Molecular Typing of Treponema pallidum: A Systematic Review and Meta-Analysis

Abstract

Syphilis is resurgent in many regions of the world. Molecular typing is a robust tool for investigating strain diversity and epidemiology. This study aimed to review original research on molecular typing of Treponema pallidum (T. pallidum) with three objectives: (1) to determine specimen types most suitable for molecular typing; (2) to determine T. pallidum subtype distribution across geographic areas; and (3) to summarize available information on subtypes associated with neurosyphilis and macrolide resistance. Two researchers independently searched five databases from 1998 through 2010, assessed for eligibility and study quality, and extracted data. Search terms included “Treponema pallidum,” or “syphilis,” combined with the subject headings “molecular,” “subtyping,” “typing,” “genotype,” and “epidemiology.” Sixteen eligible studies were included. Publication bias was not statistically significant by the Begg rank correlation test. Medians, inter-quartile ranges, and 95% confidence intervals were determined for DNA extraction and full typing efficiency. A random-effects model was used to perform subgroup analyses to reduce obvious between-study heterogeneity. Primary and secondary lesions and ear lobe blood specimens had an average higher yield of T. pallidum DNA (83.0% vs. 28.2%, χ² = 247.6, pvs. 43.1%, χ² = 102.3, pT. pallidum DNA than blood. There was wide geographic variation in T. pallidum subtypes. More research is needed on the relationship between clinical presentation and subtype, and further validation of ear lobe blood for obtaining T. pallidum DNA would be useful for future molecular studies of syphilis. Syphilis has been resurgent in many parts of the world in past decades. Understanding the epidemiology of syphilis is important for estimating disease burdens, monitoring epidemic trends, and evaluating intervention activities. Treponema pallidum (T. pallidum), the pathogen of syphilis, cannot be grown in vitro. Because T. pallidum cannot be cultured, molecular typing of T. pallidum is particularly useful and allows for investigation of infection diversity and epidemiology. We conducted a statistical analysis of available published data to investigate the current research progress of molecular typing of syphilis. Our analysis showed that primary lesion was a better specimen for obtaining T. pallidum DNA than blood. Blood specimens collected from scraping the ear lobes had high yield of T. pallidum DNA and high full typing efficiency. Ear lobe blood is a promising specimen for future T. pallidum molecular typing, but further research should verify this finding using a larger sample size. Within all studies, subtype 14d was most prevalent, and subtype distribution varied across geographic areas. Subtype data associated with macrolide resistance and neurosyphilis were limited. More research on molecular typing of T. pallidum can be useful for investigating syphilis epidemiology and designing syphilis control strategies.