When Is Syphilis Not Syphilis? Or Is It?

Lukehart, Sheila A.; Giacani, Lorenzo

doi:10.1097/olq.0000000000000179

Cited by 9 publications

(9 citation statements)

References 21 publications

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“…This finding supports the observed and consistent genetic differences between treponemal subspecies TPA, TPE, and TEN, and shows that the ways TPA and TPE strains interact with a host during infection is different. Although some authors suggest that the subspecies classification is a case of opportunity and not the consequence of genetic and biological differences [79,80], our findings support the latter explanation.…”

Section: Discussionsupporting

confidence: 53%

Identification of positively selected genes in human pathogenic treponemes: Syphilis-, yaws-, and bejel-causing strains differ in sets of genes showing adaptive evolution

et al. 2019

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Background Pathogenic treponemes related to Treponema pallidum are both human (causing syphilis, yaws, bejel) and animal pathogens (infections of primates, venereal spirochetosis in rabbits). A set of 11 treponemal genome sequences including those of five Treponema pallidum ssp. pallidum (TPA) strains (Nichols, DAL-1, Mexico A, SS14, Chicago), four T . p . ssp. pertenue (TPE) strains (CDC-2, Gauthier, Samoa D, Fribourg-Blanc), one T . p . ssp. endemicum (TEN) strain (Bosnia A) and one strain (Cuniculi A) of Treponema paraluisleporidarum ecovar Cuniculus (TPeC) were tested for the presence of positively selected genes. Methodology/Principal findings A total of 1068 orthologous genes annotated in all 11 genomes were tested for the presence of positively selected genes using both site and branch-site models with CODEML (PAML package). Subsequent analyses with sequences obtained from 62 treponemal draft genomes were used for the identification of positively selected amino acid positions. Synthetic biotinylated peptides were designed to cover positively selected protein regions and these peptides were tested for reactivity with the patient's syphilis sera. Altogether, 22 positively selected genes were identified in the TP genomes and TPA sets of positively selected genes differed from TPE genes. While genetic variability among TPA strains was predominantly present in a number of genetic loci, genetic variability within TPE and TEN strains was distributed more equally along the chromosome. Several syphilitic sera were shown to react with some peptides derived from the protein sequences evolving under positive selection. Conclusions/Significance The syphilis-, yaws-, and bejel-causing strains differed relative to sets of positively selected genes. Most of the positively selected chromosomal loci were identified among the TPA treponemes. The local accumulation of genetic variability suggests that the diversification of TPA strains took place predominantly in a limited number of genomic regions compared to the more dispersed genetic diversity differentiating TPE and TEN strains. The identification of positively selected sites in tpr genes and genes encoding outer membrane proteins suggests their role during infection of human and animal hosts. The driving force for adaptive evolution at these loci thus appears to be the host immune response as supported by observed reactivity of syphilitic sera with some peptides derived from protein sequences showing adaptive evolution.

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Section: Discussionsupporting

confidence: 53%

Identification of positively selected genes in human pathogenic treponemes: Syphilis-, yaws-, and bejel-causing strains differ in sets of genes showing adaptive evolution

et al. 2019

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“…These changes tend to be more or less bilaterally symmetrical and affect multiple bones on both sides of the skeleton (Baughn & Musher, 2005;Resnick & Niwayama, 1995;Salazar et al, 2002;Tampa et al, 2014). The congenital form of treponemal disease tends to be linked to the presence of venereal syphilis, which readily penetrates the placental barrier; however, cases of vertical transmission of yaws and bejel have also been documented (Baker et al, 2020;Lukehart & Giacani, 2014;Román & Román, 1986).…”

Section: Diagnosing Treponemal Diseasementioning

confidence: 99%

Identifying treponemal disease in early East Asia

Yawei

Gao

Zhang³

et al. 2022

American Journal of Biological Anthropology

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ObjectivesHistoric records suggest that a virulent form of treponematosis, sexually transmitted syphilis was introduced to Asia from Europe by the da Gama crew, who landed in India in 1498. Our objective is to assess the gross pathology of human skeletal remains from the Tang dynasty of China to test the presence of treponemal infection in East Asia before 1498. We interpret this paleopathological evidence in the context of site ecology and sociocultural changes during the Tang dynasty.Materials and methodsWe examined the gross pathology of 1598 human skeletons from Xingfulindai (AD 618 to AD 1279) archeological site located on the Central Plain of China. Using the modified diagnostic criteria defined by Hackett's classical work, we classify the pathology as consistent, strongly suggestive, or pathognomonic for treponemal infection.ResultsTwelve adult individuals from Xingfulindai had bone lesions suggestive of systemic pathology. Two of these individuals displayed a combination of lesion patterns pathognomonic of treponemal disease and one had lesions consistent with treponematosis. The radiocarbon dates for the bone samples from these skeletons place them before AD 1200.ConclusionsThe location of Xingfulindai in a continental climatic zone is not typical for yaws and bejel ecology, because these strains occur in the tropics, or in hot, dry environments, respectively. The urban setting, where there is documented evidence for increased interaction between multiple ethnic groups and a developed institution of courtesans during the Tang dynasty, favors sexually transmitted syphilis as the more likely diagnosis. This study supports an earlier spread of syphilis to China than 1498.

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“…Although syphilis is often said to be differentiated from yaws and bejel by its sexual mode of transmission, it was recognized centuries ago that the agent of syphilis could infect fingers and other nongenital sites when exposed to body fluids of a contagious patient (Stokes et al, ). Although symptomatic neurological, cardiovascular, and congenital manifestations have been long recognized in syphilis, there is substantial evidence in the literature that these do occur, albeit less frequently, in yaws and bejel (e.g., Akrawi, ; Edington, ; Román & Román, ; Smith et al, ; see also Giacani and Lukehart, ; Lukehart & Giacani, ). Grin (), in his extensive study of bejel in the non‐arid environment of Bosnia, also reported genital lesions and evidence of congenital infection.…”

Section: Epidemiological and Genetic Researchmentioning

confidence: 99%

Advancing the understanding of treponemal disease in the past and present

Baker

Crane-Kramer

Dee

et al. 2020

American J Phys Anthropol

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Syphilis was perceived to be a new disease in Europe in the late 15th century, igniting a debate about its origin that continues today in anthropological, historical, and medical circles. We move beyond this age-old debate using an interdisciplinary approach that tackles broader questions to advance the understanding of treponemal infection (syphilis, yaws, bejel, and pinta). How did the causative organism(s) and humans co-evolve? How did the related diseases caused by Treponema pallidum emerge in different parts of the world and affect people across both time and space? How are T. pallidum subspecies related to the treponeme causing pinta? The current state of scholarship in specific areas is reviewed with recommendations made to stimulate future work. Understanding treponemal biology, genetic relationships, epidemiology, and clinical manifestations is crucial for vaccine development today and for investigating the distribution of infection in both modern and past populations.Paleopathologists must improve diagnostic criteria and use a standard approach for recording skeletal lesions on archaeological human remains. Adequate contextualization of cultural and environmental conditions is necessary, including site dating and justification for any corrections made for marine or freshwater reservoir effects. Biogeochemical analyses may assess aquatic contributions to diet, physiological changes arising from treponemal disease and its treatments (e.g., mercury), or residential mobility of those affected. Shifting the focus from point of origin to investigating who is affected (e.g., by age/sex or socioeconomic status) and disease distribution (e.g., coastal/ inland, rural/urban) will advance our understanding of the treponemal disease and its impact on people through time. K E Y W O R D S archaeological biogeochemistry,

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When Is Syphilis Not Syphilis? Or Is It?

Cited by 9 publications

References 21 publications

Identification of positively selected genes in human pathogenic treponemes: Syphilis-, yaws-, and bejel-causing strains differ in sets of genes showing adaptive evolution

Identification of positively selected genes in human pathogenic treponemes: Syphilis-, yaws-, and bejel-causing strains differ in sets of genes showing adaptive evolution

Identifying treponemal disease in early East Asia

Advancing the understanding of treponemal disease in the past and present

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