thioacetazone and Drug-Hypersensitivity

Topics: Acne Vulgaris; Adult; Amikacin; Antitubercular Agents; Drug Hypersensitivity; Ethambutol; Ethionamide; Female; Humans; Isoniazid; Male; Middle Aged; Pellagra; Pigmentation Disorders; Prothionamide; Pyrazinamide; Rifampin; Skin Diseases; Streptomycin; Thioacetazone

Topics: Aminosalicylic Acids; Animals; Cycloserine; Drug Hypersensitivity; Drug Resistance, Microbial; Ethionamide; Geography; Guinea Pigs; Hematopoietic System; Humans; Isoniazid; Mice; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Skin Manifestations; Streptomycin; Thioacetazone; Tuberculosis

Among HIV-positive patients who received treatment for active tuberculosis, thiacetazone has been associated with cutaneous hypersensitivity and recurrent tuberculosis. No controlled trials have investigated the safety and efficacy of thiacetazone-containing regimens compared with alternative regimens among patients with HIV. In a randomised clinical trial of 191 HIV-positive patients with active pulmonary tuberculosis, we examined the safety and short-term efficacy of isoniazid, rifampicin, and pyrazinamide for two months followed by isoniazid and rifampicin for seven months (RHZ) compared with streptomycin, thiacetazone, and isoniazid for two months followed by thiacetazone and isoniazid for ten months (STH). Between May, 1990, and September, 1991, 191 HIV-positive adult Ugandan patients with acid-fast bacilli sputum smear-positive pulmonary tuberculosis (93% confirmed by culture) received either STH or RHZ. Subjects had a standard evaluation that included Mantoux skin test, complete blood count with differential white blood cell count, and chest radiography. After starting therapy, subjects were followed-up over one year for three outcomes: complications of anti-tuberculosis therapy, early sterilisation of cultures, and survival. Of 191 eligible subjects, 90 received STH and 101 received RHZ. The overall one-year survival was similar for STH and RHZ (65% vs 72%), but when controlled for baseline differences in Mantoux reaction size and absolute lymphocyte count, the relative risk of death for STH compared with RHZ was 1.57 (95% CI 1.0-2.48). Overall, 12 adverse drug reactions occurred in the STH arm (18.2 reactions per 100 person years [PYO]) compared with one in the RHZ arm (1.6 reactions per 100 PYO) for a relative risk of 11.7 (95% CI 1.52-90.0). 10 cutaneous reactions occurred in the STH arm (15.2 events per 100 PYO) compared with one event in the RHZ arm (1.6 events per 100 PYO) for a relative risk of 9.7 (95% CI: 1.24, 75.8). A greater proportion of RHZ patients compared with STH patients had sterilised their sputum within two months (74% vs 37%, p < 0.001). In developing countries, rifampicin-containing regimens should be given, when possible, to HIV-positive patients to reduce drug toxicity and to prolong survival.

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Drug Eruptions; Drug Hypersensitivity; Drug Therapy, Combination; Female; Humans; Isoniazid; Male; Middle Aged; Pyrazinamide; Rifampin; Streptomycin; Survival Rate; Thioacetazone; Tuberculosis, Pulmonary; Uganda

Topics: Antitubercular Agents; Drug Costs; Drug Hypersensitivity; Humans; Nepal; Thioacetazone; Tuberculosis, Pulmonary

Topics: Drug Hypersensitivity; HIV Seropositivity; HIV-1; Humans; Thioacetazone; Zambia

Topics: Adult; Drug Hypersensitivity; Female; Humans; Middle Aged; Stevens-Johnson Syndrome; Thioacetazone; Tuberculosis, Pulmonary

Topics: Adult; Dermatitis, Exfoliative; Drug Hypersensitivity; Humans; Male; Stevens-Johnson Syndrome; Thioacetazone; Time Factors

Topics: Clofazimine; Dapsone; Drug Hypersensitivity; Ethionamide; Humans; Leprostatic Agents; Leprosy; Rifampin; Thioacetazone

Topics: Aminosalicylic Acids; Animals; Antitubercular Agents; Capreomycin; Chemical and Drug Induced Liver Injury; Cycloserine; Deafness; Drug Hypersensitivity; Ethambutol; Ethionamide; Gastrointestinal Diseases; Goiter; Humans; Isoniazid; Kanamycin; Liver; Mental Disorders; Mice; Nervous System Diseases; Pyrazinamide; Rifampin; Streptomycin; Thioacetazone; Tuberculosis; Viomycin

Drug hepatitis occurred in 0-32 per cent of 7492 patients receiving antituberculous therapy, while the overall incidence of drug reactions was estimated at 9 per cent. PAS was the most common cause of drug hepatitis among the 38 patients analysed. The clinical, biochemical and haematological picture of antituberculous drug hepatitis was found to be fairly uniform. However, the patients with definite PAS hepatitis had lower SGOT values than those in whom there was uncertainty whether PAS or INH was implicated. Premonitory symptoms were present in all but four patients before the onset of jaundice. One or more of the features associated with dry hypersensitivity reactions, such as fever, rashes, lymphadenopathy, arthralgia, leucocytosis, eosinophilia and atypical monocytes were present in 89 per cent of cases so that confusion with viral hepatitis seldom arose. Sensitization time was less than three months in all except three patients, who were considered to be suffering from viral hepatitis. While no patients with PAS hepatitis died, the overall mortality was 17 per cent. A review of the literature stresses the frequency of asymptomatic elevations of SGOT, the value of clinical surveillance during the early months of therapy and the importance of stopping all therapy immediately warning symptoms appear.

Topics: Aminosalicylic Acids; Antitubercular Agents; Chemical and Drug Induced Liver Injury; Drug Hypersensitivity; Ethambutol; Ethionamide; Female; Gastrointestinal Diseases; Humans; Isoniazid; Jaundice; Lymphatic Diseases; Male; Pyrazinamide; Skin Diseases; Streptomycin; Thioacetazone; Tuberculosis, Pulmonary

Topics: Adolescent; Africa, Eastern; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Hypersensitivity; Drug Resistance, Microbial; Drug Therapy, Combination; Humans; Isoniazid; Mycobacterium tuberculosis; Streptomycin; Thioacetazone; Tuberculosis, Pulmonary

Topics: Child; Child, Preschool; Drug Hypersensitivity; Humans; Infant; Isoniazid; Thioacetazone; Tuberculosis, Pulmonary

As part of a large-scale international cooperative investigation into the side effects of thioacetazone-containing regimens in the treatment of tuberculosis, an evaluation has been made of the variation in the frequency of side effects between different countries and between different centres in the same country and of the likely reasons for this variation. In 3 countries patients of different racial origin were under observation in the same hospital. Over a 12-week period of treatment there was considerable variation between the countries and centres in the overall frequency of side effects and of those leading to a major departure from prescribed treatment, the variation being similar for the two thioacetazone-containing regimens and for the streptomycin plus isoniazid control regimen, though at a lower level for the latter. In Malaysia, Singapore, and Trinidad, where different racial groups were under treatment, there was no clear indication that race was an important factor in explaining the differences between countries, except for cutaneous side effects in Trinidad and possibly in Malaysia.It is concluded that the differences in the frequency of side effects to thioacetazone-containing regimens probably result from variation in the closeness of supervision of patients, in the recording and interpretation of side effects, and in environmental factors including the previous use of other medicaments or exposure to sensitizing substances.

Topics: Adult; Africa, Northern; Antitubercular Agents; Asia; Czechoslovakia; Drug Hypersensitivity; Female; Geography; Humans; International Cooperation; Male; Middle Aged; Racial Groups; Thioacetazone; Trinidad and Tobago; Tuberculosis, Pulmonary

Topics: Agranulocytosis; Aminopyrine; Analgesics; Analgesics, Non-Narcotic; Anemia; Anemia, Aplastic; Anti-Bacterial Agents; Antibiotics, Antitubercular; Antimony; Antipyretics; Antithyroid Agents; Antitubercular Agents; Arsphenamine; Bismuth; Chloramphenicol; Drug Hypersensitivity; Hypnotics and Sedatives; Japan; Mercury; Statistics as Topic; Sulfonamides; Thioacetazone; Thrombocytopenia; Toxicology