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

BMJ Open. 2023 Jul 7;13(7):e072347. doi: 10.1136/bmjopen-2023-072347.

Abstract

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 Plasmodium falciparum (Pf) 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 P. falciparum 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 P. falciparum and anopheline mosquitoes; vector parous rates, species composition, population density and sporozoite rates; prevalence of vector pyrethroid resistance; prevalence of artemisinin resistance in P. falciparum 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.

Keywords: clinical trials; epidemiologic studies; guinea-bissau; ivermectin; malaria; mass drug administration.

Publication types

  • Clinical Trial Protocol
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimalarials* / therapeutic use
  • Artemisinins* / therapeutic use
  • Guinea-Bissau / epidemiology
  • Humans
  • Ivermectin / therapeutic use
  • Malaria* / epidemiology
  • Malaria, Falciparum* / drug therapy
  • Malaria, Falciparum* / epidemiology
  • Malaria, Falciparum* / prevention & control
  • Mass Drug Administration
  • Randomized Controlled Trials as Topic

Substances

  • artenimol
  • Antimalarials
  • Ivermectin
  • Artemisinins

Associated data

  • ClinicalTrials.gov/NCT04844905