Ivermectin interrupts malaria transmission in mosquitoes

Issue: November 2015

PHILADELPHIA — Newly presented findings suggested that ivermectin is active against multiple strains of malaria and may be capable of interrupting transmission of the disease.

Ivermectin, a broad-spectrum antiparasitic agent, was initially explored for its ability to reduce parasitic infection in animals. The treatment effectively treats onchoceriasis, lymphatic filariasis and several types of soil-transmitted helminths, and recently was recognized by the Nobel Prize Committee for its role in reducing these parasitic diseases worldwide.

Mass drug administration

In one presentation given here at the American Society of Tropical Medicine and Hygiene’s annual meeting, Brian D. Foy, PhD, microbiologist at Colorado State University’s Arthropod-borne and Infectious Disease Laboratory, discussed interim data from the ongoing RIMDAMAL phase 2/3 trial examining the safety and efficacy of repeated ivermectin mass drug administration (MDA). Eight Burkinabé villages in Burkina Faso, West Africa, comprising 2,662 participants were randomly assigned either the standard, single MDA of ivermectin plus Albenza (albendazole, Amedra Pharmaceuticals) for the prevention of lymphatic filariasis and soil-transmitted helminths at the beginning of the rainy season, or an experimental dosing of the standard treatment plus five or more MDA of ivermectin every 3 weeks until the end of the rainy season.

Brian D. Foy

“The idea was born off of research that we started a long time ago, where we knew that ivermectin is toxic to the mosquitoes that transmit malaria in sub-Saharan Africa,” Foy told Infectious Disease News. “When somebody takes the drug and mosquitoes bite them, they will ingest a lethal dose of the drug in somebody’s blood, and then the mosquito will die and therefore can’t pass on malaria parasites to people.”

The primary outcome observed by Foy and colleagues was the incidence of malaria in children aged 5 years or younger, and is assessed weekly through active case surveillance. Secondary outcomes related to the infection are to be assessed by comparing blood and fecal samples taken before and after the study period. Data concerning entomological outcomes will be obtained from mosquito collections throughout the study period, and also will be available upon completion of the study.

The researchers reported a 16% reduction in malaria episodes among participants in the treatment arm, which would translate to an estimated 575 cases averted per 1,000 children annually. In addition, interim analysis on Sept. 9 showed similar incidences of adverse and serious adverse event within the two groups.

“These are preliminary results, but we expect to see further reductions in malaria fevers as we continue with the trial, which is occurring during the rainy season when malaria transmission typically peaks,” Foy said in a press release.

Neutralizing vectors

In another presentation, Kevin C. Kobylinski, PhD, National Research Council fellow at the Armed Forces Research Institute of Medical Sciences in Bangkok, Thailand, gave evidence supporting ivermectin’s effectiveness in halting Plasmodium vivax infection at its source.

Kevin C. Kobylinski

“Previous laboratory work demonstrated that ivermectin inhibits the development of Plasmodium falciparum in [Anopheles gambiae],” Kobylinski and colleagues wrote. “Here we present that ivermectin is sporontocidal to P. vivax in A. dirus when ivermectin is coingested with gametocytes.”

A. dirus mosquitoes were fed a mixture of gametocytemic blood drawn from malaria patients reporting to clinics and various dilutions of ivermectin. Researchers compared survivability and related outcomes between control mosquitoes given blood with no infection and those given ivermectin concentrations capable of killing 25% of mosquitoes (LC25), concentrations able to kill 5% of mosquitoes (LC5) and infected blood with no ivermectin.

They found that mosquitoes ingesting P. vivax were more susceptible to ivermectin LC25 than those given control blood, as evidenced by a 48% reduction in 7-day survival (P < .0001). Reductions in oocyst prevalence and intensity also were seen among mosquitoes fed ivermectin at both concentrations.

“We demonstrated that if the mosquito survives its primary ivermectin blood meal … the likelihood that it would develop the P. vivax parasite was reduced,” Kobylinski told Infectious Disease News.

While future research would involve repeating these examinations using serum from patients who had never been infected with P. falciparum, Kobylinski said these results support an MDA program in Thailand similar to the one described by Foy.

“We would be very interested in performing ivermectin MDA in the Greater Mekong Subregion for malaria-elimination efforts, and this work helps to justify that by showing that there are secondary effects against malaria transmission beyond just mosquito lethal effects,” he said. – by Dave Muoio

Reference:

Foy BD, et al. Abstract LB-5237. Presented at: American Society of Tropical Medicine and Hygiene annual meeting; Oct. 26-29, 2015; Philadelphia.

Kobylinski KC, et al. Abstract 1283. Presented at: American Society of Tropical Medicine and Hygiene annual meeting; Oct. 26-29, 2015; Philadelphia.

Disclosures: Foy and Kobylinski report no relevant financial disclosures.