Quinine treatment of severe falciparum malaria in African children: a randomized comparison of three regimens. [Treatment of cerebral malaria in African children by intravenous quinine: comparison of a loading dose regimen to a regimen without a loading dose]. Quinine loading dose in severe Falciparum malaria at Kenyatta National Hospital, Kenya. Reduction of coma by quinine loading dose in falciparum cerebral malaria.
The pharmacokinetics and effectiveness of three dosage regimens of quinine were studied in a group of 59 children with severe malaria. The children were randomized to receive high-dose intravenous or intramuscular quinine (20 mg salt/kg loading, then 10 mg salt/kg every 12 hr), or low-dose intravenous quinine (10 mg salt/kg loading, then 5 mg salt/kg every 12 hr). In the group receiving the high-dose intravenous regimen, mean high and low quinine concentrations were consistently greater than 10 and 6.5 mg/l, respectively. Peak concentrations as well as the time required to achieve them were similar in the intramuscular and high-dose intravenous groups. The low-dose intravenous quinine regimen resulted in mean peak concentrations greater than 6 mg/l and mean low concentrations greater than 3.5 mg/l. All blood concentrations exceeded the 99% in vitro inhibitory concentration (EC99) of 0.89 mg/l or less of quinine for 60 isolates of Plasmodium falciparum, which were taken from children with malaria during the same period. Judged by a number of clinical criteria, the response was better in patients receiving the high-dose than the low-dose intravenous regimen. The time taken to clear parasites with both the high-dose intravenous and intramuscular regimens were significantly shorter than those obtained in the low-dose group. We have also shown for the first time that the rate of parasite clearance can be directly related to the area under the quinine concentration versus time curve. This applied to all three quinine regimens (r = 0.4252, P less than 0.02; n less than or equal to 35). Five patients, two on the low-dose regimen, two on the intramuscular regimen, and one on the high-dose regimen, developed hypoglycemia after admission, but in these cases, insulin concentrations were correspondingly low. No significant quinine toxicity was observed in any of the cases. The high-dose intravenous quinine regimen described here may be optimal for treatment of severe falciparum malaria in areas of chloroquine resistance in Africa. Our data provide no justification for reducing the dose of quinine in the treatment of severe malaria in Africa. The intramuscular regimen could provide a satisfactory alternative in areas where intravenous administration might be delayed or is impossible. To compare in a randomized study the efficacy and the toxicity of the new WHO intravenous quinine treatment of cerebral malaria including a loading dose regimen to a regimen without loading dose.
                Seventy-two children eight months to 15 years of age with cerebral malaria were included. Quinine formiate was administered to a group of 35 patients in an initial loading dose of 20 mg salt/kg (equivalent to 17.5 mg/kg of the base) in 10 mL/kg of 5% glucose over four hours, followed eight hours later by a maintenance dose quinine of 10 mg salt/kg (equivalent to 8.7 mg/kg of the base) dissolved in 15 mL/kg of 5% glucose over and every 12 hours. The second group of 37 patients received intravenous quinine 15 mg salt/kg (13.1 mg of base) dissolved in 15 mL/kg of 5% glucose infused over 6 to 8 hours, every 12 hours. In both groups this treatment was continued until the patient could swallow, then quinine tablets were given to complete seven days treatment. The assessment of cardiovascular side effects was made by an ECG at admission, the 4th hour, the 24th hour and at the end of treatment for each patient.
                Coma mean durations were similar in the two groups: 35.5 +/- 17.8 hours and 28.6 +/- 14.4 hours respectively for the loading dose group and the group without loading dose. The two groups were comparable also for the decrease evolution of parasitemia. Case-fatality rates were also similar: 95% of healing at the 72nd hour and a lethality rate between 5 and 6% in the two groups. But a significant increase of the body temperature was noted between the 51st and the 63rd hour in the group without loading dose. No significant cardiovascular toxicity was noticed in the two groups. The mean cost of the loading dose regimen was less than that of the second regimen.
                The loading dose regimen of quinine is well tolerated and it seemed slightly more effective than the regimen without loading dose. In cases of contra-indications (patients who recently received quinine, mefloquine or halofantrine), regimens without loading dose, which remains effective, should be used. From July 1989 to February 1990, 17 non-pregnant patients with severe falciparum malaria, aged 14 years and above received an initial intravenous quinine dihydrochloride loading dose of 20 mg/kg in 500 mls of normal saline or 5% dextrose infused over 4 hours followed by 100mg/kg infused 8 hourly for at least 24 hours. Sixteen comparable controls were similarly treated but without an initial loading dose. Oral quinine bisulfate 10mg/kg 8 hourly was substituted for a total of 7 days when patients were well enough. There was no significant difference in clinical and parasitological response between the two groups. Fever clearance time in hours was 44.00 +/- 13.92 (mean +/- SD) in the study group and 51.43 +/- 19.63 (mean +/- SD) in the control group (p > 0.05). Parasite clearance time in hours was 42.40 +/- 9.75 (mean +/- SD) in the study group and 47.05 +/- 7.69 (mean +/- SD) in the control group (p > 0.05). One patient from each group died. Mild toxic effects were common in both groups. Transient partial hearing loss occurred significantly more in the study than control group (p < 0.05). Hypoglycaemia during treatment occurred in 3 (18%) patients in the study group and 1 (6%) in the control group. The mean trough and peak plasma quinine levels in 3 patients per group was persistently higher than 9mg/L after first infusion. We conclude that though fairly well tolerated, quinine loading dose appears to have no advantage over the standard treatment for severe falciparum malaria at Kenyatta National Hospital, Nairobi, Kenya. nan