Quinine loading dose in severe falciparum malaria at Kenyatta National Hospital

Abstract

From July 1989 to February 1990 inclusive, an eight-month controlled clinical trial study was conducted at Kenyatta National Hospital aiming at evaluating the efficacy of quinine in severe falciparum malaria and tolerability of quinine loading dose in adults. Thirty-three patients aged 14 years and over, exc luding pregnant mothers, were recruited into the study after obtaining wr itten informed consen t. The study group was treated with intravenous quinine starting with an initial loading dose of 20 mg/kg diluted in 500 mls of normal saline or 51. dextrose and infused over 4 hours followed by 10 mg/kg similarly infused every 8 hours. The control group was similarly treated but without an initial loading dose. Oral quinine bisulfate 10 mg/kg exery 8 hours was substituted when the patients were well enough to take orally. Seventeen patients were enrolled in the study group and 16 in the control group. The age in years for the study group ranged from 14 to 50 (27.47 + 9.32, mean + S.D.). 6 (351.) were males and 11 (651.) ""ere fema Ies. The age in years for the control group ranged from 14 to 89 (30.63 ~ 11.52, mean + S.D.). 7 (441.) were males and 9 (561.) were females. The age distribution and the sex ratios in the two groups were not statistically different (P >

0.05) . The two groups were also comparable in history of travel outside Nairobi; history of antimalarial ingestion prior to admission and severity of the illness. Only one patient presented with an unarousable coma. There was no statistically significant difference in fever clearance times and parasite clearance times in the 2 groups (P > 0.05 respectively). Thus, fever clearance time in hours was 44.00 + 13.92 (mean + S.D.) in the study group and 51.43 ~ 19.62 (mean + S.D.) in the control group. The parasite clearance time in hours was 42.40 + 9.75 (mean + S.D.) for the study group and 47.05 + 7.69 (mean + S.D.) for the control group. One patient (6%),from each group died. Thirteen patients from the study and 11 from the control groups were seen on day 15 while one patient in the study and 5 in the control groups were seen on day 28. None of those patients had a positive blood slide for malaria parasites. Mild toxic effects were fairly common in both groups. Transient partial hearing loss occurred significantly more in the study than in the control group (P < 0.05). Hypoglycaemia during treatment occurred in 3 (181.) patients in the study group and in 1 (61.) patient in the control group. The mean trough quinine concentrations in mg/l for the 3 patients in the study group ranged from 9.44 + 0.63 (mean + S.E.)

to 10.4 + 1.68 (mean + S.E.) while in the 3 control patients, it ranged from 10.8 + 2.1 (mean + S.E.) to 11.1 ~ 0.38 (mean + S.E.) On the other hand, the mean peak concentrations in mg/l ranged from 10.1 + 0.87 (mean + S.E.) to 10.7 + 0.35 (mean + S.E.) for the study group and from 9.4 +-1.77 (mean + S.E.) to 11.8 + 0.87 (mean + S.E.) for the control group. The mean trough and mean peak plasma quinine concentrations were persistently higher than 9 mg/l in both groups. In conclusion therefore, quinine was found to be so effective in the management of severe falciparum malaria in Nairobi that therei was no advantage of an initial loading dose over the standard regimen as measured by fever clearance time, parasite clearance time and mortality .