Halofantrine for the Treatment of Mefloquine Chemoprophylaxis Failures in Plasmodium Falciparum Infections

G. Dennis Shanks Departments of Medicine and Immunology, Armed Forces Research Institute of Medical Sciences, Royal Thai Navy Medical Department, Bangkok, Thailand

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George Watt Departments of Medicine and Immunology, Armed Forces Research Institute of Medical Sciences, Royal Thai Navy Medical Department, Bangkok, Thailand

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Michael D. Edstein Departments of Medicine and Immunology, Armed Forces Research Institute of Medical Sciences, Royal Thai Navy Medical Department, Bangkok, Thailand

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H. Kyle Webster Departments of Medicine and Immunology, Armed Forces Research Institute of Medical Sciences, Royal Thai Navy Medical Department, Bangkok, Thailand

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Varakorn Suriyamongkol Departments of Medicine and Immunology, Armed Forces Research Institute of Medical Sciences, Royal Thai Navy Medical Department, Bangkok, Thailand

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Chamnong Watanasook Departments of Medicine and Immunology, Armed Forces Research Institute of Medical Sciences, Royal Thai Navy Medical Department, Bangkok, Thailand

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Sukitti Panpunnung Departments of Medicine and Immunology, Armed Forces Research Institute of Medical Sciences, Royal Thai Navy Medical Department, Bangkok, Thailand

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Warasak Kowinwiphat Departments of Medicine and Immunology, Armed Forces Research Institute of Medical Sciences, Royal Thai Navy Medical Department, Bangkok, Thailand

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DOI:
https://doi.org/10.4269/ajtmh.1991.45.488
Volume/Issue:
Volume 45: Issue 4
Page(s):
488–491
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Thai soliders who became slide-positive for malaria while receiving mefloquine chemoprophylaxis were treated with halofantrine to study its efficacy against mefloquine-resistant falciparum malaria. Thirty-two patients received three doses of 500 mg (1,500 mg total) of halofantrine at six-hr intervals, and were then observed for four weeks. Parasite recrudescence following treatment (median 21 days) occurred in seven of 23 patients (30%) who had mefloquine serum concentrations indicative of regular prophylaxis (> 500 ng/ml). Serum concentrations of mefloquine in all 32 patients averaged 950 ng/ml (range 26–2,515) prior to halofantrine treatment. The halofantrine serum concentrations were higher in patients cured by halofantrine than in patients with drug failure, but this was not statistically significant. Patients who were cured by halofantrine had parasites that were more sensitive in in vitro testing to mefloquine (mean [inhibitory concentration] IC50 = 12.5 ng/ml) than in patients whose parasitemias recrudesced (mean IC50 = 23.8 ng/ml) (P < 0.01, by Wilcoxon rank sum test). These observations suggest that the current formulation and regimen of halofantrine are not optimal for the treatment of multiple drug-resistant falciparum malaria from Thailand.
Copyright:
Copyright © 1991 by The American Society of Tropical Medicine and Hygiene 1991
Published Online:
Oct 1991
Cover The American Journal of Tropical Medicine and Hygiene
The American Journal of Tropical Medicine and Hygiene
Print ISSN:
0002-9637
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