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

Cerebral malaria, one of the most serious complications of Plasmodium falciparum infection, is characterized by the sequestration of parasitized red blood cells (PRBCs) in cerebral microvascular beds. The precise mechanisms involved in the onset of neuropathology remain unknown, but parasite sequestration in the brain, metabolic disturbances, and host immune responses all play a role. Sequestration of PRBCs is mediated by different endothelial cell surface receptors, mainly ICAM-1 and CD36. In vitro studies demonstrated that PRBC adhesion to endothelial cells induces over-expression of various adhesion molecules including ICAM-1, expression of iNOS, oxidative stress and finally apoptosis in endothelial cells. In vivo studies, in humans and in mice models of cerebral malaria brought striking evidence of the implication of brain infiltrating cytotoxic effector CD8T lymphocytes in the development of murine cerebral malaria pathogenesis. These cells probably act by direct cytotoxicity against endothelial cells. Cytotoxicity and apoptosis potentially lead blood-brain-barrier disruption and could contribute to the development of cerebral malaria. We propose a key role for endothelial cells in the pathogenesis of cerebral malaria, both by suicide / apoptosis, and / or by murder / cytotoxicity.
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PMID:Blood-brain barrier breakdown during cerebral malaria: suicide or murder? 1611 23

Pediatric falciparum malaria is associated with high morbidity and mortality rates. Cerebral malaria and renal failure are common among children with a high percentage of malaria-infected red blood cells. We report 3 cases of imported pediatric falciparum malaria with central nervous system involvement and/or renal failure that were treated initially with intravenous antimalarial therapy, with no clinical improvement. Red blood cell exchange transfusion (RBCET) was started; this resulted in decreases in the percentages of parasitized red blood cells of 80% to 90%. The RBCET was performed with either an automated 1-blood volume or manual 1.5-blood volume exchange. Most cases of falciparum malaria can be treated with intravenously administered antimalarial agents alone. However, for children who have high percentages of parasitized red blood cells with central nervous system involvement and/or renal failure, the use of RBCET as an adjunct treatment should be considered.
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PMID:Red blood cell exchange transfusion as an adjunct treatment for severe pediatric falciparum malaria, using automated or manual procedures. 1616 88

Cerebral malaria (CM), one of the most common fatal complications of the heterogenous syndrome named severe malaria, is indubitably a post-infectious neurovascular pathology, as evidenced by histopathological analyses. This neurological syndrome is characterised not only by the cytoadherence of Plasmodium falciparum-infected erythrocytes, but also by morphological and functional alterations of brain microvascular endothelial cells subsequent to their interactions with circulating cells, such as platelets, monocytes, lymphocytes, and dendritic cells. During CM, host cells, in particular immune cells, are found recruited and activated at the site of sequestration, where they release various soluble molecules. Among these, cytokines play a major role in CM pathogenesis. Indeed, cerebral complications appear to be due to an imbalance between pro-inflammatory and anti-inflammatory mediators. Cytokines (notably interferon-gamma, tumour necrosis factor, lymphotoxin) and chemokine receptors (notably CCR5) are also responsible for blood-brain barrier alterations and biochemical changes leading to the brain parenchymal lesions that can be observed in CM. In return, glial cells can influence blood-borne elements, and thereby worsen the pathology. Numerous problems remain to be solved, especially the sequence of pathological events, namely the order in which the circulating cells sequester on the endothelial wall. A better understanding of the molecular mechanisms involved in CM pathogenesis is needed if we are capable of preventing cerebral complications and improving the quality of patient management.
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PMID:Cerebral malaria -- a neurovascular pathology with many riddles still to be solved. 1618 87

Cerebral malaria (CM) is a serious complication of Plasmodium falciparum malaria, and its pathogenesis leading to coma remains unknown. Heme oxygenase-1 (HO-1) catalyzes heme breakdown, eventually generating bilirubin, iron and carbon monoxide. The HO-1 gene promoter contains a polymorphic (GT)n repeat which may influence the expression level of HO-1. To explore the correlation between this (GT)n polymorphism and susceptibility to CM, we analyzed the frequencies of the (GT)n alleles in 120 Myanmarese patients with uncomplicated malaria (UM) and 30 patients with CM. The frequency of homozygotes for the short (GT)n alleles (<28 repeats) in CM patients was significantly higher than those in UM patients (P < 0.008, OR = 3.14). Thus, short (GT)n alleles represent a genetic risk factor for CM.
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PMID:Microsatellite polymorphism in the heme oxygenase-1 gene promoter is associated with susceptibility to cerebral malaria in Myanmar. 1624 18

Cerebral malaria is a potentially life-threatening complication of Plasmodium falciparum malaria. We describe a case of severe cerebral malaria in a previously healthy 63-year-old Danish female who had returned from a two-week tourist tour to Gambia. The severe course of the infection described in this case draws attention to two major aspects regarding imported cases of malaria in non-endemic countries: the need for thorough counselling, including chemoprophylaxis, and continuous focus on potential malaria infection after travelling to malaria-endemic areas.
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PMID:[Cerebral malaria after a two-week charter tour to Gambia]. 1625 Oct 92

Cerebral malaria is the most severe neurological complication of Plasmodium falciparum malaria. Even though this type of malaria is most common in children living in sub-Saharan Africa, it should be considered in anybody with impaired consciousness that has recently travelled in a malaria-endemic area. Cerebral malaria has few specific features, but there are differences in clinical presentation between African children and non-immune adults. Subsequent neurological impairments are also most common and severe in children. Sequestration of infected erythrocytes within cerebral blood vessels seems to be an essential component of the pathogenesis. However, other factors such as convulsions, acidosis, or hypoglycaemia can impair consciousness. In this review, we describe the clinical features and epidemiology of cerebral malaria. We highlight recent insights provided by ex-vivo work on sequestration and examination of pathological specimens. We also summarise recent studies of persisting neurocognitive impairments in children who survive cerebral malaria and suggest areas for further research.
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PMID:Pathogenesis, clinical features, and neurological outcome of cerebral malaria. 1629 41

Cerebral malaria is a serious complication of Plasmodium falciparum infection. We have investigated the role of perforin in the pathogenesis of cerebral malaria in a murine model (Plasmodium berghei ANKA (PbA) infection). C57BL/6 mice demonstrated the typical neuropathological symptoms of experimental cerebral malaria infection from day 5p.i. and became moribund on day 6p.i. This pathology was not seen in PbA-infected, perforin-deficient (pfp-/-) mice. From days 5-6p.i. onwards there was a significant increase in mRNA for granzyme B and CD8, but not CD4, in brain tissue from PbA-infected C57BL/6 and pfp-/- mouse brains. Perforin mRNA was strongly increased in the brains of PbA-infected C57BL/6 mice on day 6p.i. Immunohistochemistry revealed increased perforin staining and elevated numbers of CD8(+) cells within the cerebral microvessels in PbA-infected C57BL/6 at days 5 and 6p.i. compared with uninfected animals. At day 6p.i., there were TUNEL-positive cells and activated caspase-3 positive cells of endothelial morphology in the CNS of PbA-infected C57BL/6 mice. The TUNEL-positive cells were greatly reduced in pfp-/- mice. These results suggest that CD8(+)T lymphocytes induce apoptosis of endothelial cells via a perforin-dependent process, contributing to the fatal pathogenic process in murine cerebral malaria.
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PMID:Perforin mediated apoptosis of cerebral microvascular endothelial cells during experimental cerebral malaria. 1650 Jun 56

The most severe complication of Plasmodium falciparum infection is cerebral malaria (CM). Cerebral malaria implies the presence of neurological features, especially impaired consciousness. The treatment of CM is limited to: (i) a few conventional anti-malarial drugs (quinine or artemisinins), (ii) adjunctive treatments (initial stabilisation, blood exchange transfusion, osmotic diuretics and correction of hypoglycaemia, acidosis and hypovolaemia) and (iii) immunomodulation. There are clear procedures concerning treatment of CM, which include the use of the anti-plasmodial drugs. Adjunctive treatments are permissible but there is no single official guideline and immune intervention is a possibility currently being examined in rodent models only. The suggested immunomodulation approach is based on the strong likelihood that CM is the result of an immunopathological process. P. falciparum initiates the multifactorial chain of events leading to lethal CM and, after a certain stage, it is impossible to stop the progression even by using anti-malarial drugs. We present evidence that CM is a result of a dysregulated immune response. Therefore, it might be prevented by early modulation of discrete factors that participate in this process. In experimental systems, some immunomodulators delay or prevent CM without affecting the parasitaemia. Therefore, in the future the ultimate treatment of CM may be a combination of an anti-malarial and an immunomodulator. However, the overall effect of an immunomodulator would need to be carefully examined in view of concomitant infections, especially in malaria endemic areas.
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PMID:Conventional and experimental treatment of cerebral malaria. 1660 67

Malaria is one of the most important global health problems, potentially affecting more than one third of the world's population. Cerebral malaria (CM) is a deadly complication of Plasmodium falciparum infection, yet its pathogenesis remains incompletely understood. In this review, we discuss some of the principal pathogenic events that have been described in murine models of the disease and relate them to the human condition. One of the earliest events in CM pathogenesis appears to be a mild increase in the permeability to protein of the blood-brain barrier. Recent studies have shown a role for CD8+T cells in mediating damage to the microvascular endothelium and this damage can result in the leakage of cytokines, malaria antigens and other potentially harmful molecules across the blood-brain barrier into the cerebral parenchyma. We suggest that this, in turn, leads to the activation of microglia and the activation and apoptosis of astrocytes. The role of hypoxia in the pathogenesis of cerebral malaria is also discussed, with particular reference to the local reduction of oxygen consumption in the brain as a consequence of vascular obstruction, to cytokine-driven changes in glucose metabolism, and to cytopathic hypoxia. Interferon-gamma, a cytokine known to be produced in malaria infection, induces increased expression, by microvascular endothelial cells, of the haem enzyme indoleamine 2,3-dioxygenase, the first enzyme in the kynurenine pathway of tryptophan metabolism. Enhanced indoleamine 2,3-dioxygenase expression leads to increased production of a range of biologically active metabolites that may be part of a tissue protective response. Damage to astrocytes may result in reduced production of the neuroprotectant molecule kynurenic acid, leading to a decrease in its ratio relative to the neuroexcitotoxic molecule quinolinic acid, which might contribute to some of the neurological symptoms of cerebral malaria. Lastly, we discuss the role of other haem enzymes, cyclooxygenase-2, inducible nitric oxide synthase and haem oxygenase-1, as potentially being components of mechanisms that protect host tissue against the effects of cytokine- and leukocyte-mediated stress induced by malaria infection.
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PMID:Immunopathogenesis of cerebral malaria. 1667 81

Cerebral malaria is a diffuse encephalopathy associated with seizures and status epilepticus which can occur in up to one-third of children with severe malaria, particularly that caused by Plasmodium falciparum. We report a unique case of P. vivax infection complicated by status epilepticus. A 4-year-old boy was admitted to the emergency outpatient clinic with intractable seizures for the previous hour. During resuscitation, two episodes of left-focal tonic convulsions occurred and he received phenytoin. Because of a history of P. vivax infection in the family 3 months previously, a blood slide for malaria was undertaken. Thin blood smears demonstrated P. vivax. He was treated with chloroquine and primaquine. An initial EEG was normal but after 3 months of follow-up a second EEG showed generalised epileptic activity. Rarely, cerebral malaria is a presenting complication or occurs during the course of P. vivax infection. In endemic areas such as Turkey, the possibility of cerebral malaria should be considered.
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PMID:Cerebral malaria owing to Plasmodium vivax: case report. 1670 34


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