi, Nigeri, South Afric, Togo, Ugnd, Tnzni, Zmbi nd Zimbbwe) hve reported tht 8% TB ptients know their HIV sttus since 211. In seven high TB/HIV burden countries, the percentge of TB ptients who know their HIV sttus hs remined persistently low, t under 5% since 211: Chin, Congo, the Democrtic Republic of the Congo, Indonesi, Mli, Mynmr nd Sudn. 5 The percentge of TB ptients with known HIV sttus remins highest in the Africn Region, where it continues to increse nd reched 79% in 214, up from 78% in 213 (Tble 6.1, Figure 6.1). Of the 47 Africn countries, 3 countries reported 75% of TB ptients hd documented HIV test result in 214, nd 23 chieved levels of 9% (Figure 6.2). n FIGURE 6.1 Percentge of notified TB ptients with known HIV sttus, Percentge of notified TB ptients Africn region Globl Regions outside Afric In Indi, the ntionl figure fell slightly between 213 nd 214, from 63% to 61%. This reflects lrge increse in notifictions (see Chpter 3, Box 3.2) from the privte sector (included in the denomintor), without corresponding increse in reporting relted to HIV testing. When nlysis is restricted to units tht reported dt in both 213 nd 214, the percentge of TB ptients who knew their HIV sttus rose from 63% to 72%. 5 The reported figure is lso reltively low for the Russin Federtion. However, this is becuse the denomintor vilble for clcultions is the totl number of new nd relpse cses tht were notified while the numertor vilble for clcultions includes only new TB ptients in the civilin sector. In prctice, testing coverge is estimted to be close to 1% in the Russin Federtion. GLOBAL TUBERCULOSIS REPORT 215 n 79

91 n TABLE 6.1 HIV testing for TB ptients, tretment for HIV-positive TB ptients nd prevention of TB mong people living with HIV, 41 high TB/HIV burden countries nd WHO regions, 214. Numbers in thousnds except where indicted. ESTIMATED HIV-POSTIVE INCIDENT TB CASES NUMBER OF NOTIFIED TB PATIENTS WITH KNOWN HIV STATUS % OF NOTIFIED TB PATIENTS WITH KNOWN HIV STATUS % OF TB PATIENTS WITH AN HIV TEST RESULT WHO WERE HIV-POSITIVE % OF NOTIFIED HIV-POSITIVE TB PATIENTS STARTED ON ART NUMBER OF HIV-POSTIVE TB PATIENTS ON ART AS % OF ESTIMATED HIV-POSITIVE INCIDENT TB CASES b NUMBER OF HIV-POSITIVE PEOPLE PROVIDED WITH IPT % OF PEOPLE NEWLY ENROLLED IN HIV CARE WHO WERE NOTIFIED AS A TB CASE THE SAME YEAR Angol Botswn Brzil Burkin Fso Burundi Cmbodi Cmeroon Centrl Africn Republic Chd Chin Congo Côte d Ivoire Djibouti DR Congo Ethiopi c Ghn Hiti Indi Indonesi Keny Lesotho Mlwi Mli Mozmbique Mynmr Nmibi Nigeri Russin Federtion d 38 Rwnd Sierr Leone South Afric Sudn Swzilnd Thilnd Togo Ugnd Ukrine UR Tnzni Viet Nm Zmbi Zimbbwe High TB/HIV burden countries AFR AMR EMR EUR SEAR WPR Globl Blnk cells indicte dt not reported. indictes vlues tht cnnot be clculted. Best estimtes re followed by the lower nd upper bounds of the 95% uncertinty intervl. b The numertor (i.e. ll notified HIV-positive TB cses on ART) includes ll notified new, relpse nd non-relpse retretment cses. The denomintor (i.e. estimted HIV-positive incident TB cses) includes new nd relpse cses only. c In 214, ART nd IPT dt were missing for 3 of Ethiopi s 11 regions, which in previous yers hd ccounted for bout one third of the ntionl totls. In the 8 regions tht reported dt, 65% of HIV-positive TB ptients were on ART. d Dt for the Russin Federtion re for new TB ptients in the civilin sector only. 8 n GLOBAL TUBERCULOSIS REPORT 215

92 n FIGURE 6.2 Percentge of notified TB ptients with known HIV sttus by country, 214 Percentge of notified TB ptients No dt Not pplicble Dt for the Russin Federtion re for new TB ptients in the civilin sector only. In the Region of the Americs nd the Europen Region, there were smll improvements between 213 nd 214: from 72% to 74% nd from 59% to 62% respectively. 1 Lrger increses were evident in some countries in the Americs, notbly Bolivi (7% to 77%), Chile (35% to 5%), Colombi (74% to 8%), Guteml (8% to 86%), Mexico (77% to 85%), Nicrgu (69% to 77%) nd Peru (66% to 74%). In the other three WHO regions in which concentrted HIV epidemics re the norm, the percentge of TB ptients with known HIV sttus hs remined low (15% 45%). Impressive gins were mde in three countries, however: Mynmr (from 12% to 4%), Sri Lnk (from 49% to 78%) nd the Philippines (from 2% to 2%). In Cmbodi, 81% of TB ptients knew their HIV sttus in 214, similr to the level chieved in 213. It should lso be noted tht in Chin, 91% of TB ptients knew their HIV sttus in the counties defined s hving high TB/HIV burden, much higher thn the ntionl verge of 42%. In some countries with concentrted epidemics, the progrmmtic fesibility nd vlue of testing ll TB ptients for HIV hs been questioned, especilly in settings where both ccess to HIV tretment nd funding re limited. At the sme time, HIV testing for TB ptients is bsic stndrd of cre nd provides pthwy to HIV tretment nd prevention 1 Figures for the Europen Region re n underestimte, due to under-estimtion of testing coverge for the Russin Federtion. services. Ntionl progrmmes should im to ensure tht the benefits of HIV testing re vilble to TB ptients, their prtners, fmilies nd the community t lrge, in the context of their specific progrmmtic settings Levels of HIV infection mong TB ptients with HIV test results Globlly, 16% of TB ptients with n HIV test result were HIVpositive (Tble 6.1). The figure ws 18% mong the 41 high TB/ HIV burden countries tht ccounted for more thn 94% of estimted HIV-positive incident TB cses in 214. Overll, the percentge of TB ptients testing HIV-positive hs been flling globlly since 28 (Figure 6.3). The highest rtes of HIV co-infection were reported for TB ptients in the Africn Region (Tble 6.1), where 39% of those with n HIV test result were HIV-positive (compred with 41% in 213). The percentge of TB ptients found to be HIV-positive in the 28 Africn countries in the list of 41 high TB/HIV burden countries rnged from bout 1% in Angol nd Ethiopi to more thn 7% in Lesotho nd Swzilnd. In ll other regions, the percentge of TB ptients with documented HIV test result who were HIV-positive ws much lower. 2 WHO policy on collbortive TB/HIV ctivities: guidelines for ntionl progrmmes nd other stkeholders. Genev: World Helth Orgniztion; 212 (WHO/ HTM/TB/212.1). Avilble t publictions/212/ _eng.pdf GLOBAL TUBERCULOSIS REPORT 215 n 81

93 n FIGURE 6.3 Percentge of notified TB ptients with known HIV sttus who were HIV-positive, nd percentge of notified HIV-positive TB ptients enrolled on co-trimoxzole preventive therpy (CPT) nd ntiretrovirl therpy (ART), Notified TB ptients with known HIV sttus who were HIV-positive 1 Notified HIV-positive TB ptients strted on CPT 1 Notified HIV-positive TB ptients strted on ART Percentge of notified TB ptients Globlly, totl of 528 HIV-positive TB ptients were reported by NTPs in 214. This represented less thn 5% of the 1.2 million HIV-positive people estimted to hve developed TB in the sme yer (Figure 6.4), lthough there ws considerble vrition mong regions. The proportion ws highest in the Europen Region (81%), followed by the Region of the Americs (6%) nd the Africn Region (5%), nd much lower in the Estern Mediterrnen, South- Est Asi nd Western Pcific Regions (13%, 29% nd 39%, respectively). 6.3 Antiretrovirl therpy nd co-trimoxzole preventive therpy for HIV-positive TB ptients Antiretrovirl therpy ART is n intervention tht cn hve n importnt impct on TB morbidity nd mortlity mong HIV-positive TB ptients. The number of notified HIV-positive TB ptients on ART hs grown from very low level in 24 (Figure 6.4) to rech 392 in 214. Among HIV-positive TB ptients notified by NTPs in 214, 1 77% were on ART globlly (Tble 6.1, Figure 6.3), further improvement compred with 73% in 213. In the Africn Region in 214, 77% of HIV-positive TB ptients reported by NTPs were strted on ART (up from 72% in 213). ART coverge incresed in 28 of the 41 high TB/HIV burden countries between 213 nd 214 (dt not shown). Among the top-ten high TB/HIV burden countries, the biggest increses between 213 nd 214 were in the Democrtic Republic of the Congo (48% to 67%), Mozmbique (72% to 81%), the United Republic of Tnzni (73% to 83%), Nigeri (67% to 75%) nd South Afric (72% to 79%). Five other countries reported increments of more thn 1%: Cmbodi, Djibouti, Mli, Mynmr nd Viet Nm. Six of the 41 high TB/HIV burden countries hve not yet reched levels 1 In the nnul WHO TB dt collection form, countries re sked to report the number of TB ptients notified in the most recent clendr yer who were living with HIV nd who strted or continued on ART. n FIGURE 6.4 ART enrolment mong HIV-positive TB ptients compred with the reported number of HIV-positive TB ptients nd the estimted number of HIV-positive people who developed TB, Number of TB ptients (thousnds) Estimted HIV positive incident TB cses Notified HIV positive TB ptients HIV positive TB ptients on ART Notified HIV-positive TB ptients on ART includes new nd relpse TB cses plus prevlent TB cses re-registered for tretment chnge (e.g. f ter tretment filure). Estimted HIV-positive incident TB cses includes only new nd relpse TB cses. of 5%: Sudn, Ethiopi, Ghn, Indonesi, Congo nd Côte d Ivoire. In these countries, concerted ef forts re needed to improve coverge. Erly initition of ART is importnt to reduce mortlity. WHO recommends tht ART should be initited s soon s possible f ter TB tretment is strted, nd within the first two to eight weeks of tretment. WHO lso encourges progrmmes to estblish mechnisms to monitor the timeliness of ART through ntionl dt collection systems, nd hs provided guidnce bout how to do this. 2 A recent exmple from Indi is highlighted in Box 6.1. Despite overll progress in ART coverge, there is sub- 2 World Helth Orgniztion. WHO guide to monitoring nd evlution of collbortive TB/HIV ctivities. Genev: World Helth Orgniztion; 215. Avilble t 82 n GLOBAL TUBERCULOSIS REPORT 215

94 Box 6.1 Monitoring when ART is initited for HIV-positive TB ptients: n exmple from Indi In October November 214, dt from 7 fcilities in Indi where ART is provided were extrcted from system designed to cpture erly wrning indictors relted to the development of drug resistnce nd the qulity of cre. This ws done by the Ntionl AIDS Control Orgniztion nd WHO Indi. Of the 9468 people living with HIV who hd been enrolled in HIV cre, 1871 (19%) developed TB within two yers (Tble B6.1.1). Dt on the timing of initition on ART were nlysed for these individuls. TABLE B6.1.1 Initition on ART for HIV-positive TB ptients in 62 fcilities in Indi, October November 214 STUDY COHORT (ADULTS, N=9468) NUMBER Ptients dignosed with TB 1871 Ptients lredy on ART t the time of TB dignosis stntil gp between the number of HIV-positive TB ptients strted on ART, nd the estimted totl number of HIV-positive people with TB who re in need of both TB tretment nd ART. The globl number of HIV-positive TB ptients reported to be strted on ART by NTPs in 214 represented only 33% of the estimted 1.2 million HIV-positive people who developed TB in the sme yer (Tble 6.1, Figure 6.4). The rtio of ptients strted on ART in 214 to the estimted number of HIV-positive people who developed TB in 214 ws bove 5% in only 14 of the 41 high TB/HIV burden countries: Botswn, Burkin Fso, Cmbodi, Keny, Mlwi, Mli, Nmibi, Rwnd, South Afric, Swzilnd, Ugnd, Ukrine, the United Republic of Tnzni nd Zmbi (Figure 6.5). While this is n improvement from only eight countries in 213, much remins to be done to improve the detection of TB mong HIV-positive people, the coverge of HIV testing mong TB ptients, nd enrolment of HIV-positive TB ptients on ART. 362 Time between strt of TB tretment nd ART initition, for the 1429 HIV-positive TB ptients who were not lredy on ART <2 weeks 2 (14%, 95% CI: 12 16%) 2 8 weeks 933 (65%, 95% CI: 63 68%) >8 weeks 296 (21%, 95% CI: 19 23%) Medin 23 dys The medin time between the strt of TB tretment nd ART ws 23 dys. About 8% of HIV-positive TB ptients were strted on ART within eight weeks of TB dignosis, in line with WHO recommendtions. These sttistics bout ART coverge mong ll estimted HIV-positive TB cses cn lso be compred with the level of ART coverge mong ll people living with HIV. Globlly, over 15 million people were on ART s of 31 Mrch By the end of 214, 4% (uncertinty intervl, 37% 45%) of the estimted number of people living with HIV were receiving ART. This is more thn the estimted level of 33% for HIV-positive people who hve TB, but lso fr from universl coverge. Mjor ef forts re urgently required to improve ccess nd nrrow these gps. The UNAIDS fst trck tretment trgets (by 22, 9% of people living with HIV know their sttus, 9% of those who know their sttus re on ART, nd 9% of those on ART hve suppressed virl lod) provide pltform for doing this Co-trimoxzole preventive therpy Globlly, 427 HIV-positive TB ptients were enrolled on CPT in 214, representing 87% of ll notified HIV-positive TB ptients, similr to levels chieved in 213 (Figure 6.3). The Africn nd South-Est Asi regions mintined their prticulrly high levels of enrolment on CPT from 213, t 89% nd 85% respectively. Of the 34 high TB/HIV burden countries (out of totl of 41) tht reported dt, only four reported tht less thn 5% of HIV-positive TB ptients were enrolled on CPT in 214: Côte d Ivoire (24%), Congo (27%), Indonesi (41%) nd Ukrine (44%). 6.4 Intensified TB cse-finding nd initition of isonizid preventive therpy mong people living with HIV The high proportion of people with undignosed TB found in utopsy studies of HIV-positive people 3,4,5 shows tht substntil ef forts re needed to ensure ef fective TB screening mong people living with HIV, so tht TB is promptly dignosed nd treted nd so tht those without ctive TB disese re provided with IPT s well s ART. ART reduces the individul risk of TB disese mong people living with HIV by 65%, 6 irrespective of CD4 cell count. Its impct is further enhnced when IPT is lso provided. Recently, IPT for six 1 How AIDS chnged everything MDG yers, 15 lessons of hope from the AIDS response. Genev: UNAIDS; 215. Avilble t: org/en/resources/documents/215/mdg6_15yers- 15lessonsfromtheAIDSresponse 2 Understnding Fst-Trck. Genev: UNAIDS; 215. Avilble t Understnding_FstTrck_en.pdf) 3 Cox JA et.l. An utopsy study describing cuses of deth nd compring clinico-pthologicl findings mong hospitlized ptients in Kmpl, Ugnd; Plos One, 212;7(3):e doi: /journl. pone Epub 212 Mr Wong EB et.l. Cuses of deth on ntiretrovirl therpy: postmortem study from South Afric; Plos One 212;7(1):e doi: /journl.pone Epub 212 Oct Kille AM et.l. High prevlence of tuberculosis dignosed during utopsy exmintion t Muhimbili Ntionl Hospitl in Dr es Slm, Tnzni; Tnzni Journl of Helth Reserch 213; Suthr AB et l. Antiretrovirl therpy for prevention of tuberculosis in dults with HIV: systemtic review nd met-nlysis. PLoS Med 212, 9(7): e1127. doi:1.1371/journl.pmed.1127). GLOBAL TUBERCULOSIS REPORT 215 n 83

95 n FIGURE 6.5 Number of HIV-positive TB ptients on ART s percentge of estimted HIV-positive incident TB cses, 214 Percentge No dt Not pplicble The numertor (i.e. ll notified HIV-positive TB cses on ART) includes ll notified new, relpse nd non-relpse retretment cses. The denomintor (i.e. estimted HIV-positive incident TB cses) includes new nd relpse cses only. months combined with ART for people with CD4 counts of >5 cells/mm 3 ws found to reduce the risk of severe HIVrelted illness by 44% nd the risk of deth from ny cuse by 35% Intensified cse-finding Systemtic screening for TB mong people living with HIV is recommended by WHO s n essentil component of the HIV pckge of cre, long with ART, IPT nd infection control. It is the first essentil step before both IPT initition nd TB dignosis. In 214, 78 countries reported bout seven million people enrolled in HIV cre who were screened for TB, up from 5.5 million in 64 countries in 213. Being screened for TB does not necessrily gurntee completion of the TB dignostic pthwy. As prt of ef forts to improve the utility of TB screening, WHO encourges monitoring of the full cscde of intensified TB cse finding, including: 1) identifiction of TB in those who screened positive for TB symptoms; nd 2) documenttion of wht TB investigtions were done to dignose or rule out TB disese. In December 21, the rpid moleculr test Xpert MTB/RIF ws endorsed by WHO with strong recommendtion for its use s the initil dignostic test for TB in two groups: people 1 The TEMPRANO ANRS Study Group; A Tril of Erly Antiretrovirls nd Isonizid Preventive Therpy in Afric. The New Englnd Journl of Medicine 215; DOI:1. 156/NEJMo living with HIV with TB signs nd symptoms, nd people t high risk of hving MDR-TB (Chpter 5). This ws reiterted in the 213 updte to WHO policy recommendtions on the use of Xpert MTB/RIF, 2 nd in the 214 Xpert MTB/RIF implementtion mnul in which it is recommended tht people living with HIV should be prioritized for testing with Xpert MTB/RIF when resources re limited. 3 Discussions t Globl Forum of Xpert MTB/RIF implementers held in 214 indicted tht mjor motivtion for the roll-out of Xpert MTB/RIF ws of ten the ntionl response to multidrug-resistnt TB (MDR-TB), 4 rther thn dignosis of TB mong people living with HIV. To mximize the detection of TB cses mong HIV-positive people, Xpert MTB/RIF needs to be widely implemented in settings where HIV cre is provided, using ll vilble funding sources. Erly detection of TB in HIV cre settings cn in turn help to 2 Policy updte: Xpert MTB/RIF ssy for the dignosis of pulmonry nd extrpulmonry TB in dults nd children. Genev: World Helth Orgniztion; 213 (WHO/HTM/TB/213.16). Avilble t: int/tb/lbortory/xpert_policyupdte/en/ 3 Xpert MTB/RIF implementtion mnul: technicl nd opertionl how-to ; prcticl considertions. Genev: World Helth Orgniztion; 214 (WHO/HTM/TB/214.1). Avilble t: xpert_implem_mnul/en/ 4 Meeting Report of the Xpert MTB/RIF Implementers Globl Forum, 1 2 My 214. Genev: World Helth Orgniztion; 214. Avilble t: Implementers%2Globl%2Forum%2meeting%2report.pdf. 84 n GLOBAL TUBERCULOSIS REPORT 215

96 Box 6.2 The use of Xpert MTB/RIF in dignosis of TB mong people living with HIV Dt on ntionl policies for using Xpert MTB/RIF s the initil dignostic test for TB mong people living with HIV were collected s prt of the 215 round of globl TB dt collection. Additionl dt were requested from 15 countries with the highest TB/HIV burden, of which nine responded: Ethiopi, Indi, Indonesi, Lesotho, Mynmr, South Afric, Ugnd, the United Republic of Tnzni nd Zimbbwe. Of the 41 high TB/HIV burden countries, 33 (8%) hd ntionl policy on the use of Xpert MTB/RIF by the end of 214. The eight countries tht did not report hving such policy in plce were Centrl Africn Republic, Chd, Chin, Côte d Ivoire, Mynmr, Nmibi, Sierr Leone nd Sudn. Of the nine countries tht responded to the more detiled survey, ll except Mynmr reported policy tht recommended Xpert MTB/RIF s the initil dignostic test for TB mong people living with HIV. A ntionlly stndrdized TB dignostic lgorithm for people living with HIV tht included Xpert MTB/RIF ws lso reported in these eight countries. Typiclly, Xpert MTB/RIF testing ws restricted to secondry nd tertiry level helth cre fcilities. Exceptions were Ethiopi nd South Afric, which reported vilbility t ll levels including t primry helth cre fcilities. In generl, routine documenttion nd reporting of Xpert MTB/RIF test results mong people living with HIV ws stted to be mjor chllenge, reflecting the fct tht ntionl registers nd reporting systems do not cpture such dt. To improve testing for TB mong people living with HIV nd ensure tht progress cn be monitored, wider doption of the WHO recommendtion to use Xpert/MTB RIF s the initil dignostic test nd updting of ntionl monitoring nd evlution systems tht will llow systemtic recording nd reporting re required. The use of Xpert MTB/RIF by HIV service providers, including in peripherl fcilities, lso needs to be promoted. A guide to monitoring nd evlution for collbortive TB/HIV ctivities. Genev: World Helth Orgniztion; 215 (WHO/HTM/ TB/215.2). Avilble t: nd_e_document_pge/en/ ensure prompt initition of ART. Recent nlysis suggests tht there hs been progress in dopting the WHO recommendtion to use Xpert MTB/RIF s the initil dignostic test for TB mong people living with HIV, but tht more remins to be done (Box 6.2). In 214, 76 countries reported dt bout the number of notified TB cses mong those newly enrolled in HIV cre to UNAIDS (up from 59 countries in 213). Unfortuntely, there were dt qulity problems for eight of these countries. Among the remining 68 countries, 9% (211 /2 34 ) of those newly enrolled in HIV cre in 214 were lso notified with TB in the sme yer. Among the 41 high TB/HIV burden countries, the proportion rnged from 2 3% in Chin, Côte d Ivoire, Indi nd Mlwi to 38% in the Russin Federtion (Tble 6.1). Ensuring good qulity dt nd monitoring trends in this indictor re importnt to trck the impct of HIV cre, especilly ART, on the burden of TB in people living with HIV Initition on isonizid preventive therpy A totl of 49 countries (representing more thn 6% of the estimted globl burden of HIV-ssocited TB) reported inititing people living with HIV on IPT. The totl number ws 933 people in 214, n increse from just over 6 people in 213 (Figure 6.6). Thirteen of the 41 high TB/HIV burden countries reported provision of IPT in 214, nd coverge mong people living with HIV who were newly enrolled in cre ws 41%. Coverge rnged from 5% in Swzilnd to 97% in Hiti. As in previous yers, South Afric ccounted for high proportion (59%) of the globl totl in 214: 552 HIVn FIGURE 6.6 Provision of isonizid preventive therpy (IPT) to people living with HIV, Number of people living with HIV (thousnds) Rest of Afric Rest of world South Afric Globl GLOBAL TUBERCULOSIS REPORT 215 n 85

97 positive people were strted on IPT, out of 1 34 (53%) people living with HIV who were newly enrolled in cre. There ws evidence of IPT scle-up in the pst four yers in other countries in the Africn Region. Countries reporting higher numbers in 214 compred with previous yers included Mlwi (135 ), Mozmbique (94 ), Zimbbwe (3 ) Nigeri (26 ), the United Republic of Tnzni (23 ) nd Hiti (22 ). Nonetheless, 77% of countries did not report provision of IPT s prt of HIV cre in 214, including 68% (28/41) of the high TB/HIV burden countries. As with TB screening, it is cler tht countries continue to find it chllenging to provide IPT nd to record nd report dt on its provision or tretment completion. A good exmple is Nmibi, where reporting on provision of IPT ws not fesible in 214 following the withdrwl of donor funding tht hd previously supported the stf f required to record nd report dt. In 213, more thn 15 people newly enrolled in HIV cre were reported to hve been provided with IPT in Nmibi. Globl coverge of IPT is thus understted. 6.5 Improving dt qulity Ech yer, ef forts re mde to improve the qulity of dt relted to collbortive TB/HIV ctivities tht re reported s prt of globl monitoring ef forts by WHO nd UNAIDS. Two chllenges in prticulr hve been evident: discrepncies between the number of HIV-positive TB ptients on ART reported by TB nd HIV progrmmes, nd inconsistencies in the number of people reported to be newly enrolled in HIV cre for the sme country within the sme dt collection form (this number is requested twice in the WHO Universl Access Helth Sector TB indictors reported through the UNAIDS globl reporting system for HIV for two seprte indictors: enrollment on IPT, nd TB notifictions mong those newly enrolled in HIV cre). Encourgingly, the number of countries reporting discrepnt dt fell in 214 compred with 213, nd in lmost ll instnces these discrepncies were resolved following communictions with ntionl TB nd HIV progrmmes. There were two countries for which discrepnt dt on provision of ART reported by ntionl HIV nd TB progrmmes could not be reconciled (Botswn nd Côte d Ivoire) nd four countries for which discrepncies in dt bout the number of people newly enrolled in HIV cre could not be resolved (Guine-Bissu, Mongoli, Sint Vincent nd the Grendines nd Uzbekistn). In 215, WHO published A guide to monitoring nd evlution for collbortive TB/HIV ctivities 1 nd the Consolidted strtegic informtion guide for the helth sector. 2 Both documents hve hrmonized TB/HIV indictors using the sme indictor definitions, to help ensure reporting of the sme dt through globl reporting systems for HIV nd TB. These guidelines lso provide consolidted set of indictors for monitoring progress in the implementtion of collbortive TB/HIV ctivities. Countries re being encourged to dopt, monitor nd routinely report on these indictors. UNAIDS is currently undertking review of the Globl AIDS Response Progress Reporting (GARPR) indictors, in the context of these two guidnce documents. 1 World Helth Orgniztion. A guide to monitoring nd evlution of collbortive TB/HIV ctivities: 215 revision. Genev: World Helth Orgniztion; 215. Avilble t: monitoring-evlution-collbortive-tb-hiv/en/ 2 World Helth Orgniztion. Consolidted strtegic informtion guidelines for HIV in the helth sector. Genev: World Helth Orgniztion; 215. Avilble t: 86 n GLOBAL TUBERCULOSIS REPORT 215

98 CHAPTER 7 Finncing Key fcts nd messges The funding required for full response to the globl TB epidemic in low- nd middle-income countries is estimted t bout US$ 8 billion per yer in 215 (excluding reserch nd development for new TB dignostics, drugs nd vccines). Of the US$ 8 billion required in 215, bout two thirds (US$ 5.3 billion) is for the detection nd tretment of drugsusceptible TB; 2% (US$ 1.6 billion) for tretment of MDR-TB; 8% (US$.6 billion) for rpid dignostic tests nd ssocited lbortory strengthening, much of which is to improve detection of drug-resistnt TB; nd 6% (US$.5 billion) for collbortive TB/HIV ctivities. Projections mde in 213 suggested tht in 215, bout US$ 6 billion could be mobilized from domestic sources nd tht US$ 2 billion would be needed from interntionl donors. The 123 countries tht reported finncil dt to WHO in 215 ccount for 95% of reported TB cses globlly. Bsed on this self-reporting by countries, funding for TB prevention, dignosis nd tretment reched US$ 6.6 billion in 215, up from US$ 6.2 billion in 214 nd more thn double the level of 26 (US$ 3.2 billion). Compred with the estimted globl resource requirement of US$ 8 billion in 215 for full response to the TB epidemic in low nd middle-income countries, this leves gp of round US$ 1.4 billion. Countries themselves reported smller gps, mounting to US$.8 billion in 215; this reflects the fct tht ntionl plns for scling up TB prevention, dignosis nd tretment re less mbitious thn the trgets set in the Globl Pln to Stop TB, in mny countries. Overll, 87% (US$ 5.8 billion) of the US$ 6.6 billion vilble in 215 is from domestic sources. Interntionl donor funding hs incresed since 26, reching US$.8 billion in 215. However, the globl verge for the shre of funding provided from domestic sources concels enormous vrition mong individul countries s well s country groups. Domestic funding domintes (93 94% of the totl funding vilble in 215) in three (not mutully exclusive) groups: Brzil, the Russin Federtion, Indi, Chin nd South Afric (BRICS); upper middle-income countries; nd regions outside Afric nd Asi. In ddition to BRICS, only one HBC (Thilnd) hs consistently reported levels of domestic funding tht exceed contributions from interntionl donor funding in recent yers. Interntionl donor funding domintes in the group of 17 HBCs outside BRICS (72% of the totl funding vilble in 215) nd in low-income countries (81% of the totl funding vilble in 215). At the individul country level, interntionl donor funding remins bsolutely criticl in most of the 22 HBCs. In four HBCs (Afghnistn, Bngldesh, the Democrtic Republic of the Congo nd Mozmbique), 9% of vilble funding in 215 is from interntionl donor sources. The cost per ptient treted for drug-susceptible TB in 214 fell into the rnge of US$ 1 US$ 5 in most countries with high burden of TB. The cost per ptient treted for MDR-TB ws most of ten in the rnge US$ 5 1, but the verge vried from US$ in low-income countries to US$ in upper middle-income countries. Helth finncing dt from ntionl helth ccounts provide insights into the current sttus of progress towrds universl helth coverge (UHC). Two suggested benchmrks required to chieve UHC re tht helth spending reches t lest 6% of gross domestic product (GDP) nd tht out-of-pocket expenditures ccount for less thn 15% of totl helth spending. Most countries, including ll of the 22 HBCs nd ll low-income countries, hve not yet reched these benchmrks. Among HBCs, Brzil, Thilnd nd South Afric re closest to doing so. Progress in TB prevention, dignosis nd tretment requires dequte funding sustined over mny yers. WHO begn nnul monitoring of funding for TB in 22, with findings published in globl TB reports nd peer-reviewed publictions. 1 Prticulr ttention hs lwys been given to the 22 high-burden countries (HBCs) tht ccount for bout 8% 1 The most recent publiction is: Floyd K, Fitzptrick C, Pntoj A nd Rviglione M. Domestic nd donor finncing for tuberculosis cre nd control in low-income nd middle-income countries: n nlysis of trends, 22 11, nd requirements to meet 215 trgets. The Lncet Globl Helth, 213; 1: e of estimted incident cses (Chpter 2) nd bout 8% of TB cses reported by ntionl TB progrmmes (NTPs) to WHO (Chpter 3). This chpter covers five min topics. It strts with summry of the most up-to-dte estimtes of finncil resources required for full response to the TB epidemic in 215. This is followed by presenttion nd discussion of trends in funding for TB prevention, dignosis nd tretment by ctegory of expenditure nd source of funding for the period 26 (when the Stop TB Strtegy nd Globl Pln to Stop TB were GLOBAL TUBERCULOSIS REPORT 215 n 87

99 both lunched) 1,2 to 215, for 123 countries (ccounting for 95% of reported TB cses in 213) for which dt were vilble. The third prt of the chpter nlyses funding gps reported by NTPs to WHO, with brekdowns by ctegory of expenditure nd country group. The fourth prt of the chpter includes the ltest estimtes of the unit costs of tretment for drug-susceptible nd multidrug-resistnt TB (MDR-TB). The new End TB Strtegy includes 225 milestones for 75% reduction in TB deths nd 5% reduction in the TB incidence rte, compred with bseline of 215 (Chpter 1). Achievement of these milestones requires tht universl helth coverge (UHC), defined s ccess for ll to essentil preventive nd tretment helth cre interventions, with finncil protection, is in plce by ,4 In this context, the fif th nd finl prt of the chpter introduces new topic to the globl TB report: n nlysis of helth finncing dt nd wht insights these cn offer bout the current sttus of progress towrds UHC. Further country-specific dt cn be found in finnce profiles tht re vilble online Estimtes of funding required in 215 for full response to the globl TB epidemic An updted version of the Globl Pln to Stop TB , covering the lst five yers of the pln, ws issued in This set out the ctions nd estimted funding requirements for full response to the TB epidemic for the five-yer period in low nd middle-income countries, bsed on the Stop TB Strtegy, with the overll gol of chieving the 215 globl trgets for reductions in cses of nd deths from TB i.e. tht incidence should be flling nd tht prevlence nd mortlity rtes should be hlved compred with their levels in 199 (Chpter 1, Chpter 2). Key components of the pln included incresing the number of ptients detected nd treted ccording to WHO s recommended strtegy from 5.8 million in 211 to 6.9 million by 215 (equivlent to more thn 8% of the forecst number of incident cses in 215 t the time the projections were done); ensuring testing for drug susceptibility for ll previously treted ptients nd ll new ptients with known risk fctors for MDR-TB by 215; enrolment of ll reported TB ptients with MDR-TB (projected t pproximtely 3 ) in 215 on second-line tretment; HIV testing of ll ptients with TB; nd prompt initition of ART in ll HIV-positive TB ptients. 1 Rviglione M, Uplekr M. WHO s new Stop TB strtegy. Lncet 26; 367: The Globl Pln to Stop TB, Genev, World Helth Orgniztion; 26 (WHO/HTM/STB/26.35). 3 World Helth Orgnistion, World Bnk Group. Monitoring progress towrds universl helth coverge t country nd globl levels. Frmework, mesures nd trgets. Genev: World Helth Orgniztion; 214 (WHO/ HIS/HIA/14.1). 4 World Helth Orgnistion. The World Helth Report 21: Helth systems finncing: the pth to universl coverge. Genev, World Helth Orgniztion; The Globl Pln to Stop TB, Genev, World Helth Orgniztion; 21 (WHO/HTM/STB/21.2). From Jnury to Mrch 213, the Globl Pln dtsets were used in combintion with new country-specific plnning nd budgeting work with nine high TB or high MDR-TB burden countries to produce updted estimtes of funding needs for TB prevention, dignosis nd tretment in low nd middle-income countries. 7 The nine countries were Ethiopi, Indi, Indonesi, Kzkhstn, Keny, Nigeri, Pkistn, South Afric nd Ukrine. Anlyses were conducted in the context of estimtes of funding needs nd funding gps required for the Globl Fund s replenishment ef forts in WHO subsequently extended these nlyses to cover ll lownd middle-income countries, including those not eligible to pply to the fund. 9 Notble countries (in terms of TB burden nd funding requirements) tht re not eligible to pply to the Globl Fund include Brzil, Chin nd the Russin Federtion. During the course of the work done for the first prereplenishment meeting held in April 213, it should be highlighted tht the Globl Fund, WHO, UNAIDS, nd other prtners greed tht funding needs for ART for HIV-positive TB ptients should be included in estimtes of HIV resource needs to void double counting. For this reson, the estimtes of resource requirements for TB/HIV interventions included in the updted estimtes of resource needs for TB re lower thn those shown in the Globl Pln. The totl funding required in ll low nd middle-income countries ws estimted t bout US$ 8 billion in 215. Of this totl, bout two-thirds (US$ 5.3 billion) ws for the detection nd tretment of drug-susceptible TB; 2% (US$ 1.6 billion) for tretment of MDR-TB; 8% (US$.6 billion) for rpid dignostic tests nd ssocited lbortory strengthening, especilly for the detection of MDR-TB; nd 6% (US$.5 billion) for collbortive TB/HIV ctivities (excluding ART). It ws lso estimted tht of the totl required in 215, bout US$ 6 billion could be mobilized from domestic sources nd round US$ 2 billion would be needed from interntionl donor sources. The cpcities of Brzil, the Russin Federtion, Indi, Chin nd South Afric (BRICS, which collectively ccount for lmost 5% of reported TB cses worldwide) to mobilize most of their funding needs from domestic sources, in contrst with other country groups including the 17 other HBCs nd low-income countries (mostly in Afric) where lrge mounts of interntionl funding would be needed, were highlighted. 7 Funding required for reserch nd development for new TB dignostics, drugs nd vccines ws not considered. In the Globl Pln, it is estimted tht bout US$ 2 billion per yer is needed for reserch nd development. In 213, funding for reserch nd development mounted to US$.7 billion (see org/tbrd214). 8 The Globl Fund to Fight AIDS, Tuberculosis nd Mlri fourth replenishment ( ): needs ssessment. Genev, Globl Fund to Fight AIDS, Tuberculosis nd Mlri; Floyd K, Fitzptrick C, Pntoj A nd Rviglione M. Domestic nd donor finncing for tuberculosis cre nd control in low-income nd middle-income countries: n nlysis of trends, 22 11, nd requirements to meet 215 trgets. The Lncet Globl Helth, 213; 1: e n GLOBAL TUBERCULOSIS REPORT 215

100 n FIGURE 7.1 Funding for TB prevention, dignosis nd tretment by intervention re, (constnt 215 US$ billions) US$ billions Other Drug-susceptible TB TB/HIV Totl MDR-TB TB funding, overll nd by ctegory of expenditure nd source of funding, Dt reported by NTPs to WHO since 26 llowed nlysis of funding trends in 123 countries (Tble 7.1). These countries ccounted for 95% of the globl number of TB cses reported in 214, nd included 12 low nd middleincome countries plus three high TB nd/or MDR-TB burden countries tht hve reched high-income sttus (Estoni, Ltvi nd the Russin Federtion). The methods used to collect, review nd nlyse finncil dt re summrized in Box 7.1. n FIGURE 7.2 Funding for drug-susceptible TB nd MDR-TB, , by country group (constnt 215 US$ millions) BRICS 17 other HBCs Other low- nd middle-income countries (n=97) US$ millions Drug-susceptible TB MDR-TB n FIGURE 7.3 Funding for TB prevention, dignosis nd tretment by funding source, (constnt 215 US$ billions) US$ billions Totl Domestic (NTP budget) Inptient nd outptient cre (best estimte likely >95% is domestic funding ) Globl Fund (NTP budget) Other interntionl donors (NTP budget) 96% of funding for inptient nd outptient cre is ccounted for by middle nd high-income countries; such countries do not typiclly receive interntionl donor funding for inptient nd outptient cre services. Dt is n estimte bsed on country-reported utiliztion. In these 123 countries, funding for TB prevention, dignosis nd tretment reched US$ 6.6 billion in 215, up from US$ 6.2 billion in 214 nd more thn double the US$ 3.2 billion tht ws vilble in 26 (Figure 7.1). Of the totl of US$ 6.6 billion, most is for the dignosis nd tretment of drug-susceptible TB (US$ 3.9 billion). Funding for MDR-TB hs grown, especilly since 29, reching US$ 2.3 billion in 215 (Figure 7.1, Figure 7.2). However, it should be highlighted tht more thn hlf of this funding is ccounted for by the Russin Federtion (Tble 7.2), reflecting extensive use of hospitliztion for ptients with MDR-TB. Given the still lrge detection gps for MDR-TB s well s gps between the numbers of cses detected nd strted on tretment (Chpter 4), much more funding is required for MDR-TB globlly nd in most of the high MDR-TB burden countries. A detiled brekdown of the funding estimted to be required for drug-susceptible TB, MDR-TB nd collbortive TB/HIV ctivities in 215, bsed on NTPs ssessments of their needs, is shown for the 36 high TB nd MDR-TB burden countries in Tble 7.2. Domestic funding for the TB-specific budgets of NTPs ccounts for the lrgest single shre of funding, followed by funding for inptient nd outptient cre (Figure 7.3). Since GLOBAL TUBERCULOSIS REPORT 215 n 89

101 n TABLE low nd middle-income countries included in nlyses of TB finncing, by income group nd WHO region, 215 Afric LOW-INCOME (13% OF NOTIFIED CASES GLOBALLY IN 214) Benin, Burkin Fso, Burundi, Centrl Africn Republic, Chd, DR Congo, Eritre, Ethiopi, Gmbi, Guine, Guine-Bissu, Liberi, Mdgscr, Mlwi, Mli, Mozmbique, Niger, Rwnd, Sierr Leone, South Sudn, Togo, Ugnd, UR Tnzni, Zimbbwe LOWER-MIDDLE-INCOME (57% OF NOTIFIED CASES GLOBALLY IN 214) Cbo Verde, Cmeroon, Congo, Côte d Ivoire, Ghn, Keny, Lesotho, Muritni, Nigeri, So Tomé nd Principe, Senegl, Swzilnd, Zmbi Americs Hiti Bolivi, El Slvdor, Guteml, Guyn, Hondurs, Nicrgu Estern Mediterrnen Europe South-Est Asi Afghnistn, Somli Democrtic People s Republic of Kore, Nepl Djibouti, Egypt, Morocco, Pkistn, Sudn, Syri, West Bnk nd Gz Strip, Yemen Armeni, Georgi, Kyrgyzstn, Republic of Moldov, Tjikistn, Ukrine, Uzbekistn Bngldesh, Bhutn, Indi, Indonesi, Mynmr, Sri Lnk, Timor-Leste Western Pcific Cmbodi Kiribti, Lo People s Democrtic Republic, Micronesi (Federl Sttes of), Ppu New Guine, Philippines, Smo, Solomon Islnds, Vnutu, Viet Nm UPPER-MIDDLE-INCOME (25% OF NOTIFIED CASES GLOBALLY IN 214) Angol, Botswn, Gbon, Nmibi, South Afric Belize, Brzil, Colombi, Dominicn Republic, Ecudor, Jmic, Mexico, Pnm, Prguy, Peru, Surinme Irn (Islmic Republic of), Irq, Jordn, Lebnon, Tunisi Bosni nd Herzegovin, Bulgri, Kzkhstn, Montenegro, Romni, Serbi, The Former Yugoslv Republic of Mcedoni, Turkey BRICS (48% OF NOTIFIED CASES GLOBALLY IN 214) South Afric Brzil Russin Federtion 17 HIGH-BURDEN COUNTRIES EXCLUDING BRICS (33% OF NOTIFIED CASES GLOBALLY IN 214) DR Congo, Ethiopi, Keny, Mozmbique, Nigeri, Ugnd, UR Tnzni, Zimbbwe Afghnistn, Pkistn Mldives, Thilnd Indi Bngldesh, Indonesi, Mynmr, Thilnd Americn Smo, Chin, Fiji, Mlysi, Mrshll Islnds, Mongoli, Plu, Tong, Tuvlu Not included Comoros Albni, Algeri, Azerbijn, Belrus, Cost Ric, Cub, Dominic, Grend, Liby, Plu, Sint Luci, Sint Vincent nd the Grendines, Turkmenistn Chin Cmbodi, Philippines, Viet Nm 14 HIGH MDR-TB BURDEN COUNTRIES (NOT IN THE LIST OF 22 HIGH-BURDEN COUNTRIES) (2% OF NOTIFIED CASES GLOBALLY IN 214) Armeni,Bulgri, Estoni, Georgi, Kzkhstn, Kyrgyzstn, Ltvi, Republic of Moldov, Tjikistn, Ukrine, Uzbekistn Azerbijn, Belrus, Lithuni Anlyses focus primrily on low nd middle-income countries. Three high-income countries (Estoni, Ltvi nd the Russin Federtion) were included becuse they re in the list of 22 high-burden countries or the list of 27 high MDR-TB burden countries. Additionl countries included in trend nlyses of TB finncing compred with those included in previous globl reports re shown in bold. 9 n GLOBAL TUBERCULOSIS REPORT 215

102 n TABLE 7.2 TB budget reported by NTP by intervention re, nd estimted cost of inptient nd outptient cre for drug-susceptible (DS-TB) nd MDR-TB, 36 high TB or MDR-TB burden countries, 215 (current US$ millions) TB BUDGET REPORTED BY NTP RESOURCES REQUIRED FOR INPATIENT AND OUTPATIENT CARE TOTAL DS-TB MDR-TB TB/HIV DS-TB MDR-TB RESOURCES REQUIRED FOR TB CARE 22 HIGH-BURDEN COUNTRIES Afghnistn Bngldesh Brzil Cmbodi Chin DR Congo Ethiopi Indi Indonesi Keny Mozmbique Mynmr Nigeri Pkistn Philippines Russin Federtion,b South Afric Thilnd Ugnd UR Tnzni Viet Nm Zimbbwe high-burden countries REMAINING HIGH MDR-TB BURDEN COUNTRIES Armeni Azerbijn Belrus < Bulgri Estoni Georgi Kzkhstn Kyrgyzstn Ltvi Lithuni Republic of Moldov Tjikistn Ukrine Uzbekistn < high MDR-TB burden countries high-tb or high MDR-TB burden countries Blnk cells indicte dt not reported. indictes vlues tht cnnot be clculted. No mount is shown for Chin nd the Russin Federtion becuse the NTP budgets reported by those countries include ll budgets for inptient nd outptient cre. b In the Russin Federtion, the stf f nd infrstructure reported for TB cre nd control were llocted to DS-TB (23%) nd MDR-TB (77%) by WHO bsed on the proportion of bed-dys used by DS-TB nd MDR-TB ptients. GLOBAL TUBERCULOSIS REPORT 215 n 91

103 Box 7.1 Methods used to compile, vlidte nd nlyze finncil dt reported to WHO WHO begn monitoring government nd interntionl donor finncing for TB in 22. All dt re stored in the WHO globl TB dtbse. The stndrd methods used to compile, review, vlidte nd nlyse these dt hve been described in detil elsewhere.,b This box provides summry. Ech yer, WHO requests ll low nd middle-income countries (nd the Russin Federtion, the only HBC tht is high-income country) to report the funding required for TB prevention, dignosis nd tretment in their current fiscl yer, by ctegory of expenditure nd source of funding; nd expenditures for the most recently completed fiscl yer, lso by ctegory of expenditure nd source of funding. In the 215 round of globl TB dt collection, the fiscl yers were 215 nd 214, respectively. Ctegories of expenditure for dignosis nd tretment of drug-susceptible TB were synthesized compred to those used , to simplify reporting. Six ctegories were used: lbortory infrstructure, equipment nd supplies; NTP stf f (centrl unit stf f nd subntionl TB stf f); drugs to tret drug-susceptible TB; progrmme costs; ptient support; nd opertionl reserch including surveys. The min chnge ws tht severl subctegories of progrmme costs were condensed into one ctegory (this mens tht trends cn still be ssessed bck to 26). Ctegories of expenditure used for MDR-TB remined the sme s those used since 26: second-line drugs, nd progrmmtic mngement of MDR-TB. Budgets nd expenditures for collbortive TB/ HIV ctivities were requested s one consolidted ctegory of expenditure, s in previous yers. Funding vilble from four mjor sources ws requested, lso s in previous yers: domestic funding excluding lons; externl lons, lso considered domestic funding; the Globl Fund; nd grnt finncing from sources other thn the Globl Fund. A simplifiction compred with previous yers ws tht only n overll brekdown of totl funding ws requested, s opposed to brekdown for ech ctegory of expenditure. Agin, this does not f fect bility to report trends in formt consistent with those published in pst reports. For highincome countries (except the Russin Federtion which is n HBC), only totls for both funding requirements nd expenditures were requested, without ny brekdown by ctegory of expenditure or source of funding, s in previous yers. As usul in 215, ll countries were sked to report on the utiliztion of inptient nd outptient cre required for tretment of people with drug-susceptible nd MDR-TB, on per ptient bsis (i.e. the verge number of dys spent in hospitl, nd the verge number of outptient visits to helth fcility). These dt re used in combintion with other informtion to estimte the finncil resources used for TB prevention, dignosis nd tretment tht re not reflected in TB-specific reports of funding requirements, vilble funding nd expenditures (further detils re provided below). Core methods used to review nd vlidte dt hve remined consistent since 22. They include: " Routine checks for plusibility nd consistency, including vlidtion checks tht re built into the online reporting system. Exmples of vlidtion checks re checks for implusibly lrge yer-to-yer chnges (for exmple in totl reported funding by source nd by ctegory of expenditure), or implusibly high or low vlues of funding for drugs reltive to the number of TB ptients (tht dif fer substntilly from prices quoted by the Globl TB Drug Fcility). " Discussions with country respondents to resolve queries. " Tringultion with other dt sources. One exmple is the detiled budgets prepred by NTPs tht re peer-reviewed by WHO s prt of ef forts to strengthen the budgeting of ntionl strtegic plns for TB cre nd control. Comprehensive nd robust budgets for ntionl strtegic plns re now n essentil requirement for funding pplictions to the Globl Fund, s prt of this gency s new funding model introduced in 213. Two tools promoted by WHO (the WHO TB plnning nd budgeting tool nd the OneHelth tool) c,d for estimting funding requirements llow mpping of detiled budgets to the line items used in the WHO TB dt collection form, nd comprisons with dt reported online. Tringultion is lso undertken with dt vilble from the Globl Fund, e USAID, f nd the Orgniztion for Economic Coopertion nd Development s Creditor Reporting System. In 215, for exmple, reported dt were compred with dt submitted to the Globl Fund s prt of the funding gp nlyses required for funding proposls nd follow-up nd djustments mde s pproprite. In 214 nd 215, dditionl elements of review nd vlidtion included fcilittion of communictions between focl points for Ntionl Helth Accounts nd NTP mngers, with the im of using expenditure dt generted from implementtion of the System of Helth Accounts 211 (tht llows expenditures to be reported by disese) for reporting of TB expenditures wherever vilble. In reviewing nd vlidting dt, prticulr ttention hs lwys been given to the 22 HBCs. A summry of dt vlidtion methods used for HBCs is provided in Tble B7.1. TB funding reported by NTPs usully does not include the finncil costs ssocited with the inptient nd outptient cre required during TB tretment (mong HBCs, the notble exceptions re Chin nd the Russin Federtion, since tretment is provided in TB-specific clinics or hospitls for which ermrked budgets nd funding exist). Since mny detiled costing studies in wide rnge of countries show tht these costs ccount for lrge shre of the cost of treting someone with TB, g nlyses of TB finncing undertken by WHO hve lwys included estimtes of the funding used for both inptient nd outptient cre. As in pst reports, WHO estimtes the funding used for inptient nd outptient cre of TB ptients by multiplying the number of outptient visits nd dys of inptient cre per ptient (reported by NTPs ech yer) by the cost per bed-dy nd clinic visits vilble from the WHO-CHOICE dtbse h nd then by the reported number of TB ptients notified or projected to be notified. This is done seprtely for drug-susceptible TB nd MDR-TB. For further three countries (Belrus, Burkin Fso nd the Democrtic Republic of the Congo), dt from recent Ntionl Helth Account (NHA) were used. i It is hoped tht in the ner future, NHA dt will be routinely vilble for mny more countries, including brekdown by source of funding (domestic vs interntionl) tht is currently not vilble for ny country. b c Floyd K, Pntoj A, Dye C. Finncing tuberculosis monitoring system. Bulletin of the World Helth Orgniztion; 27; 85: Floyd K, Fitzptrick C., Pntoj A nd Rviglione M. Domestic nd donor funding for tuberculosis cre nd control in low-income nd middleincome countries: n nlysis of trends 22 11, nd requirements to meet 215 trgets. The Lncet Globl Helth; 1: e Plnning nd budgeting for TB control ctivities. Genev, World Helth Orgniztion; tool/en/ 92 n GLOBAL TUBERCULOSIS REPORT 215

104 TABLE B7.1 Methods used to review nd vlidte finncing dt reported by NTPs, high TB nd MDR-TB burden countries COUNTRY ROUTINE REAL-TIME CHECKS FOR PLAUSIBILITY AND INTERNAL CONSISTENCY (TRENDS OVER TIME), REVIEW AND FOLLOW-UP CHECKS BY WHO FINANCE DATA REVIEWERS, UPDATES/ CORRECTIONS ENCOURAGED REVIEW BY IN-COUNTRY WHO TB MEDICAL OFFICER NATIONAL TB STRATEGIC PLANNING AND BUDGETING AND ASSOCIATED ASSESSMENT OF SOURCES OF FUNDING USING WHO RECOMMENDED COSTING TOOLS b UNIT COST DATA AVAILABLE FROM INDEPENDENT ECONOMIC EVALUATION 22 HIGH TB BURDEN COUNTRIES Afghnistn yes yes yes (213) no Bngldesh yes yes yes (214) yes Brzil yes yes no yes Cmbodi yes yes yes (29) yes Chin yes yes no yes DR Congo yes yes yes (214) no Ethiopi yes sometimes yes (214) yes Indi yes yes yes (213) yes Indonesi yes yes yes (213) yes Keny yes yes yes (213) yes Mozmbique yes mostly yes (213) no Mynmr yes yes yes (211) no Nigeri yes yes yes (213) yes Pkistn yes yes yes (213) yes Philippines yes yes yes (211) yes Russin Federtion yes yes no yes South Afric yes yes yes (213) yes UR Tnzni yes yes no yes Thilnd yes yes yes (215) yes Ugnd yes yes yes (213) yes Viet Nm yes yes no yes Zimbbwe yes yes yes (213) yes REMAINING HIGH MDR-TB BURDEN COUNTRIES Armeni yes Wolfheze working group on finncing yes (21) no Azerbijn yes no no no Belrus yes Wolfheze working group on finncing no no Bulgri yes no no no Georgi yes no no no Kzkhstn yes no yes (213) no Kyrgyzstn yes yes yes (213) no Ltvi yes no no yes Lithuni no no no no Republic of Moldov yes no no no Tjikistn yes no no yes Ukrine yes yes yes (213) yes Uzbekistn yes no yes (211) no Source: GTB compiltion bsed on dt review process nd Lwrence Y. et l, 215. Dt for Lithuni hs never been reported to WHO. b The tools recommended by WHO re the OneHelth tool nd the WHO TB Plnning nd Budgeting tool. d e f Plnning nd budgeting for TB control ctivities s prt of sector wide ntionl strtegic helth plns nd policies. Genev, Inter-Agency working group; 215. Avilble t: For exmple, dt vilble t were ccessed in My 215. FY 213 Congressionl Budget Justifiction for Foreign Opertions. Relesed Mrch nd April 212, USAID ib/fy213cbj/pdf/ g h i Lurence YV, Grif fiths UK, Vssll A. Costs to Helth Services nd the Ptient of Treting Tuberculosis: A Systemtic Literture Review. PhrmcoEconomics. 215:1 17. Choosing interventions tht re cost ef fective (WHO-CHOICE). Genev, World Helth Orgniztion; 28. Avilble t: choice/cost-ef fectiveness/inputs/helth_service/en/ Ntionl Helth Accounts GLOBAL TUBERCULOSIS REPORT 215 n 93

105 lmost ll (96%) of the funding estimted to be used for inptient nd outptient cre is ccounted for by middle- or high-income countries, it cn be ssumed tht virtully ll of this funding is from domestic sources (interntionl donor funding for inptient nd outptient cre is only likely to occur in low-income countries, vi generl budget support to the helth sector). Overll, 87% of the estimted funding of US$ 6.6 billion in 215 is from domestic sources. Interntionl donor funding for the TB-specific budgets of NTPs hs incresed since 26, reching US$.8 billion in 215. It is importnt to highlight tht the funding reported by NTPs does not cpture ll interntionl donor funding for TB; donor funding is lso provided to entities other thn NTPs, including interntionl nd ntionl governmentl nd nongovernmentl orgniztions. A more comprehensive nlysis of interntionl donor funding, bsed on donor reports to the Orgniztion for Economic Coopertion nd Development (OECD), is provided in Box It is lso importnt to emphsize tht the globl verge for the shre of funding provided from domestic sources concels enormous vrition mong individul countries, s well s country groups tht cn be defined bsed on TB burden, geogrphy, politicl/economic profile nd income level (Figure 7.4, Tble 7.3). Domestic funding domintes (93 94% of the totl funding vilble in 215) in three (not mutully exclusive) groups: BRICS, upper middle-income countries nd regions outside Afric nd Asi. In ddition to BRICS, only one HBC (Thilnd) hs consistently reported levels of domestic funding tht exceed contributions from interntionl donor funding in recent yers. In lower middle-income countries, domestic funding hs risen from US$.2 billion in 26 to over US$.5 billion in 215, but interntionl donor funding hs lso ssumed greter nd greter importnce, reching prity with domestic funding in 215. Most of the increse in lower middle-income countries hs been driven by grnts from the Globl Fund. Interntionl donor funding domintes in the group of 17 HBCs outside BRICS (73% of the totl funding vilble in 215) nd in low-income countries (8% of the totl funding vilble in 215). At the individul country level, it remins bsolutely criticl to funding for TB prevention, dignosis nd tretment in most of the 22 HBCs, nd in four HBCs (Afghnistn, Bngldesh, the Democrtic Republic of the Congo nd Mozmbique), 9% of vilble funding in 215 is from interntionl donor sources. 1 Out-of-pocket expenditures re lso not included in NTP reports. These re nlysed in more detil in section Funding gps reported by ntionl TB progrmmes, Despite growth in funding from domestic nd interntionl donor sources, mny NTPs continue to be unble to mobilize ll the funding required for full implementtion of their ntionl strtegic plns (Figure 7.5). Funding gps (i.e. the dif ference between ssessments by NTPs of funding needs for TB prevention, dignosis nd tretment nd the ctul mount of funds mobilized) hve persisted nd in 215 mounted to totl of US$.8 billion. This is considerbly less thn the gp of US$ 1.4 billion tht exists between the US$ 8 billion estimted to be needed for full response to the TB epidemic in 215 (section 7.1) nd the US$ 6.6 billion vilble in 215 (section 7.2). The dif ference cn be explined by the fct tht ntionl strtegic plns for TB remin less mbitious thn the trgets set in the Globl Pln to Stop TB, (section 7.1) in mny countries. Lower middle-income countries ccount for the lrgest reported funding gps (bout US$.5 billion in 215), of which US$.4 billion ws in five countries (Nigeri, Indonesi, Ukrine, Viet Nm nd the Philippines, in descending order). There my be dditionl cpcity to mobilize more domestic funding in these countries. Funding gps were reltively smll in upper middle-income countries in 215 (Figure 7.5), nd hve fllen in recent yers mostly explined by lrge reductions in the funding gps reported by the Russin Federtion nd Kzkhstn. These two countries reported no funding gps in 214 or 215. Funding gps reported by low-income countries fell between 214 nd 215, reflecting shif t of some countries from the low to middle-income country group between 214 nd 215. Geogrphiclly, the Africn Region hs by fr the lrgest funding gp: US$.4 billion in 215, equivlent to hlf of the globl totl. The lrgest gp ws reported by Nigeri (US$ 154 million, see Tble 7.3). Of the US$.8 billion funding gp reported by NTPs in 215, US$.64 billion is for drug-susceptible TB nd US$.14 billion is for MDR-TB. Reltive to totl funding needs, the funding gp is lrger for drug-susceptible TB. Domestic funding ccounts for lrger shre of the funding for MDR-TB compred with drug-susceptible TB, which is not surprising given tht most of the high MDR-TB burden countries re middle or high-income countries nd 14 of 27 re in the Europen Region. 7.4 Unit costs of tretment for drugsusceptible nd MDR-TB, 214 The cost per ptient treted for drug-susceptible nd MDR- TB could be estimted for 117 countries nd 9 countries, respectively. The nlysis of the cost per TB ptient with drug-susceptible TB ws limited to countries tht hd notified t lest 1 TB cses in 214. Estimtes of the unit cost of MDR-TB tretment were restricted to countries tht reported t lest 1 ptients on second-line tretment for MDR-TB. 94 n GLOBAL TUBERCULOSIS REPORT 215

106 n TABLE 7.3 TB budget reported by NTP, vilble funding from domestic nd interntionl donor sources, funding gp nd shre of budget provided by domestic nd interntionl donor funding, 36 high TB or MDR-TB burden countries, 215 (current US$ millions) TB BUDGET REPORTED BY NTP DOMESTIC FUNDING (A) INTERNATIONAL DONOR FUNDING (B) SHARE OF AVAILABLE FUNDING (A+B) PROVIDED FROM DOMESTIC SOURCES (%) SHARE OF AVAILABLE FUNDING (A+B) PROVIDED BY INTERNATIONAL DONORS (%) 22 HIGH-BURDEN COUNTRIES Afghnistn % 92% 4. Bngldesh % 1% 14 Brzil % 1.1% 21 Cmbodi % 8% 13 Chin % 2% 28 DR Congo % 9% 24 Ethiopi % 79% 38 Indi % 54% Indonesi % 61% 88 Keny % 52% 2 Mozmbique % 92% 8.1 Mynmr % 86% 8 Nigeri % 59% 154 Pkistn % 78% 12 Philippines % 63% 4 Russin Federtion % % South Afric % 8.6% 21 Thilnd % 18% 12 Ugnd % 88% 5.2 UR Tnzni % 59% 47 Viet Nm % 63% 48 Zimbbwe % 89% 1 22 high-burden countries % 17% 614 FUNDING GAP REMAINING HIGH MDR-TB BURDEN COUNTRIES Armeni % 29% Azerbijn % 81% Belrus % 34% 4.7 Bulgri % 12% Estoni.6.6 1% <1% Georgi % 59% 3.2 Kzkhstn % % Kyrgyzstn % 63% Ltvi % % Lithuni Republic of Moldov % 41% Tjikistn % 65% 5.1 Ukrine % 32% 5 Uzbekistn % 14% 27 high MDR-TB burden countries % 15% high-tb or high MDR-TB burden countries % 17% 678 Blnk cells indicte dt not reported. indictes vlues tht cnnot be clculted. The funding gp reflects the nticipted gp for the yer t the time country reported dt in the 215 round of globl TB dt collection. GLOBAL TUBERCULOSIS REPORT 215 n 95

107 Box 7.2 Interntionl donor funding for TB prevention, dignosis nd tretment, bsed on donor reports to the Orgniztion for Economic Coopertion nd Development Interntionl donor funding provided for TB prevention, dignosis nd tretment is chnnelled to NTPs nd other recipients. The finncil dt reported to WHO by NTPs therefore understtes the totl mount of interntionl donor funding being provided ech yer. The creditor reporting system (CRS) of the Orgniztion for Economic Coopertion nd Development (OECD) is the most comprehensive source of informtion bout interntionl donor funding. Reports re provided by 31 multilterl orgniztions, FIGURE B7.2.1 Interntionl donor funding for TB prevention, dignosis nd tretment by source, US$ millions Other multilterls Other countries Globl Fund United Sttes The increse between 212 nd 213 ws mostly ccounted for by Indi, which hd Globl Fund disbursement of US$ 11 million in 212 nd US$ 165 million in 213. the 26 countries tht re members of the OECD s Development Assistnce Committee nd further two non-committee members (Kuwit nd the United Arb Emirtes). The OECD compiles dt on commitments nd disbursements from both governments nd multilterl orgniztions. Disbursement dt include both direct trnsfers to countries s well s the provision of goods nd services, such s in-kind trnsfers or technicl ssistnce. Dt on gross disbursements for TB (s opposed to commitments tht my not lwys be trnslted into ctul funding) were nlysed for All funding coded s for TB (code 12263: tuberculosis control) ws included. It should be highlighted tht funding for TB tht flows between OECD countries is not recorded in the OECD dtbse. It is lso importnt to note tht in the OECD dtbse, government contributions to multilterl orgniztions re not ttributed to the government of origin but only to the multilterl orgniztion (for exmple, funding received by countries from Globl Fund grnts re ttributed to the Globl Fund, s opposed to the originl donor to the Globl Fund). Figure B7.2.1 shows tht interntionl donor funding for TB incresed from US$ 148 million in 24 to US$ 122 million in 213. Most of the funding tht ws provided cme from the Globl Fund (72%), followed by the government of the United Sttes of Americ (14%). Remining funding for TB cme from other countries (8%) nd other multilterl orgniztions (6%), mong which the lrgest donors were the governments of Cnd (4%) nd the United Kingdom (3%). The Globl Fund hs consistently been the lrgest provider of interntionl donor funding for TB, including US$ 788 million in 213. Funding incresed stedily from 24 to 213 with the exception of drop from 21 to 211. Disbursements from the government of the United Sttes of Americ stedily incresed from 27 to 211 FIGURE B7.2.2 Interntionl donor funding for TB prevention, dignosis nd tretment by region, US$ millions Afric US$ millions Americ US$ millions Asi Europe US$ millions Globl Fund United Sttes Other countries Other multilterls 96 n GLOBAL TUBERCULOSIS REPORT 215

108 FIGURE B7.2.3 Interntionl donor funding for TB prevention, dignosis nd tretment to non-oecd countries, (constnt 213 US$, million). Donors re listed on the lef t nd recipients of donor funding re listed on the right. The Globl Fund through which much donor funding is chnnelled, is shown in the middle. USA: $177 Asi: $ 13 Frnce, Germny nd the United Kingdom: $ 538 Afric: $ 899 Other countries: $ 657 Bill & Melind Gtes Foundtion: $ 77 Other multilterls: $ 91 Globl Fund: $ 1728 Americs: $ 14 Europe: $ 19 Oceni: $ 28 nd hve since levelled of f. However, it should lso be noted tht contributions from the government of the United Sttes of Americ cptured in the OECD dtbse re lower thn of ficil lloctions. In 213, the lloction for TB ws US$ 232 million nd in ddition more thn US$ 13 million ws llocted for TB/HIV vi the President s Emergency Pln for AIDS Relief (PEPFAR). The Globl Fund disbursed TB funding (in t lest one yer between 24 nd 213) in 15 of the 19 countries tht received ny TB donor ssistnce. The top recipients of funding, with totl mounts of over US$ 1 million ech during the yers , were (in descending order of the totl funding received): Chin, Indi, Indonesi, the Philippines, Bngldesh, Nigeri nd Pkistn. Collectively, these countries ccounted for over 58% of the TB cses notified in 214. Figure B7.2.2 shows tht Afric, Asi, nd Europe ll experienced mjor increses in disbursements between 212 nd 213 while mounts disbursed to the Americs remined reltively flt. The min drivers of these chnges between 212 nd 213 were incresed finncing from the Globl Fund for Zmbi (US$ 86 million in 213), Indi (US$ 165 million in 213), nd Ukrine (US$ 17 million in 213). Figure B7.2.3 shows the flow of interntionl donor funding for TB during the period In this figure, mounts of funding flowing to the Globl Fund from countries nd other donors were estimted on the ssumption tht 18% of donor s totl contribution to the Globl Fund ws for TB, in line with the overll shre of Globl Fund finncing tht is used for TB. The Globl Fund publishes the mounts received from ech donor on its website. The four lrgest country donors (the United Sttes of Americ, Frnce, Germny nd the UK) re shown seprtely, s is the lrgest non-country donor (the Bill nd Melind Gtes Foundtion). The importnce of the United Sttes of Americ in the globl funding of TB is prticulrly evident in this presenttion of dt, since it ccounted for bout one third of contributions to the Globl Fund in ddition to funding provided vi bilterl chnnels. For comprison, the totl funding reported by countries to WHO mounted to 85% of this totl, US$ 669 million. GLOBAL TUBERCULOSIS REPORT 215 n 97

109 n FIGURE 7.4 Funding for TB prevention, dignosis nd tretment from domestic sources nd interntionl donors, , 9 country groups (constnt 215 US$ billions) 3. BRICS b. 17 HBCs excluding BRICS c. Rest of world.4 1 US$ billions US$ billions US$ billions d. Low-income countries e. Lower-middle-income countries f. Upper-middle-income countries b g. Afric h. Asi c i. Other regions d Domestic Interntionl donors e Globl Fund only b c d e Rest of the world includes 11 countries tht re not in the list of 22 high TB burden or 27 high MDR-TB burden countries. The upper-middle-income ctegory includes three high-income countries tht re in the list of TB nd/or high MDR-TB burden countries: Estoni, Ltvi nd the Russin Federtion. Asi includes the WHO regions of South-Est Asi nd the Western Pcific. Other regions consists of three WHO regions: the Estern Mediterrnen Region, the Europen Region, nd the Region of the Americs. This includes the Globl Fund. Of the 36 countries tht re in the list of high TB burden or high MDR-TB countries, 35 could be included in the nlysis (the exception ws Lithuni). Anlyticl methods re summrized in Box 7.3. Unit cost estimtes for 214 re shown for drug-susceptible nd MDR-TB in Figure 7.6 nd Figure Drug-susceptible TB The cost per ptient treted for drug-susceptible TB ws generlly in the rnge US$ 1 US$ 1. In generl, pproximtely 8% of this cost ws ccounted for by reported NTP expenditures, with the reminder being inptient nd outptient cre. The cost per ptient treted ws typiclly higher, but still quite vried, in countries of the former Soviet Union, rnging from US$ US$ In these countries, lengthy hospitliztions ply more significnt role in the totl cost of cre, with dmissions lsting up to n verge of 75 dys nd ccounting for pproximtely 4 6% of the totl cost per ptient. However, there re some striking exmples of reductions in relince on hospitliztion. 98 n GLOBAL TUBERCULOSIS REPORT 215

110 Box 7.3 Methods used to estimte the cost per ptient treted for drug-susceptible nd MDR-TB Two min dt sources were used. The first ws the vlidted expenditure dt reported by NTPs tht re stored in the WHO globl TB dtbse. The second ws country-specific estimtes of the unit costs of bed-dys nd outptient visits vilble from WHO s CHOosing Interventions tht re Cost-Effective (WHO- CHOICE) model nd ssocited dtbse (mnged by the Helth Governnce nd Finncing deprtment). In few instnces when no expenditure dt could be reported, informtion bout the totl funding vilble ws used s proxy for expenditures. For few countries, WHO-CHOICE estimtes were replced with estimtes of unit costs obtined directly from recent studies or discussions with experts. Costs were clculted seprtely for drug-susceptible nd MDR- TB. In ech cse, the numertor ws the totl estimted cost of tretment, which hs two min prts: 1) the ntionl expenditures reported by the NTP; nd 2) the costs ssocited with the utiliztion of helth services by ptients with TB nd MDR-TB. As explined in Box 7.1, ntionl NTP expenditures re reported nnully to WHO using the online WHO globl TB dt collection system, nd then reviewed nd vlidted. Ctegories of expenditure considered s costs for MDR-TB were secondline drugs, nd ll other inputs/ctivities implemented for the progrmmtic mngement of MDR-TB. All other ctegories (with the exception of collbortive TB/HIV ctivities) were ssumed to be for drug-susceptible TB. For lmost ll countries, the totl costs ssocited with utiliztion of inptient nd outptient cre were clculted using informtion bout the typicl number of dys of inptient cre nd outptient visits required on per ptient bsis during tretment (reported seprtely for drug-susceptible nd MDR-TB by NTPs) combined with WHO-CHOICE unit cost estimtes, multiplied by the number of ptients treted in given yer (bsed on notifiction dt see Chpter 3 for drug-susceptible TB nd Chpter 4 for MDR-TB). Multiplying quntities of visits nd bed-dys by their price estimtes yields the totl estimted cost of inptient nd outptient services. For three countries (Belrus, Burkin Fso nd the Democrtic Republic of the Congo), TB inptient nd outptient expenditures vilble from Ntionl Helth Accounts were used in lieu of the estimted cost from this ingredients-bsed pproch. Unit costs were then clculted s the sum of 214 NTP expenditures nd totl costs for utiliztion of inptient nd outptient cre, divided by the reported number of ptients treted. Agin, this clcultion ws crried out seprtely for drugsusceptible nd MDR-TB. n FIGURE 7.5 Funding gps for TB prevention, dignosis nd tretment reported by countries, by income group nd WHO region, (constnt 215 US$ millions) 6 Totl gp = US$.8 billion 5 Totl gp = US$.8 billion 5 4 US$ millions US$ millions Lower-middle-income countries Low-income countries Upper-middle-income countries Africn region Region of the Americs Estern Mediterrnen region Europen region South-Est Asi region Western Pcific region The upper-middle-income ctegory includes three high-income countries tht re in the list of TB nd/or high MDR-TB burden countries: Estoni, Ltvi nd the Russin Federtion. GLOBAL TUBERCULOSIS REPORT 215 n 99

111 n FIGURE 7.6 Estimted cost per ptient treted for drug-susceptible TB in 117 countries, 214 Cost per ptient treted (215 US$, log scle) TB cselod (notified TB cses) Ethiopi Cmbodi Zimbbwe Mozmbique Afghnistn Ugnd DR Congo UR Tnzni Bngldesh Pkistn Mynmr Philippines Viet Nm Nigeri Keny Indi Thilnd Indonesi Chin South Afric Russin Federtion Brzil WHO region Africn Americn Estern Mediterrnen Europen South-Est Asi Western Pcific GDP per cpit (215 US$, log scle) Limited to countries with t lest 1 notified ptients in 214. n FIGURE 7.7 Estimted cost per ptient treted for MDR-TB in 9 countries, 214 Cost per ptient treted (215 US$, log scle) MDR-TB cselod (notified cses) DR Congo Ethiopi Tjikistn Kyrgyzstn Pkistn Indi Republic of Moldov Ukrine Mynmr Uzbekistn Bngldesh Nigeri Armeni Indonesi Philippines Viet Nm Georgi South Afric Russin Federtion Belrus Bulgri Chin Azerbijn WHO region Ltvi Estoni Kzkhstn Africn Americn Estern Mediterrnen Europen South-Est Asi Western Pcific GDP per cpit (215 US$, log scle) Limited to countries with t lest 2 ptients on second-line tretment in n GLOBAL TUBERCULOSIS REPORT 215

112 Although not yet be reflected in nlyses for 214, the Russin Federtion reported hospitliztion of bout 65% of TB ptients with drug-susceptible TB in 215, compred with 93% in 214. Low-income countries spent on verge US$ 516 per TB ptient, while upper-middle-income or high-income countries invested n verge of US$ In the 22 HBCs, the estimted cost per ptient treted for drug-susceptible TB in 214 rnged from US$ 74 in Pkistn to US$ in the Russin Federtion. In ll of the 22 HBCs, the cost per ptient treted for drug-susceptible TB ws less thn gross domestic product (GDP) per cpit. Six countries Chin, Indi, South Afric, Indonesi, Bngldesh nd Pkistn, which together ccount for 58% of the globl TB burden hve costs per ptient treted tht re reltively low compred with their GDP per cpit. While the level of GDP per cpit clerly influences the cost of TB tretment, this shows tht the size of the totl ptient cselod is lso n importnt fctor (for exmple, when numbers of ptients treted re very lrge, economies of scle cn be relised) MDR-TB For MDR-TB, the cost per ptient treted rnged from n verge of US$ in low-income countries to n verge of US$ in upper middle-income countries in 214. As for drug-susceptible TB, the cost per ptient treted for MDR-TB ws typiclly higher in countries of the former Soviet Union, rnging from US$ in Uzbekistn to US$ in Ltvi (where ll ptients with MDR-TB re hospitlized for n verge of 12 dys, t n estimted cost of US$ 262 per dy). This minly reflects greter relince on inptient cre, with dmissions lsting up to n verge of 24 dys per ptient nd ccounting for bout 6% of the totl cost of tretment. 7.5 Progress towrds UHC: insights from helth finncing dt UHC is defined s ccess for ll to essentil preventive nd tretment helth cre interventions, with finncil protection. 1 In finncing terms, the bsolute level of funding for helth cre must be high enough to ensure tht it is possible to provide essentil helth services to the whole popultion; dditionlly, the costs of using those services, once vilble, must not be prohibitive (using them should not result in finncil hrdship). Mndtory pre-pyment finncing mechnisms (such s txtion or socil insurnce schemes) need to form the core of domestic helth finncing. 2 There re three helth finncing indictors for which benchmrks required to chieve UHC hve been suggested nd for which recent estimtes re vilble for ll countries 1 World Helth Orgnistion, World Bnk Group. Monitoring progress towrds universl helth coverge t country nd globl levels. Frmework, mesures nd trgets. Genev: World Helth Orgniztion; 214 (WHO/ HIS/HIA/14.1). 2 World Helth Orgniztion. The World Helth Report 21. Helth systems finncing: the pth to universl coverge. Genev: World Helth Orgniztion; 21. to which the indictor pplies. Anlysis of dt (from the WHO Globl Helth Expenditure dtbse) for these three indictors cn therefore provide useful insights into country s progress towrds, or chievement of, UHC. The three indictors re: "" Totl government spending on helth s proportion of GDP: the suggested benchmrk is 5 6%; 3,4,5 "" Government nd donor-funded helth expenditure per cpit in low-income countries: the suggested benchmrk is US$ 86 (in 212 prices); 2 "" The shre of out-of-pocket expenditures (OOP) in totl helth expenditures: the suggested benchmrk is less thn 15%. 1,6,7 OOP expenditures re defined s direct pyments mde to helth cre providers by individuls t the time of service use, excluding prepyment for helth services (for exmple in the form of txes or specific insurnce premiums or contributions) nd, where possible, net of ny reimbursements to the individul who mde the pyment. 8 The level of OOP expenditures provides proxy mesure of the degree to which people lck finncil protection Government spending on helth s proportion of GDP The ltest dt on government helth expenditures (GHE) re for GHE ws less thn 6% of GDP in most countries in 213 (149/19, 78%), including ll of the 36 countries in the current lists of high TB burden nd/or MDR-TB burden countries (Figure 7.8). Among HBCs, those t the lowest end of the rnge were Bngldesh, Indonesi, Indi, Nigeri, Mynmr, Pkistn nd the Philippines (ll <1.5%); those closest to the 6% threshold were Brzil, South Afric nd Thilnd (ll t round 4.5%). Among WHO regions, the South-Est Asi Region hd the lowest levels of helth spending s proportion of GDP. There were 41 countries where government spending on helth exceeded 6% of GDP. Of these, only six were low or lower-middle income countries: Rwnd, Swzilnd, Lesotho, Smo, Kiribti nd Micronesi. 3 World Helth Orgniztion. The World Helth Report 21. Helth systems finncing: the pth to universl coverge. Genev: World Helth Orgniztion; McIntyre et l. Fiscl Spce for Domestic Funding of Helth nd Other Socil Services. London: Chthm House; World Helth Orgniztion nd Pn Americn Helth Orgniztion. Resolution CD53.R14 Strtegy for universl ccess to helth nd universl helth coverge. 53rd Directing Council, 66th Session of the Regionl Committee of WHO for the Americs. Wshington: World Helth Orgniztion nd Pn Americn Helth Orgniztion, Xu et l, Protecting Households from Ctstrophic Helth Spending, Helth Af firs 27; 26(4): Xu et l., Household Ctstrophic Helth Expenditure: A Multicountry Anlysis, The Lncet 23;362: World Helth Orgniztion nd World Bnk. First Globl Monitoring Report on Trcking Universl Helth Coverge, helthinfo/universl_helth_coverge/report/215/en/. 9 WHO Ntionl Helth Accounts dtbse, ccessed July 215 vi pps.who.int/nh/dtbse cvv GLOBAL TUBERCULOSIS REPORT 215 n 11

113 n FIGURE 7.8 Government spending on helth, s percentge of gross domestic product (GDP), 213 Percentge of GDP <4% 4 5.9% 6 9.9% 1% No dt Not pplicble Dt for Bhrin nd Brzil re for 212. n FIGURE 7.9 Government spending on helth per cpit in low-income countries (shown in blue), 213. Middle nd high-income countries re shown in white. <US$ 5 US$ US$ US$ US$ US$ 45 6 No dt Not pplicble Countries re clssified s per the World Bnk income ctegories for 213. Avilble t: 12 n GLOBAL TUBERCULOSIS REPORT 215

114 n FIGURE 7.1 Out-of-pocket expenditures s percentge of totl helth expenditures, 213 Percentge 15% 16 29% 3 44% 45% No dt Not pplicble Government spending on helth per cpit, low-income countries In 213, government spending on helth per cpit ws fr below the suggested benchmrk of US$ 86 per cpit in ll low-income countries (Figure 7.9). Most countries spent less thn US$ 2 per cpit. The countries tht were closest to the benchmrk were Rwnd (US$ 41 per cpit) nd Kyrgyzstn (US$ 51 per cpit) Shre of out-of-pocket expenditures in totl helth expenditures In 213, OOP expenditures were less thn 15% of totl helth spending in 43 of 19 countries for which dt were vilble, including three HBCs: Mozmbique, Thilnd nd South Afric (Figure 7.1). At the other end of the scle, there were 49 countries where OOP expenditures ccounted for t lest 45% of totl helth expenditures, including ten HBCs: Bngldesh, Indi, Indonesi, Cmbodi, Nigeri, Mynmr, Pkistn, Philippines, Viet Nm nd the Russin Federtion. The globl verge in 213 ws 32%, smll reduction compred with 36% in 2. 1 The brekdown of totl helth expenditures by source of funding, including OOP expenditures, is shown for selected high TB burden nd high-income countries in Figure n FIGURE 7.11 Totl helth expenditures by source of finncing in selected high TB burden nd high-income countries, Percentge South Afric Brzil Chin Russin Federtion Indonesi Indi Nigeri Frnce United Kingdom Germny Netherlnds Cnd US Itly Privte expenditures, other Non-profit institutions serving households (e.g. NGOs) Out-of-pocket expenditures Voluntry pre-pyment Mndtory pre-pyment 1 World Helth Orgniztion nd World Bnk. First Globl Monitoring Report on Trcking Universl Helth Coverge, int/helthinfo/universl_helth_coverge/report/215/en/. GLOBAL TUBERCULOSIS REPORT 215 n 13

115 7.5.4 Beyond finncil risk protection One of the three min trgets in the End TB Strtegy ( ) is tht no TB ptients or their households should fce ctstrophic costs s result of TB disese (Chpter 1). This trget ws specificlly included becuse it is key mrker of finncil risk protection nd progress towrds UHC nd socil protection for TB-f fected households. 1 Ctstrophic cost is broder concept thn ctstrophic helth expenditure, since it includes not only direct expenditures on helth services but lso (1) non-medicl pyments (such s trnsporttion or lodging chrges) tht re directly relted to ccessing TB dignosis nd tretment nd (2) indirect costs such s income losses (for exmple, relted to time lost from work or loss of employment). The proportion of ptients nd their households tht experience ctstrophic costs cn be mesured using periodic surveys. To support such surveys, WHO estblished Tsk Force in 215. The min focus of the Tsk Force s work in 215 hs been to develop generic protocol nd ccompnying questionnires, 2 building on methods used in previous studies of ptient costs. 1 Uplekr M, Weil D, Lonnroth K, Jrmillo E, Lienhrdt C, Dis HM, et l. WHO s new End TB Strtegy. The Lncet. 215;385: See in prticulr Pnel 2 in the supplementry ppendix. 2 Protocol for survey to determine direct nd indirect costs due to TB nd to estimte proportion of TB-f fected households experiencing ctstrophic costs Field testing version, 215. Avilble from the Globl TB Progrmme in WHO upon request. 14 n GLOBAL TUBERCULOSIS REPORT 215

116 CHAPTER 8 Reserch nd development Key fcts nd messges Intensified reserch nd development is one of the three pillrs of the WHO post-215 globl TB strtegy, nd will ply crucil role in ccelerting the reductions in TB incidence nd mortlity required to rech globl TB trgets by 235. Ef forts to develop new TB dignostics, drugs, nd vccines intensified in the pst decde, but considerble progress nd investment is still needed. The dignostic technology lndscpe continues to look promising lthough very few technologies re t dequtely dvnced stges for WHO evlution. Technologies under development include rpid tests to detect TB, drug resistnce, or TB nd drug resistnce combined. Those bsed on moleculr technologies such s nucleic cid mplifiction tests re the most dvnced. A new dignostic pltform clled the GeneXpert Omni is in development. This is intended for point-of-cre testing for TB nd rifmpicin-resistnt TB using existing Xpert MTB/RIF crtridges. This new pltform will be ssessed by WHO for equivlence to the current GeneXpert pltform in 216. A nextgenertion crtridge clled Xpert Ultr is lso in development, nd is expected to replce the Xpert MTB/RIF crtridge. The Xpert Ultr ssy will be ssessed in 216 in two stges, first s replcement for the current Xpert MTB/RIF ssy nd second s replcement for conventionl dignostic culture. In 215, three dignostic tests were reviewed by WHO: Determine TB LAM (liporbinomnnn), referred to s LF-LAM; nd two new generic versions of line probe ssys (LPAs) for first-line drugs. LF-LAM is not recommended for the dignosis of TB (pulmonry nd extrpulmonry), with the exception of people living with HIV who hve low CD4 counts or who re seriously ill. WHO will updte current policy recommendtions for the use of LPAs in erly 216. Two new drugs hve recently been recommended for the tretment of MDR-TB under specific conditions. The first, bedquiline, ws pproved by the US Food nd Drug Administrtion (FDA) in December 212 nd the second, delmnid, ws pproved by the Europen Medicines Agency in November 213. WHO issued interim guidnce on the use of these two drugs in the tretment of MDR-TB in June 213 nd October 214, respectively. Additionlly, there re eight new or repurposed nti-tb drugs in dvnced phses of clinicl development. For the first time in six yers, new nti-tb drug cndidte hs entered Phse I clinicl tril: TBA-354, nitroimidzole tht is prt of the sme clss of drugs s delmnid nd pretomnid. Results from three Phse III trils investigting four-month regimens for the tretment of drug-susceptible TB tht include fluoroquinolones were relesed in 214. These shorter regimens filed to show non-inferiority to the six-month stndrd of cre regimen currently recommended by WHO. Severl new regimens, including new nd/or re-purposed drugs, re now being tested in series of Phse II/III trils for the tretment of drug-susceptible nd/or drug-resistnt TB. Two recent observtionl studies of the ef fectiveness of shorter tretment regimens for ptients with MDR-TB in Niger nd Cmeroon hve shown tht 12-month tretment regimen ws ef fective nd well-tolerted in ptients not previously exposed to second-line drugs. There re 15 vccine cndidtes in clinicl trils. Results of Phse II ef ficcy dt to determine whether BCG nd/or H4:IC31 cn prevent infection, nd M72 cn prevent disese, s well s phse III dt of whether M.vcce cn prevent disese, will shortly be vilble. Mjor shif ts in TB vccine reserch nd development include the introduction of more stringent gting criteri/mechnisms for cndidte entry into nd progress in clinicl trils; vccine discovery tht explores induction of immunity beyond conventionl T cells; nd support of experimentl medicine studies for knowledge genertion nd to better connect dt from niml models nd humn studies. The gol of the End TB strtegy endorsed by the World Helth Assembly (WHA) in My 214 is to end the globl TB epidemic (Chpter 1). Despite mjor progress in TB prevention, dignosis nd tretment since the mid-199s (Chpters 2 7), reching this gol will require mjor technologicl brekthroughs from the reserch nd development pipeline by 225; these would mke possible mjor ccelertion in the rte t which TB incidence declines compred with historic levels. Criticl components include: the vilbility of f fordble short, ef fective nd well-tolerted tretments for ll forms of TB (ltent TB infection, drug-susceptible nd drug-resistnt TB disese); point-of-cre dignostic test with cpcity to identify resistnce to the most importnt nti-tb drugs; nd n effective post-exposure vccine. This is the fif th successive yer in which chpter on reserch nd development is included in the Globl tubercu- GLOBAL TUBERCULOSIS REPORT 215 n 15

117 n FIGURE 8.1 An overview of progress in the development of moleculr TB dignostics, August 215 FOR USE IN REFERENCE -LEVEL LABORATORIES n m2 RelTime MTB ssy, Abbott, USA n TruArry MDR-TB, Akkoni, USA n BioFilmChip MDR-TB, AutoGenomics, USA n MTBC-OCTA, AutoGenomics, USA n BD ProbeTec ET Direct TB ssy, BD, USA n TB drug resistnce rry, Cpitl Bio, Chin n AMTD test, Hologic Genprobe, USA n Cobs TqMn MTB test, Roche, Switzerlnd n Anyplex, Seegene, Kore n Mgicplex MTB, Seegene, Kore n TRC Rpid M.TB, Tosoh Bioscience, Jpn n MeltPro, Zeesn Biotech, Chin FOR USE IN INTERMEDIATE-LEVEL LABORATORIES n FluoroType MTB / FluoroType MTB RNA, Hin Lifesciences, Germny n icubte System, icubte, USA n AdvnSure, LG Life sciences, Republic of Kore n LPA NTM/MTB DR, Nipro, Jpn n veremtb, Veredus Lbortories, Singpore n SPEED-OLIGO, Vircell, Spin n MolecuTech REBA, YD Dignostics, Kore n LATE-PCR, Brndeis University, USA n GeneXpert XDR crtridge, Cepheid, USA n Xpert Ultr, Cepheid, USA n Enigm ML, Enigm Dignostics, UK FOR USE IN PERIPHERAL-LEVEL LABORATORIES n Alere Q, Alere, USA n TB-LAMP, Eiken, Jpn n B-SMART, LbCorp, USA n Genedrive MTB/RIF ID, Epistem, UK n HYDRA, Insilix Inc, USA n TBDx System, KGI, USA n Truelb/Truent MTB, Molbio/bigtec Dignostics, Indi n Svnn, NWGHF, USA n EsyNAT TB Dignostic kit, Ustr Biotechnologies, Chin n EOSCAPE-TB, Wve 8 Biosciences, USA n GenePOC test, GenePOC, Cnd n Xpert Omni, Cepheid, USA This is not n exhustive list of technologies in development. Those listed re the ones documented in publictions by UNITAID nd TAG: UNITAID Tuberculosis Dignostic Technology nd Mrket Lndscpe 3rd edition. Genev: World Helth Orgniztion. Avilble t: unitid.eu/imges/mrketdynmics/publictions/unitaid_tb_dignostics_lndscpe_3rd-edition.pdf Hrrington M. The tuberculosis dignostics pipeline in 215 Pipeline Report: HIV, Heptitis C Virus (HCV) nd Tuberculosis Drugs, Dignostics, Vccines, Preventive Technologies, Reserch Towrd Cure, nd Immune-Bsed nd Gene Therpies in Development. New York, Tretment Action Group, 215. Avilble t: losis report. The sttus of progress in the development of new TB dignostics, drugs nd vccines s of August 215 is summrized, bsed on recent publictions nd communictions with nd contributions from the secretrits of the relevnt Working Groups of the Stop TB Prtnership. 8.1 New dignostics for TB The End TB strtegy trgets set for 235 re to reduce the bsolute number of TB deths by 95% nd to reduce the TB incidence rte by 9%, compred with bseline of 215 (Chpter 1). To chieve these trgets, ntionl TB progrmmes (NTPs) first need to implement strtegies tht fully optimize the use of existing dignostic technologies. Reserch nd development is required so tht new rpid tests tht cn be used t the point of cre, nd tht ccelerte ccess to testing for drug susceptibility for ll bcteriologiclly-confirmed TB cses, become vilble An overview of the dignostics pipeline Although very few technologies re t n dvnced stge of evlution, the dignostic technology lndscpe continues to look promising. An overview of the dignostic pipeline for rpid moleculr tests in August 215 is shown in Figure 8.1. The list of technologies is not necessrily complete or exhustive, but does reflect technologies tht hve been documented in recent reports published by UNITAID 1 nd Tretment Action Group (TAG). 2 Tools using moleculr technologies such s nucleic cid mplifiction tests (NAATs) re the most dvnced. Technologies under development include tests to detect TB, drug resistnce, or TB nd drug resistnce combined. These include microrry-bsed multiplexing dignostic pltforms for the simultneous detection of lrge number of resistnce-conferring muttions. Unfortuntely, most tests under development re intended for use t the reference or intermedite lbortory level only, requiring dedicted infrstructure nd experienced stf f. There re t lest three technologies tht re commercilly vilble (Epistem Genedrive, Epistem, UK; Molbio Truelb, Molbio, Indi nd EASYNAT, Ustr, Chin) tht re intended for use t the microscopy level. However, to dte no multicentre evlution nd/or demonstrtion studies in different epidemiologicl setting hve been conducted. These re necessry to generte the performnce dt required by WHO to ssess nd produce recommendtions on these technologies (Figure 8.2). Evlution studies re expensive, nd therefore dditionl funding is urgently needed, both to expedite the progress of promising new technologies through the pipeline nd to conduct the necessry evlution studies. Priority should be given to tests tht re suitble for use t the lower levels of the helth system. The Foundtion for Innovtive New Dignostics (FIND) remins the led orgniztion conducting field evlutions of dif ferent 1 UNITAID Tuberculosis Dignostic Technology nd Mrket Lndscpe 3rd edition. Genev: World Helth Orgniztion. Avilble t: UNITAID_TB_Dignostics_Lndscpe_3rd-edition.pdf 2 Hrrington M. The tuberculosis dignostics pipeline in 215 Pipeline Report: HIV, Heptitis C Virus (HCV) nd Tuberculosis Drugs, Dignostics, Vccines, Preventive Technologies, Reserch Towrd Cure, nd Immune- Bsed nd Gene Therpies in Development. New York, Tretment Action Group, 215. Avilble t: g575521/f/2157/215%2pipeline%2report%2full.pdf 16 n GLOBAL TUBERCULOSIS REPORT 215

118 n FIGURE 8.2 The phses of TB dignostics development nd ssessment for WHO recommendtion using the GRADE (Grding of Recommendtions Assessment, Development nd Evlution) process PHASE 2 Evlution nd demonstrtion PHASE 3 WHO ssessment of the evidence using GRADE tbles PHASE 4 Phsed uptke nd collection of evidence for scle-up PHASE 1 Reserch nd development PHASE 5 Scle-up nd policy refinement technologies, but the enggement of other stkeholders nd dequte funding re urgently needed. A new dignostic pltform clled the GeneXpert Omni is in development. This is intended for point-of-cre testing for TB nd rifmpicin-resistnt TB using existing Xpert MTB/ RIF crtridges. The device is expected to be smller, lighter, nd less expensive thn other currently vilble pltforms for point-of-cre nucleic cid detection. The pltform will come with built-in four-hour bttery; n uxiliry bttery tht provides n dditionl 12 hours of run time is lso vilble. In 216, this new pltform will be ssessed by WHO for non-inferiority to the current GeneXpert pltform. Mjor gps still remin in the dignostic pipeline, nd slow progress in the evlution of technologies in the lte stges of development is the mjor brrier to these tools reching the mrket. There re insuf ficient tests under development for the dignosis of TB in children, ssessment of susceptibility to drugs tht my be prt of new tretment regimens, prediction of progression from ltent TB infection (LTBI) to ctive TB disese nd lterntives to TB culture for tretment monitoring. The development nd implementtion of such tests s well s incresing ccess to technologies lredy endorsed by WHO will be essentil to meet trgets outlined in the End TB Strtegy TB dignostic tests reviewed by WHO in 215 In 215, three dignostic tests were reviewed by WHO: Determine TB LAM (liporbinomnnn), referred to s LF-LAM, developed by Alere, USA; nd two new generic versions of line probe ssys (LPAs), one developed by the Nipro Corportion, Jpn nd the other by Hin Lifesciences. LF-LAM (Alere, USA) LF-LAM is lterl flow test tht hs been evluted in severl studies for the detection of ctive TB in people living with HIV who re severely immunocompromised. Evidence from systemtic review of the performnce chrcteristics of the ssy ws considered by Guideline Development Group convened by WHO in 215. This group recommended tht LF-LAM should not be used for the dignosis of TB (pulmonry nd extrpulmonry), with the exception of people living with HIV who hve low CD4 counts or who re seriously ill. More detils on these recommendtions re provided in Chpter 5. New generic versions of LPAs (Nipro Corportion, MTBDRplus version 2) For new versions of technologies tht WHO hs lredy recommended, WHO requires hed-to-hed comprison with the existing technology. If non-inferiority (tht is, their equivlence) in performnce cn be demonstrted, then WHO will recommend the new version. In 28, WHO endorsed the use of LPAs for the rpid detection of rifmpicin resistnce, beginning wht might be considered to be the moleculr revolution in detection of drug-resistnt TB. The evidence nd subsequent recommendtions for the utility of LPAs included n ssessment of the performnce of the GenoType MTBDRplus ssy, Hin Lifescience (Hin Version 1 ssy). This ssy incorportes rpob probes for rifmpicin resistnce detection s well s ktg probes nd inha probes for the determintion of isonizid resistnce. Hin Lifesciences hve subsequently developed n updted version of their MTBDRplus line probe ssy (Hin Version 2 ssy). GLOBAL TUBERCULOSIS REPORT 215 n 17

119 Nipro Corportion, Jpn hs developed n LPA tht is similr to tht of Hin Lifesciences, which ws registered in Jpn in 212 (Nipro ssy). This ssy llows for the detection of rifmpicin nd isonizid conferring muttions, the identifiction of M. tuberculosis complex nd the identifiction of some common nontuberculous mycobcteri including M. vium, M. intrcellulre nd M. knssii. In 214 nd 215, FIND coordinted multi-center, blinded cross-sectionl study of the dignostic ccurcy of these two tests, to compre their performnce ginst tht of the Hin Version 1 ssy. A composite reference stndrd including phenotypic drug susceptibility testing (DST) nd DNA sequencing ws used. The study ws divided into two distinct phses. Phse 1 ws designed to evlute the performnce of the newer ssys on wide rnge of clinicl isoltes nd Phse 2 to evlute their performnce on sputum specimens from ptients with pulmonry TB. The study demonstrted non-inferiority of the newer LPA ssy versions (Hin Version 2 nd Nipro) in comprison with the Hin Version 1 ssy; these ssys showed comprble performnce for the detection of M. tuberculosis nd rifmpicin resistnce conferring muttions in cid-fst bcilli smer-positive smples nd isoltes of M. tuberculosis. WHO will updte current policy recommendtions for the use of LPAs nd review new evidence bout the clinicl utility of the Hin Lifescience GenoType MTBDRsl ssy nd will ssess the role of sequencing in detecting resistnce to second-line drugs in Technologies scheduled for field evlution studies in 216 There re two technologies scheduled for field evlution in 216. Xpert Ultr, Cepheid A new version of the Xpert MTB/RIF ssy, clled Xpert Ultr, is in development. The im is to improve the sensitivity nd specificity of the current ssy in detection of TB nd rifmpicin resistnce, respectively. In 216, FIND will initite two-step evlution process. The first step is rpid noninferiority study tht will compre the new Xpert Ultr ssy with the current Xpert MTB/RIF ssy. If non-inferiority is demonstrted, the Xpert Ultr ssy will be recommended s replcement for the current Xpert MTB/RIF ssy. The second step will be multi-country evlution studies. It is nticipted tht these studies will demonstrte tht the Xpert Ultr ssy hs superior performnce (for exmple, bout 95% sensitivity in detecting smer-negtive, culturepositive TB from single sputum specimen). The Xpert Ultr ssy will be developed for use on the Omni pltform (described bove). Alere Q, Alere The Alere q TB dignostic system is being developed with funding support from the Bill & Melind Gtes Foundtion. It is rpid nd sensitive test for detection of TB, followed by n immedite reflex test for full nlysis of drug resistnce for people found to hve TB. A sputum smple is collected in cup tht is then screwed onto the test crtridge, which contins ll regents. The inoculted crtridge is subsequently plced into bttery-powered stnd-lone device tht llows for smple processing, DNA mplifiction, detection nd result interprettion nd reporting in pproximtely 2 minutes. This technology is mjor step towrds chieving universl DST for ll TB cses. Multi-centre evlution studies re plnned for Tests tht predict progression from ltent to ctive TB Most people with LTBI hve no signs nd symptoms of TB disese. People with LTBI re not infectious, but they re t risk for developing ctive disese nd becoming infectious. On verge, 5 15% of those infected will develop ctive TB during their lifetime, typiclly within the first 2 5 yers f ter the initil infection. Current tests for LTBI (i.e. interferon gmm relese ssys, IGRAs; nd the tuberculin skin test, TST) re immunity-bsed nd hve very limited bility to identify which individuls re likely to progress to ctive TB. They lso hve limited sensitivity in people with HIV infection, nd re not ble to dif ferentite between recent nd remote infection or to distinguish if person hs been re-infected if re-exposed. In My 215, WHO hosted meeting on behlf of FIND nd the New Dignostics Working Group of the Stop TB Prtnership to review set of miniml nd optiml performnce chrcteristics nd develop trget product profile (TPP) for biomrker-bsed test to predict the risk of progression to ctive TB from LTBI nd rule out ctive TB. The meeting ws ttended by representtives from the dignostic development industry, universities, clinicins nd technicl prtners. Following the meeting, the process to define the TPP for test for progression of LTBI hs continued longside the development of stndrdized study protocols tht could be used to evlute the performnce of such tests. 8.2 New drugs nd drug regimens to tret TB Much progress hs been mde during the lst ten yers in the tretment of TB. The body of knowledge bout the use of vrious drugs in combintion regimens, s well their potentil interction with ARVs nd the optimum timing of ART in the tretment of HIV-positive TB ptients, hs grown substntilly. However, TB tretment remins centred on the stndrd 6 month regimen of isonizid, rifmpicin, pyrzinmide nd ethmbutol. Ensuring dherence to tretment remins chllenge, nd drug-resistnt TB remins mjor thret to globl TB prevention, dignosis nd tretment (Chpter 4). This section provides n overview of the ltest sttus of the development of new TB drugs nd new TB tretment regimens. 18 n GLOBAL TUBERCULOSIS REPORT 215

120 n FIGURE 8.3 The development pipeline for new TB drugs, August 215 Discovery Preclinicl development Clinicl development Led optimiztion Preclinicl development Good Lbortory Prctice toxicity Phse I Phse II Phse III Cyclopeptides Dirylquinolines DprE Inhibitors InhA Inhibitor, Indzoles LeuRS Inhibitors, Ures Mcrolides, Azindoles Mycobcteril Gyrse Inhibitors Pyrzinmide Anlogs Ruthenium(II) Complexes Spectinmides SPR-113 Trnslocse-1 Inhibitors TBI-166 CPZEN-45 SQ69 SQ641 DC-159 PBTZ169 Q23 TBA-354 Sutezolid (PNU- 148) SQ19 Rifpentine for DS-TB AZD5847 Bedquiline- Pretomnid- Pyrzinmide Regimen Bedquiline (TMC- 27) with OBR b for MDR-TB Delmnid (OPC ) with OBR b for MDR-TB Rifpentine for LTBI Pretomnid- Moxifloxcin- Pyrzinmide Regimen Chemicl clsses: fluoroquinolone, rifmycin, oxzolidinone, nitroimidzole, dirylquinoline, benzothizinone Detils for projects listed cn be found t nd ongoing projects without led compound series identified cn be viewed t b OBR = Optimized Bckground Regimen Source: Working Group on New TB Drugs, The pipeline of new nd re-purposed nti-tb drugs The sttus of the pipeline for new nd repurposed nti-tb drugs in August 215 is shown in Figure 8.3. There re eight drugs in Phse I, Phse II or Phse III trils for the tretment of drug-susceptible, multidrug-resistnt TB (MDR-TB) or LTBI. Two of these compounds (AZD5847 nd Sutezolid) do not pper to hve progressed in the lst two yers. However, for the first time in six yers, new nti-tb drug cndidte hs entered Phse I clinicl tril: TBA-354, nitroimidzole tht is prt of the sme clss of drugs s delmnid nd pretomnid (formerly PA-824). 1 In ddition, more diversified fundmentl reserch is being conducted to better understnd the diversity of the metbolic stges of M. tuberculosis nd ssocited host responses, nd to identify novel trgets ginst which therpeutic chemicls cn be directed. This is importnt to ensure tht drugs re ef fective throughout the vrious stges of TB from cute disese through tretment of chronic bcteril crrige to cure. Rifpentine for drug-susceptible TB Investigtion of the potentil ef fectiveness of rifpentine in the tretment of drug-susceptible TB, is continuing bsed on the results of the TB Tril Consortium (TBTC) Study 29 tht showed comprble ef ficcy of dily rifpentine 1 CliniclTrils.gov [Internet]. Bethesd (MD): Ntionl Librry of Medicine (U.S.). 2. Identifier NCT , A phse 1 study to evlute the sfety, tolerbility, nd phrmcokinetics of TBA-354 in helthy dult subjects; 214 November 7. show/nct (1 mg/kg) nd rifmpicin (1 mg/kg) when provided long side stndrd doses of isonizid, ethmbutol nd pyrzinmide. The outcome of interest is culture conversion t two months in smer-positive pulmonry TB ptients. 2 A further study (Study 29X), imed t investigting the ef fect of vrious dosges of rifpentine (1, 15 or 2 mg/kg, given seven dys week with food supplements), showed tht the substitution of high-dose dily rifpentine for rifmpicin improved the ntimicrobil ctivity of combintion chemotherpy during the intensive phse of tretment, nd tht this ctivity ws driven by rifpentine exposure. 3 The observed sfety nd tolerbility combined with the high levels of ntimicrobil ctivity observed in the groups tht received higher doses of rifpentine provide support for the evlution of high-dose dily rifpentine-contining regimens of less thn six months durtion in Phse III clinicl trils. Rifmpicin Assessment of whether higher doses of rifmpicin could reduce tretment durtion for drug-susceptible TB hs continued. Results from the PnACEA MAMS-TB-1 tril presented t the Conference on Retroviruses nd Opportunistic Infections (CROI) in Mrch 215 showed tht dily dosing with 35 mg/kg of rifmpin (in ddition to stndrd doses of isonizid, ethmbutol, nd pyrzinmide) reduced the time 2 Dormn S et l. Substitution of Rifpentine for Rifmpin During Intensive Phse Tretment of Pulmonry Tuberculosis: Study 29 of the Tuberculosis Trils Consortium. J Infect Dis. 212, 26 (7): Dormn S et l. Dily Rifpentine for Tretment of Pulmonry Tuberculosis: A Rndomized, Dose-Rnging Tril. Am J Respir Crit Cre Med 215, 191; GLOBAL TUBERCULOSIS REPORT 215 n 19

121 to stble culture conversion when mesured over 12 weeks on liquid medi, but not on solid medi, compred to the stndrd six month regimen. 1 In the sme tril, second rm in which 2 mg/kg of rifmpin + moxifloxcin ws provided showed non-significnt improvement in the time to culture conversion on liquid medi over 12 weeks, but no improvement when mesured using solid medi. Both rms ppered sfe nd well tolerted, but slightly higher percentge of ptients (14% versus 1%) experienced grde 3 dverse events compred with the control rm. There were potentilly higher rtes of heptic dverse events tht resulted in chnge of tretment in the 35 mg/kg rifmpin rm. Finl nlysis of results is underwy. Further reserch bout the sfety nd ef ficcy of higher dosges of rifmpicin, with or without moxifloxcin, nd its cpcity to shorten tretment, is needed. Fluoroquinolones The results from three Phse III trils of four-month combintion regimens for the tretment of drug-susceptible TB, ll of which included fluoroquinolone, were published in lte 214. These were: (i) the OFLOTUB tril, in which gtifloxcin ws substituted for ethmbutol; 2 (ii) the ReMOX tril, in which moxifloxcin ws substituted for either ethmbutol or isonizid; 3 nd (iii) the Rifquin tril, in which moxifloxcin ws substituted for isonizid in the intensive phse of tretment nd rifpentine ws used in the continution phse of tretment. 4 Disppointingly, ll of these trils showed tht the shortened regimen cnnot be recommended for the tretment of uncomplicted smer-positive pulmonry TB. Moreover, the inclusion of third-genertion fluoroquinolone s substitute for either ethmbutol or isonizid ws ssocited with higher risk of relpse compred with the stndrd regimen of six months. Bedquiline In December 212, bedquiline ws pproved by the US Food nd Drug Administrtion (FDA) for tretment of MDR-TB s prt of combintion therpy for dults with pulmonry TB when other lterntives re not vilble. The drug is being introduced in severl countries for the tretment of severe forms of MDR-TB (Chpter 4), following interim guidnce issued by WHO in Boeree M, Hoelscher M. High-dose rifmpin, SQ19 nd moxifloxcin for treting TB: the PnACEA MAMS-TB tril. Pper presented t: 22nd Conference on Retroviruses nd Opportunistic Infections; 215 Februry 23 26; Settle, WA. 2 Merle CS et l. A Four-Month Gtifloxcin-Contining Regimen for Treting Tuberculosis. N Engl J Med 214;371: Gillespie SH et l. Four-Month Moxifloxcin-Bsed Regimens for Drug-Sensitive Tuberculosis. N Engl J Med 214;371: Jindni A et l. High-Dose Rifpentine with Moxifloxcin for Pulmonry Tuberculosis. N Engl J Med 214;371: The use of bedquiline in the tretment of multidrug-resistnt tuberculosis: Interim policy guidnce. Genev: World Helth Orgniztion; 213 (WHO/ HTM/TB/213.6). Avilble t: bitstrem/1665/84879/1/ _eng.pdf The sfety nd ef ficcy of bedquiline in combintion with short MDR-TB regimens of six nd nine months durtion is currently being investigted s prt of the Phse III STREAM tril. These shorter regimens re being compred with the current stndrd of cre for MDR-TB recommended by WHO. Delmnid In November 213, conditionl mrketing uthoriztion for delmnid ws grnted by the Committee for Medicinl Products for Humn Use (CHMP) of the Europen Medicines Agency (EMA). Delmnid ws uthorized for use s prt of combintion regimen for pulmonry MDR-TB in dult ptients when n effective tretment regimen cnnot otherwise be composed for resons of resistnce or tolerbility. Interim guidnce on the use of delmnid ws issued by WHO in October Delmnid is currently being tested in Phse III clinicl tril, s n ddition to n optimized bckground regimen (OBR) for the tretment of MDR-TB. The tril is compring six months of tretment with delmnid plus the OBR with plcebo plus OBR. It is nticipted tht the tril will be completed in 216. Two other trils re evluting the use of delmnid in the tretment of children with MDR-TB. The first tril is 1-dy open lbel phrmcokinetic (PK) study of delmnid plus n OBR. Ptients who successfully complete this tril my then be enrolled in second, open-lbel study (Tril ) to ssess the sfety, tolerbility, PK, nd ef ficcy of delmnid plus n OBR over six-month tretment period. These trils re scheduled for completion in 217. Pretomnid Pretomnid is nitroimidzole developed by the Globl Allince for TB drug development. It is being tested s prt of three potentil combintion regimens for the tretment of both drug-susceptible nd drug-resistnt TB (further detils re provided in section 8.2.2). SQ19 Preliminry results from the PnACEA MAMS-TB-1 tril presented t CROI in Mrch 215 showed tht there ws no benefit of including SQ19 insted of ethmbutol in stndrd therpy for drug-susceptible TB, in terms of time to culture conversion mesured over 12 weeks Trils of new regimens for the tretment of drug-susceptible nd/or drug-resistnt TB Besides individul compounds, new combintions of drugs re being tested in severl Phse II or Phse III trils. The NC-2 Phse IIb tril, conducted by the Globl Alli- 6 The use of delmnid in the tretment of multidrug-resistnt tuberculosis: Interim policy guidnce. Genev: World Helth Orgniztion; 214(WHO/ HTM/TB/214.23). Avilble t: bitstrem/1665/137334/1/who_htm_tb_214.23_eng.pdf 11 n GLOBAL TUBERCULOSIS REPORT 215

122 nce for TB Drug Development (referred to in this text s TB Allince ) in South Afric nd the United Republic of Tnzni, investigted the ef ficcy, sfety nd tolerbility of the combintion of moxifloxcin + pretomnid + pyrzinmide (MPZ) f ter eight weeks of tretment in 27 dult ptients with newly dignosed drug-susceptible or smer-positive pulmonry MDR-TB. 1 Two doses of pretomnid were tested (1 mg nd 2 mg); the 26 MDR-TB ptients received only the higher dose. The primry endpoint ws the rte of chnge in colony forming units (CFUs) from sputum on solid culture over eight weeks. Results of this tril showed tht the MPZ regimen hd ctive bctericidl ctivity ginst both drug-susceptible nd MDR-TB over two months nd tht this bctericidl ctivity ws significntly greter thn tht of isonizid, rifmpicin, pyrzinmide nd ethmbutol (HRZE) therpy in ptients with drug-susceptible TB when the MP(2mg)Z regimen ws used. The frequency of dverse events ws similr to stndrd tretment in ll groups. The combintion of moxifloxcin, pretomnid, nd pyrzinmide thus ppered to be sfe, well-tolerted, nd showed superior bctericidl ctivity for tretment of drug-susceptible TB during the first eight weeks of tretment. On the bsis of the results from the Phse IIb tril, Phse III tril ws lunched in Februry 215. Known s the STAND tril, it will be implemented in 16 countries nd is prtilly rndomized clinicl tril. Tretments re ssigned to five prllel groups: P(1mg)-M-Z for 4 months for 35 ptients with drug-susceptible TB; P(2mg)-M-Z for four months for 35 ptients with drug-susceptible TB; P(2mg)-M-Z for six months for 35 ptients with drug-susceptible TB; HRZE for six months for 35 ptients with drug-susceptible TB; nd P(2mg)-M-Z for six months for 35 ptients with drug-resistnt TB. The NC-3 tril tested the 14 dy erly bctericidl ctivity (EBA) of vrious combintions of clofzimine, bedquiline, pretomnid nd pyrzinmide in ptients with drug-susceptible TB. 2 Following the results from this tril, Phse IIb tril, NC-5, hs been lunched. This is testing ll-orl combintion regimens tht include bedquiline (two dif ferent doses), pretomnid, nd pyrzinmide for ptients with drug-susceptible TB, nd these drugs in combintion with moxifloxcin for ptients with MDR-TB. The tril is mesuring the decline in CFUs over eight weeks, nd the time to positivity bsed on results from pooled sputum smpling every 16 hours. This study strted in October 214, nd results re expected in mid-216. The NiX-TB study, implemented by the TB Allince in South Afric, strted in April 215. It is investigting the sfe- 1 Dwson R et l. Ef ficiency nd sfety of the combintion of moxifloxcin, pretomnid (PA-824), nd pyrzinmide during the first 8 weeks of ntituberculosis tretment: phse 2b, open-lbel, prtly rndomised tril in ptients with drug-susceptible or drug-resistnt pulmonry tuberculosis. Lncet Everitt D et l. 14 Dy EBA study of clofzimine lone nd in combintion. 44th Union World Conference on Lung Helth, Lte-breker session, Pris, 213 ty nd ef ficcy of six month combintion of bedquiline, pretomnid nd linezolid (ll compounds tht re new or to which there is little pre-existing resistnce due to limited use) for TB ptients with XDR-TB. The primry endpoint is the incidence of bcteriologic filure or relpse or clinicl filure, with follow-up for 24 months f ter the end of tretment. Alongside the Nix-TB study, the TB Allince is undertking study of the response to dif ferent doses of linezolid in ptients with drug-susceptible TB over two weeks. This study will inform dosing djustments tht my need to be mde for linezolid in the NiX-TB tril or other regimens tht include linezolid. There re two clinicl trils scheduled to strt round the end of 215. The first is clled the endtb tril. It is Phse III tril funded by UNITAID nd implemented by Prtners in Helth nd Médecins Sns Frontières. It will evlute five new ll-orl short regimens for the tretment of MDR- TB. These regimens contin one new nti-tb drug (either bedquiline or delmnid), moxifloxcin or levofloxcin, nd pyrzinmide plus linezolid or clofzimine or both, in vrious combintions. They will be compred with the current WHO stndrd of cre. Potentil sites include Georgi, Kzkhstn, Kyrgyzstn, Lesotho nd Peru. The second is the TB-PRACTECAL tril. This is rndomized, controlled, openlbel, Phse II/III dptive tril tht will evlute the sfety nd efficcy of six-month regimens tht contin bedquiline, pretomnid nd linezolid with or without moxifloxcin or clofzimine for the tretment of dults with MDR-TB or XDR-TB. The tril is funded by Médecins Sns Frontières nd will be conducted in Uzbekistn nd Swzilnd. In ddition to trils, two recent observtionl studies investigting the ef fectiveness of shorter tretment regimens for ptients with MDR-TB in Niger 3 nd Cmeroon 4 hve shown tht 12-month tretment regimen ws effective nd well-tolerted in ptients not previously exposed to second-line drugs Tretment of ltent TB infection (LTBI) Since the publiction of WHO guidelines on the tretment of LTBI in 215, 5 new evidence bout the benefits of isonizid preventive therpy (IPT) when provided in ddition to ntiretrovirl therpy (ART) to HIV-positive people with very high CD4 counts hs become vilble from the TEMPRANO ANRS tril. 6 This tril included 256 ptients in Côte 3 Piubello A, Hroun SH, Souleymne MB et l. High Cure Rte with Stndrdised Short-Course Multidrug-Resistnt Tuberculosis Tretment in Niger: No Relpses. Int J Tuberc Lung Dis 215;18: Kubn C, Noeske J, Rieder HL et l. High Ef fectiveness of 12-Month Regimen for MDR-TB Ptients in Cmeroon. The Interntionl Journl of Tuberculosis nd Lung Disese. Int J Tuberc Lung Dis 215;19: World Helth Orgniztion. Guidelines on the mngement of ltent tuberculosis infection. Genev: World Helth Orgniztion; 215. Avilble t: en/ 6 The TEMPRANO ANRS Study Group. A Tril of Erly Antiretrovirls nd Isonizid Preventive Therpy in Afric. N Engl J Med 215; 373: GLOBAL TUBERCULOSIS REPORT 215 n 111

123 n FIGURE 8.4 The development pipeline for new TB vccines, August 215 Phse I Phse II Phse IIb Phse III Ad5 Ag85A McMster, CnSino VPM 12 (rbcg) Mx Plnck, VPM, TBVI, SII M72 + AS1E b GSK, Aers M. Vcce c Anhui Zhifei Longcom ID93 + GLA-SE IDRI, Aers H1 + IC31 SSI, TBVI, EDCTP DAR-91 Drtmouth, Aers RUTI Archivel Frm, S.L TB / FLU-4L RIBSP H4: IC31 d SSI, Snofi-Psteur, Aers Crucell Ad35 / MVA85A* Crucell, Oxford, Aers ChAdOx1.85A / MVA85A* Birminghm, Oxford MVA85A / MVA85A (ID, Aerosol)* Oxford H56: IC31 SSI, Aers MTBVAC (Attenuted M.Tb) TBVI, Zrgoz, Biofbri n Virl Vector n Protein / Adjuvnt n Mycobcteril Whole Cell or Extrct * Experimentl medicine tools / pltforms Initil sfety nd ef ficcy to begin 215 b Ef ficcy dt likely vilble in 218 c Endpoint dt should be vilble in 216 d Prevention of infection dt likely vilble in 217 Sources: Aers, Working Group on New TB Vccines, d Ivoire nd found tht IPT nd ART provided together hd higher ef ficcy in preventing TB disese thn ART lone. The study lso found lower rtes of severe illness when ART ws strted immeditely longside 6 months of IPT, compred with deferred ART nd no IPT. This ws true overll nd mong ptients with CD4 counts of 5 cells/mm 3. Study uthors lso highlighted tht isonizid cn be prescribed sfely when given erly in the course of HIV disese. 8.3 New vccines to prevent TB The slow decline in TB incidence globlly (Chpter 2) nd the persistent thret of MDR-TB both highlight the criticl need for new ef fective TB vccines. It is estimted tht t lest US$ 8 billion is required ech yer for TB dignosis nd tretment using currently vilble interventions (Chpter 7). A recent modelling study showed tht developing t lest one new TB vccine over the next 1 15 yers would cost bout US$.8 1 billion, pproximtely 1% of dignosis nd tretment costs, nd tht n dolescent nd dult vccine with 6% ef ficcy delivered to 2% of the popultion-trisk could vert s mny s 3 5 million new cses of TB by Recent modelling lso indictes tht trgeting dolescents will prevent morbidity nd mortlity in infnts nd young children, nd is more ef fective strtegy to protect 1 Aers, TB Vccine Reserch nd Development: A Business Cse for Investment. Rockville: Aers; 214. Avilble t: them from TB thn direct vccintion of infnts with similr vccine. 2 The potentil for n dult/dolescent vccine to hve meningful impct on the globl TB epidemic, compred with the limited impct of n infnt vccine, hs shif ted the focus of TB vccine development. The new prdigm emphsises the development of diverse pipeline of new TB vccine cndidtes tht trget the prevention of ctive TB in these older ge groups. Scientific dvnces hve lso enbled the pursuit of more sophisticted pproches to vccine design. The globl pipeline of TB vccine cndidtes in clinicl trils is more robust thn t ny previous period in history, now including recombinnt BCGs, ttenuted M. tuberculosis strins, recombinnt virl-vectored pltforms, protein/djuvnt combintions, nd mycobcteril extrcts. The sttus of the pipeline for new vccines in August 215 is shown in Figure 8.4. These vccines im either to prevent infection (pre-exposure) or to prevent primry progression to disese or rectivtion of ltent TB (post-exposure). Further detils re provided below. 2 White, R. Indirect ef fects in infnts on the force of TB disese from vccinting dolescents nd dults. London: TB Modelling Group, TB Centre, Centre for the Mthemticl Modelling of Infectious Diseses; n GLOBAL TUBERCULOSIS REPORT 215

124 8.3.1 Phse II nd Phse III clinicl trils There re currently eight vccines in Phse II or Phse III trils. M72/AS1E (mde by GlxoSmithKline (GSK)) is recombinnt fusion protein of the M. tuberculosis ntigens 32A nd 39A with the AS1E djuvnt. A lrge rndomized plcebo-controlled Phse IIb tril (NCT , conducted by GSK nd Aers) is enrolling pulmonry TB-negtive, IGRApositive, HIV-negtive dults in Keny, South Afric nd Zmbi. The im is to enroll 356 dults; by July 215, 296 prticipnts hd been enrolled. The primry endpoint will be the protective ef ficcy of two doses of M72/AS1E ginst pulmonry TB disese. Secondry endpoints include sfety nd immunogenicity. Three vccines re protein subunits with djuvnts, initilly developed by the Sttens Serum Institute (SSI) in Copenhgen, Denmrk. These re: "" H1:IC31 is n djuvnted subunit vccine combining the M. tuberculosis ntigens Ag85B nd ESAT-6 with Vlnev s IC31 djuvnt. The H1:IC31 vccine ws the first TB vccine to commence clinicl development by SSI, nd Aers subsequently joined this ef fort. The H1:IC31 vccine hs been evluted in three Phse I trils, which showed the vccine to be sfe nd immunogenic in HIV-negtive dults who were either M. tuberculosis nïve, BCG vccinted or ltently infected, in low- nd high TB burden settings. A Phse II double-blind nd plcebo controlled tril in HIVpositive individuls with or without LTBI confirmed tht the vccine ws sfe nd immunogenic. 1 Recently, lrge Phse II tril investigting the influence of dose, schedule nd LTBI sttus on the immunogenicity of H1:IC31 in 24 dolescents in South Afric ws finlized; H1:IC31 ws the first TB vccine to be tested in lrge tril in this importnt trget popultion. A pper in which results will be published is in preprtion. In prllel, the H1:IC31 subunit vccine construct hs been improved with the ddition of third ntigen, Rv266c, becoming H56:IC31. Clinicl dt on H1:IC31 will support the further development of H56:IC31. No further clinicl trils with H1:IC31 re plnned. "" H4:IC31 is being developed s booster vccine to BCG with Snofi Psteur. The vccine cndidte contins fusion protein of Ag85B nd TB1.4 formulted with IC31 djuvnt. H4:IC31 is currently being evluted in Phse II studies in Africn infnts with Snofi nd SSI (nd lso with the Interntionl Mternl Peditric Adolescent AIDS Clinicl Trils Group (IMPAACT) network nd the HIV Vccine Trils Network (HVTN) in conjunction with NIAID). In ddition, the H4:IC31 cndidte is being ssessed in 1 Reither K, Ktsoulis L, Bettie T et l. Sfety nd Immunogenicity of H1/ IC31, n Adjuvnted TB Subunit Vccine, in HIV-Infected Adults with CD4+ Lymphocyte Counts Greter thn 35 cells/mm 3 : A Phse II, Multi-Centre, Double-Blind, Rndomized, Plcebo-Controlled Tril. PLoS ONE. 214;9(12):e Phse II proof-of-concept study for its bility to prevent de novo infection with M. tuberculosis mong IGRA-negtive, HIV-uninfected South Africn dolescents t high risk of cquiring M. tuberculosis infection. An intensive immunogenicity study of H4:IC31 in South Africn dolescents is underwy. "" H56:IC31. This is n djuvnted subunit vccine tht combines three M. tuberculosis ntigens (Ag85B, ESAT-6, nd Rv266c) with Vlnev s IC31 djuvnt. It is being developed by SSI nd Aers. A Phse I study to evlute the sfety nd immunogenicity profile of H56:IC31 in HIVnegtive dults with nd without LTBI nd no history or evidence of TB disese hs been completed. Two Phse I studies re currently ongoing to determine the sfety nd immunogenicity profile of H56:IC31 in HIV-negtive, BCGvccinted dults with nd without LTBI nd in ptients who hve recently been treted for pulmonry TB disese, respectively. A study to determine the ef ficcy of H56:IC31 in preventing TB infection in LTBI negtive dolescents is plnned for 216. VPM 12, originlly developed t the Mx Plnck Institute of Infection Biology with further development by Vkzine Projekt Mngement, the Tuberculosis Vccine Inititive (TBVI), nd Serum Institute of Indi, is live recombinnt vccine. It hs been derived from the Prgue strin of BCG into which the listerolysin gene from Listeri monocytogenes hs been cloned, nd the urese gene deleted, to potentilly improve immunogenicity. A Phse II tril of this vccine hs been completed in South Afric. The Phse II tril (in plnning) will ssess the sfety nd immunogenicity of the vccine in HIV exposed nd unexposed newborns. RUTI is non-live nd polyntigenic vccine bsed on frgmented nd detoxified M. tuberculosis bcteri. The product is liposome suspension of the Drug Substnce with chrge excipient. RUTI is being developed by Archivel Frm s n immunotherpeutic vccine. A Phse II tril in South Afric ws completed recently nd other clinicl trils re in the plnning stges. MTBVAC is being developed by the University of Zrgos, Institut Psteur, BIOFABRI nd TBVI. It is live M. tuberculosis strin ttenuted vi deletions of the phop nd fdd26 genes. It is the first live ttenuted M. tuberculosis vccine to enter Phse I tril, which ws recently completed. The next tril will be Phse I/II tril mong dults in South Afric. The vccine is being developed both s BCG replcement vccine nd s potentil boost vccine in dolescents nd dults. M. Vcce is specified lyste developed by the phrmceuticl compny Anhui Zhifei Longcom Biologic Phrmcy Co., Ltd. nd licensed by the Chin Food nd Drug Administrtion s n immunotherpeutic gent to help shorten TB tretment for ptients with drug-susceptible TB. It is in Phse III tril to ssess its ef ficcy nd sfety in preventing TB disese in people with LTBI. The tril is being conducted in collbortion with the Gungxi Center for Disese Con- GLOBAL TUBERCULOSIS REPORT 215 n 113

125 trol nd Prevention in Chin. It is the lrgest TB vccine tril undertken in the lst decde, including 1 people ged with PPD>15mm. The tril is scheduled to be completed by April 216. Of note, MVA85A, the ttenuted vccini virus-vectored vccine cndidte expressing Ag85A of M. tuberculosis designed t Oxford University s booster vccine for BCG vccinted infnts, hs now completed Phse II sfety nd immunogenicity study. 1 The study ws conducted in 65 BCG-vccinted, HIV-positive prticipnts in Senegl nd South Afric. As in the infnt study 2, the vccine ws well tolerted nd immunogenic, but no efficcy ginst M. tuberculosis infection or disese ws demonstrted (lthough the study ws not powered to detect n ef fect ginst disese). Current nd future clinicl pproches focus on evluting MVA85A delivered by erosol, lone or in prime-boost combintion with second virlly vectored vccine, ChAdOx1.85A (see below) Phse I clinicl trils There re seven vccines in Phse I clinicl trils. ID93 + GLA-SE, developed by the Infectious Disese Reserch Institute (IDRI) in collbortion with Aers, comprises three M. tuberculosis immunodominnt ntigens (Rv268, Rv3619 nd Rv362), one M. tuberculosis ltencyssocited ntigen (Rv1813), nd the djuvnt GLA-SE. A Phse I tril in 6 dults in the United Sttes to ssess sfety nd immunogenicity ws recently completed. The vccine ws found to hve n cceptble sfety profile, nd T cell responses were seen t ll of the dose levels tht were studied. A further Phse I tril in South Afric is being conducted to describe the sfety nd immunogenicity profile of ID93 + GLA-SE in BCG-vccinted, QuntiFERON TB-Gold negtive nd positive helthy dults. A Phse II tril in South Afric, with the support of the Wellcome Trust, is evluting sfety nd immunogenicity in ptients tht hve recently completing tretment for pulmonry TB disese. A Phse IIb tril to ssess whether the vccine cn prevent recurrence of TB disese in ptients who hve recently nd successfully completed TB tretment is being plnned by IDRI nd South Africn collbortors in the sme popultion. Ad5 Ag85A is n denovirus serotype 5 vector expressing Ag85A. It hs been developed by McMster University with support from CnSino, Chinese biotechnology compny. Ad5Ag85A ws evluted in 24 helthy humn volunteers (both BCG-nïve nd previously BCG-immunized) for sfety nd immunogenicity following single intr-musculr injection in Phse I clinicl study completed t McMster 1 Ndiye BP, Thienemnn F, Ot M, et l. Sfety, immunogenicity, nd ef ficcy of the cndidte tuberculosis vccine MVA85A in helthy dults infected with HIV-1: rndomised, plcebo-controlled, phse 2 tril. Lncet Respir Med 215;3: Tmeris MD, Htherill M, Lndry BS, et l. Sfety nd ef ficcy of MVA85A, new tuberculosis vccine, in infnts previously vccinted with BCG: rndomised plcebo-controlled phse 2b tril. Lncet 213;381: University, Cnd. Immuniztion of Ad5Ag85A ws sfe nd well-tolerted in both tril volunteer groups, with only rections t the injection site. Pre-existing Ad5 ntibodies did not pper to f fect the immune response. Ad5Ag85A ws immunogenic in both groups nd stimulted polyfunctionl T cell responses, but it more potently boosted both CD4+ nd CD8+ T cell immunity in previously BCG-vccinted volunteers compred with BCG-nïve individuls. DAR 91 is het-inctivted M. obuense. It hs been developed by investigtors t Drtmouth University, USA, nd mnufctured by Aers. Enrolment in Phse I sfety nd immunogenicity study in 6 BCG-vccinted, HIV-infected nd -uninfected individuls ws recently completed in the USA. The study remins blinded while subjects continue to be followed. No serious dverse events hve been reported nd plns re underwy to complete in-depth immunologic evlutions by the end of 215, using dt for the first people enrolled in the tril. TB/FLU-4L is recombinnt influenz vectored vccine cndidte developed by the Reserch Institute for Biologicl Sfety Problems nd the Reserch Institute on Influenz in the Russin Federtion, with support nd ssistnce from interntionl experts. The influenz virus strin A/Puerto Rico/8/34 (H1N1) ws used s prent strin for construction of n ttenuted repliction-deficient vector expressing M. tuberculosis ntigens Ag85A nd ESAT-6. It ws designed s mucosl boost vccine for infnts, dolescents nd dults. A Phse I tril in BCG-vccinted QuntiFERON TB- Gold negtive helthy dult volunteers using intrnsl dministrtion ws recently completed, nd Phse II tril is plnned. ChAdOx1.85A is simin denovirus expressing ntigen 85A tht ws developed t the University of Oxford. ChAdOX1.85A is being evluted in Phse I tril in BCGvccinted dults, both lone nd s prt of prime-boost strtegy with MVA85A. In this first-in-humns study, ChAdOx1.85A is being dministered intrmusculrly. Future plns include evlution of the erosol route of delivery of ChAdOx1.85A. Crucell Ad35/AERAS-42 nd MVA85A re now being tested in combintion, to try nd induce both CD4+ nd CD8+ T cells. One or two doses of Crucell Ad35 followed by dose of MVA85A is being compred with 3 doses of Crucell Ad35 in Phse I/II tril in dults in the United Kingdom. The tril is being implemented by Oxford University, Aers nd Crucell. MVA85A (Aerosol) is n erosolized MVA85A cndidte developed by Oxford tht recently underwent Phse I double-blind tril to compre the sfety nd immunogenicity of erosol-dministered nd intrdermlly dministered MVA85A in 24 BCG-vccinted dults in the United Kingdom. The study concluded tht erosol vccintion with MVA85A ppered to be sfe nd fesible vccintion tht produced stronger CD4+ T-cell response thn intrderml MVA85A. Further studies ssessing the erosol route re necessry. 114 n GLOBAL TUBERCULOSIS REPORT 215

126 8.3.3 Erly stge, trnsltionl reserch As documented bove, there is resonbly robust pipeline of vccine cndidtes, including those bsed on whole cell pproches, ntibody-inducing vccines nd nucleic cidbsed (DNA nd RNA) vccines. This my help to diversify the clinicl portfolio nd fill the scientific gps tht currently exist. To supplement existing ef forts, there is lso re-prioritized focus on erly stge, trnsltionl reserch. This will test hypotheses bout immunologicl mechnisms, delivery methods, nd cndidte biomrkers, nd help to broden preclinicl scientific pproches, ntigen selection strtegies, nd evlution strtegies, with the overll gol of ensuring tht more diverse pipeline of new TB vccine cndidtes cn move forwrd into clinicl trils. 1 Discussions bout relevnt clinicl endpoints, beyond immunologicl mesures tht indicte prevention of disese or infection, nd how these endpoints my be ssessed through biomrkers erly in clinicl trils or pre-cliniclly to select the most promising cndidte vccines/djuvnts, re lso underwy. 8.4 The End TB Strtegy: the criticl role of reserch nd development The End TB Strtegy includes Intensified Reserch nd Innovtion s one of three fundmentl pillrs (Chpter 1). This hs two essentil nd complementry components: (1) Discovery, development nd rpid uptke of new tools, interventions nd strtegies; nd (2) Reserch to optimize implementtion nd impct. The overll im of the pillr is tht intensified reserch will result in revolutionry new technologies, strtegies nd models of service delivery tht will trnsform the wy in which TB is dignosed, treted nd prevented. As high lighted t the beginning of this chpter, such chnges re necessry by 225, so tht the rte t which TB incidence flls cn be ccelerted beyond the best-ever historic performnce nd trgets tht correspond to ending the globl TB epidemic by 235 cn be chieved. A mssive increse in funding for reserch is required. This includes funding to crete or expnd reserch-enbling environments for the next genertion of scientists in low nd middle-income countries with the lrgest burden of TB, so tht they cn ply led role in reserch bsed on domestic investments, longside estblished globl expertise. Incresed domestic investments in reserch in countries with high burden of TB will be fcilitted by dvoccy from key plyers including ntionl public helth uthorities, reserchers, cre providers, nd civil society. It is lso importnt tht high-income countries nd their institutions, interntionl gencies nd philnthropic orgniztions increse their investments in TB reserch nd trining, in close collbortion with high-burden countries. Once new technologies nd innovtive pproches re developed, they need to be trnslted into policies nd prctices, nd then dpted to prticulr country contexts s pproprite. This will require expnded efforts to disseminte reserch results, prticulrly to policy mkers. To foster nd intensify high-qulity reserch t ntionl nd interntionl levels, WHO hs developed Globl Action Frmework for Reserch towrds TB Elimintion tht covers the period This pln shows how to opertionlize Pillr 3 of the End TB Strtegy, including through the development of country-specific TB reserch strtegic plns, cpcity strengthening, nd development/reinforcement of networks t country level, nd through regulr meetings nd the development of interntionl networks for reserch, cpcity building nd dvoccy t globl nd regionl levels. 1 Brennn MJ nd Thole J, Eds. Tuberculosis vccines: A strtegic blueprint for the next decde. Tuberculosis. 212; 92: Supplement 1; S6 S13. GLOBAL TUBERCULOSIS REPORT 215 n 115

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128 A N N E X 1 Access to the WHO globl TB dtbse

129 118 n GLOBAL TUBERCULOSIS REPORT 215

130 A.1 Dtbse contents The 215 globl TB report is bsed on dt collected nnully from countries nd territories, including 194 Member Sttes. These dt re stored in the globl TB dtbse. In 215, dt were collected on the following topics: TB cse notifictions nd tretment outcomes, including brekdowns by TB cse type, ge, sex nd HIV sttus; lbortory dignostic services; monitoring nd evlution, including surveillnce nd surveys specificlly relted to drug-resistnt TB; mngement of drug-resistnt TB; collbortive TB/HIV ctivities; TB infection control; enggement of ll public nd privte cre providers in TB control; community enggement; the budgets of ntionl TB control progrmmes (NTPs) in 215; utiliztion of generl helth services (hospitliztion nd outptient visits) during tretment in 215; nd NTP expenditures in 214. A shortened version of the online questionnire ws used for highincome countries (tht is, countries with gross ntionl income per cpit of US$ in 214, s defined by the World Bnk) 1 nd/or low-incidence countries (defined s countries with n incidence rte of <2 cses per 1 popultion or <1 cses in totl). Countries reported dt using dedicted website ( which ws opened for reporting in mid- Mrch. Countries in the Europen Union submitted notifiction nd tretment outcomes dt to the TESSy system mnged by the Europen Centre for Disese Prevention nd Control (ECDC). Dt from TESSy were uploded into the globl TB dtbse. Additionl dt bout the provision of isonizid preventive therpy (IPT) to people living with HIV nd ntiretrovirl therpy (ART) for HIV-positive TB ptients were collected by the Joint United Ntions Progrmme on HIV/AIDS (UNAIDS) nd the HIV deprtment in WHO. These dt were jointly vlidted by UNAIDS nd the WHO s Globl TB Progrmme nd HIV deprtment, nd uploded into the globl TB dtbse. Following review nd follow-up with countries, the dt used for the min prt of this report were those dt vilble on 6 August 215. The number of countries nd territories tht hd reported dt by 6 August 215 is shown in Tble A1.1. n TABLE A1.1 Reporting of dt in the 215 round of globl TB dt collection COUNTRIES AND TERRITORIES WHO MEMBER STATES WHO REGION OR SET OF COUNTRIES NUMBER NUMBER THAT REPORTED DATA NUMBER NUMBER THAT REPORTED DATA Africn Region Estern Mediterrnen Region Europen Region Region of the Americs South-Est Asi Region Western Pcific Region High-burden countries World Countries tht did not report by the dedline were mostly low-incidence countries in Western Europe. A.2 Accessing TB dt using the WHO Globl TB Progrmme website You cn find most of the dt held in the globl TB dtbse by going to This web pge gives you ccess to country profiles, comm-seprted vlue (CSV) dt files nd dt visulistions. A2.1 Country profiles Profiles cn be viewed nd downloded for ll 216 countries nd territories tht report TB dt to WHO ech yer, nd not just the 22 high burden countries shown in the printed version of the globl TB report. The profiles cn be generted on-demnd directly from the globl TB dtbse nd therefore my include updtes received fter publiction of the globl TB report. TB finncil profiles cn be viewed nd downloded for over 1 countries nd territories tht report detiled TB finncil dt to WHO. 1 GLOBAL TUBERCULOSIS REPORT 215 n 119

131 n FIGURE A1.1 Interctive pge to view MDR-TB indictors by region or country nd yer A2.2 CSV dt files These files re the primry resource for nyone interested in conducting their own nlyses of the records in the globl TB dtbse. Dt reported by countries, such s time series for cse notifictions nd tretment outcomes nd WHO s estimtes of TB disese burden, cn be downloded s comm-seprted vlue (CSV) files covering ll yers for which dt re vilble. These CSV files cn be imported into mny spredsheet, sttisticl nlysis nd dtbse pckges. A dt dictionry tht defines ech of the vribles vilble in the CSV files is lso vilble nd cn be downloded. The CSV files re generted on-demnd directly from the globl TB dtbse, nd therefore my include updtes received fter publiction of the globl TB report. A2.3 Dt visulistions There re severl interctive web pges tht cn be used to view mps, grphs nd underlying dt on TB cse notifictions, drug-resistnt TB cses nd tretment outcomes, lbortory cpcity nd WHO estimtes of TB incidence, prevlence nd mortlity (Figure A1.1). A.3 Accessing TB dt using the WHO Globl Helth Observtory The WHO Globl Helth Observtory (GHO) t is WHO s portl, providing ccess to dt nd nlyses for monitoring the globl helth sitution. It includes dt repository. Key dt from WHO s globl TB dtbse cn be viewed, filtered, ggregted nd downloded from within the GHO Dt Repository t The GHO dt tble heders include links to vrible nd indictor definitions. The dt cn be downloded in mny formts, including s CSV nd Excel files (Figure A1.2). There is lso n Appliction Progrmme Interfce (API) for nlysts nd progrmmers to use GHO dt directly in their softwre pplictions. See 12 n GLOBAL TUBERCULOSIS REPORT 215

132 n FIGURE A1.2 A dt tble in the GHO Dt Repository GLOBAL TUBERCULOSIS REPORT 215 n 121

133

134 A N N E X 2 Country profiles FOR 22 HIGH-BURDEN COUNTRIES

135 124 n GLOBAL TUBERCULOSIS REPORT 215 Dt for ll yers cn be downloded from

136 Afghnistn Popultion million Estimtes of TB burden 214 NUMBER (thousnds) RATE (per 1 popultion) Mortlity (excludes HIV+TB) 14 (1 18) 44 (32 57) Mortlity (HIV+TB only).87 (.72.1).28 (.23.33) Prevlence (includes HIV+TB) 11 (56 18) 34 ( ) Incidence (includes HIV+TB) 6 (53 67) 189 ( ) Incidence (HIV+TB only).32 (.25.4) 1 (.8 1.3) Cse detection, ll forms (%) 53 (47 6) Estimtes of MDR-TB burden 214 NEW RETREATMENT % of TB cses with MDR-TB 3.2 ( ) 17 (11 23) MDR-TB cses mong notified pulmonry TB cses 75 (54 96) 36 (24 49) TB cse notifictions 214 NEW b RELAPSE Pulmonry, bcteriologiclly confirmed Pulmonry, cliniclly dignosed Extrpulmonry Totl new nd relpse Previously treted, excluding relpses 966 Totl cses notified Among new cses: (15%) cses ged under 15 yers; mle:femle rtio:.7 Reported cses of RR-/MDR-TB 214 NEW RETREATMENT TOTAL b Cses tested for RR-/MDR-TB 2 (<1%) 184 (8%) 186 Lbortory-confirmed RR-/MDR-TB cses 88 Ptients strted on MDR-TB tretment c 88 TB/HIV 214 NUMBER (%) TB ptients with known HIV sttus (32) HIV-positive TB ptients 4 (<1) HIV-positive TB ptients on co-trimoxzole preventive therpy (CPT) HIV-positive TB ptients on ntiretrovirl therpy (ART) HIV-positive people screened for TB 142 HIV-positive people provided with IPT 7 Tretment success rte nd cohort size (%) COHORT New nd relpse cses registered in 213 (88) 3 57 Previously treted cses, excluding relpse, registered in 213 (74) HIV-positive TB cses, ll types, registered in 213 RR-/MDR-TB cses strted on second-line tretment in 212 (71) 38 XDR-TB cses strted on second-line tretment in 212 Lbortories 214 Smer (per 1 popultion) 2.3 Culture (per 5 million popultion).5 Drug susceptibility testing (per 5 million popultion) Sites performing Xpert MTB/RIF 1 Is second-line drug susceptibility testing vilble? Yes, outside country Finncing TB control 215 Ntionl TB progrmme budget (US$ millions) 15 % Funded domesticlly 6% % Funded interntionlly 67% % Unfunded 27% Mortlity (excludes HIV+TB) (rte per 1 poultion per yer) Prevlence (rte per 1 poultion) Incidence (rte per 1 poultion per yer) Number of ptients Tretment success rte (%) Notified (new nd relpse) Incidence Incidence (HIV+TB only) HIV-positive TB ptients on CPT on ART New Retretment New nd relpse Retretment excluding relpse HIV-positive RR-/MDR-TB XDR-TB Dt re s reported to WHO. Estimtes of TB nd MDR-TB burden re produced by WHO in consulttion with countries. Rnges represent uncertinty intervls. b Includes cses with unknown previous TB tretment history. c Includes ptients dignosed before 214 nd ptients who were not lbortory-confirmed s hving RR-/MDR-TB. Totl budget (US$ millions) Funded domesticlly Funded interntionlly Unfunded Dt for ll yers cn be downloded from GLOBAL TUBERCULOSIS REPORT 215 n 125

137 Bngldesh Popultion million Estimtes of TB burden 214 NUMBER (thousnds) RATE (per 1 popultion) Mortlity (excludes HIV+TB) 81 (59 11) 51 (37 68) Mortlity (HIV+TB only).18 (.14.22).11 (.9.14) Prevlence (includes HIV+TB) 64 (34 1 ) 44 ( ) Incidence (includes HIV+TB) 36 (32 41) 227 (2 256) Incidence (HIV+TB only).57 (.45.71).36 (.28.45) Cse detection, ll forms (%) 53 (47 6) Estimtes of MDR-TB burden 214 NEW RETREATMENT % of TB cses with MDR-TB 1.4 (.7 2.5) 29 (24 34) MDR-TB cses mong notified pulmonry TB cses 2 1 (1 3 7) 2 7 ( ) TB cse notifictions 214 NEW b RELAPSE Pulmonry, bcteriologiclly confirmed Pulmonry, cliniclly dignosed Extrpulmonry Totl new nd relpse Previously treted, excluding relpses Totl cses notified Among new cses: (3%) cses ged under 15 yers; mle:femle rtio: 1.5 Reported cses of RR-/MDR-TB 214 NEW RETREATMENT TOTAL b Cses tested for RR-/MDR-TB (12%) (51%) Lbortory-confirmed RR-/MDR-TB cses 994 Ptients strted on MDR-TB tretment c 945 TB/HIV 214 NUMBER (%) TB ptients with known HIV sttus 1 11 (<1) HIV-positive TB ptients 45 (4) HIV-positive TB ptients on co-trimoxzole preventive therpy (CPT) 45 (1) HIV-positive TB ptients on ntiretrovirl therpy (ART) 45 (1) HIV-positive people screened for TB 726 HIV-positive people provided with IPT Tretment success rte nd cohort size (%) COHORT New nd relpse cses registered in 213 (93) Previously treted cses, excluding relpse, registered in 213 (86) HIV-positive TB cses, ll types, registered in 213 (75) 68 RR-/MDR-TB cses strted on second-line tretment in 212 (72) 55 XDR-TB cses strted on second-line tretment in 212 (25) 4 Lbortories 214 Smer (per 1 popultion).7 Culture (per 5 million popultion) <.1 Drug susceptibility testing (per 5 million popultion) <.1 Sites performing Xpert MTB/RIF 38 Is second-line drug susceptibility testing vilble? Yes, in nd outside country Finncing TB control 215 Ntionl TB progrmme budget (US$ millions) 48 % Funded domesticlly <1% % Funded interntionlly 7% % Unfunded 3% Dt re s reported to WHO. Estimtes of TB nd MDR-TB burden re produced by WHO in consulttion with countries. Rnges represent uncertinty intervls. A joint ressessment of estimtes of TB disese burden will be undertken following completion of the ntionl TB prevlence survey. b Includes cses with unknown previous TB tretment history. c Includes ptients dignosed before 214 nd ptients who were not lbortory-confirmed s hving RR-/MDR-TB. Mortlity (excludes HIV+TB) (rte per 1 poultion per yer) Prevlence (rte per 1 poultion) Incidence (rte per 1 poultion per yer) Number of ptients Tretment success rte (%) Totl budget (US$ millions) Notified (new nd relpse) Incidence Incidence (HIV+TB only) HIV-positive TB ptients on CPT on ART New Retretment New nd relpse Retretment excluding relpse HIV-positive RR-/MDR-TB XDR-TB Funded domesticlly Funded interntionlly Unfunded 126 n GLOBAL TUBERCULOSIS REPORT 215 Dt for ll yers cn be downloded from

138 Brzil Popultion million Estimtes of TB burden 214 NUMBER (thousnds) RATE (per 1 popultion) Mortlity (excludes HIV+TB) 5.3 ( ) 2.6 ( ) Mortlity (HIV+TB only) 2.4 ( ) 1.2 ( ) Prevlence (includes HIV+TB) 11 (51 18) 52 (25 89) Incidence (includes HIV+TB) 9 (86 95) 44 (42 46) Incidence (HIV+TB only) 16 (14 17) 7.6 ( ) Cse detection, ll forms (%) 82 (78 86) Estimtes of MDR-TB burden 214 NEW RETREATMENT % of TB cses with MDR-TB 1.4 (1 1.8) 7.5 ( ) MDR-TB cses mong notified pulmonry TB cses 82 (59 1 1) 95 (72 1 3) TB cse notifictions 214 NEW b RELAPSE Pulmonry, bcteriologiclly confirmed Pulmonry, cliniclly dignosed Extrpulmonry Mortlity (excludes HIV+TB) (rte per 1 poultion per yer) Prevlence (rte per 1 poultion) Totl new nd relpse Previously treted, excluding relpses Totl cses notified Among new nd relpse cses: (3%) cses ged under 15 yers; mle:femle rtio: 2.1 Reported cses of RR-/MDR-TB 214 NEW RETREATMENT TOTAL b Cses tested for RR-/MDR-TB Lbortory-confirmed RR-/MDR-TB cses 72 Ptients strted on MDR-TB tretment c 72 TB/HIV 214 NUMBER (%) TB ptients with known HIV sttus (7) HIV-positive TB ptients (17) HIV-positive TB ptients on co-trimoxzole preventive therpy (CPT) HIV-positive TB ptients on ntiretrovirl therpy (ART) HIV-positive people screened for TB HIV-positive people provided with IPT Tretment success rte nd cohort size (%) COHORT New nd relpse cses registered in 213 (72) Previously treted cses, excluding relpse, registered in 213 (38) HIV-positive TB cses, ll types, registered in 213 (46) 9 46 RR-/MDR-TB cses strted on second-line tretment in 212 (51) 825 XDR-TB cses strted on second-line tretment in 212 (25) 24 Lbortories 214 Smer (per 1 popultion) 1.6 Culture (per 5 million popultion) 7.9 Drug susceptibility testing (per 5 million popultion).6 Sites performing Xpert MTB/RIF 48 Is second-line drug susceptibility testing vilble? Yes, in country Finncing TB control 215 Ntionl TB progrmme budget (US$ millions) 77 % Funded domesticlly 72% % Funded interntionlly <1% % Unfunded 27% Dt re s reported to WHO. Estimtes of TB nd MDR-TB burden re produced by WHO in consulttion with countries. Rnges represent uncertinty intervls. b Includes cses with unknown previous TB tretment history. c Includes ptients dignosed before 214 nd ptients who were not lbortory-confirmed s hving RR-/MDR-TB. Incidence (rte per 1 poultion per yer) Number of ptients Tretment success rte (%) Totl budget (US$ millions) Notified (new nd relpse) Incidence Incidence (HIV+TB only) HIV-positive TB ptients on CPT on ART New Retretment New nd relpse Retretment excluding relpse HIV-positive RR-/MDR-TB XDR-TB Funded domesticlly Funded interntionlly Unfunded Dt for ll yers cn be downloded from GLOBAL TUBERCULOSIS REPORT 215 n 127

139 Cmbodi Popultion million Estimtes of TB burden 214 NUMBER (thousnds) RATE (per 1 popultion) Mortlity (excludes HIV+TB) 8.9 (6.3 12) 58 (41 78) Mortlity (HIV+TB only).82 (.63 1) 5.3 ( ) Prevlence (includes HIV+TB) 1 (87 12) 668 (565 78) Incidence (includes HIV+TB) 6 (54 66) 39 ( ) Incidence (HIV+TB only) 1.8 (1.6 2) 12 (1 13) Cse detection, ll forms (%) 72 (66 8) Estimtes of MDR-TB burden 214 NEW RETREATMENT % of TB cses with MDR-TB 1.4 (.7 2.5) 11 (4 22) MDR-TB cses mong notified pulmonry TB cses 33 (16 59) 2 (73 4) TB cse notifictions 214 NEW b RELAPSE Pulmonry, bcteriologiclly confirmed Pulmonry, cliniclly dignosed Extrpulmonry Totl new nd relpse Previously treted, excluding relpses 679 Totl cses notified Among new nd relpse cses: 12 5 (28%) cses ged under 15 yers; mle:femle rtio: 1.2 Reported cses of RR-/MDR-TB 214 NEW RETREATMENT TOTAL b Cses tested for RR-/MDR-TB 646 (5%) (67%) Lbortory-confirmed RR-/MDR-TB cses 11 Ptients strted on MDR-TB tretment c 11 TB/HIV 214 NUMBER (%) TB ptients with known HIV sttus (81) HIV-positive TB ptients 953 (3) HIV-positive TB ptients on co-trimoxzole preventive therpy (CPT) 938 (98) HIV-positive TB ptients on ntiretrovirl therpy (ART) 938 (98) HIV-positive people screened for TB 3 54 HIV-positive people provided with IPT 91 Tretment success rte nd cohort size (%) COHORT New nd relpse cses registered in 213 (93) Previously treted cses, excluding relpse, registered in 213 (9) 1 71 HIV-positive TB cses, ll types, registered in 213 RR-/MDR-TB cses strted on second-line tretment in 212 (79) 11 XDR-TB cses strted on second-line tretment in 212 Lbortories 214 Smer (per 1 popultion) 1.4 Culture (per 5 million popultion) 1.3 Drug susceptibility testing (per 5 million popultion) 1. Sites performing Xpert MTB/RIF 17 Is second-line drug susceptibility testing vilble? No Finncing TB control 215 Ntionl TB progrmme budget (US$ millions) 31 % Funded domesticlly 12% % Funded interntionlly 47% % Unfunded 42% Dt re s reported to WHO. Estimtes of TB nd MDR-TB burden re produced by WHO in consulttion with countries. Rnges represent uncertinty intervls. b Includes cses with unknown previous TB tretment history. c Includes ptients dignosed before 214 nd ptients who were not lbortory-confirmed s hving RR-/MDR-TB. Mortlity (excludes HIV+TB) (rte per 1 poultion per yer) Prevlence (rte per 1 poultion) Incidence (rte per 1 poultion per yer) Number of ptients Tretment success rte (%) Totl budget (US$ millions) Notified (new nd relpse) Incidence Incidence (HIV+TB only) HIV-positive TB ptients on CPT on ART New Retretment New nd relpse Retretment excluding relpse HIV-positive RR-/MDR-TB XDR-TB Funded domesticlly Funded interntionlly Unfunded 128 n GLOBAL TUBERCULOSIS REPORT 215 Dt for ll yers cn be downloded from

140 Chin Popultion million Estimtes of TB burden 214 NUMBER (thousnds) RATE (per 1 popultion) Mortlity (excludes HIV+TB) 38 (37 4) 2.8 ( ) Mortlity (HIV+TB only).7 (.53.9).5 (.4.7) Prevlence (includes HIV+TB) 1 2 ( ) 89 (78 12) Incidence (includes HIV+TB) 93 (86 1 ) 68 (63 73) Incidence (HIV+TB only) 13 (11 16).98 ( ) Cse detection, ll forms (%) 88 (82 95) Estimtes of MDR-TB burden 214 NEW RETREATMENT % of TB cses with MDR-TB 5.7 (4.5 7) 26 (22 3) MDR-TB cses mong notified pulmonry TB cses 43 (34 53 ) 8 2 ( ) TB cse notifictions 214 NEW b RELAPSE Pulmonry, bcteriologiclly confirmed Pulmonry, cliniclly dignosed Extrpulmonry Mortlity (excludes HIV+TB) (rte per 1 poultion per yer) Prevlence (rte per 1 poultion) Totl new nd relpse Previously treted, excluding relpses Totl cses notified Among new nd relpse cses: (<1%) cses ged under 15 yers; mle:femle rtio: 2.3 Reported cses of RR-/MDR-TB 214 NEW RETREATMENT TOTAL b Cses tested for RR-/MDR-TB (19%) (54%) Lbortory-confirmed RR-/MDR-TB cses 5 87 Ptients strted on MDR-TB tretment c TB/HIV 214 NUMBER (%) TB ptients with known HIV sttus (42) HIV-positive TB ptients 5 39 (2) HIV-positive TB ptients on co-trimoxzole preventive therpy (CPT) HIV-positive TB ptients on ntiretrovirl therpy (ART) (69) HIV-positive people screened for TB HIV-positive people provided with IPT Tretment success rte nd cohort size (%) COHORT New nd relpse cses registered in 213 (95) Previously treted cses, excluding relpse, registered in 213 (9) HIV-positive TB cses, ll types, registered in 213 (82) RR-/MDR-TB cses strted on second-line tretment in 212 (42) 1 96 XDR-TB cses strted on second-line tretment in 212 (13) 115 Lbortories 214 Smer (per 1 popultion).2 Culture (per 5 million popultion) 6.7 Drug susceptibility testing (per 5 million popultion) 1.5 Sites performing Xpert MTB/RIF 654 Is second-line drug susceptibility testing vilble? Yes, in country Finncing TB control 215 Ntionl TB progrmme budget (US$ millions) 34 % Funded domesticlly 9% % Funded interntionlly 2% % Unfunded 8% Dt re s reported to WHO. Estimtes of TB nd MDR-TB burden re produced by WHO in consulttion with countries. Rnges represent uncertinty intervls. b Includes cses with unknown previous TB tretment history. c Includes ptients dignosed before 214 nd ptients who were not lbortory-confirmed s hving RR-/MDR-TB. Incidence (rte per 1 poultion per yer) Number of ptients Tretment success rte (%) Totl budget (US$ millions) Notified (new nd relpse) Incidence Incidence (HIV+TB only) HIV-positive TB ptients on CPT on ART New Retretment New nd relpse Retretment excluding relpse HIV-positive RR-/MDR-TB XDR-TB Funded domesticlly Funded interntionlly Unfunded Dt for ll yers cn be downloded from GLOBAL TUBERCULOSIS REPORT 215 n 129

141 Democrtic Republic of the Congo Popultion million Estimtes of TB burden 214 NUMBER (thousnds) RATE (per 1 popultion) Mortlity (excludes HIV+TB) 52 (38 68) 69 (5 9) Mortlity (HIV+TB only) 6.3 (5 7.7) 8.4 (6.7 1) Prevlence (includes HIV+TB) 4 (21 64) 532 ( ) Incidence (includes HIV+TB) 24 (22 27) 325 ( ) Incidence (HIV+TB only) 34 (27 42) 45 (36 56) Cse detection, ll forms (%) 48 (43 52) Estimtes of MDR-TB burden 214 NEW RETREATMENT % of TB cses with MDR-TB 2.2 (.3 4.1) 11 (6.2 16) MDR-TB cses mong notified pulmonry TB cses 2 (27 3 7) 79 (45 1 1) TB cse notifictions 214 NEW b RELAPSE Pulmonry, bcteriologiclly confirmed Pulmonry, cliniclly dignosed Extrpulmonry Totl new nd relpse Previously treted, excluding relpses 1 99 Totl cses notified Among new cses: (5%) cses ged under 15 yers; mle:femle rtio: 1.3 Reported cses of RR-/MDR-TB 214 NEW RETREATMENT TOTAL b Cses tested for RR-/MDR-TB 545 (<1%) (75%) Lbortory-confirmed RR-/MDR-TB cses 442 Ptients strted on MDR-TB tretment c 436 TB/HIV 214 NUMBER (%) TB ptients with known HIV sttus (46) HIV-positive TB ptients 7 26 (14) HIV-positive TB ptients on co-trimoxzole preventive therpy (CPT) (79) HIV-positive TB ptients on ntiretrovirl therpy (ART) (67) HIV-positive people screened for TB HIV-positive people provided with IPT Tretment success rte nd cohort size (%) COHORT New cses registered in 213 (87) Previously treted cses registered in 213 (66) HIV-positive TB cses, ll types, registered in 213 RR-/MDR-TB cses strted on second-line tretment in 212 (64) 134 XDR-TB cses strted on second-line tretment in 212 Lbortories 214 Smer (per 1 popultion) 2.1 Culture (per 5 million popultion).3 Drug susceptibility testing (per 5 million popultion).2 Sites performing Xpert MTB/RIF 39 Is second-line drug susceptibility testing vilble? Yes, in nd outside country Finncing TB control 215 Ntionl TB progrmme budget (US$ millions) 55 % Funded domesticlly 5% % Funded interntionlly 5% % Unfunded 44% Dt re s reported to WHO. Estimtes of TB nd MDR-TB burden re produced by WHO in consulttion with countries. Rnges represent uncertinty intervls. b Includes cses with unknown previous TB tretment history. c Includes ptients dignosed before 214 nd ptients who were not lbortory-confirmed s hving RR-/MDR-TB. Mortlity (excludes HIV+TB) (rte per 1 poultion per yer) Prevlence (rte per 1 poultion) Incidence (rte per 1 poultion per yer) Number of ptients Tretment success rte (%) Totl budget (US$ millions) Notified (new nd relpse) Incidence Incidence (HIV+TB only) HIV-positive TB ptients on CPT on ART New Retretment HIV-positive RR-/MDR-TB XDR-TB Funded domesticlly Funded interntionlly Unfunded 13 n GLOBAL TUBERCULOSIS REPORT 215 Dt for ll yers cn be downloded from

142 Ethiopi Popultion million Estimtes of TB burden 214 NUMBER (thousnds) RATE (per 1 popultion) Mortlity (excludes HIV+TB) 32 (22 43) 33 (23 44) Mortlity (HIV+TB only) 5.5 ( ) 5.7 (4.6 7) Prevlence (includes HIV+TB) 19 (16 24) 2 ( ) Incidence (includes HIV+TB) 2 (16 24) 27 (168 25) Incidence (HIV+TB only) 19 (15 23) 19 (15 24) Cse detection, ll forms (%) 6 (49 73) Estimtes of MDR-TB burden 214 NEW RETREATMENT % of TB cses with MDR-TB 1.6 ( ) 12 (5.6 21) MDR-TB cses mong notified pulmonry TB cses 1 3 (7 2 3) TB cse notifictions 214 NEW b Pulmonry, bcteriologiclly confirmed 4 87 Pulmonry, cliniclly dignosed Extrpulmonry RELAPSE Mortlity (excludes HIV+TB) (rte per 1 poultion per yer) Prevlence (rte per 1 poultion) Totl new nd relpse Previously treted, excluding relpses Totl cses notified Among new cses: (13%) cses ged under 15 yers; mle:femle rtio: 1.2 Reported cses of RR-/MDR-TB 214 NEW RETREATMENT TOTAL b Cses tested for RR-/MDR-TB 2 45 (6%) Lbortory-confirmed RR-/MDR-TB cses 53 Ptients strted on MDR-TB tretment c 557 TB/HIV 214 NUMBER (%) TB ptients with known HIV sttus (75) HIV-positive TB ptients 8 67 (1) HIV-positive TB ptients on co-trimoxzole preventive therpy (CPT) d HIV-positive TB ptients on ntiretrovirl therpy (ART) d (39) HIV-positive people screened for TB HIV-positive people provided with IPT Tretment success rte nd cohort size (%) COHORT New cses registered in 213 (89) Previously treted cses registered in 213 HIV-positive TB cses, ll types, registered in 213 RR-/MDR-TB cses strted on second-line tretment in 212 (83) 271 XDR-TB cses strted on second-line tretment in 212 Lbortories 214 Smer (per 1 popultion) 3.1 Culture (per 5 million popultion).4 Drug susceptibility testing (per 5 million popultion).4 Sites performing Xpert MTB/RIF 28 Is second-line drug susceptibility testing vilble? Yes, in country Finncing TB control 215 Ntionl TB progrmme budget (US$ millions) 82 % Funded domesticlly 11% % Funded interntionlly 42% % Unfunded 47% Dt re s reported to WHO. Estimtes of TB nd MDR-TB burden re produced by WHO in consulttion with countries. Rnges represent uncertinty intervls. b Includes cses with unknown previous TB tretment history. c Includes ptients dignosed before 214 nd ptients who were not lbortory-confirmed s hving RR-/MDR-TB. d ART nd IPT dt were missing for 3 of Ethiopi s 11 regions, which in previous yers hd ccounted for bout one third of the ntionl totls. In the 8 regions tht reported dt, 65% of HIV-positive TB ptients were on ART. Incidence (rte per 1 poultion per yer) Number of ptients Tretment success rte (%) Totl budget (US$ millions) Notified (new nd relpse) Incidence Incidence (HIV+TB only) HIV-positive TB ptients on CPT on ART New Retretment HIV-positive RR-/MDR-TB XDR-TB Funded domesticlly Funded interntionlly Unfunded Dt for ll yers cn be downloded from GLOBAL TUBERCULOSIS REPORT 215 n 131

143 Indi Popultion million Estimtes of TB burden 214 NUMBER (thousnds) RATE (per 1 popultion) Mortlity (excludes HIV+TB) 22 (15 35) 17 (12 27) Mortlity (HIV+TB only) 31 (25 38) 2.4 (2 2.9) Prevlence (includes HIV+TB) 2 5 ( ) 195 ( ) Incidence (includes HIV+TB) 2 2 (2 2 3) 167 ( ) Incidence (HIV+TB only) 11 (96 12) 8.3 ( ) Cse detection, ll forms (%) 74 (7 8) Estimtes of MDR-TB burden 214 NEW RETREATMENT % of TB cses with MDR-TB 2.2 ( ) 15 (11 19) MDR-TB cses mong notified pulmonry TB cses 24 (21 29 ) 47 (35 59 ) TB cse notifictions 214 NEW b RELAPSE Pulmonry, bcteriologiclly confirmed Pulmonry, cliniclly dignosed Extrpulmonry Mortlity (excludes HIV+TB) (rte per 1 poultion per yer) Prevlence (rte per 1 poultion) Totl new nd relpse Previously treted, excluding relpses Totl cses notified Among new nd relpse cses: (6%) cses ged under 15 yers; mle:femle rtio: 1.9 Reported cses of RR-/MDR-TB 214 NEW RETREATMENT TOTAL b Cses tested for RR-/MDR-TB (2%) (69%) Lbortory-confirmed RR-/MDR-TB cses Ptients strted on MDR-TB tretment c TB/HIV 214 NUMBER (%) TB ptients with known HIV sttus (61) HIV-positive TB ptients (4) HIV-positive TB ptients on co-trimoxzole preventive therpy (CPT) (93) HIV-positive TB ptients on ntiretrovirl therpy (ART) 39 8 (9) HIV-positive people screened for TB HIV-positive people provided with IPT Tretment success rte nd cohort size (%) COHORT New nd relpse cses registered in 213 (88) Previously treted cses, excluding relpse, registered in 213 (66) HIV-positive TB cses, ll types, registered in 213 (76) RR-/MDR-TB cses strted on second-line tretment in 212 (46) XDR-TB cses strted on second-line tretment in 212 (33) 91 Lbortories 214 Smer (per 1 popultion) 1. Culture (per 5 million popultion).3 Drug susceptibility testing (per 5 million popultion).2 Sites performing Xpert MTB/RIF 121 Is second-line drug susceptibility testing vilble? Yes, in country Finncing TB control 215 Ntionl TB progrmme budget (US$ millions) 261 % Funded domesticlly 46% % Funded interntionlly 54% % Unfunded % Dt re s reported to WHO. Estimtes of TB nd MDR-TB burden re produced by WHO in consulttion with countries. Rnges represent uncertinty intervls. b Includes cses with unknown previous TB tretment history. c Includes ptients dignosed before 214 nd ptients who were not lbortory-confirmed s hving RR-/MDR-TB. Incidence (rte per 1 poultion per yer) Number of ptients Tretment success rte (%) Totl budget (US$ millions) Notified (new nd relpse) Incidence Incidence (HIV+TB only) HIV-positive TB ptients on CPT on ART New Retretment New nd relpse Retretment excluding relpse HIV-positive RR-/MDR-TB XDR-TB Funded domesticlly Funded interntionlly Unfunded 132 n GLOBAL TUBERCULOSIS REPORT 215 Dt for ll yers cn be downloded from

144 Indonesi Popultion million Estimtes of TB burden 214 NUMBER (thousnds) RATE (per 1 popultion) Mortlity (excludes HIV+TB) 1 (66 15) 41 (26 59) Mortlity (HIV+TB only) 22 (13 32) 8.5 (5.2 13) Prevlence (includes HIV+TB) b 1 6 (1 3 2 ) 647 ( ) Incidence (includes HIV+TB) 1 (7 1 4) 399 ( ) Incidence (HIV+TB only) 63 (41 9) 25 (16 36) Cse detection, ll forms (%) 32 (23 46) Estimtes of MDR-TB burden 214 NEW RETREATMENT % of TB cses with MDR-TB 1.9 ( ) 12 (8.1 17) MDR-TB cses mong notified pulmonry TB cses 5 6 ( ) 1 1 (77 1 6) TB cse notifictions 214 NEW c RELAPSE Pulmonry, bcteriologiclly confirmed Pulmonry, cliniclly dignosed Extrpulmonry Totl new nd relpse Previously treted, excluding relpses Totl cses notified Among new nd relpse cses: (7%) cses ged under 15 yers; mle:femle rtio: 1.4 Reported cses of RR-/MDR-TB 214 NEW RETREATMENT TOTAL b Cses tested for RR-/MDR-TB 1 58 (<1%) (88%) 9 53 Lbortory-confirmed RR-/MDR-TB cses Ptients strted on MDR-TB tretment d TB/HIV 214 NUMBER (%) TB ptients with known HIV sttus (5) HIV-positive TB ptients (16) HIV-positive TB ptients on co-trimoxzole preventive therpy (CPT) 963 (41) HIV-positive TB ptients on ntiretrovirl therpy (ART) 624 (26) HIV-positive people screened for TB HIV-positive people provided with IPT Tretment success rte nd cohort size (%) COHORT New nd relpse cses registered in 213 (88) Previously treted cses, excluding relpse, registered in 213 (64) HIV-positive TB cses, ll types, registered in 213 (49) RR-/MDR-TB cses strted on second-line tretment in 212 (54) 432 XDR-TB cses strted on second-line tretment in 212 (64) 11 Lbortories 214 Smer (per 1 popultion) 2.2 Culture (per 5 million popultion).4 Drug susceptibility testing (per 5 million popultion).3 Sites performing Xpert MTB/RIF 41 Is second-line drug susceptibility testing vilble? Yes, in country Finncing TB control 215 Ntionl TB progrmme budget (US$ millions) 133 % Funded domesticlly 13% % Funded interntionlly 21% % Unfunded 66% Dt re s reported to WHO. Estimtes of TB nd MDR-TB burden re produced by WHO in consulttion with countries. Rnges represent uncertinty intervls. b The prevlence rte of bcteriologiclly confirmed TB ws 531 ( ) per 1 popultion; the prevlence rte of cliniclly dignosed TB (i.e. smer-negtive nd culturenegtive TB, including ll extr-pulmonry cses) ws 116 (91 143) per 1 popultion; the prevlence rte of extr-pulmonry TB ( subset of those in the cliniclly dignosed ctegory) ws 58 (43 75) per 1 popultion. c Includes cses with unknown previous TB tretment history. d Includes ptients dignosed before 214 nd ptients who were not lbortory-confirmed s hving RR-/MDR-TB. Mortlity (excludes HIV+TB) (rte per 1 poultion per yer) Prevlence (rte per 1 poultion) Incidence (rte per 1 poultion per yer) Number of ptients Tretment success rte (%) Totl budget (US$ millions) Notified (new nd relpse) Incidence Incidence (HIV+TB only) HIV-positive TB ptients on CPT on ART New Retretment New nd relpse Retretment excluding relpse HIV-positive RR-/MDR-TB XDR-TB Funded domesticlly Funded interntionlly Unfunded Dt for ll yers cn be downloded from GLOBAL TUBERCULOSIS REPORT 215 n 133

145 Keny Popultion million Estimtes of TB burden 214 NUMBER (thousnds) RATE (per 1 popultion) Mortlity (excludes HIV+TB) 9.4 (6.7 12) 21 (15 28) Mortlity (HIV+TB only) 8.1 (6.4 1) 18 (14 22) Prevlence (includes HIV+TB) 12 (64 19) 266 ( ) Incidence (includes HIV+TB) 11 (11 11) 246 (24 252) Incidence (HIV+TB only) 4 (38 42) 89 (84 93) Cse detection, ll forms (%) 8 (78 82) Estimtes of MDR-TB burden 214 NEW RETREATMENT % of TB cses with MDR-TB 2.2 (.3 4.1) 14 (12 15) MDR-TB cses mong notified pulmonry TB cses 1 4 (2 2 7) 1 1 (93 1 2) TB cse notifictions 214 NEW b RELAPSE Pulmonry, bcteriologiclly confirmed Pulmonry, cliniclly dignosed Extrpulmonry Mortlity (excludes HIV+TB) (rte per 1 poultion per yer) Prevlence (rte per 1 poultion) Totl new nd relpse Previously treted, excluding relpses Totl cses notified Among new nd relpse cses: (9%) cses ged under 15 yers; mle:femle rtio: 1.5 Reported cses of RR-/MDR-TB 214 NEW RETREATMENT TOTAL b Cses tested for RR-/MDR-TB (5%) (85%) Lbortory-confirmed RR-/MDR-TB cses 644 Ptients strted on MDR-TB tretment c 544 TB/HIV 214 NUMBER (%) TB ptients with known HIV sttus (95) HIV-positive TB ptients 3 2 (36) HIV-positive TB ptients on co-trimoxzole preventive therpy (CPT) (99) HIV-positive TB ptients on ntiretrovirl therpy (ART) (87) HIV-positive people screened for TB HIV-positive people provided with IPT Tretment success rte nd cohort size (%) COHORT New cses registered in 213 (86) Previously treted cses registered in 213 (78) HIV-positive TB cses, ll types, registered in 213 (79) RR-/MDR-TB cses strted on second-line tretment in 212 (83) 197 XDR-TB cses strted on second-line tretment in 212 Lbortories 214 Smer (per 1 popultion) 4.3 Culture (per 5 million popultion).3 Drug susceptibility testing (per 5 million popultion).3 Sites performing Xpert MTB/RIF 7 Is second-line drug susceptibility testing vilble? No Finncing TB control 215 Ntionl TB progrmme budget (US$ millions) 45 % Funded domesticlly 26% % Funded interntionlly 28% % Unfunded 45% Dt re s reported to WHO. Estimtes of TB nd MDR-TB burden re produced by WHO in consulttion with countries. Rnges represent uncertinty intervls. b Includes cses with unknown previous TB tretment history. c Includes ptients dignosed before 214 nd ptients who were not lbortory-confirmed s hving RR-/MDR-TB. Incidence (rte per 1 poultion per yer) Number of ptients Tretment success rte (%) Totl budget (US$ millions) Notified (new nd relpse) Incidence Incidence (HIV+TB only) HIV-positive TB ptients on CPT on ART New Retretment New nd relpse Retretment excluding relpse HIV-positive RR-/MDR-TB XDR-TB Funded domesticlly Funded interntionlly Unfunded 134 n GLOBAL TUBERCULOSIS REPORT 215 Dt for ll yers cn be downloded from

146 Mozmbique Popultion million Estimtes of TB burden 214 NUMBER (thousnds) RATE (per 1 popultion) Mortlity (excludes HIV+TB) 18 (12 26) 67 (44 96) Mortlity (HIV+TB only) 37 (29 45) 134 (16 165) Prevlence (includes HIV+TB) 15 (8 24) 554 ( ) Incidence (includes HIV+TB) 15 (12 18) 551 (435 68) Incidence (HIV+TB only) 85 (65 11) 311 ( ) Cse detection, ll forms (%) 39 (31 49) Estimtes of MDR-TB burden 214 NEW RETREATMENT % of TB cses with MDR-TB 3.5 ( ) 11 ( 25) MDR-TB cses mong notified pulmonry TB cses 1 7 ( ) 46 ( 1 ) TB cse notifictions 214 NEW c RELAPSE Pulmonry, bcteriologiclly confirmed Pulmonry, cliniclly dignosed Extrpulmonry Totl new nd relpse Previously treted, excluding relpses 497 Totl cses notified Reported cses of RR-/MDR-TB 214 NEW RETREATMENT TOTAL b Cses tested for RR-/MDR-TB 886 (4%) 96 (22%) Lbortory-confirmed RR-/MDR-TB cses 544 Ptients strted on MDR-TB tretment c 482 TB/HIV 214 NUMBER (%) TB ptients with known HIV sttus (96) HIV-positive TB ptients (52) HIV-positive TB ptients on co-trimoxzole preventive therpy (CPT) (94) HIV-positive TB ptients on ntiretrovirl therpy (ART) (81) HIV-positive people screened for TB HIV-positive people provided with IPT Tretment success rte nd cohort size (%) COHORT New cses registered in 213 d (88) Previously treted cses registered in 213 HIV-positive TB cses, ll types, registered in 213 RR-/MDR-TB cses strted on second-line tretment in 212 (28) 214 XDR-TB cses strted on second-line tretment in 212 () 4 Lbortories 214 Smer (per 1 popultion) 1.2 Culture (per 5 million popultion).6 Drug susceptibility testing (per 5 million popultion).4 Sites performing Xpert MTB/RIF 24 Is second-line drug susceptibility testing vilble? Yes, in country Finncing TB control 215 Ntionl TB progrmme budget (US$ millions) 29 % Funded domesticlly 6% % Funded interntionlly 66% % Unfunded 28% Mortlity (excludes HIV+TB) (rte per 1 poultion per yer) Prevlence (rte per 1 poultion) Incidence (rte per 1 poultion per yer) Number of ptients Tretment success rte (%) Notified (new nd relpse) Incidence Incidence (HIV+TB only) HIV-positive TB ptients on CPT on ART New Retretment HIV-positive RR-/MDR-TB XDR-TB 4 Dt re s reported to WHO. Estimtes of TB nd MDR-TB burden re produced by WHO in consulttion with countries. Rnges represent uncertinty intervls. b Includes cses with unknown previous TB tretment history. c Includes ptients dignosed before 214 nd ptients who were not lbortory-confirmed s hving RR-/MDR-TB. d Tretment outcomes were vilble for new pulmonry bcteriologiclly confirmed cses only. Totl budget (US$ millions) Funded domesticlly Funded interntionlly Unfunded Dt for ll yers cn be downloded from GLOBAL TUBERCULOSIS REPORT 215 n 135

147 Mynmr Popultion million Estimtes of TB burden 214 NUMBER (thousnds) RATE (per 1 popultion) Mortlity (excludes HIV+TB) 28 (2 37) 53 (38 7) Mortlity (HIV+TB only) 4.1 ( ) 7.7 ( ) Prevlence (includes HIV+TB) 24 (19 31) 457 ( ) Incidence (includes HIV+TB) 2 (18 22) 369 (334 46) Incidence (HIV+TB only) 19 (15 24) 36 (28 44) Cse detection, ll forms (%) 7 (64 78) Estimtes of MDR-TB burden 214 NEW RETREATMENT % of TB cses with MDR-TB 5 ( ) 27 (15 39) MDR-TB cses mong notified pulmonry TB cses 5 6 ( ) 3 4 ( ) TB cse notifictions 214 NEW b RELAPSE Pulmonry, bcteriologiclly confirmed Pulmonry, cliniclly dignosed Extrpulmonry Mortlity (excludes HIV+TB) (rte per 1 poultion per yer) Prevlence (rte per 1 poultion) Totl new nd relpse Previously treted, excluding relpses 3 65 Totl cses notified Among new nd relpse cses: (26%) cses ged under 15 yers; mle:femle rtio: 1.6 Reported cses of RR-/MDR-TB 214 NEW RETREATMENT TOTAL b Cses tested for RR-/MDR-TB (24%) (117%) Lbortory-confirmed RR-/MDR-TB cses Ptients strted on MDR-TB tretment c TB/HIV 214 NUMBER (%) TB ptients with known HIV sttus (4) HIV-positive TB ptients (11) HIV-positive TB ptients on co-trimoxzole preventive therpy (CPT) (73) HIV-positive TB ptients on ntiretrovirl therpy (ART) (9) HIV-positive people screened for TB HIV-positive people provided with IPT Tretment success rte nd cohort size (%) COHORT New cses registered in 213 (87) Previously treted cses registered in 213 (71) HIV-positive TB cses, ll types, registered in 213 RR-/MDR-TB cses strted on second-line tretment in 212 (79) 443 XDR-TB cses strted on second-line tretment in 212 Lbortories 214 Smer (per 1 popultion).9 Culture (per 5 million popultion).3 Drug susceptibility testing (per 5 million popultion).2 Sites performing Xpert MTB/RIF 38 Is second-line drug susceptibility testing vilble? Yes, outside country Finncing TB control 215 Ntionl TB progrmme budget (US$ millions) 36 % Funded domesticlly 11% % Funded interntionlly 67% % Unfunded 22% Dt re s reported to WHO. Estimtes of TB nd MDR-TB burden re produced by WHO in consulttion with countries. Rnges represent uncertinty intervls. b Includes cses with unknown previous TB tretment history. c Includes ptients dignosed before 214 nd ptients who were not lbortory-confirmed s hving RR-/MDR-TB. Incidence (rte per 1 poultion per yer) Number of ptients Tretment success rte (%) Totl budget (US$ millions) Notified (new nd relpse) Incidence Incidence (HIV+TB only) HIV-positive TB ptients on CPT on ART New Retretment HIV-positive RR-/MDR-TB XDR-TB Funded domesticlly Funded interntionlly Unfunded 136 n GLOBAL TUBERCULOSIS REPORT 215 Dt for ll yers cn be downloded from

148 Nigeri Popultion million Estimtes of TB burden 214 NUMBER (thousnds) RATE (per 1 popultion) Mortlity (excludes HIV+TB) 17 (91 28) 97 (51 156) Mortlity (HIV+TB only) 78 (53 11) 44 (3 61) Prevlence (includes HIV+TB) 59 (45 74) 33 ( ) Incidence (includes HIV+TB) 57 (34 87) 322 ( ) Incidence (HIV+TB only) 1 (59 16) 59 (33 92) Cse detection, ll forms (%) 15 (1 26) Estimtes of MDR-TB burden 214 NEW RETREATMENT % of TB cses with MDR-TB 2.9 (2.1 4) 14 (1 19) MDR-TB cses mong notified pulmonry TB cses 2 3 ( ) 1 (75 1 4) TB cse notifictions 214 NEW c RELAPSE Pulmonry, bcteriologiclly confirmed Pulmonry, cliniclly dignosed Extrpulmonry Mortlity (excludes HIV+TB) (rte per 1 poultion per yer) Prevlence (rte per 1 poultion) Totl new nd relpse Previously treted, excluding relpses 4 89 Totl cses notified Among new nd relpse cses: (6%) cses ged under 15 yers; mle:femle rtio: 1.5 Reported cses of RR-/MDR-TB 214 NEW RETREATMENT TOTAL b Cses tested for RR-/MDR-TB Lbortory-confirmed RR-/MDR-TB cses 798 Ptients strted on MDR-TB tretment c 423 TB/HIV 214 NUMBER (%) TB ptients with known HIV sttus (92) HIV-positive TB ptients (19) HIV-positive TB ptients on co-trimoxzole preventive therpy (CPT) (91) HIV-positive TB ptients on ntiretrovirl therpy (ART) (75) HIV-positive people screened for TB HIV-positive people provided with IPT Tretment success rte nd cohort size (%) COHORT New cses registered in 213 (86) Previously treted cses registered in 213 (83) 8 44 HIV-positive TB cses, ll types, registered in 213 (8) RR-/MDR-TB cses strted on second-line tretment in 212 (62) 154 XDR-TB cses strted on second-line tretment in 212 Lbortories 214 Smer (per 1 popultion) 1. Culture (per 5 million popultion).2 Drug susceptibility testing (per 5 million popultion).2 Sites performing Xpert MTB/RIF 96 Is second-line drug susceptibility testing vilble? Yes, in country Finncing TB control 215 Ntionl TB progrmme budget (US$ millions) 228 % Funded domesticlly 13% % Funded interntionlly 19% % Unfunded 68% Dt re s reported to WHO. Estimtes of TB nd MDR-TB burden re produced by WHO in consulttion with countries. Rnges represent uncertinty intervls. b Includes cses with unknown previous TB tretment history. c Includes ptients dignosed before 214 nd ptients who were not lbortory-confirmed s hving RR-/MDR-TB. Incidence (rte per 1 poultion per yer) Number of ptients Tretment success rte (%) Totl budget (US$ millions) Notified (new nd relpse) Incidence Incidence (HIV+TB only) HIV-positive TB ptients on CPT on ART New Retretment HIV-positive RR-/MDR-TB XDR-TB Funded domesticlly Funded interntionlly Unfunded Dt for ll yers cn be downloded from GLOBAL TUBERCULOSIS REPORT 215 n 137

149 Pkistn Popultion million Estimtes of TB burden 214 NUMBER (thousnds) RATE (per 1 popultion) Mortlity (excludes HIV+TB) 48 (11 11) 26 (6 61) Mortlity (HIV+TB only) 1.3 ( ).68 (.41 1) Prevlence (includes HIV+TB) 63 (53 74) 341 (285 42) Incidence (includes HIV+TB) 5 (37 65) 27 (21 35) Incidence (HIV+TB only) 6.4 ( ) 3.4 ( ) Cse detection, ll forms (%) 62 (48 83) Estimtes of MDR-TB burden 214 NEW RETREATMENT % of TB cses with MDR-TB 3.7 (2.5 5) 18 (13 23) MDR-TB cses mong notified pulmonry TB cses 9 ( ) 2 9 ( ) TB cse notifictions 214 NEW b RELAPSE Pulmonry, bcteriologiclly confirmed Pulmonry, cliniclly dignosed Extrpulmonry Mortlity (excludes HIV+TB) (rte per 1 poultion per yer) Prevlence (rte per 1 poultion) Totl new nd relpse Previously treted, excluding relpses 8 16 Totl cses notified Among new nd relpse cses: (9%) cses ged under 15 yers; mle:femle rtio: 1. Reported cses of RR-/MDR-TB 214 NEW RETREATMENT TOTAL b Cses tested for RR-/MDR-TB 361 (<1%) (72%) Lbortory-confirmed RR-/MDR-TB cses Ptients strted on MDR-TB tretment c TB/HIV 214 NUMBER (%) TB ptients with known HIV sttus (3) HIV-positive TB ptients 9 (<1) HIV-positive TB ptients on co-trimoxzole preventive therpy (CPT) 9 (1) HIV-positive TB ptients on ntiretrovirl therpy (ART) 9 (1) HIV-positive people screened for TB HIV-positive people provided with IPT Tretment success rte nd cohort size (%) COHORT New nd relpse cses registered in 213 (93) Previously treted cses, excluding relpse, registered in 213 (8) HIV-positive TB cses, ll types, registered in 213 (81) 37 RR-/MDR-TB cses strted on second-line tretment in 212 (71) 858 XDR-TB cses strted on second-line tretment in 212 (32) 41 Lbortories 214 Smer (per 1 popultion).8 Culture (per 5 million popultion).3 Drug susceptibility testing (per 5 million popultion).1 Sites performing Xpert MTB/RIF 42 Is second-line drug susceptibility testing vilble? Yes, in country Finncing TB control 215 Ntionl TB progrmme budget (US$ millions) 5 % Funded domesticlly 17% % Funded interntionlly 6% % Unfunded 23% Dt re s reported to WHO. Estimtes of TB nd MDR-TB burden re produced by WHO in consulttion with countries. Rnges represent uncertinty intervls. b Includes cses with unknown previous TB tretment history. c Includes ptients dignosed before 214 nd ptients who were not lbortory-confirmed s hving RR-/MDR-TB. Incidence (rte per 1 poultion per yer) Number of ptients Tretment success rte (%) Totl budget (US$ millions) Notified (new nd relpse) Incidence Incidence (HIV+TB only) HIV-positive TB ptients on CPT on ART New Retretment New nd relpse Retretment excluding relpse HIV-positive RR-/MDR-TB XDR-TB Funded domesticlly Funded interntionlly Unfunded 138 n GLOBAL TUBERCULOSIS REPORT 215 Dt for ll yers cn be downloded from

150 Philippines Popultion million Estimtes of TB burden 214 NUMBER (thousnds) RATE (per 1 popultion) Mortlity (excludes HIV+TB) 1 (9 11) 1 (9.1 11) Mortlity (HIV+TB only).8 (.55.11).8 (.6.11) Prevlence (includes HIV+TB) 41 (36 47) 417 ( ) Incidence (includes HIV+TB) 29 (25 32) 288 ( ) Incidence (HIV+TB only) 2.5 (2 3.2) 2.6 (2 3.2) Cse detection, ll forms (%) 85 (76 97) Estimtes of MDR-TB burden 214 NEW RETREATMENT % of TB cses with MDR-TB 2 ( ) 21 (16 29) MDR-TB cses mong notified pulmonry TB cses 4 6 ( ) 6 5 ( ) TB cse notifictions 214 NEW c RELAPSE Pulmonry, bcteriologiclly confirmed Pulmonry, cliniclly dignosed Extrpulmonry Mortlity (excludes HIV+TB) (rte per 1 poultion per yer) Prevlence (rte per 1 poultion) Totl new nd relpse Previously treted, excluding relpses Totl cses notified Among new nd relpse cses: (12%) cses ged under 15 yers; mle:femle rtio: 1.8 Reported cses of RR-/MDR-TB 214 NEW RETREATMENT TOTAL b Cses tested for RR-/MDR-TB (5%) (67%) Lbortory-confirmed RR-/MDR-TB cses 3 Ptients strted on MDR-TB tretment c 2 68 TB/HIV 214 NUMBER (%) TB ptients with known HIV sttus (2) HIV-positive TB ptients 18 (<1) HIV-positive TB ptients on co-trimoxzole preventive therpy (CPT) 2 (19) HIV-positive TB ptients on ntiretrovirl therpy (ART) 53 (49) HIV-positive people screened for TB HIV-positive people provided with IPT Tretment success rte nd cohort size (%) COHORT New nd relpse cses registered in 213 (9) Previously treted cses, excluding relpse, registered in 213 (86) HIV-positive TB cses, ll types, registered in 213 RR-/MDR-TB cses strted on second-line tretment in 212 (43) XDR-TB cses strted on second-line tretment in 212 (1) 1 Lbortories 214 Smer (per 1 popultion) 2.6 Culture (per 5 million popultion) 1.1 Drug susceptibility testing (per 5 million popultion).2 Sites performing Xpert MTB/RIF 84 Is second-line drug susceptibility testing vilble? Yes, in country Finncing TB control 215 Ntionl TB progrmme budget (US$ millions) 16 % Funded domesticlly 23% % Funded interntionlly 39% % Unfunded 37% Dt re s reported to WHO. Estimtes of TB nd MDR-TB burden re produced by WHO in consulttion with countries. Rnges represent uncertinty intervls. b Includes cses with unknown previous TB tretment history. c Includes ptients dignosed before 214 nd ptients who were not lbortory-confirmed s hving RR-/MDR-TB. Incidence (rte per 1 poultion per yer) Number of ptients Tretment success rte (%) Totl budget (US$ millions) Notified (new nd relpse) Incidence Incidence (HIV+TB only) HIV-positive TB ptients on CPT on ART New Retretment New nd relpse Retretment excluding relpse HIV-positive RR-/MDR-TB XDR-TB Funded domesticlly Funded interntionlly Unfunded Dt for ll yers cn be downloded from GLOBAL TUBERCULOSIS REPORT 215 n 139

151 Russin Federtion Popultion million Estimtes of TB burden b 214 NUMBER (thousnds) RATE (per 1 popultion) Mortlity (excludes HIV+TB) 16 (15 16) 11 (11 11) Mortlity (HIV+TB only) 1.1 ( ).73 (.58.91) Prevlence (includes HIV+TB) 16 (7 27) 19 (49 192) Incidence (includes HIV+TB) 12 (11 13) 84 (76 93) Incidence (HIV+TB only) 5.5 ( ) 3.8 ( ) Cse detection, ll forms (%) 85 (77 94) Estimtes of MDR-TB burden b 214 NEW RETREATMENT % of TB cses with MDR-TB 19 (14 25) 49 (4 59) MDR-TB cses mong notified pulmonry TB cses 15 (11 19 ) 24 (19 29 ) TB cse notifictions 214 NEW c RELAPSE Pulmonry, bcteriologiclly confirmed Pulmonry, cliniclly dignosed Extrpulmonry Totl new nd relpse Previously treted, excluding relpses Totl cses notified Among new nd relpse cses: (3%) cses ged under 15 yers; mle:femle rtio: 2.3 Reported cses of RR-/MDR-TB 214 NEW RETREATMENT TOTAL b Cses tested for RR-/MDR-TB (84%) (28%) Lbortory-confirmed RR-/MDR-TB cses Ptients strted on MDR-TB tretment d TB/HIV 214 NUMBER (%) TB ptients with known HIV sttus e HIV-positive TB ptients HIV-positive TB ptients on co-trimoxzole preventive therpy (CPT) HIV-positive TB ptients on ntiretrovirl therpy (ART) HIV-positive people screened for TB HIV-positive people provided with IPT Tretment success rte nd cohort size (%) COHORT New nd relpse cses registered in 213 (68) Previously treted cses, excluding relpse, registered in 213 (39) HIV-positive TB cses, ll types, registered in 213 RR-/MDR-TB cses strted on second-line tretment in 212 (4) XDR-TB cses strted on second-line tretment in 212 (26) Lbortories 214 Smer (per 1 popultion) 3.7 Culture (per 5 million popultion) 14.1 Drug susceptibility testing (per 5 million popultion) 1.4 Sites performing Xpert MTB/RIF 96 Is second-line drug susceptibility testing vilble? Yes, in country Finncing TB control 215 Ntionl TB progrmme budget (US$ millions) % Funded domesticlly 1% % Funded interntionlly <1% % Unfunded % Dt re s reported to WHO. Estimtes of TB nd MDR-TB burden re produced by WHO in consulttion with countries. UN Popultion Division estimtes re lower thn the popultion registered by the Federl Stte Sttistics Service of the Russin Federtion. b Rnges represent uncertinty intervls. c Includes cses with unknown previous TB tretment history. d Includes ptients dignosed before 214 nd ptients who were not lbortory-confirmed s hving RR-/MDR-TB. e The reported number of TB ptients with known HIV sttus is for new TB ptients in the civilin sector only. It ws not possible to clculte the percentge of ll TB ptients with known HIV sttus. Mortlity (excludes HIV+TB) (rte per 1 poultion per yer) Prevlence (rte per 1 poultion) Incidence (rte per 1 poultion per yer) Number of ptients Tretment success rte (%) Totl budget (US$ millions) Notified (new nd relpse) Incidence Incidence (HIV+TB only) HIV-positive TB ptients on CPT on ART New Retretment New nd relpse Retretment excluding relpse HIV-positive RR-/MDR-TB XDR-TB Funded domesticlly Funded interntionlly Unfunded 14 n GLOBAL TUBERCULOSIS REPORT 215 Dt for ll yers cn be downloded from

152 South Afric Popultion million Estimtes of TB burden 214 NUMBER (thousnds) RATE (per 1 popultion) Mortlity (excludes HIV+TB) 24 (22 26) 44 (41 48) Mortlity (HIV+TB only) 72 (58 89) 134 (17 164) Prevlence (includes HIV+TB) 38 (21 59) 696 ( ) Incidence (includes HIV+TB) 45 (4 51) 834 ( ) Incidence (HIV+TB only) 27 (24 31) 59 ( ) Cse detection, ll forms (%) 68 (61 77) Estimtes of MDR-TB burden 214 NEW RETREATMENT % of TB cses with MDR-TB 1.8 ( ) 6.7 ( ) MDR-TB cses mong notified pulmonry TB cses 4 7 ( ) 1 5 ( ) TB cse notifictions 214 NEW c RELAPSE Pulmonry, bcteriologiclly confirmed Pulmonry, cliniclly dignosed Extrpulmonry Totl new nd relpse Previously treted, excluding relpses Totl cses notified Among new nd relpse cses: (1%) cses ged under 15 yers; mle:femle rtio: 1.3 Reported cses of RR-/MDR-TB 214 NEW RETREATMENT TOTAL b Cses tested for RR-/MDR-TB Lbortory-confirmed RR-/MDR-TB cses Ptients strted on MDR-TB tretment c TB/HIV 214 NUMBER (%) TB ptients with known HIV sttus (93) HIV-positive TB ptients (61) HIV-positive TB ptients on co-trimoxzole preventive therpy (CPT) (86) HIV-positive TB ptients on ntiretrovirl therpy (ART) (79) HIV-positive people screened for TB HIV-positive people provided with IPT Tretment success rte nd cohort size (%) COHORT New nd relpse cses registered in 213 (78) Previously treted cses, excluding relpse, registered in 213 (69) HIV-positive TB cses, ll types, registered in 213 (76) RR-/MDR-TB cses strted on second-line tretment in 212 (49) 8 84 XDR-TB cses strted on second-line tretment in 212 (2) 67 Lbortories 214 Smer (per 1 popultion).4 Culture (per 5 million popultion) 1.1 Drug susceptibility testing (per 5 million popultion) 1.1 Sites performing Xpert MTB/RIF 27 Is second-line drug susceptibility testing vilble? Yes, in country Finncing TB control 215 Ntionl TB progrmme budget (US$ millions) 248 % Funded domesticlly 84% % Funded interntionlly 8% % Unfunded 8% Dt re s reported to WHO. Estimtes of TB nd MDR-TB burden re produced by WHO in consulttion with countries. Rnges represent uncertinty intervls. b Includes cses with unknown previous TB tretment history. c Includes ptients dignosed before 214 nd ptients who were not lbortory-confirmed s hving RR-/MDR-TB. Mortlity (excludes HIV+TB) (rte per 1 poultion per yer) Prevlence (rte per 1 poultion) Incidence (rte per 1 poultion per yer) Number of ptients Tretment success rte (%) Totl budget (US$ millions) Notified (new nd relpse) Incidence (HIV+TB only) Incidence HIV-positive TB ptients on CPT on ART New Retretment New nd relpse Retretment excluding relpse HIV-positive RR-/MDR-TB XDR-TB Funded domesticlly Funded interntionlly Unfunded Dt for ll yers cn be downloded from GLOBAL TUBERCULOSIS REPORT 215 n 141

153 Thilnd Popultion million Estimtes of TB burden 214 NUMBER (thousnds) RATE (per 1 popultion) Mortlity (excludes HIV+TB) 7.4 (3.9 12) 11 (5.7 18) Mortlity (HIV+TB only) 4.5 ( ) 6.6 (3.4 11) Prevlence (includes HIV+TB) 16 (11 22) 236 ( ) Incidence (includes HIV+TB) 12 (61 19) 171 (9 276) Incidence (HIV+TB only) 15 (7.8 24) 22 (12 36) Cse detection, ll forms (%) 59 (36 11) Estimtes of MDR-TB burden 214 NEW RETREATMENT % of TB cses with MDR-TB 2 ( ) 19 (14 25) MDR-TB cses mong notified pulmonry TB cses 1 1 (78 1 6) 1 1 (8 1 5) TB cse notifictions 214 NEW b RELAPSE Pulmonry, bcteriologiclly confirmed Pulmonry, cliniclly dignosed Extrpulmonry Mortlity (excludes HIV+TB) (rte per 1 poultion per yer) Prevlence (rte per 1 poultion) Totl new nd relpse Previously treted, excluding relpses Totl cses notified Among new cses: 119 (<1%) cses ged under 15 yers; mle:femle rtio: 2.5 Reported cses of RR-/MDR-TB 214 NEW RETREATMENT TOTAL b Cses tested for RR-/MDR-TB 4 37 (13%) 2 29 (38%) 9 58 Lbortory-confirmed RR-/MDR-TB cses 56 Ptients strted on MDR-TB tretment c TB/HIV 214 NUMBER (%) TB ptients with known HIV sttus 5 67 (71) HIV-positive TB ptients (13) HIV-positive TB ptients on co-trimoxzole preventive therpy (CPT) (64) HIV-positive TB ptients on ntiretrovirl therpy (ART) (69) HIV-positive people screened for TB HIV-positive people provided with IPT Tretment success rte nd cohort size (%) COHORT New nd relpse cses registered in 213 (81) Previously treted cses, excluding relpse, registered in 213 (66) HIV-positive TB cses, ll types, registered in 213 (67) RR-/MDR-TB cses strted on second-line tretment in 212 XDR-TB cses strted on second-line tretment in 212 Lbortories 214 Smer (per 1 popultion) 1.3 Culture (per 5 million popultion) 3.9 Drug susceptibility testing (per 5 million popultion) 1.5 Sites performing Xpert MTB/RIF 14 Is second-line drug susceptibility testing vilble? Yes, in country Finncing TB control 215 Ntionl TB progrmme budget (US$ millions) 32 % Funded domesticlly 52% % Funded interntionlly 11% % Unfunded 37% Dt re s reported to WHO. Estimtes of TB nd MDR-TB burden re produced by WHO in consulttion with countries. Rnges represent uncertinty intervls. b Includes cses with unknown previous TB tretment history. c Includes ptients dignosed before 214 nd ptients who were not lbortory-confirmed s hving RR-/MDR-TB. Incidence (rte per 1 poultion per yer) Number of ptients Tretment success rte (%) Totl budget (US$ millions) Notified (new nd relpse) Incidence Incidence (HIV+TB only) HIV-positive TB ptients on CPT on ART New Retretment New nd relpse Retretment excluding relpse HIV-positive RR-/MDR-TB XDR-TB Funded domesticlly Funded interntionlly Unfunded 142 n GLOBAL TUBERCULOSIS REPORT 215 Dt for ll yers cn be downloded from

154 Ugnd Popultion million Estimtes of TB burden 214 NUMBER (thousnds) RATE (per 1 popultion) Mortlity (excludes HIV+TB) 4.5 ( ) 12 (8.4 16) Mortlity (HIV+TB only) 6.4 (5 8.1) 17 (13 21) Prevlence (includes HIV+TB) 6 (33 95) 159 (87 253) Incidence (includes HIV+TB) 61 (53 69) 161 ( ) Incidence (HIV+TB only) 28 (24 32) 73 (63 84) Cse detection, ll forms (%) 72 (64 83) Estimtes of MDR-TB burden 214 NEW RETREATMENT % of TB cses with MDR-TB 1.4 (.6 2.2) 12 (6.8 19) MDR-TB cses mong notified pulmonry TB cses 53 (23 83) 48 (27 77) TB cse notifictions 214 NEW c RELAPSE Pulmonry, bcteriologiclly confirmed Pulmonry, cliniclly dignosed Extrpulmonry Mortlity (excludes HIV+TB) (rte per 1 poultion per yer) Prevlence (rte per 1 poultion) Totl new nd relpse Previously treted, excluding relpses Totl cses notified Among new nd relpse cses: (8%) cses ged under 15 yers; mle:femle rtio: 1.8 Reported cses of RR-/MDR-TB 214 NEW RETREATMENT TOTAL b Cses tested for RR-/MDR-TB (8%) 737 (18%) Lbortory-confirmed RR-/MDR-TB cses 255 Ptients strted on MDR-TB tretment c 213 TB/HIV 214 NUMBER (%) TB ptients with known HIV sttus (95) HIV-positive TB ptients (45) HIV-positive TB ptients on co-trimoxzole preventive therpy (CPT) (98) HIV-positive TB ptients on ntiretrovirl therpy (ART) (81) HIV-positive people screened for TB HIV-positive people provided with IPT Tretment success rte nd cohort size (%) COHORT New nd relpse cses registered in 213 (75) Previously treted cses, excluding relpse, registered in 213 (67) HIV-positive TB cses, ll types, registered in 213 (73) RR-/MDR-TB cses strted on second-line tretment in 212 (8) 41 XDR-TB cses strted on second-line tretment in 212 Lbortories 214 Smer (per 1 popultion) 3.6 Culture (per 5 million popultion).7 Drug susceptibility testing (per 5 million popultion).7 Sites performing Xpert MTB/RIF 74 Is second-line drug susceptibility testing vilble? Yes, in country Finncing TB control 215 Ntionl TB progrmme budget (US$ millions) 24 % Funded domesticlly 1% % Funded interntionlly 69% % Unfunded 21% Dt re s reported to WHO. Estimtes of TB nd MDR-TB burden re produced by WHO in consulttion with countries. Rnges represent uncertinty intervls. b Includes cses with unknown previous TB tretment history. c Includes ptients dignosed before 214 nd ptients who were not lbortory-confirmed s hving RR-/MDR-TB. Incidence (rte per 1 poultion per yer) Number of ptients Tretment success rte (%) Totl budget (US$ millions) Notified (new nd relpse) Incidence Incidence (HIV+TB only) HIV-positive TB ptients on CPT on ART New Retretment New nd relpse Retretment excluding relpse HIV-positive RR-/MDR-TB XDR-TB Funded domesticlly Funded interntionlly Unfunded Dt for ll yers cn be downloded from GLOBAL TUBERCULOSIS REPORT 215 n 143

155 United Republic of Tnzni Popultion million Estimtes of TB burden 214 NUMBER (thousnds) RATE (per 1 popultion) Mortlity (excludes HIV+TB) 3 (13 54) 58 (26 14) Mortlity (HIV+TB only) 28 (15 43) 53 (3 84) Prevlence (includes HIV+TB) 27 (11 51) 528 ( ) Incidence (includes HIV+TB) 17 (8 29) 327 ( ) Incidence (HIV+TB only) 62 (29 11) 12 (56 28) Cse detection, ll forms (%) 36 (21 77) Estimtes of MDR-TB burden 214 NEW RETREATMENT % of TB cses with MDR-TB 1.1 (.5 2) 3.1 (.9 7.9) MDR-TB cses mong notified pulmonry TB cses 52 (23 94) 8 (23 2) TB cse notifictions 214 NEW b RELAPSE Pulmonry, bcteriologiclly confirmed Pulmonry, cliniclly dignosed Extrpulmonry 13 6 Totl new nd relpse Previously treted, excluding relpses 1 58 Totl cses notified Among new nd relpse cses: (1%) cses ged under 15 yers; mle:femle rtio: 1.5 Reported cses of RR-/MDR-TB 214 NEW RETREATMENT TOTAL b Cses tested for RR-/MDR-TB 9 56 (4%) 882 (34%) Lbortory-confirmed RR-/MDR-TB cses 516 Ptients strted on MDR-TB tretment c 143 TB/HIV 214 NUMBER (%) TB ptients with known HIV sttus (91) HIV-positive TB ptients 2 55 (35) HIV-positive TB ptients on co-trimoxzole preventive therpy (CPT) (97) HIV-positive TB ptients on ntiretrovirl therpy (ART) (83) HIV-positive people screened for TB HIV-positive people provided with IPT Tretment success rte nd cohort size (%) COHORT New nd relpse cses registered in 213 (91) Previously treted cses, excluding relpse, registered in 213 (79) HIV-positive TB cses, ll types, registered in 213 (72) 2 32 RR-/MDR-TB cses strted on second-line tretment in 212 (73) 45 XDR-TB cses strted on second-line tretment in 212 Lbortories 214 Smer (per 1 popultion) 1.8 Culture (per 5 million popultion).4 Drug susceptibility testing (per 5 million popultion) <.1 Sites performing Xpert MTB/RIF 59 Is second-line drug susceptibility testing vilble? Yes, in country Finncing TB control 215 Ntionl TB progrmme budget (US$ millions) 67 % Funded domesticlly % Funded interntionlly % Unfunded 1% Dt re s reported to WHO. Estimtes of TB nd MDR-TB burden re produced by WHO in consulttion with countries. Rnges represent uncertinty intervls. b Includes cses with unknown previous TB tretment history. c Includes ptients dignosed before 214 nd ptients who were not lbortory-confirmed s hving RR-/MDR-TB. Mortlity (excludes HIV+TB) (rte per 1 poultion per yer) Prevlence (rte per 1 poultion) Incidence (rte per 1 poultion per yer) Number of ptients Tretment success rte (%) Totl budget (US$ millions) Notified (new nd relpse) Incidence Incidence (HIV+TB only) HIV-positive TB ptients on CPT on ART New Retretment New nd relpse Retretment excluding relpse HIV-positive RR-/MDR-TB XDR-TB Funded domesticlly Funded interntionlly Unfunded 144 n GLOBAL TUBERCULOSIS REPORT 215 Dt for ll yers cn be downloded from

156 Viet Nm Popultion million Estimtes of TB burden 214 NUMBER (thousnds) RATE (per 1 popultion) Mortlity (excludes HIV+TB) 17 (11 23) 18 (12 25) Mortlity (HIV+TB only) 1.9 ( ) 2 ( ) Prevlence (includes HIV+TB) 18 (76 33) 198 (83 362) Incidence (includes HIV+TB) 13 (11 15) 14 ( ) Incidence (HIV+TB only) 7 ( ) 7.6 ( ) Cse detection, ll forms (%) 77 (65 94) Estimtes of MDR-TB burden 214 NEW RETREATMENT % of TB cses with MDR-TB 4 ( ) 23 (17 3) MDR-TB cses mong notified pulmonry TB cses 3 ( ) 2 1 ( ) TB cse notifictions 214 NEW c RELAPSE Pulmonry, bcteriologiclly confirmed Pulmonry, cliniclly dignosed Extrpulmonry Mortlity (excludes HIV+TB) (rte per 1 poultion per yer) Prevlence (rte per 1 poultion) Totl new nd relpse Previously treted, excluding relpses Totl cses notified Among new cses: 144 (<1%) cses ged under 15 yers; mle:femle rtio: 3. Reported cses of RR-/MDR-TB 214 NEW RETREATMENT TOTAL b Cses tested for RR-/MDR-TB (6%) (96%) Lbortory-confirmed RR-/MDR-TB cses Ptients strted on MDR-TB tretment c TB/HIV 214 NUMBER (%) TB ptients with known HIV sttus (73) HIV-positive TB ptients (5) HIV-positive TB ptients on co-trimoxzole preventive therpy (CPT) (76) HIV-positive TB ptients on ntiretrovirl therpy (ART) (73) HIV-positive people screened for TB HIV-positive people provided with IPT Tretment success rte nd cohort size (%) COHORT New nd relpse cses registered in 213 (89) Previously treted cses, excluding relpse, registered in 213 HIV-positive TB cses, ll types, registered in 213 (71) RR-/MDR-TB cses strted on second-line tretment in 212 (71) 713 XDR-TB cses strted on second-line tretment in 212 Lbortories 214 Smer (per 1 popultion) 1.1 Culture (per 5 million popultion) 1.2 Drug susceptibility testing (per 5 million popultion).1 Sites performing Xpert MTB/RIF 3 Is second-line drug susceptibility testing vilble? Yes, in nd outside country Finncing TB control 215 Ntionl TB progrmme budget (US$ millions) 66 % Funded domesticlly 1% % Funded interntionlly 17% % Unfunded 72% Dt re s reported to WHO. Estimtes of TB nd MDR-TB burden re produced by WHO in consulttion with countries. Rnges represent uncertinty intervls. b Includes cses with unknown previous TB tretment history. c Includes ptients dignosed before 214 nd ptients who were not lbortory-confirmed s hving RR-/MDR-TB. Incidence (rte per 1 poultion per yer) Number of ptients Tretment success rte (%) Totl budget (US$ millions) Notified (new nd relpse) Incidence Incidence (HIV+TB only) HIV-positive TB ptients on CPT on ART New Retretment New nd relpse Retretment excluding relpse HIV-positive RR-/MDR-TB XDR-TB Funded domesticlly Funded interntionlly Unfunded Dt for ll yers cn be downloded from GLOBAL TUBERCULOSIS REPORT 215 n 145

157 Zimbbwe Popultion million Estimtes of TB burden 214 NUMBER (thousnds) RATE (per 1 popultion) Mortlity (excludes HIV+TB) 2.3 ( ) 15 (9.5 22) Mortlity (HIV+TB only) 5.2 ( ) 34 (21 51) Prevlence (includes HIV+TB) 44 (24 71) 292 ( ) Incidence (includes HIV+TB) 42 (29 58) 278 ( ) Incidence (HIV+TB only) 25 (17 35) 167 ( ) Cse detection, ll forms (%) 7 (51 1) Estimtes of MDR-TB burden 214 NEW RETREATMENT % of TB cses with MDR-TB 2.2 (.3 4.1) 11 (6.2 16) MDR-TB cses mong notified pulmonry TB cses 54 (73 1 ) 41 (23 59) TB cse notifictions 214 NEW b RELAPSE Pulmonry, bcteriologiclly confirmed Pulmonry, cliniclly dignosed Extrpulmonry 3 99 Mortlity (excludes HIV+TB) (rte per 1 poultion per yer) Prevlence (rte per 1 poultion) Totl new nd relpse Previously treted, excluding relpses Totl cses notified Among new nd relpse cses: 2 29 (8%) cses ged under 15 yers; mle:femle rtio: 1.3 Reported cses of RR-/MDR-TB 214 NEW RETREATMENT TOTAL b Cses tested for RR-/MDR-TB 341 (3%) 237 (6%) Lbortory-confirmed RR-/MDR-TB cses 412 Ptients strted on MDR-TB tretment c 381 TB/HIV 214 NUMBER (%) TB ptients with known HIV sttus (89) HIV-positive TB ptients (68) HIV-positive TB ptients on co-trimoxzole preventive therpy (CPT) 18 2 (94) HIV-positive TB ptients on ntiretrovirl therpy (ART) (86) HIV-positive people screened for TB HIV-positive people provided with IPT 3 42 Tretment success rte nd cohort size (%) COHORT New cses registered in 213 (8) Previously treted cses registered in 213 HIV-positive TB cses, ll types, registered in 213 RR-/MDR-TB cses strted on second-line tretment in 212 (75) 234 XDR-TB cses strted on second-line tretment in 212 Lbortories 214 Smer (per 1 popultion) 1.4 Culture (per 5 million popultion).7 Drug susceptibility testing (per 5 million popultion).7 Sites performing Xpert MTB/RIF 62 Is second-line drug susceptibility testing vilble? Yes, in nd outside country Finncing TB control 215 Ntionl TB progrmme budget (US$ millions) 28 % Funded domesticlly 7% % Funded interntionlly 59% % Unfunded 34% Dt re s reported to WHO. Estimtes of TB nd MDR-TB burden re produced by WHO in consulttion with countries. Rnges represent uncertinty intervls. b Includes cses with unknown previous TB tretment history. c Includes ptients dignosed before 214 nd ptients who were not lbortory-confirmed s hving RR-/MDR-TB. Incidence (rte per 1 poultion per yer) Number of ptients Tretment success rte (%) Totl budget (US$ millions) Notified (new nd relpse) Incidence Incidence (HIV+TB only) HIV-positive TB ptients on CPT on ART New Retretment HIV-positive RR-/MDR-TB XDR-TB Funded domesticlly Funded interntionlly Unfunded 146 n GLOBAL TUBERCULOSIS REPORT 215 Dt for ll yers cn be downloded from

158 A N N E X 3 Regionl profiles FOR 6 WHO REGIONS Dt re s reported to WHO. Estimtes of TB nd MDR-TB burden re produced by WHO in consulttion with countries. Rnges represent uncertinty intervls. b Includes cses with unknown previous TB tretment history. c Includes ptients dignosed before 214 nd ptients who were not lbortory-confirmed s hving RR-/MDR-TB. Dt for ll yers cn be downloded from GLOBAL TUBERCULOSIS REPORT 215 n 147

159 148 n GLOBAL TUBERCULOSIS REPORT 215 Dt for ll yers cn be downloded from

160 WHO Africn Region Popultion million WHO MEMBER STATES 47 Estimtes of TB burden 214 NUMBER (thousnds) RATE (per 1 popultion) Mortlity (excludes HIV+TB) 45 (35 56) 46 (36 58) Mortlity (HIV+TB only) 31 (27 35) 32 (28 36) Prevlence (includes HIV+TB) 3 2 ( ) 33 ( ) Incidence (includes HIV+TB) 2 7 (2 4 3 ) 281 (25 313) Incidence (HIV+TB only) 87 (79 95) 9 (82 99) Cse detection, ll forms (%) 48 (43 54) Estimtes of MDR-TB burden 214 NEW RETREATMENT % of TB cses with MDR-TB 2.1 (.5 3.7) 11 (6.7 16) MDR-TB cses mong notified pulmonry TB cses 22 ( ) 11 ( ) TB cse notifictions 214 NEW b RELAPSE Pulmonry, bcteriologiclly confirmed Pulmonry, cliniclly dignosed Extrpulmonry Totl new nd relpse Previously treted, excluding relpses Totl cses notified Among reported new nd relpse c cses disggregted by ge, (8.6%) cses were ged < 15 yers Among reported new nd relpse c cses disggregted by sex, mle:femle rtio = 1.4 Reported cses of RR-/MDR-TB 214 NEW RETREATMENT TOTAL b Cses tested for RR-/MDR-TB 4 94 (6.4%) (33%) Lbortory-confirmed RR-/MDR-TB cses Ptients strted on MDR-TB tretment d TB/HIV 214 NUMBER (%) e TB ptients with known HIV sttus HIV-positive TB ptients HIV-positive TB ptients on co-trimoxzole preventive therpy (CPT) HIV-positive TB ptients on ntiretrovirl therpy (ART) HIV-positive people screened for TB HIV-positive people provided with IPT Tretment success rte nd cohort size (%) COHORT New nd relpse c cses registered in Previously treted cses, excluding relpse, registered in HIV-positive TB cses, ll types, registered in RR-/MDR-TB cses strted on second-line tretment in XDR-TB cses strted on second-line tretment in Lbortories 214 Smer (per 1 popultion) 1 28 out of 44 Culture (per 5 million popultion) 1 15 out of 44 Drug susceptibility testing (per 5 million popultion) 1 1 out of 44 NUMBER OF MEMBER STATES f Finncing TB control (low- nd middle-income countries) f,g 215 Ntionl TB progrmme budget (US$ millions) 1 8 % Funded domesticlly 34 % Funded interntionlly 29 % Unfunded 37 Dt re s reported to WHO. Estimtes of TB nd MDR-TB burden re produced by WHO in consulttion with countries. Rnges represent uncertinty intervls. b Includes cses with unknown previous TB tretment history. c Some countries reported on new cses only. d Includes ptients dignosed before 214 nd ptients who were not lbortory-confirmed s hving RR-/MDR-TB. e Clcultions exclude countries with missing numertors or denomintors. f Dt re not collected from ll Member Sttes. g Finncing indictors exclude funding for generl helthcre services provided outside NTPs. Mortlity (excludes HIV+TB) (rte per 1 poultion per yer) Prevlence (rte per 1 poultion) Incidence (rte per 1 poultion per yer) Number of TB ptients (thousnds) Tretment success rte (%) Totl budget (US$ millions constnt 215) Notified (new nd relpse) Incidence (HIV+TB only) Incidence HIV-positive TB ptients on CPT on ART New, or new nd relpse Retretment, or retretment excluding relpse HIV-positive RR-/MDR-TB XDR-TB Funded domesticlly Funded interntionlly Unfunded Dt for ll yers cn be downloded from GLOBAL TUBERCULOSIS REPORT 215 n 149

161 WHO/PAHO Region of the Americs Popultion million WHO MEMBER STATES 35 OTHER COUNTRIES AND TERRITORIES 11 Estimtes of TB burden 214 NUMBER (thousnds) RATE (per 1 popultion) Mortlity (excludes HIV+TB) 17 (16 18) 1.7 ( ) Mortlity (HIV+TB only) 6 (5 7).61 (.53.69) Prevlence (includes HIV+TB) 35 (27 44) 36 (28 45) Incidence (includes HIV+TB) 28 (27 29) 28 (27 29) Incidence (HIV+TB only) 36 (34 38) 3.7 ( ) Cse detection, ll forms (%) 77 (75 81) Estimtes of MDR-TB burden 214 NEW RETREATMENT % of TB cses with MDR-TB 2.4 ( ) 11 (6.5 16) MDR-TB cses mong notified pulmonry TB cses 4 ( ) 3 ( ) TB cse notifictions 214 NEW b RELAPSE Pulmonry, bcteriologiclly confirmed Pulmonry, cliniclly dignosed Extrpulmonry Totl new nd relpse Previously treted, excluding relpses Totl cses notified Among reported new nd relpse c cses disggregted by ge, (5.%) cses were ged < 15 yers Among reported new nd relpse c cses disggregted by sex, mle:femle rtio = 1.7 Reported cses of RR-/MDR-TB 214 NEW RETREATMENT TOTAL b Cses tested for RR-/MDR-TB (24%) (32%) Lbortory-confirmed RR-/MDR-TB cses Ptients strted on MDR-TB tretment d TB/HIV 214 NUMBER (%) e TB ptients with known HIV sttus HIV-positive TB ptients HIV-positive TB ptients on co-trimoxzole preventive therpy (CPT) HIV-positive TB ptients on ntiretrovirl therpy (ART) HIV-positive people screened for TB HIV-positive people provided with IPT Tretment success rte nd cohort size (%) COHORT New nd relpse c cses registered in Previously treted cses, excluding relpse, registered in HIV-positive TB cses, ll types, registered in RR-/MDR-TB cses strted on second-line tretment in XDR-TB cses strted on second-line tretment in Lbortories 214 Smer (per 1 popultion) 1 19 out of 23 Culture (per 5 million popultion) 1 2 out of 23 Drug susceptibility testing (per 5 million popultion) 1 6 out of 23 NUMBER OF MEMBER STATES f Finncing TB control (low- nd middle-income countries) f,g 215 Ntionl TB progrmme budget (US$ millions) 285 % Funded domesticlly 71 % Funded interntionlly 7.3 % Unfunded 22 Dt re s reported to WHO. Estimtes of TB nd MDR-TB burden re produced by WHO in consulttion with countries. Rnges represent uncertinty intervls. b Includes cses with unknown previous TB tretment history. c Some countries reported on new cses only. d Includes ptients dignosed before 214 nd ptients who were not lbortory-confirmed s hving RR-/MDR-TB. e Clcultions exclude countries with missing numertors or denomintors. f Dt re not collected from ll Member Sttes. g Finncing indictors exclude funding for generl helthcre services provided outside NTPs. Mortlity (excludes HIV+TB) (rte per 1 poultion per yer) Prevlence (rte per 1 poultion) Incidence (rte per 1 poultion per yer) Number of TB ptients (thousnds) Tretment success rte (%) Totl budget (US$ millions constnt 215) Notified (new nd relpse) Incidence (HIV+TB only) Incidence HIV-positive TB ptients on CPT on ART New, or new nd relpse Retretment, or retretment excluding relpse HIV-positive RR-/MDR-TB XDR-TB Funded domesticlly Funded interntionlly Unfunded 15 n GLOBAL TUBERCULOSIS REPORT 215 Dt for ll yers cn be downloded from

162 WHO Estern Mediterrnen Region Popultion million WHO MEMBER STATES 21 OTHER COUNTRIES AND TERRITORIES 1 Estimtes of TB burden 214 NUMBER (thousnds) RATE (per 1 popultion) Mortlity (excludes HIV+TB) 88 (43 15) 14 (6.8 23) Mortlity (HIV+TB only) 3 (3 4).51 (.41.62) Prevlence (includes HIV+TB) 1 (88 1 2) 16 ( ) Incidence (includes HIV+TB) 74 (61 89) 117 (96 14) Incidence (HIV+TB only) 12 (1 15) 1.9 ( ) Cse detection, ll forms (%) 61 (51 75) Estimtes of MDR-TB burden 214 NEW RETREATMENT % of TB cses with MDR-TB 3.2 ( ) 18 (12 25) MDR-TB cses mong notified pulmonry TB cses 11 ( ) 4 7 (3 6 4) TB cse notifictions 214 NEW b RELAPSE Pulmonry, bcteriologiclly confirmed Pulmonry, cliniclly dignosed Extrpulmonry Totl new nd relpse Previously treted, excluding relpses Totl cses notified Among reported new nd relpse c cses disggregted by ge, (9.5%) cses were ged < 15 yers Among reported new nd relpse c cses disggregted by sex, mle:femle rtio = 1. Reported cses of RR-/MDR-TB 214 NEW RETREATMENT TOTAL b Cses tested for RR-/MDR-TB 8 44 (4.6%) (52%) Lbortory-confirmed RR-/MDR-TB cses Ptients strted on MDR-TB tretment d TB/HIV 214 NUMBER (%) e TB ptients with known HIV sttus HIV-positive TB ptients HIV-positive TB ptients on co-trimoxzole preventive therpy (CPT) HIV-positive TB ptients on ntiretrovirl therpy (ART) HIV-positive people screened for TB HIV-positive people provided with IPT 478 Tretment success rte nd cohort size (%) COHORT New nd relpse c cses registered in Previously treted cses, excluding relpse, registered in HIV-positive TB cses, ll types, registered in RR-/MDR-TB cses strted on second-line tretment in XDR-TB cses strted on second-line tretment in Lbortories 214 Smer (per 1 popultion) 1 3 out of 15 Culture (per 5 million popultion) 1 9 out of 15 Drug susceptibility testing (per 5 million popultion) 1 4 out of 15 NUMBER OF MEMBER STATES f Finncing TB control (low- nd middle-income countries) f,g 215 Ntionl TB progrmme budget (US$ millions) 183 % Funded domesticlly 46 % Funded interntionlly 43 % Unfunded 11 Dt re s reported to WHO. Estimtes of TB nd MDR-TB burden re produced by WHO in consulttion with countries. Rnges represent uncertinty intervls. b Includes cses with unknown previous TB tretment history. c Some countries reported on new cses only. d Includes ptients dignosed before 214 nd ptients who were not lbortory-confirmed s hving RR-/MDR-TB. e Clcultions exclude countries with missing numertors or denomintors. f Dt re not collected from ll Member Sttes. g Finncing indictors exclude funding for generl helthcre services provided outside NTPs. Mortlity (excludes HIV+TB) (rte per 1 poultion per yer) Prevlence (rte per 1 poultion) Incidence (rte per 1 poultion per yer) Number of TB ptients (thousnds) Tretment success rte (%) Totl budget (US$ millions constnt 215) Notified (new nd relpse) Incidence (HIV+TB only) Incidence HIV-positive TB ptients on CPT on ART New, or new nd relpse Retretment, or retretment excluding relpse HIV-positive RR-/MDR-TB XDR-TB Funded domesticlly Funded interntionlly Unfunded Dt for ll yers cn be downloded from GLOBAL TUBERCULOSIS REPORT 215 n 151

163 WHO Europen Region Popultion million WHO MEMBER STATES 53 OTHER COUNTRIES AND TERRITORIES 1 Estimtes of TB burden 214 NUMBER (thousnds) RATE (per 1 popultion) Mortlity (excludes HIV+TB) 33 (33 34) 3.7 ( ) Mortlity (HIV+TB only) 3 (3 4).35 (.3.4) Prevlence (includes HIV+TB) 44 (33 56) 48 (36 61) Incidence (includes HIV+TB) 34 (32 35) 37 (35 39) Incidence (HIV+TB only) 2 (18 21) 2.2 (2 2.4) Cse detection, ll forms (%) 79 (75 83) Estimtes of MDR-TB burden 214 NEW RETREATMENT % of TB cses with MDR-TB 15 (1 19) 48 (43 53) MDR-TB cses mong notified pulmonry TB cses 28 (2 37 ) 44 (39 48 ) TB cse notifictions 214 NEW b RELAPSE Pulmonry, bcteriologiclly confirmed Pulmonry, cliniclly dignosed Extrpulmonry Mortlity (excludes HIV+TB) (rte per 1 poultion per yer) Prevlence (rte per 1 poultion) Totl new nd relpse Previously treted, excluding relpses Totl cses notified Among reported new nd relpse c cses disggregted by ge, (3.8%) cses were ged < 15 yers Among reported new nd relpse c cses disggregted by sex, mle:femle rtio = 2. Reported cses of RR-/MDR-TB 214 NEW RETREATMENT TOTAL b Cses tested for RR-/MDR-TB (97%) (52%) Lbortory-confirmed RR-/MDR-TB cses Ptients strted on MDR-TB tretment d TB/HIV 214 NUMBER (%) e TB ptients with known HIV sttus HIV-positive TB ptients HIV-positive TB ptients on co-trimoxzole preventive therpy (CPT) HIV-positive TB ptients on ntiretrovirl therpy (ART) HIV-positive people screened for TB HIV-positive people provided with IPT Tretment success rte nd cohort size (%) COHORT New nd relpse c cses registered in Previously treted cses, excluding relpse, registered in HIV-positive TB cses, ll types, registered in RR-/MDR-TB cses strted on second-line tretment in XDR-TB cses strted on second-line tretment in Lbortories 214 Smer (per 1 popultion) 1 1 out of 53 Culture (per 5 million popultion) 1 44 out of 53 Drug susceptibility testing (per 5 million popultion) 1 39 out of 53 NUMBER OF MEMBER STATES f Finncing TB control (low- nd middle-income countries) f,g 215 Ntionl TB progrmme budget (US$ millions) % Funded domesticlly 93 % Funded interntionlly 4.1 % Unfunded 2.5 Dt re s reported to WHO. Estimtes of TB nd MDR-TB burden re produced by WHO in consulttion with countries. Rnges represent uncertinty intervls. b Includes cses with unknown previous TB tretment history. c Some countries reported on new cses only. d Includes ptients dignosed before 214 nd ptients who were not lbortory-confirmed s hving RR-/MDR-TB. e Clcultions exclude countries with missing numertors or denomintors. f Dt re not collected from ll Member Sttes. g Finncing indictors exclude funding for generl helthcre services provided outside NTPs. Incidence (rte per 1 poultion per yer) Number of TB ptients (thousnds) Tretment success rte (%) Totl budget (US$ millions constnt 215) Notified (new nd relpse) Incidence (HIV+TB only) Incidence HIV-positive TB ptients on CPT on ART New, or new nd relpse Retretment, or retretment excluding relpse HIV-positive RR-/MDR-TB XDR-TB Funded domesticlly Funded interntionlly Unfunded 152 n GLOBAL TUBERCULOSIS REPORT 215 Dt for ll yers cn be downloded from

164 WHO South-Est Asi Region Popultion million WHO MEMBER STATES 11 Estimtes of TB burden 214 NUMBER (thousnds) RATE (per 1 popultion) Mortlity (excludes HIV+TB) 46 (35 57) 24 (19 3) Mortlity (HIV+TB only) 62 (51 74) 3.3 ( ) Prevlence (includes HIV+TB) 5 4 ( ) 286 ( ) Incidence (includes HIV+TB) 4 ( ) 211 ( ) Incidence (HIV+TB only) 21 (18 24) 11 (9.4 12) Cse detection, ll forms (%) 62 (56 68) Estimtes of MDR-TB burden 214 NEW RETREATMENT % of TB cses with MDR-TB 2.2 ( ) 16 (14 17) MDR-TB cses mong notified pulmonry TB cses 4 (35 47 ) 59 (52 65 ) TB cse notifictions 214 NEW b RELAPSE Pulmonry, bcteriologiclly confirmed Pulmonry, cliniclly dignosed Extrpulmonry Totl new nd relpse Previously treted, excluding relpses Totl cses notified Among reported new nd relpse c cses disggregted by ge, (7.%) cses were ged < 15 yers Among reported new nd relpse c cses disggregted by sex, mle:femle rtio = 1.8 Reported cses of RR-/MDR-TB 214 NEW RETREATMENT TOTAL b Cses tested for RR-/MDR-TB (3.8%) (67%) Lbortory-confirmed RR-/MDR-TB cses Ptients strted on MDR-TB tretment d TB/HIV 214 NUMBER (%) e TB ptients with known HIV sttus HIV-positive TB ptients HIV-positive TB ptients on co-trimoxzole preventive therpy (CPT) HIV-positive TB ptients on ntiretrovirl therpy (ART) HIV-positive people screened for TB HIV-positive people provided with IPT 3 49 Tretment success rte nd cohort size (%) COHORT New nd relpse c cses registered in Previously treted cses, excluding relpse, registered in HIV-positive TB cses, ll types, registered in RR-/MDR-TB cses strted on second-line tretment in XDR-TB cses strted on second-line tretment in Lbortories 214 Smer (per 1 popultion) 1 9 out of 11 Culture (per 5 million popultion) 1 3 out of 11 Drug susceptibility testing (per 5 million popultion) 1 2 out of 11 NUMBER OF MEMBER STATES f Finncing TB control (low- nd middle-income countries) f,g 215 Ntionl TB progrmme budget (US$ millions) 559 % Funded domesticlly 33 % Funded interntionlly 45 % Unfunded 22 Dt re s reported to WHO. Estimtes of TB nd MDR-TB burden re produced by WHO in consulttion with countries. Rnges represent uncertinty intervls. b Includes cses with unknown previous TB tretment history. c Some countries reported on new cses only. d Includes ptients dignosed before 214 nd ptients who were not lbortory-confirmed s hving RR-/MDR-TB. e Clcultions exclude countries with missing numertors or denomintors. f Dt re not collected from ll Member Sttes. g Finncing indictors exclude funding for generl helthcre services provided outside NTPs. Mortlity (excludes HIV+TB) (rte per 1 poultion per yer) Prevlence (rte per 1 poultion) Incidence (rte per 1 poultion per yer) Number of TB ptients (thousnds) Tretment success rte (%) Totl budget (US$ millions constnt 215) Notified (new nd relpse) Incidence (HIV+TB only) Incidence HIV-positive TB ptients on CPT on ART New, or new nd relpse Retretment, or retretment excluding relpse HIV-positive RR-/MDR-TB XDR-TB Funded domesticlly Funded interntionlly Unfunded Dt for ll yers cn be downloded from GLOBAL TUBERCULOSIS REPORT 215 n 153

165 WHO Western Pcific Region Popultion million WHO MEMBER STATES 27 OTHER COUNTRIES AND TERRITORIES 9 Estimtes of TB burden 214 NUMBER (thousnds) RATE (per 1 popultion) Mortlity (excludes HIV+TB) 88 (81 95) 4.8 ( ) Mortlity (HIV+TB only) 5 (4 6).27 (.23.31) Prevlence (includes HIV+TB) 2 1 ( ) 116 (14 128) Incidence (includes HIV+TB) 1 6 ( ) 85 (8 89) Incidence (HIV+TB only) 31 (28 35) 1.7 ( ) Cse detection, ll forms (%) 85 (81 9) Estimtes of MDR-TB burden 214 NEW RETREATMENT % of TB cses with MDR-TB 4.4 ( ) 22 (18 25) MDR-TB cses mong notified pulmonry TB cses 52 (3 75 ) 19 (16 22 ) TB cse notifictions 214 NEW b RELAPSE Pulmonry, bcteriologiclly confirmed Pulmonry, cliniclly dignosed Extrpulmonry Mortlity (excludes HIV+TB) (rte per 1 poultion per yer) Prevlence (rte per 1 poultion) Totl new nd relpse Previously treted, excluding relpses Totl cses notified Among reported new nd relpse c cses disggregted by ge, (3.4%) cses were ged < 15 yers Among reported new nd relpse c cses disggregted by sex, mle:femle rtio = 2.1 Reported cses of RR-/MDR-TB 214 NEW RETREATMENT TOTAL b Cses tested for RR-/MDR-TB (21%) (62%) Lbortory-confirmed RR-/MDR-TB cses Ptients strted on MDR-TB tretment d 8 85 TB/HIV 214 NUMBER (%) e TB ptients with known HIV sttus HIV-positive TB ptients HIV-positive TB ptients on co-trimoxzole preventive therpy (CPT) HIV-positive TB ptients on ntiretrovirl therpy (ART) HIV-positive people screened for TB HIV-positive people provided with IPT 3 68 Tretment success rte nd cohort size (%) COHORT New nd relpse c cses registered in Previously treted cses, excluding relpse, registered in HIV-positive TB cses, ll types, registered in RR-/MDR-TB cses strted on second-line tretment in XDR-TB cses strted on second-line tretment in Lbortories 214 Smer (per 1 popultion) 1 13 out of 16 Culture (per 5 million popultion) 1 1 out of 16 Drug susceptibility testing (per 5 million popultion) 1 5 out of 16 NUMBER OF MEMBER STATES f Finncing TB control (low- nd middle-income countries) f,g 215 Ntionl TB progrmme budget (US$ millions) 63 % Funded domesticlly 63 % Funded interntionlly 16 % Unfunded 22 Dt re s reported to WHO. Estimtes of TB nd MDR-TB burden re produced by WHO in consulttion with countries. Rnges represent uncertinty intervls. b Includes cses with unknown previous TB tretment history. c Some countries reported on new cses only. d Includes ptients dignosed before 214 nd ptients who were not lbortory-confirmed s hving RR-/MDR-TB. e Clcultions exclude countries with missing numertors or denomintors. f Dt re not collected from ll Member Sttes. g Finncing indictors exclude funding for generl helthcre services provided outside NTPs. Incidence (rte per 1 poultion per yer) Number of TB ptients (thousnds) Tretment success rte (%) Totl budget (US$ millions constnt 215) Notified (new nd relpse) Incidence Incidence (HIV+TB only) HIV-positive TB ptients on CPT on ART New, or new nd relpse Retretment, or retretment excluding relpse HIV-positive RR-/MDR-TB XDR-TB Funded domesticlly Funded interntionlly Unfunded 154 n GLOBAL TUBERCULOSIS REPORT 215 Dt for ll yers cn be downloded from

166 A N N E X 4 Key TB indictors FOR INDIVIDUAL COUNTRIES AND TERRITORIES, WHO REGIONS AND THE WORLD

167

168 Contents Tble A4.1 TB incidence estimtes, notifiction nd cse detection rtes, ll forms of TB cse, Tble A4.2 Estimtes of TB mortlity, Tble A4.3 TB cse notifictions, Tble A4.4 Notified new nd relpse TB cses by ge nd sex, Tble A4.5 Tretment outcomes by TB cse type, 213, nd tretment outcomes for RR-/MDR-TB cses, Tble A4.6 Mesured percentge of TB cses with MDR-TB, most recent yer vilble 181 Tble A4.7 Tble A4.8 Drug susceptibility testing for TB cses, estimted MDR-TB mong notified TB cses, RR-/MDR-TB cses detected, nd enrolments on MDR-TB tretment, 214 HIV testing for TB ptients, provision of CPT nd ART to HIV-positive TB ptients, nd initition of IPT for people newly enrolled in HIV cre, Estimtes of mortlity, prevlence nd incidence Estimted vlues re shown s best estimtes followed by lower nd upper bounds. The lower nd upper bounds re defined s the 2.5th nd 97.5th centiles of outcome distributions produced in simultions. For detils bout the methods used to produce these estimtes see the technicl ppendix t Estimted numbers re shown rounded to two significnt figures. Estimted rtes re shown rounded to three significnt figures unless the vlue is under 1, in which cse rtes re shown rounded to two significnt figures. Dt source Dt shown in this file were tken from the WHO globl TB dtbse on 7 October 215. Dt shown in the min prt of the report were tken from the dtbse on 6 August 215. As result, dt in this nnex my dif fer slightly from those in the min prt of the report. Downlodble dt This nnex is provided s reference for looking up figures s nd when needed. It is not suitble for conducting nlyses or producing grphs nd tbles. Insted, downlod dt for ll countries nd ll yers s comm-seprted vlue (CSV) files from the WHO globl TB dtbse t dt/. See Annex 1 for more detils. Country notes Bngldesh A joint ressessment of estimtes of TB disese burden will be undertken following completion of the ntionl TB prevlence survey which ws lunched in Mrch 215. Cribben Islnds Dt collection from Cribben Islnds tht re not Member Sttes of WHO ws resumed in 211 f ter brek of few yers. This includes Arub, Curço, Puerto Rico nd Sint Mrten, which re Associte Members of the Pn Americn Helth Orgniztion, plus the territories of Anguill, Bermud, Bonire, Sint Eusttius nd Sb, British Virgin Islnds, Cymn Islnds, Montserrt nd Turks nd Cicos Islnds. Dt re not currently independently collected from the US Virgin Islnds. Denmrk Dt for Denmrk exclude Greenlnd. Europen Union/ Europen Economic Are countries Notifiction nd tretment outcome dt for Europen Union nd Europen Economic Are countries re provisionl. Frnce Dt from Frnce include dt from 5 overses deprtments (French Guin, Gudeloupe, Mrtinique, Myotte nd Ré union) nd exclude French territories of the Pcific. Russin Federtion UN Popultion Division estimtes re lower thn the popultion registered by the Federl Stte Sttistics Service of the Russin Federtion. The reported number of TB ptients with known HIV sttus (Tble A4.8) is for new TB ptients in the civilin sector only. It ws not possible to clculte the percentge of ll TB ptients with known HIV sttus. United Sttes of Americ In ddition to the 51 reporting res, the USA includes territories tht report seprtely to WHO. The dt for these territories re not included in the dt reported by the USA. Definitions of cse types nd outcomes do not exctly mtch those used by WHO. GLOBAL TUBERCULOSIS REPORT 215 n 157

169 TABLE A4.1 TB incidence estimtes, notifiction nd cse detection rtes, ll forms of TB cse, 214 Incidence (including HIV) Incidence (HIV-positive) Notified cses b Cse detection Popultion (millions) Number (thousnds) Rte Number (thousnds) Rte Number Rte Percent Afghnistn 32 6 (53 67) 189 ( ).32 (.25.4) 1 (.8 1.3) (47 6) Albni 3.54 (.46.63) 19 (16 22) <.1 (<.1 <.1).12 (<.1.15) (65 88) Algeri (25 37) 78 (64 94).2 (.15.26).52 (.39.67) (62 9) Americn Smo < 1 <.1 (<.1 <.1) 7 ( ) ( <.1) <.1 (<.1 <.1) Andorr < 1 <.1 (<.1 <.1) 9.2 (8.1 1) (79 1) Angol 24 9 (58 13) 37 (24 529) 23 (14 34) 95 (58 141) (42 92) Anguill < 1 <.1 (<.1 <.1) 23 (19 27) (26 37) Antigu nd Brbud < 1 <.1 (<.1 <.1) 7.6 ( ) <.1 (<.1 <.1) 2.5 ( ) (39 5) Argentin 43 1 (9.1 12) 24 (21 27).74 (.58.92) 1.7 ( ) (78 1) Armeni ( ) 45 (4 5).8 (.71.9) 2.7 (2.4 3.) (88 11) Arub < 1.11 (<.1.13) 11 (9.6 12) (16 2) Austrli ( ) 6.4 ( ).26 (.23.3).11 (.1.13) (78 1) Austri 9.66 (.58.75) 7.8 ( ).22 (.17.28).26 (.2.33) (75 97) Azerbijn ( ) 77 (68 86).13 (.11.15) 1.4 ( ) (7 89) Bhms < 1.45 (.4.51) 12 (1 13).14 (.12.16) 3.7 ( ) (98 13) Bhrin 1.2 (.17.22) 14 (13 16) <.1 (<.1.11).68 (.57.8) Bngldesh (32 41) 227 (2 256).57 (.45.71).36 (.28.45) (47 6) Brbdos < 1 <.1 (<.1 <.1).91 (.8 1.) <.1 (<.1 <.1).91 (.8 1.) (17 22) Belrus ( ) 58 (5 67).31 (.26.37) 3.3 ( ) (6 81) Belgium 11 1 ( ) 9 (7.8 1).72 (.61.85).65 (.54.76) (78 1) Belize < 1.13 (.12.14) 37 (34 41).24 (.2.29) 6.9 ( ) (5 6) Benin ( ) 61 (5 74) 1 ( ) 9.7 (7.7 12) (49 73) Bermud < 1 Bhutn < ( ) 164 ( ).91 (.72.11) 12 (9.4 15) (77 94) Bolivi (Plurintionl Stte of) (11 14) 12 (16 135).51 (.4.63) 4.8 (3.8 6.) (57 72) Bonire, Sint Eusttius nd Sb < 1 Bosni nd Herzegovin ( ) 42 (31 55) <.1 (<.1 <.1) <.1 (<.1.1) (57 1) Botswn (8. 9.1) 385 (361 41) 4.5 (4.1 5.) 24 ( ) (66 75) Brzil 26 9 (86 95) 44 (42 46) 16 (14 17) 7.6 ( ) (78 86) British Virgin Islnds < 1 <.1 (<.1 <.1) 1.7 ( ) Brunei Drusslm < 1.26 (.23.29) 62 (54 7) <.1 (<.1 <.1) <.1 (<.1 <.1) (68 88) Bulgri ( ) 27 (24 29) <.1 (<.1 <.1) <.1 (<.1 <.1) (87 1) Burkin Fso (8.5 1) 54 (48 59) 1.2 (1. 1.3) 6.6 ( ) (53 65) Burundi (13 15) 126 ( ) 1.9 ( ) 17 (15 2) (49 58) Cbo Verde < 1.71 (.63.8) 138 ( ).66 (.55.78) 13 (11 15) (34 44) Cmbodi 15 6 (54 66) 39 ( ) 1.8 (1.6 2.) 12 (1 13) (66 8) Cmeroon 23 5 (44 56) 22 ( ) 2 (17 23) 88 (75 13) (46 59) Cnd ( ) 5.2 ( ).1 (.79.13).29 (.22.36) Cymn Islnds < 1 <.1 (<.1 <.1) 7 ( ) <.1 (<.1 <.1).28 (<.1.62) Centrl Africn Republic 5 18 (16 2) 375 (333 42) 7.6 ( ) 157 ( ) (5 64) Chd (19 24) 159 ( ) 6 ( ) 44 (35 55) (49 62) Chile ( ) 16 (14 18).13 (.1.16).73 (.57.91) (75 97) Chin (86 1 ) 68 (63 73) 13 (11 16).98 ( ) (82 95) Chin, Hong Kong SAR ( ) 74 (65 84).32 (.28.37).45 (.38.52) (79 1) Chin, Mco SAR < 1.48 (.42.54) 82 (72 93) <.1 (<.1 <.1) 1.3 ( ) (73 94) Colombi (14 17) 33 (29 37) 3.4 ( ) 7.1 ( ) (68 86) Comoros < 1.27 (.22.32) 35 (28 41) <.1 (<.1.1) 1.1 ( ) (47 68) Congo 5 17 (15 19) 381 (335 43) 5.5 ( ) 122 (96 152) (52 66) Cook Islnds < 1 <.1 (<.1 <.1) 12 (11 14) (7 9) Cost Ric 5.53 (.47.6) 11 (9.8 13).54 (.47.61) 1.1 ( ) (77 99) Croti 4.53 (.46.59) 12 (11 14) <.1 (<.1 <.1) <.1 (<.1.12) (83 11) Cub ( ) 9.4 (8.1 11).11 (.93.13).97 ( ) (6 79) Curço < 1 <.1 (<.1 <.1) 3.7 ( ) <.1 (<.1 <.1) 3.7 ( ) (77 99) Cyprus 1.61 (.54.69) 5.3 (4.6 6.) <.1 (<.1 <.1) <.1 (<.1 <.1) (56 73) Czech Republic (.43.55) 4.6 ( ) <.1 (<.1 <.1) <.1 (<.1 <.1) (86 11) Côte d'ivoire (33 4) 165 (15 179) 8.5 ( ) 39 (34 43) (59 7) Democrtic People's Republic of Kore (1 12) 442 ( ).31 (.25.38) 1.2 ( ) (87 1) Democrtic Republic of the Congo (22 27) 325 ( ) 34 (27 42) 45 (36 56) (43 52) Denmrk 6.4 (.35.45) 7.1 (6.2 8.).12 (<.1.15).22 (.17.27) (65 84) Djibouti < ( ) 619 ( ).54 (.44.65) 62 (51 74) (36 46) Dominic < 1 <.1 (<.1 <.1).71 (.62.8) (17 22) Dominicn Republic (5.5 7.) 6 (53 68) 1.7 ( ) 16 (14 19) (63 8) Ecudor (6.3 11) 54 (39 71) 1.1 ( ) 7.2 ( ) (46 82) Egypt 9 13 (12 15) 15 (13 16).35 (.28.44) <.1 (<.1 <.1) (49 6) Rtes re per 1 popultion. b New cses, relpse cses nd cses for which the tretment history is unknown. 158 n GLOBAL TUBERCULOSIS REPORT 215 Dt for ll yers cn be downloded from

170 TABLE A4.1 TB incidence estimtes, notifiction nd cse detection rtes, ll forms of TB cse, 214 Popultion (millions) Incidence (including HIV) Number (thousnds) Rte Incidence (HIV-positive) Number (thousnds) Notified cses b Cse detection Rte Number Rte Percent El Slvdor ( ) 41 (38 45).24 (.22.26) 3.9 ( ) (8 95) Equtoril Guine < ( ) 162 ( ).67 (.52.84) 82 (64 12) (77 1) Eritre 5 4 ( ) 78 (57 13).25 (.18.34) 4.9 ( ) (46 82) Estoni 1.27 (.24.3) 2 (18 23).24 (.21.27) 1.8 ( ) (78 1) Ethiopi 97 2 (16 24) 27 (168 25) 19 (15 23) 19 (15 24) (49 73) Fiji < 1.59 (.48.72) 67 (55 81).27 (.22.34) 3.1 ( ) (53 78) Finlnd 5.31 (.27.35) 5.6 ( ) <.1 (<.1 <.1).1 (<.1.13) (72 93) Frnce (5.3 6.) 8.7 ( ).34 (.28.42).53 (.43.65) (76 86) French Polynesi < 1.61 (.54.69) 22 (19 25) (81 1) Gbon ( ) 444 ( ).53 (.46.61) 32 (27 36) (67 84) Gmbi (2.8 4.) 174 (145 26).78 (.64.93) 4 (33 48) (64 91) Georgi (4. 4.6) 16 (99 114).16 (.13.19) 3.9 ( ) (7 8) Germny 81 5 ( ) 6.2 (5.4 7.).12 (.95.15).15 (.12.19) (77 1) Ghn (21 75) 165 (8 281) 11 (5.2 19) 42 (2 72) (19 69) Greece (.46.6) 4.8 ( ).16 (.12.19).14 (.11.18) (81 1) Greenlnd < 1.11 (.97.13) 197 ( ) Grend < 1 <.1 (<.1 <.1) 1.3 (1. 1.5) <.1 (<.1 <.1).11 (<.1.14) Gum < 1.67 (.59.76) 4 (35 45) <.1 (<.1 <.1) <.1 (<.1 <.1) (74 95) Guteml (8.1 1) 57 (51 64).84 (.7 1.) 5.3 ( ) (31 39) Guine (19 24) 177 ( ) 4.7 ( ) 38 (32 45) (48 61) Guine-Bissu ( ) 369 ( ) 2.9 (2. 4.) 162 (11 224) (26 49) Guyn < 1.79 (.7.89) 13 (91 116).17 (.14.2) 22 (19 26) (62 78) Hiti (19 24) 2 ( ) 3.7 ( ) 35 (31 41) (66 85) Hondurs (3. 3.9) 43 (38 48).34 (.3.39) 4.3 ( ) (73 93) Hungry (1. 1.3) 12 (11 14).11 (<.1.14).11 (<.1.14) (59 77) Icelnd < 1.11 (<.1.12) 3.3 ( ) <.1 (<.1 <.1) ( ) (65 84) Indi (2 2 3) 167 ( ) 11 (96 12) 8.3 ( ) (7 8) Indonesi (7 1 4) 399 ( ) 63 (41 9) 25 (16 36) (23 46) Irn (Islmic Republic of) (14 2) 22 (18 26).4 (.3.52).51 (.38.66) (5 74) Irq (13 17) 43 (38 49) <.1 (<.1 <.1) <.1 (<.1 <.1) (48 62) Irelnd 5.35 (.3.39) 7.4 ( ).15 (.11.18).31 (.24.39) (75 97) Isrel 8.46 (.4.52) 5.8 ( ).32 (.28.37).41 (.36.46) (71 91) Itly ( ) 6 ( ).24 (.19.3).4 (.31.5) Jmic 3.13 (.11.16) 4.7 ( ).29 (.23.36) 1.1 ( ) (55 81) Jpn (2 26) 18 (16 21).99 (.83.12) <.1 (<.1 <.1) (75 96) Jordn 7.41 (.36.46) 5.5 ( ) <.1 (<.1 <.1) <.1 ( <.1) (84 11) Kzkhstn (11 25) 99 (64 141).59 (.38.84) 3.4 ( ) (62 14) Keny (11 11) 246 (24 252) 4 (38 42) 89 (84 93) (78 82) Kiribti < 1.55 (.45.66) 497 (46 597) <.1 (<.1 <.1) 1.7 ( ) (63 92) Kuwit 4.8 (.7.91) 21 (19 24) <.1 (<.1 <.1).14 (.11.17) (81 1) Kyrgyzstn ( ) 142 (126 16).18 (.16.2) 3.1 ( ) (68 87) Lo People's Democrtic Republic 7 13 (9.5 16) 189 ( ).5 (.34.68) 7.4 (5.1 1) (26 45) Ltvi 2.98 (.91 1.) 49 (46 53).21 (.19.24) 11 (9.4 12) (71 81) Lebnon 6.92 (.8 1.1) 16 (14 19).11 (.96.13) 2 ( ) (64 84) Lesotho 2 18 (13 24) 852 ( ) 12 (8.5 16) 578 (45 781) (37 69) Liberi 4 14 (12 15) 38 ( ) 2.1 ( ) 49 (38 61) (18 23) Liby (2.1 3.) 4 (33 48).1 (.8.12) 1.6 (1.3 2.) (39 56) Lithuni (1.7 2.) 62 (57 68).57 (.5.64) 2 ( ) (75 89) Luxembourg < 1.37 (.32.41) 6.6 ( ) <.1 (<.1 <.1).49 (.38.61) (58 75) Mdgscr (49 62) 235 (27 264) 2.2 ( ) 9.5 (7.4 12) (46 58) Mlwi (2 61) 227 ( ) 19 (1 31) 115 (6 186) (27 8) Mlysi 3 31 (25 37) 13 (83 124) 2.2 ( ) 7.3 ( ) (65 96) Mldives < 1.15 (.13.17) 41 (36 47) <.1 (<.1 <.1) <.1 (<.1.11) (78 1) Mli (9.5 1) 58 (56 59).71 (.64.78) 4.1 ( ) (57 61) Mlt < 1.52 (.45.58) 12 (11 14) <.1 (<.1 <.1).52 (.37.69) (77 1) Mrshll Islnds < 1.18 (.14.21) 335 (274 42) <.1 (<.1 <.1).68 (.5.88) (67 98) Muritni ( ) 111 (79 148).41 (.27.57) 1 (6.8 14) (41 77) Muritius 1.28 (.24.31) 22 (19 24).42 (.36.48) 3.3 ( ) (41 52) Mexico (23 29) 21 (19 23) 2.1 ( ) 1.7 ( ) (72 91) Micronesi (Federted Sttes of) < 1.2 (.9.36) 195 (87 347) (52 21) Monco < 1 <.1 (<.1 <.1) 2.2 ( ) Mongoli 3 5 ( ) 17 ( ).11 (<.1.12).37 (.31.42) (8 1) Montenegro < 1.13 (.11.15) 21 (18 24) <.1 (<.1 <.1) <.1 (<.1 <.1) (77 99) Montserrt < 1 Rtes re per 1 popultion. b New cses, relpse cses nd cses for which the tretment history is unknown. Dt for ll yers cn be downloded from GLOBAL TUBERCULOSIS REPORT 215 n 159

171 TABLE A4.1 TB incidence estimtes, notifiction nd cse detection rtes, ll forms of TB cse, 214 Popultion (millions) Incidence (including HIV) Number (thousnds) Rte Incidence (HIV-positive) Number (thousnds) Notified cses b Cse detection Rte Number Rte Percent Morocco (33 39) 16 (97 115).77 (.61.94) 2.3 ( ) (77 91) Mozmbique (12 18) 551 (435 68) 85 (65 11) 311 ( ) (31 49) Mynmr 53 2 (18 22) 369 (334 46) 19 (15 24) 36 (28 44) (64 78) Nmibi 2 13 (12 15) 561 ( ) 5.6 ( ) 232 ( ) (59 76) Nuru < 1 <.1 (<.1 <.1) 73 (64 83) (95 12) Nepl (39 5) 158 ( ) 1.5 ( ) 5.4 ( ) (71 9) Netherlnds ( ) 5.8 ( ).52 (.43.61).31 (.26.36) (74 95) New Cledoni < 1.38 (.34.43) 15 (13 17) (67 86) New Zelnd 4.33 (.29.38) 7.4 ( ) <.1 (<.1 <.1) <.1 (<.1 <.1) (79 1) Nicrgu ( ) 58 (53 63).14 (.11.17) 2.3 ( ) (7 82) Niger (17 21) 98 (87 11) 1.5 ( ) 7.9 ( ) (51 65) Nigeri (34 87) 322 ( ) 1 (59 16) 59 (33 92) (1 26) Niue < 1 Northern Mrin Islnds < 1.33 (.29.38) 61 (53 69) <.1 (<.1 <.1).21 (.16.26) (69 89) Norwy 5.42 (.37.47) 8.1 ( ).12 (<.1.14).23 (.18.28) (64 83) Omn 4.41 (.36.46) 9.6 (8.4 11) <.1 (<.1 <.1).11 (<.1.12) (78 1) Pkistn (37 65) 27 (21 35) 6.4 ( ) 3.4 ( ) (48 83) Plu < 1 <.1 (<.1 <.1) 42 (36 47) <.1 (<.1 <.1) <.1 (<.1 <.1) (14 18) Pnm ( ) 46 (38 56).18 (.14.21) 4.6 ( ) (68 1) Ppu New Guine 7 31 (23 41) 417 (34 547) 3.5 ( ) 47 (32 64) (64 12) Prguy (2.7 3.) 43 (41 45).29 (.27.32) 4.5 ( ) (76 84) Peru (3 45) 12 (98 145) 2.5 (2. 3.1) 8.1 ( ) (67 99) Philippines (25 32) 288 ( ) 2.5 (2. 3.2) 2.6 (2. 3.2) (76 97) Polnd 39 8 (7. 9.) 21 (18 23).1 (.81.13).27 (.21.34) (73 94) Portugl ( ) 25 (22 28).37 (.31.43) 3.5 (3. 4.1) (74 96) Puerto Rico 4.51 (.45.58) 1.4 ( ) <.1 (<.1 <.1).2 (.17.23) (76 99) Qtr 2.63 (.55.72) 29 (26 33) <.1 (<.1 <.1) <.1 (<.1 <.1) (65 84) Republic of Kore 5 43 (41 46) 86 (81 91).19 (.15.23).37 (.3.45) (88 99) Republic of Moldov (5.5 7.) 153 ( ).5 (.43.58) 12 (11 14) (58 74) Romni 2 16 (14 18) 81 (71 91).51 (.44.59) 2.6 (2.2 3.) (83 11) Russin Federtion (11 13) 84 (76 93) 5.5 ( ) 3.8 ( ) (77 94) Rwnd ( ) 63 (54 72) 1.8 ( ) 16 (14 18) (71 94) Sint Kitts nd Nevis < 1 <.1 (<.1 <.1) 7.2 ( ) ( ) <.1 (<.1 <.1) (16 2) Sint Luci < 1.17 (.15.19) 9.1 (8. 1) <.1 (<.1 <.1) 1.4 ( ) (32 41) Sint Vincent nd the Grendines < 1.26 (.22.31) 24 (2 29) <.1 (<.1.11) 8.4 (6.7 1) (16 23) Smo < 1.37 (.3.45) 19 (16 23) (51 77) Sn Mrino < 1 <.1 (<.1 <.1) 1.6 ( ) So Tome nd Principe < 1.18 (.16.2) 97 (85 19).38 (.33.42) 2 (18 23) (78 99) Sudi Arbi ( ) 12 (11 14).13 (.11.16).43 (.36.5) (75 96) Senegl 15 2 (18 23) 138 ( ) 1.5 ( ) 1 (8.9 12) (59 75) Serbi ( ) 24 (21 27).17 (.13.21).19 (.15.24) (77 99) Seychelles < 1.25 (.22.28) 26 (23 29) <.1 (<.1 <.1).76 (.59.95) (46 6) Sierr Leone 6 2 (15 25) 31 ( ) 2.3 (1.7 3.) 37 (28 47) (5 84) Singpore ( ) 49 (43 56).75 (.65.86) 1.4 ( ) (71 92) Sint Mrten (Dutch prt) < 1 Slovki 5.36 (.32.41) 6.7 ( ) <.1 (<.1 <.1) <.1 (<.1 <.1) (78 1) Sloveni 2.16 (.14.18) 7.7 ( ) <.1 (<.1 <.1) <.1 (<.1 <.1) (79 1) Solomon Islnds < 1.49 (.41.59) 86 (71 12) (59 85) Somli (25 32) 274 (242 38) 2.2 ( ) 21 (16 26) (4 51) South Afric (4 51) 834 ( ) 27 (24 31) 59 ( ) (61 77) South Sudn (14 21) 146 ( ) 2.9 ( ) 25 (2 3) (4 58) Spin ( ) 12 (1 13).31 (.27.37).68 (.58.79) (77 1) Sri Lnk (12 15) 65 (57 73).53 (.41.66).26 (.2.32) (62 79) Sudn (2 58) 94 (52 148) 1.2 (.65 2.) 3.2 ( ) (33 95) Surinme < 1.2 (.17.25) 38 (31 46).64 (.52.77) 12 (9.6 14) (61 89) Swzilnd (6.8 12) 733 ( ) 5.9 ( ) 464 (33 619) (46 83) Sweden 1.72 (.63.82) 7.5 ( ).24 (.18.3).24 (.19.3) (77 1) Switzerlnd 8.52 (.45.59) 6.3 ( ).37 (.29.47).46 (.36.57) (72 93) Syrin Arb Republic ( ) 17 (14 2) <.1 (<.1 <.1) <.1 (<.1 <.1) (94 13) Tjikistn ( ) 91 (8 13).23 (.2.27) 2.8 ( ) (68 87) Thilnd (61 19) 171 (9 276) 15 (7.8 24) 22 (12 36) (36 11) The Former Yugoslv Republic of Mcedoni 2.32 (.28.36) 15 (13 17) <.1 (<.1 <.1) <.1 (<.1 <.1) (79 1) Timor-Leste ( ) 498 ( ).57 (.42.73) 4.9 ( ) (53 77) Rtes re per 1 popultion. b New cses, relpse cses nd cses for which the tretment history is unknown. 16 n GLOBAL TUBERCULOSIS REPORT 215 Dt for ll yers cn be downloded from

172 TABLE A4.1 TB incidence estimtes, notifiction nd cse detection rtes, ll forms of TB cse, 214 Popultion (millions) Incidence (including HIV) Number (thousnds) Rte Incidence (HIV-positive) Number (thousnds) Notified cses b Cse detection Rte Number Rte Percent Togo (3.4 5.) 58 (47 7).83 (.67 1.) 12 (9.4 14) (51 75) Tokelu < 1 Tong < 1.15 (.12.18) 14 (11 17) <.1 (<.1 <.1) <.1 (<.1 <.1) (73 11) Trinidd nd Tobgo 1.29 (.26.33) 22 (19 24).71 (.62.81) 5.3 (4.6 6.) (76 98) Tunisi (3.4 4.) 33 (31 36).23 (.18.28).2 (.16.25) (77 92) Turkey (12 16) 18 (16 21).45 (.35.57) <.1 (<.1 <.1) (82 11) Turkmenistn ( ) 64 (52 78) (62 94) Turks nd Cicos Islnds < 1 <.1 (<.1 <.1) 1 (8.8 11) <.1 (<.1 <.1) 5 (4. 6.1) (26 34) Tuvlu < 1.19 (.15.23) 19 ( ) (66 98) US Virgin Islnds < 1 <.1 (<.1 <.1) 7.7 ( ) Ugnd (53 69) 161 ( ) 28 (24 32) 73 (63 84) (64 83) Ukrine (38 48) 94 (83 16) 8.1 (7. 9.3) 18 (16 21) (66 84) United Arb Emirtes 9.14 (.1.19) 1.6 ( ) <.1 (<.1 <.1) <.1 (<.1 <.1) (32 58) United Kingdom of Gret Britin nd Northern Irelnd ( ) 12 (11 13).39 (.31.47).6 (.49.74) (79 9) United Republic of Tnzni (8 29) 327 ( ) 62 (29 11) 12 (56 28) (21 77) United Sttes of Americ (8.7 11) 3.1 ( ).6 (.52.68).19 (.16.21) (8 1) Uruguy 3 1 ( ) 3 (27 34).16 (.14.18) 4.7 (4. 5.3) (73 95) Uzbekistn (18 31) 82 (61 17).83 ( ) 2.8 ( ) (58 1) Vnutu < 1.16 (.13.19) 63 (52 74) (58 84) Venezuel (Bolivrin Republic of) ( ) 24 (21 27).7 (.6.81) 2.3 (2. 2.6) (77 99) Viet Nm (11 15) 14 ( ) 7 ( ) 7.6 ( ) (65 94) Wllis nd Futun Islnds < 1 <.1 (<.1 <.1) 3.7 ( ) West Bnk nd Gz Strip 5.26 (.23.3) 5.8 ( ) <.1 (<.1 <.1) <.1 ( <.1) (14 19) Yemen (11 14) 48 (42 54).8 (.62.1).31 (.24.38) (68 88) Zmbi (44 88) 46 ( ) 38 (25 52) 239 ( ) (43 86) Zimbbwe (29 58) 278 ( ) 25 (17 35) 167 ( ) (51 1) WHO regions Africn Region (2 4 3 ) 281 (25 313) 87 (79 95) 9 (82 99) (43 54) Region of the Americs (27 29) 28 (27 29) 36 (34 38) 3.7 ( ) (75 81) Estern Mediterrnen Region (61 89) 117 (96 14) 12 (1 15) 1.9 ( ) (51 75) Europen Region (32 35) 37 (35 39) 2 (18 21) 2.2 (2. 2.4) (78 86) South-Est Asi Region ( ) 211 ( ) 21 (18 24) 11 (9.4 12) (56 68) Western Pcific Region ( ) 85 (8 89) 31 (28 35) 1.7 ( ) (81 9) Globl (9 1 1 ) 133 ( ) 1 2 ( ) 16 (15 17) (6 66) Rtes re per 1 popultion. b New cses, relpse cses nd cses for which the tretment history is unknown. Dt for ll yers cn be downloded from GLOBAL TUBERCULOSIS REPORT 215 n 161

173 TABLE A4.2 Estimtes of TB mortlity, 214. Deths from TB mong HIV-positive people re of ficilly clssified s deths cused by HIV/AIDS in the Interntionl clssifiction of diseses. Popultion (millions) Mortlity (HIV-negtive people) Number (thousnds) Rte Mortlity (HIV-positive people) Number (thousnds) Rte Mortlity (HIV-negtive nd HIV-positive people) b Number (thousnds) Afghnistn (1 18) 44 (32 57).87 (.72.1).28 (.23.33) 14 (1 18) 44 (32 58) Albni 3.17 (.12.23).58 (.4.79) <.1 (<.1 <.1) <.1 (<.1 <.1).19 (.14.25).65 (.47.85) Algeri ( ) 11 (7.9 16).46 (.19.85).12 (<.1.22) 4.5 ( ) 12 (8. 16) Americn Smo < 1 <.1 (<.1 <.1).52 (.31.8) <.1 (<.1 <.1).52 (.31.8) Andorr < 1 <.1 (<.1 <.1).76 ( ) <.1 (<.1 <.1).76 ( ) Angol (7.5 19) 52 (31 79) 3.5 ( ) 14 (6.2 26) 16 (1 23) 67 (43 95) Anguill < 1 Antigu nd Brbud < 1 <.1 (<.1 <.1) 3.8 ( ) <.1 (<.1 <.1) 3.8 ( ) Argentin (.58.63) 1.4 ( ).58 (.23.11).13 (<.1.25).67 (.62.72) 1.5 ( ) Armeni 3.14 (.12.16) 4.7 ( ).12 (<.1.16).4 (.29.53).15 (.13.18) 5.1 ( ) Arub < 1 <.1 (<.1 <.1).9 ( ) <.1 (<.1 <.1).9 ( ) Austrli (.42.42).18 (.18.18) <.1 (<.1 <.1) <.1 (<.1 <.1).47 (.45.49).2 (.19.21) Austri 9.55 (.54.56).65 (.64.66) <.1 (<.1 <.1) <.1 ( <.1).56 (.55.57).66 (.64.67) Azerbijn 1.41 (.37.45).42 (.38.47).28 (.21.36).29 (.21.38).69 (.6.78).72 (.63.81) Bhms < 1 <.1 (<.1 <.1).63 (.6.65) <.1 (<.1 <.1).78 ( ) <.1 (<.1 <.1) 1.4 ( ) Bhrin 1 <.1 (<.1 <.1).42 (.36.47) <.1 (<.1 <.1).42 (.36.47) Bngldesh (59 11) 51 (37 68).18 (.14.22).11 (<.1.14) 82 (59 11) 51 (37 68) Brbdos < 1 <.1 (<.1 <.1) ( ) <.1 (<.1 <.1) ( ) Belrus 1.73 (.68.79) 7.7 ( ).8 (.64.98).84 (.67 1.).81 (.75.87) 8.5 ( ) Belgium (.3.32).28 (.27.29).1 (<.1.14) <.1 (<.1.13).41 (.37.46).37 (.33.41) Belize < 1 <.1 (<.1 <.1) 1.8 ( ) <.1 (<.1 <.1) 2 ( ).13 (.11.15) 3.8 ( ) Benin 11 1 ( ) 9.8 (6.8 13).31 (.24.4) 3 ( ) 1.4 (1. 1.7) 13 (9.6 16) Bermud < 1 Bhutn < 1.72 (.39.12) 9.5 (5.1 15) <.1 (<.1 <.1).13 (<.1.29).73 (.4.12) 9.6 (5.2 15) Bolivi (Plurintionl Stte of) (.21.48) 3.1 (2. 4.5).13 (.11.16) 1.2 (1. 1.5).46 (.33.61) 4.4 ( ) Bonire, Sint Eusttius nd Sb < 1 Bosni nd Herzegovin 4.15 (.13.16) 3.8 ( ).15 (.13.16) 3.8 ( ) Botswn 2.62 (.44.82) 28 (2 37) 1 (.8 1.3) 47 (36 59) 1.7 (1.4 2.) 75 (61 9) Brzil ( ) 2.6 ( ) 2.4 ( ) 1.2 ( ) 7.7 (7. 8.5) 3.8 ( ) British Virgin Islnds < 1 <.1 (<.1 <.1) 5 (5. 5.1) <.1 (<.1 <.1) 5 (5. 5.1) Brunei Drusslm < 1.15 (.14.16) 3.6 ( ).15 (.14.16) 3.6 ( ) Bulgri 7.15 (.15.16) 2.1 ( ).15 (.15.16) 2.1 ( ) Burkin Fso ( ) 9.1 (6.6 12).47 (.39.56) 2.7 ( ) 2.1 ( ) 12 (9.2 15) Burundi ( ) 23 (17 3).69 (.57.82) 6.4 ( ) 3.2 (2.5 4.) 3 (23 37) Cbo Verde < 1.16 (.11.21) 31 (22 41).26 (.22.31) 5.1 (4.2 6.).18 (.14.24) 36 (27 46) Cmbodi (6.3 12) 58 (41 78).82 (.63 1.) 5.3 ( ) 9.7 (7.1 13) 64 (46 83) Cmeroon ( ) 31 (22 41) 7.6 ( ) 34 (28 4) 15 (12 17) 65 (54 77) Cnd (.81.82).23 (.23.23).16 (<.1.25) <.1 (<.1 <.1).98 (.9.11).27 (.25.3) Cymn Islnds < 1 Centrl Africn Republic ( ) 48 (34 65) 3.1 ( ) 64 (46 86) 5.4 ( ) 113 (89 14) Chd ( ) 23 (16 3) 2.1 (1.4 3.) 15 (1 22) 5.2 ( ) 38 (3 48) Chile (.28.29) 1.6 ( ) <.1 (<.1 <.1) <.1 (<.1 <.1).29 (.29.3) 1.6 ( ) Chin (37 4) 2.8 ( ).7 (.53.9) <.1 (<.1 <.1) 39 (37 4) 2.8 ( ) Chin, Hong Kong SAR 7.18 (.18.18) 2.5 ( ).18 (.18.18) 2.5 ( ) Chin, Mco SAR < 1.23 (.22.24) 4 ( ).23 (.22.24) 4 ( ) Colombi (.71.75) 1.5 ( ).4 (.3.51).84 ( ) 1.1 (1. 1.2) 2.4 ( ) Comoros < 1.58 (.41.78) 7.5 (5.3 1).58 (.41.78) 7.5 (5.3 1) Congo ( ) 46 (32 61) 2.5 (2.1 3.) 55 (46 66) 4.6 ( ) 11 (84 119) Cook Islnds < 1 <.1 (<.1 <.1) 1.8 ( ) <.1 (<.1 <.1) 1.8 ( ) Cost Ric 5.39 (.37.41).83 (.78.87) <.1 (<.1 <.1).15 (.11.19).46 (.43.49).97 (.91 1.) Croti 4.46 (.45.46) 1.1 ( ).46 (.45.46) 1.1 ( ) Cub (.29.29).25 (.25.26) <.1 (<.1 <.1) <.1 (<.1 <.1).36 (.34.38).32 (.3.33) Curço < 1 ( <.1) ( <.1) ( ) ( ) Cyprus 1 <.1 (<.1 <.1).42 (.37.46) <.1 (<.1 <.1).42 (.37.46) Czech Republic 11.6 (.59.6).56 (.56.57).6 (.59.6).56 (.56.57) Côte d'ivoire ( ) 22 (16 29) 2.4 ( ) 11 (8.7 13) 7.2 ( ) 32 (26 4) Democrtic People's Republic of Kore 25 5 (2. 9.3) 2 (7.9 37).21 (.15.28) <.1 (<.1.11) 5 (2. 9.3) 2 (8. 37) Democrtic Republic of the Congo (38 68) 69 (5 9) 6.3 (5. 7.7) 8.4 (6.7 1) 58 (44 74) 77 (58 99) Denmrk 6.24 (.23.25).42 (.4.45) <.1 (<.1 <.1) <.1 (<.1 <.1).25 (.24.26).44 (.42.46) Djibouti < ( ) 12 (87 159).14 (.12.17) 16 (13 19) 1.2 (.9 1.5) 137 (13 175) Dominic < 1 <.1 (<.1 <.1) 2.7 ( ) <.1 (<.1 <.1) 2.7 ( ) Dominicn Republic 1.41 (.22.65) 3.9 ( ).19 (.15.24) 1.8 ( ).6 (.4.84) 5.8 (3.9 8.) Rte Rtes re per 1 popultion. b All clcultions re mde before numbers re rounded. 162 n GLOBAL TUBERCULOSIS REPORT 215 Dt for ll yers cn be downloded from

174 TABLE A4.2 Estimtes of TB mortlity, 214. Deths from TB mong HIV-positive people re of ficilly clssified s deths cused by HIV/AIDS in the Interntionl clssifiction of diseses. Popultion (millions) Mortlity (HIV-negtive people) Number (thousnds) Rte Mortlity (HIV-positive people) Number (thousnds) Rte Mortlity (HIV-negtive nd HIV-positive people) b Number (thousnds) Ecudor (.39.56) 2.9 ( ).31 (.23.4) 1.9 ( ).78 (.66.9) 4.9 ( ) Egypt 9.22 (.2.25).25 (.22.27).43 (.35.51) <.1 (<.1 <.1).27 (.24.29).3 (.27.32) El Slvdor 6.12 (.89.15) 1.9 ( ).31 (.22.41).51 (.36.68).15 (.12.18) 2.4 (1.9 3.) Equtoril Guine < 1.54 (.33.81) 6.6 (4. 9.9).49 (.33.69) 6 (4. 8.4).1 (.76.14) 13 (9.2 17) Eritre 5.71 (.46 1.) 14 (9. 2).1 (.58.15) 2 (1.1 3.).81 ( ) 16 (11 22) Estoni 1.27 (.27.27) 2.1 (2. 2.1) <.1 (<.1 <.1).3 (.2.43).31 (.3.33) 2.4 ( ) Ethiopi (22 43) 33 (23 44) 5.5 ( ) 5.7 (4.6 7.) 37 (27 48) 38 (28 5) Fiji < 1.41 (.41.42) 4.7 ( ) <.1 (<.1 <.1).56 (.45.69).46 (.45.48) 5.2 ( ) Finlnd 5.11 (.11.11).19 (.19.19).11 (.11.11).19 (.19.19) Frnce (.36.39).58 (.56.61).62 (.34.99).1 (<.1.15).43 (.4.47).68 (.62.74) French Polynesi < 1 <.1 (<.1 <.1) 1.8 ( ) <.1 (<.1 <.1) 1.8 ( ) Gbon 2.94 ( ) 55 (39 75).3 (.24.37) 18 (14 22) 1.2 ( ) 73 (56 93) Gmbi 2.35 (.24.47) 18 (12 25).14 (.1.18) 7.2 ( ).49 (.37.62) 25 (19 32) Georgi 4.27 (.2.34) 6.6 ( ).17 (.1.25).42 (.26.63).28 (.22.35) 7 ( ) Germny (.32.33).4 (.4.41).11 (<.1.15) <.1 (<.1 <.1).34 (.33.34).42 (.41.43) Ghn (4.4 17) 36 (16 64) 4.2 ( ) 16 (8.8 24) 14 (7.9 21) 52 (3 8) Greece (.11.12) 1 ( ) <.1 (<.1 <.1) <.1 (<.1 <.1).12 (.11.12) 1 ( ) Greenlnd < 1 <.1 (<.1.13) 16 (1 24) <.1 (<.1.13) 16 (1 24) Grend < 1 <.1 (<.1 <.1).44 (.43.44) <.1 (<.1 <.1).44 (.43.44) Gum < 1 <.1 (<.1 <.1) 3.3 ( ) <.1 (<.1 <.1) 3.3 ( ) Guteml (.24.28) 1.6 ( ).54 (.46.63) 3.4 ( ).8 (.72.89) 5 ( ) Guine ( ) 29 (21 39) 1.5 ( ) 12 (1 15) 5.1 (4. 6.3) 42 (33 51) Guine-Bissu (.7 1.7) 63 (39 93) 1.5 ( ) 81 (6 14) 2.6 (2. 3.3) 144 ( ) Guyn < 1.16 (.14.17) 21 (18 23).42 (.33.52) 5.5 ( ).2 (.18.22) 26 (24 29) Hiti ( ) 2 (14 27).77 (.61.95) 7.3 (5.8 9.) 2.9 ( ) 27 (21 35) Hondurs 8.75 (.75.76).95 (.94.95).46 (.34.6).58 (.43.75).12 (.11.13) 1.5 ( ) Hungry 1.69 (.69.69).7 (.7.7) <.1 (<.1 <.1) <.1 ( <.1).7 (.69.71).71 (.7.72) Icelnd < 1 <.1 (<.1 <.1).28 (.28.28) <.1 (<.1 <.1).28 (.28.28) Indi (15 35) 17 (12 27) 31 (25 38) 2.4 (2. 2.9) 25 (17 36) 2 (13 28) Indonesi (66 15) 41 (26 59) 22 (13 32) 8.5 (5.2 13) 13 (86 17) 49 (34 67) Irn (Islmic Republic of) ( ) 3.5 ( ).11 (.7.15).14 (<.1.19) 2.8 (2. 3.8) 3.6 ( ) Irq (.16 3.) 2.2 (<.1 8.6).79 (.16 3.) 2.2 (<.1 8.6) Irelnd 5.2 (.2.2).43 (.43.43).2 (.2.21).43 (.42.45) Isrel 8.14 (.13.14).17 (.17.18) <.1 (<.1 <.1) <.1 (<.1 <.1).16 (.15.17).2 (.19.21) Itly 6.26 (.26.26).44 (.43.44).31 (.19.46) <.1 (<.1 <.1).29 (.28.31).49 (.46.51) Jmic 3 <.1 (<.1.1).31 (.26.38) <.1 (<.1.11).32 (.25.41).18 (.15.21).64 (.54.74) Jpn ( ) 1.8 ( ).1 (<.1.17) <.1 ( <.1) 2.2 ( ) 1.8 ( ) Jordn 7.25 (.24.25).33 (.33.34).25 (.24.25).33 (.33.34) Kzkhstn ( ) 8.6 (7. 1).37 (<.1.11).21 (<.1.64) 1.5 ( ) 8.8 (7.1 11) Keny (6.7 12) 21 (15 28) 8.1 (6.4 1) 18 (14 22) 17 (14 21) 39 (32 47) Kiribti < 1.54 (.44.65) 49 (4 59).54 (.44.65) 49 (4 59) Kuwit 4 <.1 (<.1 <.1).16 (.16.17) <.1 (<.1 <.1).16 (.16.17) Kyrgyzstn 6.65 (.63.67) 11 (11 12).55 (.42.7).94 ( ).71 (.69.73) 12 (12 13) Lo People's Democrtic Republic ( ) 55 (36 78).28 (.21.35) 4.1 ( ) 3.9 ( ) 59 (4 82) Ltvi 2.54 (.53.55) 2.7 ( ).19 (.14.24).96 ( ).73 (.68.78) 3.7 ( ) Lebnon 6.89 (.61.12) 1.6 ( ).89 (.61.12) 1.6 ( ) Lesotho ( ) 64 (38 97) 4.9 ( ) 231 (16 315) 6.2 ( ) 296 ( ) Liberi 4 3 (2.2 4.) 68 (49 9).33 (.28.39) 7.5 ( ) 3.3 ( ) 76 (57 98) Liby 6.61 (.43.82) 9.7 (6.8 13).61 (.43.82) 9.7 (6.8 13) Lithuni 3.22 (.22.22) 7.7 ( ).2 (.15.25).69 (.53.86).24 (.24.25) 8.3 ( ) Luxembourg < 1 <.1 (<.1 <.1).16 (.15.16) <.1 (<.1 <.1).16 (.15.16) Mdgscr (8.7 16) 51 (37 68).48 (.39.58) 2 ( ) 13 (9.2 16) 53 (39 7) Mlwi ( ) 17 (9.7 26) 7 (4.1 11) 42 (25 64) 9.8 (6.6 14) 59 (4 82) Mlysi ( ) 8 (4.5 12).62 (.38.93) 2.1 ( ) 3 ( ) 1 (6.4 15) Mldives < 1 <.1 (<.1.1) 2.3 ( ) <.1 (<.1.1) 2.3 ( ) Mli ( ) 11 (7.9 14).4 (.3.52) 2.4 (1.8 3.) 2.2 ( ) 13 (1 16) Mlt < 1 <.1 (<.1 <.1).26 (.26.26) <.1 (<.1 <.1).26 (.26.26) Mrshll Islnds < 1.2 (.14.28) 38 (26 53).2 (.14.28) 38 (26 53) Muritni 4.89 ( ) 22 (14 32).26 (.2.33).65 (.5.83).91 ( ) 23 (15 33) Muritius 1.16 (.16.17) 1.3 ( ).1 (<.1.14).79 ( ).26 (.23.3) 2.1 ( ) Mexico ( ) 1.7 ( ).31 (.24.38).24 (.19.3) 2.4 ( ) 1.9 (1.9 2.) Micronesi (Federted Sttes of) < 1.17 (<.1.28) 16 (7.6 27).17 (<.1.28) 16 (7.6 27) Rte Rtes re per 1 popultion. b All clcultions re mde before numbers re rounded. Dt for ll yers cn be downloded from GLOBAL TUBERCULOSIS REPORT 215 n 163

175 TABLE A4.2 Estimtes of TB mortlity, 214. Deths from TB mong HIV-positive people re of ficilly clssified s deths cused by HIV/AIDS in the Interntionl clssifiction of diseses. Popultion (millions) Mortlity (HIV-negtive people) Number (thousnds) Rte Mortlity (HIV-positive people) Number (thousnds) Rte Mortlity (HIV-negtive nd HIV-positive people) b Number (thousnds) Monco < 1 <.1 (<.1 <.1).18 (.11.26) <.1 (<.1 <.1).18 (.11.26) Mongoli 3.64 (.59.7) 2.2 (2. 2.4) <.1 (<.1 <.1) <.1 (<.1 <.1).66 (.61.72) 2.3 ( ) Montenegro < 1 <.1 (<.1 <.1).58 (.56.6) <.1 (<.1 <.1).58 (.56.6) Montserrt < 1 <.1 (<.1 <.1) 21 (2 21) <.1 (<.1 <.1) 21 (2 21) Morocco (.22 11) 7.9 (<.1 33).12 (.66.18).34 (.19.54) 2.8 (.33 11) 8.2 (.1 33) Mozmbique (12 26) 67 (44 96) 37 (29 45) 134 (16 165) 55 (25 97) 21 (9 355) Mynmr (2 37) 53 (38 7) 4.1 ( ) 7.7 ( ) 32 (24 41) 6 (45 77) Nmibi (1.1 2.) 63 (45 83) 1.5 ( ) 64 (51 79) 3 ( ) 127 (14 152) Nuru < 1 <.1 (<.1 <.1) 6 ( ) <.1 (<.1 <.1) 6 ( ) Nepl ( ) 17 (12 24).38 (.28.5) 1.4 (1. 1.8) 5.3 ( ) 19 (13 25) Netherlnds (.21.22).13 (.13.13) <.1 (<.1 <.1) <.1 (<.1 <.1).27 (.24.29).16 (.14.17) New Cledoni < 1 <.1 (<.1 <.1) 1.2 ( ) <.1 (<.1 <.1) 1.2 ( ) New Zelnd 4 <.1 (<.1 <.1).13 (.13.13) <.1 (<.1 <.1).13 (.12.15) Nicrgu 6.21 (.16.26) 3.4 ( ).22 (.17.28).37 (.28.47).23 (.18.28) 3.8 (3. 4.7) Niger ( ) 18 (13 23).47 (.39.56) 2.5 (2. 2.9) 3.8 ( ) 2 (15 26) Nigeri (91 28) 97 (51 156) 78 (53 11) 44 (3 61) 25 (16 36) 141 (91 21) Niue < 1 Northern Mrin Islnds < 1 <.1 (<.1 <.1) 5 ( ) <.1 (<.1 <.1) 5 ( ) Norwy 5 <.1 (<.1 <.1).15 (.14.15) <.1 (<.1 <.1).15 (.14.16) Omn 4.24 (.15.35).56 (.36.82) <.1 (<.1 <.1) <.1 (<.1 <.1).25 (.16.36).59 (.38.84) Pkistn (11 11) 26 (6. 61) 1.3 ( ).68 (.41 1.) 5 (12 11) 27 (6.5 61) Plu < 1 <.1 (<.1 <.1) 1.2 (.25 3.) <.1 (<.1 <.1) 1.2 (.25 3.) Pnm 4.21 (.2.23) 5.5 ( ).46 (.34.6) 1.2 ( ).26 (.24.28) 6.7 ( ) Ppu New Guine 7 3 ( ) 4 (25 58).54 (.33.8) 7.2 (4.4 11) 3.5 ( ) 47 (32 65) Prguy 7.19 (.16.23) 2.9 ( ).53 (.42.65).81 (.64 1.).25 (.21.28) 3.7 ( ) Peru ( ) 7.2 ( ).25 (.18.34).81 ( ) 2.5 (2. 3.) 8 ( ) Philippines 99 1 (9. 11) 1 (9.1 11).8 (.55.11) <.1 (<.1.11) 1 (9.1 11) 1 (9.2 12) Polnd (.51.55) 1.4 ( ).16 (.1.23) <.1 (<.1 <.1).54 (.53.56) 1.4 ( ) Portugl 1.12 (.12.13) 1.2 ( ).38 (.23.57).37 (.22.54).16 (.15.18) 1.6 ( ) Puerto Rico 4 <.1 (<.1 <.1).19 (.19.19) <.1 (<.1 <.1).19 (.19.19) Qtr 2 <.1 (<.1 <.1).15 (<.1.23) <.1 (<.1 <.1).15 (<.1.23) Republic of Kore ( ) 3.8 ( ) <.1 (<.1.13) <.1 (<.1 <.1) 1.9 ( ) 3.8 ( ) Republic of Moldov 4.32 (.3.34) 7.8 ( ).11 (.89.14) 2.7 ( ).43 (.4.46) 11 (9.9 11) Romni ( ) 5.5 ( ).54 (.35.77).27 (.18.39) 1.1 ( ) 5.8 ( ) Russin Federtion (15 16) 11 (11 11) 1.1 ( ).73 (.58.91) 17 (16 18) 12 (11 12) Rwnd (.51.99) 6.4 ( ).31 (.21.42) 2.7 ( ) 1 ( ) 9.1 (7. 12) Sint Kitts nd Nevis < 1 <.1 (<.1 <.1) 2.7 ( ) <.1 (<.1 <.1) 2.7 ( ) Sint Luci < 1 <.1 (<.1 <.1) 2.4 ( ) <.1 (<.1 <.1) 2.4 ( ) Sint Vincent nd the Grendines < 1 <.1 (<.1 <.1) 1 (1. 1.1) <.1 (<.1 <.1) 1 (1. 1.1) Smo < 1 <.1 (<.1 <.1) 3.4 ( ) <.1 (<.1 <.1) 3.4 ( ) Sn Mrino < 1 So Tome nd Principe < 1.14 (<.1.19) 7.3 (4.8 1) <.1 (<.1.1) 2.7 ( ).19 (.12.26) 1 (6.7 14) Sudi Arbi ( ) 2.1 ( ).65 ( ) 2.1 ( ) Senegl ( ) 21 (15 28).43 (.34.52) 2.9 ( ) 3.5 ( ) 24 (18 31) Serbi 9.12 (.11.13) 1.4 ( ).12 (.11.13) 1.4 ( ) Seychelles < 1 Sierr Leone ( ) 45 (3 62).7 (.47.98) 11 (7.4 16) 3.5 ( ) 56 (4 74) Singpore 6.57 (.48.68) 1 ( ).13 (<.1.18).24 (.17.32).7 (.6.82) 1.3 ( ) Sint Mrten (Dutch prt) < 1 Slovki 5.25 (.24.25).45 (.45.46).25 (.24.25).45 (.45.46) Sloveni 2.16 (.16.16).76 (.75.76).16 (.16.16).76 (.75.76) Solomon Islnds < 1.76 (.53.1) 13 (9.3 18).76 (.53.1) 13 (9.3 18) Somli 11 7 ( ) 67 (48 88).44 (.34.56) 4.2 ( ) 7.5 ( ) 71 (52 92) South Afric (22 26) 44 (41 48) 72 (58 89) 134 (17 164) 96 (81 11) 178 (151 29) South Sudn ( ) 29 (2 39) 3.4 ( ) 29 (2 39) Spin (.23.24).5 (.5.51).61 (.36.93).13 (<.1.2).29 (.27.32).64 (.57.7) Sri Lnk (1. 1.6) 6.1 ( ).14 (.1.18) <.1 (<.1 <.1) 1.3 (1. 1.6) 6.2 ( ) Sudn (4.3 14) 21 (11 34) 1 ( ) 2.5 ( ) 9.3 (5.2 15) 24 (13 37) Surinme < 1.11 (.11.12) 2.1 (2. 2.2).11 (<.1.14) 2 ( ).22 (.19.26) 4.1 ( ) Swzilnd 1.65 (.4.95) 51 (32 75) 1.7 ( ) 135 (91 187) 2.4 ( ) 186 ( ) Sweden 1.25 (.25.26).26 (.26.27) <.1 (<.1 <.1) <.1 (<.1 <.1).27 (.27.28).28 (.27.29) Switzerlnd 8.1 (.1.1).12 (.12.13) <.1 (<.1 <.1) <.1 (<.1 <.1).12 (.11.13).15 (.13.16) Rte Rtes re per 1 popultion. b All clcultions re mde before numbers re rounded. 164 n GLOBAL TUBERCULOSIS REPORT 215 Dt for ll yers cn be downloded from

176 TABLE A4.2 Estimtes of TB mortlity, 214. Deths from TB mong HIV-positive people re of ficilly clssified s deths cused by HIV/AIDS in the Interntionl clssifiction of diseses. Popultion (millions) Mortlity (HIV-negtive people) Number (thousnds) Rte Mortlity (HIV-positive people) Number (thousnds) Rte Mortlity (HIV-negtive nd HIV-positive people) b Number (thousnds) Syrin Arb Republic (.1.13) <.1 (<.1 <.1).12 (.1.13) <.1 (<.1 <.1) Tjikistn 8.27 (.2.36) 3.3 ( ).55 (.39.74).66 (.47.89).33 (.25.42) 3.9 (3. 5.) Thilnd (3.9 12) 11 (5.7 18) 4.5 ( ) 6.6 (3.4 11) 12 (7.5 17) 18 (11 26) The Former Yugoslv Republic of Mcedoni 2.49 (.48.5) 2.3 ( ).49 (.48.5) 2.3 ( ) Timor-Leste ( ) 94 (66 126) 1.1 ( ) 94 (66 126) Togo 7.63 (.44.85) 8.8 (6.1 12).3 (.23.38) 4.2 ( ).93 ( ) 13 (1 16) Tokelu < 1 Tong < 1 <.1 (<.1 <.1) 2.1 ( ) <.1 (<.1 <.1) 2.1 ( ) Trinidd nd Tobgo 1.27 (.24.29) 2 ( ).12 (<.1.15).89 ( ).39 (.35.42) 2.8 ( ) Tunisi (.47.54) 2 ( ) <.1 (<.1.1) <.1 (<.1 <.1).23 (.52.55) 2.1 ( ) Turkey (.4.55).61 (.52.7) <.1 (<.1.12) <.1 (<.1 <.1).48 (.41.55).62 (.53.72) Turkmenistn 5.18 (.15.21) 3.4 (2.9 4.).18 (.15.21) 3.4 (2.9 4.) Turks nd Cicos Islnds < 1 <.1 (<.1 <.1).75 (.72.77) <.1 (<.1 <.1).75 (.72.77) Tuvlu < 1 <.1 (<.1 <.1) 14 (8.3 21) <.1 (<.1 <.1) 14 (8.3 21) US Virgin Islnds < 1 <.1 (<.1 <.1).98 (.96.99) <.1 (<.1 <.1).98 (.96.99) Ugnd ( ) 12 (8.4 16) 6.4 (5. 8.1) 17 (13 21) 11 (8.9 13) 29 (24 35) Ukrine ( ) 13 (13 13) 1.2 ( ) 2.7 ( ) 6.9 ( ) 15 (14 16) United Arb Emirtes 9.29 (.24.35).32 (.26.38).29 (.24.35).32 (.26.38) United Kingdom of Gret Britin nd Northern Irelnd 64.3 (.29.3).46 (.45.46).13 (<.1.24) <.1 (<.1 <.1).31 (.3.32).48 (.46.49) United Republic of Tnzni 52 3 (13 54) 58 (26 14) 28 (15 43) 53 (3 84) 58 (36 85) 112 (69 164) United Sttes of Americ (.45.47).14 (.14.15).11 (.54.19) <.1 (<.1 <.1).57 (.51.65).18 (.16.2) Uruguy 3.57 (.54.6) 1.7 ( ).24 (.17.32).7 (.51.92).81 (.73.89) 2.4 ( ) Uzbekistn ( ) 9.1 (8. 1).16 (.12.2).54 (.42.69) 2.9 ( ) 9.7 (8.5 11) Vnutu < 1.2 (.14.28) 7.9 (5.4 11).2 (.14.28) 7.9 (5.4 11) Venezuel (Bolivrin Republic of) (.54.55) 1.8 ( ).12 (.83.17).4 (.27.55).67 (.62.71) 2.2 (2. 2.3) Viet Nm (11 23) 18 (12 25) 1.9 ( ) 2 ( ) 19 (13 25) 2 (14 27) Wllis nd Futun Islnds < 1 <.1 (<.1 <.1).3 (.19.44) <.1 (<.1 <.1).3 (.19.44) West Bnk nd Gz Strip 5 <.1 (<.1 <.1).17 (.17.18) <.1 (<.1 <.1) <.1 (<.1 <.1) <.1 (<.1 <.1).2 (.19.21) Yemen ( ) 4.4 ( ).25 (.19.31).1 (<.1.12) 1.2 ( ) 4.4 ( ) Zmbi ( ) 32 (2 48) 11 (7.4 16) 72 (47 12) 16 (12 22) 14 (76 137) Zimbbwe ( ) 15 (9.5 22) 5.2 ( ) 34 (21 51) 7.6 (5.2 1) 5 (34 68) WHO regions Africn Region (35 56) 46 (36 58) 31 (27 35) 32 (28 36) 75 (65 87) 78 (67 9) Region of the Americs (16 18) 1.7 ( ) 6 ( ).61 (.53.69) 23 (22 24) 2.3 ( ) Estern Mediterrnen Region (43 15) 14 (6.8 23) 3.2 (2.6 4.).51 (.41.62) 91 (46 15) 14 (7.2 24) Europen Region (33 34) 3.7 ( ) 3.2 ( ).35 (.3.4) 37 (36 38) 4 ( ) South-Est Asi Region (35 57) 24 (19 3) 62 (51 74) 3.3 ( ) 52 (41 63) 27 (22 33) Western Pcific Region (81 95) 4.8 ( ) 4.9 ( ).27 (.23.31) 93 (86 1) 5 ( ) Globl (97 1 3) 16 (13 18) 39 (35 43) 5.3 ( ) 1 5 ( ) 21 (19 23) Rte Rtes re per 1 popultion. b All clcultions re mde before numbers re rounded. Dt for ll yers cn be downloded from GLOBAL TUBERCULOSIS REPORT 215 n 165

177 TABLE A4.3 TB cse notifictions, 214 New nd relpse Bcteriologiclly confirmed New cses Pulmonry Cliniclly dignosed Bcteriologiclly confirmed Relpses Pulmonry Cliniclly dignosed Extrpulmonry Extrpulmonry Previously treted, excluding relpse Afghnistn Albni Algeri Americn Smo Andorr Angol Anguill 1 1 Antigu nd Brbud Argentin Armeni Arub 2 2 Austrli Austri Azerbijn Bhms Bhrin Bngldesh Brbdos Belrus Belgium Belize Benin Bermud Bhutn Bolivi (Plurintionl Stte of) Bonire, Sint Eusttius nd Sb Bosni nd Herzegovin Botswn Brzil British Virgin Islnds Brunei Drusslm Bulgri Burkin Fso Burundi Cbo Verde Cmbodi Cmeroon Cnd Cymn Islnds Centrl Africn Republic Chd Chile Chin Chin, Hong Kong SAR Chin, Mco SAR Colombi Comoros Congo Cook Islnds Cost Ric Croti Cub Curço Cyprus Czech Republic Côte d'ivoire Democrtic People's Republic of Kore Democrtic Republic of the Congo Denmrk Djibouti Includes cses for which the tretment history is unknown. 166 n GLOBAL TUBERCULOSIS REPORT 215 Dt for ll yers cn be downloded from

178 TABLE A4.3 TB cse notifictions, 214 New nd relpse Pulmonry Bcteriologiclly confirmed New cses Cliniclly dignosed Bcteriologiclly confirmed Relpses Pulmonry Cliniclly dignosed Extrpulmonry Extrpulmonry Previously treted, excluding relpse Dominic 1 1 Dominicn Republic Ecudor Egypt El Slvdor Equtoril Guine Eritre Estoni Ethiopi Fiji Finlnd Frnce French Polynesi Gbon Gmbi Georgi Germny Ghn Greece Greenlnd Grend Gum Guteml Guine Guine-Bissu Guyn Hiti Hondurs Hungry Icelnd Indi Indonesi Irn (Islmic Republic of) Irq Irelnd Isrel Itly Jmic Jpn Jordn Kzkhstn Keny Kiribti Kuwit Kyrgyzstn Lo People's Democrtic Republic Ltvi Lebnon Lesotho Liberi Liby Lithuni Luxembourg Mdgscr Mlwi Mlysi Mldives Mli Mlt Mrshll Islnds Includes cses for which the tretment history is unknown. Dt for ll yers cn be downloded from GLOBAL TUBERCULOSIS REPORT 215 n 167

179 TABLE A4.3 TB cse notifictions, 214 New nd relpse Pulmonry Bcteriologiclly confirmed New cses Cliniclly dignosed Bcteriologiclly confirmed Relpses Pulmonry Cliniclly dignosed Extrpulmonry Extrpulmonry Previously treted, excluding relpse Muritni Muritius Mexico Micronesi (Federted Sttes of) Monco Mongoli Montenegro Montserrt Morocco Mozmbique Mynmr Nmibi Nuru Nepl Netherlnds New Cledoni New Zelnd Nicrgu Niger Nigeri Niue Northern Mrin Islnds Norwy Omn Pkistn Plu Pnm Ppu New Guine Prguy Peru Philippines Polnd Portugl Puerto Rico Qtr Republic of Kore Republic of Moldov Romni Russin Federtion Rwnd Sint Kitts nd Nevis Sint Luci Sint Vincent nd the Grendines Smo Sn Mrino So Tome nd Principe Sudi Arbi Senegl Serbi Serbi (without Kosovo) Kosovo Seychelles Sierr Leone Singpore Sint Mrten (Dutch prt) Slovki Sloveni Solomon Islnds Somli South Afric Includes cses for which the tretment history is unknown. 168 n GLOBAL TUBERCULOSIS REPORT 215 Dt for ll yers cn be downloded from

180 TABLE A4.3 TB cse notifictions, 214 New nd relpse Pulmonry Bcteriologiclly confirmed New cses Cliniclly dignosed Bcteriologiclly confirmed Relpses Pulmonry Cliniclly dignosed Extrpulmonry Extrpulmonry Previously treted, excluding relpse South Sudn Spin Sri Lnk Sudn Surinme Swzilnd Sweden Switzerlnd Syrin Arb Republic Tjikistn Thilnd The Former Yugoslv Republic of Mcedoni Timor-Leste Togo Tokelu Tong Trinidd nd Tobgo Tunisi Turkey Turkmenistn Turks nd Cicos Islnds Tuvlu US Virgin Islnds Ugnd Ukrine United Arb Emirtes United Kingdom of Gret Britin nd Northern Irelnd United Republic of Tnzni United Sttes of Americ Uruguy Uzbekistn Vnutu Venezuel (Bolivrin Republic of) Viet Nm Wllis nd Futun Islnds West Bnk nd Gz Strip Yemen Zmbi Zimbbwe WHO regions Africn Region Region of the Americs Estern Mediterrnen Region Europen Region South-Est Asi Region Western Pcific Region Globl Includes cses for which the tretment history is unknown. Dt for ll yers cn be downloded from GLOBAL TUBERCULOSIS REPORT 215 n 169

181 TABLE A4.4 Notified new nd relpse TB cses by ge nd sex, 214 * New cses only. Notified cses by ge (Number) Notified cses by ge group (rte per 1 popultion) 14 > 15 Unknown > 65 Afghnistn* Femle Mle Albni Femle Mle Algeri* Femle Mle Americn Smo Femle Mle Andorr Femle Mle Angol Femle Mle Anguill Femle 1 91 Mle Antigu nd Brbud Femle Mle Argentin Femle Mle Armeni Femle Mle Arub Femle 2 35 Mle Austrli Femle Mle Austri Femle Mle Azerbijn* Femle Mle Bhms Femle Mle Bhrin Femle Mle Bngldesh* Femle Mle Brbdos* Femle Mle Belrus Femle Mle Belgium Femle Mle Belize Femle Mle Benin* Femle Mle Bermud Femle Mle Bhutn Femle Mle Bolivi (Plurintionl Stte of)* Femle Mle Bonire, Sint Eusttius nd Sb Femle Mle Bosni nd Herzegovin Femle Mle Botswn Femle Mle Brzil Femle Mle British Virgin Islnds Femle Mle Brunei Drusslm Femle Mle Bulgri Femle Mle Burkin Fso* Femle Mle n GLOBAL TUBERCULOSIS REPORT 215 Dt for ll yers cn be downloded from

182 TABLE A4.4 Notified new nd relpse TB cses by ge nd sex, 214 Notified cses by ge (Number) Notified cses by ge group (rte per 1 popultion) 14 > 15 Unknown > 65 Burundi* Femle Mle Cbo Verde* Femle Mle Cmbodi Femle Mle Cmeroon Femle Mle Cnd Femle Mle Cymn Islnds Femle Mle Centrl Africn Republic* Femle Mle Chd Femle Mle Chile Femle Mle Chin Femle Mle Chin, Hong Kong SAR Femle Mle Chin, Mco SAR Femle Mle Colombi Femle Mle Comoros Femle Mle Congo* Femle Mle Cook Islnds Femle Mle Cost Ric Femle Mle Croti Femle Mle Cub Femle Mle Curço Femle Mle Cyprus Femle Mle Czech Republic Femle Mle Côte d'ivoire* Femle Mle Democrtic People's Republic of Kore* Femle Mle Democrtic Republic of the Congo* Femle Mle Denmrk Femle Mle Djibouti* Femle Mle Dominic Femle Mle 1 23 Dominicn Republic Femle Mle Ecudor Femle Mle Egypt* Femle Mle El Slvdor* Femle Mle Equtoril Guine Femle Mle * New cses only. Dt for ll yers cn be downloded from GLOBAL TUBERCULOSIS REPORT 215 n 171

183 TABLE A4.4 Notified new nd relpse TB cses by ge nd sex, 214 Notified cses by ge (Number) Notified cses by ge group (rte per 1 popultion) 14 > 15 Unknown > 65 Eritre Femle Mle Estoni Femle Mle Ethiopi* Femle Mle Fiji Femle Mle Finlnd Femle Mle Frnce Femle Mle French Polynesi Femle Mle Gbon Femle Mle Gmbi Femle Mle Georgi Femle Mle Germny Femle Mle Ghn Femle Mle Greece Femle Mle Greenlnd Femle Mle Grend Femle Mle Gum Femle Mle Guteml Femle Mle Guine* Femle Mle Guine-Bissu Femle Mle Guyn Femle Mle Hiti Femle Mle Hondurs Femle Mle Hungry Femle Mle Icelnd Femle Mle Indi Femle Mle Indonesi Femle Mle Irn (Islmic Republic of) Femle Mle Irq Femle Mle Irelnd Femle Mle Isrel Femle Mle Itly Femle Mle Jmic Femle Mle Jpn Femle Mle * New cses only. 172 n GLOBAL TUBERCULOSIS REPORT 215 Dt for ll yers cn be downloded from

184 TABLE A4.4 Notified new nd relpse TB cses by ge nd sex, 214 Notified cses by ge (Number) Notified cses by ge group (rte per 1 popultion) 14 > 15 Unknown > 65 Jordn Femle Mle Kzkhstn Femle Mle Keny Femle Mle Kiribti Femle Mle Kuwit Femle Mle Kyrgyzstn* Femle Mle Lo People's Democrtic Republic Femle Mle Ltvi Femle Mle Lebnon Femle Mle Lesotho Femle Mle Liberi* Femle Mle Liby Femle Mle Lithuni Femle Mle Luxembourg Femle Mle Mdgscr* Femle Mle Mlwi Femle Mle Mlysi Femle Mle Mldives Femle Mle Mli Femle Mle Mlt Femle Mle Mrshll Islnds Femle Mle Muritni Femle Mle Muritius Femle Mle Mexico Femle Mle Micronesi (Federted Sttes of) Femle Mle Monco Femle Mle Mongoli Femle Mle Montenegro Femle Mle Montserrt Femle Mle Morocco* Femle Mle Mozmbique Femle Mle Mynmr Femle Mle Nmibi* Femle Mle * New cses only. Dt for ll yers cn be downloded from GLOBAL TUBERCULOSIS REPORT 215 n 173

185 TABLE A4.4 Notified new nd relpse TB cses by ge nd sex, 214 Notified cses by ge (Number) Notified cses by ge group (rte per 1 popultion) 14 > 15 Unknown > 65 Nuru Femle Mle Nepl* Femle Mle Netherlnds Femle Mle New Cledoni Femle Mle New Zelnd Femle Mle Nicrgu* Femle Mle Niger* Femle Mle Nigeri Femle Mle Niue Femle Mle Northern Mrin Islnds Femle Mle Norwy Femle Mle Omn Femle Mle Pkistn Femle Mle Plu* Femle Mle Pnm Femle Mle Ppu New Guine* Femle Mle Unknown Prguy Femle Mle Peru* Femle Mle Philippines Femle Mle Polnd Femle Mle Portugl Femle Mle Puerto Rico Femle Mle Qtr Femle Mle Republic of Kore Femle Mle Republic of Moldov Femle Mle Romni Femle Mle Russin Federtion Femle Mle Rwnd Femle Mle Sint Kitts nd Nevis Femle Mle Sint Luci Femle Mle Sint Vincent nd the Grendines Femle Mle Smo Femle Mle Sn Mrino Femle * New cses only. Mle 174 n GLOBAL TUBERCULOSIS REPORT 215 Dt for ll yers cn be downloded from

186 TABLE A4.4 Notified new nd relpse TB cses by ge nd sex, 214 Notified cses by ge (Number) Notified cses by ge group (rte per 1 popultion) 14 > 15 Unknown > 65 So Tome nd Principe Femle Mle Sudi Arbi Femle Mle Senegl* Femle Mle Serbi Femle Mle Seychelles Femle Mle Sierr Leone Femle Mle Singpore Femle Mle Sint Mrten (Dutch prt)* Femle Mle Slovki Femle Mle Sloveni Femle Mle Solomon Islnds Femle Mle Somli Femle Mle South Afric Femle Mle South Sudn* Femle Mle Spin Femle Mle Sri Lnk Femle Mle Sudn* Femle Mle Surinme Femle Mle Swzilnd Femle Mle Sweden Femle Mle Switzerlnd* Femle Mle Syrin Arb Republic Femle Mle Tjikistn Femle Mle Thilnd* Femle Mle The Former Yugoslv Republic of Mcedoni Femle Mle Timor-Leste* Femle Mle Togo Femle Mle Tokelu Femle Mle Tong Femle Mle Trinidd nd Tobgo Femle Mle Tunisi Femle Mle Turkey Femle Mle Turkmenistn* Femle Mle * New cses only. Dt for ll yers cn be downloded from GLOBAL TUBERCULOSIS REPORT 215 n 175

187 TABLE A4.4 Notified new nd relpse TB cses by ge nd sex, 214 Notified cses by ge (Number) Notified cses by ge group (rte per 1 popultion) 14 > 15 Unknown > 65 Turks nd Cicos Islnds Femle Mle 1 35 Tuvlu Femle Mle US Virgin Islnds Femle Mle Ugnd Femle Mle Ukrine Femle Mle United Arb Emirtes Femle Mle United Kingdom of Gret Britin nd Northern Irelnd Femle Mle United Republic of Tnzni Femle Mle United Sttes of Americ Femle Mle Uruguy Femle Mle Uzbekistn Femle Mle Vnutu Femle Mle Venezuel (Bolivrin Republic of) Femle Mle Viet Nm* Femle Mle Wllis nd Futun Islnds* Femle Mle West Bnk nd Gz Strip Femle Mle Yemen Femle Mle Zmbi Femle Mle Zimbbwe Femle Mle WHO regions Africn Region Femle Mle Region of the Americs Femle Mle Estern Mediterrnen Region Femle Mle Europen Region Femle Mle South-Est Asi Region Femle Mle Western Pcific Region Femle Mle Unknown Globl Femle Mle Unknown * New cses only. 176 n GLOBAL TUBERCULOSIS REPORT 215 Dt for ll yers cn be downloded from

188 TABLE A4.5 Tretment outcomes by TB cse type, 213 nd tretment outcomes for RR-/MDR-TB cses, 212 Cohort (Number) New nd relpse, 213 Previously treted, excluding relpse, 213 Lost to Not Success Filed Died follow-up evluted Cohort Success Cohort (%) (%) (%) (%) (%) (Number) (%) (Number) Afghnistn Albni Algeri Americn Smo Andorr Angol Anguill Antigu nd Brbud* Argentin Armeni Arub Austrli Austri Azerbijn* Bhms Bhrin Bngldesh Brbdos* Belrus Belgium Belize Benin* Bermud Bhutn Bolivi (Plurintionl Stte of)* Bonire, Sint Eusttius nd Sb Bosni nd Herzegovin Botswn Brzil British Virgin Islnds* 1 1 Brunei Drusslm Bulgri Burkin Fso* Burundi Cbo Verde Cmbodi Cmeroon* Cnd Cymn Islnds Centrl Africn Republic* Chd* Chile Chin Chin, Hong Kong SAR Chin, Mco SAR Colombi Comoros* Congo Cook Islnds* Cost Ric Croti Cub Curço 2 1 Cyprus Czech Republic Côte d'ivoire* Democrtic People's Republic of Kore Democrtic Republic of the Congo* Denmrk Djibouti Dominic Dominicn Republic * Relpses included in the previously treted cohort. All clcultions re mde before numbers re rounded, so the totl of ll outcomes my not lwys pper s 1%. HIV-positive TB, 213 RR-/MDR-TB, 212 Success (%) Cohort (Number) Success (%) Dt for ll yers cn be downloded from GLOBAL TUBERCULOSIS REPORT 215 n 177

189 TABLE A4.5 Tretment outcomes by TB cse type, 213 nd tretment outcomes for RR-/MDR-TB cses, 212 Cohort (Number) Previously treted, excluding relpse, New nd relpse, Lost to Not Success Filed Died follow-up evluted Cohort Success Cohort Success Cohort (%) (%) (%) (%) (%) (Number) (%) (Number) (%) (Number) HIV-positive TB, 213 RR-/MDR-TB, 212 Ecudor Egypt El Slvdor Equtoril Guine Eritre Estoni Ethiopi* Fiji Finlnd Success (%) Frnce French Polynesi* Gbon Gmbi* Georgi Germny Ghn Greece Greenlnd Grend 1 1 Gum Guteml* Guine Guine-Bissu Guyn Hiti* Hondurs* Hungry Icelnd Indi Indonesi Irn (Islmic Republic of) Irq Irelnd Isrel Itly Jmic Jpn* Jordn Kzkhstn Keny* Kiribti Kuwit Kyrgyzstn* Lo People's Democrtic Republic Ltvi Lebnon Lesotho* Liberi Liby Lithuni Luxembourg Mdgscr* Mlwi Mlysi Mldives Mli Mlt Mrshll Islnds Muritni Muritius Mexico Micronesi (Federted Sttes of) * Relpses included in the previously treted cohort. All clcultions re mde before numbers re rounded, so the totl of ll outcomes my not lwys pper s 1%. 178 n GLOBAL TUBERCULOSIS REPORT 215 Dt for ll yers cn be downloded from

190 TABLE A4.5 Tretment outcomes by TB cse type, 213 nd tretment outcomes for RR-/MDR-TB cses, 212 Cohort (Number) Previously treted, excluding relpse, New nd relpse, Lost to Not Success Filed Died follow-up evluted Cohort Success Cohort Success Cohort (%) (%) (%) (%) (%) (Number) (%) (Number) (%) (Number) HIV-positive TB, 213 RR-/MDR-TB, 212 Success (%) Monco Mongoli Montenegro* Montserrt Morocco Mozmbique* Mynmr* Nmibi* Nuru Nepl Netherlnds New Cledoni* New Zelnd Nicrgu* Niger* Nigeri* Niue Northern Mrin Islnds Norwy Omn Pkistn Plu* Pnm Ppu New Guine* Prguy Peru* Philippines Polnd Portugl Puerto Rico* Qtr Republic of Kore Republic of Moldov Romni Russin Federtion Rwnd Sint Kitts nd Nevis Sint Luci* 16 1 Sint Vincent nd the Grendines* Smo Sn Mrino So Tome nd Principe Sudi Arbi Senegl Serbi Seychelles Sierr Leone* Singpore Sint Mrten (Dutch prt)* Slovki Sloveni Solomon Islnds Somli South Afric South Sudn Spin Sri Lnk Sudn Surinme Swzilnd Sweden Switzerlnd * Relpses included in the previously treted cohort. All clcultions re mde before numbers re rounded, so the totl of ll outcomes my not lwys pper s 1%. Dt for ll yers cn be downloded from GLOBAL TUBERCULOSIS REPORT 215 n 179

191 TABLE A4.5 Tretment outcomes by TB cse type, 213 nd tretment outcomes for RR-/MDR-TB cses, 212 Cohort (Number) Previously treted, excluding relpse, New nd relpse, Lost to Not Success Filed Died follow-up evluted Cohort Success Cohort Success Cohort (%) (%) (%) (%) (%) (Number) (%) (Number) (%) (Number) HIV-positive TB, 213 RR-/MDR-TB, 212 Syrin Arb Republic Tjikistn Thilnd Success (%) The Former Yugoslv Republic of Mcedoni Timor-Leste Togo Tokelu Tong Trinidd nd Tobgo Tunisi Turkey Turkmenistn* Turks nd Cicos Islnds 2 1 Tuvlu US Virgin Islnds Ugnd Ukrine United Arb Emirtes United Kingdom of Gret Britin nd Northern Irelnd United Republic of Tnzni United Sttes of Americ* Uruguy Uzbekistn Vnutu Venezuel (Bolivrin Republic of) Viet Nm Wllis nd Futun Islnds* 2 1 West Bnk nd Gz Strip Yemen Zmbi Zimbbwe* WHO regions Africn Region Region of the Americs Estern Mediterrnen Region Europen Region South-Est Asi Region Western Pcific Region Globl * Relpses included in the previously treted cohort. All clcultions re mde before numbers re rounded, so the totl of ll outcomes my not lwys pper s 1%. 18 n GLOBAL TUBERCULOSIS REPORT 215 Dt for ll yers cn be downloded from

192 TABLE A4.6 Mesured percentge of TB cses with MDR-TB, most recent yer vilble New TB cses Previously treted TB cses Yer Source Coverge Percentge Yer Source Coverge Percentge Afghnistn Albni 212 Surveillnce Ntionl.58 (<.1 3.2) 212 Surveillnce Ntionl ( 22) Algeri 22 Survey Ntionl 1.4 (.6 2.7) 22 Survey Ntionl 9.1 (1.1 29) Americn Smo Andorr 214 Surveillnce Ntionl ( 71) 214 Surveillnce Ntionl ( 98) Angol Anguill Antigu nd Brbud Argentin 25 Survey Ntionl 2.2 ( ) 25 Survey Ntionl 15 (9.8 23) Armeni 27 Survey Ntionl 9.4 (7. 12) 27 Survey Ntionl 43 (38 49) Arub Austrli 214 Surveillnce Ntionl 1.7 (.86 3.) 214 Surveillnce Ntionl 1 (2.8 24) Austri 214 Surveillnce Ntionl 2.7 ( ) 214 Surveillnce Ntionl 37 (16 62) Azerbijn 213 Survey Ntionl 13 (1 16) 213 Survey Ntionl 28 (22 34) Bhms 212 Surveillnce Ntionl 3.7 (<.1 19) 213 Surveillnce Ntionl ( 71) Bhrin 212 Surveillnce Ntionl 1.9 ( ) 212 Surveillnce Ntionl 1 (2.5 1) Bngldesh 211 Survey Ntionl 1.4 (.7 2.5) 211 Survey Ntionl 29 (24 34) Brbdos 214 Surveillnce Ntionl ( 71) 214 Surveillnce Ntionl ( ) Belrus 214 Surveillnce Ntionl 34 (32 36) 214 Surveillnce Ntionl 69 (66 72) Belgium 213 Surveillnce Ntionl 1.8 ( ) 213 Surveillnce Ntionl 2.4 (<.1 13) Belize 213 Surveillnce Ntionl 1 (29 1) Benin 21 Survey Ntionl.5 (.1 2.) 214 Surveillnce Ntionl 4.8 ( ) Bermud 212 Surveillnce Ntionl ( 84) 212 Surveillnce Ntionl ( ) Bhutn 211 Survey Ntionl 35 (21 52) Bolivi (Plurintionl Stte of) 214 Surveillnce Ntionl 1 (7.7 13) Bonire, Sint Eusttius nd Sb 211 Surveillnce Ntionl 1 (2.5 1) Bosni nd Herzegovin 213 Surveillnce Ntionl (.57) 213 Surveillnce Ntionl 1.6 (<.1 8.5) Botswn 28 Survey Ntionl 2.5 ( ) 28 Survey Ntionl 6.6 (2.4 11) Brzil 28 Survey Sub-ntionl 1.4 (1. 1.8) 28 Survey Sub-ntionl 7.5 ( ) British Virgin Islnds Brunei Drusslm 214 Surveillnce Ntionl.88 (<.1 4.8) 214 Surveillnce Ntionl ( 52) Bulgri 212 Surveillnce Ntionl 2.3 ( ) 212 Surveillnce Ntionl 23 (17 31) Burkin Fso Burundi Cbo Verde Cmbodi 27 Survey Ntionl 1.4 (.7 2.5) 27 Survey Ntionl 11 (4. 22) Cmeroon Cnd 213 Surveillnce Ntionl 1.4 (.7 2.4) 213 Surveillnce Ntionl 4.6 (.96 13) Cymn Islnds 213 Surveillnce Ntionl ( 71) 213 Surveillnce Ntionl ( ) Centrl Africn Republic 29 Survey Sub-ntionl.4 ( 2.5) Chd Chile 214 Surveillnce Ntionl 1.2 ( ) 214 Surveillnce Ntionl.56 (<.1 3.1) Chin 27 Survey Ntionl 5.7 (4.5 7.) 27 Survey Ntionl 26 (22 3) Chin, Hong Kong SAR 212 Surveillnce Ntionl.97 ( ) 212 Surveillnce Ntionl 2.6 ( ) Chin, Mco SAR 214 Surveillnce Ntionl 1.7 ( ) 214 Surveillnce Ntionl 19 (5.4 42) Colombi 25 Survey Ntionl 2.4 ( ) 212 Surveillnce Ntionl 13 (9.6 17) Comoros Congo Cook Islnds 213 Surveillnce Ntionl ( 98) 213 Surveillnce Ntionl ( ) Cost Ric 26 Survey Ntionl 1.5 ( ) 212 Surveillnce Ntionl 4.5 (.12 23) Croti 214 Surveillnce Ntionl ( 1.3) 214 Surveillnce Ntionl 6.9 (.85 23) Cub 212 Surveillnce Ntionl.74 (<.1 2.7) 214 Surveillnce Ntionl 4.2 (.51 14) Curço 214 Surveillnce Ntionl ( 6) 214 Surveillnce Ntionl ( ) Cyprus 213 Surveillnce Ntionl ( 15) 213 Surveillnce Ntionl 1 (2.5 1) Czech Republic 213 Surveillnce Ntionl ( 1.3) 213 Surveillnce Ntionl ( 31) Côte d'ivoire 26 Survey Ntionl 2.5 ( ) Democrtic People's Republic of Kore 214 Survey Sub-ntionl 1.9 (.8 3.9) 214 Survey Sub-ntionl 15 (8.8 24) Democrtic Republic of the Congo Denmrk 213 Surveillnce Ntionl.51 (<.1 2.8) 213 Surveillnce Ntionl 5 (.13 25) Empty rows indicte n bsence of high-qulity survey or surveillnce dt. In the bsence of high-qulity ntionl dt, high-qulity sub-ntionl dt re used. Dt for ll yers cn be downloded from GLOBAL TUBERCULOSIS REPORT 215 n 181

193 TABLE A4.6 Mesured percentge of TB cses with MDR-TB, most recent yer vilble New TB cses Previously treted TB cses Yer Source Coverge Percentge Yer Source Coverge Percentge Djibouti Dominic 213 Surveillnce Ntionl ( ) 213 Surveillnce Ntionl ( ) Dominicn Republic Ecudor 22 Survey Ntionl 4.9 ( ) 212 Surveillnce Ntionl 26 (23 29) Egypt 211 Survey Ntionl 3.4 ( ) 213 Surveillnce Ntionl 15 (12 18) El Slvdor 21 Survey Ntionl.33 (<.1 1.2) 214 Surveillnce Ntionl ( 4.3) Equtoril Guine Eritre Estoni 214 Surveillnce Ntionl 19 (14 27) 214 Surveillnce Ntionl 62 (42 79) Ethiopi 25 Survey Ntionl 1.6 ( ) 25 Survey Ntionl 12 (5.6 21) Fiji 26 Surveillnce Ntionl ( 8.2) 26 Surveillnce Ntionl ( 98) Finlnd 214 Surveillnce Ntionl 2.7 ( ) 214 Surveillnce Ntionl 2 (.51 72) Frnce 29 Surveillnce Ntionl.45 (.24.77) 29 Surveillnce Ntionl 13 (7.4 21) French Polynesi 214 Surveillnce Ntionl ( 13) 214 Surveillnce Ntionl ( 98) Gbon Gmbi 2 Survey Ntionl.48 (<.1 2.6) 2 Survey Ntionl ( 18) Georgi 214 Surveillnce Ntionl 12 (1 13) 214 Surveillnce Ntionl 39 (35 44) Germny 214 Surveillnce Ntionl 2.9 ( ) 214 Surveillnce Ntionl 17 (11 25) Ghn Greece 21 Surveillnce Ntionl 1.5 (<.1 8.) 21 Surveillnce Ntionl 9.1 (.23 41) Greenlnd Grend Gum 212 Surveillnce Ntionl ( 11) 212 Surveillnce Ntionl ( ) Guteml 22 Survey Ntionl 3 ( ) 22 Survey Ntionl 26 (2 34) Guine Guine-Bissu Guyn Hiti Hondurs 24 Survey Ntionl 1.8 ( ) 24 Survey Ntionl 12 (5.8 22) Hungry 21 Surveillnce Ntionl 2.5 ( ) 21 Surveillnce Ntionl 8.1 (3.3 16) Icelnd 214 Surveillnce Ntionl ( 71) 214 Surveillnce Ntionl ( 98) 21, Indi 24, 26, Multiple surveys 2.2 ( ) 26, 29 Multiple surveys 15 (11 19) 29 Indonesi 24, 26, 21 Multiple surveys 1.9 ( ) 26, 21 Multiple surveys 12 (8.1 17) Irn (Islmic Republic of) 214 Survey Ntionl.8 (.3 1.4) 214 Survey Ntionl 12 (6.2 19) Irq 213 Survey Ntionl 1.1 (.3 1.8) 213 Survey Ntionl 2 (13 27) Irelnd 214 Surveillnce Ntionl 1.6 (.2 5.8) 214 Surveillnce Ntionl ( 26) Isrel 214 Surveillnce Ntionl 6.6 (3.5 11) 214 Surveillnce Ntionl 5 (6.8 93) Itly 212 Surveillnce Ntionl 2.6 ( ) 213 Surveillnce Ntionl 4.2 ( ) Jmic 213 Surveillnce Ntionl 2.4 (<.1 13) 213 Surveillnce Ntionl ( ) Jpn 22 Surveillnce Ntionl.7 ( ) 22 Surveillnce Ntionl 9.8 (7.1 13) Jordn 29 Surveillnce Ntionl 6.3 (2.4 13) 29 Surveillnce Ntionl 29 (3.7 71) Kzkhstn 213 Surveillnce Ntionl 26 (25 27) 213 Surveillnce Ntionl 58 (57 59) Keny 214 Surveillnce Ntionl 14 (12 15) Kiribti Kuwit 214 Surveillnce Ntionl 2.2 ( ) 214 Surveillnce Ntionl ( 98) Kyrgyzstn 211 Survey Ntionl 26 (23 31) 213 Surveillnce Ntionl 55 (52 58) Lo People's Democrtic Republic Ltvi 214 Surveillnce Ntionl 8.2 (5.8 11) 214 Surveillnce Ntionl 3 (21 4) Lebnon 23 Survey Ntionl 1 ( ) 213 Surveillnce Ntionl 29 (3.7 71) Lesotho 214 Survey Ntionl 3.2 ( ) 214 Survey Ntionl 7.3 (4.2 1) Liberi Liby Lithuni 214 Surveillnce Ntionl 14 (12 16) 214 Surveillnce Ntionl 49 (43 55) Luxembourg 214 Surveillnce Ntionl ( ) 214 Surveillnce Ntionl ( ) Mdgscr 27 Survey Ntionl.49 ( ) 27 Survey Ntionl 3.9 (.48 13) Mlwi 211 Survey Ntionl.42 (.14.97) 211 Survey Ntionl 4.8 ( ) Empty rows indicte n bsence of high-qulity survey or surveillnce dt. In the bsence of high-qulity ntionl dt, high-qulity sub-ntionl dt re used. 182 n GLOBAL TUBERCULOSIS REPORT 215 Dt for ll yers cn be downloded from

194 TABLE A4.6 Mesured percentge of TB cses with MDR-TB, most recent yer vilble New TB cses Previously treted TB cses Yer Source Coverge Percentge Yer Source Coverge Percentge Mlysi 214 Surveillnce Ntionl.4 (.24.63) 214 Surveillnce Ntionl 1.1 ( ) Mldives Mli Mlt 212 Surveillnce Ntionl ( 25) 214 Surveillnce Ntionl ( 98) Mrshll Islnds 214 Surveillnce Ntionl ( 8.) 214 Surveillnce Ntionl ( 41) Muritni Muritius 214 Surveillnce Ntionl ( 3.2) 214 Surveillnce Ntionl 33 (.84 91) Mexico 29 Survey Ntionl 2.4 ( ) 29 Survey Ntionl 6.5 ( ) Micronesi (Federted Sttes of) Monco Mongoli 27 Survey Ntionl 1.4 (.7 2.5) 213 Surveillnce Ntionl 34 (29 38) Montenegro 214 Surveillnce Ntionl ( 5.7) 214 Surveillnce Ntionl 4 (5.3 85) Montserrt Morocco 214 Survey Ntionl 1 (.3 1.7) 214 Survey Ntionl 8.7 (4.8 13) Mozmbique 27 Survey Ntionl 3.5 ( ) 27 Survey Ntionl 11 ( 25) Mynmr 213 Survey Ntionl 5 ( ) 213 Survey Ntionl 27 (15 39) Nmibi 28 Survey Ntionl 3.8 ( ) 28 Survey Ntionl 16 (13 21) Nuru Nepl 211 Survey Ntionl 2.2 ( ) 211 Survey Ntionl 15 (1 23) Netherlnds 214 Surveillnce Ntionl.92 ( ) 214 Surveillnce Ntionl 13 (.32 53) New Cledoni 214 Surveillnce Ntionl ( 28) 214 Surveillnce Ntionl ( 84) New Zelnd 212 Surveillnce Ntionl.9 ( ) 212 Surveillnce Ntionl 17 (2.1 48) Nicrgu 26 Survey Ntionl.63 (<.1 2.2) 21 Surveillnce Ntionl 11 (6.2 17) Niger Nigeri 21 Survey Ntionl 2.9 (2.1 4.) 21 Survey Ntionl 14 (1 19) Niue Northern Mrin Islnds 214 Surveillnce Ntionl 5.3 (.13 26) 214 Surveillnce Ntionl ( 98) Norwy 213 Surveillnce Ntionl 2.2 ( ) 213 Surveillnce Ntionl 5.9 (.15 29) Omn 214 Surveillnce Ntionl 2.6 ( ) 214 Surveillnce Ntionl ( 41) Pkistn 213 Survey Ntionl 3.7 (2.5 5.) 213 Survey Ntionl 18 (13 23) Plu 213 Surveillnce Ntionl ( 41) 213 Surveillnce Ntionl ( ) Pnm Ppu New Guine 214 Survey Sub-ntionl 2.7 ( ) 214 Survey Sub-ntionl 19 (8.5 3) Prguy 28 Survey Ntionl.3 ( 1.7) 28 Survey Ntionl 15 (6.1 28) Peru 214 Surveillnce Ntionl 5.3 ( ) 214 Surveillnce Ntionl 2 (19 22) Philippines 212 Survey Ntionl 2 ( ) 212 Survey Ntionl 21 (16 29) Polnd 214 Surveillnce Ntionl.44 (.26.7) 214 Surveillnce Ntionl 4.4 ( ) Portugl 212 Surveillnce Ntionl.98 ( ) 212 Surveillnce Ntionl 4.9 (1.6 11) Puerto Rico 214 Surveillnce Ntionl ( 9.3) 214 Surveillnce Ntionl ( ) Qtr 214 Surveillnce Ntionl 1.3 ( ) Republic of Kore 24 Survey Ntionl 2.7 ( ) 24 Survey Ntionl 14 (1 19) Republic of Moldov 212 Surveillnce Ntionl 24 (21 26) 212 Surveillnce Ntionl 62 (59 65) Romni 24 Survey Ntionl 2.8 ( ) 24 Survey Ntionl 11 (8. 15) Russin Federtion 213 Oblsts 19 (14 25) 213 Oblsts 49 (4 59) Rwnd 214 Surveillnce Ntionl 2.2 ( ) 214 Surveillnce Ntionl 5.1 (1.7 11) Sint Kitts nd Nevis Sint Luci 213 Surveillnce Ntionl ( ) 213 Surveillnce Ntionl ( ) Sint Vincent nd the Grendines 214 Surveillnce Ntionl ( ) Smo 213 Surveillnce Ntionl ( 28) 213 Surveillnce Ntionl ( ) Sn Mrino So Tome nd Principe 212 Surveillnce Ntionl 88 (47 1) Sudi Arbi 21 Survey Ntionl 1.8 ( ) 21 Survey Ntionl 16 (12 21) Senegl 214 Survey Ntionl.4 (.8) 214 Survey Ntionl 16 (9.3 23) Serbi 213 Surveillnce Ntionl.85 ( ) 213 Surveillnce Ntionl 4.7 (1.3 11) Seychelles 214 Surveillnce Ntionl ( 41) 214 Surveillnce Ntionl ( ) Sierr Leone Singpore 214 Surveillnce Ntionl 1.1 ( ) 214 Surveillnce Ntionl 1.3 (<.1 7.1) Sint Mrten (Dutch prt) Slovki 212 Surveillnce Ntionl ( 2.6) 212 Surveillnce Ntionl 3.7 (<.1 19) Empty rows indicte n bsence of high-qulity survey or surveillnce dt. In the bsence of high-qulity ntionl dt, high-qulity sub-ntionl dt re used. Dt for ll yers cn be downloded from GLOBAL TUBERCULOSIS REPORT 215 n 183

195 TABLE A4.6 Mesured percentge of TB cses with MDR-TB, most recent yer vilble New TB cses Previously treted TB cses Yer Source Coverge Percentge Yer Source Coverge Percentge Sloveni 214 Surveillnce Ntionl ( 4.1) 214 Surveillnce Ntionl ( 41) Solomon Islnds 214 Surveillnce Ntionl ( ) Somli 211 Survey Ntionl 5.2 ( ) 211 Survey Ntionl 41 (23 58) South Afric 22 Survey Ntionl 1.8 ( ) 22 Survey Ntionl 6.7 ( ) South Sudn Spin 21, 25 Multiple surveys.22 (<.1.8) 21, 25 Multiple surveys 7.1 (3.3 13) Sri Lnk 26 Survey Ntionl.18 (.99) 213 Surveillnce Ntionl.58 (<.1 2.1) Sudn Surinme Swzilnd 29 Survey Ntionl 7.7 (4.8 11) 29 Survey Ntionl 34 (28 39) Sweden 214 Surveillnce Ntionl 3 ( ) 214 Surveillnce Ntionl 11 (1.3 33) Switzerlnd 214 Surveillnce Ntionl 3.1 (1. 7.) 214 Surveillnce Ntionl 14 (4. 33) Syrin Arb Republic 23 Survey Ntionl 6.2 ( ) 211 Surveillnce Ntionl 31 (21 44) Tjikistn 214 Surveillnce Ntionl 8.1 ( ) 214 Surveillnce Ntionl 52 (47 57) Thilnd 212 Survey Ntionl 2 ( ) 212 Survey Ntionl 19 (14 25) The Former Yugoslv Republic of Mcedoni 214 Surveillnce Ntionl 1.4 ( ) 214 Surveillnce Ntionl ( 2) Timor-Leste Togo 213 Surveillnce Ntionl 26 (15 4) Tokelu Tong Trinidd nd Tobgo Tunisi 212 Survey Ntionl.8 ( 1.7) 212 Survey Ntionl 12 (4.5 19) Turkey 213 Surveillnce Ntionl 2.5 (2.1 3.) 213 Surveillnce Ntionl 18 (15 21) Turkmenistn 213 Survey Ntionl 14 (11 17) 213 Survey Ntionl 38 (3 45) Turks nd Cicos Islnds Tuvlu US Virgin Islnds Ugnd 211 Survey Ntionl 1.4 (.6 2.2) 211 Survey Ntionl 12 (6.8 19) Ukrine 214 Survey Ntionl 22 (2 24) 214 Survey Ntionl 56 (5 61) United Arb Emirtes 213 Surveillnce Ntionl ( 52) United Kingdom of Gret Britin nd Northern Irelnd 214 Surveillnce Ntionl 1.2 ( ) 214 Surveillnce Ntionl 3.6 ( ) United Republic of Tnzni 27 Survey Ntionl 1.1 (.5 2.) 27 Survey Ntionl 3.1 (.9 7.9) United Sttes of Americ 214 Surveillnce Ntionl 1.1 ( ) 214 Surveillnce Ntionl 7.4 (4.7 11) Uruguy 212 Surveillnce Ntionl (.79) 212 Surveillnce Ntionl 2.4 (<.1 13) Uzbekistn 211 Survey Ntionl 23 (18 29) 211 Survey Ntionl 62 (52 71) Vnutu 26 Surveillnce Ntionl ( 12) Venezuel (Bolivrin Republic of) Viet Nm 212 Survey Ntionl 4 ( ) 212 Survey Ntionl 23 (17 3) Wllis nd Futun Islnds West Bnk nd Gz Strip Yemen 211 Survey Ntionl 1.7 (.5 3.) 211 Survey Ntionl 15 (8.1 22) Zmbi 28 Survey Ntionl.3 (<.1 1.2) 28 Survey Ntionl 8.1 (4.1 14) Zimbbwe Empty rows indicte n bsence of high-qulity survey or surveillnce dt. In the bsence of high-qulity ntionl dt, high-qulity sub-ntionl dt re used. 184 n GLOBAL TUBERCULOSIS REPORT 215 Dt for ll yers cn be downloded from

196 TABLE A4.7 Drug susceptibility testing for TB cses, estimted MDR-TB mong notified TB cses, RR-/MDR-TB cses detected, nd enrolments on MDR-TB tretment, 214 Confirmed new TB cses tested for RR-/MDR-TB Notified previously treted TB cses tested for RR-/MDR-TB Estimted MDR-TB mong Confirmed RR-/MDR-TB cses Cses enrolled on MDR-TB tretment (Number) (%) b (Number) (%) b notified pulmonry cses (Number) (% of estimted) c (Number)(% of notified) d Afghnistn 2 < (85 1 4) Albni ( 4.) 3 >1 Algeri (53 29) Americn Smo Andorr 4 >1 1 1 ( ) 2 Angol (63 2 5) >1 Anguill 1 1 ( ) Antigu nd Brbud ( ) Argentin (24 48) Armeni (14 19) >1 Arub ( ) 2 Austrli 954 > (1 29) 24 > Austri (12 34) 5 >1 3 6 Azerbijn 2 59 > >1 1 3 ( ) Bhms ( 5.) Bhrin Bngldesh ( ) Brbdos 3 1 ( 3.) Belrus ( ) >1 Belgium (4. 22) Belize (18 19) 1 Benin ( 6) Bermud ( ) Bhutn (26 48) 61 >1 122 >1 Bolivi (Plurintionl Stte of) (12 29) Bonire, Sint Eusttius nd Sb ( ) Bosni nd Herzegovin ( 5.) 4 > Botswn (1 21) >1 Brzil 1 8 ( ) British Virgin Islnds ( ) Brunei Drusslm ( 4.) Bulgri (53 91) Burkin Fso (74 28) Burundi (42 24) >1 Cbo Verde 8 (4. 13) Cmbodi (26 79) Cmeroon 5 < (22 1 ) Cnd Cymn Islnds ( ) Centrl Africn Republic ( 18) Chd (12 5) Chile (11 34) Chin (42 61 ) Chin, Hong Kong SAR (27 6) Chin, Mco SAR 26 > (3. 17) Colombi (26 45) Comoros 3 (1. 5.) Congo 477 >1 2 (57 35) Cook Islnds ( 2.) Cost Ric ( 13) Croti ( 6.) >1 Cub ( 14) 1 >1 1 1 Curço 4 1 ( 3.) Cyprus (3. 3.) Czech Republic ( ) Côte d'ivoire (25 9) Democrtic People's Republic of Kore ( ) >1 Democrtic Republic of the Congo (98 4 5) Bcteriologiclly confirmed pulmonry or extrpulmonry cses. b My be > 1% due to testing of extrpulmonry cses or indequte linkges between lbortory nd clinicl registers. c My be > 1% due to denomintor only including pulmonry MDR-TB cses, or if estimtes of MDR-TB re too low. d My be > 1% due to enrolment of cses without lbortory confirmtion of RR-/MDR-TB, or cses detected in previous clendr yers. Dt for ll yers cn be downloded from GLOBAL TUBERCULOSIS REPORT 215 n 185

197 TABLE A4.7 Drug susceptibility testing for TB cses, estimted MDR-TB mong notified TB cses, RR-/MDR-TB cses detected, nd enrolments on MDR-TB tretment, 214 Confirmed new TB cses tested for RR-/MDR-TB Notified previously treted TB cses tested for RR-/MDR-TB (Number) (%) b (Number) (%) b Estimted MDR-TB mong notified pulmonry cses Confirmed RR-/MDR-TB cses Denmrk ( 6.) 1 33 Cses enrolled on MDR-TB tretment (Number) (% of estimted) c (Number)(% of notified) d Djibouti (2 75) 11 > Dominic 1 ( ) Dominicn Republic (95 21) >1 Ecudor >1 31 (25 38) 451 > Egypt (18 32) El Slvdor ( 16) 15 > Equtoril Guine (2 36) Eritre 52 (21 82) >1 Estoni 175 > (48 75) Ethiopi (7 2 3) >1 Fiji ( ) 1 Finlnd 212 > (1. 14) 8 >1 9 >1 Frnce >1 332 >1 56 (34 77) 111 > French Polynesi ( ) Gbon (1 31) Gmbi ( 41) 15 >1 9 6 Georgi (59 7) >1 Germny (74 21) 9 64 Ghn >1 4 (16 64) Greece ( 22) 4 44 Greenlnd Grend ( ) Gum 34 >1 1 1 ( ) Guteml (95 17) Guine (8 38) >1 Guine-Bissu >1 45 (11 79) Guyn (18 38) Hiti (26 64) Hondurs (3 96) Hungry 339 > (14 37) Icelnd 6 >1 1 1 ( ) Indi (57 85 ) Indonesi ( ) Irn (Islmic Republic of) (79 18) >1 Irq (11 21) 196 > Irelnd 173 > ( 7.) Isrel 257 > (11 3) Itly Jmic ( 6.) Jpn (14 25) Jordn (7. 35) Kzkhstn > >1 4 9 (4 8 5 ) > >1 Keny ( ) Kiribti (15 29) Kuwit 733 > (3. 19) Kyrgyzstn 2 ( ) Lo People's Democrtic Republic (16 3) >1 Ltvi (66 1) Lebnon >1 1 ( 2) Lesotho (26 42) >1 Liberi 4 (12 68) Liby 31 (24 39) Lithuni 968 > (27 34) Luxembourg 16 >1 ( ) Mdgscr (5. 38) Mlwi (86 2) Mlysi (57 14) 319 > Bcteriologiclly confirmed pulmonry or extrpulmonry cses. b My be > 1% due to testing of extrpulmonry cses or indequte linkges between lbortory nd clinicl registers. c My be > 1% due to denomintor only including pulmonry MDR-TB cses, or if estimtes of MDR-TB re too low. d My be > 1% due to enrolment of cses without lbortory confirmtion of RR-/MDR-TB, or cses detected in previous clendr yers. 186 n GLOBAL TUBERCULOSIS REPORT 215 Dt for ll yers cn be downloded from

198 TABLE A4.7 Drug susceptibility testing for TB cses, estimted MDR-TB mong notified TB cses, RR-/MDR-TB cses detected, nd enrolments on MDR-TB tretment, 214 Confirmed new TB cses tested for RR-/MDR-TB Notified previously treted TB cses tested for RR-/MDR-TB (Number) (%) b (Number) (%) b Estimted MDR-TB mong notified pulmonry cses Confirmed RR-/MDR-TB cses Cses enrolled on MDR-TB tretment (Number) (% of estimted) c (Number)(% of notified) d Mldives (2. 2.) Mli (51 21) Mlt 24 >1 1 1 ( ) Mrshll Islnds 82 > ( ) Muritni (21 84) >1 Muritius ( 3.) Mexico (44 56) >1 Micronesi (Federted Sttes of) 63 >1 8 (4. 11) 1 12 Monco Mongoli >1 22 (19 25) 318 > Montenegro ( 8.) Montserrt ( ) Morocco (21 47) >1 Mozmbique ( ) Mynmr >1 9 ( ) Nmibi 58 (47 69) Nuru ( ) Nepl (77 1 5) Netherlnds 463 > ( 12) 7 > New Cledoni ( ) New Zelnd 3 ( 6.) Nicrgu (21 78) >1 Niger 1 < (97 41) >1 Nigeri 3 3 ( ) Niue ( ) Northern Mrin Islnds >1 1 ( 4.) 1 1 Norwy (1. 14) 8 >1 Omn 271 > (1. 11) 8 >1 8 1 Pkistn ( ) Plu 6 86 ( 5.) Pnm (28 61) Ppu New Guine 89 (54 1 2) Prguy (18 1) >1 Peru ( ) >1 Philippines ( ) Polnd (35 69) Portugl (11 31) 26 > Puerto Rico 4 >1 ( 4.) Qtr 465 >1 2 ( 7.) Republic of Kore > ( ) Republic of Moldov ( ) >1 Romni (49 81) >1 Russin Federtion (33 45 ) >1 Rwnd (83 18) Sint Kitts nd Nevis ( ) Sint Luci 6 >1 ( ) Sint Vincent nd the Grendines ( ) Smo 1 >1 ( ) Sn Mrino So Tome nd Principe (13 22) Sudi Arbi (58 86) Senegl >1 24 (15 33) Serbi (7. 29) Seychelles 7 1 ( 3.) Sierr Leone 29 (93 48) Singpore > (9. 32) Sint Mrten (Dutch prt) ( ) Slovki 156 > ( 5.) 7 > Bcteriologiclly confirmed pulmonry or extrpulmonry cses. b My be > 1% due to testing of extrpulmonry cses or indequte linkges between lbortory nd clinicl registers. c My be > 1% due to denomintor only including pulmonry MDR-TB cses, or if estimtes of MDR-TB re too low. d My be > 1% due to enrolment of cses without lbortory confirmtion of RR-/MDR-TB, or cses detected in previous clendr yers. Dt for ll yers cn be downloded from GLOBAL TUBERCULOSIS REPORT 215 n 187

199 TABLE A4.7 Drug susceptibility testing for TB cses, estimted MDR-TB mong notified TB cses, RR-/MDR-TB cses detected, nd enrolments on MDR-TB tretment, 214 Confirmed new TB cses tested for RR-/MDR-TB Notified previously treted TB cses tested for RR-/MDR-TB (Number) (%) b (Number) (%) b Estimted MDR-TB mong notified pulmonry cses Confirmed RR-/MDR-TB cses Cses enrolled on MDR-TB tretment (Number) (% of estimted) c (Number)(% of notified) d Sloveni 122 >1 7 1 ( ) Solomon Islnds (6. 14) Somli (51 1 ) South Afric 6 2 ( ) > South Sudn (95 36) Spin (9. 39) 39 >1 Sri Lnk >1 14 ( 45) 42 > Sudn (23 86) Surinme (3. 6.) 9 >1 Swzilnd 44 (32 56) >1 Sweden 498 > (6. 24) 18 > Switzerlnd (6. 27) 17 >1 Syrin Arb Republic (1 19) Tjikistn (81 95) 92 > Thilnd ( ) The Former Yugoslv Republic of Mcedoni ( 6.) Timor-Leste (87 11) Togo 1 < (39 12) Tokelu ( ) Tong 1 ( 1.) Trinidd nd Tobgo (8. 12) 1 Tunisi (7. 3) Turkey (32 41) Turkmenistn (39 52) Turks nd Cicos Islnds ( ) Tuvlu 1 (1. 1.) US Virgin Islnds Ugnd (62 1 4) Ukrine (12 14 ) >1 United Arb Emirtes ( 1.) United Kingdom of Gret Britin nd Northern Irelnd 3 82 > (39 79) 63 > United Republic of Tnzni (24 95) United Sttes of Americ > (88 14) Uruguy ( 6.) Uzbekistn > ( ) Vnutu ( ) Venezuel (Bolivrin Republic of) (11 2) Viet Nm ( ) Wllis nd Futun Islnds ( ) West Bnk nd Gz Strip 2 (1. 2.) Yemen (65 22) Zmbi 61 (26 96) Zimbbwe (43 1 5) WHO regions Africn Region (15 49 ) Region of the Americs ( ) Estern Mediterrnen Region (12 19 ) Europen Region (63 83 ) >1 South-Est Asi Region (9 11 ) Western Pcific Region (47 94 ) Globl (22 37 ) Bcteriologiclly confirmed pulmonry or extrpulmonry cses. b My be > 1% due to testing of extrpulmonry cses or indequte linkges between lbortory nd clinicl registers. c My be > 1% due to denomintor only including pulmonry MDR-TB cses, or if estimtes of MDR-TB re too low. d My be > 1% due to enrolment of cses without lbortory confirmtion of RR-/MDR-TB, or cses detected in previous clendr yers. 188 n GLOBAL TUBERCULOSIS REPORT 215 Dt for ll yers cn be downloded from

200 TABLE A4.8 HIV testing for TB ptients, provision of CPT nd ART to HIV-positive TB ptients, nd initition of IPT for people newly enrolled in HIV cre, 214 Totl TB ptients notified CPT = Cotrimoxzole preventive therpy. b ART = Anti-retrovirl therpy. c Initition of isonizid preventive therpy (IPT) for people newly enrolled in HIV cre. (Number) (%) (Number) (%) (Number) (%) (Number) (%) Afghnistn <.1 7 Albni Algeri TB ptients with known HIV sttus HIV-positve TB ptients HIV-positive TB ptients on CPT HIV-positive TB ptients on ART b HIV-positive people provided IPT c Americn Smo Andorr 6 Angol Anguill Antigu nd Brbud Argentin Armeni Arub 2 Austrli Austri 582 Azerbijn Bhms Bhrin Bngldesh Brbdos Belrus Belgium Belize Benin Bermud Bhutn Bolivi (Plurintionl Stte of) Bonire, Sint Eusttius nd Sb Bosni nd Herzegovin Botswn Brzil British Virgin Islnds Brunei Drusslm Bulgri Burkin Fso Burundi Cbo Verde Cmbodi Cmeroon Cnd Cymn Islnds Centrl Africn Republic Chd Chile Chin Chin, Hong Kong SAR Chin, Mco SAR Colombi Comoros Congo Cook Islnds 2 Cost Ric Croti 497 Cub Curço Cyprus 41 Czech Republic Côte d'ivoire Democrtic People's Republic of Kore Democrtic Republic of the Congo Denmrk 32 Dt for ll yers cn be downloded from GLOBAL TUBERCULOSIS REPORT 215 n 189

201 TABLE A4.8 HIV testing for TB ptients, provision of CPT nd ART to HIV-positive TB ptients, nd initition of IPT for people newly enrolled in HIV cre, 214 Totl TB ptients notified TB ptients with known HIV sttus HIV-positve TB ptients HIV-positive TB ptients on CPT HIV-positive TB ptients on ART b (Number) (%) (Number) (%) (Number) (%) (Number) (%) Djibouti Dominic 1 HIV-positive people provided IPT c Dominicn Republic Ecudor Egypt El Slvdor Equtoril Guine Eritre Estoni Ethiopi Fiji Finlnd Frnce French Polynesi Gbon Gmbi Georgi Germny Ghn Greece 519 Greenlnd Grend Gum Guteml Guine Guine-Bissu Guyn Hiti Hondurs Hungry 851 Icelnd Indi Indonesi Irn (Islmic Republic of) Irq Irelnd Isrel Itly Jmic Jpn Jordn Kzkhstn Keny Kiribti Kuwit Kyrgyzstn Lo People's Democrtic Republic Ltvi Lebnon Lesotho Liberi Liby Lithuni Luxembourg 24 Mdgscr Mlwi Mlysi Mldives Mli CPT = Cotrimoxzole preventive therpy. b ART = Anti-retrovirl therpy. c Initition of isonizid preventive therpy (IPT) for people newly enrolled in HIV cre. 19 n GLOBAL TUBERCULOSIS REPORT 215 Dt for ll yers cn be downloded from

202 TABLE A4.8 HIV testing for TB ptients, provision of CPT nd ART to HIV-positive TB ptients, nd initition of IPT for people newly enrolled in HIV cre, 214 Totl TB ptients notified TB ptients with known HIV sttus HIV-positve TB ptients Mlt HIV-positive TB ptients on CPT HIV-positive TB ptients on ART b (Number) (%) (Number) (%) (Number) (%) (Number) (%) Mrshll Islnds Muritni Muritius HIV-positive people provided IPT c Mexico Micronesi (Federted Sttes of) Monco Mongoli Montenegro Montserrt Morocco Mozmbique Mynmr Nmibi Nuru 8 Nepl Netherlnds New Cledoni New Zelnd Nicrgu Niger Nigeri Niue Northern Mrin Islnds Norwy 325 Omn Pkistn Plu Pnm Ppu New Guine Prguy Peru Philippines Polnd Portugl Puerto Rico Qtr Republic of Kore Republic of Moldov Romni Russin Federtion Rwnd Sint Kitts nd Nevis Sint Luci Sint Vincent nd the Grendines 6 3 Smo 23 Sn Mrino So Tome nd Principe Sudi Arbi Senegl Serbi Seychelles Sierr Leone Singpore Sint Mrten (Dutch prt) Slovki Sloveni Solomon Islnds Somli CPT = Cotrimoxzole preventive therpy. b ART = Anti-retrovirl therpy. c Initition of isonizid preventive therpy (IPT) for people newly enrolled in HIV cre. Dt for ll yers cn be downloded from GLOBAL TUBERCULOSIS REPORT 215 n 191

203 TABLE A4.8 HIV testing for TB ptients, provision of CPT nd ART to HIV-positive TB ptients, nd initition of IPT for people newly enrolled in HIV cre, 214 Totl TB ptients notified TB ptients with known HIV sttus HIV-positve TB ptients HIV-positive TB ptients on CPT HIV-positive TB ptients on ART b (Number) (%) (Number) (%) (Number) (%) (Number) (%) HIV-positive people provided IPT c South Afric South Sudn Spin Sri Lnk Sudn Surinme Swzilnd Sweden 67 Switzerlnd 473 Syrin Arb Republic Tjikistn Thilnd The Former Yugoslv Republic of Mcedoni Timor-Leste Togo Tokelu Tong Trinidd nd Tobgo Tunisi Turkey Turkmenistn Turks nd Cicos Islnds Tuvlu US Virgin Islnds Ugnd Ukrine United Arb Emirtes United Kingdom of Gret Britin nd Northern Irelnd United Republic of Tnzni United Sttes of Americ Uruguy Uzbekistn Vnutu Venezuel (Bolivrin Republic of) Viet Nm Wllis nd Futun Islnds West Bnk nd Gz Strip Yemen Zmbi Zimbbwe WHO regions Africn Region Region of the Americs Estern Mediterrnen Region Europen Region South-Est Asi Region Western Pcific Region Globl CPT = Cotrimoxzole preventive therpy. b ART = Anti-retrovirl therpy. c Initition of isonizid preventive therpy (IPT) for people newly enrolled in HIV cre. 192 n GLOBAL TUBERCULOSIS REPORT 215 Dt for ll yers cn be downloded from

204