Protocol for a Cluster Randomised Placebo-controlled Trial of Adjunctive Ivermectin Mass Drug Administration for Malaria Control on the Bijagós Archipelago of Guinea-Bissau: the MATAMAL Trial

Introduction: As malaria declines, innovative tools are required to further reduce transmission and achieve elimination. Mass drug administration (MDA) of artemisinin-based combination therapy (ACT) is capable of reducing malaria transmission where coverage of control interventions is already high, though the impact is short-lived. Combining ACT with ivermectin, an oral endectocide shown to reduce vector survival, may increase its impact, while also treating ivermectin-sensitive co-endemic diseases and minimising the potential impact of ACT resistance in this context.

Methods And Analysis: MATAMAL is a cluster-randomised placebo-controlled trial. The trial is being conducted in 24 clusters on the Bijagós Archipelago, Guinea-Bissau, where the peak prevalence of () parasitaemia is approximately 15%. Clusters have been randomly allocated to receive MDA with dihydroartemisinin-piperaquine and either ivermectin or placebo. The primary objective is to determine whether the addition of ivermectin MDA is more effective than dihydroartemisinin-piperaquine MDA alone in reducing the prevalence of parasitaemia, measured during peak transmission season after 2 years of seasonal MDA. Secondary objectives include assessing prevalence after 1 year of MDA; malaria incidence monitored through active and passive surveillance; age-adjusted prevalence of serological markers indicating exposure to and anopheline mosquitoes; vector parous rates, species composition, population density and sporozoite rates; prevalence of vector pyrethroid resistance; prevalence of artemisinin resistance in using genomic markers; ivermectin's impact on co-endemic diseases; coverage estimates; and the safety of combined MDA.

Ethics And Dissemination: The trial has been approved by the London School of Hygiene and Tropical Medicine's Ethics Committee (UK) (19156) and the Comite Nacional de Eticas de Saude (Guinea-Bissau) (084/CNES/INASA/2020). Results will be disseminated in peer-reviewed publications and in discussion with the Bissau-Guinean Ministry of Public Health and participating communities.

Trial Registration Number: NCT04844905.