Malarial toxins and the regulation of parasite density.

For over a century it has been recognized that many of the clinical symptoms of malaria are caused by toxins released by rupturing schizonts, but it is only in the past few years that the underlying mechanisms have begun to be understood. Dominic Kwiatkowski here focuses on the toxins that cause malaria fever by stimulating host cells to produce tumour necrosis factor a (TNF) and other pyrogenic cytokines. Both TNF and fever have antiparasite properties, and it is proposed that the release of these toxins plays an important role in the regulation of parasite density within the host. Cerebral malaria is related to excessive TNF production. Recent data indicate that this can be the consequence of genetic variation in the host's propensity to produce TNF.