On Tuesday, April 23, 2019, the World Health Organization (WHO) announced what could be the world’s first malaria vaccine as part of a large-scale trial project in several countries. The vaccine known as RTS, S will be given to approximately 360,000 children up to two years of age in three African countries: Malawi, Ghana, and Kenya.
Discovered in 1987, RTS, S began clinical studies at the U.S. Department of Defense’s Walter Reed Army Institute of Research (WRAIR). These clinical studies were funded by the PATH Malaria Vaccine Initiative and the Bill & Melinda Gates Foundation in hopes to discover a vaccine for children in sub-Sharan Africa. Over the next 30 years, WRAIR studied and conducted trials on RTS, S. In 2016, WHO approved the pilot implantation project, which is currently in its first stages in Malawi.
According to WHO, malaria is still a worldwide deadly killer claiming the life of a child every two minutes. In 2017, there were an estimated 219 million cases of malaria. This mosquito-borne illness claimed the lives of more than 435,000 and hundreds of millions are infected each year, some never fully recover. Now thanks to animals in research and dedicated scientists, there is hope to save lives.
Over the years, there have been many drugs and insecticides used to attack Plasmodium, the parasite that causes malaria. When a female Anopheles mosquito bites a person infected with malaria, it will carry the Plasmodium parasite and can transmit malaria to anyone it bites. Once a human or animal is bitten, the parasite enters the blood stream and begins to attack the red blood cells. This can then lead to extreme illnesses and in most cases death.
What makes malaria so difficult to overcome? Due to genetic changes over time, these female Anopheles mosquitoes become resistant to many forms of treatments. This causes scientists to constantly be on the hunt for new and better preventative measures and treatments.
Through research with animals, scientists have developed a deeper understanding of treating malaria in humans. In 1968, scientists discovered Avian malaria in African penguins which they suspected the penguins may have acquired during their migration season. Being exposed to the Plasmodium parasite has shown to be extremely fatal for the African penguin.
Since malaria has proven to affect birds the same way as it does humans, the African penguin was a fitting animal model for the research. Because of the studies done on the African penguins, scientists were able to better understand the effects of chloroquine, a popular anti-malarial drug discovered in 1950. Chloroquine prevents the growth of the Plasmodium parasite in red blood cells. It is the first-choice drug to take against malaria because it is safe for both pregnant women and children. Along with chloroquine, scientists were able to discover the effects of primaquine. Primaquine is the only drug proven to prevent a relapse of malaria and is used if chloroquine has no affect against a specific strain of malaria; but it is not safe for pregnant women and those with a deficiency of glucose-6-phosphate dehydrogenase (G6PD)- an enzyme deficiency most commonly found in males.
After administrating chloroquine and primaquine into the malaria -infected penguins, researchers discovered the mortality rate reduced from 50% to 10-15%. From these studies, researchers have been able to develop various medications containing chloroquine as an active ingredient to fight against different strains of malaria in humans. Unfortunately, over the years, the Plasmodium parasite has developed a resistance towards chloroquine, but it is still used in combination with other anti-malarial drugs to fight against this disease.
Primaquine is recommended to adults or children traveling or returning from certain areas of the world (primarily South America and Africa) known for having the malaria strains P.vivax and P.ovale. Along with penguins, scientists were able to study subacute toxicity of primaquine in dogs, monkeys, and rats. With the help from owl monkeys, scientists have been able to study chloroquine and its relation to P. falciparum – the parasite species that causes the most dangerous strain of malaria in humans.
The RTS, S vaccine took over 30 years of extensive research in which animal models have been significant contributors leading to this recent discovery. Here are just a few additional examples –
• A professor of veterinary medicine discovered in 2012 that a herd of goats were able to produce a protein (P. falciparum) in their milk that could aid in preventative measures against malaria. Today, this discovery is still under research, but scientists hope to formulate a drinkable cure in years to come.
• After a study done on mice, a drug called AB-1 was found in 2015 to cure malaria infections without any of the harmful side effects that were commonly found in drugs used against malaria. The next phase for AB-1 is human clinical trials.
• RON2L is a protein formed from the parasite that causes malaria. Non-human primates helped researchers discover in 2017 that combining an existing malaria vaccine with the protein RON2L would result in a more nullifying antibody and protect against more malaria strains. Studies continue to build upon this discovery, primarily experimenting RON2L with new vaccines.
• A study on mice in 2018 showed that a combination of transmission- blocking vaccines (TBVs) and pre-erythrocytic vaccines (PEVs) significantly reduced malaria infections by 91%. TBV prevented the mosquito from transferring the parasite while PEV focused on protecting the liver. This discovery helped scientists learn the possibility and power of combining two malaria fighting vaccines and provides a foundation for more discoveries in years to come.
These examples are just a small sampling of what animal research has done to help fight against malaria. Many of the vaccines and drugs used today to fight against and prevent malaria were discovered through years of animal testing. During clinical trials, RTS, S was able to prevent 4 in 10 malaria cases. Although this is not a 100% cure for malaria, it is clear that every step closer we have made is thanks to animal research.
By Nelia Dashiell