Can giving adolescents preventive treatment for malaria, before vaccination, improve immune responses to these vaccines?

INTERVENTION: A randomisation code will be generated by the trial statistician using a randomly permuted block size. Participants will be allocated in a 1:1 ratio to receive either (DP) or placebo. Participants in the DP arm will receive two DP doses, one month apart, prior to immunisation followed by monthly DP doses for one year thereafter. Each dose will comprise treatment once a day for three consecutive days. DP will be dosed using weight‐based guidelines targeting a total dose of 6.4 mg/kg dihydroartemisinin and 51.2 mg/kg piperaquine. Participants in the placebo arm will receive doses of placebo at the same time points as the DP arm receive DP, i.e. two doses of placebo, one month apart prior to immunisation followed by monthly placebo for one year thereafter. Both DP and placebo will be taken orally. As yet, routine preventive malaria treatment in schools is not Uganda Ministry of Health policy. CONDITION: Vaccine responses ; Not Applicable PRIMARY OUTCOME: ; 1. BCG: BCG‐specific IFN‐gamma ELIspot response 8 weeks post BCG immunisation; 2. YF‐17D: neutralising antibody titres (plaque‐reduction neutralisation test) at 4 weeks post YF immunisation; 3. Ty21a: Salmonella typhi lipopolysaccharide (LPS)‐specific immunoglobulin(Ig)G concentration at 4 weeks post Ty21a immunisation; 4. HPV: IgG specific for L1‐proteins of HPV‐16/18 at 4 weeks post HPV priming immunisation; 5. Td: tetanus and diphtheria toxoid‐specific IgG concentration at 4 weeks post Td immunisation; SECONDARY OUTCOME: ; 1. Protective immunity is measured using proportions with protective neutralising antibody (YF); protective IgG levels (TT); seroconversion rates (Ty21a) at 4 weeks post the corresponding immunisation; 2. Response waning is measured using primary outcome measures (all vaccines) repeated at week 52, and area‐under‐the curve (AUC) analyses; 3. Priming versus boosting is measured using effects on priming versus boosting will be examined for HPV only, comparing outcomes 4 weeks after the first, and 4 weeks after the second vaccine dose; 4. Current malaria infection status and intensity is assessed retrospectively by PCR on stored samples collected on immunisation days and at week 52.; INCLUSION CRITERIA: 1. Attending the selected school and planning to continue to attend the school for the duration of the study 2. Aged 9 to 17 years and enrolled in primary 1 to 6 3. Written informed assent by participant and consent by parent or guardian 4. Agree to avoid pregnancy for the duration of the trial (female only) 5. Willing to provide locator information and to be contacted during the course of the trial 6. Able and willing (in the investigator’s opinion) to comply with all the study requirements