Seroconversion in syphilis screening without positive confirmatory tests points at early infection.

INTRODUCTION: The chemiluminescence immunoassay (CLIA) is a widely used screening test for syphilis. A CLIA seroconversion in the absence of a positive line immunoassay (LIA) or rapid plasma reagin (RPR) could indicate either an early incubating syphilis or a false positive result. We aimed to evaluate the diagnostic value of such seroconversions. METHODS: We retrospectively analysed data of clients visiting the Centre for Sexual Health Amsterdam between July 2013 and August 2021 with a positive CLIA and a negative RPR and negative or indeterminate LIA (at time To), and a preceding visit (T-1) with a negative CLIA <6 months of To ('unconfirmed CLIA seroconversion'). If available, data of follow-up visits (T1) <2 months of To were also included. A syphilis diagnosis was confirmed if darkfield microscopy or PCR for Treponema pallidum was positive at T0 or T1, or if RPR and/or LIA were positive at T1. RESULTS: We included data of 107 clients with unconfirmed CLIA seroconversion. The value of CLIA seroconversion could not be established in 13 (12.1%) clients. In the remaining 94 clients, the unconfirmed CLIA seroconversion was confirmed as early syphilis in 72 (76.6%) clients and probable syphilis in 6 (6.4%) clients. In 16 (17.0%) clients, the unconfirmed CLIA seroconversion was regarded as a false positive reaction of whom 4 (5.3%) clients had a seroreversion of the CLIA at T1. CONCLUSION: The majority of unconfirmed CLIA seroconversions represented early syphilis infections. Therefore, additional T. pallidum PCR, a follow-up consultation or early treatment is recommended.

Developing a symptoms-based risk score for infectious syphilis among men who have sex with men.

BACKGROUND: Syphilis incidence is rising among men who have sex with men (MSM). An online tool based on a risk score identifying men with higher risk of infectious syphilis could motivate MSM to seek care. We aimed therefore to develop a symptoms-based risk score for infectious syphilis. METHODS: We included data from all consultations by MSM attending the Amsterdam Centre for Sexual Health in 2018-2019. Infectious syphilis (ie, primary, secondary or early latent syphilis) was diagnosed according to the centre's routine protocol. Associations between symptoms and infectious syphilis were expressed as odds ratios (OR), with 95% confidence intervals (CI). Based on multivariable logistic regression models, we created risk scores, combining various symptoms. We assessed the area under the curve (AUC) and cut-off based on the Youden Index. We estimated which percentage of MSM should be tested based on a positive risk score and which percentage of infectious syphilis cases would then be missed. RESULTS: We included 21,646 consultations with 11,594 unique persons. The median age was 34 years (IQR 27-45), and 14% were HIV positive (93% on antiretroviral treatment). We diagnosed 538 cases of infectious syphilis. Associations with syphilis symptoms/signs were strong and highly significant, for example, OR for a painless penile ulcer was 35.0 (CI 24.9 to 49.2) and OR for non-itching rash 57.8 (CI 36.8 to 90.9). Yet, none of the individual symptoms or signs had an AUC >0.55. The AUC of risk scores combining various symptoms varied from 0.68 to 0.69. For all risk scores using cut-offs based on Youden Index, syphilis screening would be recommended in 6% of MSM, and 59% of infectious syphilis cases would be missed. CONCLUSION: Symptoms-based risk scores for infectious syphilis perform poorly and cannot be recommended to select MSM for syphilis screening. All MSM with relevant sexual exposure should be regularly tested for syphilis.

Clinical outcomes of syphilis in HIV-negative and HIV-positive MSM: occurrence of repeat syphilis episodes and non-treponemal serology responses.

OBJECTIVES: HIV-positive men who have sex with men (MSM) may be at a higher risk of repeat syphilis, have different clinical manifestations and have a different serological response to treatment compared with HIV-negative MSM. The objective of this study was to assess whether HIV-negative and HIV-positive MSM with infectious syphilis (primary, secondary or early latent) differed in history of previous syphilis episodes, disease stage and non-treponemal titre of initial and repeat episodes, and the titre response 6 and 12 months after treatment. Furthermore, determinants associated with an inadequate titre response after treatment were explored. METHODS: This retrospective analysis used data of five longitudinal studies (four cohorts; one randomised controlled trial) conducted at the STI clinic in Amsterdam, the Netherlands. Participants were tested for syphilis and completed questionnaires on sexual risk behaviour every 3-6 months. We included data of participants with ≥1 syphilis diagnosis in 2014-2019. Pearson's χ² test was used to compare HIV-negative and HIV-positive MSM in occurrence of previous syphilis episodes, disease stage of initial and repeat syphilis episode and non-treponemal titre treatment responses. RESULTS: We included 355 participants with total 459 syphilis episodes. HIV-positive MSM were more likely to have a history of previous syphilis episodes compared with HIV-negative MSM (68/90 (75.6%) vs 96/265 (36.2%); p<0.001). Moreover, HIV-positive MSM with repeat syphilis were less often diagnosed with primary syphilis (7/73 (9.6%) vs 36/126 (28.6%)) and more often diagnosed with secondary syphilis (16/73 (21.9%) vs 17/126 (13.5%)) and early latent syphilis (50/73 (68.5%) vs 73/126 (57.9%)) (p=0.005). While not significantly different at 12 months, HIV-negative MSM were more likely to have an adequate titre response after 6 months compared with HIV-positive MSM (138/143 (96.5%) vs 66/74 (89.2%); p=0.032). CONCLUSIONS: In repeat syphilis, HIV infection is associated with advanced syphilis stages and with higher non-treponemal titres. HIV infection affects the serological outcome after treatment, as an adequate titre response was observed earlier in HIV-negative MSM.