The Proportion of Treponema pallidum Polymerase Chain Reaction-Positive Primary Syphilis Infections That Are Seronegative for Syphilis: A Systematic Review and Meta-analysis.

BACKGROUND

Earlier syphilis detection is needed to reduce infectiousness and transmission and to improve control. Polymerase chain reaction (PCR) for Treponema pallidum is highly sensitive for detecting primary syphilis but is not often 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 was 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). Only studies published in English were included. A pooled estimate of the proportion of PCR-positive, seronegative primary infections was calculated via a random effects model.

RESULTS

Of 2571 studies identified, 8 met inclusion criteria and were included. This contributed to 758 individuals with T pallidum PCR-positive primary lesions who had serology performed at the same initial visit. Among these, a pooled estimate of 10% (95% CI, 6%-13%; 73/758; I 2 = 65%, P < .01) was negative on all serologic markers, ranging between 4% (95% CI, 0%-7%; 4/108) and 20% (95% CI, 10%-29%; 14/71).

CONCLUSIONS

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 optimizing early detection of primary syphilis.