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Previous reports from India have been limited to the incidences of hepatitis B antigen (HB Ag) in health and disease. This paper reports on a study undertaken over the last two years to determine the incidence of hepatitis B virus infection, the serotypes prevalent among apparently healthy individuals and patients with liver diseases, and the seasonal incidence of sporadic acute hepatitis in this geographic area. The incidences of infection in health and disease show an endemic pattern. The Y subtype predominates among healthy carriers and patients with chronic liver diseases, whereas the D subtype predominates in patients with acute hepatitis. The similarity of subtypes of HB Ag among the majority of healthy carriers and patients with chronic liver diseases suggests that the majority of asymptomatic carriers (subclinically infected) would develop chronic liver disease. The proportion of HB Ag-positive cases of acute hepatitis was significantly higher during the two summer seasons than during the two winter seasons; this could be due to more frequent transmission of the virus by the faecal/urinary—oral route and its activation during the summer months, especially in areas with poor hygienic conditions. The urinary/faecal excretion of virus could thus maintain the natural transmission of the virus in such an environment.

Previous reports from the Tuberculosis Chemotherapy Centre, Madras, have established that ambulatory treatment of pulmonary tuberculosis with the combination of isoniazid and PAS, administered daily, yields satisfactory results. However, in the usage of any unsupervised regimen, reliance must be placed on the co-operation of patients in self-administering their drugs. Irregularities in drug-taking, which are not uncommon, may lead to unfavourable therapeutic results; this might be avoided by supervised administration of the drugs. Daily supervision is clearly impracticable in developing countries but regimens in which the drug is administered intermittently-say, twice a week or less frequently-are, if effective, more likely to gain general application.This paper presents the results of a controlled study of a fully supervised intermittent regimen of isoniazid (12.5-16.1 mg/kg body-weight, orally) plus streptomycin (injected in a uniform dose of 1 g), given together twice weekly, compared with a standard, unsupervised, daily, oral regimen of isoniazid (3.7-6.3 mg/kg body-weight) plus sodium PAS (0.2-0.3 g/kg body-weight), given in two doses. The intermittent regimen was at least as effective as the standard oral regimen, and although the incidence of temporary giddiness in patients receiving this regimen was rather high, this did not appear to have any long-term importance nor did it appear unduly to affect the co-operation of the patients. These encouraging findings suggest a possible change in the orientation of drug-administration for tuberculosis in developing countries.

A previous report from the Tuberculosis Chemotherapy Centre, Madras, has shown that, if standard chemotherapy is given for one year, the response of patients treated at home in very poor environmental circumstances is nearly as good as that of those treated in sanatorium under much more favourable conditions. This paper reports on a four-year follow-up of all the patients whose disease was bacteriologically quiescent at the end of the year's treatment. During this period, all the patients were managed on a domiciliary basis; about a quarter of them received chemotherapy with isoniazid alone for two years, another quarter received the drug for one year and the rest received no specific chemotherapy. Despite adverse environmental factors (poor diet; long hours of work often involving strenuous physical activity; overcrowded living conditions; and, for the sanatorium patients, the stresses of returning suddenly to the unfavourable home environment), the great majority of patients in both series maintained quiescent disease throughout the follow-up period. Furthermore, the few patients whose disease relapsed bacteriologically were at no special dietary disadvantage in comparison with those who maintained quiescent disease throughout, nor did they show any appreciable differences in occupation, physical activity or living accommodation. These findings, together with the earlier ones, indicate that, despite adverse environmental circumstances, standard chemotherapy for an adequate period of time is sufficient in the great majority of patients for the attainment of bacteriological quiescence and its maintenance thereafter.

Recent studies have shown that treatment of pulmonary tuberculosis with isoniazid plus p-aminosalicylic acid (PAS) at home is, in the majority of cases, as satisfactory as treatment with the same combination of drugs in sanatorium and does not appear to expose the patient's contacts to any special risk. Before mass domiciliary chemotherapy can be introduced, however, a question that has to be decided is what drug or drugs and what dosage and rhythm of administration will be most effective.THIS PAPER PRESENTS THE RESULTS OF A CONTROLLED COMPARISON OF FOUR CHEMOTHERAPEUTIC REGIMENS: (a) 3.9-5.5 mg/kg body-weight of isoniazid plus 0.2-0.3 g/kg body-weight of PAS (sodium salt) daily in two doses (the standard combined chemotherapy); (b) 7.8-9.6 mg/kg body-weight of isoniazid alone daily in one dose; (c) 7.8-9.6 mg/kg body-weight of isoniazid alone daily in two doses; (d) 3.9-5.5 mg/kg body-weight of isoniazid alone daily in two doses. Isoniazid plus PAS proved to be the most satisfactory regimen; it was clinically effective and there were very few toxic manifestations.

Since isoniazid is metabolized in man to several derivatives with little or no specific activity against the tubercle bacillus, its rate of inactivation in the body may have an important bearing on its efficacy as an antituberculosis drug. The inactivation rate, though constant in any one person, is known to vary from individual to individual and from race to race. A series of studies on the rate of inactivation of isoniazid in Indian patients with pulmonary tuberculosis has recently been undertaken at the Tuberculosis Chemotherapy Centre, Madras. The present paper describes the first of these studies, in which the concentration of isoniazid in the serum of patients admitted to a controlled comparison of four domiciliary chemotherapeutic regimens was determined by microbiological assay four-and-a-half hours after administration of a standard dose of isoniazid (3 mg/kg body-weight). Patients with serum levels of 0.58 mug/ml or more were classified as slow inactivators of isoniazid and those with levels below 0.58 mug/ml as rapid inactivators. By this definition, 195 (61%) of the 321 patients studied were found to be slow inactivators and 126 (39%) rapid inactivators. A relationship was shown between sex and the rate of inactivation, there being a significantly higher proportion of rapid inactivators among the females than among the males. The observed estimates of the error of the microbiological assay procedure are discussed and possible ways of reducing the error suggested.

Recent work carried out at the Tuberculosis Chemotherapy Centre, Madras, and at the Postgraduate Medical School of London has shown that isoniazid-sensitive cultures of tubercle bacilli obtained before the start of chemotherapy from South Indian patients with pulmonary tuberculosis are of lower average virulence than corresponding cultures from British patients. The present paper from the Centre extends these studies to areas outside India by comparing isoniazid-sensitive cultures from 81 Thai patients and 67 British patients for their guinea-pig virulence. As assessed by the amount of disease visible at post-mortem examination six weeks after intramuscular injection of the cultures, by the mortality of the guinea-pigs and by the results of spleen culture, the Thai cultures were less virulent than the British cultures. However, a retrospective comparison with the earlier studies suggests that the Thai cultures were intermediate in their virulence between British and Indian cultures. These findings contribute to the over-all study of the geographical distribution of attenuated tubercle bacilli.

Tuberculosis control by mass domiciliary chemotherapy is now being attempted on an increasingly large scale in the technically underdeveloped countries. The National Tuberculosis Institute in Bangalore, India, is an important centre for the development of such programmes, and the study reported in this paper is an inquiry into the working of an urban tuberculosis programme which is operated under the auspices of the Institute. The study reveals several fundamental weaknesses in the treatment organization in this particular programme, and the authors show that such weaknesses are in evidence in similar programmes elsewhere. However, the authors conclude that a great proportion of the problems of inadequate treatment can be dealt with by improved administration and organization. In the authors' opinion, such improvements merit a much higher priority than measures to perfect the technical aspects of the programmes.