Modifying Immunity in Children With DihydROartemisinin-Piperaquine (MIC-DroP)

This study is a phase III, double-blind, randomized controlled trial of 924 HIV- uninfected children. Children born to mothers enrolled in an ongoing clinical trial of different IPTp arms in pregnancy (NCT 04336189) will be enrolled in this study. In the parent IPTp study, 2757 HIV-uninfected pregnant women will be randomized to receive IPTp with monthly sulfadoxine pyrimethamine (SP) alone, monthly DP alone, or both monthly SP+DP, and followed through 4 weeks postpartum. At the 4-week postpartum visit, we will enroll and randomize 924 eligible children to one of three IPTc arms: no IPTc (the current standard of care), monthly DP from 8 weeks to 1 year of age, or monthly DP from 8 weeks to 2 years of age. Study drugs will be placebo controlled and all doses of study drug will be given by directly observed therapy (DOT). The intervention phase will be completed at 2 years of age, and children followed through 4 years of age. Study participants will be followed for all of their outpatient medical care in our dedicated study clinic. Malaria incidence will be measured via active case detection. Routine assessments will be performed in the study clinic for all study participants every 4 weeks, including passive surveillance for parasitemia by quantitive polymerase chain reaction (qPCR). Venous blood will be collected for immunologic assays three times annually from 8 weeks to 4 years of age. All maternal assessments conducted during the parent IPTp study, including assessment for maternal malaria exposure (e.g., placental histology) household survey, will be available and linked to each study participant.

Inclusion criteria

• Born to HIV-uninfected mother enrolled in parent clinical trial of intermittent preventative treatment of malaria in pregnancy (IPTp-SP vs. IPTp-DP vs. IPTp-SP+DP, NCT 04336189)
• Resident of Busia District
• Provision of informed consent by parent/guardian
• Agreement to present for any illness and avoid, where possible, medications outside the study protocol.

Exclusion criteria

• Intention of moving outside Busia district during the study period
• Active medical problem requiring in-patient evaluation or chronic medical condition requiring frequent medical attention