A Multi-Country, Diagnostic Accuracy Evaluation of a Loop Mediated Isothermal Amplification (LAMP) Test for Yaws : [Preprint]

Background: Yaws is targeted for eradication by 2030.  These efforts require highly sensitive and specific diagnostic tools. A Treponema pallidum-Haemophilus ducreyi multiplex loop-mediated isothermal amplification (TPHD-LAMP) test holds promise as a near-patient diagnostic for yaws and HD. The primary aim of this study was to conduct a prospective multi-country evaluation in Cameroon, Côte d’Ivoire, Ghana and the Republic of Congo to determine the diagnostic accuracy of the TPHD-LAMP test. Test acceptability, feasibility and cost were also assessed.

Methods: Participants with serologically confirmed active yaws provided paired lesion swabs. One swab was tested with the TPHD-LAMP at a local district lab and the other with reference qPCR tests conducted at national reference laboratories. Laboratory technicians were interviewed to gauge the test's acceptability and feasibility. Comparative costs of each test were calculated.

Findings: Between March 2021-April 2023, we enrolled 528 participants with seropositive yaws and a further 32 with negative serology. The sensitivity and specificity of the TPHD-LAMP test for detecting TP were 63.2% (95% Confidence Interval [CI]: 55.7–70.0) and 65.9% (95% CI: 60.6–70.9), respectively. Sensitivity and specificity for TP improved to 72.9% (95% CI: 62.9–81.5) (p<0.01) and 74.7% (95% CI: 68.0–80.1) (p<0.01) in HD-negative samples. Interviews highlighted challenges in user-friendliness and practicality in yaws-endemic settings. However, the cost of the test per sample was one third of that of the qPCR.

Interpretation: This was the first multicountry diagnostic evaluation of a new molecular test for yaws.  The TPHD-LAMP testing, in its current form, falls short of the World Health Organization’s target product profile criteria for yaws diagnostics. We have highlighted the importance of assessing new diagnostics in real-world conditions to ensure they are suitable for programmatic use.