In 1999, the World Health Organization (WHO) estimated that one-third of the world's population had latent tuberculosis infection (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-γ release assays (IGRAs) with a higher specificity than TST have since been widely implemented, but never used to estimate the global LTBI prevalence.We conducted a systematic review and meta-analysis of LTBI estimates based on both 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.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%) and 21.2% (95% CI 17.9–24.4%), based on IGRA and a 10-mm TST cut-off, respectively. The prevalence estimates correlated well to WHO incidence rates (Rs=0.70, p<0.001).In the first study of the global prevalence of LTBI derived from both IGRA and TST surveys, 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 eligible for preventive therapy. Enhanced efforts are needed targeting the large pool of latently infected individuals, as this constitutes an enormous source of potential active tuberculosis.

We developed a clinical score to monitor tuberculosis patients in treatment and to assess clinical outcome. We used the WHO clinical manual to choose signs and symptoms, including cough, haemoptysis, dyspnoea, chest pain, night sweating, anaemia, tachycardia, lung-auscultation finding, fever, low body-mass index, low mid-upper arm circumference giving patients a TBscore from 0 to 13. We validated the score with data from a cohort of 698 TB patients, assessing sensitivity to change and ability to predict mortality. The TBscore declined for 96% of the surviving patients from initiation to end of treatment, and declined with a similar pattern in HIV-infected and HIV-uninfected patients, as well as in smear negative and smear positive patients. The risk of dying during treatment increased with higher TBscore at inclusion. For patients with a TBscore of >8 at inclusion, mortality during the 8 months treatment was 21% (45/218) versus 11% (55/480) for TBscore <8 (p< 0.001). TBscore assessed at end of treatment also strongly predicted subsequent mortality. The TBscore is a simple and low-cost tool for clinical monitoring of tuberculosis patients in low-resource settings and may be used to predict mortality risk. Low TBscore or fall in TBscore at treatment completion may be used as a measure of improvement.