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(American Journal of Pathology. 1999;155:395-410.)
© 1999 American Society for Investigative Pathology


Regular Articles

A Quantitative Analysis of the Microvascular Sequestration of Malaria Parasites in the Human Brain

Kamolrat Silamut*, Nguyen H. Phu{dagger}, Christopher Whitty{ddagger}, Gareth D.H. Turner{ddagger}§, Karina Louwrier§, Nguyen T.H. Mai{dagger}, Julie A. Simpson*{ddagger}, Tran T. Hien{dagger} and Nicholas J. White*{ddagger}

From the Faculty of Tropical Medicine,*
Mahidol University, Bangkok, Thailand; the Center for Tropical Diseases,{dagger}
Cho Quan Hospital, Ho Chi Minh City, Viet Nam; The Oxford-Wellcome Centre for Tropical Diseases,{ddagger}
Nuffield Department of Clinical Medicine, University of Oxford, and the Department of Clinical Biochemistry and Cellular Science,§
University of Oxford, United Kingdom

Microvascular sequestration was assessed in the brains of 50 Thai and Vietnamese patients who died from severe malaria (Plasmodium falciparum, 49; P. vivax, 1). Malaria parasites were sequestered in 46 cases; in 3 intravascular malaria pigment but no parasites were evident; and in the P. vivax case there was no sequestration. Cerebrovascular endothelial expression of the putative cytoadherence receptors ICAM-1, VCAM-1, E-selectin, and chondroitin sulfate and also HLA class II was increased. The median (range) ratio of cerebral to peripheral blood parasitemia was 40 (1.8 to 1500). Within the same brain different vessels had discrete but different populations of parasites, indicating that the adhesion characteristics of cerebrovascular endothelium change asynchronously during malaria and also that significant recirculation of parasitized erythrocytes following sequestration is unlikely. The median (range) ratio of schizonts to trophozoites (0.15:1; 0.0 to 11.7) was significantly lower than predicted from the parasite life cycle (P < 0.001). Antimalarial treatment arrests development at the trophozoite stages which remain sequestered in the brain. There were significantly more ring form parasites (age < 26 hours) in the cerebral microvasculature (median range: 19%; 0–90%) than expected from free mixing of these cells in the systemic circulation (median range ring parasitemia: 1.8%; 0–36.2%). All developmental stages of P. falciparum are sequestered in the brain in severe malaria.





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