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

To investigate the therapeutic potential of increased plasma free fatty acid (FFA) and triglyceride concentrations in hypoglycaemic patients receiving quinine, 32 untreated Thai adults with uncomplicated falciparum malaria were allocated at random to one of 4 regimens: 2 mg/kg/min dextrose infused over 60 min either alone (group A) or with a prior injection of 5000 units of heparin and simultaneous Intralipid infusion (group C), or 4 min/kg/min dextrose alone (group B) or with heparin and Intralipid (group D). Quinine (10 mg/kg) was also infused over 60 min in all cases. In patients of groups A and C, mean changes in plasma glucose concentrations from the beginning to the end of the infusion were 0.1 (SD 0.8) and 1.0 (SD 0.7) mmol/L respectively (P = 0.015). In groups B and D, plasma glucose increased by 1.8 (SD 1.2) and 2.2 (SD 0.4) mmol/L respectively (P < 0.5). Plasma FFA levels fell by approximately 50% during the infusion in groups A and B but increased by a similar percentage in groups C and D. Despite significant mean increases in plasma insulin during the infusion (from 12.2 milliunits (mu)/L in group A to 38.8 mu/L in group D), no rebound hypoglycaemia was observed in any patient during the ensuing 7 h. These data suggest that the glycaemic response to dextrose given at high rates, which match average glucose utilization in a severely ill patient with malaria, is not augmented by increased plasma FFA and long-chain triglycerides. However, this strategy increases the glycaemic efficacy of lower dextrose infusion rates and the combination could, therefore, reduce the volumes of hypertonic dextrose required to prevent hypoglycaemia in severely ill patients in whom optimal fluid balance is crucial.
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PMID:The effect of plasma free fatty acids and long-chain triglycerides on glucose metabolism in uncomplicated falciparum malaria. 856 May 27

In order to examine the effects of platelet-activating factor (PAF) in complicated Plasmodium falciparum infections, plasma concentrations of lyso-PAF, stable metabolite and principal precursor of PAF, were measured in 25 Vietnamese adults with severe malaria. The concentration of PAF in the cerebrospinal fluid (CSF) was determined in a sub-group of 23 comatose patients and, together with that of lyso-PAF, in the plasma of 20 patients on recovery of consciousness. The concentration of lyso-PAF in the plasma was depressed on admission to hospital (median [range]; 21 [8-143] vs. 293 [215-410] ng/ml in 10 controls; P < 0.001). There was, however, no change in plasma activity of acetylhydrolase which converts PAF to lyso-PAF (P > 0.01 vs. controls) while simultaneous reduction in the concentration of lipoproteins associated with lyso-PAF were less than those of lyso-PAF per se in the plasma. The plasma concentration of lyso-PAF on admission was associated with parasitaemia and the concentration of serum triglycerides (rs = -0.42, P = 0.04 in each case), the latter being consistent with hepatic effects of PAF reported in previous studies. CSF concentrations of PAF on admission were low (2.3 [0.5-7.7] vs. 0.9 [0-2.5] ng/ml after recovery, P < 0.01) compared with values reported previously in bacterial meningitis. Plasma concentrations of lyso-PAF after recovery lay between admission and control values. While increased availability of PAF may reflect parasite burden and may modulate liver-mediated metabolic disturbances such as hypoglycaemia and lactic acidosis, the role of PAF in cerebral malaria is uncertain.
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PMID:The metabolism of platelet-activating factor in severe and cerebral malaria. 858 36

BACKGROUND Salicylates continue to be marketed and to be used in developing countries as over-the-counter (OTC) antipyretics in children, whereas in developed countries they are no longer used in children because of safety concerns. The presenting signs of salicylate poisoning, especially chronic (repeated administration of therapeutic or excessive doses for longer than 12 h), can include metabolic acidosis, hypoglycaemia, lethargy, and coma and fits. These signs are also common in severe malaria in African children. Admission of two probable cases of chronic salicylate poisoning prompted us to look for other cases among children presenting to our hospital in Kenya, apparently with severe malaria. METHODS All children admitted to Kilifi District Hospital between July and September, 1994, who had a positive blood film for Plasmodium falciparum, and one or more of coma, prostration, or respiratory distress were eligible. As well as routine tests for malaria and routine biochemistry, salicylate concentrations were measured. Management of children (aged 6 months to 10 years) in the community was assessed by a cross-sectional survey of 463 households and by interviews with mothers 2 days after they had bought OTC drugs for a child with fever. FINDINGS Data were available for 143 of 154 children with initial primary diagnoses of severe malaria. 129 (90 percent) had detectable (>l mg/dL) salicylate. Six of these had salicylate concentrations of 20 mg/dL or higher. All six had neurological impairment and metabolic acidosis and four were, or became, hypoglycaemic. OTC drugs were the first-line treatment in 188 (74 percent) of 254 fever episodes during the 2 weeks before the cross-sectional survey. Of 250 mothers who bought drugs for a febrile child, 236 (94 percent) bought a preparation containing salicylates and 50 (21 percent) gave a dose higher than the manufacturer's recommended maximum. INTERPRETATION These cases suggest that in some children salicylate poisoning may cause or contribute to the development of metabolic acidosis and hypoglycaemia, complications of severe malaria associated with high mortality.
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PMID:Chronic salicylate poisoning and severe malaria. 865 7

We have investigated the metabolic disturbances in 2 murine models of blood-stage malaria, Plasmodium chabaudi and Plasmodium yoelii. Blood glucose, plasma insulin and parasitaemia were measured in normal and infected mice before and after treatment with diazoxide, adrenaline, Sandostatin and quinine. Severe hypoglycaemia and marked hyperinsulinaemia developed during both infections. A single injection of diazoxide (25 mg/kg i.p.) or adrenaline (0.03 mg s.c.) lowered insulin concentrations in normal mice, reversed the hypoglycaemia in both infections and significantly reduced the hyperinsulinaemia in P. chabaudi-infected mice (P < 0.0001). Higher doses of Sandostatin (500 micrograms/kg s.c.) were required to reverse hypoglycaemia. Quinine (25 mg/kg i.p.) significantly increased blood glucose in normal and infected mice (P < 0.0010 and no hypoglycaemia was observed in mice with normal blood glucose for more than 3 h. This study shows that the major cause of hypoglycaemia in murine malaria is hyperinsulinaemia rather than high consumption of glucose by host and parasites or chemotherapy with quinine, and that hypoglycaemia can be reversed by correcting the hyperinsulinaemia.
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PMID:Reversal of hypoglycaemia in murine malaria by drugs that inhibit insulin secretion. 868 25

Increasing drug resistance in Plasmodium falciparum and a resurgence of malaria in tropical areas have effected a change in treatment of malaria in the last two decades. Symptoms of malaria are fever, chills, headache, and malaise. The prognosis worsens as the parasite counts, counts of mature parasites, and counts of neutrophils containing pigment increase. Treatment depends on severity, age of patient, degree of background immunity, likely pattern of susceptibility to antimalarial drugs, and the cost and availability of drugs. Chloroquine should be used for P. vivax, P. malariae, and P. ovale. P. vivax has shown high resistance to chloroquine in Oceania, however. Primaquine may be needed to treat P. vivax and P. ovale to rid the body of hypnozoites that survive in the liver. Chloroquine can treat P. falciparum infections acquired in North Africa, Central America north of the Panama Canal, Haiti, or the Middle East but not in most of Africa and some parts of Asia and South America. In areas of low grade resistance to chloroquine, amodiaquine can be used to effectively treat falciparum malaria. A combination of sulfadoxine-pyrimethamine is responsive to falciparum infections with high grade resistance to chloroquine. Mefloquine, halofantrine, or quinine with tetracycline can be used to treat multidrug-resistant P. falciparum. Derivatives of artemisinin obtained from qinghao or sweet wormwood developed as pharmaceuticals in China are the most rapidly acting of all antimalarial drugs. Children tend to tolerate antimalarial drugs well. Children who weigh less than 15 kg should not be given mefloquine. Health workers should not prescribe primaquine to pregnant women or newborns due to the risk of hemolysis. Chloroquine, sulfadoxine-pyrimethamine, quinine, and quinidine can be safely given in therapeutic doses throughout pregnancy. Clinical manifestations of severe malaria are hypoglycemia, convulsions, severe anemia, acute renal failure, jaundice, pulmonary edema, cerebral malaria, shock, and acidosis. Health workers should be prepared to treat these symptoms accordingly.
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PMID:The treatment of malaria. 904 53

Malaria toxin causes hypoglycemia and induction of tumor necrosis factor. Extracts of parasitized erythrocytes which were coeluted and copurified with one of the two subtypes of mammalian insulin-mimetic inositolphosphoglycans similarly induced fibroblast proliferation in the absence of serum. In addition, induction of tumor necrosis factor in macrophages by malaria toxin and by lipopolysaccharide from Escherichia coli was enhanced by pretreatment of these toxins with alpha-galactosidase. Thus, parasitized erythrocytes contain both soluble inositolphosphoglycan-like insulin second messengers and endotoxin-like lipidic molecules.
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PMID:Structural similarities among malaria toxins insulin second messengers, and bacterial endotoxin. 875 90

Severe falciparum malaria usually occurs in children, but also occurs in nonimmune migrants or partially immune adults in areas of unstable transmission. We have studied prospectively 70 adult patients with strictly defined severe malaria from the south coast of Papua New Guinea where malaria transmission is not intense. Only 19 (27.1%) were migrants from areas where malaria transmission does not occur; many other patients were periurban dwellers who had become infected after visits to their home villages. The most common clinical features were jaundice or hepatic dysfunction, impaired consciousness, renal failure, cerebral malaria, and anemia. Hypoglycemia was common following treatment with quinine. The overall case fatality rate was 18.6%; renal failure and cerebral malaria in particular were associated with a poor outcome. Reduction in mortality might be achieved by aggressive therapy of renal failure with earlier institution of dialysis; the use of preventive measures for immigrants or urban dwellers returning to high transmission areas might reduce the incidence of this dangerous disease.
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PMID:Severe and complicated falciparum malaria in Melanesian adults in Papua New Guinea. 878 Apr 47

Hypoglycaemia in falciparum malaria is associated with a poor prognosis and is correlated with mortality. High levels of serum TNF are also correlated with disease severity and mortality, and it has been suggested that TNF may cause the hypoglycaemia. However hypoglycaemia in mice infected with Plasmodium chabaudi or the lethal strain of P. yoelii YM is related to hyperinsulinaemia. Its development was not prevented by treatments which diminished TNF activity or production without affecting levels of plasma insulin. Conversely, it was inhibited by diazoxide, which inhibited insulin secretion but did not affect TNF production. Furthermore, in mice exhibiting neurological symptoms during infection with P. berghei, blood glucose concentrations were significantly raised when TNF levels were high, and TNF levels in the spleen were highest of all in non-lethal P. yoelii infections in which hypoglycaemia does not occur. Administration of human rTNF to normal animals caused an increase rather than a drop in blood glucose levels. Mice transgenic for human TNF did not develop hypoglycaemia when infected with P. yoelii YM, but showed signs of insulin resistance. In line with current views on the role of TNF in obesity and the control of glucose homeostasis, we conclude that the hypoglycaemia of malaria is not caused by increased levels of TNF, which may in fact be beneficial, but is secondary to a hyperinsulinaemia that is probably stimulated directly by products of the parasite.
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PMID:Malaria, blood glucose, and the role of tumour necrosis factor (TNF) in mice. 880 32

This study reflected that administration of tetracycline along with quinine and cotrimoxazole can reduce mortality from cerebral malaria significantly. In this five year prospective study in an endemic zone, the authors assessed the outcome of treatment with or without tetracycline among 254 cases of cerebral malaria. 100 patients were treated with quinine and cotrimoxazole and 154 patients were given triple therapy-quinine, cotrimoxazole and tetracycline. Fatality in group without tetracycline was 18%, whereas in the tetracycline group it was 12.33%. One interesting observation was that the parasite count was not proportional to the severity of disease. Out of 254 patients of this series, 136 patients (53.54%) had low parasite count (less than 1,000/cumm) and only 26 patients (10.23%) had infinity count. Quinine induced cardiac arrhythmia or hypoglycaemia was not seen in any patient.
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PMID:Triple drug therapy with quinine, cotrimoxazole and tetracycline in the management of cerebral malaria--A review of 254 cases. 881 66

Alternative drugs to chloroquine are required to prevent the deleterious effects of malaria in pregnancy. Fear of potential toxicity has limited antimalarial drug use in pregnancy. Animal toxicity studies have documented teratogenicity when antimalarials are administered at high dosages. Excepting the tetracyclines, there is no evidence to suggest that, at standard dosages, any of the antimalarial drugs are teratogenic. Primaquine is not recommended because of the potential risk of haemolytic effects in the fetus. Rates of spontaneous abortion and birth defects were comparable in pregnant women taking mefloquine, compared with chloroquine-proguanil, or pyrimethamine-sulfadoxine prophylaxis, in the first trimester of pregnancy. Standard doses of quinine do not increase the risk of abortion or preterm delivery. Therapeutic mefloquine does not provoke hypoglycaemia. There is no evidence in the literature to support the hypothetical risk of kernicterus in the newborn, following exposure to antimalarial drugs containing sulphonamides or sulphones prior to delivery. Documentation of the safety of doxycycline, halofantrine, and the artemisinin derivatives in the treatment of malaria in pregnant women is currently limited.
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PMID:The safety of antimalarial drugs in pregnancy. 893 76


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