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Ivermectin shows promise as antimalaria tool
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A common antiparasitic drug first used in animals almost 40 years ago may be a promising new tool for malaria elimination, researchers said.
According to study findings from Kenya, multiple high doses of ivermectin were well-tolerated in malaria patients and killed feeding Anopheles gambiae mosquitoes for at least 28 days after the treatment, Menno R. Smit, MD, doctoral candidate in malaria epidemiology at the Liverpool School of Tropical Medicine, and colleagues reported in The Lancet Infectious Diseases.
According to WHO, at least 216 million people were infected with malaria in 2016 — an increase of about 5 million cases over 2015 — and an estimated 445,000 of them died, mostly in Africa. Progress to reduce malaria deaths in Africa and other regions has stalled, and mortality has actually increased in others.
According to Smit and colleagues, “ivermectin is being considered for mass drug administration for malaria due to its ability to kill mosquitoes feeding on recently treated individuals.” However, despite evidence of ivermectin’s toxicity in mosquitoes, the effects of standard, single doses of the drug — 150 to 200 g/kg to treat onchocerciasis and lymphatic filariasis — have been short-lived, they said.
For their randomized, double-blind, placebo-controlled superiority trial, Smit and colleagues compared 3-day courses of high-dose ivermectin with placebo in adults aged 18 to 50 years who were also being treated for Plasmodium falciparum malaria.
Between July 20, 2015, and May 7, 2016, they randomly assigned 141 participants to receive 3 days of ivermectin 300 g/kg (n = 48), ivermectin 600 g/kg (n = 47) or placebo (n = 46). They drew blood from participants several times over 28 days and fed it to lab-reared Anopheles gambiae mosquitoes, assessing the insects’ daily survival for 4 weeks. The primary outcome was 14-day cumulative mortality of mosquitoes fed 7 days after treatment.
According to Smit and colleagues, 41.4% of mosquitoes in the placebo arm had died by day 14 after treatment compared with 96.7% and 92.7% in the ivermectin 600 g/kg and 300 g/kg arms, respectively. The effect of high-dose ivermectin on mosquito mortality declined over the course of the study but “remained significantly increased” 28 days after treatment, they reported.
Using population-level modeling, Smit and colleagues showed that adding high doses of ivermectin to regular malaria treatment could reduce malaria prevalence by at least an additional 44.4% in low-prevalence areas and up to an additional 61% in high-prevalence areas.
“Our study showed that ivermectin was well-tolerated and able to kill mosquitoes feeding on people for at least 28 days after treatment, making it a promising new tool for malaria elimination,” they wrote. “Next steps should include assessment of high-dose ivermectin safety, tolerability, mosquitocidal efficacy, and pharmacokinetics in younger age groups, and with repeated courses, before its effect on malaria transmission can be assessed through mass drug administration.”
In a related editorial, N. Regina Rabinovich, MD, MPH, scholar in residence in the Harvard T.H. Chan School of Public Health, wrote about repurposing “an old drug” as a tool for malaria control.
“Given the high variability of the vector and the parasite, more than one approach will probably be needed to confront this challenge,” Rabinovich wrote. “Studies to repurpose ivermectin could be completed by 2022 if financed soon, and this would provide a short-term option for the field. If ivermectin is effective, new endectocides that could safely provide similar benefits with improved characteristics like longer duration of action, could be developed.” – by Gerard Gallagher
Disclosures: The authors report no relevant financial disclosures. Rabinovich reports being the chair of the Malaria Eradication Scientific Alliance, which originally funded this trial several years ago but has not been involved in the design, review or writing of the project.
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