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Mistakenly believed to be a disease of the past, syphilis is one of the most common sexually transmissible infections worldwide1 and a current concern for global health. Late-stage syphilis can be characterised by serious clinical manifestations, including blindness, dementia and paralysis. Vertical transmission of the disease to the fetus during pregnancy can result in stillbirth, spontaneous abortion and neonatal death, and syphilis-affected individuals are at greater risk to acquire HIV. The estimated worldwide yearly incidence of syphilis in 1999 was ~12 million, with an overall prevalence of at least 25 million.1 Within the last 10 years, the incidence of syphilis in the US and Europe has increased, particularly among men who have sex with men.2-5 This is a worrying trend as syphilis is easily preventable with the use of condoms, can be quickly diagnosed with a variety of laboratory tests and can effectively be treated by administration of penicillin. The disappointing results of existing public health efforts to control syphilis worldwide emphasise the need for more effective methods of syphilis prevention and control strategies.
Treponema pallidum subsp. pallidum (T. pallidum hereafter), the aetiological agent of syphilis, is an obligate human pathogen, and therefore constantly exposed to host defenses throughout its lifecycle. Genetic variation forms the basis of antigenic evolution that facilitates survival and adaptation of pathogens to host immune mechanisms. At the same time, however, genetic variability allows development of molecular methods that allow differentiation and categorisation of treponemal strains. The same efforts that aim to find and improve typing systems for T. pallidum will eventually facilitate the differentiation of subspecies pallidum from closely related pathogens that belong to other subspecies, such as T. pallidum subspecies pertenue that causes yaws, and subspecies endemicum that causes endemic syphilis (or bejel).
Treponema pallidum was initially thought to be a genetically uninteresting organism because of a 'stable' intractable chromosome lacking significant genetic variation, despite the impressive range of disease manifestations in its natural host. Over the last 15 years, whole genome and targeted sequencing efforts have uncovered a vast reservoir of genome plasticity among and within strains and organisms in patient lesions. Such genetic diversity is the basis of current efforts for developing typing methods of utility for several purposes, including: (i) surveillance...