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

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Bringing antiretroviral drugs to children

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

The challenge

An estimated 350 million people are at risk of developing leishmaniasis, infection with the single-celled Leishmania parasite. The most severe form of the disease, visceral leishmaniasis or kala azar, is particularly common in East Africa.

Treatment and control would benefit greatly from reliable point-of-care diagnostics to detect new infections as well as ‘test-of-cure’ tools to assess the success of treatment. However, methods to detect parasites or antibodies against Leishmania are either not available in East Africa or perform poorly, especially in people living with HIV. Although molecular tests show excellent performance, they require specialist training and facilities and are expensive.

In his EDCTP Senior Fellowship, Dr Dawit Wolday is evaluating two possible alternative methods for diagnosing new Leishmania infections and for monitoring treatment responses.

The first is based on a method for amplification of parasite DNA that does not require repeated cycles of heating and cooling, central to conventional tools based on the polymerase chain reaction (PCR). Loop-mediated isothermal amplification (LAMP) methods show good specificity, generate easy-to-interpret results and require no cold chain. However, despite this promise, there are few data on their use in Africa.

Dr Wolday will also evaluate a novel PCR-based test, known as db-PCR-NALFIA, which can be used directly on blood samples without the need for extraction of DNA.

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.

Dr Wolday’s Senior Fellowship project will provide key data on two new point-of-care tools for diagnosing visceral leishmaniasis and for monitoring patient responses and test of cure. The two tools will be tested in people with and without HIV, and results compared with rigorous laboratory-based assessments.

The results will provide policymakers in Ethiopia and other East African countries with key evidence of the effectiveness of the new tests. The project will also build capacity in research on neglected infectious diseases at Mekelle University College of Health Sciences in Ethiopia, including the training of two master’s and one PhD student.

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