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Background: Strain typing is a tool for determining the diversity and epidemiology of infections., Methods: Treponema pallidum DNA was isolated from 158 patients with syphilis from the United States, China, Ireland, and Madagascar and from 15 T. pallidum isolates. Six typing targets were assessed: (1) the number of 60‐bp repeats in the acidic repeat protein gene, (2) restriction fragment length polymorphism (RFLP) analysis of T. pallidum repeat (tpr) subfamily II genes, (3) RFLP analysis of the tprC gene, (4) determination of tprD allele in the tprD gene locus, (5) the presence of a 51‐bp insertion between tp0126 and tp0127, and (6) sequence analysis of an 84‐bp region of tp0548. The combination of targets 1 and 2 comprises the Centers for Disease Control and Prevention (CDC) T. pallidum subtyping method., Results: Adding sequence analysis of tp0548 to the CDC method yielded the most discriminating typing system. Twenty‐five strain types were identified and designated as "CDC subtype/tp0548 sequence type." Type 14d/f was found in samples from 5 of 6 locations. In Seattle, Washington, strain types changed from 1999 through 2008 (P < .001). Twenty‐one (50%) of 42 patients infected with type 14d/f had neurosyphilis compared with 10 (24%) of 41 patients infected with any of the other types combined (P = .02)., Conclusion: We describe an enhanced T. pallidum strain typing system that shows biological and clinical relevance.

A subset of patients (50%) with neuroborreliosis (Lyme disease) showed IgG reactivity to cardiolipin in solid phase ELISA. In addition, a subset of patients with neuroborreliosis (29%) and syphilis (59%) had IgM reactivity to gangliosides with a Gal(beta 1-3) GalNac terminal sequence (GM1, GD1b, and asialo GM1). Anti-ganglioside IgM antibodies were significantly more frequent in these two groups of patients compared to patients with cutaneous and articular Lyme disease, primary antiphospholipid syndrome, systemic lupus erythematosus and normal controls. Correlative evidence and adsorption experiments indicated that antibodies to cardiolipin had separate specificities from those directed against the gangliosides. IgM antibodies to Gal(beta 1-3) GalNac gangliosides appeared to have similar specificities since these were positively correlated and inhibitable by cross adsorption assays. Given the clinical associations of patients with neuroborreliosis and syphilis with IgM reactivity to gangliosides sharing the Gal(beta 1-3) GalNac terminus, we suggest that these antibodies could represent a response to injury in neurological disease or a cross reactive event caused by spirochetes.