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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

Intestinal schistosomiasis, specifically at the chronic stage, constitutes a health risk for 230 million people worldwide. The disease morbidity primarily results from the infected individuals’ poor ability to immune-regulate their response to parasite eggs trapped in their liver. A progressive fibroproliferative response ensues leading to organ impairment, pathology and - when left untreated - death. The molecular mechanisms behind schistosomiasis-driven liver fibrosis remain elusive. The challenge is to determine these mechanisms.

Dr Nono reasons that a differential expression profile in schistosomiasis-diseased patients with a comparable egg burden but a different stage of advancement of the liver fibrosis may unveil candidate factors in the host that, by their sole differential expression, alter the progression of liver fibrosis in those patients.

The present study conducted by Dr Nono and his team investigates through full-genome mRNA sequencing of blood cells the factors which are differentially expressed by school children with schistosomiasis, factors that that associate with the rapid onset and/or fast progression of liver fibrosis.

The study takes place at a highly endemic site for schistosomiasis in the locality of Yoro in Cameroon around the Mbam river and is rooted in a cross-sectional study on 1000 school children. The study specifically aims to define the knowledge, habits and practices of school children regarding schistosomiasis and the risk the disease represents in the area. Egg-defined prevalence of the disease will be related to individual habits. Secondly, the study assesses the advancement of liver fibro-pathology in the recruited children by ultrasonography and defines comparative clusters of individuals with similar parasitological status but different fibro-pathological (liver) status. Finally, the study determines by next-generation sequencing of children’s PBMCs-derived mRNA the differences in transcriptional profiles between children with fibrotic and non-fibrotic livers.

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 different aims of our project are expected to yield an updated map of the prevalence of schistosomiasis in the locality of Yoro. Unprecedentedly, it will define an ultrasonographic profile of the liver pathology in the children of this hepato-intestinal schistosomiasis endemic area. Potentially, it may unveil a unique library of host factors involved in the progression of pathological liver fibrosis in general and during schistosomiasis in particular.

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