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Isoniazid plus thioacetazone compared with two regimens of isoniazid plus PAS in the domiciliary treatment of pulmonary tuberculosis in South Indian patients.

Previous reports from the Tuberculosis Chemotherapy Centre, Madras, have established that ambulatory treatment of pulmonary tuberculosis with a standard daily regimen of isoniazid plus PAS for one year yields satisfactory results. However, this regimen may be unsuitable for large-scale use in many developing countries, because PAS is expensive, bulky and unpleasant to take, and has poor keeping qualities, especially in tropical countries. It might be possible to overcome these disadvantages, by substituting for the PAS a drug which is equally effective but less expensive and more acceptable, or by reducing the daily dosage of PAS and the period for which it is prescribed.This paper presents the results over a 12-month period of a controlled comparison of (a) the standard regimen of isoniazid (average 4.5 mg/kg body-weight) plus sodium PAS (average 0.22 g/kg), daily in two divided doses; (b) a regimen of isoniazid (average 6.9 mg/kg) plus thioacetazone (average 3.4 mg/kg), daily in one dose; and (c) a 2-phase regimen of isoniazid (average 5.5 mg/kg) plus sodium PAS (average 0.17 g/kg), daily in one dose for 6 months, followed by isoniazid alone (average 6.8 mg/kg), daily in one dose for the second 6 months. The regimen of isoniazid plus thioacetazone was found to be therapeutically as effective as the standard regimen of isoniazid plus PAS; however, it was associated with a higher incidence of minor side-effects, and three cases of exfoliative dermatitis. The 2-phase regimen of isoniazid plus PAS followed by isoniazid alone was less effective.These findings are encouraging for the large-scale use in developing countries of the relatively inexpensive regimen of isoniazid plus thioacetazone; however, any such step should be preceded by carefully planned studies to investigate, under local conditions, the toxicity and the efficacy of the regimen.

Aminosalicylic Acids↗

Human immunodeficiency virus type-1 infection in Zambian children with tuberculosis: changing seroprevalence and evaluation of a thioacetazone-free regimen.

SETTING: This study was conducted at the Department of Paediatrics and Child Health, University Teaching Hospital (UTH), in Lusaka, Zambia. OBJECTIVES: To monitor the seroprevalence of HIV type-1 in children with tuberculosis and to evaluate the response to anti-tuberculosis therapy using a thioacetazone-free treatment regimen. DESIGN: A prospective cross-sectional study of all consecutive newly diagnosed cases of TB in children from 1 month-15 years of age seen at the University Teaching Hospital (UTH) in Lusaka, Zambia between 1 October 1991 and 31 May 1992. RESULTS: 120 children with a clinical diagnosis of tuberculosis and 167 controls were enrolled in the study. The overall HIV type-1 seroprevalence rate in children with tuberculosis was 55.8% (67/120) compared to 9.6% (16/167) amongst the control group (P < 0.0001: odds ratio = 11.50; 95% CI = 5.99-22.7). Common clinical presentations among children with TB were bronchopneumonia (45/162), miliary TB (30/162) and tuberculous lymphadenopathy (21/33). There were no significant differences in clinical presentation of TB between the HIV-negative and HIV-positive groups. The follow-up of those patients with tuberculosis was poor, with only 65 patients (55%) returning to the clinic for scheduled appointments after discharge. All the 16 patients who died did so within 60 days of discharge from hospital; all of them were seropositive for HIV. There were no deaths among the HIV-negative group. Despite the exclusion of thioacetazone from the treatment regimen, cutaneous reactions occurring within 8 weeks of commencing treatment were observed in 7 of the 65 (11%) patients, 2 of whom developed fatal Stevens-Johnson syndrome. All 7 patients were seropositive for HIV-1. CONCLUSIONS: The seroprevalence rate of HIV type-1 among children with tuberculosis in Lusaka continues to rise; careful monitoring of anti-TB therapy (even in regimens excluding thioacetazone) for potentially lethal side effects should be carried out.

Adolescent↗

A second international co-operative investigation into thioacetazone side-effects. 1. The influence of a vitamin and antihistamine supplement.

As part of a large-scale international, co-operative investigation into the side-effects produced by thioacetazone employed in the treatment of tuberculosis, an evaluation has been made of a supplement incorporating vitamins and an antihistamine as a prophylactic.Over a 12-week period of treatment, the additive supplement failed to reduce the over-all frequency of side-effects or the frequency of side-effects leading to a major departure from prescribed treatment. There was also no evidence that the more serious side-effects, particularly rashes, jaundice and agranulocytosis, were reduced by the additives, although the occurrence of vomiting, which was however infrequent, was reduced.In view of this lack of appreciable benefit, as well as the higher cost and impaired keeping properties of tablets containing thioacetazone plus isoniazid when the supplement is added, the use of the supplement as a prophylactic cannot be recommended.

Adolescent↗

Extension of the intensive phase reduces unfavourable outcomes with the 8-month thioacetazone regimen.

SETTING: Damien Foundation tuberculosis (TB) control projects in Bangladesh. OBJECTIVE: To assess the effectiveness of a 1-month extension of the intensive phase for smear-positives at 2 months of an 8-month regimen with a continuation phase consisting of isoniazid (INH) and thioacetazone (Th). DESIGN: A prospective study of two cohorts of newly registered smear-positive cases, with extension of the intensive phase for the control cohort, but not for the study cohort. Culture and drug susceptibility testing (DST) of smear-defined failures and relapses and of random samples of new cases. RESULTS: Among 8230 study patients (86.7% 2-month conversion) and 7206 controls (83.4% conversion), smear-defined failure or relapse outcome was 3.0% for 2-month smear-negatives vs. 3.1% for 2-month smear-positives with extension (non-significant, NS), and 8.2% for 2-month smear-positives with no extension (P < 0.00001). Culture-confirmed failure and relapse reached 1.9% in 2-month smear-negatives and 1.6% (NS) in 2-month smear-positives with vs. 3.7% (P < 0.001) in 2-month smear-positives with no extension. The relative risk (RR) of non-extension in 2-month smear-positives was 2.4 (cultures) to 2.7 (smears). The same RR and borderline significance was found for non-extension of patients with pan-susceptible strains. CONCLUSIONS: Extension of the intensive phase considerably reduces failures and relapses with a weaker regimen in patients smear-positive at 2 months. Its effectiveness may vary with extent of initial drug resistance vs. power of the regimen.

Antitubercular Agents↗