Contemporary syphilis epidemics: efforts to improve syphilis diagnostics
8 December 2017
UAntwerp, Campus Drie Eiken, Building S, Auditorium S1 - Universiteitsplein 1 - 2610 Wilrijk (Antwerp) (route: UAntwerpen, Campus Drie Eiken
4:00 PM - 6:00 PM
Xaveer Van Ostade, Chris Kenyon
PhD defence Kara Osbak - Department of Biomedical Sciences
Syphilis, a multistage curable chronic disease caused by the spirochete Treponema pallidum ssp. pallidum (T. pallidum), has re-emerged during the last 15 years as a major global public health problem, with an estimated 6 million new infections each year worldwide. If not treated promptly, syphilis can cause serious morbidity and adverse pregnancy events.
Work presented in Section I of this thesis aimed to answer two important questions related to the relationship between syphilis and HIV. First, we assessed if there was a country-level association between antenatal syphilis prevalence from early in the HIV epidemics (1990-1999) and peak HIV prevalence to help better elucidate the underlying determinants of variations in HIV spread. Linear regression analyses of data from 76 countries revealed that syphilis prevalence in the 1990s predicted approximately 53% of the variation in peak HIV prevalence. Second, we assessed if we could use the HIV phylogenetic tree constructed from HIV-1 sequences of 1169 clients in follow-up at a cohort in Antwerp, Belgium to see if there was evidence for clustering of syphilis infections. No evidence of clustering was found, however, analyses revealed potential cases of sexual identity misclassification of men who have sex with men as heterosexuals. We discuss the role these individuals may play as a high-risk bridge population.
Section II of this thesis details studies related to improving syphilis diagnostics. First, in vivo rabbit cultured T. pallidum were purified to study the T. pallidum proteome during infection via complementary mass spectrometric (MS) approaches, resulting in the most extensive proteome investigation of T. pallidum to date. In total, 54% of the whole T. pallidum proteome (577 proteins) were characterized and semi-quantified, yielding novel insights into T. pallidum biology and potential biomarkers for diagnostic applications. Eleven candidate biomarker proteins were shortlisted from this analysis and incorporated into a targeted multiple reaction monitoring assay. No endogenous T. pallidum peptide signals were detected in undepleted protein extracts from urine and plasma from individuals with syphilis, likely due to the very low (femtomoles/liter) predicted concentrations of biomarker proteins. Nevertheless, findings from this pioneering study could be useful to other researchers considering employing similarly challenging techniques. Lastly, an automated immunoturbidimetric nontreponemal assay was evaluated for clinical appropriateness using serum samples collected during a two-year observational cohort study of syphilis patients (N=120) and controls (N=30). Test performance deficiencies were highlighted. Independent and comprehensive assay evaluations using well-characterized clinical samples are essential to improving diagnostic methods.