“
test the safety and efficacy of this new formulation in young children

”

Bringing antiretroviral drugs to children

The CHAPAS trials have ensured that many more children with HIV have benefited
from life-saving antiretrovirals.

The challenge

Yaws is a neglected tropical disease mostly affecting children. Caused by the bacterium Treponema pallidum pertenue, it is characterised by disfiguring skin lesions that can progress to major destruction of muscle and bone tissue.

Control of yaws has been greatly aided by the development of a highly effective treatment, single-dose azithromycin. There are hopes that yaws could be eradicated, but this would require sensitive tests to detect infections. Unfortunately, existing antibody-based tests cannot distinguish current from past infections, or discriminate between infections with T. pallidum pertenue and Haemophilus ducreyi, which causes similar symptoms.

The LAMP4YAWS project is evaluating a new yaws diagnostic with significant advantages over existing tools. It can be used to identify (and discriminate between) both T. pallidum pertenue and H. ducreyi and is also able to detect mutations responsible for resistance to azithromycin.

The diagnostic detects the pathogens’ genetic material. However, unlike standard molecular testing using the polymerase chain reaction (PCR), it uses a technology known as ‘loop-mediated isothermal amplification’ (LAMP), which does not require repeated cycles of heating and cooling. This means it is more amenable to near-point-of-care applications. 

Laboratory studies have shown that the LAMP-based diagnostic has good sensitivity (85%) and specificity (96%). The LAMP4YAWS project will compare its performance at district hospitals (where suspected yaws cases are normally investigated) with processing of samples by PCR at national reference laboratories in three countries with the highest burden of yaws cases – Cote d’Ivoire, Ghana and Cameroon, which collectively see 15,000 cases a year.

The project

The later CHAPAS-3 trial compared the efficacy and safety of three fixed-dose combinations including two without stavudine (found to have some long-term side effects in adults, leading to a recommendation that its use be discontinued in children). The trial the first of its kind in Africa studied nearly 500 children at four sites in two African countries.

The LAMP4YAWS project will provide key data on a diagnostic tool that could support more effective control of yaws and accelerate its eventual eradication. It will provide data on its use in programmatic settings in three of the countries in the region most badly affected by the disease. By engaging closely with local policymakers, researchers and national control programmes, the project has ensured that its results will generate the evidence required to support national decision-making on use of the new approach to testing.

ratios forfixed-dose combinations and on appropriatedosage according to weight. 

The CHAPAS-3 trial confirmed the effectiveness of fixed-dose combinations, providing further impetus to the rollout of antiretrovirals to children. Its evidence on abacavir informed the WHO recommendation of abacavir-containing combinations for first-line therapy in children. Trial data have also been used to support applications for regulatory approval for new scored efavirenz tablets.

Impact