Fig. 1. : understanding the natural evolution of malaria outcomes by parasitaemia, immunity, and period of exposure in endemic areas. In endemic settings, the natural evolution of malaria is initiated when uninfected individuals become infected for the first time, usually children who then develop a severe form of the illness. It is known that subjects with severe malaria have high parasitaemias and overall low protective immunity against malaria. In subsequent malarial infections, individuals initiate a more robust immune response against the parasites and exhibit lower levels of parasitaemia and milder forms of this disease. After many years of exposure to malaria and its vector, older people become resistant to malaria by exhibiting higher levels of antiparasitic immunity. Adapted from Andrade and Barral-Netto (2011).