Prevalence and risk factors associated with Haemophilus ducreyi cutaneous ulcers in Cameroon.

Epidemics of yaws-like cutaneous ulcers are regularly documented in children in the tropics. They occur mainly in poor and remote communities without access to health facilities. The integration of molecular tools into yaws control efforts has made it possible to describe Haemophilus ducreyi (HD) as a major cause of cutaneous ulcers. The objective of this study was to determine the prevalence of HD as cause of cutaneous ulcers, investigate its presence in asymptomatic individuals and identify associated risk factors. A cross-sectional study was conducted in yaws endemic districts of Cameroon. Participants included people presenting yaws-like ulcers and asymptomatic individuals. Swab samples were collected from each participant and tested for HD and Treponema pallidum (TP) using an established qPCR method. Additionally, demographic, habitat, proximity, and hygiene characteristics were collected using a structured questionnaire. A total of 443 individuals participated in the study, including 271 ulcer cases and 172 asymptomatic contacts. The prevalence of HD in ulcers was 30.3% (Confidence Interval (CI) 95% [24.8-35.7]) and the prevalence of asymptomatic HD carriage was 8.6% (CI95% [4.5-12.9]). TP was also detected in our sample among ulcer cases but in lower proportion (5.2% CI95% [2.5-7.8]) compared to HD. The adjusted logistic regression model showed that women were as much at risk of having HD cutaneous ulcer as men regardless of age. Physical proximity to a confirmed ulcer case was the major factor identified favouring HD transmission. HD ulcers were more likely to be present on Bantu individuals compared to Baka as well as HD colonization. These findings highlight HD as the most common cause of cutaneous ulcers in yaws-endemic communities in Cameroon. The exact implications of detecting HD on intact skin are not yet clear. Further studies are needed to understand the significance of this carriage in the spread dynamics of the disease.

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.

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.

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.

Two Streptococcus pyogenes emm types and several anaerobic bacterial species are associated with idiopathic cutaneous ulcers in children after community-based mass treatment with azithromycin.

BACKGROUND: In yaws-endemic areas, two-thirds of exudative cutaneous ulcers (CU) are associated with Treponema pallidum subsp. pertenue (TP) and Haemophilus ducreyi (HD); one-third are classified as idiopathic ulcers (IU). A yaws eradication campaign on Lihir Island in Papua New Guinea utilizing mass drug administration (MDA) of azithromycin initially reduced but failed to eradicate yaws; IU rates remained constant throughout the study. Using 16S rRNA gene sequencing, we previously determined that Streptococcus pyogenes was associated with some cases of IU. Here, we applied shotgun metagenomics to the same samples we analyzed previously by 16S rRNA sequencing to verify this result, identify additional IU-associated microorganisms, and determine why S. pyogenes-associated IU might have persisted after MDA of azithromycin. METHODOLOGY/PRINCIPAL FINDINGS: We sequenced DNA extracted from 244 CU specimens separated into four groups based upon microorganism-specific PCR results (HD+, TP+, TP+HD+, and TP-HD- or IU). S. pyogenes was enriched in IU (24.71% relative abundance [RA]) specimens compared to other ulcer sub-groups, confirming our prior results. We bioinformatically identified the emm (M protein gene) types found in the S. pyogenes IU specimens and found matches to emm156 and emm166. Only ~39% of IU specimens contained detectable S. pyogenes, suggesting that additional organisms could be associated with IU. In the sub-set of S. pyogenes-negative IU specimens, Criibacterium bergeronii, a member of the Peptostreptococcaceae, and Fusobacterium necrophorum (7.07% versus 0.00% RA and 2.18% versus 0.00% RA, respectively), were enriched compared to the S. pyogenes-positive sub-set. Although a broad range of viruses were detected in the CU specimens, none were specifically associated with IU. CONCLUSIONS/SIGNIFICANCE: Our observations confirm the association of S. pyogenes with IU in yaws-endemic areas, and suggest that additional anaerobic bacteria, but not other microorganisms, may be associated with this syndrome. Our results should aid in the design of diagnostic tests and selective therapies for CU.

Improved rapid diagnostic tests to detect syphilis and yaws: a systematic review and meta-analysis.

BACKGROUND: Current rapid tests for syphilis and yaws can detect treponemal and non-treponemal antibodies. We aimed to critically appraise the literature for rapid diagnostic tests (RDTs) which can better distinguish an active infection of syphilis or yaws. METHODS: We conducted a systematic review and meta-analysis, searching five databases between January 2010 and October 2021 (with an update in July 2022). A generalised linear mixed model was used to conduct a bivariate meta-analysis for the pooled sensitivity and specificity. Heterogeneity was assessed using the I2 statistic. We used the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) to assess the risk of bias and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) to evaluate the certainty of evidence. RESULTS: We included 17 studies for meta-analyses. For syphilis, the pooled sensitivity and specificity of the treponemal component were 0.93 (95% CI: 0.86 to 0.97) and 0.98 (95% CI: 0.96 to 0.99), respectively. For the non-treponemal component, the pooled sensitivity and specificity were 0.90 (95% CI: 0.82 to 0.95) and 0.97 (95% CI: 0.92 to 0.99), respectively. For yaws, the pooled sensitivity and specificity of the treponemal component were 0.86 (95% CI: 0.66 to 0.95) and 0.97 (95% CI: 0.94 to 0.99), respectively. For the non-treponemal component, the pooled sensitivity and specificity were 0.80 (95% CI: 0.55 to 0.93) and 0.96 (95% CI: 0.92 to 0.98), respectively. CONCLUSIONS: RDTs that can differentiate between active and previously treated infections could optimise management by providing same-day treatment and reducing unnecessary treatment. PROSPERO REGISTRATION NUMBER: CRD42021279587.

Diagnostics to support the eradication of yaws-Development of two target product profiles.

BACKGROUND: Yaws is targeted for eradication by 2030, using a strategy based on mass drug administration (MDA) with azithromycin. New diagnostics are needed to aid eradication. Serology is currently the mainstay for yaws diagnosis; however, inaccuracies associated with current serological tests makes it difficult to fully assess the need for and impact of eradication campaigns using these tools. Under the recommendation of the WHO Diagnostic Technical Advisory Group (DTAG) for Neglected Tropical Diseases(NTDs), a working group was assembled and tasked with agreeing on priority use cases for developing target product profiles (TPPs) for new diagnostics tools. METHODOLOGY AND PRINCIPAL FINDINGS: The working group convened three times and established two use cases: identifying a single case of yaws and detecting azithromycin resistance. One subgroup assessed the current diagnostic landscape for yaws and a second subgroup determined the test requirements for both use cases. Draft TPPs were sent out for input from stakeholders and experts. Both TPPs considered the following parameters: product use, design, performance, configuration, cost, access and equity. To identify a single case of yaws, the test should be able to detect an analyte which confirms an active infection with at least 95% sensitivity and 99.9% specificity. The high specificity was deemed important to avoid a high false positive rate which could result in unnecessary continuation or initiation of MDA campaigns. If used in settings where the number of suspected cases is low, further testing could be considered to compensate for imperfect sensitivity and to improve specificity. The test to detect azithromycin resistance should be able to detect known genetic resistance mutations with a minimum sensitivity and specificity of 95%, with the caveat that all patients with suspected treatment failure should be treated as having resistant yaws and offered alternative treatment. CONCLUSIONS: The TPPs developed will provide test developers with guidance to ensure that novel diagnostic tests meet identified public health needs.

Yaws in the Philippines: A clinico-seroprevalence study of selected communities in Mindanao.

BACKGROUND: Yaws is a chronic, highly contagious skin and bone infection affecting children living in impoverished, remote communities. It is caused by Treponema pallidum subsp. pertenue. We report the prevalence of active yaws among elementary schoolchildren based on clinical and serological criteria in selected municipalities of Southern Philippines. METHODS: From January to March 2017, exploratory cross-sectional surveys and screening of skin diseases were conducted in the Liguasan Marsh area of the provinces Maguindanao, Sultan Kudarat, and Cotabato. We included 9 municipalities and randomly selected one public elementary school per municipality. Members of students' households and the communities were also examined and treated. Yaws suspects and contacts had blood tests for treponemal and non-treponemal antibodies using Dual Pathway Platform and Treponema pallidum particle agglutination (TPPA) tests. RESULTS: A total of 2779 children and adults were screened for any skin disease: 2291 students, 393 household members, and 95 community members. Among 210 yaws suspects and contacts, 150 consented to serologic tests. The estimated prevalence of active yaws among schoolchildren screened was 1 out of 2291 (0.04%). Among 2532 children who were 14 years old and younger, 4 (0.2%) had active yaws. Eight adult household contacts and community members had latent yaws and 2 had past yaws. Five out of 9 municipalities were endemic for yaws. CONCLUSIONS: This study confirmed that the Philippines is endemic for yaws but at a low level in the schools surveyed. This is an under-estimation due to the limited sampling. The lack of proper disease surveillance after the eradication campaign in the 1960's has made yaws a forgotten disease and has led to its resurgence. Yaws surveillance is needed to determine the extent of yaws in the Philippines and to help develop a strategy to eradicate yaws by 2030.

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.

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.

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.

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.

Novel Diagnostics for Kaposi Sarcoma and Other Skin Diseases in Resource-Limited Settings.

In resource-limited settings, point-of-care diagnostic devices have the potential to reduce diagnostic delays and improve epidemiologic surveillance of dermatologic conditions. We outline novel-point-of care diagnostics that have recently been developed for dermatologic conditions that primarily affect patients living in resource-limited settings, namely, Kaposi sarcoma, cutaneous leishmaniasis, leprosy, Buruli ulcer, yaws, onchocerciasis, and lymphatic filariasis. All of the technologies described in this article are prototypes, and some have undergone field testing. These devices still require validation in real-world settings and effective pricing to have a major impact on dermatologic care in resource-limited settings.

Integrated approach in the control and management of skin neglected tropical diseases in three health districts of Côte d'Ivoire.

BACKGROUND: Neglected tropical diseases (NTDs) comprise 20 communicable diseases that are prevalent in rural poor and remote communities with less access to the health system. For effective and efficient control, the WHO recommends that affected countries implement integrated control interventions that take into account the different co-endemic NTDs in the same community. However, implementing these integrated interventions involving several diseases with different etiologies, requiring different control approaches and driven by different vertical programs, remains a challenge. We report here the results and lessons learned from a pilot test of this integrated approach based on integrated screening of skin diseases in three co-endemic health districts of Côte d'Ivoire, a West African country endemic for Buruli ulcer, leprosy and yaw. METHOD: This cross-sectional study took place from April 2016 to March 2017 in 3 districts of Côte d'Ivoire co-endemic for BU, leprosy and yaws. The study was carried out in 6 stages: identification of potentially co-endemic communities; stakeholder training; social mobilization; mobile medical consultations; case detection and management; and a review meeting. RESULTS: We included in the study all patients with skin signs and symptoms at the screening stage who voluntarily accepted screening. In total, 2310 persons screened had skin lesions at the screening stage. Among them, 07 cases were diagnosed with Buruli ulcer. There were 30 leprosy cases and 15 yaws detected. Other types of ulcerations and skin conditions have been identified and represent the majority of cases detected. We learned from this pilot experience that integration can be successfully implemented in co-endemic communities in Côte d'Ivoire. Health workers are motivated and available to implement integrated interventions instead of interventions focused on a single disease. However, it is essential to provide capacity building, a minimum of drugs and consumables for the care of the patients identified, as well as follow-up of identified patients, including those with other skin conditions. CONCLUSIONS: The results of this study show that the integration of activities can be successfully implemented in co-endemic communities under the condition of staff capacity building and minimal care of identified patients.

Ocular syphilis in Pacific peoples-are we making misdiagnoses secondary to yaws?

AIMS: To determine the demographic and clinical features of patients with ocular disease consistent with syphilis and positive treponemal serology in Auckland, and to compare patients who lived in a Pacific nation before 1960 with all other patients with regard to these features, considering a possible history of yaws infection. METHODS: Retrospective review of subjects seen in uveitis and neuroophthalmology clinics at Auckland District Health Board between January 2006 and June 2019. RESULTS: Two thousand four hundred and ninety-three subjects were reviewed in uveitis clinics during the timeframe, of whom 45 were diagnosed with syphilitic uveitis (1.8%). Mean age was 56.2±14.8 years and 34 (75.5%) were male. Ethnicity was Caucasian in 16 (35.5%), Pacific peoples in 16 (35.5%), Maori in two (4.4%), Asian in six (13.3%) and other in five (11.1%). Pacific peoples were older at presentation (p=0.001) and 75.0% were aged >60 compared to 24.1% of non-Pacific peoples (p=0.002). Comparing Pacific people born prior to 1960 (aged >60) to the rest of the cohort, older Pacific subjects had lower RPR titres (median 3 vs 32 p=0.004), less optic nerve swelling (0% vs 28.0% eyes p=0.014) and less posterior uveitis (6.25% vs 32.0% eyes p = 0.033). No difference was observed in anterior and intermediate uveitis between the groups. No difference was observed in the resolution or recurrence of inflammation between the groups. CONCLUSION: Syphilitic uveitis is common in New Zealand, occurring in 1 in 55 patients seen in consultant uveitis clinics. Clinicians should consider a history of yaws in Pacific peoples presenting with ocular inflammation and positive treponemal serology. In these cases alternative causes of ocular pathology should be included as differentials. In cases of diagnostic uncertainty, the risk of treatment versus the potentially severe sequelae of untreated syphilis need to be considered.

A Loop-Mediated Isothermal Amplification Assay for the Detection of Treponema pallidum subsp. pertenue.

The eradication of yaws caused by Treponema pallidum subsp. pertenue is constrained by the lack of rapid, accurate diagnosis. We sought to develop a molecular point-of-care test for the diagnosis of yaws. A loop-mediated isothermal amplification (LAMP) assay with primers targeting the conserved gene, tp0967, with visual detection by lateral flow test strip was developed and optimized. The limit of detection was evaluated while 63 samples from clinical cases of yaws and five samples with polymerase chain reaction (PCR)-confirmed syphilis were used to determine the sensitivity and specificity of the assay compared with the current molecular testing protocol. The developed LAMP assay was found to be optimal when run at 65°C for 30 minutes. The limit of detection from extracted DNA was 2.7 × 104 DNA copies/mL. The sensitivity of the LAMP assay using unextracted and DNA extracted samples were 0.67 and 1.00, respectively. None of the syphilis samples tested positive in any of the assays. We show the development of a fast and sensitive LAMP assay for yaws detected by lateral flow test strip. Using extracted DNA, the assay sensitivity is at par with real-time PCR-based detection. The assay can be adapted to minimal sample processing required for infield detection without DNA extraction.

Factors associated with cutaneous ulcers among children in two yaws-endemic districts in Ghana.

BACKGROUND: Yaws is a chronic relapsing disease caused by Treponema pallidum subspecies pertunue, which can result in severe disability and deformities. Children below the age of 15 years in resource-poor communities are the most affected. Several non-specific factors facilitate the continuous transmission and resurgence of the disease. Endemic communities in rural Ghana continue to report cases despite the roll out of several intervention strategies in the past years. The objective of this study was to determine the factors associated with cutaneous ulcers among children in two yaws-endemic districts in Ghana. METHODS: A community-based unmatched 1:2 case-control study was conducted among children between 1 and 15 years. Data on socio-demographic, environmental and behavioral factors were collected using a structured questionnaire. Active case search and confirmation was done using the Dual Path Platform (DPP) Syphilis Screen and Confirm test kit. Data were analyzed using STATA 15. Logistic regression was done to determine the exposures that were associated with yaws infection at 0.05 significant level. RESULTS: Sixty-two cases and 124 controls were recruited for the study. The adjusted multivariable logistic regression model showed that yaws infection was more likely among individuals who reside in overcrowded compound houses (aOR = 25.42, 95% CI: 6.15-105.09) and with poor handwashing habits (aOR = 6.46, 95% CI: 1.89-22.04). Male (aOR = 4.15, 95% CI: 1.29-13.36) and increasing age (aOR = 5.90, 95% CI: 1.97-17.67) were also associated with yaws infection. CONCLUSIONS: Poor personal hygiene, overcrowding and lack of access to improved sanitary facilities are the factors that facilitate the transmission of yaws in the Awutu Senya West and Upper West Akyem districts. Yaws was also more common among males and school-aged children. Improving living conditions, access to good sanitary facilities and encouraging good personal hygiene practices should be core features of eradication programs in endemic communities.

Multiplex Mediator Displacement Loop-Mediated Isothermal Amplification for Detection of Treponema pallidum and Haemophilus ducreyi.

Yaws, a neglected tropical disease caused by the bacterium Treponema pallidum subspecies pertenue, manifests as ulcerative skin lesions. Nucleic acid amplification tests, like loop-mediated isothermal amplification (LAMP), are versatile tools to distinguish yaws from infections that cause similar skin lesions, primarily Haemophilus ducreyi. We developed a novel molecular test to simultaneously detect T. pallidum and H. ducreyi based on mediator displacement LAMP. We validated the T. pallidum and H. ducreyi LAMP (TPHD-LAMP) by testing 293 clinical samples from patients with yaws-like lesions. Compared with quantitative PCR, the TPHD-LAMP demonstrated high sensitivity and specificity for T. pallidum (84.7% sensitivity, 95.7% specificity) and H. ducreyi (91.6% sensitivity, 84.8% specificity). This novel assay provided rapid molecular confirmation of T. pallidum and H. ducreyi DNA and might be suitable for use at the point of care. TPHD-LAMP could support yaws eradication by improving access to molecular diagnostic tests at the district hospital level.