MULTI DRUG RESISTANT TUBERCULOSIS

1. MULTI DRUG RESISTANT TUBERCULOSIS CHAIRPERSON : DR MAYUR S S PRESENTER : DR JYOTSNA R

2. INTRODUCTION Tuberculosis is an ancient disease that has caused inestimable suffering and claimed millions of lives over the centuries Discovery of effective anti TB drugs in 1940 – a medical milestone Misuse of these “miracle” drugs has resulted in new public problem – Drug Resistant TB

3. Emergence of drug resistance tuberculosis and particularly MDR TB – public health problem An obstacle to effective TB control program First WHO endorsed DOTS Plus program – 2000 27 countries with high burden of MDR TB – responsible for 85% of global burden

4. China and India account for 50% of estimated global burden of MDR TB • Population based survey –Gujarat and Maharashtra estimated • 3% among New cases • 12-17% among Retreatment cases

5. MDR TB cases estimated in 2010 • 21000 among new TB cases • 43000 among retreatment cases • Confirmed cases of MDR TB- 2967 • Magnitude of problem remains to be inadequately determined because of inadequate culture and DST facilities.

11. DRUG RESISTANCE • Definition: • Capacity of an organism and its progeny to remain viable or multiply in the presence of a concentration of a drug that would normally destroy them or inhibit their growth

12. CLASSIFICATION • TYPES : • Primary resistance • Secondary / Acquired resistance

13. DEPENDING ON DRUG SENSITIVITY TESTS : • Mono resistance • Poly resistance • Multi drug resistance • Extensively drug resistance

14. FACTORS RELATED TO MDR TB MDR-TB is a man-made phenomenon poor treatment, poor drugs and poor adherence lead to the development of MDR-TB. Most powerful predictor of presence of MDR-TB is a history of previous treatment In management most common error is adding single drug to failing regimen

15. CAUSES • Microbial • Clinical • Programmatic

16. Contd…. • PROGRAMS OR PROVIDERS : Inadequate regimens • Absence or inappropriate guidelines • Non compliance with guidelines • Inadequate training of health staff • Non monitoring of treatment • Poorly organized or funded TB control programs

17. DRUGS : Inadequate supply or quality • Non availability of drugs • Poor quality • Poor storage conditions • Wrong dosages or combination

18. PATIENTS : Inadequate drug intake • Poor adherence • Lack of information • Non availability of free drugs • Adverse drug reactions • Social and economic barriers • Malabsorption • Substance abuse disorders

19. Spontaneous mutations develop as bacilli proliferate to >108

20. INH RIF PZA Multidrug therapy: No bacteria resistant to all 3 drugs Drug-resistant mutants in large bacterial population Monotherapy: INH-resistant bacteria proliferate INH

21. Spontaneous mutations develop as bacilli proliferate to >108 INH resistant bacteria multiply to large numbers INH RIF INH INH mono-resist. mutants killed, RIF-resist. mutants proliferate  MDR TB

22. GENETIC SITES FOR DRUG RESISTANCE

23. ORGANIZATION OF LABORATORY NETWORK RNTCP has 3 tier laboratory network system Designated Microscopy Centres (DMC) Intermediate Reference Laboratory (IRL) National Reference Laboratory (NRL)

24. IRL 27 IRL in India Training of personnel under DOTS Plus sites External Quality Assessment (EQA) of sputum smear microscopy network in the districts and DMCs Culture and Drug Susceptibility Testing (DST) for first line drugs for M tuberculosis

26. NRL 4 NRL in India Trainings of IRL staff EQA of sputum smear microscopy network in the states alloted Culture and DST for both first and second line drugs

28. SUPRANATIONAL REFERENCE LABORATORY NETWORK Comprises 28 laboratories world wide Acts as a global mechanism to ensure the quality of laboratory data through a system of proficiency tests

30. MDR TB SUSPECT • MDR TB Suspect : • Any patient who fails Cat I treatment regimen • Any Cat II patient who remains smear positive at the 4th month of treatment or later • Contacts of MDR TB cases

31. DIAGNOSIS OF MDR TB • PURELY A LABORATORY DIAGNOSIS • QUALITY ASSURED ACCREDITED LABORATORIES MANDATORY FOR DIAGNOSIS

32. CASE FINDING STRATEGY

35. DIAGNOSIS OF MDR TB • Sputum Smear microscopy • Culture • Drug Susceptibility Testing • Absolute Concentration method • Resistance Ratio method • Proportionate method – method recommended for DOTS Plus sites in India

36. SPUTUM COLLECTION FOR CULTURE Two morning samples : early morning and spot Collected at DMC and sent or collected at DTC From DTC samples transported to the laboratory for culture and DST If delay in transportation > 72hrs, samples transported in 1% CetylPyridinium Chloride (CPC) & 2% NaCl MDR TB suspect continues to take treatment till results are available

37. Samples sent to accredited laboratory for culture and DST Decontamination and homogenisation of samples done Specimens inoculated and incubated Cultures examined after 48-72hrs for gross contamination Cultures examined weekly, upto 8wks

38. Typical colonies of M tuberculosis are rough, crumbly, waxy, buff coloured Colonies with doubtful morphology are confirmed with ZN staining The positive cultures are subjected for drug sensitivity testing by proportionate method

39. PROPORTIONATE METHOD • Ratio of the number of colonies growing on drug containing media to the number of colonies growing on drug free media – proportion of drug resistant bacilli present in the bacterial population

41. CONFIRMED MDR TB CASE : • A MDR TB suspect • Sputum culture positive • TB is due to Mycobacterium tuberculosis • Resistant to Isoniazid and Rifampicin, • With or without resistance to other anti TB drugs

42. References Revised national Tuberculosis Programme DOTS-Plus guidelines – 2010. Guidelines for surveillance of drug resistance in tuberculosis, 4thed – World Health Organisation (WHO). Management of MDR-TB – A field guide – WHO 2009.

43. CONTD… Text book of Tuberculosis, A Mohan and SK Sharma 2004 Park’s Textbook of Preventive and Social Medicine, 21sted - 2011

45. THANK YOU