Publications

Funding for clinical research |drugs, vaccines, microbicides, diagnostics | HIV/AIDS, tuberculosis, malaria, other infectious diseases |sub-Saharan Africa

EDCTP portfolio: Career Development Fellowships

Dr Mariama Combassere-Cherif will conduct a proof of concept study for improving interventions which target the asymptomatic malaria parasite reservoir.

Impact of seasonal malaria chemoprevention on protective immunity

Seasonal Malaria Chemoprevention (SMC) is a new strategy to reduce the malaria burden in young children in Sahelian countries. SMC consists of the administration of full treatment courses at regular intervals during the malaria high-transmission season. However, it is not clear if there is a cumulative effect of SMC on the acquisition of antibodies to malaria antigens.

The challenge

Dr Combasssere-Cherif intends to establish the key elements for understanding the potential role of seasonal malaria chemoprevention (SMC) in the buildup of immunity against clinical malaria in Burkina Faso. Specifically, sho proposed to study how SMC during low and high transmission affects parasite presence, density, and diversity (or clones), and host antibodies response. She aims to establish the relationship between asexual parasite densities, multiclonal infections with Plasmodium falciparum and immune responses before and after SMC.

Building on existing collaborations, she and her team will conduct a prospective cohort study following the national health policy of SMC in Burkina Faso. It is a full treatment course of sulfadoxine-pyrimethamine plus amodiaquine (SP+AQ) given to 6-59 months old children at monthly intervals during the malaria high-transmission season from July to October. The project comprises five cross-sectional surveys to establish the relationship between SMC, malaria prevalence, parasite densities, the number of new P. falciparum clones as well as the immune responses across surveys, before and after SMC.

The project

The approach used in this project could be implemented as part of a surveillance program to explain the impact of SMC in Burkina Faso where malaria is endemic, stable and seasonal. This study will serve as a proof of concept in order to optimise the design of interventions targeting the asymptomatic reservoir of the parasite.

Impact


test the safety and efficacy of this new formulation in young children

Bringing antiretroviral drugs to children

The CHAPAS trials have ensured that many more children with HIV have benefited
from life-saving antiretrovirals.

EDCTP portfolio: HIV & HIV-associated infections

The challenge

Seasonal Malaria Chemoprevention (SMC) is a new strategy to reduce the malaria burden in young children in Sahelian countries. SMC consists of the administration of full treatment courses at regular intervals during the malaria high-transmission season. However, it is not clear if there is a cumulative effect of SMC on the acquisition of antibodies to malaria antigens.

Dr Combasssere-Cherif intends to establish the key elements for understanding the potential role of seasonal malaria chemoprevention (SMC) in the buildup of immunity against clinical malaria in Burkina Faso. Specifically, sho proposed to study how SMC during low and high transmission affects parasite presence, density, and diversity (or clones), and host antibodies response. She aims to establish the relationship between asexual parasite densities, multiclonal infections with Plasmodium falciparum and immune responses before and after SMC.

Building on existing collaborations, she and her team will conduct a prospective cohort study following the national health policy of SMC in Burkina Faso. It is a full treatment course of sulfadoxine-pyrimethamine plus amodiaquine (SP+AQ) given to 6-59 months old children at monthly intervals during the malaria high-transmission season from July to October. The project comprises five cross-sectional surveys to establish the relationship between SMC, malaria prevalence, parasite densities, the number of new P. falciparum clones as well as the immune responses across surveys, before and after SMC.

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 approach used in this project could be implemented as part of a surveillance program to explain the impact of SMC in Burkina Faso where malaria is endemic, stable and seasonal. This study will serve as a proof of concept in order to optimise the design of interventions targeting the asymptomatic reservoir of the parasite.

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

L’homme RF et al. Nevirapine, stavudine and lamivudine pharmacokinetics in African children on paediatric fixed-dose combination tablets. AIDS. 2008;22(5):557–65.

Mulenga V et al. Abacavir, zidovudine, or stavudine as paediatric tablets for African HIVinfected children (CHAPAS-3): an open-label, parallel-group, randomised controlled trial. Lancet Infect Dis. 2016;16(2):169–79.

WHO. Guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. 2010.

WHO. Consolidated guidelines on the use of antiretroviral drugs
for treating and preventing

HIV infection: Recommendations for a public health approach
(second edition). 2016

Projects: Children with HIV in Africa Pharmacokinetics and Adherence of Simple Antiretroviral Regimens (CHAPAS): CHAPAS-1 and -3

Project lead: Professor Chifumbe Chintu, University Teaching Hospital, Zambia (CHAPAS-1); Dr Veronica Mulenga, University Teaching Hospital, Zambia (CHAPAS-3)

Target population(s): Children with HIV

Sample size: 71 (CHAPAS-1); 480 (CHAPAS-3)

Countries involved: Ireland, the Netherlands, the UK, the USA, Zambia (CHAPAS-1); Uganda, Zambia (CHAPAS-3)

Project duration: 2005–2009 (CHAPAS-1); 2010 –2011 (CHAPAS-3)

EDCTP funding: €1.2M (CHAPAS-1); €4.6M (CHAPAS-3)

Total project funding: €1.2M (CHAPAS-1); €5.0M