Evaluating the potential of a long-acting injectable ivermectin formulation in cattle against Greater Mekong Subregion Anopheles
Pre-clinical trials in Burkina Faso demonstrate that a novel long-acting injectable ivermectin formulation (mdc-STM-001) administered to cattle at a 1.0 mg/kg dose effectively kills Greater Mekong Subregion malaria vectors for up to 112 days, supporting its further evaluation for human use to aid malaria elimination efforts.
Original paper licensed under CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). This is an AI-generated explanation of the paper below. It is not written or endorsed by the authors. For technical accuracy, refer to the original paper. Read full disclaimer
Malaria remains one of the world's most persistent health challenges, particularly in the Greater Mekong Subregion, where the disease thrives in forested areas and is carried by mosquitoes that often bite people outdoors, away from the protection of nets and indoor sprays. For decades, scientists have looked for ways to break the cycle of transmission by targeting the mosquitoes themselves. One promising approach involves using a drug called ivermectin, which is already well-known for treating parasitic infections in humans and animals. When a mosquito bites a person or animal that has taken ivermectin, the drug acts as a poison to the insect, killing it before it can pass malaria to the next person. However, the standard version of this drug leaves the body relatively quickly, meaning the mosquito-killing effect lasts only about two weeks. To protect communities through an entire malaria season, researchers need a way to keep the drug in the bloodstream for months at a time, creating a long-lasting shield that turns the host into a lethal trap for the biting insects.
A team of researchers set out to test a new solution: a long-acting injectable form of ivermectin designed to release the medicine slowly over many months. They conducted their initial tests in cattle, which served as a practical model for how the drug would behave in a living host. The study took place in two phases in Burkina Faso, where different versions of the new injection were given to groups of cows at varying doses. After the injections, the researchers collected blood plasma from the animals at regular intervals over the course of nearly four months. They then brought these samples to a laboratory in Thailand, where they mixed the plasma with fresh red blood cells to create a meal for two specific types of mosquitoes that are major carriers of malaria in Southeast Asia: Anopheles dirus and Anopheles minimus. By feeding these mosquitoes the treated blood and watching how many survived over two weeks, the team could measure exactly how long the drug remained potent enough to kill them.
The results revealed a clear winner among the different formulations tested. One specific version of the long-acting injection, administered at a dose of 1.0 milligrams per kilogram of body weight, proved remarkably effective. The blood from cattle treated with this formulation continued to kill both species of mosquitoes for up to 112 days after the single injection. This duration is significant because it covers the majority of a typical malaria transmission season. While a higher dose of 1.5 milligrams per kilogram showed similar results, the researchers found no substantial benefit in increasing the dose beyond 1.0 milligrams, suggesting that the lower amount is sufficient to maintain the lethal effect while being more cost-effective and safer. Another version of the drug tested in the first phase of the study lost its ability to kill mosquitoes after about 49 days, highlighting that not all long-acting designs are equally successful.
The study also compared the effectiveness of the drug against the two different mosquito species. The results showed that the drug worked well against both, though the mosquitoes known as Anopheles minimus were slightly more sensitive to the treatment than Anopheles dirus, which is known to be one of the most tolerant mosquito species to ivermectin. Even against this tougher species, the long-acting injection maintained a strong lethal effect for the full 112-day period. The researchers calculated that the risk of a mosquito dying after feeding on the treated blood was more than four times higher than the risk of dying from natural causes, a level of effectiveness that meets international standards for new malaria control tools.
These findings offer a compelling path forward for malaria elimination in the Greater Mekong Subregion. Because the drug can be delivered as a single injection that lasts for months, it could potentially replace the need for repeated treatments that are difficult to organize and often lead to people missing doses. The researchers suggest that if this formulation proves safe and effective in humans, it could be used in mass drug administration campaigns to protect entire communities. By keeping the drug in the blood for the duration of the transmission season, such a strategy could directly target the outdoor-biting mosquitoes that have long evaded traditional control methods, offering a powerful new tool to help end malaria in the region.
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