Low genetic diversity of Treponema pallidum ssp. pertenue (TPE) isolated from patients' ulcers in Namatanai District of Papua New Guinea: Local human population is infected by three TPE genotypes.

Yaws is an endemic disease caused by Treponema pallidum subsp. pertenue (TPE) that primarily affects children in rural regions of the tropics. The endemic character of yaws infections and the expected exclusive reservoir of TPE in humans opened a new opportunity to start a yaws eradication campaign. We have developed a multi-locus sequence typing (MLST) scheme for TPE isolates combining the previously published (TP0548, TP0488) and new (TP0858) chromosomal loci, and we compared this typing scheme to the two previously published MLST schemes. We applied this scheme to TPE-containing clinical isolates obtained during a mass drug administration study performed in the Namatanai District of Papua New Guinea between June 2018 and December 2019. Of 1081 samples collected, 302 (28.5%) tested positive for TPE DNA, from which 255 (84.4%) were fully typed. The TPE PCR-positivity in swab samples was higher in younger patients, patients with single ulcers, first ulcer episodes, and with ulcer duration less than six months. Non-treponemal serological test positivity correlated better with PCR positivity compared to treponema-specific serological tests. The MLST revealed a low level of genetic diversity among infecting TPE isolates, represented by just three distinct genotypes (JE11, SE22, and TE13). Two previously used typing schemes revealed similar typing resolutions. Two new alleles (one in TP0858 and one in TP0136) were shown to arise by intragenomic recombination/deletion events. Compared to samples genotyped as JE11, the minor genotypes (TE13 and SE22) were more frequently detected in samples from patients with two or more ulcers and patients with higher values of specific TP serological tests. Moreover, the A2058G mutation in the 23S rRNA genes of three JE11 isolates was found, resulting in azithromycin resistance.

Is there still yaws in Nigeria? Active case search in endemic areas of southern Nigeria.

BACKGROUND: Yaws is a disease caused by the bacteria Treponema pallidum subspecies pertenue, which is most commonly seen among children below 15 years. In the twentieth century yaws was endemic in Nigeria but eradication strategies markedly reduced the disease burden. Currently there is minimal data on the ongoing transmission of yaws in Nigeria, despite reports of confirmed yaws cases in neighbouring West African countries. METHODS: We conducted both community and school-based active yaws case search among school-aged children in southeast Nigeria. Children were screened by trained community volunteers. Suspected yaws cases were clinically reviewed and tested using rapid diagnostic serological tests. RESULTS: Between February and May 2021, up to 28 trained community volunteers screened a total of 105,015 school children for yaws. Overall, 7,706 children with various skin lesions were identified. Eight (8) suspected cases of yaws were reported, reviewed and screened, but none was confirmed using rapid diagnostic tests. The four most common skin conditions identified were scabies (39%), papular urticaria (29%), tinea corporis (14%) and tinea capitis (12%). CONCLUSIONS: No case of yaws was confirmed in this large population of children in south-east Nigeria. Continuous community awareness and yaws case finding activities have been recommended across Nigeria.

Prospecting for yaws in the Mbaïki Health District in the Central African Republic.

Introduction: yaws is endemic in the Central African Republic. The last cases of yaws notified by CAR to WHO date back to 2012. The objective of this study was to measure the prevalence of yaws in the health district of Mbaïki and to describe its clinical and epidemiological characteristics. Methods: this is a descriptive cross-sectional study, conducted from April 10 to 18, 2020 in the Mbaïki health district. Yaws cases were sought in 570 households in the 38 selected villages of the district. Any consenting individual over the age of one year with yaws-like skin lesions was a suspected case of yaws and included in the study. Blood was taken from suspected cases for serological testing (TDR, RPR and TPHA). Any suspected case of yaws with positive RPR and TPHA was considered a confirmed case. Results: a total of 1967 people were examined, of whom 113 were considered suspected cases of yaws. All suspected cases were RPR-positive, 41 TPHA-positive and 13 RDT-positive. Forty-one cases of yaws were confirmed in 18 (47.37%) villages. The prevalence of yaws in the Mbaïki health district was 2.08%. Among the cases, 38.94% were children aged 1 to 14. The sex ratio was 1.69. Lesions clinically suggestive of yaws were papilloma-like in 77.00% of cases, followed by micropapules (8.00%) and ulcerations (5.00%). Conclusion: eight of the nine communes in the Mbaïki health district are yaws-endemic. This result suggests the need to implement the Morges strategy in the Mbaïki health district.

Endemic infectious cutaneous ulcers syndrome in the Oti Region of Ghana: Study of cutaneous leishmaniasis, yaws and Haemophilus ducreyi cutaneous ulcers.

BACKGROUND: A recent study detected cutaneous leishmaniasis (CL) in 31.9% of persons with skin ulcers in the Oti Region of Ghana, resulting in a need to investigate other potential causes of the unexplained skin ulcers. METHODOLOGY/PRINCIPAL FINDINGS: A community based cross-sectional study was conducted in the Oti region to investigate skin ulcers of undetermined aetiologies. To confirm a diagnosis of cutaneous leishmaniasis, Buruli ulcer, Haemophilus ducreyi ulcers, or yaws, DNA obtained from each patient skin ulcer sample was systematically subjected to polymerase chain reaction (PCR) for Leishmania spp., Mycobacterium ulcerans, Haemophilus ducreyi, and Treponema pallidum sub species pertenue. A total of 101 skin ulcer samples were obtained from 101 persons. Co-infection of more than one organism was observed in 68.3% of the samples. Forty (39.6%) participants had a positive result for Leishmania spp., 68 (67.3%) for Treponema pallidum sub. Sp. pertenue, and 74 (73.3%) for H. ducreyi. Twenty (19.8%) of the patient ulcers were simultaneously infected with Leishmania spp., Treponema pallidum sub. Sp. pertenue, and H. ducreyi. None of the patients' lesions yielded a positive result for Mycobacterium ulcerans. CONCLUSIONS/SIGNIFICANCE: This study detected single and mixed occurrence of the causative organisms of CL, yaws, and H. ducreyi cutaneous ulcers in CL endemic communities of the Oti Region in Ghana. These findings emphasize the importance of integrating multiple skin diseases on a common research platform and calls for the development of a comprehensive guideline for diagnosing and treating tropical ulcers in the study areas.

The genomes of the yaws bacterium, Treponema pallidum subsp. pertenue, of nonhuman primate and human origin are not genomically distinct.

BACKGROUND: Treponema pallidum subsp. pertenue (TPE) is the causative agent of human yaws. Yaws is currently reported in 13 endemic countries in Africa, southern Asia, and the Pacific region. During the mid-20th century, a first yaws eradication effort resulted in a global 95% drop in yaws prevalence. The lack of continued surveillance has led to the resurgence of yaws. The disease was believed to have no animal reservoirs, which supported the development of a currently ongoing second yaws eradication campaign. Concomitantly, genetic evidence started to show that TPE strains naturally infect nonhuman primates (NHPs) in sub-Saharan Africa. In our current study we tested hypothesis that NHP- and human-infecting TPE strains differ in the previously unknown parts of the genomes. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we determined complete (finished) genomes of ten TPE isolates that originated from NHPs and compared them to TPE whole-genome sequences from human yaws patients. We performed an in-depth analysis of TPE genomes to determine if any consistent genomic differences are present between TPE genomes of human and NHP origin. We were able to resolve previously undetermined TPE chromosomal regions (sequencing gaps) that prevented us from making a conclusion regarding the sequence identity of TPE genomes from NHPs and humans. The comparison among finished genome sequences revealed no consistent differences between human and NHP TPE genomes. CONCLUSION/SIGNIFICANCE: Our data show that NHPs are infected with strains that are not only similar to the strains infecting humans but are genomically indistinguishable from them. Although interspecies transmission in NHPs is a rare event and evidence for current spillover events is missing, the existence of the yaws bacterium in NHPs is demonstrated. While the low risk of spillover supports the current yaws treatment campaign, it is of importance to continue yaws surveillance in areas where NHPs are naturally infected with TPE even if yaws is successfully eliminated in humans.

Treponemal Antibody Seroprevalence Using a Multiplex Bead Assay from Samples Collected during the 2018 Nigeria HIV/AIDS Indicator and Impact Survey: Searching for Yaws in Nigeria.

Yaws is a chronic, relapsing disease of skin, bone, and cartilage caused by Treponema pallidum subsp. pertenue. Yaws was last reported in Nigeria in 1996, although neighboring countries have recently reported cases. We investigated serological evidence for yaws among children aged 0-14 years in Nigeria by measuring antibodies to the treponemal antigens rp17 and TmpA in blood specimens from a 2018 nationally representative HIV survey using a multiplex bead assay. The presence of antibodies to both antigens ("double positive") likely reflects current or recent treponemal infection. Overall, 1.9% (610/31,549) of children had anti-TmpA antibodies, 1.5% (476/31,549) had anti-rp17 antibodies, and 0.1% (39/31,549) were double positive. Among households, 0.5% (84/18,021) had a double-positive child, with a clustering of double-positive children. Although numbers are low, identification of antibodies to both TmpA and rp17 may warrant investigation, including more granular epidemiologic and clinical data, to assess the potential for continuing yaws transmission in Nigerian children.

No evidence for yaws infection in a small-scale cross-sectional serosurvey in Ghanaian monkeys.

BACKGROUND: Treponema pallidum (TP) is a spirochaete bacterium with subspecies that in humans cause syphilis (subsp. pallidum), bejel (subsp. endemicum) and yaws (subsp. pertenue; TPE). The latter is target for eradication which requires detailed information on yaws epidemiology. It has been shown that African nonhuman primates (NHPs) are infected with TPE strains that are closely related to the human infecting yaws bacterium. While human yaws infection is known to be endemic in Ghana, there is a paucity of information regarding TPE infection of Ghana's native NHPs. OBJECTIVES: The objective was to perform a small-scale cross-sectional serological screening for antibodies against TPE in Ghanaian monkeys. Due to the reports of TPE-infected NHPs from neighbouring Côte d'Ivore, we hypothesised that monkeys in Ghana are infected with TPE and, therefore, are seropositive for antibodies against-Treponema. METHODS: We sampled blood from 37 NHPs representing four species: Erythrocebus patas (16/37) 43.2%, Papio anubis (15/37) 40.5%, Chlorocebus sabaeus (3/37) 8.1% and Cercopithecus mona (3/37) 8.1%. Samples were tested using the NHP validated treponemal test ESPLINE TP. RESULTS: All 37 animals were seronegative for yaws infection. CONCLUSIONS: We cannot exclude yaws infection in NHPs in Ghana at this point. Our study, in combination with the absence of reports of clinically infected NHPs in a yaws endemic country is, however, supportive for the current thinking that interspecies infection with TPE is extremely rare. This is an important finding for the current ongoing yaws eradication campaign.

Finding Yaws among Indigenous People: Lessons from Case Detection Surveys in Luzon and Visayas Island Groups of the Philippines.

Yaws is a chronic, highly contagious skin and bone infection caused by Treponema pallidum subspecies pertenue, usually affecting children in impoverished and remote communities. Yaws lesions have thick yellow crusts on pink papillomas that ulcerate and leave deep scars. Yaws cases were confirmed in the Liguasan Marsh, Mindanao Island group, Southern Philippines, in 2017, but there were no cases confirmed in the Luzon and Visayas Island groups. We aimed to detect at least one active or latent yaws case in the island groups of Luzon and Visayas. Active yaws surveillance was conducted by inviting healthcare providers to report yaws suspects. Five remote villages were included in the case detection surveys: three in Luzon and two in the Visayas Island groups. Two indigenous peoples communities were included: Aetas of Quezon and Dumagat/Remontados of Rizal provinces. Trained field personnel conducted free skin check-ups of children, household contacts, and community members. Yaws suspects underwent point-of-care serologic tests for T. pallidum and nontreponemal antibodies. A total of 239 participants were screened for skin diseases, and 103 had serologic tests. Only the Aetas of Quezon province, Luzon, had confirmed yaws cases. Nineteen cases (54.3%) were detected among 35 Aetas: five active yaws (four children, one adult), two latent yaws (adults), and 12 past yaws (1 child, 11 adults). An 8-year-old boy had yaws with skeletal deformities. We report the first yaws cases among the Aetas of Quezon, Luzon Island group. Active yaws surveillance and case detection in remote areas and among indigenous peoples should continue.

Mathematical modelling Treponema infection in free-ranging Olive baboons (Papio anubis) in Tanzania.

Yaws is a chronic infection caused by the bacterium Treponema pallidum susp. pertenue (TPE) that was thought to be an exclusive human pathogen but was recently found and confirmed in nonhuman primates. In this paper, we develop the first compartmental ODE model for TPE infection with treatment of wild olive baboons. We solve for disease-free and endemic equilibria and give conditions on local and global stability of the disease-free equilibrium. We calibrate the model based on the data from Lake Manyara National Park in Tanzania. We use the model to help the park managers devise an effective strategy for treatment. We show that an increasing treatment rate yields a decrease in disease prevalence. This indicates that TPE can be eliminated through intense management in closed population. Specifically, we show that if the whole population is treated at least once every 5-6 years, a disease-free equilibrium can be reached. Furthermore, we demonstrate that to see a substantial decrease of TPE infection to near-elimination levels within 15 years, the whole population needs to be treated every 2-3 years.

Yaws elimination in Ecuador: Findings of a serological survey of children in Esmeraldas province to evaluate interruption of transmission.

BACKGROUND: The WHO roadmap for neglected tropical diseases includes yaws eradication requiring certification of elimination of transmission in all endemic and formerly endemic countries worldwide. A community-based programme for yaws control was considered to have achieved elimination of the infection in the endemic focus in Ecuador after 1993. We did a serosurvey of children in this focus to provide evidence for interruption of transmission. METHODS: Survey of serum samples collected from children aged 2 to 15 years living in the formerly endemic and in geographically contiguous areas. A convenience sample of sera collected between 2005 were 2017 from non-yaws studies, were analyzed using immunochromatic rapid tests to screen (OnSite Syphilis Ab Combo Rapid Test) for Treponema pallidum-specific antibodies and confirm (DPP Syphilis Screen and Confirm) seroreactivity based on the presence antibodies to treponemal and non-treponemal antigens. RESULTS: Seroreactivity was confirmed in 6 (0.14%, 95% CI 0.06-0.30) of 4,432 sera analyzed and was similar in formerly endemic (0.11%, (95% CI 0.01-0.75) and non-endemic (0.14%, 95% CI 0.06-0.34) communities. All seroreactors were of Afro-Ecuadorian ethnicity and most were male (4/6) and aged 10 or more years (5/6), the latter possibly indicating venereal syphilis. Only 1 seroreactor lived in a community in the Rio Santiago, that was formerly hyperendemic for yaws. CONCLUSION: We observed very low levels of treponemal transmission in both formerly endemic and non-endemic communities which might be indicative of congenital or venereal syphilis and, if yaws, would likely be insufficient to maintain transmission of this endemic childhood infection. Additional surveys of children aged 1 to 5 years are planned in Rio Santiago communities to exclude yaws transmission.

Yaws recurrence in children at continued risk of infection.

BACKGROUND: In yaws-endemic areas, children with Treponema pallidum subsp. pertenue infection may suffer recurrent episodes due to either reinfection or relapse. However, the possibility of infection with other cutaneous ulcer causative agents and difficulties in interpreting standard laboratory results challenges the estimation of yaws recurrence rates. METHODS: We estimated the rates of yaws recurrences in the Lihir Island (Papua New Guinea) using two approaches: passive surveillance based on a retrospective screening of electronic medical records of cutaneous ulcers diagnosed using serological testing between 2005 and 2016, and active surveillance conducted during a cross-sectional prevalence study which included PCR analyses of ulcers of all suspected cases of yaws. The risk of recurrent infection was assessed based on data from the passive surveillance analysis and using two Cox regression models (crude and multivariate), stratified by year of index episode. Data gathered from the active surveillance was used to characterize the recurrences and no hypothesis testing was performed. RESULTS: The electronic medical records included 6,125 patients (7,889 ulcer episodes) with documented serological results of cutaneous ulcers of which1,486 were diagnosed with yaws. Overall, 1,246/6,125 patients (20.3%) presented more than once with a cutaneous ulcer, and 103/1,486 (6.7%) patients had multiple episodes of yaws. The risk of yaws recurrence significantly increased with age and was higher in patients with ≥3 recurrent episodes. In the active surveillance, we identified 50 individuals with recurrent cutaneous ulcer that had PCR results available for both the index and recurrent episode. Of 12 individuals with T. pallidum in the index ulcer, 8 (66%) had T. pallidum in subsequent assessments, relapse related to macrolide-resistance was identified in two of these cases. CONCLUSIONS: Our results confirm the need for active follow-up of yaws patients after treatment, particularly children and individuals with a history of recurrence.

LAMP4yaws: Treponema pallidum, Haemophilus ducreyi loop mediated isothermal amplification - protocol for a cross-sectional, observational, diagnostic accuracy study.

INTRODUCTION: Yaws, caused by the bacterium Treponema pallidum subsp. pertenue, is a neglected tropical disease targeted for eradication by 2030. Improved diagnostics will be essential to meet this goal. Diagnosis of yaws has relied heavily on clinical and serological tools. However, the presence of coendemic cutaneous skin ulcer diseases, such as lesions caused by Haemophilus ducreyi (HD), means these techniques do not provide a reliable diagnosis. Thus, new diagnostic tools are needed. Molecular tools such as PCR are ideal, but often expensive as they require trained technicians and laboratory facilities, which are often not available to national yaws programmes. METHODS AND ANALYSIS: The LAMP4yaws project is a cross-sectional, observational, diagnostic accuracy study of a combined Treponema pallidum (TP) and HD loop mediated isothermal amplification (TPHD-LAMP) test performed under real world conditions in three endemic countries in West Africa. Individuals with serologically confirmed yaws will be recruited in Cameroon, Côte d'Ivoire and Ghana. Each participant will provide paired swabs, one of which will be sent to the respective national reference laboratory for yaws quantitative PCR and the other will be tested for both TP and HD using the TPHD-LAMP test at local district laboratories. Sensitivity and specificity of the TPHD-LAMP test will be calculated against the reference standard qPCR. We will also assess the acceptability, feasibility and cost-effectiveness of the test. We anticipate that results from this study will support the adoption of the TPHD-LAMP test for use in global yaws eradication efforts. ETHICS AND DISSEMINATION: We have received ethical approval from all relevant institutional and national ethical committees. All participants, or their parents or guardians, must provide written informed consent prior to study enrolment. Study results will be published in an open access journal and disseminated with partners and the World Health Organization. TRIAL REGISTRATION NUMBER: NCT04753788.

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.).

Conformity of yaws clinical features to combined rapid diagnostic test in children aged 2-15 years in an endemic area.

INTRODUCTION: The diagnosis of yaws is established by clinical examination and confirmed through a laboratory test. Unrecognized lesions may lead to a missed opportunity for diagnosis and complete eradication of yaws. The use of Dual Path Platform (DPP® RDT) Syphilis Screen and Confirm RDT (Chembio, Medford, New York) has been recommended by the World Health Organization (WHO) for endemic areas with limited laboratory facilities. To date, there have not been any studies assessing the conformity of clinical features based on the WHO guidelines with DPP® RDT. METHODOLOGY: A cross-sectional study was conducted to evaluate the conformity of yaws clinical features based on the WHO guidelines to the DPP® RDT. We recruited children aged 2-15 years old in Alor, Indonesia. All subjects underwent clinical examination and were tested with DPP® RDT. Fisher's exact test was used to analyze the overall agreement between the clinical features and the DPP® RDT results. RESULTS: A total of 197 study subjects (mean age 9 years) were enrolled. The most frequent skin lesion was a yaws scar (79.7%). Eight subjects (3%) were diagnosed with yaws based on the DPP® RDT examination. The overall agreement between clinical features and DPP® RDT was 26.9% (p = 0.202). CONCLUSIONS: The conformity of clinical features in suspected yaws to DPP® RDT is low; thus, clinical features should not be used as a sole initial reference in establishing yaws diagnosis, even in endemic areas.

No Serological Evidence of Trachoma or Yaws Among Residents of Registered Camps and Makeshift Settlements in Cox's Bazar, Bangladesh.

Successful achievement of global targets for elimination of trachoma as a public health problem and eradication of yaws will require control efforts to reach marginalized populations, including refugees. Testing for serologic evidence of transmission of trachoma and yaws in residents of registered camps and a Makeshift Settlement in Cox's Bazar District, Bangladesh, was added to a serosurvey for vaccine-preventable diseases (VPDs) conducted April-May 2018. The survey was primarily designed to estimate remaining immunity gaps for VPDs, including diphtheria, measles, rubella, and polio. Blood specimens from 1- to 14-year-olds from selected households were collected and tested for antibody responses against antigens from Treponema pallidum and Chlamydia trachomatis using a multiplex bead assay to evaluate for serologic evidence of the neglected tropical diseases (NTDs) yaws and trachoma, respectively. The prevalence of antibodies against two C. trachomatis antigens in children ranged from 1.4% to 1.5% for Pgp3 and 2.8% to 7.0% for CT694. The prevalence of antibody responses against both of two treponemal antigens (recombinant protein17 and treponemal membrane protein A) tested was 0% to 0.15% in two camps. The data are suggestive of very low or no transmission of trachoma and yaws, currently or previously, in children resident in these communities. This study illustrates how integrated serologic testing can provide needed data to help NTD programs prioritize limited resources.

Ulcerative skin lesions among children in Cameroon: It is not always Yaws.

Outbreaks of yaws-like ulcerative skin lesions in children are frequently reported in tropical and sub-tropical countries. The origin of these lesions might be primarily traumatic or infectious; in the latter case, Treponema pallidum subspecies pertenue, the yaws agent, and Haemophilus ducreyi, the agent of chancroid, are two of the pathogens commonly associated with the aetiology of skin ulcers. In this work, we investigated the presence of T. p. pertenue and H. ducreyi DNA in skin ulcers in children living in yaws-endemic regions in Cameroon. Skin lesion swabs were collected from children presenting with yaws-suspected skin lesions during three outbreaks, two of which occurred in 2017 and one in 2019. DNA extracted from the swabs was used to amplify three target genes: the human ß2-microglobulin gene to confirm proper sample collection and DNA extraction, the polA gene, highly conserved among all subspecies of T. pallidum, and the hddA gene of H. ducreyi. A fourth target, the tprL gene was used to differentiate T. p. pertenue from the other agents of human treponematoses in polA-positive samples. A total of 112 samples were analysed in this study. One sample, negative for ß2-microglobulin, was excluded from further analysis. T. p. pertenue was only detected in the samples collected during the first 2017 outbreak (12/74, 16.2%). In contrast, H. ducreyi DNA could be amplified from samples from all three outbreaks (outbreak 1: 27/74, 36.5%; outbreak 2: 17/24, 70.8%; outbreak 3: 11/13, 84.6%). Our results show that H. ducreyi was more frequently associated to skin lesions in the examined children than T. p. pertenue, but also that yaws is still present in Cameroon. These findings strongly advocate for a continuous effort to determine the aetiology of ulcerative skin lesions during these recurring outbreaks, and to inform the planned mass treatment campaigns to eliminate yaws in Cameroon.

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.

Yaws, Haemophilus ducreyi, and Other Bacterial Causes of Cutaneous Ulcer Disease in the South Pacific Islands.

Cutaneous ulcers in the tropics are a painful and debilitating condition that anchors people into poverty. In rural regions of the South Pacific, infectious cutaneous ulcers are caused mainly by bacteria, including Treponema pallidum pertenue (yaws), Haemophilus ducreyi, and polymicrobial ulcers. For this group of infections the term cutaneous ulcer disease (CUD) is proposed. Some infections can cause malformations on the bone that have a permanent impact on lives in endemic communities. Better characterization of CUD may help design diagnostic tools and more effective antimicrobial therapies. This review updates the knowledge of CUD and discusses optimized terminology and syndromic management.

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.