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(American Journal of Pathology. 2002;160:655-666.)
© 2002 American Society for Investigative Pathology

Regular Articles

Axonal Injury in Cerebral Malaria

Isabelle M. Medana^*, Nicholas P. Day, Tran Tinh Hien, Nguyen Thi Hoang Mai, Delia Bethell, Nguyen Hoan Phu, Jeremy Farrar^¶, Margaret M. Esiri, Nicholas J. White^¶ and Gareth D. Turner^*

From the Nuffield Departments of Clinical LaboratorySciences^*
and Medicine,
andthe Department of Neuropathology,
Universityof Oxford, Oxford, United Kingdom; and the Centre for TropicalDiseases
and the Wellcome TrustResearch Unit,^¶
Cho Quan Hospital, Ho ChiMinh City, Viet Nam

Impairment of consciousness and other signs of cerebral dysfunction are common complications of severe Plasmodium falciparum malaria. Although the majority of patients make a complete recovery a significant minority, particularly children, have sequelae. The pathological process by which P. falciparum malaria induces severe but usually reversible neurological complications has not been elucidated. Impairment of transport within nerve fibers could induce neurological dysfunction and may have the potential either to resolve or to progress to irreversible damage. ß-amyloid precursor protein (ß-APP) immunocytochemistry, quantified using digital image analysis, was used to detect defects in axonal transport in brain sections from 54 Vietnamese cases with P. falciparum malaria. The frequency and extent of ß-APP staining were more severe in patients with cerebral malaria than in those with no clinical cerebral involvement. ß-APP staining was often associated with hemorrhages and areas of demyelination, suggesting that multiple processes may be involved in neuronal injury. The age of focal axonal damage, as determined by the extent of the associated microglial response, varied considerably within tissue sections from individual patients. These findings suggest that axons are vulnerable to a broad range of cerebral insults that occur during P. falciparum malaria infection. Disruption in axonal transport may represent a final common pathway leading to neurological dysfunction in cerebral malaria.

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