Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several neurological complications are associated with complicated and severe falciparum malaria. Cerebral malaria is one of the most dreaded complication. The children are particularly more vulnerable to have this complication. Despite availability of several potent antimalarial drugs in recent past, the mortality status has not changed. A large number of survivors are left with disabling neurological sequelae. Few patients may experience post-malaria neurological syndrome after recovery from complicated falciparum infection. Various psychiatric syndromes have been described either as early manifestation of cerebral malaria or part of post malaria neurological syndrome. From Indian subcontinent several patients of delayed cerebellar ataxia have also been described following recovery from clinical malaria. In paediatric patients, convulsions of cerebral malaria need to be differentiated from febrile convulsions. Falciparum malaria is also associated specifically with convulsions in uncomplicated patients of malaria. Several isolated case reports of various other neurological syndromes like peripheral neuropathies, various movement disorders, myelopathies and stroke like syndrome have been described. However association of these neurological manifestations with malaria remains doubtful.
 ...
PMID:Neurological manifestations of malaria : an update. 1040 29

Severe forms of malaria in children are responsible for 1 million deaths yearly in young children in hyperendemic areas. The main objective of this study was to identify and compare common manifestations of different forms of severe malaria and to evaluate the prognosis for hospital treatment in an endemic area. 271 files of children admitted into hospital between March 1991 and September 1996 were analysed. These children were confirmed to have Plasmodium falciparum in their peripheral blood. 78 patients (29%) had the severe form of malaria. 43 patients (53%) were under 5 years of age. The 5 severe types identified were characterized by very high temperatures 28 cases (36%), cerebral malaria 20 cases (26%), prostration and weakness 15 cases (19%), severe anaemia 14 cases (18%) and haemoglobinuria 1 case (1.3%). Cerebral malaria and severe anaemia were more common in children under 5 years old. The average parasitemia was 16,366 +/- 1390 parasites per microlitre. Clearance of parasitemia was obtained on day 3 in almost all cases; 6 patients with very high temperatures presented neither sign of visceral complications nor convulsions. The average period in coma for cases of cerebral malaria was 1.7 days; 12 anaemic patients were transfused. There were no deaths. No abnormality was found on physical examination after an average hospitalisation of 5.3 days. An early diagnosis and adequate treatment of severe forms of malaria in children by qualified personnel will usually result in a favourable prognosis in our area.
 ...
PMID:[Severe forms of malaria in children in a general hospital pediatric department in Yaounde, Cameroon]. 1047 38

Pro- and antiinflammatory cytokines were measured on admission in 287 consecutive Vietnamese adults with severe falciparum malaria. Plasma interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-alpha concentrations and the IL-6: IL-10 ratio were significantly higher in patients who died than in survivors (P<.001). On multivariate analysis, hyperparasitemia, jaundice, and shock were all associated independently with raised IL-6, IL-10, and interferon-gamma, and acute renal failure specifically with raised TNF-alpha levels. Cerebral malaria patients, particularly those without other vital organ dysfunction, had significantly lower levels of these cytokines (P=.006), reflecting a more localized pathology. Serial IL-6 and IL-10 measurements made on 43 patients who died and matched survivors indicated a relative deficiency in IL-10 production as death approached. Elevated plasma cytokines in severe malaria are associated with systemic pathologic abnormalities, not cerebral involvement. Both the overall magnitude of the cytokine responses and the eventual imbalance between the pro- and antiinflammatory responses are important determinants of mortality.
 ...
PMID:The prognostic and pathophysiologic role of pro- and antiinflammatory cytokines in severe malaria. 1047 60

In susceptible mouse strains, infection of mice with Plasmodium berghei ANKA (PbA) results in a lethal complication, cerebral malaria. Cerebral malaria is due to the immune response induced by the parasite, which results in an increased production of TNF, known to increase the expression of adhesion molecules on the endothelia. To investigate the role of the adhesion molecule ICAM-1 (CD54), we infected wild-type (+/+) and ICAM-1-deficient (-/-) mice with PbA. While +/+ mice died 6-8 days after infection, -/- mice survived > 15 days. Parasitaemia was similar in +/+ and -/- mice. Serum TNF concentration was increased by the infection and was significantly higher in infected +/+ than in -/- mice. However, TNF mRNA levels in spleen, lungs, and brain were elevated in both infected +/+ and -/- mice. For IFN-gamma, serum levels were similar in both groups. A breakdown of the blood-brain barrier was evident in infected +/+ mice only. Interestingly, thrombocytopenia was profound in infected +/+, but practically absent in -/- mice. Moreover, macrophage sequestration was evident in brain venules and lung capillaries of +/+ mice and was significantly less important in the alveolar capillaries of infected -/- mice. In contrast, neutrophil sequestration in the lung was similar in both +/+ and -/- mice. Sequestration of parasitized red blood cells was significantly greater in the alveolar capillaries from +/+ than -/- mice. These results indicate that while the immune response is similar in both +/+ and ICAM-1(-/-) mice, the absence of mortality in ICAM(-/-) mice correlates with a decrease of macrophage and parasitized RBC trapping and a less severe thrombocytopenia.
 ...
PMID:Role of ICAM-1 (CD54) in the development of murine cerebral malaria. 1061 27

Cerebral malaria is one of the commonest causes of an acute neurological syndrome in malaria-endemic areas. However, there are few detailed reports of findings on clinical neurological examination of the condition. The neurological features of cerebral malaria in 103 children aged 5 years or less were studied in Ibadan, Nigeria, an area of high malaria transmission. The correlation of these features with prognosis was also studied. Convulsions occurred in 87% of subjects and were in most cases of a generalized tonic-clinic nature. Abnormalities of posture were observed in 41%, abnormal tone in 70% and abnormal deep tendon reflexes in 74%. Absent corneal reflexes were found in about 14%. The time interval between the last seizure episode and presentation in hospital, abnormal posture (decerebrate or decorticate), absence of corneal reflex and depth and duration of coma were indicators of poor prognosis. In this study, cerebral malaria presented with non-specific features of diffuse, symmetrical, upper motor neurone dysfunction, and some specific neurological features were associated with poor prognosis. It is important that cerebral malaria be considered in any child with features of acute encephalopathy in a malaria-endemic area. Careful clinical examination of such children is essential as neurological features of the condition may provide a clue to prognosis.
 ...
PMID:Neurological features of cerebral malaria in Nigerian children. 1071 24

Cerebral malaria may be the most common non-traumatic encephalopathy in the world. The pathogenesis is heterogeneous and the neurological complications are often part of a multisystem dysfunction. The clinical presentation and pathophysiology differs between adults and children. Recent studies have elucidated the molecular mechanisms of pathogenesis and raised possible interventions. Antimalarial drugs, however, remain the only intervention that unequivocally affects outcome, although increasing resistance to the established antimalarial drugs is of grave concern. Artemisinin derivatives have made an impact on treatment, but other drugs may be required. With appropriate antimalarial drugs, the prognosis of cerebral malaria often depends on the management of other complications-for example, renal failure and acidosis. Neurological sequelae are increasingly recognised, but further research on the pathogenesis of coma and neurological damage is required to develop other ancillary treatments.
 ...
PMID:Cerebral malaria. 1099 May

Cerebral malaria depends largely on the capacity of Plasmodium falciparum infected red blood cells to adhere to the endothelia of microvessels, leading to their occlusion. The most important players include receptors expressed on the surface of the endothelial cell and known to interact with the parasite, cytokines modulating the expression of these adhesion molecules and nitric oxide (NO). Platelets, monocytes and lymphocytes have the ability to adhere to these endothelial receptors and to one another, leading to a more complex situation and an increase in the degree of vessel occlusion. The polymorphism of all these molecules, implicated either in adhesion, in modulation of this adhesion or activation of the expression of diverse endothelial mediators should be an important field of study. Polymorphism of five of these molecules has been explored so far: ICAM-1, TNF-alpha, IL-1-beta, inducible NOS and complement receptor-1 (CR-1). To these studies can be added those concerning mannose binding protein (MBP), a protein playing a role in innate immunity, and the class-I antigen HLA-B53. To date, the only clear cut result concerns TNF-alpha. With the other polymorphisms, either no association is found (IL-1RA, CR-1, MBP), or the results are geographically heterogeneous (ICAM-1, HLA-B53), or contradictory (iNOS2). Most often, the candidate gene approach has been followed, as part of case control studies. One of the main problems in this approach is the difficulty of establishing the control cohort. This difficulty disappears in family studies, which include their own controls. So far, the only results based on complex segregation analysis have been focused on parasite multiplication and not on cerebral malaria.
 ...
PMID:Cerebral malaria and immunogenetics. 1112 53

Cerebral malaria is a rapidly progressive potentially fatal complication of Plasmodium falciparum infection. It is characterized by unarousable and persistent coma along with symmetrical motor signs. Children, pregnant women and non-immune adults are more susceptible to have cerebral malaria. Several clinical, histopathological and laboratory studies have suggested that cytoadherence of parasitized erythrocytes (mechanical hypothesis), and neuronal injury by malarial toxin and excessive cytokine (e.g. tissue necrosis factor-alpha) production (cytotoxic hypothesis) are possible pathogenic mechanisms. Several associated systemic complications like hypoglycemia, hypovolemia, hyperpyrexia, renal failure, bleeding disorders, anemia, lactic acidosis and pulmonary oedema may contribute in the pathogenesis of coma, and are responsible for high mortality. The meticulous supportive care along with intravenous administration of antimalarial drugs are corner-stone of the treatment. Quinine is currently, drug of choice. Artimisinin derivatives are equally effective and can be used by intramuscular route. In severe cases exchange blood transfusion may be an effective alternative. Corticosteroids has no place in the management of cerebral malaria. The occurrence of convulsions are common in children, these can be prevented with the use of single intramuscular administration of phenobarbitone. Despite advances in the management mortality and morbidity have not changed much. A large number of surviving patients are left with permanent neurological sequelae. There is a need to search for effective malaria prevention and interventional strategies to avert high mortality and morbidity associated with cerebral malaria.
 ...
PMID:Cerebral malaria. 1184 24

Cerebral malaria (CM) is a major life-threatening complication of Plasmodium falciparum infection in humans, responsible for up to 2 million deaths annually. The mechanisms underlying the fatal cerebral complications are still not fully understood. Many theories exist on the aetiology of human CM. The sequestration hypo-thesis suggests that adherence of parasitized erythrocytes to the cerebral vasculature leads to obstruction of the microcirculation, anoxia or metabolic disturbances affecting brain function, resulting in coma. This mechanism alone seems insufficient to explain all the known features of CM. In this review we focus on another major school of thought, that CM is the result of an over-vigorous immune response originally evolved for the protection of the host. Evidence in support of this second hypothesis comes from studies in murine malaria models in which T cells, monocytes, adhesion molecules and cytokines, have been implicated in the development of the cerebral complications. Recent studies of human CM also indicate a role for the immune system in the neurological complications. However, it is likely that multiple mechanisms are involved in the induction of cerebral complications and both the presence of parasitized erythrocytes in the central nervous system (CNS) and immunopathological processes contribute to the pathogenesis of CM. Most studies examining immunopathological responses in CM have focused on reactions occurring primarily in the systemic circulation. However, these also do not fully account for the development of cerebral complications in CM. In this review we summarize results from human and mouse studies that demonstrate morphological and functional changes in the resident glial cells of the CNS. The degree of immune activation and degeneration of glial cells was shown to reflect the extent of neurological complications in murine cerebral malaria. From these results we highlight the need to consider the potentially important contribution within the CNS of glia and their secreted products, such as cytokines, in the development of human CM.
 ...
PMID:Central nervous system in cerebral malaria: 'Innocent bystander' or active participant in the induction of immunopathology? 1126 3

Cerebral malaria (CM) is a serious complication of Plasmodium falciparum infection. Binding of parasitized erythrocytes to cerebral endothelium plays a key role in disease pathogenesis. Central nervous system signs and symptoms (coma, seizures, raised intracranial pressure) predominate in African children, whereas in adults, multiorgan system failure is more common. In this study we investigated whether changes in blood-brain barrier (BBB) structure and function are compatible with the signs and symptoms observed in Malawian children with CM. Immunohistochemistry on autopsy brain tissues from eight cases of CM showed activation of endothelial cells and macrophages, and disruption of endothelial intercellular junctions in vessels containing sequestered parasitized erythrocytes, but no gross leakage of plasma proteins. Examination of the partition of albumin between circulating plasma and the cerebrospinal fluid from 72 cases of CM showed subtle but measurable changes compatible with impaired BBB function in malaria. These findings suggest that BBB breakdown occurs in areas of parasite sequestration in CM in African children.
 ...
PMID:Blood-brain barrier function in cerebral malaria in Malawian children. 1144 19


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>