Insights from Phase 3 Trial in Burkina Faso on Ivermectin’s Role in Malaria Control
Sunil Parikh, MD, MPH, discussed how challenges like drug resistance and the limitations of current methods hindered ivermectin’s effectiveness in reducing malaria incidence.
A large clinical trial in Burkina Faso, RIMDAMAL II (NCT03967054), found that repeated high-dose ivermectin mass drug administration (MDA) did not significantly reduce malaria incidence in children when integrated with seasonal malaria chemoprevention (SMC). The study, published in The Lancet, evaluated ivermectin’s safety and efficacy in killing malaria-carrying mosquitoes that feed on treated individuals. Despite its safety and potential to impact mosquito survival, ivermectin MDA did not provide meaningful malaria control benefits in this setting, leading researchers to suggest further studies to assess its role in vector control under varied epidemiological conditions.
While mosquito survival decreased in the ivermectin group immediately post-treatment in 2019 (P <.0001), this effect was not sustained. Additionally, children in the ivermectin group showed greater improvements in hemoglobin levels (P = .007). Although, external factors such as the government’s distribution of insecticide-treated nets during the trial and the high diversity of parasites and mosquito species may have influenced the results.
The phase 3, double-blind, placebo-controlled, cluster-randomized trial was conducted across 14 villages over two rainy seasons (2019–2020). Communities were assigned to receive either ivermectin or a placebo, with over 4,000 participants monitored. Malaria incidence among children remained similar between the intervention (1.78 cases per 100 person-weeks) and control groups (1.84 cases per 100 person-weeks; P = .8723).
In this first part of our interview with investigator Sunil Parikh, MD, MPH, professor at Yale School of Public Health, we opened up discussing the broader challenges of malaria control and the rationale behind integrating ivermectin with seasonal malaria chemoprevention
“Now, we’ve been really throwing the kitchen sink against malaria for over a couple of decades, and we’ve made a lot of progress—not going to deny that. In fact, really from 2000 until 2015, we reduced malaria rates tremendously in Sub-Saharan Africa and the rest of the world. However, I’d say about 5, 6, or 7 years ago, we started to see a plateau in our ability to control and lower rates of disease and death,” he said.
According to Parikh, the resurgence in malaria cases is due to multiple challenges, including drug and insecticide resistance. While bed nets remain a key tool in malaria prevention, they primarily target indoor-biting mosquitoes, leaving outdoor exposure unaddressed.
“There has been growing resistance to drugs and growing resistance to insecticides. One of the major ways we have reduced malaria is by using bed nets, and those bed nets contain insecticides. But the bed nets are only really effective for mosquitoes that bite people inside the house or rest inside. As we all know, you get bitten by mosquitoes outside as well,” Parikh said.
Parikh explained that ivermectin offers a unique approach by targeting mosquitoes at all times. The drug, which has been widely used for parasitic disease control, kills mosquitoes when they bite a treated individual.
“The idea behind ivermectin is to try to fill another hole in our armamentarium against malaria by targeting mosquitoes all the time. And the clever way to do that is with ivermectin, which has been given for decades to eliminate some of the lesser-known parasitic diseases in Africa and elsewhere. If an individual takes it and a mosquito bites them while there’s enough drug in their blood system, the mosquitoes die.”
He elaborated on the study design: “The idea here was to integrate giving ivermectin more frequently to populations alongside another intervention that was already being delivered at the same time, so that we could hit the malaria parasite with a bunch of different control measures.”
A key focus of the study was ensuring practical implementation if the intervention worked. “Just to summarize—a lot of times we do studies and try to show an effect of something, but we don’t often think about, ‘Well, if that was an effective strategy, how do we then implement it?’ So the way we designed the study was that if it was going to be effective, we would also have a way to roll it out,” he said.
Part 2 of our interview discussed the implications of these results in greater depth, and Parikh provided further insights into the study's implications: Ivermectin Does Not Reach Primary Endpoint in Burkina Faso Malaria Trial
