ABSTRACT Background The World Health Organization recommends the use of isoniazid (INH) alone or combination INH and rifapentine therapy to treat latent tuberculosis infection (LTBI) in groups at high risk of tuberculosis (TB) progression. The recent rise of INH– and multi–drug resistant (MDR) TB has complicated the choice of LTBI treatment regimen. We examine the risk of TB disease among household contacts (HHCs) who received INH after being exposed to patients with drug–sensitive, INH–resistant, or MDR tuberculosis. Methods In this prospective cohort study conducted Between September 2009 and August 2012 in Lima, Peru, we identified 4,500 index TB patients and measured incident TB disease in their 14,044 HHCs over a one–year follow–up period. HHCs under 19 years of age were offered INH preventive therapy (IPT). We used a Cox frailty proportional hazards model to evaluate whether the effect of IPT on incident TB disease varied by the resistance profile of the index case. We repeated the analyses in a second independent dataset. Findings Among 4,216 HHCs under 19 years of age, 2,106 (50%) initiated IPT at enrolment. The protective effect of INH was more extreme in HHCs exposed to drug–sensitive (Hazard Ratio [95% confidence interval]=0·2[0·20–0·50]) and to MDR–TB (0·26[0·08–0·77]) compared to those exposed to mono–INH–resistant (0·80[0·23 to 2·79]). Among those who received at least three months of INH, effectiveness increased across all three groups (INH–sensitive:0·20 [0·10 to 040]; MDR:0·16 [0 02–127]; mono–INH–resistant:0·72 [0·16–3·16]). In the second independent study, TB occurred in none of the 76 HHCs who received IPT compared to 3% (8/273) of those who did not. Interpretation We found that IPT use is associated with reduced incidence of TB disease among contacts of MDR–TB patients. This finding suggests that INH may have role in the management of MDR–LTBI. Funding National Institutes of Health and the National Institute of Allergy and Infectious Diseases CETR (U19AI109755) and TBRU (U19AI111224)

The impact of isoniazid preventive therapy on tuberculosis among household contacts of isoniazid-resistant patients