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Updated: May 22, 2026

A High-throughput Compatible Assay to Evaluate Drug Efficacy against Macrophage Passaged Mycobacterium tuberculosis
Published on: March 24, 2017
Extension of the intensive phase reduces relapse but not failure in a regimen with rifampicin throughout
K J M Aung1, E Declercq, Md A Ali
1Damien Foundation Bangladesh, Dhaka, Bangladesh.
Setting:
Damien Foundation tuberculosis (TB) control projects in Bangladesh.
Objective:
To assess the effectiveness of extending the intensive phase (P1) of treatment by 1 month for patients who are smear-positive after 2 months of a 6-month regimen containing rifampicin (RMP) throughout.
Design:
Prospective operational study randomising P1 extension for new smear-positive cases with any number of acid-fast bacilli in the 2-month smear (2M+). Smear-defined failures and relapses underwent culture and drug susceptibility testing in addition to DNA sequencing of the rpoB gene before and after treatment.
Results:
Of 16,708 patients evaluated, 12,967 were smear-negative at 2 months (2M-); 1871 and 1870 2M+ were randomised to no extension or extension. Respectively 0.3% (95%CI 0.2-0.4), 1.2% (95%CI 0.7-1.8) and 2.0% (95%CI 1.4-2.8) smear- and culture-positive failures, and 1.2% (95%CI 1.0-1.4), 2.6% (95%CI 1.9-3.4) and 0.9% (95%CI 0.5-1.4) relapses were detected. Extension significantly reversed the relative risk (RR) of relapse of 2M+ vs. 2M- patients from 2.2 (95%CI 1.6-3.0) to 0.7 (95%CI 0.4-1.2). The RR for failure remained high, at 7.3 (95%CI 4.7-11.5) with and 4.2 (95%CI 2.5-7.2) without extension. More multi-drug resistance was found after extension, but acquired RMP resistance was similar in all arms. The fair sensitivity of the 2-month smear for failure or relapse (40%) was offset by a very low positive predictive value (3%).
Conclusions:
Extension of P1 is very inefficient with this 6-month regimen. Operational research should define appropriate algorithms allowing an earlier switch to the next higher regimen for those in need, using follow-up smears for screening.
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