Impact of directly observed treatment and extended age range of seasonal malaria chemoprevention with sulfadoxine-pyrimethamine plus amodiaquine in Burkina Faso: a three-group, open-label, cluster-randomised, controlled trial.

Abstract

Seasonal malaria chemoprevention (SMC) currently targets children younger than 5 years but can be extended to wider age ranges to reduce clinical burden in older populations. We aimed to evaluate the effect of programmatic SMC versus SMC via directly observed treatment (DOT) and the effect of extending SMC to children younger than 10 years on malaria clinical incidence, parasite carriage, and gametocyte carriage in individuals targeted and untargeted by SMC. We conducted a three-group, open-label, cluster-randomised trial in Saponé (Burkina Faso) with three study groups: (1) programmatic SMC in children younger than 5 years; (2) SMC in children younger than 5 years with DOT (DOTu5); and (3) SMC in children younger than 10 years with DOT (DOTu10). The trial involved 61 programmatic SMC and 62 (each DOT group) clusters of three compounds. Eligible compounds had at least one child younger than 5 years and aged 5-9 years who had not participated in recent vaccine trials. Clusters were randomised (approximately 1:1:1) to the study groups by computer generation. Eligible children received four cycles of SMC with sulfadoxine-pyrimethamine and amodiaquine. The primary endpoint was Plasmodium falciparum parasite prevalence at the end of the transmission season in SMC-targeted age groups and compared between study groups. No formal missing data strategy was conducted; a modified intention-to-treat analysis was used based on those assessed during the endline survey. Secondary endpoints included drug plasma concentrations after the fourth cycle of SMC and incidence of clinical malaria during the entire malaria season. The trial is registered with ClinicalTrials.gov, NCT05878366, and is completed. Between 13 July and 29 Aug 2023, 3467 participants of all ages were enrolled, including 980 SMC-targeted individuals (236 in the programmatic SMC group, 231 in the DOTu5 group, and 513 in the DOTu10 group). The parasite prevalence at the end of transmission season in children younger than 5 years was 24·9% (52 of 209 participants) in the programmatic SMC group compared with 19·7% (40 of 203 participants) in the DOTu5 group (rate ratio [RR] 0·84, 95% CI 0·55-1·30; p=0·4419). Parasite prevalence in children aged 5-9 years was lower in the DOTu10 group (28·1% [63 of 224 participants]) compared with the DOTu5 group (47·1% [98 of 208 participants]; RR 0·56, 95% CI 0·43-0·74; p<0·0001). The incidence of clinical malaria in children younger than 5 years was lower in the DOTu5 group compared with the programmatic SMC group (protective efficacy 0·57, 95% CI 0·29-0·74; p=0·0009) and lower in children aged 5-9 years in the DOTu10 group compared with the DOTu5 group (0·72, 0·54-0·83; p<0·001). Clinical incidence after the 4th cycle of SMC was also lower in individuals who were scored as adherent based on plasma drug concentrations compared with those who were scored as non-adherent (incidence rate ratio 0·21, 95% CI 0·09-0·51; 0·0006). We observed no significant difference in parasite prevalence between programmatic SMC and SMC delivered through DOT in children younger than 5 years. Extending SMC to children aged 5-9 years reduced parasite carriage and incidence of clinical malaria in this age group. Although these findings support extending the SMC age range to older children, potential logistical and financial barriers need to be examined. Gates Foundation.