The proportion of Treponema pallidum PCR-positive primary syphilis infections which are seronegative for syphilis: a systematic review and meta-analysis

Background Earlier syphilis detection is needed to reduce infectiousness, transmission and to improve control. Polymerase chain reaction (PCR) for Treponema pallidum is highly sensitive for detecting primary syphilis but often is not widely available or used. The aim of this systematic review and meta-analysis was to investigate the proportion of PCR-positive, seronegative primary syphilis infections, when serology is performed at clinical presentation. Methods We undertook a systematic review and meta-analysis to identify studies of patients presenting with primary syphilis where T. pallidum PCR was performed on the primary syphilis lesion and serology for syphilis was performed on the same occasion. The review was conducted according to the Cochrane protocol. Medline, Embase and PubMed were searched from 1 January 2000 to 27 November 2022 (date of search 27th November 2022). Only studies published in English were included. A pooled estimate of the proportion of PCR-positive seronegative primary infections was calculated using a random effects model. Results Of 2,571 studies identified, 8 studies met inclusion criteria and were included. This contributed to a total of 758 individuals with T. pallidum PCR-positive primary lesions that had serology performed at the same initial visit. Among these, a pooled estimate of 10% (95% CI: 6-13%, 73/758, I2=65%, p=<0.01) were negative on all serological markers, ranging between 4% (95% CI: 0-7%, 4/108) and 20% (95% CI: 10-29%, 14/71). Conclusion T. pallidum was detected by PCR in 10% cases, which would have been missed if serology alone was used. T. pallidum PCR is important for optimising early detection of primary syphilis.