Clinical comparison of artemether and quinine treatment of severe and complicated falciparum malaria patients in Indonesia a preliminary report

Abstract

In order to evaluate artemether as an alternative to quinine in the treatment of severe and complicated falciparum malaria, a multi center randomized comparative study of artemether and quinine treatment was being conducted at Bethesda Hospital, Balikpapan and Mataram General Hospital, Indonesia. This study began in 1994. The objectives of this study were to determine the clinical manifestations of severe and complicated falciparum malaria, to assess and compare the efficacy and tolerance of intramuscular artemether and intravenous quinine dihydrochloride. Fifty-two out of 180 targetted severe and complicated falciparum malaria patients were randomized to receive artemether intramuscularly 1.6 mg/kg b.w/dose bid on day 0 and followed by a daily dose on day 1-4 or quinine dihydrochloride intravenously 20 mg salt/kg b.w in 5% dextrose 10 ml/kg b.w in 4 hours followed by 10 mg salt/kg b.w tid until the patient was able to swallow oral quinine up to 21 doses. They were hospitalized for at least 14 days or until clinically and parasitologically cured. The single complication cases were found in 30 (57.7%) of the 52 severe falciparum malaria patients. The most common complications were hyperbilirubinaemia (50%), cerebral malaria (26.9%) and hyperparasitaemia (25%). While the highest fatality rates were associated with septic shock (100%), pulmonary edema (100%), bleeding (100%) and hyper- creatinaemia (83.3%). The overall case fatality rate was 19.2% (10/52), 14.3% (4/28) in the artemether group and 25% (6/24) in the quinine group. This difference was not statiscally signifi¬cant. The risk of death increased with the number of complica¬tions and was 100% if there were more than 3 complications. Until day 14, between the treatment groups, there were no significant differences in the cure rates (100% vs 100%), mean fever clearance rimes (34±33 h vs 33±17 h) and mean parasite clearance times (35±14 h vs 46±26 h). However, the mean coma resolution time was faster in the artemether group than in the quinine group (29.6±8.4 h vs 105.3±66.6 h). This 3.5-fold reduction in coma duration, suggestive reduced fatality, few and mild side effects and convenience of intramuscular treatment indicated advantages of intramuscular artemether therapy.