Isoniazid Preventive Therapy in Contacts of Multidrug-Resistant Tuberculosis

Abstract

Rationale: The World Health Organization recommends the use of isoniazid (INH) alone or in combination with rifapentine to treat latent tuberculosis infections. The recent rise of drug-resistant tuberculosis has complicated the choice of treatment regimen for latent tuberculosis infection.Objectives: To evaluate the effects of INH preventive therapy on the contacts of patients with multidrug-resistant tuberculosis.Methods: In a prospective cohort study conducted between September 2009 and August 2012, we identified 4,500 index patients with tuberculosis and 14,044 tuberculosis-exposed household contacts who we followed for 1 year for the occurrence of incident tuberculosis disease. Although Peruvian national guidelines specify that INH preventive therapy should be provided to contacts aged 19 years old or younger, only half this group received INH preventive therapy.Measurements and Main Results: Among 4,216 contacts under 19 years of age, 2,106 contacts (50%) initiated INH preventive therapy at enrollment. The protective effect of INH was more extreme in contacts exposed to drug-sensitive tuberculosis (adjusted hazard ratio, 0.30; 95% confidence interval, 0.18-0.48) and to multidrug-resistant tuberculosis (adjusted hazard ratio, 0.19; 95% confidence interval, 0.05-0.66) compared with those exposed to mono-INH-resistant tuberculosis (adjusted hazard ratio, 0.80; 95% confidence interval, 0.23-2.80). In the second independent study, tuberculosis occurred in none of the 76 household contacts who received INH preventive therapy compared with 3% (8 of 273) of those who did not.Conclusions: Household contacts who received INH preventive therapy had a lower incidence of tuberculosis disease even when they had been exposed to an index patient with multidrug-resistant tuberculosis. INH may have a role in the management of latent multidrug-resistant tuberculosis infection.

Keywords: INH; INH preventive therapy; multidrug-resistant tuberculosis; tuberculosis.

Figure 1.

Effect of isoniazid preventive therapy on disease incidence of household contacts ≤19 years of age. Multivariate model adjusted for index case age, recreational drug use, household contact age, sex, bacillus Calmette-Guérin vaccination scar, nutritional status, being a student or not, tuberculosis history, household socioeconomic status, and household residential district.

Figure 2.

The effect of isoniazid preventive therapy on tuberculosis incidence in household contacts 19 years old or younger by the isoniazid resistance status of index patient adjusted for index case age, recreational drug use, household contact age, sex, bacillus Calmette-Guérin vaccination scar, nutritional status, being a student or not, tuberculosis history, household socioeconomic status, and household residential district. INH-mono = mono–isoniazid resistant; MDR = multidrug resistant; SEN = sensitive.

Figure 3.

(A and B) The effect of ≥3 months (A) or <3 months (B) of isoniazid preventive therapy on tuberculosis incidence in household contacts 19 years old or younger by the isoniazid resistance status of the index patient adjusted for index case age, recreational drug use, household contact age, sex, bacillus Calmette-Guérin vaccination scar, nutritional status, being a student or not, tuberculosis history, household socioeconomic status, and household residential district. For definition of abbreviations, see Figure 2.