Feasibility, Acceptability, and Protective Efficacy of Seasonal Malaria Chemoprevention Implementation in Nampula Province, Mozambique: Protocol for a Hybrid Effectiveness-Implementation Study
Authors: Baker Kevin , Aide Pedro , Bonnington Craig A , Rassi Christian , Richardson Sol , Roca-Feltrer Arantxa , Rodrigues Maria , Sitoe Mercia , Pulido Tarquino Ivan Alejandro , Enosse Sonia , McGugan Caitlin , de Carvalho Eva Amelia , Saute Francisco , Mayor Aparicio Alfredo Gabriel , Candrinho Baltazar 
Published: July 2022

Background
Seasonal malaria chemoprevention (SMC) is a highly effective community-based intervention to prevent malaria infections in areas where the malaria burden is high and transmission occurs mainly during the rainy season. In Africa, so far, SMC has been implemented in the Sahel region. Mozambique contributes 4% of the global malaria cases, and malaria is responsible for one-quarter of all deaths in the country. Based on recommendations in the Malaria Strategic Plan, the Malaria Consortium, in partnership with the National Malaria Control Programme in Mozambique, initiated a phased SMC implementation study in the northern province of Nampula. The first phase of this 2-year implementation study was conducted in 2020-2021 and focused on the feasibility and acceptability of SMC. The second phase will focus on demonstrating impact. This paper describes phase 2 of the implementation study.

Objective
Specific objectives include the following: (1) to determine the effectiveness of SMC in terms of its reduction in incidence of malaria infection among children aged 3 to 59 months; (2) to determine the chemoprevention efficacy of sulfadoxine-pyrimethamine plus amodiaquine (SP+AQ) when used for SMC in Nampula Province, Mozambique, and the extent to which efficacy is impacted by drug resistance and drug concentrations; (3) to investigate the presence and change in SP+AQ– and piperaquine-resistance markers over time as a result of SMC implementation; and (4) to understand the impact of the SMC implementation model, determining the process and acceptability outcomes for the intervention.

Methods
This type 2, hybrid, effectiveness-implementation study uses a convergent mixed methods approach. SMC will be implemented in four monthly cycles between December 2021 and March 2022 in four districts of Nampula Province. Phase 2 will include four components: (1) a cluster randomized controlled trial to establish confirmed malaria cases, (2) a prospective cohort to determine the chemoprevention efficacy of the antimalarials used for SMC and whether drug concentrations or resistance influence the duration of protection, (3) a resistance marker study in children aged 3 to 59 months to describe changes in resistance marker prevalence over time, and (4) a process evaluation to determine feasibility and acceptability of SMC.

Results
Data collection began in mid-January 2022, and data analysis is expected to be completed by October 2022.

Conclusions
This is the first effectiveness trial of SMC implemented in Mozambique. The findings from this trial will be crucial to policy change and program expansion to other suitable geographies outside of the Sahel. The chemoprevention efficacy cohort study is a unique opportunity to better understand SMC drug efficacy in this new SMC environment.

Trial Registration
ClinicalTrials.gov NCT05186363; https://clinicaltrials.gov/ct2/show/NCT05186363

International Registered Report Identifier (IRRID)
DERR1-10.2196/36403