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

Abstract

BackgroundSyphilis 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.Methodology/Principal FindingsTwo 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, p<0.001) and an average higher efficiency of full molecular typing (80.9% vs. 43.1%, χ2 = 102.3, p<0.001) compared to plasma, whole blood, and cerebrospinal fluid. A pooled analysis of subtype distribution based on country location showed that 14d was the most common subtype, and subtype distribution varied across geographic areas. Subtype data associated with macrolide resistance and neurosyphilis were limited.Conclusions/SignificancePrimary lesion was a better specimen for obtaining T. 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.

Molecular Typing of Treponema pallidum in Ocular Syphilis

“…13 Since the development of this molecular typing system, substantial diversity has been identified in strains of T. pallidum globally. 14 In Seattle, a specific strain type (14d/f) was associated with neurosyphilis, suggesting enhanced neurotropism by certain strains, 13 which had been suggested previously in observational studies. 15 …”

Sensitivity, specificity and likelihood ratios of PCR in the diagnosis of syphilis: a systematic review and meta-analysis

“…The potential explanations are that DNA extraction from blood provided a lower yield than skin lesions,24 27 thus postulating a higher T. pallidum load in skin lesions than in blood,28 but also that substances may be present in whole blood and inhibit PCR 29. Nonetheless, clinical lesions are only present in the early symptomatic phase of the disease.…”

2014 European guideline on the management of syphilis

“…• Subtypowanie krętka bladego (metodą PCR-restriction fragment length polymorphism -RFLP i/lub przez sekwencjonowanie DNA) może być wykonane w różnym materiale klinicznym, ale jego zdolność różnicująca jest nieduża (w Europie i na świecie dominuje podtyp 14d) [21][22][23][24].…”