Pyrosequencing for diagnosis of multidrug and extensively drug-resistant tuberculosis: A systemic review and meta-analysis

Getachew, Emnet; Adebeta, Tsegaye; Gebrie, Desye; Charlie, Loveness; Said, Bibie; Assefa, Dawit Getachew; Wanjiru, Cathrine Lydiah; Zeleke, Eden Dagnachew; Tesfahunei, Hanna Amanuel; Abebe, Mekdelawit; Joseph, Michele; Manyazewal, Tsegahun

BACKGROUND: Multidrug and extensively drug-resistant tuberculosis (M/XDR-TB) pose major threats to global health. Diagnosis accuracy and delay have been the major drivers for the upsurge of M/XDR-TB. Pyrosequencing (PSQ) is a novel, real-time DNA sequencing for rapid detection of mutations associated with M/XDR-TB. We aimed to systematically synthesize the evidence on the diagnostic accuracy of PSQ for M/XDR-TB. METHODS: We conducted an electronic search of PubMed, Embase, Biosis, Web of Science, and Google Scholar up to March 2020. We used the QUADAS‐2 (Quality Assessment of Diagnostic Accuracy Studies) tool to assess the quality of studies, the BRMA (bivariate random‐effects meta-analysis) model to synthesize diagnostic accuracies, and the Rev-Man 5.4 software to perform the meta-analyses. We analyzed dichotomous data using the risk ratio (RR) with a 95% confidence interval. PROSPERO Registration ID: CRD42020200817. RESULTS: The analysis included seven studies, with a total sample of 3,165. At 95% confidence interval, the pooled sensitivity and specificity of PSQ were 89.7 (CI: 83.5–93.8) and 97.8 (CI: 94.9–99.1) for Isoniazid, 94.6 (CI: 90.9–96.8) and 98.5 (CI: 96.5–99.3) for Rifampicin, 87.9 (CI: 81.2–92.4) and 98.8 (CI: 97.2–99.5) for Fluoroquinolone, 83.5 (CI: 72.8–90.5) and 99.4 (CI: 98.3–99.8) for Amikacin, 79 (CI: 67–8-87) and 97.9 (CI: 95.5–99) for Capreomycin, and 69.6 (CI: 57–79.8) and 98.2 (CI: 95.9–99.2) for Kanamycin. The overall pooled sensitivity and specificity were 85.8 (CI: 76.7–91.7) and 98.5 (CI: 96.5–99.3), respectively. CONCLUSION: According to the pooled data, PSQ is highly sensitive and specific for detecting M/XDR-TB, both from clinical specimens and culture isolates, and within a shorter turnaround time. We suggest a continued synthesis of the evidence on the cost-effectiveness and technical feasibilities of PSQ in low-income countries context, including sub-Saharan Africa.