IMMUNOPATHOLOGICAL CHANGES IN HUMAN CEREBRAL MALARIA

Pathogenic mechanisms in human cerebral malaria remain unclear. We ree valuate the role of cell-mediated immune mechanisms in the pathogenesi s of this disease based on autopsy findings in a 34-year-old Caucasian male. Histologic examination of brain tissue showed typical features of severe malaria infection (sequestration of Plasmodium falciparum-in fected erythrocytes in vessels, cerebral oedema, petechial lesions and Durck granulomas). In addition to these classical changes, we found t hat leukocytes that stained positively in immunohistochemistry for CD6 8 and tumor necrosis factor-alpha (TNF) coexisted with infected erythr ocytes in capillaries, whereas in venules the monocyte population outn umbered the erythrocytes. Notable expression of ICAM-1 on endothelial cell surface was detected by immunohistochemistry in vessels with sequ estered cells but not in unaffected vessels. These changes are identic al to those of the murine model of the disease, in which cell-mediated immune mechanisms and TNF have been implicated. In vitro, ICAM-1 has been shown to be a potential ligand for P. falciparum-infected erythro cytes. In malaria patients, high serum TNF levels, which have been det ected in close correlation with disease severity, may thus favor adhes ion to endothelial cells of either red or white blood cells via enhanc ed ICAM-1 expression. The present observations are further evidence fo r a role of cell-mediated immunity in the pathogenesis of human cerebr al malaria.