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Diagnostics for Yaws Eradication: Insights From Direct Next-Generation Sequencing of Cutaneous Strains of Treponema pallidum.

ABSTRACT: Background:Yaws-like chronic ulcers can be caused by Treponema pallidum subspecies pertenue, Haemophilus ducreyi, or other, still-undefined bacteria. To permit accurate evaluation of yaws elimination efforts, programmatic use of molecular diagnostics is required. The accuracy and sensitivity of current tools remain unclear because our understanding of T. pallidum diversity is limited by the low number of sequenced genomes. Methods:We tested samples from patients with suspected yaws collected in the Solomon Islands and Ghana. All samples were from patients whose lesions had previously tested negative using the Centers for Disease Control and Prevention (CDC) diagnostic assay in widespread use. However, some of these patients had positive serological assays for yaws on blood. We used direct whole-genome sequencing to identify T. pallidum subsp pertenue strains missed by the current assay. Results:From 45 Solomon Islands and 27 Ghanaian samples, 11 were positive for T. pallidum DNA using the species-wide quantitative polymerase chain reaction (PCR) assay, from which we obtained 6 previously undetected T. pallidum subsp pertenue whole-genome sequences. These show that Solomon Islands sequences represent distinct T. pallidum subsp pertenue clades. These isolates were invisible to the CDC diagnostic PCR assay, due to sequence variation in the primer binding site. Conclusions:Our data double the number of published T. pallidum subsp pertenue genomes. We show that Solomon Islands strains are undetectable by the PCR used in many studies and by health ministries. This assay is therefore not adequate for the eradication program. Next-generation genome sequence data are essential for these efforts.

SUBMITTER: Marks M

PROVIDER: S-EPMC5848336 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Diagnostics for Yaws Eradication: Insights From Direct Next-Generation Sequencing of Cutaneous Strains of Treponema pallidum.

Marks Michael M Fookes Maria M Wagner Josef J Butcher Robert R Ghinai Rosanna R Sokana Oliver O Sarkodie Yaw-Adu YA Lukehart Sheila A SA Solomon Anthony W AW Mabey David C W DCW Thomson Nicholas N

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20180301 6

<h4>Background</h4>Yaws-like chronic ulcers can be caused by Treponema pallidum subspecies pertenue, Haemophilus ducreyi, or other, still-undefined bacteria. To permit accurate evaluation of yaws elimination efforts, programmatic use of molecular diagnostics is required. The accuracy and sensitivity of current tools remain unclear because our understanding of T. pallidum diversity is limited by the low number of sequenced genomes.<h4>Methods</h4>We tested samples from patients with suspected yaw ...[more]

PMID: 29045605

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Project description:BackgroundYaws 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 findingsThe 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.ConclusionsThe TPPs developed will provide test developers with guidance to ensure that novel diagnostic tests meet identified public health needs.

Dataset Information

Diagnostics for Yaws Eradication: Insights From Direct Next-Generation Sequencing of Cutaneous Strains of Treponema pallidum.

Publications

Diagnostics for Yaws Eradication: Insights From Direct Next-Generation Sequencing of Cutaneous Strains of Treponema pallidum.

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