Endothelial cell activation in muscle biopsy samples is related to clinical severity in human cerebral malaria

To test the hypothesis of vascular sequestration of parasitized erythrocyte s in Plasmodium falciparum malaria in vivo, a pathologic and immunohistoche mical study was done of the microvasculature of skeletal muscle biopsy samp les from P. falciparum malaria patients at different stages of severity. Pa rasitized red blood cells sequestered in the skeletal muscle vessels were o bserved in samples from necropsies but were never demonstrated in biopsy sp ecimens. Vascular cell adhesion molecule-1 and E-selectin expression was co nsistent only in specimens from cerebral malaria patients, Samples from suc h patients had strong staining of the constitutive endothelial adhesion mol ecules tested. The staining intensity gradually decreased in samples from p ersons with milder forms of the disease. Four of 13 patients with severe ma laria had aggregates of red blood cells, occasionally parasitized inside th e muscle fibers. These data suggest that skeletal muscle biopsy could be a useful model for the study of the pathogenesis of malaria in vivo.