Extending seasonal malaria chemoprevention to older children: a non-inferiority randomized controlled trial of Dihydroartemisinin–piperaquine as a policy alternative in Mali
Year: 2026
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: Background: Seasonal malaria chemoprevention (SMC) with Sulfadoxine-pyrimethamine plus amodiaquine (SPAQ) reduces malaria in children under five, but substantial burden remains among children 5-9 years. Emerging SP/AQ resistance and adherence challenges underscore the need for alternative regimens. Dihydroartemisinin-piperaquine (DHAPQ) is a promising option, although evidence from multi-season programmatic settings in the Sahel is limited. We aimed to evaluate the effectiveness and safety of DHAPQ compared with SPAQ when SMC was extended to children aged 3 months to 9 years. Methods: We conducted a two-year, three-arm, cluster-randomized crossover trial in nine health-catchment clusters in Mali. Clusters received standard SPAQ SMC (<5 years), extended-age SPAQ (<10 years), or (3) extended-age DHAPQ (<10 years), crossing over to a different regimen in year two. The primary outcome was the incidence of clinical malaria, analyzed using mixed-effects negative binomial models that accounted for clustering, period effects, and recurrent events. Non-inferiority was predefined as an upper 95% CI < 1.25. Findings: Among 12,854 children, DHAPQ was non-inferior to extended-age SPAQ (HR = 0.7, 95% CI 0.6-0.9) and achieved higher intervention coverage, with no serious adverse events reported. Children aged 5-9 years had a lower hazard of clinical malaria than children younger than 5 years (HR = 0.9, 95% CI 0.8-0.9). Interpretation: Extending SMC to children aged 5-9 years substantially reduced malaria burden. DHAPQ was safe, effective, and operationally feasible, supporting its consideration as an alternative to SPAQ where adherence or resistance threatens SMC effectiveness. Funding: NIH/NIAID-ICEMR-WAF.
Authors: Mahamoudou Toure, Soumba Keita, Fousseyni Kane, Daouda Sanogo, Ibrahim Sanogo, Moussa Keita, Ibrahim M. Sissoko, Mountaga Diallo, Hamady Coulibaly, Bourema Cisse, Drissa Konate, Issaka Guindo, Mossa Ag Malle, Cheick Oumar Tangara, Sory I Diawara, Mady Cissoko, Vincent Sanogo, Aissata Kone, Sidi Niare, Aissatou Maiga, Nafomon Sogoba, Helle Holm Hansonn, Michael Alifrangis, Mahamadou Diakite, Jeffrey G. Shaffer, Seydou Doumbia
Language: English
Topic: Malaria Research and Control
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7202364152