The Impact of Isoniazid Preventive Therapy on Tuberculosis Infection and Disease Progression

Tuberculosis (TB) causes major morbidity and mortality among children worldwide. Isoniazid preventive therapy (IPT) protects against progression to TB disease, but its effect on preventing new TB infection remains uncertain.

We conducted a longitudinal cohort study in Lima, Peru, enrolling adults with microbiologically confirmed pulmonary TB and their household contacts (HHCs). We assessed HHCs at baseline and 6 months for TB infection using tuberculin skin testing (TST) and for TB disease through clinical evaluation. We assessed two outcomes in relation to IPT initiation: TB infection among HHCs under 5 years of age, indicated by an increase in TST induration of ≥6 mm from baseline to 6 months, and progression to TB disease among HHCs of all ages, diagnosed between 15 days and 12 months after enrollment.

Among 666 under-5-year-olds included assessed for TST conversion, 361 (54.2%) had initiated IPT. Overall, 103 (15.5%) converted at 6 months; IPT initiation was not associated with conversion (adjusted OR 1.01; 95% CI, 0.64-1.59). Index-participant cavitary disease was associated with an increased risk of conversion. In contrast, IPT initiation was associated with reduced risk of progression to TB disease among 14,032 HHCs of all ages (adjusted HR 0.45; 95% CI, 0.32-0.64) with more pronounced efficacy among under-5s (adjusted HR 0.19; 95% CI, 0.10-0.36).

IPT was not associated with reduced TST conversion among children under 5 years, but it was strongly associated with reduced progression to TB disease among HHCs of all ages.