Trial of Three Rounds of Mass Azithromycin Administration for Yaws Eradication.

BACKGROUND: Treponema pallidum subspecies pertenue causes yaws. Strategies to better control, eliminate, and eradicate yaws are needed. METHODS: In an open-label, cluster-randomized, community-based trial conducted in a yaws-endemic area of Papua New Guinea, we randomly assigned 38 wards (i.e., clusters) to receive one round of mass administration of azithromycin followed by two rounds of target treatment of active cases (control group) or three rounds of mass administration of azithromycin (experimental group); round 1 was administered at baseline, round 2 at 6 months, and round 3 at 12 months. The coprimary end points were the prevalence of active cases of yaws, confirmed by polymerase-chain-reaction assay, in the entire trial population and the prevalence of latent yaws, confirmed by serologic testing, in a subgroup of asymptomatic children 1 to 15 years of age; prevalences were measured at 18 months, and the between-group differences were calculated. RESULTS: Of the 38 wards, 19 were randomly assigned to the control group (30,438 persons) and 19 to the experimental group (26,238 persons). A total of 24,848 doses of azithromycin were administered in the control group (22,033 were given to the participants at round 1 and 207 and 2608 were given to the participants with yaws-like lesions and their contacts, respectively, at rounds 2 and 3 [combined]), and 59,852 doses were administered in the experimental group. At 18 months, the prevalence of active yaws had decreased from 0.46% (102 of 22,033 persons) at baseline to 0.16% (47 of 29,954 persons) in the control group and from 0.43% (87 of 20,331 persons) at baseline to 0.04% (10 of 25,987 persons) in the experimental group (relative risk adjusted for clustering, 4.08; 95% confidence interval [CI], 1.90 to 8.76). The prevalence of other infectious ulcers decreased to a similar extent in the two treatment groups. The prevalence of latent yaws at 18 months was 6.54% (95% CI, 5.00 to 8.08) among 994 children in the control group and 3.28% (95% CI, 2.14 to 4.42) among 945 children in the experimental group (relative risk adjusted for clustering and age, 2.03; 95% CI, 1.12 to 3.70). Three cases of yaws with resistance to macrolides were found in the experimental group. CONCLUSIONS: The reduction in the community prevalence of yaws was greater with three rounds of mass administration of azithromycin at 6-month intervals than with one round of mass administration of azithromycin followed by two rounds of targeted treatment. Monitoring for the emergence and spread of antimicrobial resistance is needed. (Funded by Fundació "la Caixa" and others; ClinicalTrials.gov number, NCT03490123.).

Treponema peruense sp. nov., a commensal spirochaete isolated from human faeces.

A Gram-stain-negative, obligatory anaerobic spirochaete (RCC2812T) was isolated from a faecal sample obtained from an individual residing in a remote Amazonian community in Peru. The bacterium showed highest 16S rRNA gene sequence similarity to the pig intestinal spirochete Treponema succinifaciens (89.48 %). Average nucleotide identity values between strain RCC2812T and all available Treponema genomes from validated type strains were all <73 %, thus clearly lower than the species delineation threshold. The DNA G+C content of RCC2812T was 41.24 mol%. Phenotypic characterization using the API-ZYM and API 20A systems confirmed the divergent position of this bacterium within the genus Treponema. Strain RCC2812T could be differentiated from the phylogenetically most closely related T. succinifaciens by the presence of alkaline phosphatase and α -glucosidase activities. Unlike T. succinifaciens, strain RCC2812T grew equally well with or without serum. Strain RCC2812T is the first commensal Treponema isolated from the human faecal microbiota of remote populations, and based on the collected data represents a novel Treponema species for which the name Treponema peruense sp. nov. is proposed. The type strain is RCC2812T (=LMG 31794T=CIP 111910T).

A filter-assisted culture method for isolation of Treponema spp. from bovine digital dermatitis and their identification by MALDI-TOF MS.

Digital dermatitis (DD) is a major infectious foot disease of cattle worldwide. Some DD stages are associated with lameness, and the disease has significant economic and animal welfare consequences. The pathogenesis of the disease is not yet fully understood, but Treponema spp. have been associated consistently with clinical cases. Isolation of these fastidious bacteria is difficult and cumbersome. We describe an improved method enabling the culturing of the 3 Treponema spp. (T. pedis, T. phagedenis, and T. medium) from bovine foot specimens derived from DD lesions, using a combination of membrane filtering and subsequent growth on selective agar media. The entire procedure from sampling to verification of individual Treponema spp. takes up to 24 d. In addition, we established a MALDI-TOF MS-based identification method to be applied for confirmation of the different Treponema spp. This scheme provides an unambiguous, simple, and straightforward identification procedure for DD-associated Treponema spp.

BEARING DOWN ON TREPONEMES: AN ATYPICAL PRESENTATION OF SYPHILITIC UVEITIS.

PURPOSE: To present an atypical case of syphilis that presented with findings concerning for endocarditis and valsalva retinopathy. METHODS: History and clinical examination of 42-year-old white man who presented to the emergency department with acute onset vision changes associated with gastrointestinal symptoms, otalgia, and constitutional symptoms. RESULTS: The review of this case highlights the atypical nature in which syphilis can present and can remain undiagnosed even in the face of extensive workups for other systemic conditions. CONCLUSION: We present a case of syphilis in a patient with multiorgan involvement in whom the diagnosis was made based on atypical ocular examination findings.

Comparative analysis of oral microbiome from Zang and Han populations living at different altitudes.

OBJECTIVES: The aim of this study was to obtain greater insight into the environmental and genetic factors affecting the oral microbiome. DESIGN: To this end, we investigated the oral microbiome composition in Han and Zang populations living at different altitudes. The saliva microbiome in 115 individuals from Zang and Han populations living at different altitudes was analyzed using the 16 s rRNA gene sequencing method on the Illumina MiSeq platform. The dominant species in the oral microbiome were verified by quantitative real-time polymerase chain reaction (qPCR) analysis. RESULTS: The Han population, living at an altitude of 500 m, had higher microbiome diversity than the Zang population living at altitudes of 3000-4000 m. People living at 3000 m had a higher relative abundance of Leptothrix genus, but people living at 500 m had a higher relative abundance of Capnocytophaga genus according to Lefse difference analysis (P < 0.05). Compared to the Zang population, the Han population had higher relative abundances of Porphyromonas and Treponema genus organisms, especially Porphyromonas (P < 0.001). qPCR analysis confirmed that people living at high altitudes had the highest relative abundance of Porphyromonas gingivalis (P < 0.01). CONCLUSIONS: This study showed that both genetics and the environment had significant influences on the oral microbiome composition. The study proposed a meaningful research direction to explore the relationship between different ethnic and altitude groups and oral diseases, such as periodontal diseases.

Geographically structured genomic diversity of non-human primate-infecting Treponema pallidum subsp. pertenue.

Many non-human primate species in sub-Saharan Africa are infected with Treponema pallidum subsp. pertenue, the bacterium causing yaws in humans. In humans, yaws is often characterized by lesions of the extremities and face, while T. pallidum subsp. pallidum causes venereal syphilis and is typically characterized by primary lesions on the genital, anal or oral mucosae. It remains unclear whether other T. pallidum subspecies found in humans also occur in non-human primates and how the genomic diversity of non-human primate T. pallidum subsp. pertenue lineages is distributed across hosts and space. We observed orofacial and genital lesions in sooty mangabeys (Cercocebus atys) in Taï National Park, Côte d'Ivoire and collected swabs and biopsies from symptomatic animals. We also collected non-human primate bones from 8 species in Taï National Park and 16 species from 11 other sites across sub-Saharan Africa. Samples were screened for T. pallidum DNA using polymerase chain reactions (PCRs) and we used in-solution hybridization capture to sequence T. pallidum genomes. We generated three nearly complete T. pallidum genomes from biopsies and swabs and detected treponemal DNA in bones of six non-human primate species in five countries, allowing us to reconstruct three partial genomes. Phylogenomic analyses revealed that both orofacial and genital lesions in sooty mangabeys from Taï National Park were caused by T. pallidum subsp. pertenue. We showed that T. pallidum subsp. pertenue has infected non-human primates in Taï National Park for at least 28 years and has been present in two non-human primate species that had not been described as T. pallidum subsp. pertenue hosts in this ecosystem, western chimpanzees (Pan troglodytes verus) and western red colobus (Piliocolobus badius), complementing clinical evidence that started accumulating in Taï National Park in 2014. More broadly, simian T. pallidum subsp. pertenue strains did not form monophyletic clades based on host species or the symptoms caused, but rather clustered based on geography. Geographical clustering of T. pallidum subsp. pertenue genomes might be compatible with cross-species transmission of T. pallidum subsp. pertenue within ecosystems or environmental exposure, leading to the acquisition of closely related strains. Finally, we found no evidence for mutations that confer antimicrobial resistance.

Removal of bovine digital dermatitis-associated treponemes from hoof knives after foot-trimming: a disinfection field study.

BACKGROUND: Bovine digital dermatitis (BDD) is an infectious foot disease found commonly in dairy herds. Foot-trimming is an important husbandry procedure for reducing the ensuing lameness; however, epidemiological, and microbiological studies have identified this as a risk activity for transmitting BDD. Three disinfectants have previously been identified in laboratory work as effective for removing viable BDD-associated Treponema spp., from hoof knife blades. The present study enrolled 133 dairy cattle with BDD lesions, and swabbed hoof knife blades before and after foot-trimming, and after knife disinfection with one of three disinfectants (1:100 FAM30®, 2% Virkon® and 2% sodium hypochlorite) to assess their efficacy under field conditions. RESULTS: Detection of BDD treponeme phylogroup DNA was undertaken by direct PCR of swabs, and viable treponemes were detected by PCR of swab cultures after 6 weeks' incubation. Where hoof knives did not contact the lesion, BDD-associated treponemes were detected after foot-trimming in 12/22 (54.5%) cases by direct PCR and 1/22 (4.5%) cases by PCR of cultured organisms. Where contact was made with the lesion, 111/111 (100%) samples taken after trimming were positive by direct PCR and 47/118 (39.8%) were positive by culture PCR. Viable organisms were identified in cultures from lesion stages M2, M3, M4 and M4.1. No viable organisms were detected after disinfection of hoof knives. CONCLUSIONS: Hoof knives post-trimming were frequently contaminated with BDD-associated treponeme DNA. Viable organisms were identified in cultures whether contact had been made between hoof knife and lesion or not, although contact clearly increased the frequency of detection of viable organisms. The three disinfectants tested were effective for removing viable organisms. The disinfection protocol used in this study should therefore be considered reliable for adoption as standard industry practice.

A retrospective study on nested PCR detection of syphilis treponemes in clinical samples: PCR detection contributes to the diagnosis of syphilis in patients with seronegative and serodiscrepant results.

Syphilis, caused by Treponema pallidum ssp. pallidum (TPA), is a persisting global health problem. Although syphilis diagnostics relies mainly on serology, serological tests have some limitations, and it is recommended that the final diagnosis be supported by additional tests. The purpose of this study was to analyze the relationship between serology and PCR in syphilis diagnostics. From the year 2004 to May 2019, a total of 941 samples were taken from 833 patients suspected of having syphilis, in Czech Republic. In all these samples, both nested PCR detection of TPA and serology testing were performed. Of the 941 samples, 126 were seronegative, 651 were seropositive, and 164 were serodiscrepant. Among seronegative samples (n = 126), 11 were PCR-positive (8.7%). Among seropositive samples (n = 651; i.e., samples positive for both non-treponemal and treponemal serology tests), 368 samples were PCR-positive (56.5%). The remaining 164 serodiscrepant samples included RPR negative and treponemal serological test-positive samples (n = 154) and a set of 10 RPR-positive samples negative in treponemal serological tests. While the first group revealed 73 PCR-positive samples (47.4%), the second revealed 5 PCR positive samples (50.0%). PCR detection rates were highest in primary syphilis, with lower rates in the secondary and undetermined syphilis stages. As shown here, the nested PCR can improve diagnostics of syphilis, especially in seronegative patients and in patients with discrepant serology.

First cases of contagious ovine digital dermatitis in Germany.

Contagious ovine digital dermatitis (CODD) is a significant disease of the ovine foot characterised by severe lameness and progressive separation of the hoof horn capsule from the underlying tissue. Similar to bovine digital dermatitis (BDD), pathogenic members of the genus Treponema including the Treponema medium phylogroup, Treponema phagedenis phylogroup and Treponema pedis are frequently found together in CODD lesions. To date, CODD was only described in Ireland and the United Kingdom. In northern Germany, cases of an unusually severe lameness presented in a sheep flock that had been affected by footrot for several years. These cases were non-responsive to conventional footrot therapies, with some sheep exhibiting substantial lesions of the claw horn that resulted in horn detachment. Lesion swab samples were collected from both clinically affected and asymptomatic animals. In all clinically affected sheep, CODD-associated Treponema phylogroups were detected by polymerase chain reaction. This is the first report of CODD in Germany and mainland Europe, indicating a wider geographic spread than previously considered. In cases of severe lameness attributed to claw lesions in sheep that fail to respond to footrot treatment, CODD should be considered irrespective of geographic location.

Detection of Treponema spp. in bovine digital dermatitis in the Amazon biome, Brazil / Detecção de Treponema spp. em dermatite digital bovina no bioma amazônico, Brasil

Bovine digital dermatitis (BDD) is a polybacterial claw disease that is endemic to dairy cattle kept in loose house systems, and treponemas are the main bacteria implicated in this disease. The objective of this study was to report the occurrence of Treponema spp. in BDD from crossbred dairy cattle (Holstein x Zebu) kept in a pasture in the Brazilian Amazon biome. The diagnostic of BDD was performed by inspecting the distal extremities of cattle during milking in one or more visits comprising 15 farms. In total, it could be inspected 1,847 cows from August 2016 to July 2017, and 25 lesions of BDD were diagnosed. The feet were scored (System M: M0 = no lesion, M1 = ulcer stage <2cm, M2 = ulcer stage >2cm, M3 = healing stage, M4 = chronic stage, M4.1 = chronic stage with ulcer area). Twenty four biopsy samples were taken from feet with BDD and five biopsy samples from feet with no lesions. The histopathology of stained tissues was performed by hematoxylin and eosin and Warthin-Starry method. The samples were also tested by nested PCR for the three previously isolated BDD Treponema phylogroups (T. medium/T. vincentii-like, T. phagedenis-like and T. putidum/T. denticola-like). Spirochetes were observed in 54.2% (13/24) of the lesions, and in 91.7% (22/24) of the samples were detected the DNA of this spirochete belonging to the treponema phylogroups implicated in BDD. In 25% (6/24) of the lesions were detected all the phylogroups. Forty percent (40%, 2/5) of the M0 samples were also positive for the nested Polymerase Chain Reaction (nested-PCR), as 8.3% (2/24) of the lesions were negative in both techniques employed. Treponema putidum/T. denticola-like was the most detected bacterial in all the stages, and active lesions (M2 and M4.1) presented a greater proportion of T. medium/T. vincentii-like and T. phagedenis-like, but no statistical differences were observed (p>0.05). It could be concluded that BDD lesions in crossbred dairy cattle kept to pasture in the Amazon biome were classified as "polytreponemal" infections and the phylogroup T. putidum/T. denticola-like was the most frequent in the lesions.(AU)

Dermatite digital bovina (DDB) é uma enfermidade polibacteriana dos dígitos endêmica em vacas leiteiras criadas em estábulos e as treponemas são as principais bactérias envolvidas. Este estudo teve como objetivo relatar a ocorrência de Treponema spp. em DDB em bovinos leiteiros mestiços (Holandês x Zebu) criados a pasto no bioma amazônico brasileiro. O diagnóstico da DDB foi realizado pela inspeção, em uma ou mais visitas, das extremidades distais das vacas durante a ordenha em 15 propriedades. No total, foram inspecionadas 1.847 vacas de agosto de 2016 a julho de 2017 e diagnosticou-se 25 lesões de DDB. As extremidades distais inspecionadas foram classificadas em escores (M0 = sem lesão, M1 = estágio ulcerado <2cm, M2 = estágio ulcerado >2cm, M3 = estágio em cicatrização, M4 = estágio crônico, M4.1 = estágio crônico com área ulcerada) e realizada 24 biópsias de dígitos com DDB e cinco biópsias de dígitos em estágio M0. Foram realizadas a histopatologia pelas colorações de hematoxilina e eosina e pelo método de Warthin-Starry, e a nested de reação em cadeia de polimerase (nested-PCR) para os três filogrupos de treponemas previamente isolados de DDB (Treponema medium/T. vincentii-like, T. phagedenis-like e T. putidum/T. denticola-like). Espiroquetas foram observadas em 54,2% (13/24) das lesões e em 91,7% (22/24) detectou-se o DNA de, pelo menos, um dos filogrupos de treponemas pesquisados. Em 25% (6/24) das lesões foram detectados o DNA dos três filogrupos. Em 40% (2/5) das amostras em estágio M0 também foram positivas na nested-PCR, assim como 8,3% (2/24) das lesões foram negativas em ambas as técnicas empregadas. T. putidum/T. denticola-like foi o filogrupo mais detectado em todos os estágios e lesões ativas (M2 e M4.1) apresentaram uma maior proporção para Treponema medium/T. vincentii-like e T. phagedenis-like, mas não se obteve diferença estatística na ocorrência dos filogrupos entre os estágios das lesões (P>0,05). Conclui-se que lesões de DDB em rebanhos leiteiros mestiços criados a pasto no bioma amazônico brasileiro são "politreponemais" e o filogrupo T. putidum/T. denticola-like é o mais frequente nas lesões.(AU)

Origin and Health Status of First-Generation Africans from Early Colonial Mexico.

The forced relocation of several thousand Africans during Mexico's historic period has so far been documented mostly through archival sources, which provide only sparse detail on their origins and lived experience. Here, we employ a bioarchaeological approach to explore the life history of three 16th century Africans from a mass burial at the San José de los Naturales Royal Hospital in Mexico City. Our approach draws together ancient genomic data, osteological analysis, strontium isotope data from tooth enamel, δ13C and δ15N isotope data from dentine, and ethnohistorical information to reveal unprecedented detail on their origins and health. Analyses of skeletal features, radiogenic isotopes, and genetic data from uniparental, genome-wide, and human leukocyte antigen (HLA) markers are consistent with a Sub-Saharan African origin for all three individuals. Complete genomes of Treponema pallidum sub. pertenue (causative agent of yaws) and hepatitis B virus (HBV) recovered from these individuals provide insight into their health as related to infectious disease. Phylogenetic analysis of both pathogens reveals their close relationship to strains circulating in current West African populations, lending support to their origins in this region. The further relationship between the treponemal genome retrieved and a treponemal genome previously typed in an individual from Colonial Mexico highlights the role of the transatlantic slave trade in the introduction and dissemination of pathogens into the New World. Putting together all lines of evidence, we were able to create a biological portrait of three individuals whose life stories have long been silenced by disreputable historical events.

Treponema spp., the dominant pathogen in the lesion of bovine digital dermatitis and its characterization in dairy cattle.

This study examined the presence of Treponema in lesions using conventional PCR detection methods and investigated the microbiome by performing high-throughput DNA sequencing. Twenty-nine bovine digital dermatitis (BDD) lesions were collected from 25 dairy farms in South Korea that were tested by PCR amplification using sets of one universal, one genus-specific, and three species specific Treponema PCR primers. Three BDD samples were randomly selected and normal tissue samples were submitted for 16S rRNA sequencing using the Illumina MiSeq platform. The dominant phylum present in all tested BDD lesions was Spirochaetes with a mean relative abundance of 46.9 %, and Treponema was the most abundant genus. Spirochaetes abundance was followed by the phyla Tenericutes and Bacteroidetes with 14.1 % and 11.8 % mean abundances, respectively. Co-infecting bacteria from phyla Tenericutes and Bacteroidetes may be involved in the progression of BDD. Bovine digital dermatitis infection is polymicrobial in nature, but Treponema spp. are the main etiologic agents of the disease. In the microbiome results, Treponema pedis had the highest mean relative abundance (20.9 %) in the BDD lesions in this study followed by T. denticola, T. medium, T. lecithinolyricum, Spirochaeta africana, and Sediminispirochaeta bajacalifoniensis. All 29 samples were positive in the genus-specific Treponema PCR results. The species-specific PCR resulted in 75.9 %, 86.2 %, and 69.0 % of samples in groups T. medium/T. vincentii-like, T. phagedenis-like, and T. pedis, respectively. Understanding how these microorganisms mutually interact in the host during certain stages of infection may help in the development of better practices for controlling BDD.

Prevalence of sexually transmissible infections and HIV in men attending sex-on-premises venues in Australia: a systematic review and meta-analysis of observational studies.

Background In Australia, men who have sex with men (MSM) have high rates sexually transmissible infections (STIs) and sex-on-premises venue (SOPV) patrons are at risk. This paper assesses Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT), syphilis and HIV prevalence in men tested at Australian SOPVs and describes testing services. METHODS: EMBASE, Medline, PubMed and international conference proceedings were searched for articles reporting on-site SOPV testing between 1 January 2000 and 31 January 2017. Meta-analysis calculated pooled prevalence estimates of STIs by anatomical site. RESULTS: Twelve cross-sectional studies were identified. Most (8/12) were local sexual health clinics (SHC) outreach services. Participants' mean age was 41.1 years (95% confidence interval (CI) 37.0-43.3; range 17 to 84 years). Testing included CT and NG (9/12), HIV (8/12) and syphilis (5/12). CT and NG prevalence overall summary estimates were 3.4% (95% CI 1.9-5.2%, I2 = 88.7%, P < 0.01) and 1.3% (95% CI 0.7-2.2%, I2 = 75.5%, P < 0.01) respectively. CT and NG prevalence was highest in the ano-rectum and oro-pharynx respectively. The HIV and syphilis pooled estimates were 2.3% (95% CI 1.6-2.9%, I2 = 93.1%, P < 0.01) and 3.2% (95% CI 1.8-4.6%, I2 = 72.8%, P < 0.01) respectively. Participation rate varied. CONCLUSION: This review examines HIV and STI testing in Australian SOPVs before HIV pre-exposure prophylaxis (PrEP). Findings indicate a high prevalence of STIs. PrEP use and resultant condomless sex may influence STI prevalence. Further research is required to determine the effect of PrEP on the STI prevalence among SOPV patrons.

Comparative genomics and full-length Tprk profiling of Treponema pallidum subsp. pallidum reinfection.

Developing a vaccine against Treponema pallidum subspecies pallidum, the causative agent of syphilis, remains a public health priority. Syphilis vaccine design efforts have been complicated by lack of an in vitro T. pallidum culture system, prolific antigenic variation in outer membrane protein TprK, and lack of functional annotation for nearly half of the genes. Understanding the genetic basis of T. pallidum reinfection can provide insights into variation among strains that escape cross-protective immunity. Here, we present comparative genomic sequencing and deep, full-length tprK profiling of two T. pallidum isolates from blood from the same patient that were collected six years apart. Notably, this patient was diagnosed with syphilis four times, with two of these episodes meeting the definition of neurosyphilis, during this interval. Outside of the highly variable tprK gene, we identified 14 coding changes in 13 genes. Nine of these genes putatively localized to the periplasmic or outer membrane spaces, consistent with a potential role in serological immunoevasion. Using a newly developed full-length tprK deep sequencing protocol, we profiled the diversity of this gene that far outpaces the rest of the genome. Intriguingly, we found that the reinfecting isolate demonstrated less diversity across each tprK variable region compared to the isolate from the first infection. Notably, the two isolates did not share any full-length TprK sequences. Our results are consistent with an immunodominant-evasion model in which the diversity of TprK explains the ability of T. pallidum to successfully reinfect individuals, even when they have been infected with the organism multiple times.

Treponema phagedenis (ex Noguchi 1912) Brumpt 1922 sp. nov., nom. rev., isolated from bovine digital dermatitis.

'Treponema phagedenis' was originally described in 1912 by Noguchi but the name was not validly published and no type strain was designated. The taxon was not included in the Approved Lists of Bacterial Names and hence has no standing in nomenclature. Six Treponema strains positive in a 'T. phagedenis' phylogroup-specific PCR test were isolated from digital dermatitis (DD) lesions of cattle and further characterized and compared with the human strain 'T. phagedenis' ATCC 27087. Results of phenotypic and genotypic analyses including API ZYM, VITEK2, MALDI-TOF and electron microscopy, as well as whole genome sequence data, respectively, showed that they form a cluster of species identity. Moreover, this species identity was shared with 'T. phagedenis'-like strains reported in the literature to be regularly isolated from bovine DD. High average nucleotide identity values between the genomes of bovine and human 'T. phagedenis' were observed. Slight genomic as well as phenotypic variations allowed us to differentiate bovine from human isolates, indicating host adaptation. Based on the fact that this species is regularly isolated from bovine DD and that the name is well dispersed in the literature, we propose the species Treponema phagedenis sp. nov., nom. rev. The species can phenotypically and genetically be identified and is clearly separated from other Treponema species. The valid species designation will allow to further explore its role in bovine DD. The type strain for Treponema phagedenis sp. nov., nom. rev. is B43.1T (=DSM 110455T=NCTC 14362T) isolated from a bovine DD lesion in Switzerland.

Yaws in the Philippines: first reported cases since the 1970s.

BACKGROUND: Yaws is a chronic, highly contagious skin and bone infection affecting children living in impoverished, remote communities and caused by Treponema pallidum subspecies pertenue. The Philippines was thought to be free of yaws following the 1950s eradication campaign but it has been reported in the Liguasan Marsh area, Central Mindanao. This is the first documentation of yaws cases in the Philippines since the 1970s. We describe active and latent yaws recently detected in the Southern Philippines. CASE PRESENTATION: Cross-sectional surveys and screening of skin diseases were conducted in one randomly selected public elementary school per selected municipality in Liguasan Marsh, covering three municipalities per province. Yaws suspects underwent screening and confirmatory serologic tests for Treponema pallidum using Dual Path Platform Syphilis Screen and Confirm Assay (DPP) and Treponema pallidum Particle Agglutination (TPPA). Children with yaws skin lesions and reactive confirmatory tests for T. pallidum and non-treponemal antibodies were considered confirmed yaws cases. Four children aged 5-10 years old had confirmed secondary yaws in Tulunan Municipality, Cotabato Province and in Lambayong Municipality, Sultan Kudarat Province. All had secondary yaws lesions such as moist, cauliflower-like papillomas, thick yellow crusts on pink papules and nodules, whitish, papulosquamous papules and plaques, or hypopigmented patches with small papules on the periphery. Yaws papillomas and erosions were also found on the soles of the feet of one child. The index case had a skin punch biopsy of a partially treated papilloma on his axilla. Histopathological findings showed lichenoid psoriasiform dermatitis with plasma cells, consistent with yaws. CONCLUSIONS: The clinical, serological, and histopathological confirmation of four yaws cases among children has made the Philippines the 14th country endemic for yaws. This report can help health personnel recognize hidden cases of yaws based on skin signs and serological tests. Yaws remained unrecognized and unreported in the Philippines and in countries previously endemic for yaws probably due to the unsustained integration of the yaws program in the general health services and complacency after the 1950s eradication campaign. Our findings have provided the necessary evidence and stimulus to develop a yaws control and eradication program as one of the country's neglected tropical diseases.

Molecular detection of Treponema species organisms in foremilk and udder cleft skin of dairy cows with digital dermatitis.

Identification of reservoirs and transmission routes of digital dermatitis (DD)-associated Treponema spp. is considered an effective means for controlling DD infection in dairy cows. The objective of this study is to identify and characterize the potential reservoir niches for DD-associated Treponema spp. from healthy udder cleft skin and foremilk in lactating dairy cows. A large dairy farm was visited weekly from March to July 2015. Clinical investigation revealed that a total of 25 lame cows had DD lesions located at the plantar aspect of the interdigital cleft. A total of 75 samples, three per cow, were collected including deep swabs from DD lesions (n = 25), non-aseptically collected foremilk samples (n = 25) and skin swabs from udder cleft (n = 25). Treponema spp. were identified using nested PCR assays and confirmed by DNA sequencing. Results revealed that Treponema phagedenis (T. phagedenis)-like was the most identified species in the foremilk 40% (10/25), in comparison with DD lesions and udder cleft skin samples with 32% (8/25) and 20% (5/25), respectively. On the other hand, Treponema pedis (T. pedis) was the most identified species in the udder cleft skin 80% (20/25), in comparison with DD lesions and foremilk samples with 68% (17/25) and 60% (15/25), respectively. None of the examined samples were identified by PCR as containing DNA from Treponema medium (T. medium) or Treponema vincentii (T. vincentii)-like. To the best of our knowledge, this is the first report for detection of T. phagedenis-like and T. pedis from healthy skin of udder cleft and foremilk samples. Detection of DD Treponema spp. from udder cleft skin and foremilk samples indicates that these sites could be potential reservoirs for spirochetes involved in DD. Udder cleft skin and foremilk may have a role in transmission routes of DD Treponema in dairy farms.

Measuring the subgingival microbiota in periodontitis patients: Comparison of the surface layer and the underlying layers.

Periodontitis is a major cause of tooth loss in adults that initially results from dental plaque. Subgingival plaque pathogenesis is affected by both community composition and plaque structures, although limited data are available concerning the latter. To bridge this knowledge gap, subgingival plaques were obtained using filter paper (the fourth layer) and curette (the first-third layers) sequentially and the phylogenetic differences between the first-third layers and the fourth layer were characterized by sequencing the V3-V4 regions of 16S rRNA. A total of 11 phyla, 148 genera, and 308 species were obtained by bioinformatic analysis, and no significant differences between the operational taxonomic unit numbers were observed for these groups. In both groups, the most abundant species were Porphyromonas gingivalis and Fusobacterium nucleatum. Actinomyces naeslundii, Streptococcus intermedius, and Prevotella intermedia possessed relatively high proportions in the first-third layers; while in the fourth layer, both traditional pathogens (Treponema denticola and Campylobacter rectus) and novel pathobionts (Eubacterium saphenum, Filifactor alocis, Treponema sp. HOT238) were prominent. Network analysis showed that either of them exhibited a scale-free property and was constructed by two negatively correlated components (the pathogen component and the nonpathogen component), while the synergy in the nonpathogen component was lower in the first-third layers than that in the fourth layer. After merging these two parts into a whole plaque group, the negative/positive correlation ratio increased. With potential connections, the first-third layers and the fourth layer showed characteristic key nodes in bacterial networks.

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.

Treponeme-Associated Hoof Disease of Free-Ranging Elk ( Cervus elaphus) in Southwestern Washington State, USA.

A novel foot disease in free-ranging elk ( Cervus elaphus) in southwestern Washington State emerged in 2008 and spread throughout the region. Initial studies showed adult elk had chronic hoof overgrowth, sole ulcers, and sloughed hoof capsules, but no cause was determined. To identify possible causes and characterize the earliest lesions, 9-, 7-, and 3-month-old elk were collected. Nine-month-old elk had sole ulcers (3/9 elk) and sloughed/overgrown hoof capsules (4/9 elk) similar to adults. Histologically, lesions consisted of coronary, heel bulb, and interdigital ulcers with suppurative inflammation, epithelial hyperplasia, deeply invasive spirochetes, and underrunning of the hoof capsule and heel-sole junction. Spirochetes were identified as Treponema via immunohistochemistry and polymerase chain reaction (PCR). Seven-month-old elk had similar underrunning foot ulcers (6/8 elk) with Treponema identified in all lesions but no chronic overgrowth or sloughed hoof capsules. Three-month-old calves had superficial coronary erosions with no inflammation or identifiable spirochetes (3/5 elk) but were culture/PCR positive for Treponema, suggesting possible early lesions. Lesions from 9- and 7-month-old elk included aerobic and anaerobic bacteria, many of which are associated with infectious foot disease in livestock. Antibody enzyme-linked immunosorbent assay of 7- and 3-month-old elk from the enzootic region showed a trend toward increased Treponema antibody titers compared to normal control elk from outside the region, further supporting the significance of Treponema in the pathogenesis of foot disease. Treponeme-associated hoof disease (TAHD) in elk, a debilitating and progressive condition, shares similarities to bovine digital dermatitis and contagious ovine digital dermatitis.