Background Serology is negative in a proportion of primary syphilis cases where Treponema pallidum PCR testing is positive. We aimed to identify discordant, T. pallidum PCR-positive, serology-negative primary syphilis cases and any clinical or laboratory factors associated with failure to subsequently seroconvert.
Methods Serodiscordant primary syphilis cases that were T. pallidum PCR-positive and serology-negative (including rapid plasma reagin, T. pallidum particle agglutination, T. pallidum enzyme immunoassay or T. pallidum chemiluminescence assay) were identified from the Melbourne Sexual Health Centre electronic records between April 2011 and December 2019. Clinical and laboratory associations were examined.
Results There were 814 primary syphilis cases in the study period and 38 (4.7%) were serodiscordant, 35 in men who have sex with men. Thirty-two had follow-up serology performed a median of 24 days later, of which 16 (50%) seroconverted, mostly (81%) within 6 weeks. Failure to seroconvert was significantly associated with treatment on day 1. Of the 12 cases treated on day 1, 10 (83%) failed to seroconvert compared with 6 of 20 (30%) among those who were treated after day 1.
Discussion Earlier treatment of primary syphilis can prevent the development of serological markers. T. pallidum PCR can identify primary syphilis lesions before the development of serological markers and improve diagnosis of early primary syphilis lesions. Serology alone will miss a proportion of primary syphilis infections and should be repeated if a diagnosis of syphilis is being considered.
Data availability statement
All data relevant to the study are included in the article or uploaded as supplementary information.
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Handling editor Henry John Christiaan de Vries
Twitter @drdebwilliamson, @EricPFChow
Deceased DEL died on 4 July 2018
Contributors DEL conceived and designed the study and drafted the original manuscript. FA performed the laboratory testing. Data analysis was performed by JMT. JMT and MYC drafted the final version of the manuscript. EPFC and LZ provided advice on statistical analysis. All authors except DEL (deceased in 2018) critically reviewed the manuscript for important intellectual content and approved the final version.
Funding JMT is supported by a Monash University Research Training Program Stipend and by a Royal Australasian College of Physicians Foundation Research Entry Scholarship. DW and EPFC are supported by an Australian NHMRC Emerging Leadership Investigator Grant (GNT1174555 and GNT1172873, respectively). CKF is supported by an Australian National Health and Medical Research Council (NHMRC) Leadership Investigator Grant (GNT1172900).
Competing interests MYC has received donated materials from SpeeDx.
Provenance and peer review Not commissioned; externally peer reviewed.
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