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.
Competing Interests: Competing interests: BLH, GCB, ST, LAB, KOH, LB, NB, TC, TH, SL, CR, IA, AS, MSKS, JPNN, PA, AT, ENT, DKA, SNK, SE, KWA, EMHE, SK, OM and MM declare no competing interests. SF, MB and EL are employees of Mast Diagnostics GmbH, which produce and sell the TPHD LAMP kits and products. A patent covering the mediator displacement probe technique a component of the TPHD-LAMP assay described in the paper has been applied for by the University of Freiburg and Hahn-Schickard.
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