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

A number of drugs have been studied for their effect on the metabolism of the antimalarial drug mefloquine by human liver microsomes (N = 6) in vitro. The only metabolite generated was identified as carboxymefloquine by co-chromatography with the authentic standard. Ketoconazole caused marked inhibition of carboxymefloquine formation with IC50 and Ki values of 7.5 and 11.2 microM, respectively. The inhibition of ketoconazole, a known inhibitor of cytochrome P450 isozymes, and the dependency of metabolite formation on the presence of NADPH indicated that cytochrome P450 isozyme(s) catalysed metabolite production. Of compounds actually or likely to be coadministered with mefloquine to malaria patients only primaquine and quinine produced marked inhibition (IC50, 17.5 and 122 microM; Ki, 8.6 and 28.5 microM, respectively). However, despite these in vitro data with primaquine, clinical studies have failed to show any significant effect of single dose primaquine on the pharmacokinetics of mefloquine. With quinine, because peak plasma concentrations are very close to the Ki value, there is likely to be inhibition of mefloquine metabolism in patients receiving both drugs. Sulfadoxine, artemether, artesunate and tetracycline did not significantly inhibit carboxymefloquine formation.
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PMID:Mefloquine metabolism by human liver microsomes. Effect of other antimalarial drugs. 159 83

Compliance with malaria prophylaxis or reserve drugs was investigated in 477 individuals travelling to regions with endemic malaria. Correct intake of prophylactic medication was confirmed in 225 out of 285 (= 78%). Compliance was independent of type of drug (Mefloquine, Sulfadoxine-Pyrimethamine, Chloroquine). Two tourists missed to start prophylaxis one week before the onset of their travel. 14 travellers stopped prophylactic medication too early after their return, 31 tourists took too high doses of mefloquine. None of the tourists travelling to countries with a therapeutic reserve only became sick, whereas two travelling to Africa contracted malaria.
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PMID:[Malaria study]. 199 82

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

During the period of June to October 1985, a study in vivo was made on 162 patients suffering from malaria by P. falciparum, in order to evaluate the sensitivity of the parasite to the drugs: Chloroquine, Amodiaquine and Pyrimethamine-Sulfadoxine (Fansidar). As an alternative treatment, in the resistant cases, Quinine with Fansidar or Quinine with Tetracycline was given. The following cases of resistance were found: 17 cases to Chloroquine (5-RI, 9-RII, 3-RIII), 7 cases to Amodiaquine (5-RI, 2-RII) and 2 cases to Fansidar (1-RI, 1-RII). It is recommended that the epidemiologic studies of the resistance by P. falciparum to the anti-malarials be increased, following up the evolution of its scope, and the organization of a program to fight against malaria. Also the use of Fansidar is recommended as the principal medicine against P. falciparum in malaria without complications, in the zones where there is strong resistance to the 4-amino-quinoleines. In case of multi-resistance in malaria by P. falciparum, the use of Quinine is recommended. At a prophylactic level we do not advise the use of Chloroquine as the only medicine, nor the use of Fansidar because of its potential toxic effects.
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PMID:[Pharmacoresistance of Plasmodium falciparum in Rwanda: an in vivo study]. 331 Nov 92

A double-blind, randomized phase I clinical trial was carried out to compare mefloquine with sulfadoxine-pyrimethamine for safety and tolerance. Twenty adult male Brazilian subjects from areas endemic for malaria were studied for a period of 66 days, which included 2 days of basal studies and a 63-day follow-up after drug administration. Subjects received either mefloquine, given as a single oral dose of 1000 mg (4 x 250-mg tablets) or sulfadoxine-pyrimethamine (2 tablets, each containing 500 mg of sulfadoxine plus 25 mg of pyrimethamine). Clinical examination, electrocardiogram, chest X-ray, and haematological, biochemical, stool, and urine analyses were carried out before drug administration and at various intervals afterwards. Peripheral blood smears were examined for malarial parasites.Both drugs were well tolerated and safe as seen from the absence of drug-induced changes in the various laboratory assay results. There was an improvement in body weight, red blood cell count, haemoglobin, and erythrocyte volume fraction values for all patients during the study. In subjects who had positive smears for Plasmodium falciparum, mefloquine produced complete clearance on day 1 with an S-type response (3 cases). Sulfadoxine-pyrimethamine produced complete clearance on day 2 in 5 subjects, but a delayed RI-type response (recrudescence) was observed in 2 cases and an early RI response in one case. P. vivax relapses occurred in both groups. Side-effects of mefloquine included mild diarrhoea (20%) and dizziness (40%); dizziness was also observed with sulfadoxine-pyrimethamine (20%). In both groups, side-effects were mild, short-lived and needed no specific treatment.Thus, mefloquine in an oral dose of 1000 mg was found to be well tolerated and safe in adult male Brazilian volunteers from endemic areas. No drug-related adverse reactions were observed. In cases where P. falciparum infection was present, there was a complete parasite clearance with no recrudescence.
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PMID:A phase I clinical trial of mefloquine in Brazilian male subjects. 636 Apr

Mefloquine was compared with sulfadoxine-pyrimethamine for safety and efficacy in a randomized, double-blind clinical trial in adult males from a malaria-endemic area of Brazil. A total of 99 oligosymptomatic and symptomatic volunteers with Plasmodium falciparum parasitaemia took part in the trial; 49 were given 1000 mg of mefloquine and the remainder received 1500 mg of sulfadoxine plus 75 mg of pyrimethamine, in a single oral dose.Mefloquine was 100% successful in clearing parasitaemia within 7 days; there were no recrudescences. Sulfadoxine-pyrimethamine was less successful; 35 cases showed an S-type response, 8 an RI response, 3 an RII, and 2 an RIII response. The side-effects of mefloquine were mild and transient and included headache, nausea, vomiting, dizziness, and diarrhoea. A satisfactory weight gain and rise in haemoglobin level were seen in both groups.
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PMID:A phase II clinical trial of mefloquine in Brazilian male subjects. 636 Apr 1

Since 1978 several cases of chloroquine-resistant falciparum malaria have been reported from East Africa (Petterson et al., 1981). Sulfadoxine-pyrimethamine (Fansidar) has been advised by W.H.O. (Wkly Epidem. Rec., 1982) for therapeutic management of these patients. We describe here a non-immune female expatriate from Tanzania suffering from falciparum malaria, which was resistant to chloroquine (R II-III). She had been working as a medical technician in the Morogoro region, a hyperendemic malarious area. After being treated with Fansidar she was transferred to the Netherlands where a recrudescence developed. She was then treated with a combination of quinine and tetracycline which resulted in the clearance of the parasitaemia. This is the third report of Fansidar-resistant falciparum malaria from Tanzania in the Netherlands (de Geus et al., 1982; Timmermans et al., 1982).
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PMID:Fansidar-resistant Plasmodium falciparum infection from Tanzania. 675 46

In Papua New Guinea, Plasmodium falciparum and P. vivax are common causes of acute malaria in children and P. malariae an uncommon cause. The increasing prevelance of chloroquine-resistant strains of P. falciparum in Papua New Guinea has prompted the search for alternatives to chloroquine as standard presumptive treatment. Sulfadoxine-pyrimethamine, either alone or in combination with a single dose of chloroquine, was compared with chloroquine alone for treatment of acute vivax malaria in children in Madang. Fever resolution was slowest in the group treated with sulfadoxine-pyrimethamine alone, and time to clearance of parasitemia was significantly longer in this group (P less than 0.001). Where possible, species identification should be undertaken in acute malaria and cases of P. vivax treated with chloroquine.
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PMID:Sulfadoxine-pyrimethamine for the treatment of acute malaria in children of Papua New Guinea. II. Plasmodium vivax. 703 65

Resettlement to the United States of malaria-infected refugees can pose problems for both the refugees and their resettlement communities. To formulate malaria management strategies for East African refugees before resettlement to the United States, epidemiologic data were reviewed and malaria prevalence surveys were conducted among refugees awaiting resettlement in Mombasa, Kenya, and Khartoum, Sudan, in 1993. Overall, 279 Somali (Mombasa) and 127 Ethiopian (Khartoum) refugees were surveyed. Malaria contributed significantly to morbidity in Mombasa: 15% (43/279) of Somalis were parasitemic; 39 infections (91%) were due to Plasmodium falciparum. Sulfadoxine-pyrimethamine was effective treatment. In Khartoum, only 0.8% (1/127) were parasitemic; recent fever or antimalarial use were uncommon. Presumptive sulfadoxine-pyrimethamine treatment before departure was recommended for all resettling refugees from Mombasa; in Khartoum, individual assessment of febrile illness was recommended. Prevention of malaria parasitemia by mass drug administration or individual therapy can minimize the burden of malarial illness to refugees and their resettlement communities.
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PMID:Malaria in east African refugees resettling to the United States: development of strategies to reduce the risk of imported malaria. 784 98

Although malaria has been largely eradicated from temperate countries, it is on the increase in the tropics. Infection with Plasmodium falciparum affects a vast number of people and kills over a million annually. Severe malaria is a multisystem disease affecting particularly the central nervous system (causing coma and convulsions), the kidneys (resulting in acute tubular necrosis), and the liver (contributing to lactic acidosis and hypoglycaemia). Acute pulmonary oedema (acute respiratory distress syndrome) may occur in adults particularly in association with renal impairment. In children these symptoms are rare, whereas hypoglycaemia, lactic acidosis and severe anaemia are more common. Malaria should be suspected in any febrile patient living in or returning from the tropics, and a blood smear examined. Chloroquine has been the mainstay of antimalarial treatment for the past 40 years, but resistance in P. falciparum is now widespread throughout the tropics and has recently been recognised in P. vivax from Oceania. Sulfadoxine-pyrimethamine resistance is also common. Fortunately, quinine, and the newly introduced compounds, halofantrine and mefloquine, can be relied upon nearly everywhere. The most rapidly acting and effective of all antimalarial drugs, artemisinin and its derivatives, have come from China. They offer a genuine prospect of reducing mortality from malaria in the tropics.
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PMID:Clinical malaria in the tropics. 833 22


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