Cerebral malaria (CM) is a serious complication of Plasmodium falciparum infection. Binding of parasitized erythrocytes to cerebral endothelium plays a key role in disease pathogenesis. Central nervous system signs and symptoms (coma, seizures, raised intracranial pressure) predominate in African children, whereas in adults, multiorgan system failure is more common. In this study we investigated whether changes in blood-brain barrier (BBB) structure and function are compatible with the signs and symptoms observed in Malawian children with CM. Immunohistochemistry on autopsy brain tissues from eight cases of CM showed activation of endothelial cells and macrophages, and disruption of endothelial intercellular junctions in vessels containing sequestered parasitized erythrocytes, but no gross leakage of plasma proteins. Examination of the partition of albumin between circulating plasma and the cerebrospinal fluid from 72 cases of CM showed subtle but measurable changes compatible with impaired BBB function in malaria. These findings suggest that BBB breakdown occurs in areas of parasite sequestration in CM in African children.

Evidence from clinical studies and murine models supports a role for cytokines in the pathogenesis of human cerebral malaria (CM). In this study, reverse transcriptase-polymerase chain reaction (RT-PCR) was used to investigate expression of mRNA for transforming growth factor (TGF)-beta, interleukin (IL)-1beta, and tumor necrosis factor (TNF)-alpha in human postmortem tissue. Immunohistochemistry was used to examine the distribution of cytokine protein. TGF-beta was expressed in normal brain, in CM, and in meningitis and encephalitis. IL-1beta was absent from normal brain but was detected in CM and other cerebral infections. TNF-alpha mRNA was expressed only in CM, although TNF-alpha protein was also seen in meningitis. Cytokine mRNA expression in the brain did not correlate with the density of parasitized erythrocytes detected using RT-PCR for major surface protein-2. This report of RT-PCR on postmortem human tissues infected with CM demonstrates induction of the proinflammatory cytokines TNF-alpha and IL-1beta in the brain.

Journal Article Chloroquine-induced pruritus in Malawi: lack of association with onchocerciasis Get access Gilbert Burnham, Gilbert Burnham aMalamulo Hospital, P.O. Makwasa, Malawi Search for other works by this author on: Oxford Academic PubMed Google Scholar Anthony Harries, Anthony Harries bKamuzu Central Hospital, P.O. Box 149, Lilongwe, Malawi Search for other works by this author on: Oxford Academic PubMed Google Scholar Alan Macheso, Alan Macheso bKamuzu Central Hospital, P.O. Box 149, Lilongwe, Malawi Search for other works by this author on: Oxford Academic PubMed Google Scholar Jack Wirima, Jack Wirima bKamuzu Central Hospital, P.O. Box 149, Lilongwe, Malawi Search for other works by this author on: Oxford Academic PubMed Google Scholar Malcolm Molyneux Malcolm Molyneux ∗ cLiverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK ∗Address for correspondence: Dr Malcolm Molyneux, Department of Tropical Medicine, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK. Search for other works by this author on: Oxford Academic PubMed Google Scholar Transactions of The Royal Society of Tropical Medicine and Hygiene, Volume 83, Issue 4, July-August 1989, Pages 527–528, https://doi.org/10.1016/0035-9203(89)90278-2 Published: 01 July 1989 Article history Received: 24 January 1989 Revision received: 24 February 1989 Accepted: 28 February 1989 Published: 01 July 1989