The relative merits of a fully supervised twice weekly regimen of Streptomycin and INH (SHtW) and an unsupervised daily regimen of INH and Thioacetazone (TH) in routine programme conditions in an urban area are compared in terms of acceptability and response to treatment at one year. Of the 474 newly diagnosed sputum positive cases at Lady Willingdon TB Demonstration & Training Centre, Bangalore during 1968-69, 134 were allocated to SHtW regimen and 189 to TH regimen. All others who were unwilling to take the allocated regimen or were excretors of bacilli resistant to INH and or SM were analysed as a subsidiary group.

About 25% of the patients allocated to SHtW regimen expressed unwillingness to start treatment on account of unsuitability of working hours and or distance. Refusal to TH regimen was negligible (5%). As regards drug acceptability after start of treatment, while the duration of treatment taken was similar for both the regimens, the level of drug intake achieved by the SHtW patients was lower compared with TH patients i.e., 31.3% of the SHtW patients and 56.1% of TH patients took more than 80% of treatment. If concealed irregularity among TH patients is taken into consideration, it is likely that the drug intake among TH patients would be similar to the drug intake among SHtW patients. The acceptability was therefore almost similar among SHtW and TH patients. Very low level (28%) of treatment completion was achieved by SHtW patients. With TH regimen, 46% had made 10 or more monthly collections during 12 months. Among the SHtW patients there was greater irregularity in the later months which was not apparent among TH patients. However, the favourable response among patients on SHtW and on TH regimen was 68% and 60% respectively. Deaths among SHtW patients were 4%, 13.5% among TH patients, the difference being statistically significant. The response was directly related to the level of drug collection or supervised consumption. The large proportion of the patients who stopped treatment prematurely, continued to remain positive with drug sensitive organisms, if initially they were so. In the subsidiary group there were 62 patients who were excretors of drug resistant organisms. They were treated with drugs to which their organisms were resistant and nearly 30% of these patients had negative culture at the end of one year.

It is concluded that (i) SHtW regimen was superior to TH as it prevented deaths and showed better bacteriological conversion among patients with level 3 & 4 of treatment and (ii) treatment organization is the most important factor in obtaining better results in routine chemotherapy with available drug regimens.

A controlled clinical trial of the three Short Course Chemotherapy (SCC) regimens was carried out at the Lady Willingdon State Tuberculosis Centre, Bangalore and Tuberculosis Research Centre, Madras with the collaboration of National Tuberculosis Institute, Bangalore. The regimens were (1) R3: (rifampicin, streptomycin, isoniazid and pyrazinamide daily for 3 months (3RSHZ); (2) R5: same as regimen R3, followed by streptomycin, isoniazid, pyrazinamide twice weekly for 2 months (3RSHZ/2S2H2Z2); (3) Z5: same as regimen R5 but without rifampicin (3SHZ/2S2H2Z2). Newly diagnosed tuberculosis patients who were aged 12 years or more had no history of previous treatment and two sputum cultures positive for M.tuberculosis were taken to the study and allocated at random to one of the above stated three regimens. The patients were given supervised chemotherapy as out patients. Sputum specimens were examined by fluorescent microscopy, culture by modified Petroff's method, tested for sensitivity to INH, rifampicin, streptomycin and ethambutol. The follow up was done by sputum smear and culture examination at the end of every month for 2 years. The distribution of various pre treatment characteristics like age, sex, and initial sensitivity status were similar in the three series. At the end of 3 months, of the 455 patients on R3, and R5 series, 96% with drug sensitive organism became culture negative and of 235 on Z5 series 93% became culture negative. For R5 and Z5 series favourable response at the end of chemotherapy were 96%, 99% and 97% respectively. In all, 6 patients (3 R3 & 3 Z5) were classified as having unfavourable response. At the end of 24th month from the date of start of treatment, 20% of the 200 patients on R3, 4% of 187 patients on R5 and 13% of 199 patients on Z5 had bacteriological relapse. The difference between R3 and Z5 series was highly significant. (p = 0.00001). The relapse rates in R3 & Z5 series were significantly higher than that in R5. Of the 57 patients with initial drug resistance organisms in R3 and R5 series combined 4 had an unfavourable response to treatment compared with 13 of 26 in the Z5 series (p = 0.0001). Of the 4 patients with an unfavourable response in R3 and R5 series combined, resistance to rifampicin emerged in 2 patients. Complaints of arthralgia were made by 45% of the R3 and R5 patients combined and 70% of Z5 patients (p = 0.00001). However, chemotherapy was modified in only 5 and 12% respectively. Jaundice occurred in 7% of the R3 and R5 patients and 1% of the Z5 patients (p = 0.0001).

In a study of feasibility of treatment of smear positive patients with Short Course Chemotherapy (SCC) regimens under District TB Programme (DTP) conditions in a city, adverse drug reactions in terms of frequency of episodes, incidence in the cohort of patients, time of occurrence, major adverse reactions requiring modification of chemotherapy and or symptomatic treatment, were investigated.

Patients were allocated to one of the two 8 month SCC regimens i.e., Regimen 'A' 1 SHRZ/6TH, Regimen 'B' 2SHR/6TH. Overall incidence of adverse drug reaction in cohort of 265 patients was 37%, 9% of which were considered as major in nature. 34 episodes of such reactions resulted in modification of chemotherapy in 15 patients during intensive phase. Though gastro intestinal symptoms were predominant, cutaneous toxicity was the pre eminent cause of modification of regimen. No case of exfoliative dermatitis occurred. A total of 333 episodes of adverse drug reactions of minor nature occurred; 50% being gastro intestinal symptoms followed by cutaneous symptoms. More than 70% of all adverse drug reactions of intensive phase occurred in the first half of the period. There was no significant difference between the two regimens in the incidence of adverse drug reactions of either major or minor in nature.

SCC is being implemented in a phased manner in the DTP. Before introducing SCC in large number of districts, it would be prudent to find out whether SCC would be acceptable to both doctor and patient in terms of adverse drug reactions.
It can, therefore, be concluded that adverse reactions may not be a major constraint for inclusion of SCC under DTP for treating sputum positive tuberculosis patients provided that additional resources and man power are allocated to the DTCs to manage patients in the centre and extend effective guidance to staff working in peripheral centres.

An operational study of two regimens of Short Course Chemotherapy (SCC) to assess their efficacy under programme conditions, applicability and feasibility in District TB Programme (DTP) was undertaken in an urban TB centre. The two regimens studied were 1SHRZ/7TH and 2SHR/6TH. Their operational efficacy (efficiency) was found to be 87% and 92% respectively which had already been reported in an earlier paper. The various factors i.e., initial willingness, drug default, treatment completion pattern, adverse drug reactions and initial drug resistance with their potential harmful effects on the treatment outcome as well as work load and extra cost these regimens entail for DTP organisation are discussed in this paper.

Out of a total of 1822 smear positive patients diagnosed at the Lady Willingdon State TB Centre during intake period (Feb '84 to March '85), 1126 were residents of Bangalore City. Of these 695 (61.7%) were unwilling to attend the clinic daily for 2 months, 27 were unfit and one was excluded by mistake. Thus, 403 (38.3%) initially willing patients were classified either as 'core group' or 'Non core group’, according to the history of previous anti TB treatment (321 and 82 respectively). Of the 695 (77.6%) unwilling persons, majority were those who pleaded inability to attend daily for 2 months without specifying any particular reason. Refusal of SCC due to injections accounted for 12.8% and 9.5% wanted to take treatment elsewhere. Old age influenced willingness adversely.

Of the 321 patients in the core group, 56 were excluded due to missing more than 50% of intensive phase doses. Among the remaining patients, 61 (48%) out of 127 patients on Regimen A and 48 (34%) out of 138 on Regimen B, did not make a single default in the intensive phase. Of the total 910 defaults for which actions were taken, 640 (70%) were retrieved by letter writing, among the remaining 293 (72%) were retrieved by home visiting. Main reasons for default elicited during home visits were: going out of station (52.9%) followed by patients being busy with work (19.1%). Compensatory phase was availed by 156 of the 265 patients who missed one or more doses due to default in the treatment. The pattern of treatment completion of 321 core group patients in the two regimens were similar i.e., in both the phases 65% for Regimen A and 63% for Regimen B. Incidence of minor adverse reactions was 28% and major toxic reactions were experienced by 8.4% of patients. Workload for treating 321 patients was due to supervised administration of drug 45 patients per day. Letter writing to 3.1 per patients, home visiting 1.1 per patient and doctor's attention for adverse reaction 2 occasions per patient. This could be managed with the existing staff. The cost of Regimen A was Rs.220/ per patient and for Regimen B, 268/ per patient. Cost to patient for transportation was Rs.70/ and Rs.113/ for Regimen A and B respectively.The major disturbing finding of the study was initial low acceptability of about 40% for SCC. The home visiting which was crucial in increasing the completion rate in this study is usually not available in most of the DTCs. Workload, adverse reactions etc. were not of any problem for implementation of SCC in the programme.