Prevalence of long-term physical sequelae among patients treated with multi-drug and extensively drug-resistant tuberculosis: a systematic review and meta-analysis.

Background: Physical sequelae related to multi-drug resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) are emerging and under-recognised global challenges. This systematic review and meta-analysis aimed to quantify the prevalence and the types of long-term physical sequelae associated with patients treated for MDR- and XDR-TB. Methods: We systematically searched CINAHL (EBSCO), MEDLINE (via Ovid), Embase, Scopus, and Web of Science from inception through to July 1, 2022, and the last search was updated to January 23, 2023. We included studies reporting physical sequelae associated with all forms of drug-resistant TB, including rifampicin-resistant TB (RR-TB), MDR-TB, Pre-XDR-TB, and XDR-TB. The primary outcome of interest was long-term physical sequelae. Meta-analysis was conducted using a random-effect model to estimate the pooled proportion of physical sequelae. The sources of heterogeneity were explored through meta-regression using study characteristics as covariates. The research protocol was registered in PROSPERO (CRD42021250909). Findings: From 3047 unique publications identified, 66 studies consisting of 37,380 patients conducted in 30 different countries were included in the meta-analysis. The overall pooled estimate was 44.4% (95% Confidence Interval (CI): 36.7-52.1) for respiratory sequelae, 26.7% (95% CI: 23.85-29.7) for hearing sequelae, 10.1% (95% CI: 7.0-13.2) for musculoskeletal sequelae, 8.4% (95% CI: 6.5-10.3) for neurological sequelae, 8.1% (95% CI: 6.3-10.0) for renal sequelae, 7.3% (95% CI: 5.1-9.4) for hepatic sequelae, and 4.5% (95% CI: 2.7-6.3) for visual sequelae. There was substantial heterogeneity in the estimates. The stratified analysis showed that the pooled prevalence of hearing sequelae was 26.6% (95% CI: 12.3-40.9), neurological sequelae was 31.5% (95% CI: 5.5-57.5), and musculoskeletal sequelae were 21.5% (95% CI: 9.9-33.1) for patients with XDR-TB, which were higher than the pooled prevalence of sequelae among patients with MDR-TB. Respiratory sequelae were the highest in low-income countries (59.3%) and after completion of MDR-TB treatment (57.7%). Interpretation: This systematic review found that long-term physical sequelae such as respiratory, hearing, musculoskeletal, neurological, renal, hepatic, and visual sequelae were common among survivors of MDR- and XDR-TB. There was a significant difference in the prevalence of sequelae between patients with MDR- and XDR-TB. Post-MDR- and XDR-TB treatment surveillance for adverse outcomes needs to be incorporated into the current programmatic management of MDR-TB to enable early detection and prevention of post-treatment sequelae. Funding: Australian National Health and Medical Research Council, through an Emerging Leadership Investigator grant, and the Curtin University Higher Degree Research scholarship.