Implementation and effectiveness of intermittent preventive treatment in school aged children using dihydroartemisinin-piperaquine to reduce malaria burden: an implementation research of a cluster randomised trial in Tanzania.

Background: In malaria endemic areas, malaria is a major contributor for half of the mortality in school-aged children (5-15 years old). Most infections are asymptomatic, contributing to anaemia, poor cognitive development, and reduced school performance. School-aged children often show low adherence to preventive and curative measures, and malaria control programs rarely target this group. We evaluated the pilot implementation of intermittent preventive treatment of malaria in schoolchildren (IPTsc) using Dihydroartemisinin-Piperaquine (DP) delivered by schoolteachers, to assess the implementation feasibility and effectiveness on asymptomatic and clinical malaria in a high endemic area in Tanzania. Methods: This study used a cluster-randomised design in which each ward (cluster) was assigned to implement IPTsc or serve as a control. All schoolchildren in primary schools under the intervention arm received three annual rounds of DP aligned with malaria transmission seasons. The primary implementation end point was IPTsc coverage, defined as the proportion of enrolled schoolchildren completing the full DP therapeutic course. For the effectiveness, 12 wards were randomly selected per arm, and one school per ward contributed outcome data. The primary effectiveness endpoints were (1) protective effectiveness of IPTsc on clinical malaria incidence and (2) reduction in parasite prevalence. Data were analysed using cluster-adjusted intention-to-treat (ITT) methods. The study was conducted from February 2020 to July 2021 and is registered with ClinicalTrials.gov (NCT04245033). Findings: Three rounds of DP dispensing covered 127 schools with more than 73,000 schoolchildren. IPTsc coverage reached 77% (range: 69-83%), 73% (64-81%), and 80% (76-85%) in August 2020, November 2020 and March 2021, respectively. DP was well tolerated. In the effectiveness evaluation, 1971 schoolchildren were enrolled in DP arm and 1781 in control arm. After one year, IPTsc reduced clinical malaria incidence by 41% overall (95% CI: 31-49; p < 0.001) and by 54% (95% CI: 44.2-62.6; p < 0.001) in high endemic strata (≥10% baseline prevalence). Parasite prevalence decreased by 81% overall (95% CI: 56.3-100; p < 0.001) ranging from 58% (95% CI: 10.9-100; p = 0.18) in low endemic to 83% (95% CI: 62.7-100; p < 0.001) in high endemic strata. Interpretation: Large scale implementation of IPTsc achieved impact comparable to randomised trials and was operationally feasible and well accepted by communities and teachers. This study sets a benchmark for school-based malaria chemoprevention in Tanzania and provides groundwork for national policy adoption. Funding: The Global Fund, through the Ministry of Health, Tanzania, funded the study.