Extension of the intensive phase reduces relapse but not failure in a regimen with rifampicin throughout.
METHODS
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.


METHODS
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.
Damien Foundation Bangladesh, Dhaka, Bangladesh.
K J M
KJ
Aung
E
E
Declercq
Md A
MA
Ali
S
S
Naha
S C
SC
Datta Roy
Md A
MA
Taleb
Md A
MA
Hossain
L
L
Rigouts
A
A
Gumusboga
A
A
Van Deun
D000995:Antitubercular Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001459:Bangladesh; D004334:Drug Administration Schedule; D006801:Humans; D008826:Microbial Sensitivity Tests; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012293:Rifampin / Q000008:administration & dosage / Q000627:therapeutic use*; D055502:Secondary Prevention; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA; D013183:Sputum / Q000382:microbiology; D016896:Treatment Outcome; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy* / Q000453:epidemiology / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000382:microbiology
D000995:Antitubercular Agents; D012293:Rifampin