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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

Infections with schistosomes, parasitic flatworms, affect hundreds of millions of people globally – schistosomiasis is the second most socioeconomically impactful parasitic disease after malaria. Africa accounts for 90% of cases, with children and young adults bearing the brunt of disease.

Mass drug administration programmes with praziquantel have been the cornerstone of schistosome control efforts. However, in badly affected countries such as Uganda, despite good coverage, many children are still being infected and developing debilitating symptoms. In particular, inflammatory responses to schistosome parasites can cause the build-up of fibrous tissue (fibrosis) in blood vessels in the liver, which can lead to dangerously high blood pressure.

The FibroScHot study is evaluating whether increasing the frequency of mass drug administration reduces the prevalence of liver fibrosis in hotspots of persistent schistosomiasis.

In areas where schistosomiasis is less common, mass drug administration campaigns target school children. The FibroScHot study will carry out a controlled trial in areas of high transmission, comparing usual community campaigns with an intensified campaign that includes treatment in schools, to see if this reduces the prevalence of liver fibrosis.

The project will also explore community attitudes to mass drug administration campaigns, immune responses associated with liver fibrosis, and genetic features of parasites associated with fibrosis and poor responses to drug treatment.

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 study will determine whether a readily implementable intervention, building on existing approaches to schistosomiasis control, protects more children against a common, debilitating and potentially deadly neglected infectious disease. The approach would be practical to adopt in Uganda and other countries in which childhood schistosomiasis persists.

It will also establish an integrated trial platform spanning Makerere University and the Ministry of Health in Uganda, increasing capacity for clinical trials on neglected infectious disease, and build research capacity in a range of areas, including parasite genomics, immunology and anthropology.

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