Clinical Efficacy and Pharmacokinetics of Micronized Halofantrine for the Treatment of Acute Uncomplicated Falciparum Malaria in Nonimmune Patients

Bouchaud, Olivier; Basco, Léonardo K.; Gillotin, Catherine; Gimenez, François; Ramiliarisoa, O.; Genissel, Bernadette; Bouvet, E; Farinotti, Robert; Bras, J. Le; Coulaud, J P

doi:10.4269/ajtmh.1994.51.204

Cited by 24 publications

(12 citation statements)

References 8 publications

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“…Reappearance of parasites after halofantrine or artesunate treatment requires the dosage of plasmatic drug level few hours or days after drug administration because recrudescence is known to occur due to inadequate drug absorption or rapid elimination. [34][35][36][37] The results of our study do not agree with the results of some of the previous studies. In the study of Babiker and others, 25 six Sudanese isolates obtained from patients responding with early and late RI chloroquine treatment failure (from Day 9 to Day 30) had identical MSA-1 and MSA-2 alleles, leading the investigators to conclude that RI chloroquine resistance is due to recrudescence.…”

Section: Discussioncontrasting

confidence: 99%

Molecular epidemiology of malaria in Yaounde, Cameroon. VII. Analysis of recrudescence and reinfection in patients with uncomplicated falciparum malaria.

Basco

Ringwald²

2000

The American Journal of Tropical Medicine and Hygiene

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Abstract. In an endemic area where malaria transmission is intense and continuous, reappearance of asexual parasites may be ascribed to either recrudescence or reinfection. To distinguish between recrudescence and reinfection after oral treatment with chloroquine, amodiaquine, pyronaridine, sulfadoxine-pyrimethamine, halofantrine, or artesunate, three polymorphic markers (circumsporozoite protein, merozoite surface antigens 1 and 2) from pre-treatment and post-treatment samples were amplified by the polymerase chain reaction, and the in vitro response to chloroquine was determined for comparison. Of 52 paired samples, 22 (42%) were reinfections. Recrudescence occurred more frequently on or before Day 14 (22 of 30 cases, 73%). Except for one case, all reinfections were observed beyond Day 14. The phenotype determination was not sufficiently precise to distinguish between recrudescence and reinfection. Our results suggest that beyond Day 14 (and until Day 42), recrudescence and reinfection cannot be distinguished at our study site unless molecular techniques are used and that some results derived from the polymerase chain reaction need to be compared with the microscopic examination of thick blood smear to exclude gametocyte carriers without asexual parasites after treatment.

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Section: Discussioncontrasting

confidence: 99%

Molecular epidemiology of malaria in Yaounde, Cameroon. VII. Analysis of recrudescence and reinfection in patients with uncomplicated falciparum malaria.

Basco

Ringwald²

2000

The American Journal of Tropical Medicine and Hygiene

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“…Halofantrine levels measured by HPLC were available in three cases: two considered in the normal therapeutic range for both halofantrine and N-desbutyl-halofantrine [20] and one with high values (respectively 879 and 510 ng/mL) supporting a possible overdose [15,19]. Five cases occurred in children less than 16 y (three males and two females), living in a developing country (four) or in France (one).…”

Section: Resultsmentioning

confidence: 99%

Fatal cardiotoxicity related to halofantrine: a review based on a worldwide safety data base

Bouchaud

Imbert

et al. 2009

Malar J

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BackgroundHalofantrine (HF) was considered an effective and safe treatment for multi-drug resistant falciparum malaria until 1993, when the first case of drug-associated death was reported. Since then, numerous studies have confirmed cardiac arrythmias, possibly fatal, in both adults and children. The aim of the study was to review fatal HF related cardiotoxicity.MethodsIn addition, to a systematic review of the literature, the authors have had access to the global safety database on possible HF related cardiotoxicity provided by GlaxoSmithKline.ResultsThirty-five cases of fatal cardiotoxicity related to HF, including five children, were identified. Females (70%) and patients from developing countries (71%) were over-represented in this series. Seventy-four percent of the fatal events occurred within 24 hours of initial exposure to HF. Twenty six patients (74%) had at least one predisposing factor for severe cardiotoxicity, e.g., underlying cardiac disease, higher than recommended doses, or presence of a concomitant QT-lengthening drug. All (100%) of the paediatric cases had either a contraindication to HF or an improper dose was given. In six cases there was no malaria.ConclusionA distinction should be made between common but asymptomatic QT-interval prolongation and the much less common ventricular arrhythmias, such as torsades de pointes, which can be fatal and seem to occur in a very limited number of patients. The majority of reported cardiac events occurred either in patients with predisposing factors or with an improper dose.Therefore, in the rare situations in which HF is the only therapeutic option, it can still be given after carefully checking for contraindications, such as underlying cardiac disease, bradycardia, metabolic disorders, personal or family history of long QT-interval or concomitant use of another QT-prolonging drug (e.g., mefloquine), especially in females.

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“…Given that recrudescence occurs usually between day 14 and day 30 after treatment, physicians should organize a “recapture” system for these patients, even limited to a call, in order to identify promptly a possible recrudescence [15,19,36]. …”

Section: Discussionmentioning

confidence: 99%

Therapy of uncomplicated falciparum malaria in Europe: MALTHER – a prospective observational multicentre study

Bouchaud

Mühlberger²,

Parola³

et al. 2012

Malar J

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BackgroundMalaria continues to be amongst the most frequent infectious diseases imported to Europe. Whilst European treatment guidelines are based on data from studies carried out in endemic areas, there is a paucity of original prospective treatment data. The objective was to summarize data on treatments to harmonize and optimize treatment for uncomplicated malaria in Europe.MethodsA prospective observational multicentre study was conducted, assessing tolerance and efficacy of treatment regimens for imported uncomplicated falciparum malaria in adults amongst European centres of tropical and travel medicine.ResultsBetween December 2003 and 2009, 504 patients were included in 16 centres from five European countries. Eighteen treatment regimens were reported, the top three being atovaquone-proguanil, mefloquine, and artemether-lumefantrine. Treatments significantly differed with respect to the occurrence of treatment changes (p = 0.005) and adverse events (p = 0.001), parasite and fever clearance times (p < 0.001), and hospitalization rates (p = 0.0066) and durations (p = 0.001). Four recrudescences and two progressions to severe disease were observed. Compared to other regimens, quinine alone was associated with more frequent switches to second line treatment, more adverse events and longer inpatient stays. Parasite and fever clearance times were shortest with artemether-mefloquine combination treatment. Vomiting was the most frequent cause of treatment change, occurring in 5.5% of all patients but 9% of the atovaquone-proguanil group.ConclusionsThis study highlights the heterogeneity of standards of care within Europe. A consensus discussion at European level is desirable to foster a standardized management of imported falciparum malaria.

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Clinical Efficacy and Pharmacokinetics of Micronized Halofantrine for the Treatment of Acute Uncomplicated Falciparum Malaria in Nonimmune Patients

Cited by 24 publications

References 8 publications

Molecular epidemiology of malaria in Yaounde, Cameroon. VII. Analysis of recrudescence and reinfection in patients with uncomplicated falciparum malaria.

Molecular epidemiology of malaria in Yaounde, Cameroon. VII. Analysis of recrudescence and reinfection in patients with uncomplicated falciparum malaria.

Fatal cardiotoxicity related to halofantrine: a review based on a worldwide safety data base

Therapy of uncomplicated falciparum malaria in Europe: MALTHER – a prospective observational multicentre study

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