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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

Human schistosomiasis is a neglected tropical disease caused by schistosome helminth worms with terrifying epidemiological statistics: 800 million people at risk in 78 countries, more than 230 million infected and over 200 000 deaths each year. The disease is highly endemic in sub-Saharan Africa where it persists despite mass drug administration with praziquantel (PZQ).

Some schistosomes are specific to humans and induce two main disease forms (either mesenteric or urogenital) while others are associated with wild animals. However, hybridisation can occur between different schistosome species. In northern Senegal, hybridisation between schistosome species is now known to be frequent with the potential risk of zoonotic transmission. Additionally, hybrids may present greater vigour compared to their pure parental forms and may be less sensitive to PZQ.

Dr Senghor aims to better understand the role of hybridisation plays in the dynamics of human and livestock schistosomiasis transmission in Senegal. The objectives of this study are to 1) determine the current prevalence and intensities of human schistosomiasis; 2) study the outcomes of S. haematobium x S. bovis hybrids on snail infectivity; 3) evaluate the sensitivity of hybrids schistosome populations to PZQ according to parasite genetic introgression levels; and 4) characterise the frequency of hybrids and their level of genomic introgression.

To achieve these objectives, an integrative approach will be used, i.e. a genetic monitoring study of the parasite communities infecting human populations in areas with high hybrid prevalence in Senegal before and after repeated PZQ treatment. Parental and hybrid life-history traits (i.e. sensibility to PQZ; host spectrum) will be investigated in controlled laboratory experiments.

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.

This project will allow Dr Senghor to train and initiate a biomedical research career on schistosomiasis in Senegal in the context of the One-health approach. The study also constitutes an opportunity to consolidate partnerships with European and local laboratories, health organisations and universities. The aim is to build a locally managed network to undertake larger projects with the ultimate goal of better understanding the dynamics of schistosome populations and in particular the emergence of hybrids. Eventually, the network will take part in the reflection on the strategies of schistosomiasis elimination in Senegal and more broadly in sub-Saharan Africa.

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