Rapid Serologic Test for Diagnosis of Yaws in Patients with Suspicious Skin Ulcers.

The Chembio DPP (Dual Path Platform) Syphilis Screen & Confirm kit (https://chembio.com) is a rapid serologic test that can be used to diagnose yaws. We evaluated its capacity to detect patients with ulcers that tested PCR positive for Treponema pallidum subsp. pertenue. DPP detected 84% of ulcers that were positive by PCR.

Epidemiologic and Genomic Reidentification of Yaws, Liberia.

We confirmed endemicity and autochthonous transmission of yaws in Liberia after a population-based, community-led burden estimation (56,825 participants). Serologically confirmed yaws was rare and focal at population level (24 cases; 2.6 [95% CI 1.4-3.9] cases/10,000 population) with similar clinical epidemiology to other endemic countries in West Africa. Unsupervised classification of spatially referenced case finding data indicated that yaws was more likely to occur in hard-to-reach communities; healthcare-seeking was low among communities, and clinical awareness of yaws was low among healthcare workers. We recovered whole bacterial genomes from 12 cases and describe a monophyletic clade of Treponema pallidum subspecies pertenue, phylogenetically distinct from known TPE lineages, including those affecting neighboring nonhuman primate populations (Taï Forest, Côte d'Ivoire). Yaws is endemic in Liberia but exhibits low focal population prevalence with evidence of a historical genetic bottleneck and subsequent local expansion. Reporting gaps appear attributable to challenging epidemiology and low disease awareness.

Yaws Disease Caused by Treponema pallidum subspecies pertenue in Wild Chimpanzee, Guinea, 2019.

Yaws-like lesions are widely reported in wild African great apes, yet the causative agent has not been confirmed in affected animals. We describe yaws-like lesions in a wild chimpanzee in Guinea for which we demonstrate infection with Treponema pallidum subsp. pertenue. Assessing the conservation implications of this pathogen requires further research.

Modeling Treatment Strategies to Inform Yaws Eradication.

Yaws is a neglected tropical disease targeted for eradication by 2030. To achieve eradication, finding and treating asymptomatic infections as well as clinical cases is crucial. The proposed plan, the Morges strategy, involves rounds of total community treatment (i.e., treating the whole population) and total targeted treatment (TTT) (i.e., treating clinical cases and contacts). However, modeling and empirical work suggests asymptomatic infections often are not found in the same households as clinical cases, reducing the utility of household-based contact tracing for a TTT strategy. We use a model fitted to data from the Solomon Islands to predict the likelihood of elimination of transmission under different intervention schemes and levels of systematic nontreatment resulting from the intervention. Our results indicate that implementing additional treatment rounds through total community treatment is more effective than conducting additional rounds of treatment of at-risk persons through TTT.

Serosurvey of Treponema pallidum infection among children with skin ulcers in the Tarangire-Manyara ecosystem, northern Tanzania.

BACKGROUND: The first yaws eradication campaign reduced the prevalence of yaws by 95%. In recent years, however, yaws has reemerged and is currently subject to a second, ongoing eradication campaign. Yet, the epidemiological status of Tanzania and 75 other countries with a known history of human yaws is currently unknown. Contrary to the situation in humans in Tanzania, recent infection of nonhuman primates (NHPs) with the yaws bacterium Treponema pallidum subsp. pertenue (TPE) have been reported. In this study, we consider a One Health approach to investigate yaws and describe skin ulcers and corresponding T. pallidum serology results among children living in the Tarangire-Manyara ecosystem, an area with increasing wildlife-human interaction in northern Tanzania. METHODS: To investigate human yaws in Tanzania, we conducted a cross-sectional study to screen and interview skin-ulcerated children aged 6 to 15 years, who live in close proximity to two national parks with high numbers of naturally TPE-infected monkeys. Serum samples from children with skin ulcers were tested for antibodies against the bacterium using a treponemal (Treponema pallidum Particle Agglutination assay) and a non-treponemal (Rapid Plasma Reagin) test. RESULTS: A total of 186 children aged between 6 and 15 years (boys: 10.7 ± 2.1 (mean ± SD), N = 132; girls: 10.9 ± 2.0 (mean ± SD), N = 54) were enrolled. Seven children were sampled at health care facilities and 179 at primary schools. 38 children (20.4%) reported active participation in bushmeat hunting and consumption and 26 (13.9%) reported at least one physical contact with a NHP. None of the lesions seen were pathognomonic for yaws. Two children tested positive for treponemal antibodies (1.2%) in the treponemal test, but remained negative in the non-treponemal test. CONCLUSIONS: We found no serological evidence of yaws among children in the Tarangire-Manyara ecosystem. Nevertheless, the close genetic relationship of human and NHPs infecting TPE strains should lead to contact prevention with infected NHPs. Further research investigations are warranted to study the causes and possible prevention measures of spontaneous chronic ulcers among children in rural Tanzania and to certify that the country is free from human yaws.

Survey of Treponemal Infections in Free-Ranging and Captive Macaques, 1999-2012.

Survey results showed treponemal infection among pet macaques in Southeast Asia, a region with a high prevalence of human yaws. This finding, along with studies showing treponemal infection in nonhuman primates in Africa, should encourage a One Health approach to yaws eradication and surveillance activities, possibly including monitoring of nonhuman primates in yaws-endemic regions.

Coinfection of a yaws patient with two closely related Treponema pallidum subsp. pertenue strains: A rare event with potential evolutionary implications.

The etiological agent of yaws is the spirochete Treponema pallidum (TP) subsp. pertenue (TPE) and infects the children of Papua New Guinea, causing ulcerative skin lesions that impairs normal growth and development. Closely related strains of Treponema pallidum subsp. pertenue, JE11, and TE13 were detected in an ulcer biospecimen derived from a 5-year-old yaws patient. Cloning experiments validated the presence of two distinct but similar genotypes, namely TE13 and JE11, co-occurring within a single host. While coinfection with highly related TPE strains has only limited epidemiological and clinical relevance, this is the first documented coinfection with genetically distinct TP strains in a single patient. Similar coinfections in the past were explained by the existence of over a dozen recombinant loci present in the TP genomes as a result of inter-strain or inter-subspecies recombination events following an anticipated scenario of TP coinfection, i.e., uptake of foreign DNA and DNA recombination.

Streptococcus pyogenes Is Associated with Idiopathic Cutaneous Ulcers in Children on a Yaws-Endemic Island.

Exudative cutaneous ulcers (CU) in yaws-endemic areas are associated with Treponema pallidum subsp. pertenue (TP) and Haemophilus ducreyi (HD), but one-third of CU cases are idiopathic (IU). Using mass drug administration (MDA) of azithromycin, a yaws eradication campaign on Lihir Island in Papua New Guinea reduced but failed to eradicate yaws; IU rates remained constant throughout the campaign. To identify potential etiologies of IU, we obtained swabs of CU lesions (n = 279) and of the skin of asymptomatic controls (AC; n = 233) from the Lihir Island cohort and characterized their microbiomes using a metagenomics approach. CU bacterial communities were less diverse than those of the AC. Using real-time multiplex PCR with pathogen-specific primers, we separated CU specimens into HD-positive (HD+), TP+, HD+TP+, and IU groups. Each CU subgroup formed a distinct bacterial community, defined by the species detected and/or the relative abundances of species within each group. Streptococcus pyogenes was the most abundant organism in IU (22.65%) and was enriched in IU compared to other ulcer groups. Follow-up samples (n = 31) were obtained from nonhealed ulcers; the average relative abundance of S. pyogenes was 30.11% in not improved ulcers and 0.88% in improved ulcers, suggesting that S. pyogenes in the not improved ulcers may be azithromycin resistant. Catonella morbi was enriched in IU that lacked S. pyogenes As some S. pyogenes and TP strains are macrolide resistant, penicillin may be the drug of choice for CU azithromycin treatment failures. Our study will aid in the design of diagnostic tests and selective therapies for CU.IMPORTANCE Cutaneous ulcers (CU) affect approximately 100,000 children in the tropics each year. While two-thirds of CU are caused by Treponema pallidum subspecies pertenue and Haemophilus ducreyi, the cause(s) of the remaining one-third is unknown. Given the failure of mass drug administration of azithromycin to eradicate CU, the World Health Organization recently proposed an integrated disease management strategy to control CU. Success of this strategy requires determining the unknown cause(s) of CU. By using 16S rRNA gene sequencing of swabs obtained from CU and the skin of asymptomatic children, we identified another possible cause of skin ulcers, Streptococcus pyogenes Although S. pyogenes is known to cause impetigo and cellulitis, this is the first report implicating the organism as a causal agent of CU. Inclusion of S. pyogenes into the integrated disease management plan will improve diagnostic testing and treatment of this painful and debilitating disease of children and strengthen elimination efforts.

Optimising the use of molecular tools for the diagnosis of yaws.

BACKGROUND: Yaws is a neglected tropical disease and results in lesions of skin, soft tissues and bones. PCR plays an important part in surveillance. METHODS: Children suspected to have yaws were enrolled. From the largest lesion, paired swabs were collected, one in transport medium and one as a dry swab. In children with multiple lesions we collected additional swabs from up to four subsequent lesions. Swabs in transport medium were maintained in a cold chain while dry swabs were stored at ambient temperature. Swabs were tested by PCR for Treponema pallidum and Haemophilus ducreyi. RESULTS: Of 55 individuals, 10 (18%) had at least one positive PCR for T. pallidum and 12 (22%) had at least one positive result for H. ducreyi. Concordance was 100% between swabs in transport medium and dry swabs. One patient had PCR-confirmed yaws on the swab of a third lesion when both the first and second lesions were PCR-negative. CONCLUSIONS: Storing swabs in transport medium and transporting in a cold chain did not improve yield, however, detection of T. pallidum is increased by swabbing additional lesions. As the target for yaws is eradication, approaches to sample collection need revisiting to ensure cases are not missed.

Genetics of human and animal uncultivable treponemal pathogens.

Treponema pallidum is an uncultivable bacterium and the causative agent of syphilis (subsp. pallidum [TPA]), human yaws (subsp. pertenue [TPE]), and bejel (subsp. endemicum). Several species of nonhuman primates in Africa are infected by treponemes genetically undistinguishable from known human TPE strains. Besides Treponema pallidum, the equally uncultivable Treponema carateum causes pinta in humans. In lagomorphs, Treponema paraluisleporidarum ecovar Cuniculus and ecovar Lepus are the causative agents of rabbit and hare syphilis, respectively. All uncultivable pathogenic treponemes harbor a relatively small chromosome (1.1334-1.1405 Mbp) and show gene synteny with minimal genetic differences (>98% identity at the DNA level) between subspecies and species. While uncultivable pathogenic treponemes contain a highly conserved core genome, there are a number of highly variable and/or recombinant chromosomal loci. This is also reflected in the occurrence of intrastrain heterogeneity (genetic diversity within an infecting bacterial population). Molecular differences at several different chromosomal loci identified among TPA strains or isolates have been used for molecular typing and the epidemiological characterization of syphilis isolates. This review summarizes genome structure of uncultivable pathogenic treponemes including genetically variable regions.

Yaws.

Yaws is a non-venereal endemic treponemal infection caused by Treponema pallidum sub-species pertenue, a spirochaete bacterium closely related to Treponema pallidum ssp. pallidum, the agent of venereal syphilis. Yaws is a chronic, relapsing disease predominantly affecting children living in certain tropical regions. It spreads by skin-to-skin contact and, like syphilis, occurs in distinct clinical stages. It causes lesions of the skin, mucous membranes and bones which, without treatment, can become chronic and destructive. Treponema pallidum ssp. pertenue, like its sexually-transmitted counterpart, is exquisitely sensitive to penicillin. Infection with yaws or syphilis results in reactive treponemal serology and there is no widely available test to distinguish between these infections. Thus, migration of people from yaws-endemic areas to developed countries may present clinicians with diagnostic dilemmas. We review the epidemiology, clinical presentation and treatment of yaws.

Epidemiology of yaws: an update.

Yaws, a neglected tropical disease, is targeted for eradication by 2020 through large-scale mass-treatment programs of endemic communities. A key determinant for the success of the eradication campaign is good understanding of the disease epidemiology. We did a review of historical trends and new information from endemic countries, with the aim of assessing the state of knowledge on yaws disease burden. Transmission of yaws is now present in Africa, Asia, and the South Pacific. At least 12 countries are known to harbor yaws cases and 21 to 42 million people live in endemic areas. Between 2008 and 2012 more than 300,000 new cases were reported to the World Health Organization. Yaws presented high geographical variation within a country or region, high seasonality for incidence of active disease, and evidence that low standards of hygiene predispose to suffering of the disease. Key data issues include low levels of reporting, potential misdiagnosis, and scarce documentation on prevalence of asymptomatic infections. Currently available data most likely underestimates the magnitude of the disease burden. More effort is needed in order to refine accuracy of data currently being reported. A better characterization of the epidemiology of yaws globally is likely to positively impact on planning and implementation of yaws eradication.