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.

Short communication: Screening stable flies and house flies as potential vectors of digital dermatitis in dairy cattle.

Digital dermatitis is a bacterial infection that causes lesions above the heel bulbs on cattle hooves, and several bacterial species from the genus Treponema are suspected to be causative agents of this polymicrobial condition. Transmission of the bacteria to healthy cows is understudied, particularly with regard to potential insect vectors. Therefore, the objective of this research was to determine if flies captured from a dairy farm known to have digital dermatitis are contaminated with Treponema bacteria. The DNA-based assays did not detect any Treponema phagedenis from stable flies and house flies collected at a dairy experiencing an outbreak of digital dermatitis. Other potential means of bacterial transmission are discussed.

Survival of bovine digital dermatitis treponemes on hoof knife blades and the effects of various disinfectants.

BACKGROUND: Bovine digital dermatitis (BDD) is a painful infectious foot disease of cattle, and much evidence implicates a pathogenic role for treponemes. This study measured the survival of BDD treponemes on hoof knife blades and tested the efficacy of relevant disinfectants under laboratory conditions. METHODS: Two strains of BDD treponemes were applied to hoof knife blades under aerobic conditions. Swabs were taken at different time points (10 minutes, one hour, two hours, four hours and 18 hours) and again after 20-second disinfection time with one of five disinfectants. Swabs were used directly for nested PCR to detect treponemes or inoculated for anaerobic growth, and subsequently examined using phase contrast microscopy and PCR. RESULTS: BDD treponeme DNA was detectable by nested PCR at all survival time points, and these organisms were culturable from hoof knives for two hours after exposure under aerobic conditions in the laboratory. Three of the five disinfectants-1 per cent volume per volume (v/v) FAM30®, 2 per cent weight per volume (w/v) Virkon® or 2 per cent (v/v) sodium hypochlorite-were effective at preventing visible growth of treponemes following 20-seconds contact, and 1 per cent (v/v) FAM30® also prevented detection of treponemes by PCR. CONCLUSION: Treponeme viability of two hours under aerobic conditions suggests BDD treponemes could be transmitted between cows on hoof knives. It is therefore important to apply a disinfection protocol during foot-trimming; the authors have identified three common disinfectants that may be suitable.

Strain diversity of Treponema pallidum subsp. pertenue suggests rare interspecies transmission in African nonhuman primates.

In our most recent study, we found that in Tanzania infection with Treponema pallidum (TP) subsp. pertenue (TPE) is present in four different monkey species. In order to gain information on the diversity and epidemiological spread of the infection in Tanzanian nonhuman primates (NHP), we identified two suitable candidate genes for multi-locus sequence typing (MLST). We demonstrate the functionality of the MLST system in invasively and non-invasively collected samples. While we were not able to demonstrate frequent interspecies transmission of TPE in Tanzanian monkeys, our results show a clustering of TPE strains according to geography and not host species, which is suggestive for rare transmission events between different NHP species. In addition to the geographic stability, we describe the relative temporal stability of the strains infecting NHPs and identified multi-strain infection. Differences between TPE strains of NHP and human origin are highlighted. Our results show that antibiotic resistance does not occur in Tanzanian TPE strains of NHP origin.

Experimental Transmission of Bovine Digital Dermatitis to Sheep: Development of an Infection Model.

Digital dermatitis is an infectious cause of lameness primarily affecting cattle but also described in sheep, goats, and wild elk. Digital dermatitis is a polymicrobial infection, involving several Treponema species and other anaerobic bacteria. Although the exact etiology has not been demonstrated, a number of bacterial, host, and environmental factors are thought to contribute to disease development. To study host-bacterial interactions, a reproducible laboratory model of infection is required. The objective of this study was to demonstrate key aspects of bovine digital dermatitis lesions in an easy-to-handle sheep model. Crossbred sheep were obtained from a flock free of hoof disease. Skin between the heel bulb and dewclaw was abraded before wrapping to emulate a moist, anaerobic environment. After 3 days, abraded areas were inoculated with macerated lesion material from active bovine digital dermatitis and remained wrapped. By 2 weeks postinoculation, experimentally inoculated feet developed erosive, erythematous lesions. At 4 weeks postinoculation, microscopic changes in the dermis and epidermis were consistent with those described for bovine digital dermatitis, including erosion, ulceration, hyperkeratosis, ballooning degeneration of keratinocytes, and the presence of neutrophilic infiltrates. Silver staining of lesion biopsy sections confirmed that spirochetes had penetrated the host epidermis. The model was then perpetuated by passaging lesion material from experimentally infected sheep into naïve sheep. This model of bovine digital dermatitis will allow for future novel insights into pathogenic mechanisms of infection, as well as the development of improved diagnostic methods and therapeutics for all affected ruminants.

Treponemes detected in digital dermatitis lesions in Brazilian dairy cattle and possible host reservoirs of infection.

The main pathogenic treponemes causing bovine digital dermatitis were identified from 17 infected herds in southern Brazil for the first time in this study using PCR. We did not find a relationship between treponeme phylogroup composition and clinical classification. Treponema phagedenis was present in all lesions. Rumen fluid was implicated as a reservoir location for these pathogens.

Presence of digital dermatitis treponemes on cattle and sheep hoof trimming equipment.

Digital dermatitis (DD) is an infectious foot disease causing severe lameness in dairy cattle (worldwide) and sheep (UK). This study investigated whether DD Treponema phylogroups can be present on equipment used to trim ruminant hooves and, therefore, consider this trimming equipment as a possible vector for the transmission of DD. Equipment was tested after being used to trim DD symptomatic and asymptomatic cattle and sheep hooves, and subsequently after disinfection of equipment. After trimming, 'Treponema medium/Treponema vincentii-like', 'Treponema phagedenis-like' and 'Treponema denticola/T putidum-like' DD spirochaetes, were shown to be present on 23/37 (62%), 21/37 (57%) and 20/37 (54%) of knives, respectively. After disinfection, detection rates for the DD treponemes were 9/37 (24%), 6/37 (16%) and 3/37 (8%), respectively. Following culture of a swab, an isolate belonging to the T phagedenis-like spirochaetes was identified from a knife sample after trimming a DD positive cow. No isolates were obtained from knife samples after disinfection. This new data has, for the first time, identified treponemes in the farm environment, and highlighted disinfection of hoof trimming equipment between animals and between farms, as a logical precaution to limit the spread of DD.

Prevalence survey of infection with Treponema pallidum among HIV-positive patients in Tehran.

OBJECTIVE: To identify the frequency of syphilis among Iranian HIV-positive patients. METHODS: A cross-sectional study on the prevalence of syphilis and HIV co-infection among 450 patients diagnosed with HIV infection was conducted between 2004 and 2008 at Imam Khomeini hospital, Tehran, Iran. The lab tests including CD4 cell count, cerebrospinal fluid, veneral disease research laboratory (VDRL), fluorescent treponema antibody-absorption (FTA-Abs) and viral load were performed for all the patients. Data regarding medical history and their demographics were also collected. RESULTS: Of all 450 HIV-positive patients, 24 (5.3%) had a positive VDRL test and only two men had a FTA-Abs positive test which means 0.45% of them had a definite co-infection of syphilis. 65.3% of the HIV-positive patients were injection drug users that the co-infection prevalence of them was 0.7%. We did not find any patient with neurosyphilis. CONCLUSIONS: Considering the increasing prevalence of HIV and also extensive use of highly active antiretroviral therapy in developing nations, the diagnosis of syphilis should be timely established using screening tests among such patients.

Host and environmental reservoirs of infection for bovine digital dermatitis treponemes.

Bovine digital dermatitis (BDD) is a global infectious disease causing lameness of cattle and is responsible for substantial animal welfare issues and economic losses. The causative agents are considered to be spirochetal bacteria belonging to the genus Treponema, which have consistently been identified in BDD lesions worldwide. One potential means of controlling infection is the disruption of transmission; however, the infection reservoirs and transmission routes of BDD treponemes have yet to be elucidated. To address these issues, we surveyed for evidence of BDD treponeme presence in the dairy farm environment, in bovine tissues and in bovine gastrointestinal (GI) tract contents. A total of 368 samples were tested using PCR assays specific for each of three currently recognised, isolated phylotypes of BDD treponemes. All environmental samples, together with insects and GI tract content samples were negative for BDD treponeme DNA from the three phylotypes. However, we identified BDD treponemes in two non-pedal bovine regions: the oral cavity (14.3% of cattle tested) and the rectum (14.8% of cattle tested). Whilst only single phylotypes were detected in the oral cavity, two of the rectal tissues yielded DNA from more than one phylotype, with one sample yielding all three BDD treponeme phylotypes. Whilst it might be considered that direct skin to skin contact may be a major transmission route of BDD treponemes, further studies are required to characterise and determine the potential contribution of oral and rectal carriage to BDD transmission.

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.

Anti-HBc screening in Egyptian blood donors reduces the risk of hepatitis B virus transmission.

Occult hepatitis B virus (HBV) in blood donors is considered as a potential risk for transmission of HBV infection. The aim of this study was to determine the prevalence of anti-hepatitis B core antibody (anti-HBC) positivity in Egyptian blood donations as well as to estimate the frequency of HBV-DNA in anti-HBc-positive donations. The study included 760 Egyptian healthy blood donors, representing 26 different Egyptian governorates screened according to routine practice for the presence of hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibodies (Abs), HIV-1/2 Abs and Treponema Abs. The accepted blood units for donation were tested for the presence of total anti-HBc Abs by two tests. Positive units for anti-HBc were further tested for HBV-DNA by polymerase chain reaction. According to routine screening, a total of 48/760 units (6.3%) were rejected [38 (5%) HCV-Ab-positive units, 9 (1.18%) HbsAg-positive units and 1 (0.13%) Treponema-Ab-positive unit]. Among the accepted blood units for donation, prevalence of anti-HBc was 78/712 units (10.96%). HBV-DNA was detected in 9/78 (11.54%) of the anti-HBc-positive units, and thus, occult HBV infection was detected in 9/712 (1.26%) of the accepted blood donations. Implementing anti-HBc test to the routine assay for the forthcoming two decades would certainly eliminate possible HBV-infected units. Rejection of these units will be beneficial to decrease the risk of HBV transmission with its potential consequences particularly in immunocompromised recipients.

Experimental transmission of rabbit syphilis.

Rabbit syphilis was experimentally transmitted from clinical cases to healthy rabbits. The purpose was to evaluate changes in RPR titers during the course of infection and to detect the pathogenic organism. Two of three littermate rabbits were inoculated topically. One rabbit became symptomatic, with typical clinical signs on its genitalia about 8 weeks after inoculation and a marked rise in RPR titers, another remained asymptomatic with a moderate rise in titers, and the control rabbit remained negative. These results supported the specific relationship between clinical signs and RPR titers. Histopathological examination of the skin lesion from the symptomatic rabbit revealed spirochetes.

Diagnóstico antenatal de sífilis congénita por PCR en líquido amniótico y sus posibles aplicaciones / Prenatal diagnosis of congenital syphilis by PCR in amniotic liquid and its possible applications

Se presenta un caso clínico de sífilis congénita diagnosticada antenatalmente mediante el uso de la reacción de la polimerasa en cadena (PCR) en líquido amniótico. La PCR permitiría identificar la espiroqueta en diferentes medios, como en sangre, líquido amniótico y líquido céfalo-raquídeo. Deberán desarrollarse nuevos protocolos para poder probar la efectividad de los tratamientos en base a esta técnica diagnóstica.

Treponemal infection rates, risk factors and pregnancy outcome in a rural area of Senegal.

A rural population of east Senegal has been under demographic surveillance for more than 30 years and a high rate of infertility has been reported. The aim of the study is to describe HIV and treponemal infection epidemiology and association with outcome of pregnancy in a population of rural Senegal. A population-based cross-sectional study was conducted among 952 randomly-selected adults of a rural community of Senegal. No participant was found to be infected with HIV, 11% had evidence of past syphilis and 5% of active syphilis. Active syphilis was associated among men with age, long-term mobility and having partners in an urban area in the last 12 months and among women with being divorced or widowed. No association was found between past or active syphilis and abortion or stillbirth but women aged 40 and more with past or active syphilis were significantly more likely to have had no history of gestation than women with no evidence of syphilis infection. In conclusion our results call for more research to understand the epidemiology of treponemal infection and to elucidate types of Treponema pallidum involved.

Serological markers for treponemal infection in children in rural Kilimanjaro, Tanzania: evidence of syphilis or non-venereal treponematoses?

OBJECTIVE: To determine the seroprevalence of treponemal infection and possible risk factors among children aged 0-14 in the general population of a rural Tanzanian village. METHODS: The survey was conducted as a part of a cross section study of a total village population on HIV and sexually transmitted disease. Among 1708 registered children aged 0-14, the 553 first attending were tested for treponemal infection with both rapid plasma reagin test (RPR) and Treponema pallidum Haemagglutination test (TPHA). These children belonged to a household cohort--also including their parents, siblings, and other household members--with 1339 members; 1224 (91.4% participated in the survey and 82.1% of these were tested for treponemal infection. RESULTS: The overall prevalence for the TPHA test was 6.4% among girls and 1.1% among boys (odds ratio, OR = 6.5; 95% confidence interval, CI: 1.9-22.3). The sex difference was most pronounced in the age group 10-14; 11.1% among girls versus 1.0% among boys (OR = 12.8; CI: 1.6-101.9). Among the 20 children who were TPHA positive, we found two cases of active, congenital syphilis. There was a lack of association between positive serology in children and positive serology in their parents. CONCLUSION: The highly significant predominance of girls testing positive for TPHA, and the concomitant lack of association between parents' and children's serostatus might point to sexual transmission as being the most common route of transmission of treponemal infection in girls during childhood in this village. The sources of infection for the seropositive girls are possibly found outside the family.

Sexually transmitted diseases in children in developing countries.

PIP: The populations of developing countries have younger age structures than the populations of more developed, Western countries. That is, children, adolescents, and youth constitute a far greater proportion of the populations of developing countries than in developed countries. These young people experiment with sex and sexual intercourse or have coitus on a regular basis depending upon their individual personalities and circumstances. The prevalence of sexually transmitted diseases (STD) among younger age groups in developing countries is not well documented. It may, however, be inferred on the basis of reported experience of STD in surveys of adolescents and young adults that many children are infected with STDs. Some young people have sex consensually, some are coaxed into it, and others are coerced. On the one hand, young children have been thought to contract STD by sitting on the laps of infected, scantily-clad adults where such limited attire is the norm. Close contact between youngsters such as communal sleeping, for example, could then facilitate the spread of the STD among children. Sex, consensual or otherwise, is not involved in such infection and transmission beyond the index adult. On the other hand, however, many children and adolescents are forced to have sexual relations and/or intercourse either directly against their will or as a result of the primal need to ensure their individual survival. For example, there are an estimated 100-200 million street children worldwide; many have little alternative but to sell sex to survive. When having sex, they may not use condoms because they are unaware of the STD risk they face, they have no access to free condoms, clients/employers/peers prevent them from using condoms, or due to a myriad of other reasons. Struggling to survive, many such kids place condom use very low on their list of priorities. Children and adolescents can also become infected and transmit STDs to others by engaging in sexual intercourse under more narrowly-defined cultural norms. For example, the belief exists that a male with urethritis can be cured by sexual intercourse with a virgin or prepubertal girl. Elsewhere, it is normal practice for an adult male, typically a boy's uncle, to have anal insertive sexual intercourse with the boy on a regular basis over the period of a couple years to facilitate his transition into manhood. People in young age groups around the world have sex for a range of reasons under a variety of conditions. Measures are needed to ensure that they have the means to prevent infection with STDs and control that infection, if possible, once acquired. Sections discuss vulvovaginitis, donovanosis, chancroid, and venereal and nonvenereal treponematosis, as well as prevention and future research.^ieng