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Mosquito Control Drug Shows Promise as Malaria Preventive

Mass administration of ivermectin, a wormicide that’s also lethal to mosquitoes, was linked with a reduction in malaria transmission among African children, a randomized trial found.

The cumulative malaria incidence was significantly lower over 18 weeks in the intervention group who received the drug than among controls (estimated mean 2.00 episodes/child vs estimated mean 2.49 episodes/child, respectively; risk difference -0.49, 95% CI -0.79 to -0.21, P=0.0009), reported Brian D. Foy, PhD, of Colorado State University in Fort Collins, and colleagues, writing in The Lancet.

They noted that ivermectin is “regularly distributed in mass drug administration” for parasitic nematode infections such as onchocerciasis, and it has certain “mosquitocidal effects.” In addition, it can “induce transmission-blocking activity against Plasmodium falciparum parasites in surviving mosquitoes.”

“Ivermectin reduces new cases of malaria by making a person’s blood lethal to the mosquitoes who bite them, killing mosquitoes and therefore reducing the likelihood of infection of others,” Foy said in a statement. “Because ivermectin has a unique mode of action compared to other malaria control insecticides and antimalarial drugs, it could be used alongside drugs that treat malaria to combat residual transmission of the disease.”

The Repeat Ivermectin Mass Drug Administrations for Control of Malaria (RIMDAMAL) trial was a cluster-randomized, parallel-group study conducted in eight villages in Burkina Faso during the 2015 rainy season. Villages were randomly assigned to either the intervention group or control group. While all eligible participants received a single oral dose of ivermectin and albendazole, the intervention group received five additional doses of ivermectin at 3-week intervals during the next 18 weeks of treatment.

Overall, there were 2,712 participants, about evenly distributed by sex, who were a median age of 15, including 590 children ages ≤5. A total of 1,447 were in the intervention group and 1,265 in the control group, although 23% of the intervention group and 18% of the control group met the exclusion criteria for mass drug administration (defined as height <90 cm, pregnancy, breastfeeding if the infant was within 1 week of birth, and a history of travel to countries endemic for Loa Loa).

There was a significant difference in the incidence of malaria between the intervention and control groups, with the authors noting malaria incidence differed the most between the two groups around weeks 8 and 16, about 1-2 weeks after the third and sixth mass drug administrations.

“This lag between the drug administration and its effect on incidence possibly reflects the pharmacokinetics and mosquitocidal activity of ivermectin,” the team wrote.

Moreover, Foy and co-authors found that the proportion of children with zero malaria episodes in the intervention group was more than twice that in the control group (64 vs 23, respectively), with a longer median time to first malaria episode in the intervention group.

There were adverse events recorded in 65 of 2,712 participants, with the authors noting 32 adverse events from the child cohort. Of the 65 adverse events, 55 were classified as not related to the intervention. Those that were related were classified as “adverse reactions,” such as vomiting, pruritus, and edema in the limbs, or tremors. There were also 20 deaths over the study period, though the authors said they were either “unlikely or not related” to the intervention.

An accompanying editorial by Carlos Chaccour, MD, of Universidad de Navarra in Pamplona, Spain, and N. Regina Rabinovich, MD, of the Harvard T.H. Chan School of Public Health in Boston characterized the study as “an important step for a promising, preventive intervention for malaria.”

“These results provide the first evidence of an effect of mass ivermectin administration that goes beyond mosquito mortality, showing a measurable reduction in malaria incidence in children aged 5 years or younger, thereby demonstrating the concept of community effects,” the editorialists wrote. “This trial continues to build the evidence base and, thus, increase interest in the repurposing of an existing drug that could help bridge to a more effective malaria strategy.”

Limitations to the data noted by Foy and colleagues include the absence of making the study population or study team, given that the authors could not provide mass administration of placebo for the control villages in this trial. The researchers also said that bias could have been introduced from the selection of villages for the study.

This study was supported by the Bill & Melinda Gates Foundation, with additional support from Laboratoire Mixte International sur les Maladies à Vecteurs.

The authors reported having no competing interests.

Chaccour and Rabinovich disclosed co-authoring three papers on this general topic with two of the article’s authors, Brian Foy and Hannah Slater, both of whom are participants in the Malaria Ivermectin Roadmap, which they are leading.