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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cerebral malaria is a severe complication of infection with Plasmodium berghei ANKA involving the Th1 cytokines TNF-alpha and IFN-gamma. Suppressor of cytokine signalling-1 (SOCS1) is an important component in the regulatory cascade controlling inflammatory responses and signalling through IFN-gamma. Contrary to the expectation that SOCS1-deficient mice, in which IFN-gamma responses are uncontrolled and which are more sensitive to IFN-gamma, may show heightened susceptibility, mice lacking SOCS1 were protected from cerebral malaria. Unlike the controls and despite similar parasitaemia, infected SOCS1 null mice showed no inflammation or haemorrhaging in the brains. Mice lacking SOCS1 exhibited decreased splenic cellularity and a reduced ratio of CD4 : CD8 lymphocytes, which were maintained during infection. However, the ratio of IFN-gamma to IL-4 mRNA expression during infection was similar in SOCS1 -/- and control mice suggesting that a dramatic shift in the ratio of Th1 : Th2 responses does not account for the resistance to disease. Resistance conferred by the lack of SOCS1 is specific since the related SOCS2, also implicated in Th1-mediated responses, did not seem to be involved in the development of disease. Understanding the mechanism by which SOCS1 deficiency protects mice from cerebral malaria may allow the manipulation of its activity and alleviate pathology.
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PMID:The lack of suppressor of cytokine signalling-1 (SOCS1) protects mice from the development of cerebral malaria caused by Plasmodium berghei ANKA. 1291 18

Cerebral malaria (CM) is a devastating form of Plasmodium falciparum malaria, in which adherence and sequestration of infected red blood cells in cerebral blood vessels play a major role. In order to determine whether a distinct parasite phenotype favours the development of this severe complication, P. falciparum isolates from Gabonese children suffering from CM or uncomplicated malaria (UM) were analysed for their binding phenotypes and their recognition in flow cytometry. CM isolates exhibited the ability to form rosettes and to bind ICAM-1, in line with previous studies correlating these phenotypes with CM disease pathology. CM isolates were more reactive with plasma from our cohort than UM parasites. This observation, together with the finding that some CM isolates were highly correlated with each other in their immunoreactivities, confirms that common parasites bearing conserved epitopes, which are capable of inducing cross-reactive antibodies, can cause CM in children.
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PMID:Commonly recognised Plasmodium falciparum parasites cause cerebral malaria. 1368 Mar 76

Physiologically in the brain, cytokines such as tumor necrosis factor-alpha (TNalpha) are released by the immune system and can modulate neurological responses. Conversely, the central nervous system (CNS) is also able to modulate cytokine production. In the case of CNS disorders, cytokine release may be modified. Cerebral malaria (CM) is a complication of Plasmodium falciparum infection in humans and is characterized by a reversible encephalopathy with seizures and loss of consciousness. Central clinical signs are partly due to sequestration of parasitized red blood cells in the brain microvasculature due to interactions between parasite proteins and adhesion molecules. TNFalpha is produced and released by host cells following exposure to various malarial antigens. The increase of TNFalpha release is responsible for the overexpression of adhesion molecules. This article reviews the involvement of TNFalpha in cerebral malaria and the relation with all the processes involved in this pathology. It shows that (i). TNFalpha levels are increased in plasma and brain but with no clear correlation between TNFalpha levels and occurrence and severity of CM; (ii). TNFalpha is responsible for intercellular adhesion molecule-1 upregulation in CM, the relation being less clear for other adhesion molecules; (iii). TNFalpha receptors are upregulated in CM, with TNF receptor 2 (TNFR2) showing a higher upregulation than TNFR1 in vivo; (iv). in murine CM, low doses of TNFalpha seem to protect from CM, whereas excess TNFalpha induces CM and anti-TNFalpha therapies (antibodies, pentoxifylline) did not show any efficiency in protection from CM. Moreover, the involvement of lymphotoxin a, which shares with TNFalpha the same receptors with similar affinity, appears to be an interesting target for further investigation.
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PMID:Tumor necrosis factor alpha in the pathogenesis of cerebral malaria. 1450 53

Cerebral malaria (CM) is one of the most serious complications of Plasmodium falciparum infection. It is characterized by sequestration of parasitized red blood cells (PRBC) in cerebral capillaries and venules. Although the exact cause of CM remains unclear, current evidence has clearly implicated metabolic disturbances and host immune responses. Studies on mouse CM models suggest the involvement of host cells and in particular platelets. These results led us to study the role of platelets in human CM. Our findings demonstrated that significantly greater accumulation of platelets occurred in capillaries and venules of Malawian patients who died from CM than from other diseases. We also assessed the role of platelets in cytoadherence of PRBCs using PRBC adhering only on CD36, platelets and endothelial cells (EC) constitutively devoid of CD36. Cultures using the three components showed that platelets played a role in inducing cytoadherence of PRBC on EC via a cellular bridging resistant to physiological flow conditions. Having established the link between platelets and sequestration, the next step will be to examine the link between platelets and CM. A combination of approaches from different disciplines will be needed to gain further insight into the mechanisms underlying the complications of malaria.
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PMID:[Pathogenesis of cerebral malaria: facts and hypotheses]. 1457 62

Cerebral malaria (CM) is a major cause of death in severe Plasmodium falciparum malaria. We present quantitative electron microscopic findings of the neuropathologic features in a prospective clinicopathologic study of 65 patients who died of severe malaria in Thailand and Vietnam. Sequestration of parasitized red blood cells (PRBCs) in cerebral microvessels was significantly higher in the brains of patients with CM compared with those with non-cerebral malaria (NCM) in all parts of the brain (cerebrum, cerebellum, and medulla oblongata). There was a hierarchy of sequestration with more in the cerebrum and cerebellum than the brain stem. When cerebral sequestration was compared with the peripheral parasitemia pre mortem, there were 26.6 times more PRBCs in the brain microvasculature than in the peripheral blood. The sequestration index was significantly higher in CM patients (median = 50.7) than in NCM patients (median = 6.9) (P = 0.042). The degree of sequestration of P. falciparum-infected erythrocytes in cerebral microvessels is quantitatively associated with pre-mortem coma.
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PMID:An ultrastructural study of the brain in fatal Plasmodium falciparum malaria. 1464 Apr 92

Common causes of coma in falciparum malaria are cerebral malaria, hypoglycaemia and electrolyte disturbances. Focal deficits due to arterial infarcts may sometimes occur in children, but are rare in adults. Three adults with falciparum malaria who had fever, altered consciousness and focal neurological deficits (one of whom also had seizures) are being reported here. CT scan of the brain revealed haemorrhagic infarction of the cerebral cortex and subcortical white matter with surrounding oedema suggestive of venous infarction in all three patients. The diagnosis of cerebral venous thrombosis was missed in the first patient, and was detected only at autopsy. In the next two patients, superior sagittal sinus thrombosis was confirmed angiographically. Only one patient survived; the other two died of increased intracranial pressure. Two of the three patients also had Plasmodium vivax co-infection. A hypercoagulable state resulting from severe malaria may be responsible for this rare and potentially fatal complication. Cerebral malaria may be associated with raised intracranial pressure due to cerebral oedema. Cerebral venous thrombosis may worsen this and adversely affect outcome. This diagnosis should be suspected in patients with severe malaria who develop focal neurological deficits and confirmed by appropriate imaging; judicious use of local thrombolytic therapy may help improve outcome.
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PMID:Cerebral venous and dural sinus thrombosis in severe falciparum malaria. 1466 96

Cerebral malaria (CM) is a severe complication of malaria, in which cytokine production can produce immunopathological consequences. Cytokines can up-regulate prostaglandin synthesis via an increase in cyclooxygenase (COX) enzyme activity. We investigated the expression of COX enzymes, COX-1 and COX-2, in the brain by use of murine models of CM and of malaria without cerebral involvement. Although COX-1 mRNA was induced in the brain in both models of malaria, COX-2 mRNA was induced specifically in CM. Inhibition of COX-2 with celecoxib resulted in an earlier onset of CM. Treatment with celecoxib did not alter the outcome of malaria infection without cerebral involvement. These data suggest that induction of COX-2 expression and prostaglandin synthesis may have a protective effect in CM.
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PMID:Cyclooxygenase-2 in the pathogenesis of murine cerebral malaria. 1476 31

Despite treatment, cerebral malaria still has a high mortality. This study describes the clinical features, immediate outcome and prognostic factors for childhood cerebral malaria in Mulago Hospital, Kampala, Uganda. One hundred children who met the WHO criteria for cerebral malaria were prospectively recruited and followed up until discharge or death. Mortality was 7% and neurological sequelae occurred in 5% of survivors. Independent predictors of mortality were respiratory distress [adjusted OR 1.2 (95% CI 1.1-1.3)], circulatory failure [adjusted OR 2.1 (95% CI 1.8-2.4)], generalised hyporeflexia [adjusted OR 1.2 (95% CI 1.1-1.3)] and parasite density > or =500,000/microl [adjusted OR 1.02 (95% CI 1.01-1.2)]. Circulatory failure could be predicted by a combination of hypothermia, cold peripheries and dehydration. Death occurred within 12 hours of admission only in children with these predictors, and the risk of death increased with the number of risk factors. Multiple convulsions at admission predicted neurological sequelae [adjusted OR 12.8, 95% CI 3.0-211, p=0.014)]. Cerebral malaria mortality is predictable. Patients with respiratory distress, circulatory failure, generalised hyporeflexia and parasite density > or =500,000/microl need urgent treatment to prevent death. In primary health units, health workers may use a combination of cold peripheries, hypothermia and dehydration to predict circulatory failure.
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PMID:Immediate outcome and prognostic factors for cerebral malaria among children admitted to Mulago Hospital, Uganda. 1500 62

For over a century it has been recognized that many of the clinical symptoms of malaria are caused by toxins released by rupturing schizonts, but it is only in the past few years that the underlying mechanisms have begun to be understood. Dominic Kwiatkowski here focuses on the toxins that cause malaria fever by stimulating host cells to produce tumour necrosis factor a (TNF) and other pyrogenic cytokines. Both TNF and fever have antiparasite properties, and it is proposed that the release of these toxins plays an important role in the regulation of parasite density within the host. Cerebral malaria is related to excessive TNF production. Recent data indicate that this can be the consequence of genetic variation in the host's propensity to produce TNF.
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PMID:Malarial toxins and the regulation of parasite density. 1527 84

A prospective hospital based study on severe malaria in under-five children was carried out over a period of one year in a district hospital of Ethiopia to determine the case fatality rate (CFR), factors contributing for high mortality, health seeking behaviour of the care takers, direct cost and feasibility of operating the WHO treatment guidelines at a district level. One hundred and one children aged between 6 and 59 months fulfilling the criteria of severe malaria have been recruited in the study and treated according to WHO guidelines. The most frequently encountered clinical manifestations of severe malaria were prostration and hypoglycaemia, the prevalence being 28.7% respectively. The over all case fatality rate of severe malaria was 11.9%. Cerebral malaria was the only isolated form of severe malaria with high CFR (OR=5.06, 95%CI 1.01-25.1). The hospital CFR of severe anaemia was 16.7%, which could have been reduced by provision of safe blood transfusion. Most of the children (80.2%) presented to the hospital in more than 24 hours after the onset of the illness. Forty seven percent of children received drugs at home and in 96% of the cases it was antimalarial drugs. The antimalarial drug treatment (dose/duration) was adequate in 71%. Children receiving appropriate anti-malaria treatment at home show a tendency towards a lower CFR. The total direct cost per disease episode ranged from USD 13.75 to 27.5. Eighty five percent of the direct cost was due to expenditures in the hospital. Implementation of the management protocol based on the WHO guidelines has required substantial input of resources. Major constraints noted were related to availability of safe blood andfollow-up after discharge. The study provides useful information for improved case management of severe malaria thereby reduce mortality of the under-five children due to severe malaria.
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PMID:Severe malaria in the under-fives--clinical featrues, management and outcome in a district hospital. 1529 12


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