title: Burden of childhood tuberculosis in 22 high-burden countries: a mathematical modelling study.
abstract: BACKGROUND
  Confirmation of a diagnosis of tuberculosis in children (aged <15 years) is challenging; under-reporting can result even when children do present to health services. Direct incidence estimates are unavailable, and WHO estimates build on paediatric notifications, with adjustment for incomplete surveillance by the same factor as adult notifications. We aimed to estimate the incidence of infection and disease in children, the prevalence of infection, and household exposure in the 22 countries with a high burden of the disease.
  
  
  METHODS
  Within a mechanistic mathematical model, we combined estimates of adult tuberculosis prevalence in 2010, with aspects of the natural history of paediatric tuberculosis. In a household model, we estimated household exposure and infection. We accounted for the effects of age, BCG vaccination, and HIV infection. Additionally, we tested sensitivity to key structural assumptions by repeating all analyses without variation in BCG efficacy by latitude.
  
  
  RESULTS
  The median number of children estimated to be sharing a household with an individual with infectious tuberculosis in 2010 was 15,319,701 (IQR 13,766,297-17,061,821). In 2010, the median number of Mycobacterium tuberculosis infections in children was 7,591,759 (5,800,053-9,969,780), and 650,977 children (424,871-983,118) developed disease. Cumulative exposure meant that the median number of children with latent infection in 2010 was 53,234,854 (41,111,669-68,959,804). The model suggests that 35% (23-54) of paediatric cases of tuberculosis in the 15 countries reporting notifications by age in 2010 were detected. India is predicted to account for 27% (22-33) of the total burden of paediatric tuberculosis in the 22 countries. The predicted proportion of tuberculosis burden in children for each country correlated with incidence, varying between 4% and 21%.
  
  
  CONCLUSIONS
  Our model has shown that the incidence of paediatric tuberculosis is higher than the number of notifications, particularly in young children. Estimates of current household exposure and cumulative infection suggest an enormous opportunity for preventive treatment.
  
  
  BACKGROUND
  UNITAID and the US Agency for International Development.
authors.affiliation: Health Economics and Decision Science, School of Health and Related Research, University of Sheffield, Sheffield, UK. Electronic address: p.j.dodd@shef.ac.uk.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Dodd
authors.affiliation: Global Alliance for TB Drug Development, New York, NY, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Gardiner
authors.affiliation: TESS Development Advisors, Geneva, Switzerland.
authors.forename: Renia
authors.initials: R
authors.lastname: Coghlan
authors.affiliation: Department of Paediatric Infectious Diseases, Imperial College London, London, UK.
authors.forename: James A
authors.initials: JA
authors.lastname: Seddon
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D017281:Cost of Illness; D003906:Developing Countries; D005260:Female; D006801:Humans; D015994:Incidence; D007223:Infant; D008962:Models, Theoretical; D015995:Prevalence; D014376:Tuberculosis / Q000453:epidemiology*