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Tissue distribution of migration inhibitory factor and inducible nitric oxide synthase in falciparum malaria and sepsis in African children

Clark, Ian A., Awburn, Melissa M., Whitten, Richard O., Harper, Clive G., Liomba, N. George, Molyneux, Malcolm E and Taylor, Terrie E. (2003) 'Tissue distribution of migration inhibitory factor and inducible nitric oxide synthase in falciparum malaria and sepsis in African children'. Malaria Journal, Vol 2.

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Background: The inflammatory nature of falciparum malaria has been acknowledged since
increased circulating levels of tumour necrosis factor (TNF) were first measured, but precisely
where the mediators downstream from this prototype inflammatory mediator are generated has
not been investigated. Here we report on the cellular distribution, by immunohistochemistry, of
migration inhibitory factor (MIF) and inducible nitric oxide synthase (iNOS) in this disease, and in
Methods: We stained for MIF and iNOS in tissues collected during 44 paediatric autopsies in
Blantyre, Malawi. These comprised 42 acutely ill comatose patients, 32 of whom were diagnosed
clinically as cerebral malaria and the other 10 as non-malarial diseases. Another 2 were nonmalarial,
non-comatose deaths. Other control tissues were from Australian adults.
Results: Of the 32 clinically diagnosed cerebral malaria cases, 11 had negligible histological change
in the brain, and no or scanty intravascular sequestration of parasitised erythrocytes, another 7 had
no histological changes in the brain, but sequestered parasitised erythrocytes were present (usually
dense), and the remaining 14 brains showed micro-haemorrhages and intravascular mononuclear
cell accumulations, plus sequestered parasitised erythrocytes. The vascular walls of the latter group
stained most strongly for iNOS. Vascular wall iNOS staining was usually of low intensity in the
second group (7 brains) and was virtually absent from the cerebral vascular walls of 8 of the 10
comatose patients without malaria, and also from control brains. The chest wall was chosen as a
typical non-cerebral site encompassing a range of tissues of interest. Here pronounced iNOS
staining in vascular wall and skeletal muscle was present in some 50% of the children in all groups,
including septic meningitis, irrespective of the degree of staining in cerebral vascular walls. Parasites
or malarial pigment were rare to absent in all chest wall sections. While MIF was common in chest
wall vessels, usually in association with iNOS, it was absent in brain vessels.
Conclusions: These results agree with the view that clinically diagnosed cerebral malaria in
African children is a collection of overlapping syndromes acting through different organ systems,
with several mechanisms, not necessarily associated with cerebral vascular inflammation and
damage, combining to cause death.

Ian A Clark*1, Melissa M Awburn1, Richard O Whitten2, Clive G Harper3, N
George Liomba4, Malcolm E Molyneux5,6 and Terrie E Taylor6,7

Item Type: Article
Additional Information: Published: 8 April 2003. 7 pages (page numbers not for citation purposes). The electronic version of this article is the complete one and can be found online at:
Subjects: ?? R1 ??
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
WS Pediatrics > By Age Groups > WS 430 Infancy
WS Pediatrics > By Age Groups > WS 440 Preschool child
Faculty: Department: Groups (2002 - 2012) > Clinical Group
Digital Object Identifer (DOI):
Related URLs:
Depositing User: Ms Julia Martin
Date Deposited: 11 Jul 2008 14:28
Last Modified: 09 Aug 2017 01:02


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