Viability of Chlamydia trachomatis in different anatomical sites - a systematic review & meta-analysis.

BACKGROUND: Modern assays for the detection of Chlamydia trachomatis (CT) rely on nucleic acid amplification testing (NAAT) of DNA or ribosomal RNA. However, it is also known that both viable ("living") & non-viable ("dead") CT can be detected by NAAT. Multiple laboratory techniques to measure CT viability have emerged. METHODS: We searched PubMed, EMBASE, Scopus and Dimensions as well as conference abstracts for entries between January 2000 to May 2023. We included any studies that measured CT viability among NAAT-positive samples. Viability assays include enhanced cell culture, direct fluorescent antibody (DFA), messenger RNA (mRNA) detection via digital droplet PCR (ddPCR), viability PCR (V-PCR) & real-time PCR measuring RNA-to-DNA ratio (RDR) (e.g. InSignia®). A meta-analysis was performed on the proportions of non-viable CT by anatomical site. RESULTS: We screened 31,342 records and included 16 studies in the analysis. The pooled proportions of non-viable CT by site were: 33% (95%CI 19-47%) in rectal swabs (eight studies), 17% (95%CI 7-27%) in cervical swabs (six studies), 15% (95%CI 6-25%) in vaginal swabs (six studies) and 11% (95%CI 9-17%) in urine/urethral swabs (two studies). CONCLUSION: All included studies found that a proportion of NAAT-detected CT is non-viable. The findings have far-reaching implications for screening programs and studies evaluating new STI tests and antimicrobial regimens.