Disease relevance of Malaria, Cerebral

• High-dose dexamethasone was compared with placebo in a double-blind trial involving 100 comatose patients with strictly defined cerebral malaria [1].
• Interleukin 6 production in experimental cerebral malaria: modulation by anticytokine antibodies and possible role in hypergammaglobulinemia [2].
• Glycaemic status on hospital admission was compared in 97 children with severe falciparum malaria (36 with cerebral malaria) and 89 children with other serious illnesses (32 in coma; 57 with acute pneumonia, not in coma) [3].
• Murine AIDS protects mice against experimental cerebral malaria: down-regulation by interleukin 10 of a T-helper type 1 CD4+ cell-mediated pathology [4].
• No relation between plasma endothelin concentrations and parasitemia, fever, or other indices of severe infection (hypotension, renal, hepatic or pulmonary impairment, cerebral malaria) existed [5].

Psychiatry related information on Malaria, Cerebral

• A self-limiting psychosis characterized by visual and auditory hallucinations with or without aggressive behavior developed in two children 4 to 5 days after complete recovery from a cerebral malaria coma [6].

High impact information on Malaria, Cerebral

• Cerebral malaria has a mortality rate of 10 to 30 percent despite treatment with parenteral quinine, a situation that may worsen with the spread of quinine resistance [7].
• To determine whether combining iron chelation with quinine therapy speeds the recovery of consciousness, we conducted a randomized, double-blind, placebo-controlled trial of the iron chelator deferoxamine in 83 Zambian children with cerebral malaria [8].
• Interferon-gamma (IFN-gamma)-essential for the development of cerebral malaria in the mouse-was found to augment adhesion of human pRBCs to PECAM-1/CD31 on endothelial cell monolayers [9].
• Variation in the TNF-alpha promoter region associated with susceptibility to cerebral malaria [10].
• The portion of the CD36 molecule that reverses cytoadherence may be useful therapeutically for rapid reversal of sequestration in cerebral malaria [11].

Chemical compound and disease context of Malaria, Cerebral

• Tumor necrosis factor (cachectin) as an essential mediator in murine cerebral malaria [12].
• Phenobarbital for children with cerebral malaria [13].
• Nitric oxide and cerebral malaria [14].
• Low plasma arginine concentrations in children with cerebral malaria and decreased nitric oxide production [15].
• Cerebrospinal-fluid (CSF) lactate concentrations were elevated in all but 1 of 45 patients with cerebral malaria [16].

Biological context of Malaria, Cerebral

• Post-mortem brain tissue from patients who died from cerebral malaria expressed multiple cell adhesion molecules including ELAM-1 and VCAM-1 on cerebral microvascular endothelium not expressed in brains of individuals who died from other causes [17].
• To assess the hypothesis that nitric oxide is critical in the pathogenesis of cerebral malaria, we analysed genetic variation in the proximal promoter region of NOS2A, the gene encoding inducible nitric oxide synthase [18].
• Expression of major histocompatibility complex antigens on mouse brain microvascular endothelial cells in relation to susceptibility to cerebral malaria [19].
• Steady state plasma concentrations over 7 days ranged from 300 to 1,050 (mean 561) ng/g. Bioavailability of mefloquine suspension in cerebral malaria therefore appears to be adequate for treatment in all but the most severely ill patients [20].
• These observations suggest that chloroquine may help to prevent cerebral malaria whatever the drug sensitivity of the parasite strain, and may provide new tools for an anti-disease therapy regardless of the emergence of parasite multi-drug resistance [21].

Anatomical context of Malaria, Cerebral

• In mice with cerebral malaria, the cerebral vessels showed focal accumulations of packed macrophages often containing infected erythrocytes; this lesion was not seen in mice treated with antibody to TNF-alpha or in untreated mice without cerebral malaria [12].
• During acute cerebral malaria in humans, the expression of intercellular adhesion molecule-1 (ICAM-1) is induced in vascular endothelium by inflammatory reactions [22].
• Leukocyte NOS2 antigen was detectable in all control children tested and in all those with subclinical infection, but was undetectable in all but one subject with cerebral malaria [23].
• Reactive changes of retinal microglia during fatal murine cerebral malaria: effects of dexamethasone and experimental permeabilization of the blood-brain barrier [24].
• Treatment of mice with liposome-encapsulated dichloromethylene diphosphonate (lip-Cl2MDP), used to eliminate macrophages (an important source of TNF), prevented the development of cerebral malaria, but only when given before day 5 of infection [25].

Gene context of Malaria, Cerebral

• Locally up-regulated lymphotoxin alpha, not systemic tumor necrosis factor alpha, is the principle mediator of murine cerebral malaria [26].
• CD36 is shown to be present on brain endothelium in both individuals without malaria and individuals with cerebral malaria [27].
• We addressed the direct and indirect effects of tumor necrosis factor (TNF) on endothelial cells that can be relevant for the pathogenesis of septic shock, with particular attention to the acute respiratory distress syndrome (ARDS) and to cerebral malaria (CM) [28].
• We found increased concentrations of IL-6, sIL-6R, IL-1ra, and some immunoglobulin M antibodies against PI in children with cerebral malaria, but those who died had decreased concentrations of beta-2-glycoprotein I [29].
• Cyclooxygenase-2 in the pathogenesis of murine cerebral malaria [30].

Analytical, diagnostic and therapeutic context of Malaria, Cerebral

• Effect of phenobarbital on seizure frequency and mortality in childhood cerebral malaria: a randomised, controlled intervention study [31].
• Emergency therapy at interfering with cytoadherence could be considered in the treatment of cerebral malaria in man, in which high blood TNF levels are also observed [32].
• Cerebral expression of c-fos protein was studied by immunocytochemistry in murine cerebral malaria (CM) and malaria without cerebral involvement (non-CM). c-fos expression, low in the brains of uninfected mice, increased in frequency, intensity, and distribution during the course of fatal CM (e.g., a 70-fold increase on day 7 after inoculation) [33].
• Complement receptor-1 (CR1) is a ligand for rosette formation, a phenomenon associated with cerebral malaria (CM) [34].
• Serum neopterin, interleukin-4, and interleukin-6 concentrations in cerebral malaria patients and the effect of iron chelation therapy [35].

References