A study on the pathogenesis of human cerebral malaria and cerebral babesiosis

Abstract

Cerebral complications are important, but poorly understood pathological features of infections caused by some species of Plasmodium and Babesia. 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 patients were filled with a mixture of parasitized and unparasitized erythrocytes, 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 knobs on the membrane of PRBC that formed focal junctions with the capillary endothelium. A number of host cell molecules such as CD36, thrombospondin (TSP) and intercellular adhesion molecule I (ICAM-1) may function as endothelial cell surface receptors for P. falciparum-infected erythrocytes. Affinity labeling of CD36 and TSP to the PRBC surface showed these molecules specifically bind to the knobs. Babesia bovis infected erythrocytes produce projections of the erythrocyte membrane that are similar to knobs. When brain tissue from B. bovis-infected cattle was examined, cerebral capillaries were packed with PRBC. Infected erythrocytes formed focal attachments with cerebral endothelial cells at the site of these knob-like projections. These findings indicate that cerebral pathology caused by B. bovis is similar to human cerebral malaria. A search for cytoadherence proteins in the endothelial cells of cattle may lead to a better understanding of the pathogenesis of cerebral babesiosis.

Platelets Potentiate Brain Endothelial Alterations Induced byPlasmodium falciparum

“…Also, CD31 is frequently lost in EC lines whereas it is expressed on primary cells (71,72). The absence of CD36 on HBEC-5i cells is consistent with previous data (2,61,70) showing a low and irregular CD36 expression among brain microvessel walls. In a more recent study, CD36 was not found in brain microvessels, except in children who died from CM; in this case, the CD36 labeling appeared to be restricted to bound platelets (29).…”

“…The effect of platelets on PRBC cytoadherence was evaluated by a prior incubation of the HBEC-5i cells with or without platelets before the cytoadherence assay was run (F). Results are expressed in bound PRBC per mm 2 . Bars represent standard deviations of four determinations in four experiments.…”

Pathogenesis of Cerebral Malaria: Recent Experimental Data and Possible Applications for Humans

“…Based on reports describing only the pRBC sequestration in human CM (2,95), attention has focused on developing a model of pRBC binding. The presence of leukocytes and platelets in human CM lesions, however, prompts the need for studying threeparty and even four-party-interaction models in more depth.…”

Characterization of the Unusual Bidirectional ves Promoters Driving VESA1 Expression and Associated with Antigenic Variation in Babesia bovis

“…B. bovis cytoadhesion may occur in essentially any major organ (55)(56)(57), including the brain (1), and adhesive parasites may be selected which cytoadhere in vitro to cultured bovine brain capillary (39) and umbilical vein (34) endothelial cells. The sequestration of the mature developmental stages through cytoadhesion presumably precludes their passage through the spleen and thus mediates avoidance of splenic clearance (4).…”