THE MALARIAL FEVER RESPONSE - PATHOGENESIS, POLYMORPHISM AND PROSPECTS FOR INTERVENTION

It is estimated that over 200 million people each pear suffer debilita ting attacks of malarial fever, and roughly 2 million of these episode s are fatal. The fever is caused by tumour necrosis factor (TNF) and o ther pyrogenic cytokines that are released by the host immune system i n response to products of schizont rupture. TNF has anti-parasitic pro perties but excessive TNF production is thought to play an important r ole in the pathogenesis of cerebral malaria. This review summarizes re cent attempts to achieve molecular characterization of the parasite co mponents that stimulate the host TNF response, and to define the host and parasite factors that affect the level of TNF production. Of parti cular interest are host polymorphisms that may regulate TNF gene expre ssion, and naturally acquired antibodies that prevent the parasite fro m inducing TNF, both of which correlate with the clinical severity of infection. Our understanding of these processes, which are potentially of considerable therapeutic relevance, remains very limited at both t he molecular and the epidemiological level.