Background:
Yaws is a skin neglected tropical disease, caused by Treponema pallidum pertenue (TPE) and targeted for eradication by 2030. Yaws is endemic in 16 countries, but up-to-date epidemiological data for over 70 countries is lacking. Prevalence estimates are often unsystematically derived. Diagnosis has historically relied on clinical examination and serological testing, approaches which have demonstrated poor diagnostic performance as many clinically suspected yaws cases are caused by Haemophilus ducreyi or are idiopathic.
Methods:
This PhD aimed to address yaws diagnostic gaps, evaluate a novel molecular test, and characterise the microbial landscape of cutaneous ulcers. This was achieved through three primary objectives:
Objective 1:
To assess how nationally reported yaws prevalence estimates have been derived and to highlight gaps in diagnostic capacity, using an online questionnaire targeting national program managers and laboratory staff in endemic countries.
Objective 2:
To gauge the diagnostic accuracy of the T. pallidum, H. ducreyi loop-mediated isothermal amplification (TPHD-LAMP) test and assess its acceptability, feasibility and cost by coordinating and analysing findings from a multi-country, real-world diagnostic evaluation. This included, determining sensitivity and specificity of the TPHD-LAMP conducted at district laboratories, in comparison to reference standard qPCR conducted at reference laboratories as well administering surveys to laboratory staff and conducting a costing exercise to compare the assay’s acceptability, feasibility and costs with those of qPCR.
Objective 3:
To characterise the microbial landscape of cutaneous ulcers by analysing retrospective 16S rRNA sequencing data from lesion samples collected in Ghana and the Solomon Islands and performing Oxford Nanopore sequencing on samples obtained during the LAMP4yaws project in West Africa.
Results:
Objective 1: Responses were received from 14 of the 15 yaws-endemic countries surveyed. Five of 14 respondent countries had no yaws eradication policy in place. Only four countries had an established molecular qPCR test, but were lacking an established external quality assurance scheme, and there was still a heavy overreliance of clinical diagnosis with 95% of the yaws cases reported to World Health Organization (WHO) in the five preceding years being solely diagnosed on clinical findings, without serological or molecular confirmation.
Objective 2: The results of the diagnostic evaluation, performed on 525 participant samples, demonstrated the TPHD-LAMP test was not accurate enough or user-friendly enough for adoption, in its current form, to support eradication efforts worldwide. The test had a sensitivity of 63% (95% CI 56–70) and 67% (95% CI 61–73) for detecting TPE and H. ducreyi respectively and a specificity of 66% (95% CI 61–71) and 67% (95% CI 62–73). Although it was seen as cost effective in relation to qPCR, it was found to be too technical to perform.
Objective 3: The metagenomic analysis identified a diverse range of bacteria that could be contributing to the burden of cutaneous ulcer disease (CUD) in yaws-endemic countries. Streptococcus pyogenes and Staphylococcus aureus were found in high abundance in ulcer samples and could have implications for management and treatment.
Conclusion:
Yaws eradication efforts face significant diagnostic and operational challenges, including limited diagnostic capacity and diagnostic ambiguity due to other causes of yaws-like lesions. Strengthening laboratory capacity, designing simple molecular diagnostics, and incorporating research into alternative causes of cutaneous ulcers are essential for reaching eradication goals and improving health in endemic communities.
BT - Department of Clinical Research DA - 01/2026 DO - 10.17037/PUBS.04680220 LA - ENG M3 - Phd Thesis N2 -Background:
Yaws is a skin neglected tropical disease, caused by Treponema pallidum pertenue (TPE) and targeted for eradication by 2030. Yaws is endemic in 16 countries, but up-to-date epidemiological data for over 70 countries is lacking. Prevalence estimates are often unsystematically derived. Diagnosis has historically relied on clinical examination and serological testing, approaches which have demonstrated poor diagnostic performance as many clinically suspected yaws cases are caused by Haemophilus ducreyi or are idiopathic.
Methods:
This PhD aimed to address yaws diagnostic gaps, evaluate a novel molecular test, and characterise the microbial landscape of cutaneous ulcers. This was achieved through three primary objectives:
Objective 1:
To assess how nationally reported yaws prevalence estimates have been derived and to highlight gaps in diagnostic capacity, using an online questionnaire targeting national program managers and laboratory staff in endemic countries.
Objective 2:
To gauge the diagnostic accuracy of the T. pallidum, H. ducreyi loop-mediated isothermal amplification (TPHD-LAMP) test and assess its acceptability, feasibility and cost by coordinating and analysing findings from a multi-country, real-world diagnostic evaluation. This included, determining sensitivity and specificity of the TPHD-LAMP conducted at district laboratories, in comparison to reference standard qPCR conducted at reference laboratories as well administering surveys to laboratory staff and conducting a costing exercise to compare the assay’s acceptability, feasibility and costs with those of qPCR.
Objective 3:
To characterise the microbial landscape of cutaneous ulcers by analysing retrospective 16S rRNA sequencing data from lesion samples collected in Ghana and the Solomon Islands and performing Oxford Nanopore sequencing on samples obtained during the LAMP4yaws project in West Africa.
Results:
Objective 1: Responses were received from 14 of the 15 yaws-endemic countries surveyed. Five of 14 respondent countries had no yaws eradication policy in place. Only four countries had an established molecular qPCR test, but were lacking an established external quality assurance scheme, and there was still a heavy overreliance of clinical diagnosis with 95% of the yaws cases reported to World Health Organization (WHO) in the five preceding years being solely diagnosed on clinical findings, without serological or molecular confirmation.
Objective 2: The results of the diagnostic evaluation, performed on 525 participant samples, demonstrated the TPHD-LAMP test was not accurate enough or user-friendly enough for adoption, in its current form, to support eradication efforts worldwide. The test had a sensitivity of 63% (95% CI 56–70) and 67% (95% CI 61–73) for detecting TPE and H. ducreyi respectively and a specificity of 66% (95% CI 61–71) and 67% (95% CI 62–73). Although it was seen as cost effective in relation to qPCR, it was found to be too technical to perform.
Objective 3: The metagenomic analysis identified a diverse range of bacteria that could be contributing to the burden of cutaneous ulcer disease (CUD) in yaws-endemic countries. Streptococcus pyogenes and Staphylococcus aureus were found in high abundance in ulcer samples and could have implications for management and treatment.
Conclusion:
Yaws eradication efforts face significant diagnostic and operational challenges, including limited diagnostic capacity and diagnostic ambiguity due to other causes of yaws-like lesions. Strengthening laboratory capacity, designing simple molecular diagnostics, and incorporating research into alternative causes of cutaneous ulcers are essential for reaching eradication goals and improving health in endemic communities.
PB - London School of Hygiene & Tropical Medicine PY - 2026 SP - 1 EP - 263 T2 - Department of Clinical Research TI - Evaluating novel diagnostic strategies to support yaws eradication UR - https://researchonline.lshtm.ac.uk/id/eprint/4680220/1/2026_ITD_PhD_Handley_R.pdf VL - Doctor of Philosophy ER -