title: Investigating long-term immunosuppression in adults infected with Plasmodium falciparum
Creators: name: McKinnon-Snell, Tate Xanthe
Publisher: name: The University of Edinburgh
Year: 2023
Subjects: subject: long-term immunosuppression
subject: Plasmodium falciparum
subject: Malaria
subject: controlled-human malaria infection model
subject: infected EBV cells
subject: CMV seropositive

description: Malaria is a disease caused by a parasite, namely a specific type Plasmodium falciparum is the most deadly, the disease is highly damaging to the body and has categories of disease ranging from mild to severe. Malaria causes over 600,000 deaths per year with children under 5 the most at risk from life-threatening severe disease. This risk of severe disease decreases with increasing infection number, and regardless of how many parasites one is infected with immunity to severe disease is acquired quickly, but how this happens is unknown. When volunteers have been infected with malaria, previous work has observed an immense adaptive immune response in first infection which was dramatically reduced in subsequent infection. This reduction in response correlated with reduced collateral damage in reinfection and protected important tissues, this may be a form of disease tolerance which protects the host and reduces the damage of infection without directly affecting the parasite itself. However, is has been argued that malaria causes suppression of immune responses. For example, experiments have observed that already present infections are less able to be controlled during malaria infection, others have shown the ability to produce effective immune responses following vaccination is diminished in people that live in areas where malaria is endemic compared to those who have never had malaria, and other studies have shown malaria may possibly be a contributing factor to increasing susceptibility to other diseases. Thus, investigating if this control of immune responses, which may be beneficial for those to not progress to severe disease, results in off-target effects or increase susceptibility to other diseases is vital in understanding how the body responds to malaria. To examine whether tolerance to malaria results in long-term immune suppression, samples were taken from a study in which volunteers who had never had malaria were infected and reinfected with P. falciparum and had samples taken before, during, 1 month and 3 months after infection. I tested the response of the adaptive immune response in two ways: a specific subset of adaptive cells to a virus that they have previously encountered, and also in a way which tests the functional ability of all adaptive immune cells. I compared the adaptive immune response before and 3 months after malaria infection, and I found change in the immune cell’s number or ability to respond to stimulation via a previously encountered virus. However, during infection, there was a decrease in response to previously encountered virus, this decrease in response was also observed across all adaptive immune cells but was resolved 3 months after infection. This data proposes that a single malaria infection does not lead to long-term immune suppression but may result in a short-term reduction in immune responses.