Redefining the treponemal history through pre-Columbian genomes from Brazil.

The origins of treponemal diseases have long remained unknown, especially considering the sudden onset of the first syphilis epidemic in the late 15th century in Europe and its hypothesized arrival from the Americas with Columbus' expeditions1,2. Recently, ancient DNA evidence has revealed various treponemal infections circulating in early modern Europe and colonial-era Mexico3-6. However, there has been to our knowledge no genomic evidence of treponematosis recovered from either the Americas or the Old World that can be reliably dated to the time before the first trans-Atlantic contacts. Here, we present treponemal genomes from nearly 2,000-year-old human remains from Brazil. We reconstruct four ancient genomes of a prehistoric treponemal pathogen, most closely related to the bejel-causing agent Treponema pallidum endemicum. Contradicting the modern day geographical niche of bejel in the arid regions of the world, the results call into question the previous palaeopathological characterization of treponeme subspecies and showcase their adaptive potential. A high-coverage genome is used to improve molecular clock date estimations, placing the divergence of modern T. pallidum subspecies firmly in pre-Columbian times. Overall, our study demonstrates the opportunities within archaeogenetics to uncover key events in pathogen evolution and emergence, paving the way to new hypotheses on the origin and spread of treponematoses.

Human major infections: Tuberculosis, treponematoses, leprosy-A paleopathological perspective of their evolution.

The key to evolution is reproduction. Pathogens can either kill the human host or can invade the host without causing death, thus ensuring their own survival, reproduction and spread. Tuberculosis, treponematoses and leprosy are widespread chronic infectious diseases whereby the host is not immediately killed. These diseases are examples of the co-evolution of host and pathogen. They can be well studied as the paleopathological record is extensive, spanning over 200 human generations. The paleopathology of each disease has been well documented in the form of published synthetic analyses recording each known case and case frequencies in the samples they were derived from. Here the data from these synthetic analyses were re-analysed to show changes in the prevalence of each disease over time. A total of 69,379 skeletons are included in this study. There was ultimately a decline in the prevalence of each disease over time, this decline was statistically significant (Chi-squared, p<0.001). A trend may start with the increase in the disease's prevalence before the prevalence declines, in tuberculosis the decline is monotonic. Increase in skeletal changes resulting from the respective diseases appears in the initial period of host-disease contact, followed by a decline resulting from co-adaptation that is mutually beneficial for the disease (spread and maintenance of pathogen) and host (less pathological reactions to the infection). Eventually either the host may become immune or tolerant, or the pathogen tends to be commensalic rather than parasitic.

Treponematosis in a pre-Columbian hunter-gatherer male from Antofagasta (1830 ± 20 BP, Northern Coast of Chile).

OBJECTIVE: This paper reports a new case of treponemal disease in a pre-Columbian hunter-gatherer inhabiting the desert coast of South America. MATERIALS: A well-preserved adult male skeleton from the "Vertedero Municipal" archaeological cemetery, located near the city of Antofagasta (Northern Chile). METHODS: The skeleton was radiocarbon dated, and isotopic analyses were performed to assess diet and mobility. Lytic and proliferative lesions identified were evaluated macroscopically and radiologically. RESULTS: A radiocarbon date of 1830 ± 20 BP and isotopic values indicating a marine diet and coastal residence were obtained. The cranium shows reactive changes as focal superficial cavitation, radial scarring and nodular cavitation, while the ribs, sternum, clavicles, and scapulae exhibit multiple lytic and proliferative lesions. The right femur has a node while both tibiae show mild anterior cortical thickening with a narrowed medullary cavity. CONCLUSIONS: Cranial lesions are pathognomonic for treponemal disease while postcranial changes are typical, and highly consistent with this pathology. SIGNIFICANCE: The type, morphology, and pattern of lesions make this case a good candidate for venereal syphilis. The case is relevant to the origin of venereal syphilis due to the lifestyle, temporal and ecological context of the individual. LIMITATIONS: Diagnosis of venereal syphilis is based on skeletal lesions; thus, it must be confirmed by molecular analysis. SUGGESTIONS FOR FURTHER RESEARCH: A comprehensive review of cases of pre-Columbian treponemal disease in South America as well as molecular studies are needed to confirm the presence of venereal syphilis in the New World before European contact.

Advancing the understanding of treponemal disease in the past and present.

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.

A singular case of advanced caries sicca in a pre-Columbian skull from East Tennessee.

OBJECTIVE: Documentation of an advanced case of tertiary stage treponemal disease. MATERIALS: The well-preserved cranium and mandible of an adult male (Burial G) from the Early Woodland period (900 BCE-200 CE) Wilhoite site (40GN10) from east Tennessee. METHODS: Macroscopic examination of the cranio-facial periostosis on Burial G for pathognomonic indicators of treponemal disease. RESULTS: There are extensive contiguous nodular lesions on the frontal, parietals, temporals, and occipital bones. The frontal squama additionally exhibits radial scaring and circumvallate cavitating lesions. Radial scars are also present on both zygomatic bones and the endocranial surface of the calotte. There is rounding of the nasal margins in addition to periostosis on the palate. CONCLUSIONS: Burial G unequivocally exhibits the pathognomonic reactive changes of caries sicca, radial scarring, and cavitating lesions. SIGNIFICANCE: The Early Woodland date in combination with the advanced degree of pathognomonic reactive change is exceptional, and to date, without parallel in the pre-Columbian archaeological record of North America. Any case approaching the severity displayed here is invariably late prehistoric. LIMITATIONS: The absence of postcrania does not permit assessment of frailty or synergism of secondary conditions. SUGGESTIONS FOR FURTHER RESEARCH: More comprehensive documentation of pre-Columbian treponemal cases is merited.

First Paleogenetic Evidence of Probable Syphilis and Treponematoses Cases in the Brazilian Colonial Period.

Despite interest in the origins of syphilis, paleopathological analysis has not provided answers, and paleogenetic diagnosis remains a challenge. Even venereal syphilis has low infectivity which means there are few circulating bacteria for most of the individual's life. Human remains recovered from the Nossa Senhora do Carmo Church (17th to 19th centuries) and the Praça XV Cemetery (18th to 19th centuries), Rio de Janeiro, Brazil, were subjected to Treponema paleogenetic analysis. Historical data point to endemic treponemal infections in the city, including venereal syphilis. Based on the physiopathology of Treponema pallidum infection, 25 samples, mostly from skull remains of young adults, with no visible paleopathological evidence of treponematoses, were analyzed. PCR with three molecular targets, tpp47, polA, and tpp15, were applied. Ancient DNA tpp15 sequences were recovered from two young adults from each archaeological site and revealed the polymorphism that characterizes T. p. subsp. pallidum in a female up to 18 years old, suggesting a probable case of syphilis infection. The results indicated that the epidemiological context and the physiopathology of the disease should be considered in syphilis paleogenetic detection. The findings of Treponema sp. aDNA are consistent with historical documents that describe venereal syphilis and yaws as endemic diseases in Rio de Janeiro. Data on the epidemiological characteristics of the disease and its pathophysiology offer new perspectives in paleopathology.

Between Colonial, National, and International Medicine: The Case of Bejel.

In the 1920s and 1930s, doctors stationed in the Middle East and North Africa debated whether bejel, a form of endemic syphilis, was an Arab version of syphilis, or a separate disease altogether. Using their clinical experience in the region, they tried to weave this unfamiliar phenomenon into a civilizational narrative, which placed European civilization at the top of a hierarchy. The assumption was that there was something inherent to Islamic societies and their hygienic habits that accounted for this difference. After World War II, the eradication of bejel was declared to be one of the objectives of both the Iraqi government and the newly founded World Health Organization. Examining the postwar life of bejel, I question how colonial legacies affected postcolonial and international medical theories and practices, on both national and international levels.

Ancient pathogens in museal dry bone specimens: analysis of paleocytology and aDNA.

Bone samples investigated in this study derive from the pathologic-anatomical collection of the Natural History Museum of Vienna. In order to explore the survival of treponemes and treponemal ancient DNA in museal dry bone specimens, we analyzed three individuals known to have been infected with Treponema pallidum pallidum. No reproducible evidence of surviving pathogen's ancient DNA (aDNA) was obtained, despite the highly sensitive extraction and amplification techniques (TPP15 and arp). Additionally, decalcification fluid of bone sections was smear stained with May-Gruenwald-Giemsa. The slides were examined using direct light microscope and dark field illumination. Remnants of spirochetal structures were detectable in every smear. Our results demonstrate that aDNA is unlikely to survive, but spirochetal remains are stainable and thus detectable.

Evidence of skeletal treponematosis from the medieval burial ground of St. Mary Spital, London, and implications for the origins of the disease in Europe.

Treponematosis is a syndrome of chronic infectious diseases. There has been much debate on its origins and spread, particularly with regard to venereal syphilis, an unsightly and debilitating disease in preantibiotic populations. The osteological analysis of 5,387 individuals excavated by Museum of London Archaeology from the medieval burial ground of St. Mary Spital in London (dated c 1120-1539) provided an unprecedented opportunity to investigate the nature and prevalence of disease over a period of time. Twenty-five individuals were found with suspected treponematosis, originating from all but the earliest period of the burial ground. Descriptions of affected individuals from each period, together with supporting images, are provided. In this work, particular emphasis was given to the distribution of lesions on the skeleton and the variation in patterns by sex and over time. Little change was observed in the distribution of bony change between individuals dated to pre- and post-Columbian periods. However, a dramatic rise in the prevalence of the disease in the final period (c 1400-1539) may reflect documentary reports of a European epidemic from the late 15th century.

Endemic syphilis in Europe.

Nonvenereal syphilis (endemic syphilis) has existed in Europe since the 16th century. Main characteristics of the disease are its presence for a longer time in a specific territory and its transmission regardless of age and sex, mainly extragenitally in unsanitary living conditions. Nonvenereal syphilis was described under different names in almost all regions of Europe. The primary genital chancre was absent, and lesions were most frequently found in the mouth and affected mostly children. The disease spread in rural areas with poor economic and hygienic conditions. The disease was eradicated in Europe in the 20th century, but it is still present in some rural regions of the Arabian Peninsula, Southwest Asia, and North Africa.

Isotopic tracing of the impact of mobility on infectious disease: The origin of people with treponematosis buried in hull, England, in the late medieval period.

Treponematosis has been one of the most studied and debated infectious diseases in paleopathology, particularly from the standpoint of its origin, evolution, and transmission. This study links evidence for treponematosis in skeletons from the 14th-16th century AD cemetery of the Augustinian friary of Hull Magistrates Court, England, with data from stable isotope analysis to test the hypothesis that the people with treponemal disease buried at this site were not locally born and raised. The objective is to explore the potential of using stable isotope data to track the place of origin and extent of mobility of individuals with an infectious disease. Dental enamel samples of 12 skeletons were selected for strontium ((87) Sr/(86) Sr ratio) and oxygen (δ(18) O) stable isotope analysis based on the presence (six - diseased) or absence (six - controls) of bone changes associated with treponemal disease. The oxygen isotope ratios of all but three individuals (1047, 1121, 823) overlapped at two standard deviations with the inferred local precipitation range, and only one individual (1216) had a strontium isotope ratio outside the regional range. Two of the four had probable/possible treponemal bone changes. Those with treponemal bone changes were not demonstrably more likely to be migrants than those without such lesions. However, because of extensive documentary evidence for trade with the Baltic Sea area, and for merchants from towns such as Stralsund, Danzig and Elbing being in Hull, it is very plausible that the four migrants came from the Baltic area or even southern Sweden.

What skeletons tell us. The story of human paleopathology.

Human skeletal paleopathology provides important insight regarding the antiquity of some diseases and their distribution in past human groups. The history of human skeletal paleopathology extends back more than 150 years. Rudolf Virchow published reports on the subject, and research on paleopathology has provided critical data on important topics such as the origin of syphilis. With the development of powerful new research tools, human paleopathology will continue to be a source of data on the development of disease and its effect on human biological and cultural development.

Rheumatic diseases in the ancient Americas: the skeletal manifestations of treponematoses.

INTRODUCTION: The effect of rheumatic and infectious diseases on skeletal remains provides an important source of information for knowledge of contemporary medicine. Few pathologic conditions have attracted so much interest as treponematoses. One of these, syphilis, was the most feared venereal disease throughout the civilized world until the introduction of penicillin in the 20th century. OBJECTIVE: To describe paleopathological and ceramic illustrations of treponematoses in ancient Mexico. MATERIALS AND METHODS: Paleopathological and ceramic material examples from the National Institute of Anthropology and History of Mexico were reviewed. RESULTS: A unique paleopathologic site for treponemal diseases comprises the La Candelaria Cave skeletal collection from northern Mexico. The cave was used as a burial site and contained the bones of at least 83 adults and 33 subadults. Fifty-one percent of the recovered skulls possess erosions of the vault consistent with treponematoses. Some of these exhibit the impressive frontal bone lytic changes with irregular borders typical of caries sicca. In addition, periostosis of the long bones was found in up to 88% of the study sample, including 6 examples of saber-shin deformity of tibias. Radiocarbon dating (-C) of a bone retrieved from the cave ranges from 1100 to 1300 A.D. Additionally, a Pre-Hispanic ceramic figurine from the Mexican state of Nayarit depicting a lame man with multiple nodular skin lesions that suggest gummatous treponemal infection is described. CONCLUSIONS: These ancient specimens reinforce the notion that treponemal infection was present on the American Continent before European penetration of the New World. These very advanced paleopathologic lesions and ceramic representations demonstrate the degree to which these diseases wrought devastation before the antibiotic era. In ancient times, treponematoses were true rheumatic diseases that produced profound skeletal abnormalities marked by periosteal accretion and bone destruction.

Climate and New World periosteal reaction patterns: implications for migration routes into the western hemisphere.

The presence of the diseases yaws and bejel are indicated by periosteal reaction patterns. The distributions of these two diseases in ancient North American human populations show evidence of climatic influence. Those ancient populations lacking either yaws or bejel (the null periosteal reaction pattern) can be found in the coldest parts of the Cold Winter Regions. Those populations with yaws (the poly-ostotic periosteal reaction) can be found in the milder portions of the Cold Winter Regions. The populations with bejel (the pauci-ostotic periosteal reaction) are found either outside of or marginal to Cold Winter Regions. The Bering Strait area is considered to be the gateway to the ancient New World. The cold climates present in this area should have influenced the routes available for the diseases to spread from population to population or by migration of infected populations into the Western Hemisphere. It is suggested that the coastal route with its milder maritime climate was the route taken by yaws when it entered the New World. The presence of bejel in ancient North America presents a conundrum. The climate would have blocked the spread of the disease from Siberia to Alaska in either Late Glacial or Holocene times. This suggests that our present view of migration routes is incomplete.

Bejel: acquirable only in childhood?

Bejel clearly has a long history in the Middle East and the Sudan, but was it transmitted to Europe? As the major manifestation of bejel is presence of periosteal reaction in 20-40% of afflicted populations, absence of significant population frequency of periosteal reaction in Europe would exclude that diagnosis. Examination of skeletal populations from continental Europe revealed no significant periosteal reaction at the time of and immediately subsequent to the Crusades. Thus, there is no evidence for bejel in Europe, in spite of clear contact (the mechanism of bejel transmission in children) between warring groups, at least during the Crusades. This supports the hypothesis that bejel is a childhood-acquired disease and apparently cannot be contracted in adulthood.

Treponemal disease in the middle Archaic to early Woodland periods of the western Tennessee River Valley.

The high frequency of late prehistoric New World treponemal disease is attributable to the demographic changes concomitant with the adoption of agriculture. However, these demographic changes in group mobility and site density episodically preceded intensive plant domestication, suggesting possible staggered temporal change in observed treponemal disease case frequency. Thirteen convincing and an additional two probable (N = 581) cases of treponemal disease were identified in an eight-site skeletal sample spanning the Middle (6,000-3,000 BCE) to Late (2,500-ca. 1,000 to 500 BCE) Archaic and Early Woodland (500 BCE-0 CE) periods from the western Tennessee River Valley. Treponemal disease cases are infrequent in both the Middle (3/115, 2.6%) and Late (2 to 4 cases,

Regional, social, and evolutionary perspectives on treponemal infection in the Southeastern United States.

The origin and geographic distribution of syphilis, a form of treponemal infection, have long been regarded as among the most important medical riddles of prehistoric and historic disease evolution. In this study, we expand on previous discussions of the origin, evolution, and relationship of treponemal infections as they occur in the prehistoric southeastern United States. Individuals from 25 skeletal series (n = 2,410 individuals) were examined for cranial and dental lesions characteristic of treponemal infection. They lived between the Archaic period (8000-1000 BC) and protohistoric period (AD 1500-1600), and in physiographic zones from the coast to the mountains of Alabama, Florida, North Carolina, and Tennessee. Radial cranial scars were found for 47 individuals, but none of the four cases of dental lesions could be attributed to congenital syphilis. Differences in frequency of cranial lesions by region were minimal, with the least number of cases found for the mountains, but the frequency of positive cases tended to increase through time. It is suggested that increasing population density and changing behaviors, rather than novel strains of the treponemal pathogen, are responsible for the chronological increase in the frequency of positive cases.

La treponematosis precolombina en Cuba / Pre-Columbian treponematosis in Cuba

Se realiza una revisión de la infección por treponema pallidum, agente de la sífilis, en aborígenes cubanos con una discusión sobre su existencia en la Isla en una etapa presumiblemente anterior al 3 000 ANE, habida cuenta la antigüedad de los restos datados y los contextos culturales a que estos están asociados. Se presume que la entidad se presentó en su variante endémica y no bajo las formas venéreo o congénitas. Las poblaciones más atacadas fueron las del período mesolítico cubano, sin que existan reportes dentro del material estudiado que alcancen a los sujetos ubicados dentro del neolítico del occidente del país, detalle que contrasta con los hallazgos de Luna Calderón en La Española. Se analizan además, las posibles vías de migración de la entidad patológica a Cuba, excluyendo la ruta norte-sur, toda vez que las dataciones de restos con evidencias de treponematosis aborigen americana no alcanzan datas remotas como las observadas en Cuba. En su lugar se plantea la ruta sur-norte desde el continente a la Isla , sin cruzar, en esta etapa, por el arco de las Antillas. En este estudio se presentan las características de las secuelas óseas y sus elementos diferenciales con otras noxas infecciosas en aborígenes(AU)