What can be done against XDR-TB?

Transcription

1 What can be done against XDR-TB? Dr Matteo Zignol Stop TB Dep. World Health Organization Geneva 16 th Swiss Symposium on tuberculosis Münchenwiler, 22 March 2007

2 XDR-TB Extensive Drug Resistance XDR = Resistance to at least INH and RIF (MDR) PLUS resistance to three of the six classes of second-line anti-tb drugs. Of 17,690 isolates from 49 countries during % were MDR and 2% were XDR XDR found in: USA: 4% of MDR Latvia: 19% of MDR S Korea: 15% of MDR XDR found in Southern Africa associated with HIV

3 Second-Line Drug Classes for MDR TB Treatment Aminoglycosides Amikacin, Kanamycin Polypeptides Capreomycin First line drugs + Fluoroquinolones Thioamides Serine analogues Ciprofloxacin, Ofloxacin Ethionamide, Prothionamide Cycloserine PAS WHO. Guidelines for the programmatic management of drug-resistant tuberculosis

4 Number of MDR and XDR Cases, Latin America MDR 543 XDR 32 (6%) Ind. Nations MDR 821 XDR 53 (6%) E. Europe MDR 406 XDR 55 (14%) Asia MDR 274 XDR 4 (1%) Rep. Korea MDR 1298 XDR 200 (15%) Africa, Middle East MDR 156 XDR 1 (< 1%) Isolates contributed to survey Total MDR= 3520; XDR= 347 (~ 10% of MDR)

5 Global XDR-TB Task Force New definition Principles: Public health surveillance Reliable DST methodology Clinical relevance Relatively simple XDR = Resistance to at least INH and RIF (MDR) PLUS resistance to fluoroquinolones, AND one of the second-line injectable drugs (amikacin, kanamycin, or capreomycin) Global XDR TB Task Force Meeting. Oct 9, 2006

6 More reports on XDR-TB

7 KZN XDR-TB Survey Characteristics No. (%) No prior TB Treatment 26 (51) Prior TB treatment - Cure or Completed treatment 14 (28) - Treatment Default or Failure 7 (14) HIV-infected (44 tested) 44 (100) Dead (includes 34% on ARV) 52 (98) Identical M. tb spoligotype 26/30 Gandhi NR et al. Lancet 368:

8 The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the WHO concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. WHO All rights reserved Countries with XDR-TB Confirmed cases to date Argentina Armenia Azerbaijan Bangladesh Lithuania Brazil Mexico Canada Netherlands Chile Norway China, Hong Kong SAR Czech Republic Peru Ecuador Portugal Estonia Republic of Korea France Romania Georgia Russian Federation Germany South Africa Ireland Spain Islamic Republic of Iran Israel Sweden Italy Thailand Japan UK Latvia USA Based on information provided to WHO Stop TB Department - March 2007

9 Treatment outcomes XDR-TB Cure Completion Death Default Failed Continue Tx HIV+ HR+AG+FQ HR+INJ+FQ HR+3SLD MDR-TB All Leimane V et al. First Global XDR TB Task Force Meeting. Oct 9, 2006 (from N = 820 evaluated) %

10 What can be done against XDR-TB? 1. Strengthen basic TB and HIV/AIDS control, to avoid creation of MDR-TB and XDR-TB 2. Scale-up programmatic management of MDR-TB and XDR-TB 3. Strengthen laboratory services for adequate and timely diagnosis of MDR-TB and XDR-TB 4. Expand MDR-TB and XDR-TB surveillance 5. Introduce infection control, especially in high HIV prevalence settings 6. Strengthen advocacy, communication and social mobilization 7. Pursue resource mobilization at global, regional and country levels 8. Promote research and development into new diagnostics, drugs and vaccines Global XDR TB Task Force Meeting. Oct 9, 2006

11 1. Strengthen basic TB control Reasons for failure W Pacific SE Asia Europe Died Failed Defaulted Transfered Not Evaluated E Med Americas Africa Percent of cohort WHO. Global TB report 2006.

12 1. Strengthen basic TB control DOTS on the ground + patient support = cure Commitment Lab diagnosis Standard SCC, support and supervision Drug supply Monitoring and evaluation Centro de Salud Lima Norte, Peru

13 1. Strengthen basic TB control Involving all providers

14 2. Scale-up programmatic management of MDR & XDR MDR-TB prevalence in new cases, Kazakhstan Israel Russia (Tomsk) Uzbekistan Estonia China (Liaoning) Lithuania Latvia Russia (Ivanovo) China (Henan) Dominican Rep Ivory Coast Iran Ecuador Aziz MA et al. Lancet. 2006; 368:

15 2. Scale-up programmatic management of MDR & XDR Estimated number of MDR-TB cases, 2004 Latin America, 11,301 Africa low HIV incidence, 10,449 Established Market Economies, 1,681 Central Europe, 1,462 Eastern Mediterranean Region, 18,330 Western Pacific Region, 152,018 Africa high HIV incidence, 48,141 Global burden: 424,203 cases Eastern Europe, 65,853 South-east Asia, 114,967 Zignol M et al. JID :479-85

16 2. Scale-up programmatic management of MDR & XDR Estimated number of MDR-TB cases, 2004 MDR-TB number 650, , , , , , , , , , , ,000 50,000 0 Total China + India + Russian Federation China India Russian Federation Zignol M et al. JID :479-85

17 2. Scale-up programmatic management of MDR & XDR GLC-approve projects, end 2006 GLC-approved projects 40 countries

18 2. Scale-up programmatic management of MDR & XDR Availability of 2 nd line anti-tb drugs Source: WHO/STB/THD No information Second-line drugs NOT available Second-line drugs widely available

19 2. Scale-up programmatic management of MDR & XDR The challenge of Human resources Density per 1000 population 5 4,5 4 3,5 3 2,5 2 1,5 1 0,5 0 Global Average Physicians African Region Average Nurses and Midwives

20 3. Strengthen laboratory services The Supranational Lab Network Coordinating Centre SRL

21 3. Strengthen laboratory services The gap 450, , , , ,000 with estimated 60% case detection rate 200, , ,000 50,000 with estimated 5% DST coverage 0 Cases estimated detected with TB diagnosed with MDR-TB Source: WHO/STB/THD

22 4. Expand MDR-TB and XDR-TB surveillance Coverage of the Global Project, 2006 Baseline achieved Ongoing/Finalizing Planned

23 The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the WHO concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. WHO All rights reserved 4. Expand MDR-TB and XDR-TB surveillance Confirmed XDR-TB cases to date Argentina Armenia Azerbaijan Bangladesh Lithuania Brazil Mexico Canada Netherlands Chile Norway China, Hong Kong SAR Czech Republic Peru Ecuador Portugal Estonia Republic of Korea France Romania Georgia Russian Federation Germany South Africa Ireland Spain Islamic Republic of Iran Israel Sweden Italy Thailand Japan UK Latvia USA Based on information provided to WHO Stop TB Department - March 2007

24 5. Introduce infection control

25 6. Strengthen advocacy, communication and social mobilization Role of community workers in TB control R.J. State, Brazil

26 7. Pursue resource mobilization Cost per MDR-TB patient treated US$ sear wpr lac emr eeur afr low afr high Drugs Hospitalization DOT visits Sputum smears, cultures, DST and X-rays Training Programme and data management Food parcels Adverse events Other STOP TB Partnership. Global Plan to STOP TB,

27 7. Pursue resource mobilization Total amount needed to treat MDR-TB, US$ (thousands) Total: US$ 5,3 billion EEUR WPRO SEA R A FR High AFR Low LAC EMR STOP TB Partnership. Global Plan to STOP TB,

28 8. Promote research and development into new diagnostics, drugs and vaccines No global "movement" attempting at convening basic scientists involved in upstream research or implementers involved in operational research Scarcity of funds (1/10 of HIV R&D devoted to TB) and scarcity of coordination and debate world-wide Without basic science, research in immunology, pathogenesis, genomics etc, scarcity of products to get into pipeline for development Most people involved in control activities have no interest in advocating for intensified and well financed research

29 8. Promote research and development into new diagnostics, drugs and vaccines MDR-TB and XDR-TB diagnosis based on long and old procedures, at times unreliable - lack of new rapid culture and DST (in developing countries) Defaulting a major issue in many programmes due to long duration of treatment - long intermittency or shorter regimens not available - no new drugs MDR/XDR-TB/HIV co-infection - interactions between 2 nd line anti-tb drugs and ARVs largely unknown A largely ineffective vaccine

30 Conclusions The next steps to control XDR-TB 1. Strengthen basic TB and HIV/AIDS control, to avoid creation of MDR-TB and XDR-TB 2. Scale-up programmatic management of MDR-TB and XDR-TB 3. Strengthen laboratory services for adequate and timely diagnosis of MDR-TB and XDR-TB 4. Expand MDR-TB and XDR-TB surveillance 5. Introduce infection control, especially in high HIV prevalence settings 6. Strengthen advocacy, communication and social mobilization 7. Pursue resource mobilization at global, regional and country levels 8. Promote research and development into new diagnostics, drugs and vaccines Global XDR TB Task Force Meeting. Oct 9, 2006