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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

Asymptomatic malaria parasitaemia poses a serious threat to malaria control efforts. Persons carrying the malaria parasite but showing no symptoms, constitute a reservoir that fuels the transmission process.

Mass parasite clearance can deplete these parasite reservoirs and lower the transmission potential. Therefore, efforts are made to scale up current effective interventions such as the use of long-lasting insecticidal nets (LLIN), intermittent preventive treatment in children (IPTc), and test, treat and track (TTT) programmes. However, in designing interventions to reduce the burden of malaria in children under five, mass TTT has largely been left out. Adults, usually not targeted, remain reservoirs for transmission. Mass testing, treating and tracking (MTTT) of the whole population is needed to reduce the parasite load before implementing the interventions mentioned.

Seasonal malaria chemoprophylaxis (SMC) has been adopted for selected localities in Ghana. The impact of these interventions could be enhanced if associated with MTTT at baseline to reduce the parasite load. In a pilot with MTTT in Ghana, coverage of more than 75% was achieved in target communities. This reduced asymptomatic parasitaemia by 27.4% from July 2017 to July 2018. It is important to continue this work so as to generate time-series data to better analyse and understand the prevalence trends and bottlenecks. However, questions remain on what we need for MTTT scale-up and must be addressed.

The hypothesis is that implementing MTTT complemented by community-based case management can reduce the prevalence of asymptomatic malaria parasite carriage in endemic communities. Thus, Dr Cheng will conduct an MTTT programme in the Pakro subdistrict of Ghana among household members two months and older. All cases of confirmed asymptomatic parasitaemia or clinical malaria will be treated. The entire population will be followed up in two years. Hospital records will be studied to document trends in malaria admissions in the area during the study.

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.

In addition to bringing a concrete community health benefit and documenting trends in asymptomatic malaria parasitaemia in the study population, this implementation study will also analyse the challenges and bottlenecks associated with scaling up mass test, treatment and tracking programmes. In addition, the project will have a strong capacity development component, not only for the fellow and his development as a researcher and trainer of junior scientists but also for his research team. This comprises nurses, community health workers (HWs) and research assistants who will be trained on ethics, good clinical practice, population engagement and sensitisation techniques.

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