title: Bacillus Calmette-Guérin and isoniazid preventive therapy protect contacts of patients with tuberculosis.
abstract: BACKGROUND
  Individuals living with patients with tuberculosis (TB) are at elevated risk of infection and disease, with children at greatest risk. The World Health Organization recommends isoniazid preventive therapy (IPT) for HIV-positive contacts and those younger than 5 years. Despite these recommendations, household-level IPT programs are rarely implemented in high TB burden settings. Evidence is scarce about the age-specific efficacy of interventions, such as IPT and bacillus Calmette-Guérin (BCG) vaccination for preventing TB disease among exposed contacts.
  
  
  OBJECTIVE
  We estimate the age-specific efficacy of IPT and BCG for preventing TB disease using data from a large observational prospective cohort study of household contacts of patients with TB in Lima, Peru.
  
  
  METHODS
  We identified all adults (>15 yr) with incident pulmonary TB (index cases) diagnosed at 106 public health centers in Lima from September 2009 to August 2012. Among 14,041 household contacts (of 3,446 index cases) assessed for infection and disease during the year-long follow-up period, we identified 462 additional TB cases. We estimate risk ratios (RR) for pulmonary TB associated with BCG, IPT, and latent TB infection.
  
  
  RESULTS
  BCG confers protection against coprevalent and incident TB among HIV-negative children younger than 10 years (RR, 0.35; 95% confidence interval, 0.19-0.66). IPT confers protection against incident TB among HIV-negative contacts younger than 30 years (RR, 0.33; 95% confidence interval, 0.20-0.54). Risk of incident TB associated with latent TB infection is greatest for children younger than 5 years and decreases with age.
  
  
  CONCLUSIONS
  These findings support the use of IPT in older children and young-adult household contacts, in addition to children younger than 5 years.
authors.affiliation: 1 Department of Ecology and Evolutionary Biology, Princeton University, Princeton, New Jersey.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Zelner
authors.forename: Megan B
authors.initials: MB
authors.lastname: Murray
authors.forename: Mercedes C
authors.initials: MC
authors.lastname: Becerra
authors.forename: Jerome
authors.initials: J
authors.lastname: Galea
authors.forename: Leonid
authors.initials: L
authors.lastname: Lecca
authors.forename: Roger
authors.initials: R
authors.lastname: Calderon
authors.forename: Rosa
authors.initials: R
authors.lastname: Yataco
authors.forename: Carmen
authors.initials: C
authors.lastname: Contreras
authors.forename: Zibiao
authors.initials: Z
authors.lastname: Zhang
authors.forename: Bryan T
authors.initials: BT
authors.lastname: Grenfell
authors.forename: Ted
authors.initials: T
authors.lastname: Cohen
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000995:Antitubercular Agents / Q000627:therapeutic use*; D001500:BCG Vaccine; D002648:Child; D002675:Child, Preschool; D016358:Contact Tracing; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007538:Isoniazid / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D008962:Models, Theoretical; D015999:Multivariate Analysis; D016017:Odds Ratio; D010568:Peru; D011446:Prospective Studies; D016896:Treatment Outcome; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis / Q000517:prevention & control* / Q000635:transmission; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D001500:BCG Vaccine; D007538:Isoniazid