A study was carried out to investigate the applicability of INH-Thiacetazone (TH) combination with special reference to acceptability and toxicity in Tumkur district. 150 patients from Tumkur town and some nearby villages were discovered during a mass Case-finding programme. Of them, 127 including 43 sputum positives were given chemotherapy with 300 mgm INH and 150 mgm thiacetazone (TH), in a single tablet to be taken once a day. All but one patient had the treatment on an ambulatory basis. Results of treatment in respect of 103 patients are presented in the paper.

The overall death rate was of the order of 15%. About twice the number of deaths occurred among the sputum positive patients than among the negative ones. About 40% of deaths occurred during the first quarter. In all, 23 patients developed side effects, in 18 of them thiacetazone had to be withdrawn. Serious side effects occurred among 5 (4%) patients. These patients did not report to the treatment centre by themselves and could not have been detected, if home visits were not made, thus giving an erroneous impression about side effects with TH. The sputum conversion at the end of one year was of the order of 50% among all survivors. Among those who were drug sensitive and examined at one year, conversion rate was 63%. Favourable radiological response was seen in 74%.

Thus, though cheap and clinically effective, Thioacetazone in combination with INH was found to produce serious and significant side effects. Hence, vigilance by the treatment centres were thought to be necessary when the patients are on this regimen.

Application of a combined regimen of INH and Thioacetazone (TH) under conditions of District Tuberculosis Programme having become a distinct possibility, the study observed its applicability and toxicity. In all, 127 patients discovered during a mass Case-finding investigation were treated in their homes with 300 mgm of INH and 150 mgm of thioacetazone in a single tablet once a day. Close supervision of patients, laboratory or clinical examination to elicit toxic/side effects were not practicable. During their initial motivation, patients were asked to report back in the event of occurrence of unpleasant symptoms. At subsequent drug collection, indirect questioning for side effects was done. An active search for toxicity was also made by the home visiting staff when they visited patients' homes for defaulter retrieval.

In all, 23 patients complained of possible side effects of thioacetazone, of which 5 were major and 18 of minor nature. Among the 5 patients, two had exfoliative dermatitis and three had generalised petechial haemorrhages. All were males above the age of 40 years. All recovered with withdrawal of drugs and anti histamines. The minor side effects were giddiness and vomiting. None died of thioacetazone toxicity. It is concluded that TH regimen can be used for mass application on account of therapeutic efficacy and low price but consequences of side effects must be borne in mind while using this drug combination under district programme conditions.

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.

The effect of specific anti TB drugs on patients having smear negative radiologically positive pulmonary tuberculosis (suspect cases), was studied in Lady Willingdon Tuberculosis Demonstration & Training Centre (LWTDTC), Bangalore during 1975 & 1976. The main objective was to know the proportion of suspect cases treated under the programme requiring the specific treatment with anti TB drugs. A total of 457 suspect cases were randomly allocated to one of the two regimens; 228 patients were treated with INH + Thioacetazone (TH) and 229 with calcium gluconate (Placebo) regimens, for one year. The placebo group allowed a concurrent comparison of status of suspect cases without any specific treatment. After the intake, sputum examination by direct smear, culture for M.tuberculosis and sensitivity for drugs as well as X-ray examinations were carried out at 0, 2nd, 4th, 6th, 9th and 12th month of treatment.

Among the 228 patients on TH, 103 (45.2%) were real suspect cases, 83 (36.4%) sputum positive and remaining 42 non- tubercular. Similarly, out of the 229 patients on placebo regimen, 110 (48%) were real suspect cases, 61 (26.5%) sputum positive and 58 non- tubercular. The effect of treatment was measured by observing the incidence of bacteriologically positive or radiologically active disease from among the real suspect cases of the two groups. At the end of the treatment period, 12.6% of TH group and 29.7% of placebo group were broken down, the difference being statistically significant. Further, an element of self healing was also observed, as about 40% of patients in placebo group showed either clearance of lesions or continuing regression which could be due to self healing or the lesion being non- tubercular in nature. About 30% of the 457 patients at the start of the study were real cases of tuberculosis who under the programme were missed and 20% broke down with bacteriological positive or progress to radiologically active disease when treatment was not offered. Thus, nearly 50% of the suspect cases diagnosed in the programme required anti TB treatment and for those requiring treatment, perhaps TH is not sufficient, as 12.6% broke down in spite of treatment. It would be appropriate to treat suspect cases both from the clinical and epidemiological point of view after taking due precautions to remove non- tubercular cases by doing repeat sputum examination.