Neglected Diseases

Yaws

Yaws is a chronic skin infection caused by the spirochaete, Treponema pallidum subspecies pertenue, which is closely related to the bacteria that causes syphilis and other endemic treponematoses – pinta and benjel. The disease is endemic in 15 countries, with endemicity still unknown in more than 70 countries worldwide. In 2021, over 120,000 suspected yaws cases were reported from 13 countries, with 1,102 confirmed cases from 9 countries. More than 80% of suspected cases were from the West Pacific region.

It is a highly contagious disease primarily affecting children under 15 years of age and those residing in poor communities in low- and middle-income countries. Transmission from person to person occurs through skin-to-skin contact with infectious skin lesions. Like syphilis, yaws is characterized by chronic relapsing skin manifestations, which is often associated with stigma and significant socioeconomic implications. Yaws is typically responsive to a single dose of azithromycin which is currently used in both mass treatment campaigns and targeted treatment of individual identified cases. Additionally, benzathine benzylpenicillin is a widely available safe and efficacious second line treatment for azithromycin-resistant cases. If left untreated, the lesions can progress to affect cartilages, joints, and bones, resulting in disfigurement and disability. Yaws is classified as a neglected tropical disease (NTD) of the skin by WHO and is targeted in the latest Roadmap for eradication by 2030.

R&D needs

Historically, laboratory-based serological tests have been widely used in diagnosing treponemal infections, but these are unable to distinguish yaws from syphilis infection. These tests are expensive, resource-intensive, require highly skilled personnel, and are associated with a long wait-time for results, leading to delays in initiating treatment. Multiple affordable treponemal rapid point-of-care tests are available. However, these tests cannot distinguish between past and present infection, limiting their use in monitoring the interruption of yaws transmission. Chembio’s novel Dual Path Platform Syphilis Screen and Confirm assay is capable of distinguishing active and past infection but its high cost makes it unsuitable for low resource settings.  A by the WHO Diagnostic Technical Advisory Group (DTAG) for NTDs suggests the sensitivity and specificity of the currently used point-of-care tests are suboptimal for disease surveillance and eradication. DTAG has endorsed a target product profile (TPP) for the development of new diagnostic tools for case detection and identification of azithromycin-resistant cases, owing to reports of a small number of azithromycin resistant cases. DTAG is also developing a TPP for affordable, sensitive, rapid point-of-care molecular tests for diagnosing single yaws cases. With the global distribution of yaws undefined, improving understanding of yaws epidemiology is critical to guide its eradication. Research into non-human primates as potential reservoirs also remains a priority.

Pipeline spotlight

The clinical evaluation of the LAMP4Yaws project’s Treponema pallidum, Haemophilus ducreyi loopmediated isothermal test (TPHD-LAMP) was completed in September 2023. Another LAMP assay, based on a lateral flow strip, is being developed as a point-of-care field test that can deliver results in 30 minutes.