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

Date Published: October 25, 2016

Publisher: Public Library of Science

Author(s): Rein M. G. J. Houben, Peter J. Dodd, John Z Metcalfe

Abstract: BackgroundThe 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 FindingsWe 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.ConclusionsWe 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.

Partial Text: Infection with Mycobacterium tuberculosis (M.tb) is the precursor to TB disease, which is responsible for 1.5 million deaths each year—more than any other infectious disease [1]. Once infected, the individual is at highest risk of developing TB disease within the first two years, but can remain at risk for their lifetime [2]. The population carrying a latent TB infection (LTBI) is commonly quoted as “one-third” of the global population, a reservoir of approximately 2.3 billion individuals [3–6].

To estimate the burden of LTBI, we reconstructed country trends in annual risk of M.tb infection (ARI) and combined these historical projections with demographic data to estimate burden of recent and all-time infection by age. ARI trends were modelled for 168 countries (comprising >99.9% of the world population) using a flexible non-parametric regression framework accounting for measurement uncertainty and applied to two sources of data.

The global burden of LTBI is just under a quarter of the population—around 1.7 billion individuals—with substantial geographical and age variation. We estimate 56 million people are at high risk of developing TB disease because of a recent (re-)infection, 11% of whom are carrying an isoniazid-resistant strain. With reasonable assumptions for reactivation risks, incident TB disease arising from the 2014 LTBI reservoir alone would prohibit reaching the 2035 and 2050 End TB Strategy goals.

We estimate that approximately 1.7 billion individuals were latently infected with 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 TB community is to reach the 2050 target of eliminating TB.

Source:

http://doi.org/10.1371/journal.pmed.1002152

 

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