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Cerebral malaria (CM) is a major cause of death in severe Plasmodium falciparum malaria. We present quantitative electron microscopic findings of the neuropathologic features in a prospective clinicopathologic study of 65 patients who died of severe malaria in Thailand and Vietnam. Sequestration of parasitized red blood cells (PRBCs) in cerebral microvessels was significantly higher in the brains of patients with CM compared with those with non-cerebral malaria (NCM) in all parts of the brain (cerebrum, cerebellum, and medulla oblongata). There was a hierarchy of sequestration with more in the cerebrum and cerebellum than the brain stem. When cerebral sequestration was compared with the peripheral parasitemia pre mortem, there were 26.6 times more PRBCs in the brain microvasculature than in the peripheral blood. The sequestration index was significantly higher in CM patients (median = 50.7) than in NCM patients (median = 6.9) (P = 0.042). The degree of sequestration of P. falciparum-infected erythrocytes in cerebral microvessels is quantitatively associated with pre-mortem coma.
Received February 18, 2003. Accepted for publication May 30, 2003.
Acknowledgments: We thank the staff in Vietnam and Thailand for their assistance in clinical care and specimen collection. We also thank Marie Rychetinic and Andrew Skinner (Electron Microscopy Unit in Oxford) for help with processing the electron microscopic samples.
Financial support: This work was supported by grants from the Faculty of Tropical Medicine of Mahidol University and The Wellcome Trust of Great Britain directly to the research unit in Vietnam and as part of the Wellcome Trust-Mahidol University, Oxford Tropical Medicine Research Programme. Emsri Pongponratn received a Wellcome Trust traveling fellowship as part of this project.
Authors’ addresses: Emsri Pongponratn, Parnpen Viriyavejakul, and Sornchai Looareesuwan, Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. Gareth D. H. Turner and David J. P. Ferguson, Nuffield Department of Clinical Laboratory Sciences, Level 1 Pathology, Electron Microscopy Unit, The John Radcliffe Hospital, Oxford OX3 9 DU, United Kingdom, Telephone: 44-1865-220-514, Fax: 44-1865-220-524, E-mail: david.ferguson{at}ndcls.ox.ac.uk. Nicholas P. J. Day, Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam and Center for Tropical Diseases, Nuffield Department of Medicine, The John Radcliffe Hospital, Oxford, OX3 9DU, United Kingdom. Nguyen Hoan Phu, Nguyen Thi Hoan Mai, Tran Tinh Hien, Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam. Julie A. Simpson and Kasia Stepniewska, Wellcome Trust Clinical Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. Nicholas J. White, Center for Tropical Diseases, Nuffield Department of Medicine, The John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom and Wellcome Trust Clinical Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
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