Perennial Malaria Chemoprevention in the Malaria Vaccine Era (PMC-VAC)

Malaria continues to result in 597,000 deaths annually, mainly due to Plasmodium falciparum in young African children. An affordable malaria vaccine, R21, was recently approved by the World Health Organization (WHO) for infants beginning at 5-6 months of age and will soon be deployed in Uganda and other African countries. However, in perennial, high transmission settings, the burden of malaria can be high prior to the age at which R21-elicited protection is expected to begin, and vaccine efficacy and durability are expected to be sub- optimal. In these settings, additional interventions will be needed to best protect young children. A promising approach to enhance protection against malaria in young children is to administer vaccine with antimalarial chemoprevention. In settings with perennial transmission, the WHO recently recommended perennial malaria chemoprevention (PMC), although optimal regimens and dosing schedules are undefined. Two promising regimens for PMC include sulfadoxine-pyrimethamine + amodiaquine (SPAQ), which is currently used for seasonal malaria chemoprevention, and dihydroartemisinin-piperaquine (DP), which we have found to be safe and highly effective when used as monthly chemoprevention in infants. However, the extent of protection offered by these drugs when given at the time of routine expanded programme on immunization (EPI) visits has not been evaluated. This project will test the hypothesis that R21 combined with either PMC-DP or PMC-SPAQ will offer better protection against malaria compared with R21 alone, that PMC-DP will be more efficacious and better tolerated than PMC-SPAQ, and that both PMC arms will enhance R21 immunogenicity and durability without significantly impacting parasite drug resistance. It will test these hypotheses in Busia District, Uganda, an area with high, perennial malaria transmission. This project will randomize 1290 infants 1:1:1 to receive 8 doses of PMC-DP, PMC-SPAQ, or placebo between 10 weeks and 18 months of age, given at the time of scheduled EPI childhood visits. All study subjects will receive R21 at 6, 7, and 8 months of age, with a booster dose at 18 months of age, the new standard of care in Uganda. Children will be followed up to 5 years of age to determine the long-term effects of the interventions on malaria and immunity. This will be the first trial comparing the efficacy and safety of PMC-DP vs. PMC-SPAQ vs. placebo in a high, perennial transmission setting in which R21 is being administered, and testing whether PMC impacts the drug resistance landscape and R21-specific vaccine immunogenicity and memory. Extended follow-up through 5 years of age to characterize the durability of protection was recently recommended by the WHO. The trial will thus have clear and achievable policy implications.

NIH Project details

Combination of Interventions
Drug-based Strategies
Vaccines
Vulnerable Populations

May 2026 — Apr 2033

$563,176

Uganda