Control of tuberculosis in Serbia: UNIVERSITY 0F BELGRADE FACULTY OF MEDICINE Control of tuberculosis in Serbia: role of the mycobacteriology laboratory Savic Branislava1, Vukovic D1, Dakic I1, Lukovic B2, Arandjelovic I1 National Reference Laboratory for Tuberculosis,  1Institute of Microbiology and Immunology, Faculty of Medicine, University of Belgrade,  2Department of Microbiology, Clinical Center of Serbia, Belgrade, Serbia International Forum on TB in Central and Eastern Europe, 4-6th November 2016, Warsaw

Advance in TB laboratory diagnostics “Control of Tuberculosis in Serbia” MINISTRY OF HEALTH OF THE REPUBLIC OF SERBIA 2004-2015 Advance in TB laboratory diagnostics Reorganisation of TB laboratory network Equipment SOPs Uniform laboratory documentation Education Software for TB laboratories Supervisory visits External quality control Rapid diagnostics of TB and mycobacterioses

TB laboratory network NRL + 30 laboratories

Guidelines National Guidelines for Microbiological Diagnostics of TB (2007, 2009, 2015) National Biosafety Guidelines (2013) 2015. 2007. 2009. 2013.

Laboratory diagnosis of tuberculosis WHO recommendations (years) Diagnostic methods Application in Serbia 2007. liquid media (MGIT, BacT/Alert) Rapid identification of culture (detection of Ag) 2008. 2011. LPA for MDR-TB (Line Probe Assay) 2010. Xpert MTB/RIF Laboratorijska dijagnostika tuberkuloze – šta kaže svet, šta može Srbija Bakteriološki potvrđen slučaj TB je osoba čiji je biološki uzorak pozitivan, što je dokazano direktnom mikroskopijom, kultivacijom ili brzim dijagnostičkim metodama koje preporučuje SZO. ( WRD –WHO approved rapid diagnostics ).

Line Probe Assay (LPA) in NRL for TB identification of mycobacteria from cultures HAIN GenoType MTBC HAIN GenoType Mycobacterium CM/AS) detection of resistance of M. tuberculosis to INH i Rif HAIN GenoType MTBDRplus Molekularni test za detekciju rezistencije na rifampicin i izonijazid, HAIN – Preporuka SZO od 2008. A u nasoj NRL od dec. 2008. HAIN sl za detekciju rezistencije bacila tuberkuloze na fluorohinolone, amikacin-capreomycin i ethambutol – SZO preporuka 2016 detection of resistance of M. tuberculosis to fluoroquinolones, amikacin-capreomycin, and ethambutol HAIN GenoType MTBDRsl

- Minimal recommendations for Serbia - Line Probe Assay in NRL - Minimal recommendations for Serbia - HAIN GenoType MTBDRplus for: Previous treated patients Contact with MDR–TB Monoresistance to Rifampicin or Isoniazid Confirmation of MDR-TB Patients with positive culture after 3 months of treatment Specimens from institutions with high number of M/XDR-TB In 2013 – 7 MDR, 2 monorez. na Rif specimens: AF +/ sputum or culture

1st line DST in 4 laboratories 93% DST coverage among culture + TB proportion method on LJ media HAIN GenoType MTBDRplus in NRL EQA 2nd line DST in Borstel (2008-2014) 123 MDR-TB 11/123 XDR-TB

Serbia Population: 7.3 million Epidemiology of TB, 2014 S e r b i a Estimated TB incidence rates, 2014. No notified TB patients 1051 TB notification rate 15/100.000 New TB cases PTB - 86 % EPTB - 14 % 952 (91%) MDR-TB 14 (1.3%) Source: WHO Global TB Report 2014.

Treatment for MDR-TB in Serbia According to WHO recommendations - all MDR-TB cases are treated from 1 September 2009 - within the Global Fund TB project of the Ministry of Health Inpatient Phase: Special Hospital for Lung Diseases „Ozren“- Sokobanja Special Hospital for Lung Diseases „Dr Budislav Babic“- Bela Crkva (mentally disabled patients) Outpatient Phase: health care institutions where patients live

10 beds

Special Hospital for Pulmonary and Psihiatrics Diseases, Bela Crkva 2011

48% treatment success globally Treatment outcomes for MDR-TB, 2007-2012 Global 48% treatment success globally Treatment outcomes of MDR-TB in Serbia 60% treatment success

M. tuberculosis vs. NTM (2009 - 2014) Identification: GenoType Mycobacterium CM/AS (HAIN Lifescience) The annual rates of NTM among patients with positive mycobacterial cultures

case rate of NTM disease (2009 – 2014): NTM pulmonary disease Total 83 patients 1. M. xenopi (n=32; 38.6%) 2. M. avium (n=10; 12.0%) M. abscessus (n=10; 12.0%). Procenat NTM je od 2009 do 2013, dodaj i 2014 !!!!!!!!!!!! case rate of NTM disease (2009 – 2014): 0.08 - 0.31 per 100,000 population The isolation rates of NTM from respiratory specimens as well as the case rates of pulmonary NTM disease are increasing in Serbia.

Many Thanks to all!