A Roadmap for the Development of Ivermectin as a Complementary Malaria Vector Control Tool

Abstract

In the context of stalling progress against malaria, resistance of mosquitoes to insecticides, and residual transmission, mass drug administration (MDA) of ivermectin, an endectocide used for neglected tropical diseases (NTDs), has emerged as a promising complementary vector control method. Ivermectin reduces the life span of Anopheles mosquitoes that feed on treated humans and/or livestock, potentially decreasing malaria parasite transmission when administered at the community level. Following the publication by WHO of the preferred product characteristics for endectocides as vector control tools, this roadmap provides a comprehensive view of processes needed to make ivermectin available as a vector control tool by 2024 with a completely novel mechanism of action. The roadmap covers various aspects, which include 1) the definition of optimal dosage/regimens for ivermectin MDA in both humans and livestock, 2) the risk of resistance to the drug and environmental impact, 3) ethical issues, 4) political and community engagement, 5) translation of evidence into policy, and 6) operational aspects of large-scale deployment of the drug, all in the context of a drug given as a prevention tool acting at the community level. The roadmap reflects the insights of a multidisciplinary group of global health experts who worked together to elucidate the path to inclusion of ivermectin in the toolbox against malaria, to address residual transmission, counteract insecticide resistance, and contribute to the end of this deadly disease.

Potential metabolic resistance mechanisms to ivermectin in Anopheles gambiae: a synergist bioassay study

“…Endectocides are antiparasitic drugs with activity against endoparasites and ectoparasites such as mosquitoes which feed on treated humans or animals. Importantly, endectocides can target exophilic and exophagic vectors, tackling the problem of residual transmission, while perfectly complementing the indoor vector control measures [9].…”

A Generalized Overview of the Possible Pharmacotherapy and Treatments against SARS-CoV-2

“…It is a potent macro-cyclic lactone, showing potential microfilaricidal activity against major filarial parasites of humans and, currently a drug of choice for human onchocerciasis [82]. It has the potentiality in reducing malaria transmission by mosquito killing which is under review in several trials worldwide [83]. Caly et al recently proposed that ivermectin has in vitro wide spectrum antiviral activity and is a potent inhibitor against SARS-CoV-2 replication.…”

Mass Drug Administration With High-Dose Ivermectin and Dihydroartemisinin-Piperaquine for Malaria Elimination in an Area of Low Transmission With High Coverage of Malaria Control Interventions: Protocol for the MASSIV Cluster Randomized Clinical Trial

“…It targets malaria vectors regardless of biting behavior (it kills exophagic and exophilic mosquitoes, including early biting vectors) and reduces vectorial capacity [15,33]. Research has shown that IVM is a potentially valuable addition to the existing tools to decrease malaria transmission [15,16,18,33,34]. Modeling showed that three monthly rounds of MDA with IVM at 300 μg/kg/day daily for three days with 70% coverage would reduce clinical incidence by 70% and prevalence by 34% in a highly seasonal moderate transmission setting [15].…”