title: Global and Regional Burden of Isoniazid-Resistant Tuberculosis.
abstract: BACKGROUND
  Isoniazid has been the backbone of tuberculosis chemotherapy for 6 decades. Resistance to isoniazid threatens the efficacy of treatment of tuberculosis disease and infection. To inform policies around treatment of tuberculosis disease and infection in children, we sought to estimate both the proportion of child tuberculosis cases with isoniazid resistance and the number of incident isoniazid-resistant tuberculosis cases in children, by region.
  
  
  METHODS
  We determined the relationship between rates of isoniazid resistance among child cases and among treatment-naive adult cases through a systematic literature review. We applied this relationship to regional isoniazid resistance estimates to estimate proportions of childhood tuberculosis cases with isoniazid resistance. We applied these proportions to childhood tuberculosis incidence estimates to estimate numbers of children with isoniazid-resistant tuberculosis.
  
  
  RESULTS
  We estimated 12.1% (95% confidence interval [CI] 9.8% to 14.8%) of all children with tuberculosis had isoniazid-resistant disease, representing 120,872 (95% CI 96,628 to 149,059) incident cases of isoniazid-resistant tuberculosis in children in 2010. The majority of these occurred in the Western Pacific and Southeast Asia regions; the European region had the highest proportion of child tuberculosis cases with isoniazid resistance, 26.1% (95% CI: 20.0% to 33.6%).
  
  
  CONCLUSIONS
  The burden of isoniazid-resistant tuberculosis in children is substantial, and risk varies considerably by setting. The large number of child cases signals extensive ongoing transmission from adults with isoniazid-resistant tuberculosis. The risk of isoniazid resistance must be considered when evaluating treatment options for children with disease or latent infection to avoid inadequate treatment and consequent poor outcomes.
authors.affiliation: Division of Global Health Equity, Brigham and Women's Hospital, Boston, Massachusetts;
authors.forename: Courtney M
authors.initials: CM
authors.lastname: Yuen
authors.affiliation: Division of Global Health Equity, Brigham and Women's Hospital, Boston, Massachusetts;
authors.forename: Helen E
authors.initials: HE
authors.lastname: Jenkins
authors.affiliation: Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts; and.
authors.forename: Carly A
authors.initials: CA
authors.lastname: Rodriguez
authors.affiliation: Division of Global Health Equity, Brigham and Women's Hospital, Boston, Massachusetts; Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts; and Partners In Health, Boston, Massachusetts.
authors.forename: Salmaan
authors.initials: S
authors.lastname: Keshavjee
authors.affiliation: Division of Global Health Equity, Brigham and Women's Hospital, Boston, Massachusetts; Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts; and Partners In Health, Boston, Massachusetts mbecerra@post.harvard.edu.
authors.forename: Mercedes C
authors.initials: MC
authors.lastname: Becerra
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology; D014943:Global Health; D006801:Humans; D015994:Incidence; D007538:Isoniazid / Q000494:pharmacology*; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy / Q000453:epidemiology*
chemical_list: D000995:Antitubercular Agents; D007538:Isoniazid