Diagnosis of TB in Belarus, statistics and challenges of establishing an accurate and timely DR-TB diagnosis in high MDR-TB prevalence settings

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Tuberculosis in 2017: Searching for new solutions in the face of new challenges 6th TB Symposium Ministry of Health of the Republic of Belarus, Republican Scientific and Practical Center for Pulmonology and Tuberculosis, and Médecins Sans Frontières 1-2 March, 2017, MINSK, BELARUS Diagnosis of TB in Belarus, statistics and challenges of establishing an accurate and timely DR-TB diagnosis in high MDR-TB prevalence settings Elena Nikolenko, National TB laboratory

Elena Nikolenko, National TB laboratory (NRL) March 01-02, 2017, Minsk

SNRL NRL Laboratories Labaratory Network: 3 BSL laboratories (7) 2 BSL laboratories (19) 1 BSL laboratories (128) TB - Laboratory Network RRL BELARUS

Laboratory network (new methods are included) NRL (GX-2) 3 BSL laboratories (GX-8) 2 BSL laboratories (GX-13) 1 BSL laboratories (GX-7) Grodno Minsk Vitebsk Mogilev Gomel Brest RRL BELARUS

25 20 15 Doctors 10 5 0 Laboratory technicians

XpertMTB/Rif 1 st sputum sample Microscopy Culture / drug susceptibility testing on solid and soft media 2nd sputum sample Microscopy Culture / drug susceptibility testing on solid and soft media LPA Microbiological diagnostics of TB

AFB+, GX+ RIF - S RIF - R LPA MTBDRplus DST for 1 st line drugs LPA MTBDRsl DST for 1 st and 2 nd line drugs Microbiological diagnostics of TB

722257 577932 605632 245351 1993 1995 1997 1999 2001 2003 2005 2007 2009 2011 2013 2015

SGM, Isolation Rate (%), 1993-2016 15 14.2 12.3 11.5 10 9.9 5 0

27000 25778 25610 25000 23000 21751 21737 21000 19000 17000 16834 15000 2012 2013 2014 2015 2016

2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 3 2.5 2.5 2.2 2.2 2 1.5 1 0.5 0.1 0.3 0.5 0.6 0.9 1.5 0

Xpert MTB/RIF 4000 3500 3000 2500 2000 3265 2597 3391 2244 1773 2153 3439 2012 2013 1500 1289 2014 1000 500 0 570 2015 2016 Brest Vitebsk Gomel Grodno Minsk Oblast Mogilev Minsk Correctional facility No. 12 NRL

1000 900 800 700 689 600 557 2012 500 400 300 200 100 0 0 218 196 0 362 0 2013 2014 2015 2016 Brest Vitebsk Gomel Grodno Minsk Mogilev Correctional facility No. 12 NRL

720 716 620 520 420 2012 320 220 120 106 156 121 257 2013 2014 2015 2016 20 0 0 0-80

This method is called "sputum smear microscopy. 163304 Sputum culture 124126 Sputum culture 17094 18020 0 40000 80000 120000 160000 Final outcome: Final outcome:

Microscopy Z-N Culture Löwenstein Jensen 6.5 0.9 Culture MGIT 17 GX GX RIF-R 48 13 negative result, % positive result, % LPA MTBDRplus RIF-R 36.3 LPA MTBDRsl Ag-R LPA MTBDRsl FQ-R 21.2 9.6 40 50 60 70 80 90 100

Efficiency of microscopic test carried to analyze the deposit in compliance with Ziehl-Neelsen method, Republic of Belarus (2016) 100% 98% 96% 3.7 7.6 45.0 40.0 35.0 30.0 41.3 94% 92% 90% 96.3 92.4 AFB+ AFB- 25.0 20.0 15.0 10.0 17.4 22.9 18.5 diagnostics treatment 88% 5.0 monitoring 0.0

DST for diagnostics, 2016 H,R,E,Z Am,Km,Cm, Lfx,Mfx, Lzd 2045 H,R,E, Am,Km,Cm, 2800

Insufficient use of molecular tests (LPA & GX) and prolonged waiting for the LPA results Dependence on external supplies and irregularities in supplies Insufficient number of staff members Need to undertake reorganization in some 3 BSL laboratories

Increased efficiency and quality of tests, improved quality control of laboratory tuberculosis diagnostics During several last years the country s laboratories have been enrolled in external quality control of DST with excellent results Development of international co-operation

45 40 35 30 25 OBJECTIVR:50%: 42.3 31.1 74 73 72 71 New cases OBJECTIVE: 70% 72.9 72.3 Relapses: Objectives: 100% 100 99.6 99.5 98.9 99.1 99 20 15 10 5 0 2013 2014 2015 2016 70 69 68 67 66 68.2 69.3 98.5 98 97.5 97 97.8 BACTERIOLOGICAL CONFIRMATION OF RESPIRATORY TUBERCULOSIS AMONG PRIMARY TB CASES (MOH, REPUBLIC OF BELARUS) 65 2013 2014 2015 2016 96.5 2013 2014 2015 2016 BACTERIOLOGICAL CONFIRMATION OF RESPIRATORY TUBERCULOSIS (MOH, REPUBLIC OF BELARUS)

Confirmed TB cases among children in 2016, % Confirmed TB of other organs, 2016 (%) 60 50 54.1 12 10 9.8 40 8 30 24.3 6 20 4 10 2 0 AFB+ Mycobacterium tuberculosis+ 0 Mycobacterium tuberculosis+

FIND Expand TB (technical assistance to the NRL and the laboratory of Minsk Oblast TB Dispensary) Expert ULTRA TB-SLMTA National Institutes of Health / National Institute of Allergy and Infection Diseases (NIH/NIAID): complete genomic sequencing

1) Genomic analysis of globally diverse Mycobacterium tuberculosis strains provides insights into the emergence and spread of multidrug resistance Abigail L Manson, Keira A Cohen, Thomas Abeel, Christopher A Desjardins, Derek T Armstrong, Clifton E Barry III, Jeannette Brand, TBResist Global Genome Consortium, Sinéad B Chapman, Sang-Nae Cho, Andrei Gabrielian, James Gomez, Andreea M Jodals, Moses Joloba, Pontus Jureen, Jong Seok Lee, Lesibana Malinga, Mamoudou Maiga, Dale Nordenberg, Ecaterina Noroc, Elena Romancenco, Alex Salazar, Willy Ssengooba, A A Velayati, Kathryn Winglee, Aena Skrahina, Sven Hoffner et al. Nature Genetics (2017) doi:10.1038/ng.3767, Received 30 June 2016 Accepted 14 December 2016 Published online 16 January 2017 2) Whole genome sequencing of Mycobacterium tuberculosis provides insight into the evolution and genetic composition of drug-resistant tuberculosis in Belarus. Wollenberg KR, Desjardins CA, Zalutskaya A, Slodovnikova V, Oler AJ, Quiñones M, Abeel T, Chapman SB, Tartakovsky M, Gabrielian A, Hoffner S, Skrahin A, Birren BW, Rosenthal A, Skrahina A, Earl AM. J Clin Microbiol. 2016 Nov 30. 3) Multidrug-resistant Myobacterium tuberculosis caused by the Beijing genotype and a specific T1 genotype clone (SIT No. 266) is widely transmitted in Minsk Aksana Zalutskaya, Maria Wijkander, Pontus Jureen, Alena Skrahina, Sven Hoffner Int J of Mycobacteriology 2013; 2: 194 198

Introduction of a new diagnostics algorithm Capacity to apply rapid methods and molecular tests (GX and LPA) while diagnosing patients Centralization of the Laboratory Network Conduction of external quality assessment Preparation of the NRL for accreditation Increasing capacities of the NRL to ensure regular conduction of clinical and scientific trials

Acknowledgements