The utility of combined syphilis PCR and serology during an outbreak in Western Australia: A multicentre retrospective diagnostic evaluation

Objectives: Syphilis has re-emerged as a global public health concern. Although serology is well established, the role of PCR remains unclear. We evaluated the diagnostic utility of combined syphilis PCR of anogenital lesions and serology during a sustained outbreak in Western Australia. Methods: Syphilis PCR data from anogenital samples from individuals aged ≥16 years, collected between January 2021 and June 2024, were paired with serology results within the preceding 7 days to 24 hours after collection. PCR tests from multiple sites collected within 24 hours were combined as a single event and categorized as positive if any positive. Positive serology results were classified into first infection, past infection, or reinfection. Results: Of 3382 PCR events (9.4% positive), 1976 had paired serology (58.4%). Serology demonstrated higher sensitivity than PCR for first infections (95%, 95% CI 92–97% vs. PCR 80%; 95% CI 74–85%) and comparable sensitivity for reinfections (81%; 95% CI 69–90% vs. PCR 76%; 95% CI 64–86%). When added to serology, PCR identified one additional first infection for every 139 events tested (95% CI, 80–269) and one reinfection for every 20 events (95% CI, 12–39). Conclusions: Clinician education is essential to reinforce the critical role of serology as the principal diagnostic test for first infections and reinfections. When used alongside serology, PCR has limited additional benefit for the diagnosis of a first syphilis infection. Combined serology and PCR testing can improve the detection of syphilis reinfections and may have increased utility in specific high-risk populations.