Role of IgM testing in the diagnosis and post-treatment follow-up of syphilis: a prospective cohort study

Objectives The diagnosis of repeat syphilis and its followup remains challenging. We aimed to investigate if IgM testing may assist in the diagnosis of syphilis reinfection/ relapse and its treatment follow-up. Methods This substudy was conducted in the context of a syphilis biomarker discovery study (ClinicalTrials. gov Nr: NCT02059525). Sera were collected from 120 individuals with a new diagnosis of syphilis (72 with repeat infections) and 30 syphilis negative controls during a cohort study investigating syphilis biomarkers conducted at a sexually transmitted infection/HIV clinic in Antwerp, Belgium. Syphilis was diagnosed based on a simultaneous positive treponemal and non-treponemal assay result and/ or positive serum PCR targeting polA. Specimens collected at visit of diagnosis, and 3 and 6 months post-treatment were tested by two enzyme immunoassays (EIAs), recomWell (Mikrogen; MI) and Euroimmun (EU), to detect anti-treponemal IgM. Baseline specimens were also tested for anti-treponemal IgM using a line immunoassay (LIA) recomLine (MI). Quantitative kinetic decay curves were constructed from the longitudinal quantitative EIA results. Results An overall sensitivity for the diagnosis of syphilis of 59.8% (95% CI: 50.3%–68.7%), 75.0% (95% CI: 66.1%–82.3%) and 63.3% (95% CI: 54.8%–72.6%) was obtained for the EU, MI EIAs and MI LIA, respectively. When only considering repeat syphilis, the diagnostic sensitivity decreased to 45.7% (95% CI: 33.9%–58.0%), 63.9% (95% CI: 51.7%–74.6%) and 47.2% (95% CI: 35.5%–59.3%), respectively. IgM seroreverted in most cases 6 months after treatment. Post-treatment IgM concentrations decreased almost 30% faster for initial syphilis compared with repeat infection. The IgM EIAs and IgM LIA agreed from fairly to moderately (Cohen’s kappa (κ): 0.36 (EU EIA); κ: 0.53 (MI EIA); κ: 0.40 (MI LIA)) with the diagnosis of syphilis. Conclusions IgM detection was not a sensitive method to diagnose syphilis and was even poorer in the diagnosis of syphilis repeat infections

Superimposing incident sexually transmitted infections on HIV phylogram to investigate possible misclassification of men who have sex with men as heterosexuals in a cohort in Antwerp, Belgium

NoIn this study, we assessed if the superimposition of incident sexually transmitted infections (STIs) on HIV phylogenetic analyses could reveal possible sexual behaviour misclassifications in our HIV-infected population. HIV-1 sequences collected between 1997 and 2014 from 1169 individuals attending a HIV clinic in Antwerp, Belgium were analysed to infer a partial HIV transmission network. Individual demographic, clinical and laboratory data collected during routine HIV follow-up were used to compare clustered and non-clustered individuals using logistic regression analyses. In total, 438 (37.5%) individuals were identified in 136 clusters, including 76 transmission pairs and 60 clusters consisting of three or more individuals. Individuals in a cluster were more likely to have a history of syphilis, Chlamydia and/or gonorrhoea (P < 0.05); however, when analyses were stratified by HIV transmission risk groups (heterosexual and men who have sex with men [MSM]), this association only remained significant for heterosexuals with syphilis (P = 0.001). Under closer scrutiny, this association was driven by six heterosexual men who were located in six almost exclusively MSM clusters. A parsimonious conclusion is that these six individuals were potentially misclassified as heterosexual. Improving the accuracy of sexual behaviour reporting could improve care

Candidate Treponema pallidum biomarkers uncovered in urine from individuals with syphilis using mass spectrometry

NoAim: A diagnostic test that could detect Treponema pallidum antigens in urine would facilitate the prompt diagnosis of syphilis. Materials & methods: Urine from 54 individuals with various clinical stages of syphilis and 6 controls were pooled according to disease stage and interrogated with complementary mass spectrometry techniques to uncover potential syphilis biomarkers. Results & conclusion: In total, 26 unique peptides were uncovered corresponding to four unique T. pallidum proteins that have low genetic sequence similarity to other prokaryotes and human proteins. This is the first account of direct T. pallidum protein detection in human clinical samples using mass spectrometry. The implications of these findings for future diagnostic test development is discussed. Data are available via ProteomeXchange with identifier PXD009707