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

Neuropathologic examination of 19 fatal cases of cerebral malaria and a review of the literature showed that the epidemiologic, clinical, and pathologic features of this entity suggest consideration of cerebral malaria as a form of disseminated vasculomyelinopathy, a hyperegic reaction of the CNS to the antigenic challenge of Plasmodium falciparum infection. Experimental evidence also substantiates this view The initial event seems to be vasculopathy, with alteration of the endothelial permeability, followed by brain edema, perivascular infiltrates and ring hemorrhages, perivascular demyelination, and gliosis (malarial granuloma) in the late stages. This chain of events could be interrupted early in its course by corticosteroids. Parenteral dexamethasone should then be seriously considered at the first signs of involvement of the CNS during P falciparum malaria along with the standard forms of antimalarial therapy.
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PMID:Cerebral malaria. A disseminated vasculomyelinopathy. 34 69

A case is reported of a 40-year-old woman presenting with cerebral malaria complicated by an adult respiratory distress syndrome (ARDS). The patient was admitted to the intensive care unit in a coma, scored 5 on the Glasgow scale. Plasmodium falciparum parasitaemia was, at the time, 50%. A continuous intravenous quinine infusion (25 mg.kg-1.day-1) was started, together with the required symptomatic treatment. Blood was transfused because of increasing anaemia (haemoglobin 60 g.l-1). After 24 h, parasitaemia was 12%, consumption of clotting factors broke out (prothrombine 43%, fibrin degradation products greater than 40 micrograms.ml-1, platelets 45 G.l-1). Hypoxaemia (PaO2 = 46 mmHg) and hypocapnia (PaCO2 = 32 mmHg) became obvious, together with bilateral diffuse alveolar infiltrates on chest X-ray. Haemodynamic data suggested non cardiogenic oedema: PEEP 20 cm H2O, cardiac output 6.15 l.min-1, mean pulmonary arterial pressure 35 mmHg, pulmonary wedged pressure 15 mmHg. The hypoxia worsened and the patient died on the 15th day after associated with high levels of parasitaemia. Several reports have suggested that it may be related to increased capillary permeability. Initial fluid overload should therefore be avoided. Parenteral quinine remains the mainstay of treatment, because of its rapid schizonticidal activity. Although exchange transfusion seems to be a valuable adjunct to chemotherapy, it requires further assessment.
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PMID:[Fatal pulmonary edema in a pernicious malaria attack]. 227 23

There is no information and therefore no consensus on how chloroquine should be administered to persons with severe malaria. Although widely considered dangerous, parenteral chloroquine is extensively used. We studied the acute disposition and toxicity of intravenous (iv), intramuscular (im), subcutaneous (sc), and oral chloroquine in 60 adult Zambian patients hospitalized with falciparum malaria. Plasma concentration profiles after parenteral administration were characterized by wide fluctuations between peak and trough values. Absorption of im and sc chloroquine was rapid, with a median time to peak concentration of 30 min and a peak plasma concentration five times higher than after oral administration. The pharmacokinetic data suggest that the acute toxicity of parenteral chloroquine is related to transiently high concentrations in blood and result from incomplete distribution out of a relatively small central compartment. Parenteral chloroquine may be administered safely by simply giving smaller, more-frequent doses than are currently used or, in the case of iv administration, by using continuous infusion.
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PMID:Parenteral chloroquine for treating falciparum malaria. 354 46

The development of new sensitive and specific assays (HPLC) have enabled the pharmacokinetics of antimalarial drugs to be studied. Parameters such as half-life distribution volume, clearance and bioavailability, are defined. In healthy subjects, quinine is rapidly eliminated (t1/2 beta: 6-12 h). Hepatic biotransformation accounts for approximately 80% of its total clearance. In malaria, the pharmacokinetic properties of quinine (decrease in the apparent volume of distribution, prolongation of the t1/2 beta, reduction in systemic clearance), are altered in proportion to the severity of infection. Red cell concentrations and plasma binding are increased. Parenteral quinine should be given by slow intravenous infusion and a loading dose is recommended in severe infections. Chloroquine (t1/2 beta: 6-50 days) and mefloquine (t1/2 beta: 6-33 days) have extensive tissue distribution and prolonged activity after a single dose. Both drugs are concentrated in erythrocytes and are bound considerably to plasma proteins. Amodiaquine is not found in the blood after oral administration. Hepatic biotransformation accounts for almost all orally administered drug. Its antiplasmodial activity is thus almost entirely due to monodesethylamodiaquine, the main metabolite. In healthy subjects, the t1/2 beta of this metabolite is 9 to 18 days in plasma. Amodiaquine is concentrated in erythrocytes. The protein binding of this drug has not been studied to date. For prophylaxis, it has been suggested that the dosage of 10 mg/kg/wk should be spread over the week (3.5 mg/kg every other day, or 1.5 every day). Halofantrine has an elimination half-life of between 1.3 and 6.6 days. This drug has been suggested as a single-dose treatment. No pharmacokinetic studies of qinghaosu have been reported in humans. In rabbits, the elimination half-life in plasma was found to be 40 min. Although rapidly eliminated, this drug appears to be highly effective. More information is required on the pharmacokinetics of these drugs in malaria, during pregnancy, in children and in renal and hepatic failure.
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PMID:[Pharmacokinetics of antimalarials: quinine and mefloquine, halofantrine, qinghaosu, amino-4-quinolines]. 354 4

For the past 300 years antimalarial dosage regimens have not been based on pharmacokinetic information. However, now that this information is available, it is appropriate to examine current recommendations for prophylaxis and treatment. In healthy subjects, the cinchona alkaloids (quinine and quinidine), primaquine and proguanil (chloroguanide) are all rapidly eliminated with half-lives (t1/2 beta) of between 6 and 12 hours. Hepatic biotransformation accounts for approximately 80, 96 and 50% of their total clearance, respectively. In malaria, the pharmacokinetic properties of quinine and quinidine are significantly altered with a decrease in the apparent volume of distribution (Vd), prolongation of the elimination half-life, and a reduction in systemic clearance (CL) that is proportional to the severity of infection. Red cell concentrations and plasma protein binding are both increased in severe disease. Parenteral quinine or quinidine should be given by slow intravenous infusion rather than by intravenous or intramuscular injection, and a loading dose is necessary in severe infections. Chloroquine (t1/2 beta 6 to 50 days) and mefloquine (t1/2 beta 6.5 to 33 days) have extensive tissue distribution and prolonged activity after a single dose. Both drugs are concentrated in erythrocytes and 55% of chloroquine and 98% of mefloquine in plasma is bound to protein. The pharmacokinetics of chloroquine are complex and, because of the extremely long beta phase, difficult to accurately define. Pyrimethamine (t1/2 35 to 175 hours) has more limited tissue distribution, plasma and erythrocyte concentrations are similar, and 85% of the drug in plasma is bound to plasma proteins. The clearance of quinine, mefloquine and pyrimethamine appears to be higher in children than in adults. Currently, most of the information available on disposition of antimalarial drugs in humans is derived from studies in healthy adult subjects. More information is required on their pharmacokinetics in malaria, pregnancy, and in young children.
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PMID:Clinical pharmacokinetics of antimalarial drugs. 389 40

Parenteral quinine is the most effective treatment for severe falciparum malaria. It is not easily available in Switzerland and so dangerous delays treating patients may occur. The antiarrhythmic drug quinidine, usually stocked by hospitals, is an alternative drug for malaria treatment. We report the cases of two patients with severe malaria imported from Kenya. They were treated first with intravenous quinidine sulfate over 3 days and for another 4 days with peroral quinidine sulfate. The therapeutic response was excellent. During the 2 months posttherapeutic period no recrudescence of Plasmodium falciparum occurred. 20 mg/kg b.w./die of quinidine given intravenously seems to be an adequate dose in severe falciparum malaria.
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PMID:[The anti-arrhythmia drug quinidine as an alternative in the treatment of severe falciparum malaria]. 634 Jan 87

Ninety-two children with complicated, but not cerebral, Plasmodium falciparum malaria, aged 1-9 years, were recruited between August 1992 and December 1994 to an open, randomized trial of parenteral chloroquine (28), pyrimethamine-sulfadoxine (P-S) (36) and quinine (28). The median fever clearance time was shorter for chloroquine (27 hours) than for quinine (42 hours) or for P-S (36 hours) (P = 0.02 and P = 0.06, respectively). The parasite clearance times were similar for chloroquine and P-S, but significantly shorter for chloroquine compared with quinine (54 hours vs 66 hours) (P = 0.007) and for P-S compared with quinine (42 hours vs 66 hours) (P < 0.001). However, three children who received chloroquine and three who received P-S required a change to treatment with quinine because of a clinical failure of their initial treatment. Four children died, one in the chloroquine group, one in the quinine group and two in the P-S group. Despite a high level of chloroquine resistance in the community, the majority of Gambian children with complicated malaria responded satisfactorily to parenteral chloroquine given under supervision. The clinical failure rates of chloroquine and P-S were similar. Parenteral chloroquine and P-S remain adequate treatments for complicated, non-cerebral malaria in Gambian children, provided children can be kept under close clinical observation so as to detect early any treatment failures. Parenteral P-S has the advantage that only one dose is required.
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PMID:A comparative study of parenteral chloroquine, quinine and pyrimethamine-sulfadoxine in the treatment of Gambian children with complicated, non-cerebral malaria. 879 Jun 70

Malaria is associated with a reduction in the systemic clearance and apparent volume of distribution of the cinchona alkaloids; this reduction is proportional to the disease severity. There is increased plasma protein binding, predominantly to alpha 1-acid glycoprotein, and elimination half-lives (in healthy adults quinine t1/2z = 11 hours, quinidine t1/2z = 8 hours) are prolonged by 50%. Systemic clearance is predominantly by hepatic biotransformation to more polar metabolites (quinine 80%, quinidine 65%) and the remaining drug is eliminated unchanged by the kidney. Quinine is well absorbed by mouth or following intramuscular injection even in severe cases of malaria (estimated bioavailability more than 85%). Quinine and chloroquine may cause potentially lethal hypotension if given by intravenous injection. Chloroquine is extensively distributed with an enormous total apparent volume of distribution (Vd) more than 100 L/kg, and a terminal elimination half-life of 1 to 2 months. As a consequence, distribution rather than elimination processes determine the blood concentration profile of chloroquine in patients with acute malaria. Parenteral chloroquine should be given either by continuous intravenous infusion, or by frequent intramuscular or subcutaneous injections of relatively small doses. Oral bioavailability exceeds 75%. Amodiaquine is a pro-drug for the active antimalarial metabolite desethylamodiaquine. Its pharmacokinetic properties are similar to these of chloroquine although the Vd is smaller (17 to 34 L/kg) and the terminal elimination half-life is 1 to 3 weeks.
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PMID:Pharmacokinetics of quinine, chloroquine and amodiaquine. Clinical implications. 898 59

During a period of 1 year from July 95 to June 96, 60 patients with falciparum malaria were treated with quinine at Kasturba Medical College Hospital, Mangalore. Of these, 24 patients developed adverse effects to quinine. They were cinchonism (15) cardiotoxicity (10) hypoglycemia (9) hyperventilation (3) hypersensitivity reactions (3) and hypokalemia (1). Cardiotoxicity was noted in 4 of the 7 patients who received intravenous quinine and all four had renal and hepatic failure and prolonged Q-Tc on electrocardiogram. All 4 died of cardiac arrhythmias, 2 had broad QRS tachycardia and 2 had sinus bradycardia. We conclude that: 1. Quinine should be used cautiously in patients with impaired hepatic or renal function and in those with prolonged QTc as it can lead to cardiotoxicity in the form of I0 AV block, prolonged Q-Tc, broad QRS tachycardai or fatal bradyarrhythmia. Dosage reduction to 5 mg/kg body weight in the patients seem to be safer. 2. Hypoglycemia is a very frequent complication of quinine therapy and special care and frequent blood sugar estimations are required especially if the patient has vomiting. 3. Parenteral quinine is more likely to cause toxicity than oral quinine as earlier described.
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PMID:Experience with quinine in falciparum malaria. 1069 26

Cerebral malaria is one of the most common nontraumatic encephalopathies in the world. Children living in sub-Saharan Africa bear the brunt of the disease, but cerebral malaria is being seen increasingly in adults throughout the world, including outside malarious areas. There are differences in the clinical presentation and pathophysiology between African children and nonimmune adults from any region. Mortality is high (10-20%). Parenteral antimalarials are the only interventions that have been shown to affect outcome. The cinchona alkaloids (quinine and quinidine) are the mainstay of antimalarial treatment, but the artemisinin derivatives are increasingly being used. Aggressive treatment and prevention of convulsions may be important, particularly in children. Other ancillary treatments that can be used to augment standard antimalarial drugs, such as exchange blood transfusions, osmotic diuretics and pentoxifylline, may improve outcome but have not been subjected to rigorous clinical trials. There is little support for corticosteroids or deferoxamine (desferrioxamine) in cerebral malaria. Other adjuncts have not been adequately tested. Further research is required on drugs that interfere with the pathophysiological processes to prevent neurological complications and death.
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PMID:Cerebral malaria: optimising management. 1261 95


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