Cited by 2,054Tuberculosis Research and EpidemiologyHIV, TB, and STIs EpidemiologyInfectious Diseases and Tuberculosis

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The Global Burden of Latent Tuberculosis Infection: A Re-estimation Using Mathematical Modelling

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Houben, Rein M. G. J., Dodd, Peter J.·2016·PLOS Medicine

DOI 10.1371/journal.pmed.1002152PMC PMC5079585

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Abstract

BACKGROUND: The existing estimate of the global burden of latent TB infection (LTBI) as "one-third" of the world population is nearly 20 y old. Given the importance of controlling LTBI as part of the End TB Strategy for eliminating TB by 2050, changes in demography and scientific understanding, and progress in TB control, it is important to re-assess the global burden of LTBI. METHODS AND FINDINGS: We constructed trends in annual risk in infection (ARI) for countries between 1934 and 2014 using a combination of direct estimates of ARI from LTBI surveys (131 surveys from 1950 to 2011) and indirect estimates of ARI calculated from World Health Organisation (WHO) estimates of smear positive TB prevalence from 1990 to 2014. Gaussian process regression was used to generate ARIs for country-years without data and to represent uncertainty. Estimated ARI time-series were applied to the demography in each country to calculate the number and proportions of individuals infected, recently infected (infected within 2 y), and recently infected with isoniazid (INH)-resistant strains. Resulting estimates were aggregated by WHO region. We estimated the contribution of existing infections to TB incidence in 2035 and 2050. In 2014, the global burden of LTBI was 23.0% (95% uncertainty interval [UI]: 20.4%-26.4%), amounting to approximately 1.7 billion people. WHO South-East Asia, Western-Pacific, and Africa regions had the highest prevalence and accounted for around 80% of those with LTBI. Prevalence of recent infection was 0.8% (95% UI: 0.7%-0.9%) of the global population, amounting to 55.5 (95% UI: 48.2-63.8) million individuals currently at high risk of TB disease, of which 10.9% (95% UI:10.2%-11.8%) was isoniazid-resistant. Current LTBI alone, assuming no additional infections from 2015 onwards, would be expected to generate TB incidences in the region of 16.5 per 100,000 per year in 2035 and 8.3 per 100,000 per year in 2050. Limitations included the quantity and methodological heterogeneity of direct ARI data, and limited evidence to inform on potential clearance of LTBI. CONCLUSIONS: We estimate that approximately 1.7 billion individuals were latently infected with Mycobacterium tuberculosis (M.tb) globally in 2014, just under a quarter of the global population. Investment in new tools to improve diagnosis and treatment of those with LTBI at risk of progressing to disease is urgently needed to address this latent reservoir if the 2050 target of eliminating TB is to be reached.

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Authors: Houben, R. M. G. J., & Dodd, P. J.
Affiliations: London School of Hygiene & Tropical Medicine (GB)
University of Sheffield (GB)
Corresponding author: Houben, Rein M. G. J.
ORCID: Houben, Rein M. G. J.
Dodd, Peter J.
Venue: PLOS Medicine
Publisher: Public Library of Science (PLoS)
Published: 2016-10-25
Volume: 13
Issue: 10
Pages: e1002152
ISSN: 1549-1277 (ISSN-L)
1549-1676
DOI: 10.1371/journal.pmed.1002152
PMC: PMC5079585
OpenAlex: W2533230523
Cited by: 2,054
References: 26
Citations by year: 2026: 160 · 2025: 259 · 2024: 242 · 2023: 243 · 2022: 208 · 2021: 237 · 2020: 257 · 2019: 205 · 2018: 167 · 2017: 67 · 2016: 5
FWCI: 22.73
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: PLoS Medicine (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Figshare (submittedVersion, cc-by)
Funders: Bill and Melinda Gates Foundation (US) (OPP1084276)
Topics: Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
Health Sciences › Medicine › Public Health, Environmental and Occupational Health › HIV, TB, and STIs Epidemiology
Health Sciences › Medicine › Infectious Diseases › Infectious Diseases and Tuberculosis
Keywords: latent tuberculosis infection, global burden of disease, annual risk of infection, isoniazid-resistant tuberculosis, recent infection, End TB Strategy, Gaussian process regression, WHO regions, tuberculosis control, uncertainty quantification, demography
MeSH terms: Antitubercular Agents, Humans, Isoniazid, Mycobacterium tuberculosis, Risk, Global Health, Incidence, Prevalence, Tuberculosis, Multidrug-Resistant, Latent Tuberculosis

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The Global Burden of Latent Tuberculosis Infection: A Re-estimation Using Mathematical Modelling

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