Is human malarial coma caused, or merely deepened, by sequestration?

Much research into falciparum malaria coma assumes the primary event to be vascular obstruction by parasitized red blood cells. Recent evidence that vivax malaria, caused by a parasite traditionally thought not to block blood flow, seems to alter brain function to the same degree as falciparum malaria has seriously questioned this. These data are a timely call to reassess whether vascular obstruction should still be considered the primary cause of the coma of falciparum disease. They add to a growing literature that suggests that enhancement of brain-origin cytokines, such as tumour necrosis factor, by non-brain systemic inflammation and an appreciation of the degree to which neuronal homeostasis depends on them provide a more fruitful research direction.