Experimental Malaria Infection of Healthy Malaria-Naive Adults by Mosquito Bite with the Genetically Modified Plasmodium Falciparum NF54/iGP3 GAP

Malaria is caused by the Plasmodium parasite and is spread through the bite of mosquitos. During the blood stage of a malaria infection, the parasite can be found in four different forms. Most antimalarial drugs effectively kill the parasites, however, they do not kill one form of the parasite known as gametocytes. Gametocytes are important in the spread of malaria as they are the only form which can be passed from human back to a mosquito.

Currently, primaquine (an antimalarial drug) is the only medicine which kills gametocytes. However, this cannot be given to everyone. Individuals with certain genetic and metabolic disorders, including glucose-6-phosphate dehydrogenase (G6PD) deficiency, face severe health risks if they take Primaquine. Testing for G6PD deficiency is expensive and not available worldwide, which further reduces the number of individuals who can safely take this medication. Therefore, researchers need to develop new antimalarial drugs which kill gametocytes that are safe for all people.

Developing an improved controlled human malaria infection (CHMI) model which produces more gametocytes is a crucial step in advancing antimalarial research, especially targeting the transmission stage. To achieve this, the investigators have created a laboratory made genetically modified (change in DNA), malaria parasite known as Plasmodium falciparum NF54/iGP3, which makes an increased number of gametocytes in comparison with naturally occurring malaria parasites.

The purpose of this study is to develop a CHMI with NF54/iGP3 genetically altered parasites to assess the safety of infecting humans with this malaria parasite as well as determine the growth of the malaria parasites in humans and the effect of anti-malarial drugs. Samples from this study will be used to create a master cell bank of the NF54/iGP3 parasite, so that future research can be carried out using a malaria blood-stage infection model that will produce a greater proportion of gametocytes during infection.

The importance of this research is crucial for the future development and testing of new treatments and vaccines against malarial gametocytes. The development of new antimalarial drugs against malarial gametocytes will over time prevent malaria being transmitted from humans to mosquitos ultimately eliminating the continual spread of malaria.