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Query: UMLS:C0024530 (malaria)
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The continuing spread of multidrug resistance in Plasmodium falciparum malaria makes the search for alternative treatments ever more urgent. We have investigated the relative efficacy of halofantrine and mefloquine in two paired randomised trials on the Thai-Burmese border, a multidrug-resistant area. In the first trial, 198 patients with acute uncomplicated falciparum malaria were randomly assigned either the standard halofantrine regimen (24 mg/kg) or mefloquine (25 mg/kg). The cumulative failure rates by day 28 were 35% with halofantrine and 10% with mefloquine (p = 0.0002). In the second study of 437 patients, a higher dose of halofantrine (8 mg/kg every 8 h for 3 days = 72 mg/kg) was both more effective and better tolerated than mefloquine 25 mg/kg; the failure rates were 3% and 8% (p = 0.03), respectively, or 1% vs 6% after adjustment for possible reinfections (p = 0.009). The rate of failure was higher after retreatment than after primary treatment in all study groups. Halofantrine 72 mg/kg was especially effective in the retreatment of these recrudescent infections; the failure rate was 44% with mefloquine and 15% with high-dose halofantrine (relative risk 3.0 [95% CI 1.2-7.3], p = 0.008). Thus, high-dose halofantrine is better tolerated and more effective than mefloquine for the treatment of uncomplicated falciparum malaria in this area. However, evidence of possible cardiotoxicity will need to be investigated fully before a role can be established for halofantrine in the treatment of multidrug-resistant malaria.
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PMID:Halofantrine versus mefloquine in treatment of multidrug-resistant falciparum malaria. 809 90

New treatments for malaria are urgently needed in areas such as Thailand where highly drug-resistant strains of Plasmodium falciparum are prevalent. Mefloquine is rapidly losing efficacy and conventional doses of halofantrine are infective. We therefore used pharmacokinetic stimulation to design an extended-dose halofantrine regimen and tested it in 26 soldiers stationed along the Thai-Cambodian border. Halofantrine was given after meals as three doses of 500 mg each at 4-hr intervals on the first day, followed by 500 mg a day for six days (total dose 4.5 g). Twenty-six soldiers treated with quinine-tetracycline for seven days (Q7T7) served as controls. There were no significant differences in efficacy between halofantrine and Q7T7 (P > 0.1) as assessed by cure rate (92% versus 85%), mean parasite clearance time (82 hr versus 81 hr), or mean fever clearance time (93 hr versus 99 hr). Halofantrine was better tolerated than Q7T7. The side effects score was lower (2 versus 11; P < 0.001), there were less days on which side effects occurred (2.0 days versus 5.5 days; P < 0.001), and fewer patients had adverse effects on every treatment day (4% versus 42%; P < 0.01). High-dose halofantrine is as effective and better tolerated than quinine-tetracycline for multidrug-resistant falciparum malaria.
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PMID:Efficacy and tolerance of extended-dose halofantrine for drug-resistant falciparum malaria in Thailand. 811 11

Incidence and malignant forms of imported Plasmodium falciparum malaria are increasing, and chemoprevention is more and more replaced by stand-by treatment and radical cure in preventing access on return from malaria areas. Halofantrine is recommended for this radical cure: it's an habitually well-tolerated amino-alcohol with very few side-effects. We report three cases of long QT-interval due to halofantine: three different young women coming back from Africa took halofantrine (500 mg (2 tablets) six hourly for three doses on the first and the seventh day) and all presented with syncopal episodes. Serum electrolyte concentrations and echocardiograms were normal. In one case only, a diagnosis of Plasmodium falciparum malaria was made, without severe manifestations, and in the two other cases, treatment was a radical cure. In two cases, several bursts of torsades de pointes ventricular tachycardia due to halofantrine were proven and electrophysiological cardiac tests concluded that they had a congenital long QT-interval/Romano-Ward syndrome). So far halofantrine cardiac toxicity was unknown with single dose of 24 mg/kg/d. This phenomenon can be very severe in case of preexisting cardiopathy. In spite of the rarity on the congenital Romano-Ward syndrome, systematic electrocardiogram is necessary before giving halofantrine.
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PMID:[Ventricular arrhythmia and halofantrine intake. Probable deleterious effect. Apropos of 3 cases]. 812 7

A 44-year-old male, who had been to Lagos, Nigeria, was admitted to our hospital because of a high grade fever on July 20, 1993. On admission, Plasmodium falciparum was detected in his blood smears and the antibody titers against P. falciparum and Plasmodium vivax antigens were 1:256 and < 1:4 respectively by the indirect fluorescent antibody test. Therefore, he was diagnosed as having P. falciparum malaria. He was treated with halofantrine (Halfan: Smith Kline Beecham Pharmaceuticals, England), two tablets at six-hourly intervals, a total of six tablets (1500 mg). Parasites were cleared rapidly and remission was achieved without any adverse reactions. Halofantrine can therefore be recommended for the treatment of imported P. falciparum malaria.
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PMID:[A case of Plasmodium falciparum malaria successfully treated with halofantrine]. 817 81

The clinical efficacy and tolerability of halofantrine, a new antimalarial schizontocide, was studied in a multi-centre trial involving 268 patients ranging in age from 6 months to 58 years. The patients were suffering from acute uncomplicated malaria due to either P. vivax or P. falciparum. Patients were treated orally with 3 doses of halofantrine hydrochloride, 500 mg/6-hourly in adults or 8 mg/kg body weight 6-hourly in children. The overall cure rate was 96.9%. The mean fever clearance time for different species was as follows: P. vivax--39.1 hours, P. falciparum--43.2 hours, mixed infection--60.0 hours, and the mean parasitaemia clearance times were 47.7, 55.1 and 72.0 hours, respectively. Recrudescence was reported in 11 (4.1%) patients, although all of them were parasite-free on Day 7 post-treatment. No haematological or biochemical abnormalities were noted. The drug was very well tolerated and no significant side-effects were reported. Halofantrine was found to be highly effective in acute malaria and offers an important alternative to existing medications.
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PMID:Halofantrine in the treatment of acute malaria: a multi-centre study in 268 patients. 822 41

Twenty southern African isolates of Plasmodium falciparum and a 'control' Gambian strain were tested in vitro for their sensitivity to halofantrine. The concentration required to inhibit 50% of parasite growth, the IC50, ranged from 0.039 to 15.000 nmol/litre, with a mean of 4.619 nmol/litre. These IC50 values were comparable with those obtained in studies carried out in West Africa but were higher than the IC50 of South-East Asian isolates. All 21 isolates examined in the present study had minimum inhibitory concentrations (MIC) of 32 nmol/litre or less, with a median MIC value of 8 nmol/litre. Halofantrine was equally active against chloroquine-sensitive and chloroquine-resistant isolates and was also active against pyrimethamine-resistant strains. Indications are that this drug would be suitable for the treatment of P. falciparum malaria in the southern African region.
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PMID:In vitro sensitivity of southern African isolates of Plasmodium falciparum to halofantrine. 825 33

Halofantrine was administered as prophylaxis for malaria to mine workers returning from endemic areas of Papua New Guinea. The men were randomly assigned to receive 500 mg of halofantrine daily for 3 days (n = 195) or 6 days (n = 150) or a total dose of 1,500 mg of chloroquine over 3 days (n = 55). None of the men receiving halofantrine developed falciparum malaria during the subsequent 28 days, whereas three men receiving chloroquine did develop this disease (P < .02). The administration of halofantrine after departure from an endemic area is one strategy for the prevention of falciparum malaria after short-term exposure.
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PMID:Postexposure administration of halofantrine for the prevention of malaria. 826 42

Fifty patients suffering from acute malaria were treated with 'Halofantrine Hydrochloride'. They were observed for 4 weeks. Clinical, haematological and biochemical parameters were assessed for evaluation of halofantrine in acute malaria, with special reference to its effectiveness, tolerability and side effects.
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PMID:Clinical evaluation of halofantrine in acute malaria. 782 50

Clinical trial of halofantrine was conducted in 32 cases of acute malaria. Twenty four patients with P. vivax and eight patients with P. falciparum infection were treated with 3 doses of halofantrine (500 mg each) orally, after food, at intervals of 6 hours. Mean parasite clearance time of P. vivax was 57.75 h and for P falciparum 75 h and mean defervescence time was 31.08 h and 34 h respectively. Post treatment followup was for 28 days. Clinical symptoms related to malaria cleared within the first 48 h. Mild adverse reactions of abdominal pain in one patient and vomiting in one patient were encountered which did not require any treatment. Halofantrine was found to be very effective and free from significant adverse events when used for the treatment of acute malaria.
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PMID:Efficacy and safety of halofantrine in acute malaria. 782 50

The number of chloroquine-resistant Pl. falciparum malaria cases in the last decade dramatically increased. This fact causes significant problems not only in the therapy but in the malaria chemoprophylaxis as well. Presently, in accordance with the WHO's recommendations, the drug of choice in the malaria chemoprophylaxis is mefloquine. Other drugs can be used only when there is a problem (medical or other) in mefloquine-use. Halofantrine (Halfan) or the so-called "double-acting" drugs (e.g. Fansidar) are not recommended in the malaria chemoprophylaxis.
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PMID:[Current possibilities of malaria chemoprophylaxis]. 830 80


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