HALOFANTRINE VERSUS MEFLOQUINE IN TREATMENT OF MULTIDRUG-RESISTANT FALCIPARUM-MALARIA

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 mefloq uine in two paired randomised trials on the Thai-Burmese border, a mul tidrug-resistant area. In the first trial, 198 patients with acute unc omplicated falciparum malaria were randomly assigned either the standa rd halofantrine regimen (24 mg/kg) or mefloquine (25 mg/kg). The cumul ative 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 bo th more effective and better tolerated than mefloquine 25 mg/kg; the f ailure rates were 3% and 8% (p = 0.03), respectively, or 1% vs 6% afte r adjustment for possible reinfections (p = 0.009). The rate of failur e was higher after retreatment than after primary treatment in all stu dy groups. Halofantrine 72 mg/kg was especially effective in the retre atment of these recrudescent infections, the failure rate was 44% with mefloquine and 15% with high-dose halofantrine (relative risk 3.0 [95 % Cl 1.2-7.3], p = 0.008). Thus, high-dose halofantrine is better tole rated and more effective than mefloquine for the treatment of uncompli cated falciparum malaria in this area. However, evidence of possible c ardiotoxicity will need to be investigated fully before a role can be established for halofantrine in the treatment of multidrug-resistant m alaria.