No evidence for multiple-drug prophylaxis for tuberculosis compared with isoniazid alone in southeast Asian refugees and migrants: Completion and compliance are major determinants of effectiveness

Background. The use of multiple-drug prophylaxis for tuberculosis (TB) has not been shown to be more effective than prophylaxis with isoniazid alone. The boundary between inactive pulmonary TB (class 4 TB) and culture-negative "active" pulmonary TB (class 3 TB) is often unclear, as is the intention to treat such patients as a preventive measure or as a curative measure. Methods. We compared the effectiveness of single drug preventive therapy with isoniazid to the effectiveness of multiple drug preventive therapy for patients with asymptomatic, inactive TB, in a retrospective cohort study of 984 Southeast (SE) Asian migrants and refugees who received prophylaxis between 1978 and 1980. Results. The rate of TB developing in this cohort was 122 per 100,000 person-years. There was no significant difference in development of TB between people who received isoniazid only and those who received multiple drugs. The only significant predictor of TB was noncompletion of prophylaxis [relative risk (RR) = 62, 95% confidence interval (CI) = 20-194]. Subgroup analysis on people who had completed therapy showed noncompliance as a significant predictor of TB (RR = 16, 95% CI = 1.4-179). The risk of noncompletion (RR = 4.7, 95% CI = 2.37-9.39, P < 0.0001) and noncompliance (RR = 2.2, 95% CI = 1.03-4.7, P = 0.03) was higher for patients who received multiple drugs compared with isoniazid alone. Multiple-drug therapy cost 30 times more than isoniazid alone. Conclusions. We did not find evidence in support of the empirical practice of giving multiple drugs for prevention of TB. This practice is also more costly and more likely to result in noncompliance and adverse drug reactions. (C) 2000 American Health Foundation and Academic Press.