MalariaMalaria is an infectious disease that occurs in large parts of Africa, Asia, and South America. The disease is caused by an infection by the Plasmodium parasite, which is transferred through the bite of the female Anopheles mosquito. There are five species of the Plasmodium parasite that can infect humans, with Plasmodium falciparum (malignant malaria) being the most dangerous and deadly type.
If a person is bitten by an infected mosquito, the parasite can enter the body. After infection, the parasite first settles in the liver and then moves on to the red blood cells. Seven to ten days after infection, a person starts to exhibit symptoms like headaches, muscle pain, fevers, and chills.
A malaria infection can develop into a life-threatening illness, causing anemia, coma, seizures, and organ failure (e.g. the liver or spleen). These symptoms can be fatal, especially when patients experiencing malaria for the first time are not treated quickly enough with antimalarials. These are often young children or tourists in the tropics.
How common is malaria?In 2015, 214 million people were diagnosed with malaria worldwide and the illness resulted in 438,000 deaths. The vast majority of cases occur in Africa, primarily in children under five years of age (WHO, Malaria World Report 2015). In the Netherlands, 356 cases of malaria occurred in tourists and immigrants from the tropics during 2015.
Malaria preventionMalaria infection can be prevented in two ways. The transmission of the disease from a mosquito to human can be prevented by taking measures to repel mosquitoes such as insecticide-treated bed nets. The preventive use of antimalarials, such as by tourists temporarily visiting a region where malaria is present, can stop the parasite from causing illness in the human after transmission.
Thanks to global attention to the spread of malaria, the number of malaria cases has dropped by nearly 50% over the past ten years. However, malaria still continues to be responsible for a great deal of suffering and death. Additionally, resistance to current antimalarials is growing. In the fight to wipe out malaria entirely, the development of an effective vaccine that could prevent malaria would be an enormous breakthrough.
Malaria-ResearchAn effective vaccine is imperative in the fight against malaria. The Center for Clinical Malaria Studies has been performing research for more than fifteen years to contribute toward the development of such a vaccine.
Controlled human malaria infections in volunteersDuring controlled human malaria infections (CHMI), we infect healthy volunteers with malaria by having them bitten by malaria-infected mosquitoes. Over the course of the infection, doctors and researchers are able to acquire information about the illness, which they can use to develop better treatment methods. In this way, the effectiveness of a new malaria vaccine can also be tested.
Human testing is necessary because the current animal testing models are not precise enough for human malaria. At the Center for Clinical Malaria Studies at Radboud university medical center, we have more than fifteen years of experience with experimental human malaria studies.
What takes place during a controlled human malaria infection?Step 1: Medical examination
Volunteers will receive a comprehensive medical examination. A volunteer can only participate in the study if he or she is completely healthy.
Step 2: The malaria infection
A cage containing mosquitoes infected with Plasmodium falciparum parasites is placed onto the forearms of the volunteers. These mosquitoes are bred in the malaria unit of Radboud university medical center and have never been in the outside world. The malaria parasites are bred according to the highest quality standards and are susceptible to standard antimalarials.
Step 3: Close medical monitoring
Our clinical-researchers monitor the volunteers daily to see if they develop malaria. If the malaria infection was successful, this is always the case. A volunteer will develop malaria within a maximum of 21 days, but usually between the 7th and 11th day after exposure to the infected mosquitoes. For this reason, beginning on the 6th day after exposure, volunteers will be tested daily during which blood samples will be taken until the infection is detected.
Step 4: Malaria treatment
As soon as the malaria parasites appear in the blood, we will treat the volunteer with highly effective antimalarials. It is expected that the malaria infection will cause most volunteers to develop flu-like symptoms such as headaches, muscle pain, fatigue, and sometimes fever. These symptoms usually disappear within a few days. After this malaria treatment, the malaria parasites will disappear from the body entirely and there is no chance that the infection will return.
Malaria vaccin developmentThrough controlled human malaria infections in healthy volunteers, researchers can study the immune response to malaria. We use this knowledge to develop new, better malaria vaccines.
We research how the malaria parasite itself can be used as a vaccine by repeatedly infecting healthy volunteers with malaria while they take antimalarials. The antimalarials prevent the volunteers from becoming ill, but the immune system comes into contact with the parasite and learns how to destroy it. If these volunteers are bitten by mosquitoes with malaria again, they will no longer become sick even without the antimalarials.
Together with the Leiden University Medical Center and the American company Sanaria Inc., a weakened malaria parasite has been developed at Radboud university medical center, in which two genes have been removed. This “genetically modified” parasite stops developing early on, which, as expected, results in no symptoms occurring in the human subject, but it is still recognized by the immune system. In 2017, we will test if this parasite can be used as a vaccine.
Testing malaria vaccinesTesting of a potential vaccine must first be done extensively on laboratory animals. At a later stage, the vaccines will be tested on healthy volunteers. After a malaria vaccine is found to be safe in healthy volunteers, it will be tested whether the vaccine is effective in preventing malaria. Sometimes, this research is conducted among a group of volunteers in countries where malaria is very common, like in Africa. However, these types of studies are often difficult to set up and conduct in Africa. In order to advance the development of malaria vaccines, these types of studies can also be performed in countries where malaria does not occur naturally. This involves healthy volunteers receiving the new vaccine and being exposed to malaria under strictly controlled conditions in order to see whether the vaccine can effectively prevent malaria.
The Center for Clinical Malaria Studies (CCMS) of Radboud university medical center in Nijmegen is one of the few places in the world where the malaria vaccine can be tested on healthy volunteers. In the meantime, the CCMS has accumulated over fifteen years of experience in this area.
In the years to come, multiple studies with promising malaria vaccines will be performed at the CCMS.