By Mary Guiden
Published March 13, 2019

Since his days in graduate school, Brian Foy has been fascinated with pathogens transmitted by mosquitos, and figuring out how to block the transmission of diseases like malaria. The dilemma he’s been exploring: Can you get the right disease and the right drug that blocks transmission, which could be tested in a situation where you could actually reduce disease in people?

Foy, a professor in the Department of Microbiology, Immunology and Pathology at Colorado State University, now has some answers to this quandary.

Brian Foy in the lab
Colorado State University Microbiology, Immunology and Pathology professor Brian Foy in his lab, October 2018.

A team of international scientists, led by Foy and including researchers from West Africa, France, United Kingdom and the United States, found that they were able to reduce cases of malaria in children under five years old in several villages in Burkina Faso by 20 percent, using a drug called ivermectin.

When the team looked more closely at the group of children in the clinical trial who received repeated doses of ivermectin, they found a 44 percent reduction in malaria, which Foy described as remarkable and unexpected.

“Not only did we kill the mosquitos with this drug, which blocks the transmission of malaria, but we also reduced parasite transmission to these children,” he said. “A group of them had an additional reduction in malaria, and we think the ivermectin affected the parasites in these children.”

The new study, “Repeat ivermectin mass drug administrations for control of malaria: a cluster-randomized trial to evaluate efficacy and risk of harms,” was published March 13 in The Lancet.

Deadly parasite kills hundreds of millions each year

Foy said the novel design used in this study has broad implications for attacking malaria, a preventable disease transmitted by mosquitos that affects more than 200 million people worldwide and kills 445,000 people, mostly children, each year.

The research encompassed eight villages and nearly 3,000 participants in Burkina Faso, and was conducted during the rainy season, when malaria is readily transmitted by mosquitos.

“Mostly adults received the drug, but the idea is that the mosquito that would have bitten and transmitted parasites to the kids will die,” explained Foy. “That means these kids should have less disease, less fever and less chills. And we’d see fewer deaths, too.”

Ivermectin was first discovered in the late 1970s by Walter Campbell, a biologist who worked at what is now Merck & Co., and Satoshi Omura, a microbiologist at the Kitasato Institute in Tokyo.

The drug was originally used to treat parasitic worms in livestock and pets, but in the 1980s, scientists found that ivermectin also had an effect on parasitic worms that afflict humans. Since the 1990s, it has been given to hundreds of millions of people to prevent river blindness, or onchocerciasis, and lymphatic filariasis, a tropical disease that affects the lymph nodes and lymph vessels.

Burkina Faso map

Campbell and Omura were awarded with the Nobel Prize in Physiology or Medicine in 2015 for their discovery. They shared the honor with YouyouTu, a chief scientist at the China Academy of Traditional Chinese Medicine. She was lauded for her discoveries concerning a novel substance used to fight malaria.

Children hit the hardest by malaria

In Burkina Faso, having malaria is a part of life. In the villages included in the study, during the rainy season, nearly every single person has malaria parasites in his or her system, said Foy.

Small children who have not developed an immunity to the parasite get the disease repeatedly in their young lives. In this study, researchers found that each child had, on average, 2.5 cases of malaria during the rainy season.

Side effects from malaria include fever and chills; the disease can also be fatal. Children whose families choose to go to a traditional healer instead of a hospital or clinic often die, said Foy.

A small child who is sick with malaria grasps his mother's skirt.
A small child who is sick with malaria grasps his mother's skirt.
In the villages included in the study, during the rainy season, nearly every single person has malaria parasites in his or her system, said Foy.

In the study, ivermectin was given to entire villages, which is known as a mass drug administration. This strategy has been used to effectively eliminate conditions like river blindness from Central America.

The drug is typically given to people based on weight. But Foy said the research team used a height measurement, since carrying scales to villages would not have been easy. Children who were less than 90 centimeters, or almost three feet tall, did not get the drug.

Ivermectin kills worms and mosquitos, but the research team did not expect to see the effect on malaria parasites. In fact, other researchers have suggested that this effect does not occur. But it’s the best explanation for the large 44 percent reduction in malaria cases that was found in children who received the ivermectin, said Foy.

A nurse pricks the finger of a young boy.
A nurse pricks the finger of a young boy to diagnose whether he has malaria.

“When the parasite gets inside a human’s body, it morphs a lot,” he explained. “The first place it goes is into your liver, but then a different stage emerges from your liver and invades your red blood cells, causing the disease’s symptoms. What takes place in the liver stage happens quickly and is hard to examine. Based on what we found, we believe there might be effects of ivermectin on the stage of the parasite that is in a person’s liver.”

Foy said this unexpected finding opens up the idea that health officials can give ivermectin to communities through mass drug administration, and the benefits will show up not only for the community, but also for the individuals who receive the drug.

What’s next … in West Africa, Colorado

Foy recently received a $3.6 million grant from the National Institutes of Health to continue this malaria research, working with the Institut de Recherche en Sciences de la Sante in Burkina Faso and researchers from the Yale School of Public Health, among others.

He and a team from CSU are also using the same concept to study possible ways to reduce West Nile virus transmission in Fort Collins, Colorado by feeding wild birds ivermectin-treated bird seed.

“We have some evidence that there are fewer West Nile-infected mosquitoes after we’ve put out this bird seed in the field,” said Foy.

Researchers have not yet been able to investigate possible disease reduction in humans. To do that, Foy said the team would need to enroll entire neighborhoods and test people’s blood for antibodies to the West Nile virus.

“We’d need so many people to do that, because the disease is less intense than malaria in West Africa,” he added.

This research on a novel West Nile virus transmission control strategy was recently published in PLOS Neglected Tropical Diseases.

Co-authors of the study include researchers from Yale School of Public Health, Institut de Recherche en Sciences de la Sante in Burkina Faso, Laboratorie Mixte International sur les Maladies a Vecteurs in Burkina Faso, University of Montpellier in France, Imperial College London in the UK, Ministry of Health in Burkina Faso and Centre MURAZ, also in Burkina Faso.

The research was funded by a Grand Challenges Exploration grant through the Bill & Melinda Gates Foundation.

More stories about research at Colorado State University.