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

Abstract

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.