Rectal versus intravenous quinine for the treatment of childhood cerebral malaria in Kampala, Uganda: A randomized, double-blind clinical trial

Background. Although artemesinin derivatives are promising for the treatment of severe Plasmodium falciparum malaria, intravenous quinine remains the most affordable treatment. However, administration of intravenous quinine is often not feasible in rural areas in Africa because of the lack of simple equipment or trained staff. We compared the efficacy and safety of intrarectal quinine with those of intravenous quinine in the treatment of childhood cerebral malaria. Methods. In a randomized, double-blind clinical trial at Mulago Hospital (Kampala, Uganda), Uganda's national referral hospital, we studied 110 children aged 6 months to 5 years who had cerebral malaria. Patients were randomized to receive either intrarectal or intravenous quinine. Main outcome measures included parasite clearance time, fever clearance time, coma recovery time, time to sit unsupported, time to begin oral intake, time until oral quinine was tolerated, and death. Results. Overall, there was no difference in the clinical and parasitological outcomes between the 2 groups (data are deviation, intrarectal quinine group vs. intravenous quinine group): coma recovery time, h versus mean +/- standard 19.4 +/- 18.1 h; fever clearance time, h versus h; and parasite clearance time, h versus 17.0 +/- 12.1 h; fever clearance 26.7 +/- 16.1 h versus 29.9 +/- 18.1 h; and parasite clearance 43.2 +/- 14.2 h. Mortality was similar in both groups; 4 of 56 patients in the intrarectal quinine group died, and 5 of 54 patients 41.9 +/- 15.2 in the intravenous quinine group died (odds ratio, 1.3; 95% confidence interval, 0.3-5.2). Intrarectal quinine was well tolerated, and no major immediate adverse events occurred. Conclusions. Intrarectal quinine is efficacious and could be used as an alternative in the treatment of childhood cerebral malaria, especially in situations in which intravenous therapy is not feasible.