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The pathophysiology of falciparum malaria

Clark, Ian A; Cowden, William

Description

Falciparum malaria is a complex disease with no simple explanation, affecting organs where the parasite is rare as well as those organs where it is more common. We continue to argue that it can best be understood in terms of excessive stimulation of normally useful pathways mediated by inflammatory cytokines, the prototype being tumor necrosis factor (TNF). These pathways involve downstream mediators, such as nitric oxide (NO) that the host normally uses to control parasites, but which, when...[Show more]

dc.contributor.authorClark, Ian A
dc.contributor.authorCowden, William
dc.date.accessioned2015-12-13T23:08:19Z
dc.date.available2015-12-13T23:08:19Z
dc.identifier.issn0163-7258
dc.identifier.urihttp://hdl.handle.net/1885/86622
dc.description.abstractFalciparum malaria is a complex disease with no simple explanation, affecting organs where the parasite is rare as well as those organs where it is more common. We continue to argue that it can best be understood in terms of excessive stimulation of normally useful pathways mediated by inflammatory cytokines, the prototype being tumor necrosis factor (TNF). These pathways involve downstream mediators, such as nitric oxide (NO) that the host normally uses to control parasites, but which, when uncontrolled, have bioenergetic failure of patient tissues as their predictable end point. Falciparum malaria is no different from many other infectious diseases that are clinically confused with it. The sequestration of parasitized red blood cells, prominent in some tissues but absent in others with equal functional loss, exacerbates, but does not change, these overriding principles. Recent opportunities to stain a wide range of tissues from African pediatric cases of falciparum malaria and sepsis for the inducible NO synthase (iNOS) and migration inhibitory factor (MIF) have strengthened these arguments considerably. The recent demonstration of bioenergetic failure in tissue removed from sepsis patients being able to predict a fatal outcome fulfils a prediction of these principles, and it is plausible that this will be demonstrable in severe falciparum malaria. Understanding the disease caused by falciparum malaria at a molecular level requires an appreciation of the universality of poly(ADP-ribose) polymerase-1 (PARP-1) and Na+/K+-ATPase and the protean effects of activation by inflammation of the former that include inactivation of the latter.
dc.publisherPergamon-Elsevier Ltd
dc.sourcePharmacology and Therapeutics
dc.subjectKeywords: adenosine triphosphatase (potassium sodium); bacterial toxin; cytokine; immunoglobulin enhancer binding protein; lymphotoxin; migration inhibition factor; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase; nitric oxide; nitric oxi Malaria; Na+/K+-ATPase; Nitric oxide; Poly(ADP-ribose) polymerase; Sepsis; Tumor necrosis factor
dc.titleThe pathophysiology of falciparum malaria
dc.typeJournal article
local.description.notesImported from ARIES
local.description.refereedYes
local.identifier.citationvolume99
dc.date.issued2003
local.identifier.absfor110803 - Medical Parasitology
local.identifier.ariespublicationMigratedxPub15542
local.type.statusPublished Version
local.contributor.affiliationClark, Ian A, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationCowden, William, College of Medicine, Biology and Environment, ANU
local.bibliographicCitation.issue2
local.bibliographicCitation.startpage221
local.bibliographicCitation.lastpage260
local.identifier.doi10.1016/S0163-7258(03)00060-3
dc.date.updated2015-12-12T08:13:06Z
local.identifier.scopusID2-s2.0-0042346427
CollectionsANU Research Publications

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