Monitoring and Evaluation of MDR TB

1. Monitoring and Evaluation of MDR TB Kęstutis Miškinis, Medical officer, WHO Ukrainian country office

2. What is multidrug-resistant tuberculosis (MDR-TB)? • TB bacilli resistant to at least two of the most powerful anti-TB agents: isoniazid and rifampicin; • One of the main aims of any national TB program is to minimize the development of drug (multidrug) resistance;

3. Effectiveness of National TB Programme • High cure rate of new TB cases; • Low (and constantly decreasing) MDR-TB rate; • Ultimately, high case-detection rate; Potential criteria: • Ability to analyze cohort data; • Default and transfer rates less than 10%; • Continual supply of 1st line anti-TB drugs; • Application of DOT in 90% of all cases;

4. Effectiveness of National TB Programme (con’t.) • Surveillance of anti-TB drug resistance is an essential tool for monitoring the effectivness of TB control programme in any country; • The use of drug-sensitivity tests (DST) was recommended many years ago;

5. Cause of anti-TB drug resistance • (M)DR-TB is man-made! Naturally drug-resistant organisms arising through spontaneous mutations are selected by inadequate drug regimens; • Reasons – exposure to a single drug due to: • Poor adherence; • Inappropriate prescription; • Irregular drug supply; • Poor drug quality;

6. MDR-TB • Problems: • longer to treat (up to 24 months); • more expensive (up to 100x); • more side-effects; • demanding follow-up mechanism; • requires complex diagnostics;

7. Prevalence of (M)DR-TB in some regions WHO / IUATLD / DZK / AKM 1997-1999 Germany Italy Israel Latvia Tomsk Oblast Ivanovo Oblast China Henan Estonia 0% 20% 40% 60% 80% 100% susceptible MDR TB resistant

8. Countries/settings with MDR rates higher than 10% among combined cases

9. Boxplots of MDR prevalence rates among New Cases by European Sub-regions 3rd Global Report of WHO

10. MDR Trends among New Cases in Lithuania and Estonia Confidence-bounded MDR trend among new patients in Lithuania Confidence-bounded MDR trend among new patients in Estonia

11. Establishment of drug-resistance surveillance system • The sample of specimens should be representative of the TB patients; • The patient’s history should be carefully obtained (available to determine whether the patient has previously received anti-TB drugs); • The laboratory methods should meet internationally recommended standards;

12. DST methods • Proportion; • Resistance ratio; • Absolute concentration; • BACTEC 460 radiometric; Comparability of data is assured by: • Quality assurance; • Proficiency testing performed by Supranational Reference Laboratories

13. Choice of drugs Four out of six 1st line drugs: • Isoniazid (H); • Rifampicin (R); • Streptomycin (S); • Ethambutol (E); Why these four? • Widely used; • Resistance can be reliably measured by standardized techniques;

14. Definitions of resistance • Resistance among previously treated cases (having been treated for tuberculosis for one month or more); • Resistance among new TB cases (denies having had prior anti-TB treatment); • Multi-drug resistance;

15. National Reference Laboratory Is a reference institution on MDR surveillance. It: • Prepares cultures; • Undertakes identification of Mycobacteria; • Undertakes DST; • Ensures quality of DST performed by regional labs; • Establishes a regular “on-site” supervision;

16. Organizing of surveillance • Laboratories and diagnostic centers; • Sample size and sampling strategies; • Organization and survey outline (preparation, sampling, training, logistics); • Intake of patients (inclusion criteria, sputum-collection, registration, transport); • National Reference laboratory; • Data management and analysis;

17. Ukraine • NRL is established, but not functioning; • QA is not implemented; • Proficiency testing hasn’t started yet; • Laboratory standards are defined, but not strictly followed; • Equipment is poor, purchase of new equipment and necessary supplies is often delayed; • Staff needs retraining and rejuvenation;

18. Trends in Anti-TB-Drug-Resistance in UkraineFeshchenko et al., Ukraine Chemotherapeutical Journal, 2000/3

19. Trends in Anti-TB-Drug-Resistance in UkraineFeshchenko et al., Ukraine Chemotherapeutical Journal, 2000/3 70 Monodrug resistance Multidrug resistance MDR 60 Polydrug resistance 50 40 Drug resistance (%) 30 20 10 1990 1991 1992 1994 1995 1996 1993 1997 1998 1999 Year

20. MDR survey results in Donetska oblast (28 02 2006)

21. Drug Resistance Surveillance • Magnitude and trend of drug resistance prevalence among new and re-treatment cases; • Useful parameter to evaluate current and past treatment programme; • Useful information for selection of effective initial treatment and retreatment regimens;

22. Should we treat persons with MDR-TB? • Yes…for humanitarian reasons • But health policy is not only driven by values, facts also matter • No... unless it is proven that it is feasible and cost-effective • But can we afford not to respond?

24. DOTS-Plus: working definition • DOTS-Plus is a case-management strategy under development designed to manage MDR-TB using 2nd line drugs within the DOTS strategy in low- and middle-income countries; DISCLAIMER: DOTS-Plus means DOTS first

25. Prevention of MDR TB Correct operations of the TB programme: • Diagnosis based on bacteriological examination; • Standard treatment under strict observation (DOT); • Uninterrupted supply of good-quality TB drugs (recommended FDC); • Proper recording and reporting;