Ivermectin to reduce malaria transmission II. Considerations regarding clinical development pathway

Abstract

The development of ivermectin as a complementary vector control tool will require good quality evidence. This paper reviews the different eco-epidemiological contexts in which mass drug administration with ivermectin could be useful. Potential scenarios and pharmacological strategies are compared in order to help guide trial design. The rationale for a particular timing of an ivermectin-based tool and some potentially useful outcome measures are suggested.

Ivermectin Dosing Strategy to Achieve Equivalent Exposure Coverage in Children and Adults

“…Ivermectin is known to bind to glutamate‐gated chlorine channels blocking synaptic transmission, leading to hyperpolarization, paralysis, and death of nematodes, making it an effective anthelmintic drug. As ivermectin is also capable of killing various invertebrates, including mosquitoes, mass drug administration of ivermectin in targeted populations may reduce the transmission of malaria …”

“…As ivermectin is also capable of killing various invertebrates, including mosquitoes, 1,10 mass drug administration of ivermectin in targeted populations may reduce the transmission of malaria. 10,11 Ivermectin is not approved in children weighing < 15 kg; hence, this age group is excluded from official treatment programs. The drug has been widely used off-label in a single-dose administration for various indications, and given that young children may have high prevalence of helminth infections [12][13][14][15] and scabies 16,17 and serve as an important reservoir of Plasmodium, 18,19 there is a need to build an evidence base to determine safe and effective ivermectin doses in the Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?…”

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

“…This is a modified version of an original figure in by Chaccour and Rabinovich. 19 sustained in the blood for as long as possible, while avoiding human toxicity and minimizing the number of MDA campaigns required. Ivermectin's toxicity in humans is the result of crossbinding to GABA-gated channels which are only present in the central nervous system (CNS) and, hence, protected by the blood brain barrier (BBB).…”

“…15,16 More recently, the results of several modeling, pharmacological, and insectary-based research studies, as well as several clinical and field MDA trials, have positioned ivermectin as a first-inclass tool to enhance malaria control. [17][18][19] After recognizing the potential for endectocides to tackle the issue of residual transmission, the WHO held a technical consultation on ivermectin in 2016. Subsequently, preferred product characteristics (PPCs) for endectocides against malaria were published with ivermectin as a reference product.…”

“…A launch meeting took place at the 2017 Annual Meeting of the American Society of Tropical Medicine and Hygiene (ASTMH) in Baltimore (US). The multidisciplinary team included global health experts whose backgrounds encompassed entomology, infectious diseases, vaccines, veterinary, environmental sciences, ethics, financing systems, clinical trials, supply chain management, and scaling-up of interventions, among others (see full list of contributors on pages [18][19].…”