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

The origin of illness and pathology in malaria is now largely attributed to high levels of circulating tumour necrosis factor (TNF), released from cells of macrophage lineage after triggering by the products of malarial schizogony. The role of lymphocytes and their products in malarial pathology is not yet known. This paper reports the presence of a related cytokine, lymphotoxin, which is produced only by lymphocytes, in the serum of malarial patients. This is the first report of raised serum levels of lymphotoxin in a systemic disease state. When injected into mice, recombinant human lymphotoxin induced hypoglycaemia and increased serum levels of interleukin-6. These changes, which are seen in severe experimental and human malaria, were also provoked by TNF. Both of these cytokines acted synergistically with interleukin-1, which has also been reported to be raised in malaria, to produce these alterations. These observations imply that lymphotoxin, as well as TNF, may contribute to the hypoglycaemia and raised serum interleukin-6 observed in malaria. This reduces the likelihood of effectively blocking the pathology of this disease by the use of neutralizing antibody directed against just one member of this family of functionally overlapping mediators.
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PMID:Increased lymphotoxin in human malarial serum, and the ability of this cytokine to increase plasma interleukin-6 and cause hypoglycaemia in mice: implications for malarial pathology. 128 10

This paper reviews the neurological complications of malaria. Cerebral malaria, the acute encephalopathy which complicates exclusively the infection by Plasmodium falciparum commonly affects children and adolescents in hyperendemic areas. Plugging of cerebral capillaries and venules by clumped, parasitized red blood cells causing blood sludging in the capillary circulation is one hypothesis to explain its pathogenesis. The other is a humoral hypothesis which proposes a nonspecific, immune-mediated, inflammatory response with release of vasoactive substances capable of producing endothelial damage and alterations of permeability. Cerebral malaria has a mortality rate up to 50%, and also a considerable longterm morbidity, particularly in children. Hypoglycemia, largely in patients treated with quinine, may complicate the cerebral symptomatology. Other central nervous manifestations of malaria include intracranial hemorrhage, cerebral arterial occlusion, and transient extrapyramidal and neuropsychiatric manifestations. A self-limiting, isolated cerebellar ataxia, presumably caused by immunological mechanisms, in patients recovering from falciparum malaria has been recognized in Sri Lanka. Malaria is a common cause of febrile seizures in the tropics, and it also contributes to the development of epilepsy in later life. Several reports of spinal cord and peripheral nerve involvement are also available. A transient muscle paralysis resembling periodic paralysis during febrile episodes of malaria has been described in some patients. The pathogenesis of these neurological manifestations in malaria remains unexplored, but offers excellent perspectives for research at clinical as well as experimental level.
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PMID:Neurological complications of malaria. 129 73

From July 1989 to February 1990, 17 non-pregnant patients with severe falciparum malaria, aged 14 years and above received an initial intravenous quinine dihydrochloride loading dose of 20 mg/kg in 500 mls of normal saline or 5% dextrose infused over 4 hours followed by 100mg/kg infused 8 hourly for at least 24 hours. Sixteen comparable controls were similarly treated but without an initial loading dose. Oral quinine bisulfate 10mg/kg 8 hourly was substituted for a total of 7 days when patients were well enough. There was no significant difference in clinical and parasitological response between the two groups. Fever clearance time in hours was 44.00 +/- 13.92 (mean +/- SD) in the study group and 51.43 +/- 19.63 (mean +/- SD) in the control group (p > 0.05). Parasite clearance time in hours was 42.40 +/- 9.75 (mean +/- SD) in the study group and 47.05 +/- 7.69 (mean +/- SD) in the control group (p > 0.05). One patient from each group died. Mild toxic effects were common in both groups. Transient partial hearing loss occurred significantly more in the study than control group (p < 0.05). Hypoglycaemia during treatment occurred in 3 (18%) patients in the study group and 1 (6%) in the control group. The mean trough and peak plasma quinine levels in 3 patients per group was persistently higher than 9mg/L after first infusion. We conclude that though fairly well tolerated, quinine loading dose appears to have no advantage over the standard treatment for severe falciparum malaria at Kenyatta National Hospital, Nairobi, Kenya.
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PMID:Quinine loading dose in severe Falciparum malaria at Kenyatta National Hospital, Kenya. 129 31

The involvement of the nervous system in malaria is reviewed in this paper. Cerebral malaria, the acute encephalopathy which complicates exclusively the infection by Plasmodium falciparum commonly affects children and adolescents in hyperendemic areas. Plugging of cerebral capillaries and venules by clumped, parasitized red cells causing sludging in the capillary circulation is one hypothesis to explain its pathogenesis. The other is a humoral hypothesis which proposes nonspecific, immune-mediated, inflammatory responses with release of vasoactive substances capable of producing endothelial damage and alterations of permeability. Cerebral malaria has a mortality rate up to 50%, and also a considerable longterm morbidity, particularly in children. Hypoglycemia, largely in patients treated with quinine, may complicate the cerebral symptomatology. Other central nervous manifestations of malaria include intracranial hemorrhage, cerebral arterial occlusion, and transient extrapyramidal and neuropsychiatric manifestations. A self-limiting, isolated cerebellar ataxia, presumably caused by immunological mechanisms, in patients recovering from falciparum malaria has been recognized in Sri Lanka. Malaria is a common cause of febrile seizures in the tropics, and it also contributes to the development of epilepsy in later life. Several reports of spinal cord and peripheral nerve involvement are also available. A transient muscle paralysis resembling periodic paralysis during febrile episodes of malaria has been described in some patients. The pathogenesis of these neurological manifestations remains unexplored, but offers excellent perspectives for research at a clinical as well as experimental level.
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PMID:Neurological manifestations of malaria. 130 75

1. Hypoglycaemia and lactic acidosis are important manifestations of severe falciparum malaria. To investigate hepatic gluconeogenesis in acute falciparum malaria, liver blood flow and galactose clearance were estimated in seven adult patients with moderately severe infection and seven patients with severe infection (three of whom died later). Nine patients were restudied in convalescence. 2. Liver blood flow, determined from the plasma clearance of Indocyanine Green, was lower in acute illness than in convalescence [16.1 (7.0) versus 23.9 (7.2) ml min-1 kg-1, mean (SD)], but this difference was not statistically significant (P = 0.15). There was a significant inverse correlation between admission venous plasma lactate concentrations and the liver blood flow estimated from the clearance of Indocyanine Green (rs = 0.71, P = 0.004). 3. The plasma clearance of galactose after intravenous injection was similar in the acute [15.4 (4.90) ml min-1 kg-1] and convalescent study [12.8 (2.1) ml min-1 kg-1]. The ratio of galactose clearance to Indocyanine Green clearance was significantly higher in acute disease [1.41 (0.51)] than in convalescence [0.70 (0.34)], largely because of the elevated ratios in severely ill patients [1.48 (0.50)]. 4. The rise in blood glucose concentration after galactose administration was significantly higher during acute illness [1.48 (0.72) mmol/l] than in convalescence [0.67 (0.41) mmol/l, P = 0.022], but the insulin response was similar, indicating reduced tissue insulin sensitivity. There was no significant change in the plasma concentrations of other metabolites (lactate, pyruvate, alanine and triacylglycerol) in either study. 5. These results suggest that the segment of the glycolytic pathway between galactose and glucose is unimpaired in patients with severe falciparum malaria.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hepatic blood flow and metabolism in severe falciparum malaria: clearance of intravenously administered galactose. 131 Sep 19

Malaria is a major problem in children in many parts of Papua New Guinea; it has a high mortality and, if observations from other countries are applicable, significant long-term morbidity. Standard treatment regimens are the backbone of management of malaria throughout the country, but these must continue to be reviewed and updated in the face of changing patterns of parasite drug sensitivity. Diagnosis of malaria will for practical purposes remain primarily clinical for the foreseeable future. There is a need for uniform reporting of malaria statistics using the established definitions of uncomplicated, treatment failure and severe malaria, in order to assess incidence and outcome throughout the country, and to compare malaria patterns and outcome in Papua New Guinea with those in other parts of the world. Congenital malaria should always be considered in a febrile or ill neonate. Awareness of the complications of severe malaria, particularly hypoglycaemia, needs to be increased. Methods for the diagnosis and facilities for treatment of hypoglycaemia should be widely available. The characteristics of those children most at risk from hypoglycaemia need elucidation, and the current standard management regimen for severe malaria needs to be assessed for its propensity both to cause and to prevent hypoglycaemia. It would be reasonable to incorporate phenobarbitone prophylaxis of convulsions into the standard management regimen for cerebral malaria.
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PMID:Malaria in children in Papua New Guinea. 134 Oct 86

Hypoglycaemia is associated with severe malaria and is an important prognostic indicator. Molecules liberated during overnight incubation of erythrocytes infected with Plasmodium yoelii induce marked hypoglycaemia in normal mice, with a delayed time course compared with insulin; some, though weaker, activity could also be obtained by overnight incubation of uninfected erythrocytes. The active component shares many properties with the phospholipid-containing molecules which we have previously shown to be toxic and to induce the release of tumour necrosis factor (TNF) from macrophages. However a MoAb which neutralizes the cytotoxicity of tumour necrosis factor in vitro did not prevent this induction of hypoglycaemia, whereas antiserum against the toxic antigens did, as did immunization of normal (but not the immunoglobulin-deficient SCID) mice with the same material. Furthermore, normal mice injected with the antigens after immunization with phosphatidyl inositol or inositol monophosphate did not develop hypoglycaemia; the latter compound was also inhibitory when mixed with the antigens before injection. These compounds were previously shown to block the induction of TNF by the antigens and to induce the production of inhibitory antibodies. The role of these molecules in the etiology of the hypoglycaemia of malaria is discussed.
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PMID:Phospholipid-containing toxic malaria antigens induce hypoglycaemia. 139 89

Hypoglycaemia is a major complication of severe malaria [(1990) Trans. Roy. Soc. Trop. Med. 84 (suppl. 2) 1-65], especially cerebral malaria, in which it is associated with increased mortality [(1990) Lancet 336, 1039-1043; (1989) Quart. J. Med. (New series) 71, 441-459]; however, the mechanisms responsible have not been fully explained. Preparations containing toxic malaria antigens (TMA) released by blood stage Plasmodium yoelii malaria parasites have been shown to induce hypoglycaemia in mice lasting at least 8 h [(1992) Clin. Exp. Immunol. (in press)]. Here we report that TMAs can act synergistically with insulin in both stimulating lipogenesis and inhibiting lipolysis in rat adipocytes in vitro, and, furthermore, that they act synergistically with insulin in the induction of hypoglycaemia in vivo.
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PMID:Malarial toxic antigens synergistically enhance insulin signalling. 139 20

We report a patient with diabetes mellitus who suffered severe falciparum malaria complicated by profound and persistent hypoglycaemia. The hypoglycaemia evolved before therapy with quinine was begun and resolved with eradication of the parasitaemia. The patient reverted to her baseline hyperglycaemia despite continuation of quinine. This case illustrates the critical role of falciparum malaria in the pathogenesis of malaria-associated hypoglycaemia, rather than quinine-mediated mechanisms. Anticipation of hypoglycaemia in falciparum malaria and its vigorous treatment may improve the poor prognosis associated with this complication.
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PMID:Falciparum malaria-induced hypoglycaemia in a diabetic patient. 832 5

An audit of the management of falciparum malaria was carried out over a 12 month period in a north-west Tanzanian district hospital; 1494 patients were studied, 75% being children under 5 years. Chloroquine was effective in 1128 cases (79%), 68 patients died, of whom 64 were aged under 5 years; 30 of them died fewer than 2 d after admission; 14 had received quinine chemotherapy. Management can be improved by better diagnosis of anaemia and hypoglycaemia, changing the dose of injectable chloroquine, earlier use of quinine, and enabling doctors to see very ill patients earlier.
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PMID:An audit of the management of malaria in a Tanzanian district hospital. 836 81


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