Observed every April 25, World Malaria Day is a call to action against the disease. Awareness saves lives. So does research.
What Is Malaria?
Malaria is a life-threatening infectious disease caused by Plasmodium parasites that are spread by mosquitoes. It remains one of the most serious public health challenges in the world today. According to the World Health Organization (WHO), there were an estimated 263 million cases of malaria globally in 2023, resulting in approximately 597,000 deaths. Children under the age of five accounted for nearly three-quarters of all fatalities worldwide (WHO, 2024). For reference, that’s roughly four times as many children dying from malaria compared to cancer.
Early signs of malaria typically include fever, chills, and headache, which can range from mild to severe. In serious cases, the disease progresses to fatigue, confusion, seizures, and organ failure. Without prompt treatment, severe malaria can be fatal.
How Is Malaria Spread?
Humans contract malaria through the bites from infected Anopheles mosquitoes. When an infected mosquito bites a person, it introduces Plasmodium parasites into the skin. The parasites then crawl around, trying to find a blood vessel so they can break in and travel to the liver via the bloodstream. In the liver, they mature and multiply from one parasite to roughly 50,000 before re-entering the bloodstream in an entirely new form that infects red blood cells. As the parasites reproduce inside red blood cells and cause them to rupture, the characteristic cycles of fever and chills associated with the disease emerge (CDC, 2024). Some parasites develop into a third form that can be picked up by a new mosquito biting an infected person, and that mosquito can then pass the parasite along to another person, starting the cycle anew.
Why Does Malaria Research Depend on Animal Studies?
Malaria is the most complex pathogen for which researchers have tried to develop a vaccine. Compared to viruses which enter cells, make copies of themselves, and emerge in the same form, the Plasmodium parasite is far more intricate. Its life cycle goes from mosquito, to the skin, the blood, the liver, back into the blood, and then again into the mosquito, directly interacting with many different cell types across many different organs. During this time, it not only looks different to researchers under the microscope but also looks different to the body’s immune system, meaning that fighting this single parasite is more akin to fighting four different bugs in one.
Finding safe, effective treatments and vaccines for malaria requires understanding and targeting the parasite’s complexity rather than simplifying it. This includes how it interacts with the immune system across multiple organs over the repeated, weeks-long infections that children will endure in malaria-endemic areas. Researchers use a range of tools to study malaria, including cell cultures, computer models, and animal studies, with each contributing something different. Cell cultures and computer models can capture parts of how the parasite behaves, but they cannot account for all of the variables involved in malaria, like a person’s age, how many times they’ve had malaria, and how the immune system is shaped by the parasite’s defenses, which hijack and shape our biology.
Different types of malaria infect different types of species. Mice, in particular, have served as important models for learning about the parasite. However, the Plasmodium that infects mice is not the same as that which infects humans, and mice have a very different immune system. A monkey’s immune system, on the other hand, more closely mirrors our own, and the species of Plasmodium that naturally infect monkeys are extremely similar to those that infect us humans, even crossing over in areas where monkeys and humans live near each other. This makes monkeys uniquely valuable for learning how the human body responds to infection and how new vaccines and interventions can fight off malaria (National Academies of Sciences, Engineering, and Medicine, 2011).
Oregon’s Role in the Fight Against Malaria
At the Oregon National Primate Research Center (ONPRC), researchers are working to advance promising vaccine candidates and even open entirely new avenues for vaccines in general with the help of the monkeys. An example of the ongoing research is understanding how a vaccine can get around the many defenses the parasite uses as it hides out in the liver (an organ which contains dozens of unique cell types that change with age, environment, and infection). This complex organ provides more accurate data when studied in monkeys than in mice or even advanced organ-on-chips, which recapitulate only small, disconnected pieces of liver that do not interact with the rest of the immune system. The world-class veterinary surgeons at ONPRC have refined minimally invasive liver biopsies using advanced surgical techniques with small incisions similar to a meniscus repair or vasectomy. Using this technique, researchers have for the first time discovered that there are pieces of the parasite which can be targeted by your immune system, specifically your T cells. These parasite pieces, called “antigens”, are the key parts used in vaccines to build up immune defenses. Because T cells can last for decades, unlike short-lived antibodies, and because these newly discovered parasite antigens are the same across every strain and species of Plasmodium, this research has laid the first path for a universal malaria vaccine capable of lasting for a lifetime.
To understand what monkeys can and, just as importantly, what they cannot predict, scientists at ONPRC are comparing other malaria vaccines where results differed between rodents and humans. These results are also being compared to the latest non-animal or “in vitro” assays with the explicit goal of replacing animals where possible and reducing their use to specific questions when and if they are still needed.
These and other studies are addressing complex questions like how to make malaria vaccines resistant to pathogen escape, work specifically in children, last longer with fewer doses, combine with multiple vaccines, target the pathogen in the organs that matter most, and make them accessible to the world’s most vulnerable kids. While these questions are malaria-specific, they address the same needs of all vaccines, and success in any of these areas will improve and accelerate vaccines for everything from flu to cancer. These are the ways in which animals in science are helping to prevent disease in children across the globe.
Oregon’s Malaria Research in the News
OHSU News. (2019, January 23). New vaccine offers fresh take on malaria fight. Oregon Health & Science University. https://news.ohsu.edu/2019/01/23/new-vaccine-offers-fresh-take-on-malaria-fight
OHSU News. (2024, May 10). Immunology researcher uses science to make a difference in battle against malaria. Oregon Health & Science University. https://news.ohsu.edu/2024/05/10/immunology-researcher-uses-science-to-make-a-difference-in-battle-against-malaria
References
Centers for Disease Control and Prevention (CDC). (2024). About malaria. U.S. Department of Health and Human Services. https://www.cdc.gov/malaria/about/index.html
National Academies of Sciences, Engineering, and Medicine. (2011). Guide for the care and use of laboratory animals (8th ed.). National Academies Press. https://doi.org/10.17226/12910
Hansen, S. G., Womack, J., Scholz, I., Renner, A., Edgel, K. A., Xu, G., Ford, J. C., Grey, M., St. Laurent, B., Turner, J. M., Planer, S., Legasse, A. W., Richie, T. L., Aguiar, J. C., Axthelm, M. K., Villasante, E. D., Weiss, W., Edlefsen, P. T., Picker, L. J., & Früh, K. (2019). Cytomegalovirus vectors expressing Plasmodium knowlesi antigens induce immune responses that delay parasitemia upon sporozoite challenge. PLOS ONE, 14(1), e0210252. https://doi.org/10.1371/journal.pone.0210252
World Health Organization (WHO). (2024). World malaria report 2024. https://www.who.int/teams/global-malaria-programme/reports/world-malaria-report-2024