Worldwide, malaria continues to be an important driver of public health. Over 90% of malaria cases are in Africa.1 Human infection begins when an Anopheles mosquito probes for blood during a bite. The infected mosquito introduces malaria sporozoites into the human host where they begin a complex life cycle. Clinical illness falls into two main categories: uncomplicated malaria (a flu-like illness) or severe disease, marked by end-organ involvement or high blood parasite densities. Of the severe malaria syndromes, the one with the highest mortality risk is cerebral malaria, clinically defined as coma with Plasmodium infection, and no other explanation for illness. For children with cerebral malaria who survive acute illness, many are left with long-term neurologic, cognitive, and behavioral sequelae.2

Human malarial disease is caused by five species of multi-celled parasites in the genus Plasmodium. Of these, the most important from a public health standpoint is Plasmodium falciparum, the species responsible for the vast majority of severe malaria and malaria-related deaths, most of which are in African children.1 Of the other four species, Plasmodium vivax and Plasmodium knowlesi both have infrequently been reported as causative agents of cerebral malaria. Plasmodium malariae and Plasmodium ovale rarely cause severe illness. Here we confine our discussion to malaria caused by Plasmodium falciparum.

Climate change is modifying disease epidemiology worldwide.3 As the Anopheles habitat shifts and expands, malaria is reappearing in areas (such as the southern United States) where it has long been considered eradicated. This reappearance of malaria into populations which have no immunity increases the likelihood that an individual patient will develop severe disease.