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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

The tools used in measuring malaria transmission intensity have different sensitivities at different geographical scales over time and space. This reflects changes in vector exposure, parasite infections and the dynamics of changing human immunity. Therefore, the intrinsic sensitivity of tools to detect short term changes in transmission is highly desirable. Accurate data on transmission intensity will be crucial for directing control efforts, developing and testing new interventions, as well as predicting the effects of these interventions under various conditions.

However, current tools have limitations in sensitivity at low-level transmission or lack the inherent ability to track short-term changes. Changes measured by traditional tools reflect either parasite or vector exposure but not both. The challenge is to develop an ‘ideal’ tool for tracking malaria transmission intensity. It should reflect both exposure to the vector, parasite infection and human immunity, detect short-term changes and be applicable at both individual and population level.

Sporozoite and ookinete proteins have been identified as a promising marker for an infectious bite as human immune response correlates with seasonal vector and parasite exposure and thus. The role of infectious-bite markers to detect short-term changes in malaria transmission has not been thoroughly studied.

Dr Badu proposed to evaluate candidate biomarkers to address the current challenges regarding tools to measure malaria transmission. It is hoped that these biomarkers will prove to be sensitive for the identification of transmission hotspots, vulnerable populations and inform focused interventions to speed up malaria elimination. Using longitudinal community cohorts, under varying transmission levels, Dr Badu is studying the dynamics of antibody response to candidate biomarkers in comparison to other salivary proteins to validate infectious-bite markers.

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 research capacity of the fellow will be enhanced for protein chemistry, bioinformatics and project management. Moreover, standard infectious-bite markers developed in the study may be applied in other parts of 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