Accurate diagnosis of latent tuberculosis in children, immunocompromised, and recently arrived people from high tuberculosis incidence countries: a systematic review

Article type
Authors
Tsertsvadze A1, Auguste P1, Pink J1, Court R1, Kandala N1, Clarke A1, Sutcliffe P1
1Division of Health Sciences, Warwick Medical School, the University of Warwick, United Kingdom
Abstract
Background: Tuberculosis (TB) is a major cause of morbidity and mortality globally. Nearly one-third of the world’s population is infected with Mycobacterium tuberculosis (MTB). About 30% of all MTB-exposed people develop latent tuberculosis infection (LTBI). Three population groups, namely, children, immunocompromised people, and those who have recently arrived from high-incidence countries are at higher risk of progression from LTBI to active TB. Diagnosis of LTBI is difficult, owing to the absence of a 'gold standard' test. Timely detection of LTBI using existing screening tests in these subgroups is of public health importance.
Objectives: To compare the diagnostic performance of interferon-gamma release assays (IGRAs) and tuberculin skin test (TST) in detecting LTBI in children, the immunocompromised, and people who have recently arrived from countries with a high incidence of TB.
Methods: We searched MEDLINE, EMBASE, Cochrane Library, and other databases. Searches were updated in December 2014. We included studies comparing commercially available IGRAs (QuantiFERON-TB Gold-In-Tube and T-SPOT.TB) to TST for identifying LTBI in children, the immunocompromised, and people recently arrived from high TB incidence countries. We screened, extracted, and undertook risk of bias assessment independently. Two constructs of validity for LTBI were defined: a) incidence of active TB and b) prior exposure to active TB defined by proximity, duration, or dose-response gradient. The strength of association between the test results and LTBI construct were summarised using cumulative incidence ratios (CIRs) and diagnostic odds ratios (DORs). The effect measures comparing diagnostic performance of IGRAs to TST were summarised as ratios of CIRs (R-CIR) and DORs (R-DOR) with 95% confidence intervals. Data were stratified by study design, type of IGRA, TST threshold, TB burden, and study setting. CIRs and R-DORs were pooled using a random-effects model.
Results and Conclusions: This information is confidential until the National Institute for Health and Care Excellence approves the report. The findings will be presented at the Colloquium.