A STUDY ON THE PATHOGENESIS OF HUMAN CEREBRAL MALARIA AND CEREBRAL BABESIOSIS

Cerebral complications are important, but poorly undestood pathologica l features of infections caused by some species of Plasmodium and Babe sia. Patients dying from P. falciparum were classified as cerebral or non-cerebral cases according to the cerebral malaria coma scale. Light microscopy revealed that cerebral microvessels of cerebral malaria pa tients were filled with a mixture of parasitized and unparasitized ery throcytes, with 94% of the vessels showing parasitized red blood cell (PRBC) sequestration. Some degree of PRBC sequestration was also found in non-cerebral malaria patients, but the percentage of microvessels with sequestered PRBC was only 13%. Electron microscopy demonstrated k nobs on the membrane of PRBC that formed focal junctions with the capi llary endothelium. A number of host cell molecules such as CD36, throm bospondin (TSP) and intercellular adhesion molecule I (ICAM-1) may fun ction as endothelial cell surface receptors for P. falciparum-infected erythrocytes. Affinity labeling of CD36 and TSP to the PRBC surface s howed these molecules specifically bind to the knobs. Babesia bovis in fected erythrocytes produce projections of the erythrocyte membrane th at are similar to knobs. When brain tissue from B. bovis-infected catt le was examined, cerebral capillaries were packed with PRBC Infected e rythrocytes formed focal attachments with cerebral endothelial cells a t the site of these knob-like projections. These findings indicate tha t cerebral pathology caused by B. bovis is similar to human cerebral m alaria. A search for cytoadherence proteins in the endothelial cells o f cattle may lead to a better understanding of the pathogenesis of cer ebral babesiosis.