Burden of childhood tuberculosis in 22 high-burden countries: a mathematical modelling study

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 in...

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Main Authors: Dr. Peter J Dodd, PhD, Elizabeth Gardiner, MSc, Renia Coghlan, MPH, James A Seddon, PhD
Format: Article
Language:English
Published: Elsevier 2014-08-01
Series:The Lancet Global Health
Online Access:http://www.sciencedirect.com/science/article/pii/S2214109X14702451
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spelling doaj-800e21b64f5043dea1d3afc47e1f5b692020-11-25T01:28:34ZengElsevierThe Lancet Global Health2214-109X2014-08-0128e453e45910.1016/S2214-109X(14)70245-1Burden of childhood tuberculosis in 22 high-burden countries: a mathematical modelling studyDr. Peter J Dodd, PhD0Elizabeth Gardiner, MSc1Renia Coghlan, MPH2James A Seddon, PhD3Health Economics and Decision Science, School of Health and Related Research, University of Sheffield, Sheffield, UKGlobal Alliance for TB Drug Development, New York, NY, USATESS Development Advisors, Geneva, SwitzerlandDepartment of Paediatric Infectious Diseases, Imperial College London, London, UKBackground: 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. Findings: 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%. Interpretation: 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. Funding: UNITAID and the US Agency for International Development.http://www.sciencedirect.com/science/article/pii/S2214109X14702451
collection DOAJ
language English
format Article
sources DOAJ
author Dr. Peter J Dodd, PhD
Elizabeth Gardiner, MSc
Renia Coghlan, MPH
James A Seddon, PhD
spellingShingle Dr. Peter J Dodd, PhD
Elizabeth Gardiner, MSc
Renia Coghlan, MPH
James A Seddon, PhD
Burden of childhood tuberculosis in 22 high-burden countries: a mathematical modelling study
The Lancet Global Health
author_facet Dr. Peter J Dodd, PhD
Elizabeth Gardiner, MSc
Renia Coghlan, MPH
James A Seddon, PhD
author_sort Dr. Peter J Dodd, PhD
title Burden of childhood tuberculosis in 22 high-burden countries: a mathematical modelling study
title_short Burden of childhood tuberculosis in 22 high-burden countries: a mathematical modelling study
title_full Burden of childhood tuberculosis in 22 high-burden countries: a mathematical modelling study
title_fullStr Burden of childhood tuberculosis in 22 high-burden countries: a mathematical modelling study
title_full_unstemmed Burden of childhood tuberculosis in 22 high-burden countries: a mathematical modelling study
title_sort burden of childhood tuberculosis in 22 high-burden countries: a mathematical modelling study
publisher Elsevier
series The Lancet Global Health
issn 2214-109X
publishDate 2014-08-01
description 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. Findings: 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%. Interpretation: 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. Funding: UNITAID and the US Agency for International Development.
url http://www.sciencedirect.com/science/article/pii/S2214109X14702451
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