Comparing Sulfadoxine-Pyrimethamine+Chloroquine and Dihydroartemisinin-Piperaquine to Control for Malaria Prevention in Malawian School Children: Results from a Randomized Controlled Trial

Malaria remains a significant global health challenge. Intermittent Preventive Treatment of malaria in school-age children (IPTsc) is recommended to reduce disease burden, but optimal drug choice is unclear. Dihydroartemisinin-Piperaquine (DP) is highly efficacious but there are concerns about widespread use given emerging artemisinin resistance and its role as an alternative first line treatment. Thus, non-artemisinin alternatives to DP are needed. 646 Malawian primary school children participated in the second stage of a 3-arm randomized controlled trial. Participants were allocated to IPTsc with 1) DP, 2) Sulfadoxine-Pyrimethamine+Chloroquine (SP+CQ) or 3) Control (no treatment). Study drugs were administered at three six-weekly visits. Outcomes were measured 6-8 weeks later. The primary outcome was Plasmodium falciparum (Pf) prevalence detected by qPCR. Secondary outcomes included clinical malaria and anemia. Analysis was modified intention-to-treat. Outcome assessment included 588 (91%) participants. Prevalence of Pf infection was 18% (34/198) in the IPTsc-DP arm, 27% (52/200) in the IPTsc-SP+CQ arm, and 48% (89/190) in the control arm. Compared to control, both IPTsc-DP (adjusted Odds Ratio [aOR] 0.22, 95%CI:0.14-0.36, p<0.001) and IPT-SP+CQ (aOR 0.38, 95%CI:0.24-0.59, p<0.001) significantly reduced odds of infection. Both regimens also decreased anemia (DP: aOR 0.45, 95%CI:0.21-0.93, p=0.035; SP+CQ: aOR 0.47, 95%CI:0.22-0.98, p=0.048) and clinical malaria (DP: adjusted Incidence Rate Ratio [aIRR] 0.41, 95%CI:0.28-0.60), p<0.001; SP+CQ: aIRR 0.60, 95%CI:0.43 - 0.84, p=0.003). In Malawi and settings with similar malaria drug resistance profiles, SP+CQ may be a suitable alternative to DP for IPTsc. Clinical Trial Registration ClinicalTrials.gov ID: NCT05980156