title: Risk of Disease After Isoniazid Preventive Therapy for Mycobacterium tuberculosis Exposure in Young HIV-uninfected Children.
abstract: BACKGROUND
  The risk of developing tuberculosis (TB) disease in HIV-uninfected children after isoniazid preventive therapy (IPT) for a positive QuantiFERON-TB Gold In-Tube test (QFT-GIT) is unknown. The aim of this study was to evaluate risk of TB disease after IPT in young HIV-uninfected children with a positive QFT-GIT result, or household TB contact.
  
  
  METHODS
  HIV-uninfected South African infants aged 4-6 months were screened for enrolment in a TB vaccine trial. Baseline household TB contact and positive QFT-GIT result were exclusion criteria, and these infants were referred for IPT. Outcome data are reported for 36 months after IPT referral.
  
  
  RESULTS
  Four thousand seven hundred forty-nine infants were screened. Household TB contact was reported in 131 (2.8%) infants; 279 (6.0%) were QFT-GIT positive, and 138 of these 410 infants (34.0%) started IPT. Forty-four cases of TB disease (11.0%) were recorded within 991 child years of observation. TB disease incidence was 4.8 versus 3.6 per 100 child years in household exposed versus QFT-GIT-positive children [incidence rate ratio: 1.35; 95% confidence interval (CI): 0.67-2.88] and 2.4 versus 5.5 per 100 child years in children who received versus did not receive IPT, respectively (incidence rate ratio: 0.44; 95% CI: 0.17-0.96). Adjusted hazard ratio (Cox regression) for TB disease was 0.48 (95% CI: 0.21-1.05) for those who received IPT.
  
  
  CONCLUSIONS
  In young HIV-uninfected children, the effect of IPT on risk of TB disease is similar, whether TB exposure was defined by household contact history or by positive QFT-GIT result. International IPT guidelines for HIV-uninfected children with a positive QFT-GIT result should be updated.
authors.affiliation: From the *South African Tuberculosis Vaccine Initiative (SATVI), Institute of Infectious Disease and Molecular Medicine (IDM), University of Cape Town; †Western Cape Government; ‡Stellenbosch University, Cape Town, South Africa; §Jenner Institute, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom; and ¶Aeras, Rockville, Maryland.
authors.forename: Kany Kany A
authors.initials: KK
authors.lastname: Luabeya
authors.forename: Michele D
authors.initials: MD
authors.lastname: Tameris
authors.forename: Hennie D
authors.initials: HD
authors.lastname: Geldenhuys
authors.forename: Humphrey
authors.initials: H
authors.lastname: Mulenga
authors.forename: Amaryl
authors.initials: A
authors.lastname: Van Schalkwyk
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Hughes
authors.forename: Asma
authors.initials: A
authors.lastname: Toefey
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Scriba
authors.forename: Gregory
authors.initials: G
authors.lastname: Hussey
authors.forename: Hassan
authors.initials: H
authors.lastname: Mahomed
authors.forename: Helen
authors.initials: H
authors.lastname: McShane
authors.forename: Bernard
authors.initials: B
authors.lastname: Landry
authors.forename: Willem A
authors.initials: WA
authors.lastname: Hanekom
authors.forename: Mark
authors.initials: M
authors.lastname: Hatherill
mesh_terms: D019072:Antibiotic Prophylaxis / Q000706:statistics & numerical data*; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007538:Isoniazid / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D009169:Mycobacterium tuberculosis; D013019:South Africa; D014376:Tuberculosis / Q000188:drug therapy / Q000453:epidemiology / Q000517:prevention & control
chemical_list: D000995:Antitubercular Agents; D007538:Isoniazid