Malaria--still unconquered.

T mere mention of malaria evokes visions of the devastating effects of this still unconquered disease. Just how much damage it inflicts is highlighted by a recent observational study of the natural history of complicated falciparum malaria reported in this issue1 of the journal. The authors found cerebral malaria, jaundice and renal failure as the most common combination of multiorgan dysfunction. The mortality rate rose from 14.6% in patients with a single organ dysfunction to 100% in those with multiorgan dysfunction. The previous major study on malaria reported in the journal related to cerebral manifestations of malaria.2 How does such tissue and organ system damage occur when there is no known malaria toxin? The sporozoites injected by the mosquito invade hepatocytes by attachment to the heparan sulfate glycoproteins and LDL receptors.3 While invasion by P. vivax is restricted to the reticulocytes, P. falciparum invades RBCs of all stages. Cycles of invasion and growth in RBCs produce a parasite biomass that enlarges exponentially causing fever, anemia and sequestration in microvascular beds. Rosetting and cytoadherence mediated by PfEMP-1 is central to the pathogenesis of severe falciparum malaria.4 These proteins exposed on RBC knobs have domains that adhere to host molecules including CD36 in the systemic vasculature, ICAM-1 in the cerebral circulation and syncytiotrophoblastic CSA in the placenta.5-7 Sequestration and binding stimulates local inflammatory cytokines and mediators such as TNFα and NO. Functional obstruction occurs rather than physical occlusion as in a thrombotic stroke. Delivery of oxygen and glucose is reduced, but recovery can occur rapidly in most patients. Metabolic acidosis, hypoglycemia, non-convulsive status epilepticus, superimposed bacterial infection are the consequences of this infection. Therefore severe falciparum malaria must be treated as a medical emergency. The diagnosis of severe falciparum malaria is established by any of the features set out by WHO, in the presence of P. falciparum infection and with reasonable exclusion of an alternative diagnosis.8 Blood smears should be prepared and examined by