The Global Prevalence of Latent Tuberculosis: A Systematic Review and Meta-Analysis

Abstract

Background: In 1999, the WHO estimated that one-third of the world's population had latent tuberculosis (LTBI) which was recently updated to one-fourth. However, this is still based on controversial assumptions in combination with tuberculin skin test (TST) surveys. Interferon-gamma release assays (IGRAs) with a higher specificity than TST have since been widely implemented, but never used to estimate the global LTBI prevalence. Methods: We conducted a systematic review and meta-analysis of LTBI estimates based on IGRA and TST results published between 2005 and 2018. Regional and global estimates of LTBI prevalence were calculated. Stratification was performed for low, intermediate and high TB incidence countries and a pooled estimate for each area was calculated using a random effects model. Findings: Among 3280 studies screened, we included 88 studies from 36 countries with 41 IGRA (n=67 167) and 67 TST estimates (n=284 644). The global prevalence of LTBI was 24.8% (95% CI: 19.7-30.0%) based on IGRA and 21.2% (95% CI: 17.9-24.4%) and 24.1% (95% CI: 19.7-29.9%) based on a 5 and 10 mm TST cut-offs, respectively. The prevalence estimates correlated significantly to WHO incidence rates. Interpretation: In the first study of the global prevalence of LTBI derived from both IGRA and TST, we found that one-fourth of the world's population is infected. This is of relevance as both tests, although imperfect, are used to identify individuals for preventive therapy. Enhanced efforts are needed to target the large pool of latently infected as they continuously constitutes a source of potential active TB. Funding Statement: This study was supported by NovoNordisk Foundation (NNF15OC0018034; CW), the Swedish Research Council (201602043; TS) and the Swedish Heart and Lung Foundation (20150236; TS). Declaration of Interests: The authors declare no competing interests.