Within the BPRC, one of the research themes is focused on two important infectious diseases that affect the poorest people in the world: malaria and tuberculosis. More information on tuberculosis can be found here. Malaria is caused by a parasite that is transmitted by mosquitoes and annually up to a million people, mostly children under the age of 5 in sub-Saharan Africa, die because of the disease. Existing drugs rapidly loose their activity due to the development of resistance by the parasite and really effective vaccines are not yet available. Given that policy makers are more and more convinced that malaria needs to be eradicated, research is focusing on development of new vaccines and drugs. Both vaccines and drugs are indispensable in a successful campaign to eradicate malaria. The malaria parasite has a complicated lifecycle, with development in the malaria mosquito as well as in liver and blood of its human host. This enormously complicates research on vaccines and drugs.
Malaria parasites can infect humans, primates, rodents, birds and reptiles. We work with primate malarias in animal models, as the primate parasites are closely related to the human malaria parasites and the host, the rhesus monkey, is closely related to humans. Thus metabolism and immune system of the monkey are very similar to those of the human and studies in rhesus monkeys will be very predictive of the human situation. In addition, one of the most important human parasites uniquely can form dormant parasites in the liver that can re-activate at certain times and again cause malaria. This unique trait is only found in a few primate malarias and can thus only be studied in primates. The primate models we use are very well positioned to improve our understanding of malaria biology and to pre-clinically evaluate safety and efficacy of new vaccines and drugs. Apart from working with primate models we also put a lot of emphasis on refinement and reduction of animal use e.g. by developing culture systems for various developmental forms of malaria.
A large part of our research, that initially takes place with cultured parasites, focuses on discovery and development of new vaccines and drugs. We exploit the newest technologies to understand how a parasite works, how it interacts with its host and where it would be vulnerable. We also test new drugs against liver forms of the parasite in a uniquely developed culture model. Here our focus is on the sleeping liver forms that are extremely difficult to kill. Only when compounds have shown activity in this culture model they will be further evaluated in the primate infection model. Within the BPRC, a new vaccine, called AMA1, against the blood forms of malaria has been developed. The use of primate malaria models and vaccine production and analysis techniques has resulted in the first clinical testing of this vaccine in humans. This testing takes many years and is first only on safety, followed later by testing on efficacy.