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

The antimalarial efficacy of halofantrine was compared with mefloquine in an open-label, randomized comparative trial in adult male patients with acute uncomplicated falciparum malaria. Twenty-eight patients received halofantrine and 27 received mefloquine. Halofantrine was administered in 3 doses of 500 mg at 6 hour intervals and mefloquine was administered in divided doses of 1,250 mg or 1,500 mg depending on whether the patients weighed less than or more than 60 kg. The patients were followed for 42 days and observed for drug tolerance and evidence of recrudescence. Response to treatment was favorable with both drugs, but three patients (two treated with halofantrine and one with mefloquine) did not completely eliminate malaria parasites from peripheral blood films in seven days. The parasite and fever clearance times were 75.6 and 55.7 hours, and 80.1 and 61.3 hours, respectively for halofantrine and mefloquine. However, 12 patients recrudesced during the 42 day follow-up period. Nine of these had been treated with halofantrine and three with mefloquine. The 42-day cure rate for the two drugs was 56% and 84%, respectively. The side-effects of halofantrine and mefloquine were comparable and transient. These are diarrhea, dizziness, orthostatic hypotension and black out. However, vomiting was found to be more common in mefloquine group (41% vs 22%).
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PMID:Clinical trials with halofantrine in acute uncomplicated falciparum malaria in Thailand. 836 5

The aim of this study was 1) to assess the incidence of electrocardiographic changes after treatment with halofantrine and 2) to study the relationship between these changes and plasma levels of halofantrine and its main metabolite, N-desbutyl-halofantrine. Thirty-four male patients with uncomplicated falciparum malaria were enrolled in this study. Halofantrine was administered on two separate days at a total oral dosage of 24 mg/kg/day in three doses over a 12-hr period. The interval between the two treatments was seven days. Twelve-lead electrocardiography (ECG) was performed to measure the QT interval (QTc), ambulatory ECG monitoring was done to detect ventricular arrhythmia, signal-averaged ECG was performed to detect late ventricular potentials, and blood tests were performed to determine plasma concentrations of halofantrine and N-desbutyl-halofantrine. Maximum QTc was observed at 12 hr after both the first (P < 0.0002) and second treatments (P < 0.03). Signal-averaged ECG revealed late potentials in four cases (72 hr after the first treatment in one case and 24 hr after the second treatment in three cases). Ventricular arrhythmia was not observed. Significantly higher plasma concentrations of halofantrine were observed 2 hr after the second treatment. At this time, both the time effect and time interaction were significant (P < 0.008 and P < 0.02, respectively). The QTc interval was significantly correlated with the plasma halofantrine level (r = 0.41, P < 0.01) but not with the plasma N-desbutyl-halofantrine level (r = 0.30, not significant). In three cases, late ventricular potentials were associated with a maximum concentration of halofantrine. Our findings indicate that electrocardiographic changes are dose-dependent and that a second treatment at the same dosage may be hazardous.
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PMID:Electrocardiographic changes and halofantrine plasma level during acute falciparum malaria. 860 Jul 54

In the last decade, Plasmodium falciparum resistance to a number of commonly used anti-malarials especially chloroquine, has increased considerably. Newer anti-malarial drugs are therefore being aggressively evaluated as alternatives. A randomized double-blind controlled trial was therefore undertaken, to compare the efficacy of halofantrine to that of metakelfin, in the treatment of moderately severe infections of Plasmodium falciparum in an endemic malaria area in Kenya. Three hundred and thirty five subjects with laboratory confirmed malaria were recruited and randomized to receive treatment with either halofantrine (171 subjects) or metakelfin (164 subjects). Two thirds (66%) of the study subjects were under the age of five years, and were therefore considered to have minimal immunity. All study subjects were initially admitted to hospital for three days and then followed up as out-patients on days 7, 14, 21, and 28. The level of parasitaemia, the presence of fever and the occurrence of adverse effects were evaluated. Halofantrine was found to be comparable to metakelfin in terms of resolution of fever (mean time 45 and 51 hours respectively). No major adverse side effects were observed. Halofantrine is a viable drug in the treatment of uncomplicated P. falciparum malaria.
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PMID:Efficacy of halofantrine in the treatment of uncomplicated falciparum malaria. 868 80

A randomised controlled trial was carried out to determine the relative efficacy of four commonly used antimalarial drugs in children aged three to twelve years presenting with uncomplicated malaria at the Eldoret District Hospital, Kenya. One hundred and eighty eight children were studied between July 1993 and July 1994. There were no significant baseline differences between treatment groups with respect to age, sex, weight, ethnicity, haemoglobin, white blood cell (WBC) counts, parasite counts, previous exposure to malaria and prior treatment. Of the 188 patients, eleven were lost to follow-up while twelve were discontinued from the study due to poor clinical response. Most of the latter (eight out of twelve) were in the chloroquine group. By day seven, there were significant differences (p = 0.004) in parasite clearance between groups. There were no significant statistical differences between the groups (p = 0.12) with regard to the fever clearance time. However, there was a significant statistical difference (p = 0.00003) between the treatment groups in the cure rates. Halofantrine was the most efficacious drug with 82% of the cases cured followed by fansidar(R)(62%), amodiaquine (55%) and chloroquine (29%). RI and RII resistance were observed in all the treatment groups, i.e. halofantrine (18%), fansidar (38%), amodiaquine (45%) and chloroquine (67%) while RIII resistance was only observed in the chloroquine group(3%).
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PMID:A randomised controlled trial to assess the relative efficacy of chloroquine, amodiaquine, halofantrine and Fansidar in the treatment of uncomplicated malaria in children. 869 11

Halofantrine and mefloquine are antimalarial drugs used in the treatment of malaria, including that caused by chloroquine-resistant Plasmodium falciparum. Reports of drug-associated adverse reactions, including sudden death in one patient, have prompted concerns over the safety of halofantrine and the potential for drug-drug interactions. We used the isolated perfused rat liver (IPRL) model to investigate a possible hepatic metabolic or pharmacokinetic drug-drug interaction between halofantrine and mefloquine. Pharmacokinetic parameter estimates for halofantrine in the IPRL reflected the pattern seen in in-vivo studies with doses comparable with clinical doses. Halofantrine parameter estimates (mean +/- s.d.) were: volume of distribution (Vd), 7.53 +/- 1.45 mL (g liver)-1; clearance (CL), 0.11 +/- 0.07 mL min-1 (g liver)-1; initial distribution half-life (initial t1/2), 14.62 +/- 2.38 min; terminal half-life (terminal t1/2), 138.7 +/- 178.8 min; AUC 606 +/- 194 mg mL-1 min-1 (g liver)-1; elimination rate constant (Ke), 0.0135 +/- 0.012 min-1. Prior dosing with mefloquine did not affect halofantrine perfusate pharmacokinetic parameter estimates of Vd, Ke, initial and terminal t1/2 (P > 0.05). A single dose, short term (4-6 h) interaction showed significant changes in the perfusate clearance of halofantrine in mefloquine-pretreated livers using higher doses of halofantrine. Substantial changes were seen in bile production (P < 0.05) and biliary clearance (P < 0.05) of halofantrine in mefloquine-pretreated livers. These findings may have clinical implications in models utilizing multiple drug dosages or in patients with severe malaria who have disease-related cholestasis.
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PMID:Mefloquine effect on disposition of halofantrine in the isolated perfused rat liver. 886 37

The combination of halofantrine and primaquine therapies was calculated as a regimen for achieving radical curve of falciparum or vivax malaria in Irian Jaya, Indonesia, and compared with combined chloroquine and primaquine therapies. The patients who volunteered for the study [adult, male, Indonesian immigrants with no previous exposure to endemic malaria, normal glucose-6-phosphate dehydrogenase (G6PD) activity, uncomplicated malaria illness, no prior use of antimalarials, and parasitaemias of 0.001%-1.1%] were randomized to receive either halofantrine (24 mg base/kg bodyweight, in three equal doses over 12 h) or chloroquine (25 mg base/kg bodyweight over 48 h, in doses of 10, 10 and 5 mg base/kg at 24-h intervals). Each patient also received concurrent daily primaquine (0.5 mg base/kg bodyweight) for 14 days followed by the same dose on alternate days to day 28. A recurrent parasitaemia during the 28 days of follow-up constituted drug failure. Of the 40 cases of falciparum malaria and 26 cases of vivax malaria treated with halofantrine-primaquine, none had a recurrent parasitaemia (100% efficacy). In contrast, 20 of 30 patients with falciparum malaria and three of 27 with vivax malaria had recurrent parasitaemias after chloroquine-primaquine, giving efficacies of 33% and 89%, respectively. Halofantrine-primaquine was significantly more effective than chloroquine-primaquine against falciparum malaria (P < 0.001) but was similarly efficacious against vivax malaria (P = 0.23). On average, fever associated with falciparum or vivax malaria cleared 17 h faster with halofantrine-primaquine (P < 0.01) although there were no significant differences (P > 0.4) in parasite-clearance times between the two regimens. The halofantrine-primaquine regimen was also associated with a more rapid and significant decline in malaria-related physical complaints.
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PMID:Halofantrine and primaquine for radical cure of malaria in Irian Jaya, Indonesia. 909 24

Several important developments have occurred in recent years in the chemotherapy for and prophylaxis of parasitic infections. Although mefloquine is clearly the most effective agent for prevention of chloroquine-resistant falciparum malaria, its use has been compromised by side effects, both real and imagined. Well-designed studies have shown that side effects occur no more frequently with low-dose mefloquine than with chloroquine. Use of mefloquine in pregnant women has not been associated with birth defects, but the incidence of stillbirths may be increased. Malarone is a new agent that combines atovaquone and proguanil, and it may be as effective as mefloquine; however, it is not yet available in the United States. Several newer agents have appeared in response to the development of multidrug resistant Plasmodium falciparum, especially in Southeast Asia. Halofantrine is available for the treatment of mild to moderate malaria due to P. falciparum and for P. vivax infections. Because of severe toxic effects, use of halofantrine should be restricted to only those unusual and rare situations in which other agents cannot be used. Artemisinin (an extract of the Chinese herbal remedy qinghaosu) and two derivatives, artesunate and artemether, are active against multidrug resistant P. falciparum and are widely used in Asia in oral, parenteral, and rectal forms. The antibacterial azithromycin in combination with atovaquone or quinine has now been reported to treat babesiosis effectively in experimental animals and in a few patients. Azithromycin in combination with paromomycin has also shown promise in the treatment of cryptosporidiosis (and toxoplasmosis when combined with pyrimethamine) in patients with the acquired immunodeficiency syndrome (AIDS). Albendazole is currently the only systemic agent available for treatment of microsporidiosis, an infection primarily of patients with AIDS. In addition, albendazole and ivermectin have emerged as effective broad-spectrum antihelminthics, with albendazole becoming the drug of choice for hydatid disease (echinococcosis), neurocysticercosis, and most intestinal nematode infections (except strongyloidiasis and trichuriasis). Liposomal amphotericin B is the first drug approved by the Food and Drug Administration for the treatment of visceral leishmaniasis.
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PMID:Antiparasitic agents. 1056 Jun 6

The authors evaluated the efficacy and safety of halofantrine in 19 patients with acute uncomplicated falciparum malaria. Each patient received oral halofantrine hydrochloride 500 mg every 6 hours, for a total of 3 doses (total 1.5 g). In almost all the patients clinical symptoms of malaria and parasitemia disappeared within 2 and 3 days, respectively, of starting treatment. They observed no recurrence of parasitemia during 14 days of follow-up. Tolerance to halofantrine was good except for minor and self-limiting gastrointestinal side effects. Hematological and biochemical indices were not seriously affected. Halofantrine-induced prolongation of Q-T/Q-Tc intervals was the consistent cardiac manifestation in 84% of patients. The Q-T/Q-Tc interval prolongation increased with each dose; it reached a maximum between 18 and 24 hours and thereafter returned to baseline. These preliminary data indicate that, apart from the cardiac side effects, halofantrine is an effective and safe drug, well tolerated by most of the patients in the study.
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PMID:Halofantrine in the treatment of uncomplicated falciparum malaria with a three-dose regimen in Papua New Guinea: a preliminary report. 1074 Nov 74

Halofantrine is a newer antimalarial drug which has not been approved for clinical use in Papua New Guinea. The authors assessed 21 Central Province isolates of Plasmodium falciparum for their in vitro susceptibility to halofantrine. The concentration required to inhibit 50% of parasite growth (IC50) ranged from 0.05 to 7.0 nmol with a mean of 1.90 nmol and a median of 1.50 nmol. The minimum inhibitory concentration (MIC) values ranged from 2.5 to 50 nmol with a median of 5.0 nmol. All but one isolate had an MIC of 10 nmol or less. These results indicate that halofantrine would be a suitable alternative for the treatment of P. falciparum malaria in the region in the future, if and when the need arises, provided that its use was carefully monitored.
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PMID:In vitro susceptibility of Plasmodium falciparum isolates to halofantrine in the Central Province of Papua New Guinea. 1074 Nov 75

The standard first-line treatment for malaria in adults in Papua New Guinea is chloroquine; for severe and treatment-failure malaria standard therapy is a combination of quinine and Fansidar (sulphadoxine-pyrimethamine). These standard treatments are currently under revision. The present study evaluated the effect of halofantrine in treatment-failure falciparum malaria in adults in Port Moresby compared to standard therapy. In the halofantrine group all parasites were cleared by day 5 after starting therapy, in the quinine-Fansidar group by day 7. There was no evidence of recurrence of parasitaemia during the 21-day follow-up in either group. Nausea was associated with halofantrine use in 68% of patients. In the quinine-Fansidar group 79% had muffled deafness, 32% tinnitus and 26% dizziness; 32% of patients withdrew from treatment on day 2 because of intolerance to quinine. Halofantrine in this study population provided an efficacy against treatment-failure falciparum malaria similar to that of quinine-Fansidar, with a more favourable profile of adverse effects.
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PMID:Halofantrine versus quinine-Fansidar combination in the treatment of post-chloroquine falciparum parasitaemia. 1093 52


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