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

Early diagnosis and differentiation of a probably mild course are the first steps in treatment of severe malaria tropica. After confirming the diagnosis by identification of Plasmodium falciparum in blood smears, causal therapy with quinine should be started immediately, followed by a 2. schizontozidal drug (chloroquine or mefloquine depending on the country of origin). To prevent the typical organ failures adjuvant therapies are as important as the causal therapy with quinine: besides continuous monitoring of vital functions and treatment according to the guidelines of intensive care, packed red cells should be given generously as well as fresh-frozen plasma in complex coagulation disturbances. Prophylactic administration of heparine is of questionable value, corticosteroids should not be given any more in cerebral malaria. Early start with renal replacement therapy (hemodialysis, hemofiltration or peritoneal-dialysis) in oligo-anuric renal failure improves the prognosis in severe malaria. In comatose patients and at signs of multi-organ failure plasma exchange by plasmapheresis and/or whole blood exchange should be performed.
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PMID:[Therapy of severe malaria]. 266 20

We studied the relationship between presenting features and outcome in 131 Malawian children admitted with cerebral malaria (P. falciparum malaria and unrousable coma). A method was devised for the measurement of depth of coma in children too young to speak. Twenty patients (15 per cent) died and 12 (9 per cent) recovered with residual neurological sequelae. Presenting clinical signs significantly associated with adverse outcome (death or sequelae) were profound coma, signs of decerebration, absence of corneal reflexes, convulsions at the time of admission and age under three years. Laboratory findings of prognostic significance were hypoglycaemia, leucocytosis, hyperparasitaemia, elevated plasma concentrations of alanine and 5'-nucleotidase, and elevated plasma or cerebrospinal fluid lactate. A prognostic index based on eight of these risk factors that can readily be ascertained at the bedside or in a ward sideroom, was more accurately predictive of outcome than any single feature. Such an index may be valuable as a measure of severity of illness for establishing the comparability of study groups, and for evaluating the role of other factors in the pathogenesis of cerebral malaria.
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PMID:Clinical features and prognostic indicators in paediatric cerebral malaria: a study of 131 comatose Malawian children. 269 Jan 75

In 12 patients comatose with cerebral malaria, cerebral blood flow was 52.2 (SE 4.0) ml/100 g per min, within the reported range for healthy controls, but cerebral vascular resistance was raised at 1.66 (0.19) mm Hg/ml per 100 g per min. Cerebral oxygen consumption (1.90 [0.23] ml/100 g per min), and cerebral arteriovenous oxygen content difference (3.5 [0.43] ml/dl) were subnormal, while cerebral venous pO2 (5.7 [0.2] kpA) was raised. After recovery of consciousness there were significant decreases in arterial lactate concentration (2.44 [0.45] to 1.19 [0.45] mumol/l) and cerebral lactate production (17.4 [7.9] to 5.6 [1.1] mmol/100 g per minute). These results provide evidence of cerebral anaerobic glycolysis associated with inadequate oxygen delivery to the brain consistent with either inhibition of cerebral oxidative metabolism or the microcirculatory obstruction envisaged in the "mechanical" hypothesis for cerebral malaria.
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PMID:Cerebral anaerobic glycolysis and reduced cerebral oxygen transport in human cerebral malaria. 290 Sep 21

A series of 170 patients with non-traumatic coma seen over a 16-month period is reported. The Glasgow coma scale significantly correlated with outcome (P less than 0.001). The diagnosis was also important in determining outcome. Hospital mortality was lowest in patients with cerebral malaria (22.7%), eclamptic coma (36.4%), and organophosphorous poisoning (30.4%). A diagnostic approach to non-traumatic coma is outlined and the management of the different causes is discussed. Most hospitals in tropical Africa should be able to diagnose up to 90% of cases with non-traumatic coma and simple therapy is likely to be effective in the majority of cases.
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PMID:Non-traumatic coma in Zambia. 292 23

We compared placebo and dexamethasone (initial dose, 3 mg/kg; total, 11.4 mg/kg per 48 h) in a double-blind trial involving 10 stuporous and 28 comatose patients with cerebral malaria. Patients were 18 mo to 42 y of age (geometric mean, 10.2 y), and the 19 patients in each group were comparable on admission. All patients received intravenous quinine therapy. Four patients (21%) in each group died. There were no significant differences between the placebo- and dexamethasone-treated groups in time until patients became afebrile (median, 51 vs. 19 h), the level of consciousness became normal (mean, 80 vs. 83 h), or parasitemia was cleared (mean, 2.1 vs. 3.4 d) or in the incidence of complications. Coma or hyperparasitemia (greater than or equal to 5% of erythrocytes parasitized) at the time of admission and hypoglycemia at any time during hospitalization were significantly correlated with a fatal outcome, which was not improved by using dexamethasone. We conclude that high-dose dexamethasone is not indicated for treating cerebral malaria.
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PMID:High-dose dexamethasone in quinine-treated patients with cerebral malaria: a double-blind, placebo-controlled trial. 304 74

Although empirical regimens of parenteral chloroquine have been used extensively to treat severe malaria for 40 years, recent recommendations state that parenteral chloroquine should no longer be used because of potential toxicity. We studied prospectively the pharmacokinetics and toxicity of seven chloroquine regimens in 58 Gambian children with severe chloroquine-sensitive falciparum malaria. In all regimens the total cumulative dose was 25 mg of chloroquine base per kilogram of body weight. Chloroquine was rapidly absorbed after either intramuscular or subcutaneous administration (5 mg of base per kilogram every 12 hours), producing high peak blood concentrations but transient hypotension in 5 of 18 patients (28 percent). Intermittent intravenous infusion (5 mg of base per kilogram over 4 hours, repeated every 12 hours) also produced wide fluctuations in chloroquine levels, suggesting incomplete distribution from a small central compartment. Continuous infusion (0.83 mg of base per kilogram per hour for 30 hours) and smaller, more frequent intramuscular or subcutaneous injections of chloroquine (3.5 mg of base per kilogram every 6 hours) produced smoother blood-concentration profiles with lower early peak levels and no adverse cardiovascular or neurologic effects. Chloroquine given by nasogastric tube (initial dose, 10 mg of base per kilogram) was absorbed well, even in comatose children. We conclude that simple alterations in dosage and frequency of administration can give parenteral chloroquine an acceptable therapeutic ratio and reinstate it as the treatment of choice for severe malaria in areas where chloroquine resistance is not a major problem.
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PMID:Chloroquine treatment of severe malaria in children. Pharmacokinetics, toxicity, and new dosage recommendations. 305 58

Changes in plasma glucose and insulin concentrations were monitored over 24 hours in 28 African patients receiving quinine intravenously in an average dose of 8.5 mg base/kg over one hour eight hourly for severe malaria. The patients (nine children and 19 adults) were moderately undernourished; none was pregnant or had renal insufficiency. Plasma insulin concentrations rose during the infusion and then declined. Plasma glucose concentrations were decreased at two, three, and four hours after the start of the infusion. Insulin: glucose ratios were raised between half an hour and two hours after the start of the infusion. The three infusions of quinine increased plasma insulin concentrations in a similar way. In nine patients, including four children, plasma glucose concentrations fell below 2.8 mmol/l on one or two occasions. At the time of the hypoglycaemia plasma insulin concentrations were inappropriately high as shown by a consistent and often considerable increase in the insulin:glucose ratio. Hypoglycaemia that may pass unnoticed in comatose patients is thus a common complication of treating severe malaria with quinine, in particular in children. Its high incidence calls for attentive monitoring and preventive measures.
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PMID:High incidence of hypoglycaemia in African patients treated with intravenous quinine for severe malaria. 311 15

A 42-year-old man was admitted to hospital with, previously wrongly diagnosed, fulminant falciparum malaria, 14 days after a two-week trip to Kenya. He had a high fever and was jaundiced, with severe anaemia and thrombocytopenia. He was given quinine intravenously and pyrimethamine/sulfadoxine (Fansidar) by mouth. He developed acute renal failure and increasingly severe cerebral symptoms, at times coma. An exchange transfusion and several plasmaphereses were, therefore, performed. The cerebral symptoms quickly abated during the exchange transfusion, but renal function failed to improve. Because of continuing fever, mefloquin (Lariam) and doxy-cycline (Vibramycin) were also administered. After several dialysis periods the patient improved gradually and was discharged after three weeks in generally good condition with normal renal function.
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PMID:[Exchange transfusion and (or) plasmapheresis: effective measures in severe tropical malaria?]. 328 61

The toxicities of antimalarial drugs vary because of the differences in the chemical structures of these compounds. Quinine, the oldest antimalarial, has been used for 300 years. Of the 200 to 300 compounds synthesised since the first synthetic antimalarial, primaquine in 1926, 15 to 20 are currently used for malaria treatment, most of which are quinoline derivatives. Quinoline derivatives, particularly quinine and chloroquine, are highly toxic in overdose. The toxic effects are related to their quinidine-like actions on the heart and include circulatory arrest, cardiogenic shock, conduction disturbances and ventricular arrhythmias. Additional clinical features are obnubilation, coma, convulsions, respiratory depression. Blindness is a frequent complication in quinine overdose. Hypokalaemia is consistently present, although apparently self-correcting, in severe chloroquine poisoning and is a good index of severity. Recent toxicokinetic studies of quinine and chloroquine showed good correlations between dose ingested, serum concentrations and clinical features, and confirmed the inefficacy of haemodialysis, haemoperfusion and peritoneal dialysis for enhancing drug removal. The other quinoline derivatives appear to be less toxic. Amodiaquine may induce side effects such as gastrointestinal symptoms, agranulocytosis and hepatitis. The main feature of primaquine overdose is methaemoglobinaemia. No cases of mefloquine and piperaquine overdose have been reported. Overdose with quinacrine, an acridine derivative, may result in nausea, vomiting, confusion, convulsion and acute psychosis. The dehydrofolate reductase inhibitors used in malaria treatment are sulfadoxine, dapsone, proguanil (chloroguanide), trimethoprim and pyrimethamine. Most of these drugs are given in combination. Proguanil is one of the safest antimalarials. Convulsion, coma and blindness have been reported in pyrimethamine overdose. Sulfadoxine can induce Lyell and Stevens-Johnson syndromes. The main feature of dapsone poisoning is severe methaemoglobinaemia which is related to dapsone and to its metabolites. Recent toxicokinetic studies confirmed the efficacy of oral activated charcoal, haemodialysis and haemoperfusion in enhancing removal of dapsone and its metabolites. No overdose has been reported with artemesinine, a new antimalarial tested in the People's Republic of China. The general management of antimalarial overdose include gastric lavage and symptomatic treatment.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Clinical features and management of poisoning due to antimalarial drugs. 330 66

This report describes a Danish patient with severe Plasmodium falciparum infection and Pseudomonas aeruginosa septicaemia. The patient had been sailing along the coast of West Africa for ten years without taking any antimalaria prophylaxis and without any apparent previous history of malaria. He presented with severe form of malaria, progressing rapidly into coma and died within a short time. P. aeruginosa was isolated from his blood taken on the day of admission. His neutrophils were all occupied by P. falciparum. The unusual combination of severe falciparum malaria infection and P. aeruginosa septicaemia with extensive involvement of neutrophils lends further support for the role of phagocytic defence in malaria.
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PMID:Pseudomonas aeruginosa septicaemia in a patient with severe Plasmodium falciparum. 332 35


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