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

Mefloquine pharmacokinetics were studied in Kenyan African normal volunteers and in patients with severe acute attack of Plasmodium falciparum malaria. Peak concentrations were achieved in both groups at 20-24 hours. The mean half-life of elimination was 385 +/- 150 hours (mean +/- SD) in normal subjects while in severe malaria it was 493 +/- 215 hours which was significantly longer (P less than or equal to 0.001). The volume of distribution was significantly smaller in severe malaria where it was 30.76 +/- 10.50 l/kg (mean +/- SD) while in the normal subjects it was 40.90 +/- 20.70 l/kg (mean +/- SD) (P less than or equal to 0.001). The total body clearance in severe malaria was 3.75 +/- 1.51 l/h (mean +/- SD). This was significantly lower than in the normal subjects where it was 5.15 +/- 1.50 l/h (mean +/- SD) (P less than or equal to 0.001).
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PMID:Mefloquine disposition in normals and in patients with severe Plasmodium falciparum malaria. 266 7

In the treatment of severe Plasmodium falciparum infection antimalarial drugs should, ideally, be given by controlled rate intravenous infusion until the patient is able to swallow tablets. In cases where infection has been acquired in a chloroquine resistant area, and where it has broken through chloroquine prophylaxis or where the geographical origin or species are uncertain, quinine is the treatment of choice. When access to parenteral quinine is likely to be delayed, parenteral quinidine is an effective alternative. A loading dose of quinine is recommended in order to achieve therapeutic plasma concentrations as quickly as possible. In the case of chloroquine sensitive P. falciparum infection, chloroquine, which can be given safely by slow intravenous infusion, may be more rapidly effective and has fewer toxic effects than quinine. There is limited experience with parenteral administration of pyrimethamine sulphonamide combinations such as Fansidar, and resistance to these drugs has developed in South East Asia and elsewhere. Mefloquine and halofantrine cannot be given parenterally. Qinghaosu derivatives are not readily available and have not been adequately tested outside China. Supportive treatment includes the prevention or early detection and treatment of complications, strict attention to fluid balance, provision of adequate nursing for unconscious patients and avoidance of harmful ancillary treatments. Anaemia is inevitable and out of proportion to detectable parasitaemia. Hypotension and shock ('algid malaria') are often attributable to secondary gram-negative septicaemia requiring appropriate antimicrobial therapy and haemodynamic resuscitation. Many patients with severe falciparum malaria are hypovolaemic on admission to hospital and require cautious fluid replacement. Failure to rehydrate these patients may lead to circulatory collapse, lactic acidosis, renal failure and severe hyponatraemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Treatment of severe malaria. 269 26

The most recent acquisitions on chemotherapy and chemoprophylaxis of malaria are reviewed. With regard to chemotherapy, candidate antimalarial compounds have been divided into four groups, according to their stages of development. Mefloquine and the combination of mefloquine with sulfadoxine/pyrimethamine belong to the first group: they have completed clinical trials and have been registered in several countries for routine clinical use. The second group is characterized by chemical compounds which are in an advanced stage of development, including clinical trials. The compounds considered in this group are: a) the 9-phenanthrenemethanols, among which halofantrine is the most promising one; b) the sesquiterpene lactones such as Qinghaosu, artemether, artesunate, artesunic acid and arteether which must be further tested in order to find more effective drug regimens capable of eliminating recrudescences and for the completion of toxicity studies; c) pyronaridine, which appears to be a promising antimalarial, effective also against chloroquine-resistant P. falciparum, but still requiring further investigations on resistance and cross-resistance, as well as its pharmacokinetics, tolerability and bioavailability; d) enpiroline, another promising compound, which needs to be further studied in Phase II and Phase III investigations with naturally acquired malaria. The third group is composed of seven chemical classes of compounds that are in an advanced pre-clinical development, namely: the 4-aminoquinolines, such as dabechin, piperaquine, hydroxypiperaquine, tripiperaquine, dichlor-quinazine and the Mannich base compounds, the 8-aminoquinolines, the 4-quinolinemethanols, the quinolones, the naphthoquinones, the quinazolines and the dihydrotriazines. Among the many antimalarial compounds of interest, which can be considered at the moment as leads for further studies, only the acridandione derivatives such as floxacrine, the antibiotics, antifungal agents or their metabolites, plant substances such as Yingzhaosu A and quassinoids have been mentioned. Malaria chemoprophylaxis, especially in chloroquine-resistant P. falciparum areas, has become a real problem. The attempts to secure protection under these circumstances with the utilization of amodiaquine, the combination of sulfadoxine/pyrimethamine (Fansidar), sulfalene/pyrimethamine (Metakelfin), of pyrimethamine/dapsone (Maloprim), with or without chloroquine, had to be abandoned or to be used with caution in view of the severe complications following the weekly administration of these drugs. The combination of chloroquine with proguanil or chlorproguanil, which could be recommended on theoretical bases, did not meet the expectations when tested in the field. (ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Recent acquisitions on chemotherapy and chemoprophylaxis of malaria. 269 8

Two randomised double-blind trials were conducted to examine the activity and tolerability of mefloquine alone and in combination with sulfadoxine/pyrimethamine (MSP). In one trial mefloquine was compared with chloroquine in 40 patients with Plasmodium vivax malaria and in the other one mefloquine was compared with MSP in 40 patients with P falciparum malaria. The former trial showed that both a single oral dose of 250 mg mefloquine and a single oral dose of 450 mg chloroquine (base) were highly effective in relieving symptoms of malaria and in clearing P vivax parasitaemia. No side-effects and no changes in laboratory variables attributable to the test drugs were observed. The other trial showed that a single oral dose of 750 mg mefloquine and a single oral dose of MSP (750 mg mefloquine plus 3 tablets of 'Fansidar', were equally effective in the treatment of falciparum malaria. 2/4 treatment failures in the mefloquine group and 2/3 treatment failures in the MSP group were due to low plasma drug levels resulting from vomiting soon after ingestion of the tablets. Gametocytes of P falciparum were unaffected by either mefloquine or MSP. 5 patients in each group had side-effects such as vomiting, skin rash, diarrhoea, and transient mental confusion. Mefloquine was well tolerated by patients with glucose-6-phosphate dehydrogenase deficiency or heterozygous haemoglobin E.
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PMID:Trials of mefloquine in vivax and of mefloquine plus 'fansidar' in falciparum malaria. 285 43

Halofantrine (WR 171,669) hydrochloride was administered orally to 82 patients infected with Plasmodium falciparum malaria on the Thai-Kampuchean border between June 1982 and December 1983 in a randomized double-blind treatment trial which compared the efficacy of halofantrine with that of mefloquine. Halofantrine was curative with oral treatment on a single day in 65% of patients (13/20) who received 1000 mg followed 6 hours later by an additional 500 mg, and in 88% of patients (53/60) who received 500 mg every 6 hours for 3 doses. Mefloquine was curative in 88% of patients (22/25) given a single oral dose of 1000 mg and in 97% of patients (38/39) given a single oral dose of 1500 mg. The difference in cure rates between the 3-dose halofantrine regimen and either of the mefloquine regimens was not significant. The mean parasite clearance time for all regimens ranged from 75 to 84 hours. The mean fever clearance time for all four treatment groups was in the range 50-60 hours, with no significant differences between groups. Post-dosing side-effects in patients treated with halofantrine consisted of nausea, vomiting, abdominal pain and diarrhoea and were not significantly different from those treated with mefloquine. Halofantrine therefore appeared to be of comparable efficacy to mefloquine in the treatment of multidrug-resistant P. falciparum malaria.
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PMID:Malaria: treatment efficacy of halofantrine (WR 171,669) in initial field trials in Thailand. 329 28

Mefloquine is a highly effective drug for the treatment of falciparum malaria among adults, but studies of its effects on children are lacking. An open, noncomparative trial of mefloquine was therefore carried out among 84 children aged 5-12 years who were patients at the Hospital for Tropical Diseases, Mahidol University, Bangkok, Thailand. The drug was administered as a single dose of 18-29 mg base per kg body weight. Eighty-two of the 84 children completed a 42-day period of post-treatment observation. The drug was well tolerated also by 11 children with glucose-6-phosphate dehydrogenase deficiency, and all the children in the study cleared their parasitaemia initially (average clearance time, 65 hours). Furthermore, the clinical-chemical parameters measured exhibited no drug-related changes during the study. The radical cure rate of nearly 98% and high tolerance indicate that mefloquine can be used effectively and safely for the treatment of children aged 5-12 years who are suffering from uncomplicated falciparum malaria.
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PMID:A phase-III clinical trial of mefloquine in children with chloroquine-resistant falciparum malaria in Thailand. 330 Oct 42

In different countries opinions differ as to which chemotherapeutic methods should be used for malaria prophylaxis. It has long been the opinion of the Nordic countries, that WHO should give an official recommendation and the result is reflected now in the publication "Vaccination certificate requirements and health advice for internation travel." The malaria-endemic regions of the world are divided into 3 categories: regions without risk and no need for prophylaxis, low risk regions (A) with predominantly vivax inflections, risk regions (B) with predominantly chloroquine sensitive P. falciparum, and high risk regions (C) with often both chloroquine as well as sulfa/pyrimethamine resistance. Chloroquine is a sufficient prophylaxis for A-regions. For B-regions proguanil should be added and for C-regions only mefloquine is given. Proguanil was reintroduced basically because of Swedish research results in Liberia. An American initiative recommends for all regions, A-C, chemorprophylaxis as an alternative. However, a precondition is an observant traveller and clear instructions for self-treatment. Travellers who fall ill in a B-region should choose between Fansidar, mefloquine and quinine for self-treatment. Mefloquine has the least serious side effects, whereas quinine is therapeutically more safe. Fansidar very seldom gives any side effects. For C-regions only mefloquine is recommended for self-treatment. Nordic colleagues have recommended to double prophylaxis (chloroquine + Paludrine) treatment for the entire African tropical region. For short-time travellers to Kenya, Tanzania and Uganda, 6 tablets Lariam should be added. Only chloroquine is recommended for India and the Amazon region of South America. No chemoprophylaxis can guarantee full protection. Insect protection is therefore more important than ever. Malaria decreases the unspecific immune defense system. Surprisingly, repeated tests have shown that the AIDS frequency is not higher in patients with chronic malaria than for persons without plasmodia in the blood. In WHO's new little yellow booklet, a page concerning prophylaxis against AIDS appears. Equipment that is not new should be steamed or cooked for a least 20 minutes or treated with chemical disinfectants for at least 30 minutes. These measures should be enough to prevent HIV-infection.
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PMID:[Malaria and HIV prevention in WHO's "little gem"]. 338 44

Mefloquine--a quinolinemethanol--opens new aspects in the therapy and prophylaxis of malaria. Since this drug will be soon available in Austria, a review of the pharmacological and clinical data is given. Preliminary results of studies dealing with resistance induction against mefloquine showed that Plasmodium falciparum can develop resistance to this substance in vivo as well as in vitro. Hence, some guidelines are given, in particular with regard to the use of mefloquine as a prophylactic drug. It should be used only in malaria endemic zones in which highly chloroquine resistant Plasmodium falciparum is prevalent and the duration of prophylactic administration should be limited to 3 months in order to prevent the development of resistance. However, mefloquine has proved to be a valuable new drug, well tolerated in clinical trials and with pharmacological properties that make its use simple and safe.
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PMID:[New ways of treating and preventing malaria: mefloquine (Lariam)]. 349 15

Mefloquine-sulphadoxine-pyrimethamine (MSP) in combination has proved effective against multiple-drug-resistant falciparum malaria, but nothing is known about mefloquine absorption when it is given in this formulation. Nine Thai patients, aged 15-51 years with uncomplicated chloroquine-resistant falciparum malaria, took 11.2-16.7 mg of mefloquine base per kilogram bodyweight as MSP tablets. All patients responded to treatment with fever and parasite clearance times of 61 +/- 29 h (mean +/- s.d.) and 52 +/- 24 h, respectively. The mean apparent absorption half-time (t1/2abs) of mefloquine was 4.89 h (range 2.25-9.72) and mean peak plasma concentration was 1815 ng ml-1 (range 725-3368). Peak plasma mefloquine concentrations in three patients who vomited within 2 h of treatment were 725, 956 and 1972 ng ml-1. There was no significant difference between plasma and whole blood mefloquine concentrations during the first 48 h of treatment. Based on the elimination of parasitaemia, the plasma mefloquine concentrations are adequate for therapy of uncomplicated falciparum malaria although the relationship between plasma concentrations and therapeutic efficacy of mefloquine requires further study.
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PMID:Plasma and whole blood mefloquine concentrations during treatment of chloroquine-resistant falciparum malaria with the combination mefloquine-sulphadoxine-pyrimethamine. 355 81

Parasitic infections are endemic in children in Africa, making eradication an impossibility. Therapy is directed towards the individual manifesting an imbalance in the host-parasite relationship. Sanitation education is often disappointing, and until effective vaccines are developed, drug therapy remains the only worthwhile intervention. In order for a drug to be used on a mass campaign basis, financial considerations and side effects are of primary importance. Mefloquine has been shown to be a useful second line drug for chloroquine resistant strains of malaria in our Parasitology department. Benzimidazoles in a single dose are useful for intestinal nematode infections. New drugs are now available for schistosomiasis, filariasis, and protozoan infections.
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PMID:[Antiparasitic therapy of children in Equatorial Africa]. 383 10


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