Human-specific evolution of sialic acid targets: Explaining the malignant malaria mystery?

Malaria caused by Plasmodium falciparum (“malignant malaria”) is one of the most devastating pathogens of humans (1). Plasmodium reichenowi, which infects chimpanzees and gorillas, is the closest relative of P. falciparum (2). In early 20th-century experiments (never to be replicated), blood from P. reichenowi-infected chimpanzees was injected into humans, but failed to produce infections (3). Conversely, chimpanzees injected with P.falciparum-infected human blood suffered no in fection. Taken together, these data suggested that each parasite had coevolved with its host, but did not rule out chimpanzee to human transmission, or vice versa. In this issue of PNAS, Rich et al. (4) provide an answer to this malignant malaria “mystery” and confirm a prediction that we and our colleagues made earlier (5).