The effectiveness of isoniazid preventive treatment among contacts of multidrug-resistant tuberculosis: a systematic review and individual-participant meta-analysis.
Journal
American journal of respiratory and critical care medicine
Journal Volume
212
Journal Issue
1
Start Page
129-137
ISSN
1535-4970
Date Issued
2026-01-01
Author(s)
Martinez, Leonardo
Campbell, Jeffrey I
Linde, Lauren
Boulahbal, Fadila
Cayla, Joan A
Chakhaia, Tsira
Chan, Pei-Chun
Chen, Cheng
Fox, Greg
Grandjean, Louis
Hannoun, Djohar
Hesseling, Anneke
Horsburgh, C Robert
Huang, Li-Min
Liu, Qiao
Mazahir, Rufaida
Lee, Chih-Hsin
Bennet, Rutger
Nejat, Sahar
Gupta, Amita
Das, Mrinalini
Murray, Megan
Huang, Chuan-Chin
Del Corral, Helena
Benjumea-Bedoya, Dione
Shen, Ye
Becerra, Mercedes
Chang, Vicky
Krishnan, Sonya
Heinmueller, Petra
Brewer, Timothy
Isaakidis, Petros
Hauri, Anja M
Shah, Lena
Trieu, Lisa
Seddon, James A
Abstract
Rationale: Recent empirical research suggests that isoniazid may lead to a risk reduction of incident tuberculosis (TB) among close TB contacts of someone with multidrug-resistant TB (MDR-TB).
Objectives: To evaluate the association between isoniazid TB preventive treatment (TPT), compared to no treatment, upon incident TB in household contacts of MDR-TB cases using a large global consortium of TB contact tracing studies.
Methods: We conducted a systematic review and individual-participant meta-analysis among observational studies of household contact tracing studies. Participants were included if they were exposed to someone with MDR-TB and were given either 6 months of isoniazid TPT or no TPT. Our primary outcome was incident TB in contacts exposed to TB. We derived adjusted hazard ratios (aHRs) using mixed-effects, multivariable survival regression models with study-level random effects. The effectiveness of isoniazid TPT against incident TB was estimated through propensity score matching.
Measurements and main results: We included participant-level data from 6668 contacts exposed to MDR-TB from 17 countries. The effectiveness of isoniazid TPT against incident TB in contacts of MDR-TB was 57% (aHR, 0.43 [95% CI, 0.26-0.71]) and did not appreciably change with adjustment for additional potential confounders. The reduction in incident TB was marginally greater among child (<20 years old) contacts (aHR, 0.51 [95% CI, 0.28-0.92) compared to adult contacts (aHR, 0.69 [95% CI, 0.22-2.20]). The reduction in incidence was 73% (aHR, 0.27 [95% CI, 0.11-0.70]) in the first year of follow-up; effectiveness dropped to 60% (aHR, 0.40 [95% CI, 0.15-1.06]) from 12 to 23 months of follow-up and was nonsignificant after 2 years (28% effectiveness; aHR, 0.72 [95% CI, 0.33-1.54]).
Conclusions: Among >6500 contacts of MDR-TB, isoniazid TPT was highly effective in preventing incident TB. The reduction was greatest in high-burden countries and waned after 2 years of follow-up.
Publisher
American journal of respiratory and critical care medicine
Type
journal article