Scientific Basis of RNTCP

Transcription

1 Scientific Basis of RNTCP * Dr. (Mrs) T. Santha Devi 1 Longitudinal survey at Tiruvallur showed a reduction of only 1.4% per annum in the 2 prevalence of Tuberculosis Prevalence (per population) Prevalence - C+ Prevalence - S+C '99-1 Period in years TRC 1 M agnitude of TB problem (Per population) Community NSS Pos. cases Ø 85 5 x 1.7 NSS Neg. cases Ø 85 % of NSS+ cases EPTB cases Ø 17 % of NSS+ cases R/F/TAD cases Ø 43 5% of NSS+ cases cases Ø 23 Based on TRC,NTI and New Delhi TB centre average ARTI is 1.7% Styblo 1989 Magnitude M of TB problem 3 4 (Per population) Community Ø 97 NSS Pos. cases 57 x 1.7 NSS Neg. case % of NSS+ cases EPTB cases % of NSS+ cases R/F/TAD cases 5% of NSS+ cases cases Ø 97 Ø 19 Ø 48 Ø 261 Based on TRC,NTI NTI and New Delhi TB TB centre centre average average ARTI ARTI is 1.7% is 1.7% TRC 1 Ø Diagnosis of TB primarily based on sputum microscopy ØShort course chemotherapy ØDirectly observed treatment A re w e finding all the cases in the community? 5 6 Ø > 8% of the chest sym ptomatics (CS) consult a health provider ØFelt Need Ø 9% of the sputum positive PTB cases can be diagnosed with 3 sputa examinations from the CS ØTechnology available Tools Tuberculin test X-ray Sputum Sm. Microscopy Culture for MTB Diagnosis of tuberculosis Merits Can identify infection Good epidemiological tool Sensitive Definitive diagnosis Easy to perform at the periphery Replicability Less costly Highly sensitive & specific: Gold standard Demerits Cannot differentiate infection & disease Less specific Less Sensitive Costly, not freely available long waiting period * Sr. Deputy Director, Tuberculosis Research Centre, Chennai. 21

2 Microscopy is more objective and reliable than X-rayX % AFB Microscopy 7% X-ray Inter-observer agreement NTI,Bangalore,1968 X-ray for TB diagnosis How accurate we are? Culture Results Positive Negative X-Ray Yes (37%) 227 Tubercu No lo sis (%) NTI 197 % agreement There is a high Inter and Intra-reader reader variation in X-ray X interpretation When Xray is used as a screening tool in survey, only % is confirm ed by culture TB by X ray cult. Pos 57 Reader 1 vs Reader 2 Reader 1 vs Reader 3 Reader 2 vs Reader 3 TRC, unpublished 6 TB both readers TB one reader TB TRC Current study 11 Sputum based Diagnosis & role of X-rayX 3 weeks of Productive cough Examine 3 sputum 2 or 3 pos. 1 pos. X ray chest 3 neg. Antibiotics 1 days Symptoms persist X ray chest Cumulative Positivity % 5% Cases among chest symptomatics 78% 98% % C um ulative Positivity % 5% 92% 99% % Sm.pos TB Abnormal suggestive of TB Normal Non TB Abnormal Sm Neg TB % First Second Third NTI, Bangalore % First Second Third TRC,unpublished 22

3 13 14 Ø Diagnosis of TB primarily based on sputum microscopy Ø Directly observed treatment N eed for domiciliary treatment ØTB situation in 195s in India Ø hospital beds available 23, ØNo. of sputum positive patients 1,5, ØPatients were being treated at home ØConcern: Spread of disease and increase in the burden of illness ØTB situation in India now ØBeds available 47, ØNo. of sputum positive patients 3,5, 15 TRC studies dem onstrated that sm ear positive TB 16 patients can be treated effectively at home with no added risk to contacts Series Patients Home San Favorable Response contacts Attack rate TRC, 1959 Domiciliary Chemotherapy Advantages Ø Dom iciliary chem otherapy as effective as sanatorium treatm ent Ø No additional benefit by bed rest, special diet etc. Ø Contacts not at a higher risk Ø No need for hospitalisation Ø Econom ic benefit Self administration of drugs Ø Long term self administration of anti TB drugs is problematic ØNeed for research concerning general reliability of patients in the self administration of drug over a long period Fox W,TRC-1957 Problem of self administration of drugs Tuberculosis Hammersmith London 5 % of 151 pts. on PAS at home were irregular Leprosy Ross Innes Self administration of medicaments is rarely reliable, need to devise some method of regular supervised admin. Other conditions Malaria, Diabetes, Epilepsy, Rheumatic fever, Hypothyroidism. Fox W

4 Default 19 To default is the natural reaction of normal, sensible people; the person who continues to swallow drugs or have injections with complete regularity in the absence of encouragement and help from others is the abnormal one. Annik Roullion How to reduce default Ø Supervised drug administration v Daily difficult for patient v Intermittent more feasible Ø Taking treatment closer to the patient Ø Reducing the duration of treatment Ø Diagnosis of TB primarily based on sputum microscopy Ø Directly observed treatment Genesis of intermittent chemotherapy Ø Isoniazid given in single dose more effective than divided doses Ø 8% drug intake was found to be adequate Ø Experimental evidence Concept of intermittent chemotherapy: Animal studies Growth of M Tb during & after exposure to INH Guinea pigs: Copper & Cohn (1947): Strep. once in 5 days Palmer(1956) : INH once in 7 days Mouse: Grumbach(1952) Bloch (1961) : Strep & INH once in 3 days : INH once in 7 days Log Viable Units of M Tb INH added All anti-tuberculosis drugs except Thioacetazone, have a lag phase INH washed Lag phase Days 24

5 25 26 Intermittent Supervised Chemotherapy is Effective Fav Resp Patients % % Effective oral intermittent regimens Patients Response PH PH PH SH TRC, 1963 SHE / EH SHE / EH TRC, 1973, 1981 Advantages of intermittent treatment Ø As effective as daily treatment Ø Facilitates observation Ø Prevents concealed irregularity Ø Less adverse reactions Ø drugs consumed - less Ø Less costly Ø Diagnosis of TB primarily based on sputum microscopy Ø Directly observed treatment 29 3 Efficacy of SCC regimens Rhythm Tot.Pts. Fav.Resp. 2HREZ/6HE Daily HRZS/5HZS HRZS/2HZS 2 Partially intermittent HRZS/3HSZ HRZE 3 /4HR HRZE 2 /4HR E HRZE 3 /3HR 2 Fully intermittent HRZS 3 /4HR (S) 2or HRZS 2 /4HR (S) 2or TRC Regim en 2HRZS/4HR 2HRZS/4HR 2HRZS/6HT 2HRZS/4SHZ 2 2HRZ/4HR 2 2HRZE/4HR 2 2HRZS 3 /4HRZ 2 Efficacy of SCC s Rhythm Daily Partially interm ittent Fully interm ittent No Place & year of study Singapore 1973 East Africa 1978 East Africa 1972 Poland 1984 Zaire 1989 South Africa

6 31 32 Adverse Reactions with SCC regimens Type Arthralgia Hepato-toxicity Gastro-intestinal, Giddiness & others Daily 24 45% 4 8% 9 27% Intermittent 3-8% 1% 1 6% TRC Response related to prior treatment % 8% N = 1324 N = 431 Un Fav 3% Fav 1% % 4% 97% P =.1 9% % % Prior Rx < 1 mo Prior Rx > 1 mo TRC SCC in Extra Pulmonary TB No. of Fav. Follow up Studies pts Resp. period(m) TB spine 6 HR TRC,1998 9HR Pott s paraplegia TRC,1997 2SHER/7HR TB lymphadenitis TRC,199 2SHRZ 3 /4SH TB Abdomen TRC,1997 2HRZ/4HR 1SEH/11EH TB Skin TRC, Unpublished 9HR Brain tuberculoma 3HRZ/3HR TRC,1995 3HRZ3/6HR Basis of regimens for 3 categories CAT I: New sputum sm. Pos. patients with high bacillary population, Chances for naturally occurring resistant mutants more, hence 4 drugs in IP CAT II: Having received earlier treatment - more drugs and longer duration. Hence 5 drugs in IP and 8 months duration CAT III: Smear negative with low bacillary population - lower chance of resistant organisms, hence 3 drugs 26

7 37 38 Ø Diagnosis of TB primarily based on sputum microscopy Ø Directly Observed Treatment Directly irectly Observed Treatment (DOT) vs DOTS 39 4 Ø Directly observed treatment (DOT) is one element of the DOTS strategy Ø An observer watches and helps the patient swallow the tablets Ø Direct observation ensures treatment for the entire course ü with the right drugs ü in the right doses ü at the right intervals Directly Observed Treatment is the Standard of Care DOT has emerged as the standard of care (Bayer, Lancet, 1995) Every patient with TB in this country should receive DOT (Iseman, NEJM, 1993) DOT seems imperative where the disease has become epidemic (Chaulk, JAMA, 1996) 41 Is DOTS Essential? DOTS is not the final answer There will be a better way! BUT DOTS is the BEST strategy for controlling TB that we have TODAY BUT The most contentious part of DOTS is DO Ian Smith 27