Ivermectin is an anti-parasite medication used to treat parasitic diseases, including parasitic worms, hookworm, whipworm, and external parasites and many others off label. Ivermectin works by paralyzing muscles in parasites, causing them to die. Since malaria is supposedly caused by a plasmodium parasite transmitted by mosquito bites, one might expect this powerful anti-parasitic medication to prevent malaria.
And indeed an article in this week’s MalariaWorld tests this hypothesis. ‘Safety and efficacy of repeat ivermectin mass drug administrations for malaria control (RIMDAMAL II): a phase 3, double-blind, placebo-controlled, cluster-randomised, parallel-group trial’ by Somé et al was published by The Lancet Infectious Diseases. Unfortunately, the full article is behind a paywall, but the summary does provide sufficient information for a preliminary examination and study details are available on clinicaltrials.
The study aimed to test the safety of repeated, high-dose ivermectin mass drug administration (MDA) and its efficacy for reducing malaria incidence among children when integrated with seasonal malaria chemoprevention (SMC) delivery. They provided background that previous studies had shown that ivermectin in the blood could kill mosquitos that fed on it.
They conducted a double-blind, placebo-controlled, trial in southwest Burkina Faso over two consecutive rainy seasons (2019–20). 14 villages were randomly assigned (1:1) to ivermectin or placebo MDA by random draw. Each rainy season, eligible participants from the intervention group clusters received monthly high-dose oral ivermectin MDA (three daily doses, approximately 300 μg/kg dosed by height bands) and those from the control group received monthly oral placebo MDA for up to eight treatment rounds. All participants and study personnel, apart from the pharmacist, were masked to group assignment. The primary outcome was weekly malaria incidence in children aged 10 years and younger, as assessed by weekly active case detection until week 16 of year 2, by intention to treat. Adverse events were monitored in all MDA participants through active and passive surveillance. Blood was sampled for secondary parasitological outcomes, including analysis of parasite species distribution among malaria cases. Mosquitos were sampled from pre-selected households in three clusters per group for secondary entomological outcomes, including analysis of blood-fed mosquito survivorship, mosquito biting rates, and entomological inoculation rates.
The average estimated weekly malaria incidence rate per 100 person-weeks among children in the test group was 1·78 (95% CI 1·24–2·53) and 1·84 (1·29–2·64) in the control group (statistically indistinguishable). The risk of adverse events was lower in test group (arthralgia and skin conditions higher in control group), but risk of death (0.27% vs 0.16%) and serious adverse events greater in test group (0.36% vs 0.31%). There was evidence of mosquito deaths in test group week after test but not three weeks later.
Repeated high-dose ivermectin MDA integrated with SMC distributions at the study site did not reduce malaria incidence among children relative to placebo.