Isoniazid Preventive Therapy in Contacts of Multidrug-resistant Tuberculosis

RATIONALE: The World Health Organization recommends the use of isoniazid alone or in combination with rifapentine to treat latent tuberculosis infection. The recent rise of drug-resistant tuberculosis has complicated the choice of latent tuberculosis infection treatment regimen. OBJECTIVES: To evaluate the effects of isoniazid preventive therapy on contacts of multidrug-resistant tuberculosis patients Methods: In a prospective cohort study conducted between September 2009 and August 2012, we identified 4,500 index tuberculosis patients and 14,044 tuberculosis-exposed household contacts whom we followed for one year for the occurrence of incident tuberculosis disease. Although Peruvian national guidelines specify that isoniazid preventive therapy should be provided to contacts aged 19 and under, only half this group received isoniazid preventive therapy. MEASUREMENTS AND MAIN RESULTS: Among 4,216 contacts under 19 years of age, 2,106 (50%) initiated isoniazid preventive therapy at enrollment. The protective effect of isoniazid was more extreme in contacts exposed to drug-sensitive (adjusted hazard ratio, 0.30 [95% confidence interval, 0.18-0.48]) and to multidrug-resistant tuberculosis (0.19 [0.05-0.66]) compared to those exposed to mono-isoniazid-resistant (0.80 [0.23-2.80]). In the second independent study, tuberculosis occurred in none of the 76 household contacts who received isoniazid preventive therapy compared to 3% (8/273) of those who did not. CONCLUSION: Household contacts who received isoniazid preventive therapy had a lower incidence of tuberculosis disease even when they had been exposed to an index patient with multidrug-resistant tuberculosis. Isoniazid may have a role in the management of latent multidrug-resistant tuberculosis infection