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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 probably related to an overstimulation of the immune system and the cytokine network. We have previously demonstrated that tumour necrosis factor (TNF) secretion by human macrophages can be induced by soluble and heat-stable malarial antigens. Indirect evidence from epidemiological and in vitro studies suggests that Pf155/RESA can be considered as a candidate for triggering TNF secretion. Thus we conducted experiments to investigate the relationship between Pf155/RESA and TNF production. The SGE1 strain of Plasmodium falciparum was compared with the P. falciparum FCR3 strain, which does not express Pf155/RESA protein, for ability to induce TNF secretion by normal human macrophages in vitro. Synthetic peptides from the Pf155/RESA antigen ((EENV)4, (EENVEHDA)4, (DDEHVEEPTVA)3), were used in some experiments. TNF levels were measured by an immunoradiometric assay. We observed that the RESA-defective strain induces lower levels of TNF after schizont rupture than the SGE1 strain. Moreover, substantial TNF secretion was detected when macrophages were incubated with all three peptides, maximum levels being obtained with the (EENV)4 peptide. Although previous reports have described TNF-inducing activity of phospholipid from P. falciparum, these findings strengthen the evidence for Pf155/RESA antigens also being involved in TNF production during malaria.
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PMID:Ring-infected erythrocyte surface antigen (Pf/155RESA) induces tumour necrosis factor-alpha production. 768 75

Cerebral malaria is one of the major and deadly complications of malaria. In Cameroon, recent reports indicate that severe cases of malaria are increasingly more prevalent, particularly in children. The present study aims at describing the clinical presentation and laboratory findings of cerebral malaria in children in Yaounde. All patients admitted in the paediatric ward of Yaounde Central Hospital with malaria, who presented neurological signs and were tested positive for Plasmodium in their peripheral blood were recruited into the study. 36 cases were enrolled in all, making up 2.7% of all admissions. The patients' median age was 4.5 years. 52.8% were on malaria prophylaxis. Convulsions and coma with preceding hyperthermia were present in more than 90% of the patients. Blood parasites level median was 1.3% on admission. One patient had hypoglycaemia on admission and two others had it later on after admission; 16.7% had neurological sequels at discharge and two children died (5.6%). Delay in diagnosis and initiation of treatment with quinine adversely affected the prognosis of cerebral malaria in the study group.
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PMID:[Cerebral malaria in children in Yaounde, Cameroon. Clinical, paraclinical and developmental aspects]. 784 Jun 87

A small proportion of individuals infected with Plasmodium falciparum develop cerebral malaria. Why it affects some infected individuals but not others is poorly understood. Since tumor necrosis factor (TNF) has been implicated strongly in the pathogenesis of cerebral malaria, here we have compared different parasite isolates for their ability to induce TNF production by human mononuclear cells in vitro. Wild isolates were collected from 34 Gambian children with cerebral malaria and 66 children with uncomplicated malaria fever. Cerebral malaria isolates tended to stimulate more TNF production than mild malaria isolates, but there was considerable overlap between the two groups, and the present data provide only limited support for the hypothesis that cerebral malaria is caused by strains of P. falciparum inducing high levels of TNF. However, it is notable that the amounts of TNF induced by different wild isolates from a single locality differed by over 100-fold. The biological significance of this polymorphism deserves further scrutiny in view of the central role that TNF is believed to play in host defense and in the clinical symptomatology of human malaria.
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PMID:Strain variation in tumor necrosis factor induction by parasites from children with acute falciparum malaria. 789 Mar 68

Cerebral malaria in man and in mice is the consequence of a cascade of events, involving the production of toxins by the parasite and cytokines by the host, and eventually leading to the amplification of the expression of the receptors for cytoadherence on brain capillary endothelial cells. Variations in the intrinsic characteristics of parasite isolates or the genetic make-up of the host and the degree of antimalarial immunity can modulate this sequence of events. A working hypothesis is proposed in which two features of the parasite, the ability to cytoadhere and to produce toxins, are clearly dissociated and where the amplification of cytoadherence receptors is considered crucial. This hypothesis, illustrated by new data from human malaria and rodent models, suggests that cerebral malaria may occur when these features occur together during an infection, while not necessarily within the same parasite clone.
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PMID:Amplification of cytoadherence in cerebral malaria: towards a more rational explanation of disease pathophysiology. 812 26

Mice infected with Plasmodium berghei K173-parasitized erythrocytes develop severe hypothermia followed by death as a consequence of murine cerebral malaria early in the second week after infection. A single intraperitoneal injection of 10(5) Units of IFN-gamma given between Day 4 and Day 6 postinfection results in a transient decrease of body temperature. No effect on parasitemia and cerebral malaria is obtained by this treatment. Daily injections of relatively low doses of IFN-gamma delays the patency of the infection for 2 days. Furthermore the proliferation rate of the parasites is reduced and the development of cerebral malaria is also delayed for 2 days. The reduction of body temperature, as found in untreated infected mice, is absent. Administration of IFN-gamma by means of a continuous delivery from intraperitoneally inserted osmotic pumps (1.2 x 10(4) Units of IFN-gamma/24 hr) also delays patency and inhibits parasitemia. Body temperature decreases during infection but mice are protected against the development of cerebral malaria. In nude mice, this treatment inhibits parasitemia to the same extent. However, reduction of body temperature was also prevented. High doses of IFN-gamma delivered by osmotic pumps (2.5 x 10(4) or 10(5) Units of IFN-gamma/24 hr) appear to be lethally toxic in conventional as well as in nude mice, independently of infection. Cerebral malaria-like symptoms are found in these mice. Treatment of infected C57BL/6J mice with antibody to IFN-gamma 4 days before and after infection as well as on the day of infection enhances parasitemia but does not affect the development of murine cerebral malaria. Single injections of anti-IFN-gamma-antibody 6 hr prior to infection or 7 days after infection have no effect. In CBA/Ca mice, treatment with anti-IFN-gamma-antibody enhances parasitemia; furthermore protection against cerebral malaria was obtained in part of the mice.
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PMID:Plasmodium berghei: recombinant interferon-gamma and the development of parasitemia and cerebral lesions in malaria-infected mice. 837 90

Cerebral malaria (CM) is the most common cause of death in severe malaria; more than two million children die of CM annually. Although the mechanisms of this neurologic complication remain poorly understood, studies in an experimental model of CM suggest that a natural body protein seems to be a major cause of this deadliest complication of malaria, a finding that could point towards new methods of treatment. We have explored the pathogenesis of CM with particular attention to the possible relationship between susceptibility or resistance to CM and cytokine expression and secretion patterns. We found that CM is associated with an increased expression of tumor necrosis factor (TNF) and interferon (IFN)-gamma and a reduced expression of interleukin-4 (IL-4) and transforming growth factor (TGF)-beta. The data obtained are consistent with a predominantly Th1 response in mice developing the cerebral complications of malaria. The overexpression of TNF in brain was also correlated with the augmented expression of adhesion molecules involved in the sequestration of leukocytes in brain vessels, a distinctive feature of CM. These observations were seen in relation to the immune status of man, in which, akin to the mouse model, a predominant Th1 response and upregulation of adhesion molecules in brain endothelium appear to be associated with susceptibility to the neurological complications of CM.
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PMID:Role of cytokines and adhesion molecules in malaria immunopathology. 845 80

Elevated levels of methaemoglobin, the ferric form of haemoglobin incapable of oxygen transport, have been previously found during Plasmodium vivax infections and in acidotic infants. We measured methaemoglobin in the following 5 groups of children with P. falciparum malaria admitted to Muhimbili Medical Centre, Dar es Salaam, Tanzania. (i) Cerebral malaria (CM) with unrousable coma (n = 50), including 32 with complete recovery (CMCR) and 18 with death or neurological sequelae (CMDS); (ii) malaria with severe anaemia but without severe respiratory distress (SA; n = 6); (iii) uncomplicated malaria (UM; n = 37); (iv) asymptomatic parasitaemia (AP; n = 5); and (v) healthy controls (HC; n = 34). Mean methaemoglobin levels were elevated in all groups with malaria, forming up to 16.4% of circulating haemoglobin. The degree of methaemoglobinaemia correlated with disease severity and severity of anaemia. Mean methaemoglobin levels in children with AP, UM, SA, CMCR and CMDS were 3.3%, 4.1%, 5.6%, 4.7% and 5.8% respectively; the mean levels in those with clinical disease were significantly higher than those in healthy controls (2.0%). Methaemoglobinaemia > 10% was found in 5.4%, 16.7%, 12.5%, and 22.2% of those with UM, SA, CMCR and CMDS, respectively. In the presence of parasite sequestration, impaired tissue perfusion, and a reduction in oxygen carrying capacity of blood due to anaemia, a further reduction in oxygen carrying capacity from even a modest concentration of methaemoglobin is likely to exacerbate tissue hypoxia, perhaps critically so in a minority of anaemic and acidotic patients with severe falciparum malaria.
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PMID:Elevated levels of methaemoglobin in Tanzanian children with severe and uncomplicated malaria. 876 75

The various stages of Plasmodium falciparum (sporozoites and liver stages, asexual blood stages and gametocytes) each interact in a particular way with the human immune system. Specific immunity against the liver stages is achieved through a coordinated action of CD8 T cells and specific antibodies, the latter in collaboration with NK cells and macrophages. In this reaction, interferon-gamma plays an essential role. A non-specific "concomitant" immunity against sporozoites is based on a cytokine reaction, elicited by the blood stages. In practice, the high variability in the immunogenic structures of the sporozoite precludes completely protection against recurrent infections. The spleen macrophages have a pivotal role in the immune defense against the asexual blood stages. The elimination of merozoites and parasitized red blood cells (RBC) is facilitated by specific antibodies, produced under the control of CD4 T cells. There are, however, multiple mechanisms of immune deviation, suppression and evolutionary adaptation, which inhibit a sterilizing immunity against the blood stages. Nevertheless, symptoms may be absent in exposed adults, even when parasitemia persists. This clinical resistance, however, is relatively short-lived, once exposition is interrupted. The observation that HIV infection has no adverse effect on malaria also is a remarkable but consistent finding. All these data indicate that a strong T cell-mediated immune memory is absent in human P. falciparum infections. Cerebral malaria and some other serious complications are the consequence of insufficient elimination of parasitized erythrocytes by the spleen, presumably in combination with parasite factors (particular variant surface structures) and with human host genetics (HLA type, blood group etc.). Parasitized RBC massively stick to the endothelium of the micro-vessels and non-parasitized RBC roset around the parasitized ones. Eventually, serious problems in the micro-perfusion and in the local metabolism occur and organ failure may finally ensue. The immune reaction against the surface-antigens of the sexual stage is limited and insufficient, most probably for similar reasons as in the asexual stages. Internal structures of the gametocytes, however, are highly immunogenic, but, unfortunately. Normally cannot be reached by the immune system. Based on these fundamental data, some of the perspectives of vaccination and new therapeutic tools are critically discussed.
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PMID:[Immunology of human Plasmodium falciparum malaria]. 884 94

Cerebral malaria causes major neurological sequelae in a proportion of survivors and may lead to neuropsychological sequelae in children who seem to have made a good recovery. If this is the case, cerebral malaria could have a dramatic impact on the development of thousands of African children. The present study was carried out to provide information on the incidence and type of neuropsychological sequelae in children who survive the disease without major neurological sequelae. A matched case-control study design was used in which 36 pairs of children were assessed. The cases had been treated for cerebral malaria a mean of 3.4 years before testing. No evidence of a serious long-term impact on most assessed neuropsychological functions was found in these children. Only in the balance test did cases perform less well than their matched controls, but the difference between the 2 groups was only of borderline significance. These findings suggest that the long-term impact of cerebral malaria on the development of children who recover without major neurological sequelae is not as serious as had been feared.
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PMID:Absence of neuropsychological sequelae following cerebral malaria in Gambian children. 888 84

Cerebral malaria, a severe complication of malaria, is caused by the obstruction of cerebral microvessels by Plasmodium falciparum-infected erythrocytes. Such cells adhere to endothelial cells by means of "knobs" induced on the red cell membrane by the parasites. When atomic force microscopy was used to investigate the structure of the knobs of unfixed infected red cells, each knob was found to consist of two distinct subunits, knob components that have never been seen in chemically fixed knobs examined by conventional transmission electron microscopy. Surface potential spectroscopy revealed that the knobs have a positive charge (+20 mV), whereas the remainder of the red cell plasma membrane is negatively charged. Since endothelial plasma membranes have a negative charge, the charge difference between knobs and endothelium may play a significant role in cytoadherence between the two cell types. The subunit structure of the knobs may be a steric necessity to align adherence molecules so that they can exert their effect. This study shows that the atomic force microscope has great potential for examination of cells in their native state; in combination with surface potential spectroscopy, it may uncover fundamental processes and mechanisms in cell function.
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PMID:Membrane knobs of unfixed Plasmodium falciparum infected erythrocytes: new findings as revealed by atomic force microscopy and surface potential spectroscopy. 894 23


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