Risk of progression to active tuberculosis for indeterminate interferon-gamma release assay in immunocompromised individuals: a systematic review and meta-analysis

Background Limited data exist on assessing the risk of active tuberculosis (TB) in immunocompromised individuals during screening for latent tuberculosis infection (LTBI). Objectives To assess the risk of progression to active TB for indeterminate interferon-γ release assays (IGRA) results in immunocompromised individuals during screening for LTBI. Data Sources PubMed, Embase, Web of Science, and the Cochrane Library were searched without start date or language restrictions on April 18, 2023. Study eligibility criteria Cohort study or randomized controlled trials that investigated the risk of progression to active TB for indeterminate IGRA during LTBI screening. Participants Immunocompromised individuals. Test IGRA (T-SPOT.TB and QuantiFERON). Reference standard None. Assessment of risk of bias A modified version of the Newcastle-Ottawa Scale. Methods of data synthesis Fixed effects meta-analysis was used to obtain two pooled risk ratios (RRs). RR-ip represented disease progression rate in untreated individuals with indeterminate IGRA versus positive IGRA. RR-in represented disease progression rate in untreated individuals with indeterminate IGRA versus negative IGRA. Results Among the 5,102 identified studies, 28 (14,792 immunocompromised individuals) were included. The pooled RR-ip and RR-in for cumulative incidence were 0.51 (95% confidence interval [CI], 0.32–0.82; I2 = 0%) and 2.94 (95% CI, 1.78–4.85; I2 = 0%), respectively. Additionally, 11 studies reporting person-year data were included to verified the reliability of cumulative incidence results. The pooled RR-ip and RR-in for person-year incidence were 0.40 (95% CI, 0.19–0.82; I2 = 13%) and 2.67 (95% CI, 1.24–5.79; I2 = 23%), respectively. Concussion Indeterminate IGRA results in immunocompromised individuals may represent an intermediate risk of progression to active TB, with half the risk for positive results and three times for negative results. Proper follow-up and management of patients with indeterminate results are crucial for mitigating progression risk and improving patient outcomes.