PATHOPHYSIOLOGY OF CEREBRAL MALARIA

Although simple animal models relevant to human disease are lacking, m any recent clinical and experimental studies have focused on the patho physiology of cerebral malaria. Evidence of sequestration of parasitiz ed erythrocytes is found in the cerebral capillaries of patients dying from cerebral malaria. Cytoadherence of parasitized red blood cells t o endothelium is an essential process. However, no correlation was fou nd between in vitro cytoadherence of clinical isolates and the presenc e of cerebral symptoms. Resetting is defined by the agglutination of n onparasitized erythrocytes around red cells containing mature forms of the parasite, and probably contributes to the intravascular sequestra tion of erythrocytes. This phenomenon occurs in vitro, and isolates fr om patients with cerebral malaria appear to have increased resetting p roperties. The excellent recovery of most survivors, even after a deep and lengthy coma, suggests that microvascular obstruction causing cer ebral hypoxia is not the main factor contributing to cerebral dysfunct ion. Raised intra cranial pressure with or without cerebral oedema is common in children, and contributes to mortality. The nonspecific immu ne inflammatory response of the host to the malarial parasite, with re lease of various mediators, seems to be of paramount importance. Among cytokines, tumor necrosis factor (TNF) appears to be associated with mortality; although plasma levels of TNF are not correlated with neuro logical dysfunction, this does not exclude a role of this cytokine at a paracrine level. Cytoadherence of parasitized red blood cells to end othelium and concomitant activation of mononuclear blood cells may be responsible for a local synthesis of cytokines, or even neurotransmitt ers that remain to be identified.