Randomized comparison of intramuscular artemether and intravenous quinine in adult, Melanesian patients with severe or complicated, Plasmodium falciparum malaria in Papua New Guinea

Abstract

An open-label, randomized, controlled trial was used to compare the safety and efficacy of intramuscular artemether (a loading dose of 3.2 mg/kg, followed by 1.6 mg/kg daily for 4 days) and intravenous quinine (a loading dose of 20 mg quinine dihydrochloride/kg, followed first by 10 mg/kg every 8 h, each injection taking 4 h, for at least 48 h, and then oral quinine for a total of 7 days) in the management of strictly defined severe/complicated malaria in Melanesian adults. Four (12%) of the 33 patients who enrolled and completed follow-up died (one of the 15 who received artemether and three of the 18 who received quinine). Overall, cerebral malaria was uncommon (6%) whilst jaundice was common (76%). The time taken to clear 50% of parasites was less in those treated with artemether (median = 8 h; range = 2-24 h) than in the patients given quinine (median = 14 h; range = 2-25 h; P = 0.05). Temperature defervescence was also quicker in those treated with artemether (median = 32 hours; range = 20-112 h) than in those in the quinine group (median = 48 h; range = 28-88 h; P = 0.034). Hypoglycaemia was not observed in any patient treated with artemether but complicated therapy in 11 (79%) of the 14 patients given quinine who had not had pre-treatment spontaneous hypoglycaemia. No serious adverse effects were attributable to artemether. The Plasmodium falciparum infections observed during the 1 month of follow-up, in three patients who had received artemether and two who had been given quinine, were probably due to recrudescence. Plasmodium vivax parasitaemias were also observed during follow-up, in one or two patients in each treatment group. Artemether appears safe in Melanesian adults and is probably as effective as intravenous quinine in the treatment of severe or complicated falciparum malaria.