A randomised trial of the efficacy and cost of artesunate and three quinine regimens in the treatment of severe malaria in children at the Ebolowa Regional Hospital

ETHE MAKA Daniel Adrien (e_makadaniel@yahoo.fr)
Paediatrics, Yaounde I
June, 2014
 

Abstract

Introduction
Severe malaria is a medical emergency with high mortality in children below five years of age especially in sub-Saharan Africa. Recently quinine has been replaced by artesunate as the first-line drug in the treatment of severe malaria in Cameroon. However, the drug is not yet widely used and cost of treatment is a key issue given that Cameroon is a low to moderate income country. No study has yet been conducted to evaluate the efficacy and cost of artesunate with respect to the different quinine regimens used in Cameroon. Such data is fundamental for both care givers and health planners. Thus we undertook this study at the Ebolowa Regional Hospital (ERH) which is located in a region of perennial transmission of malaria.

Objectives
The main objective of the study was to compare the efficacy and the direct costs during hospitalisation of artesunate and three quinine regimens in the treatment of severe malaria in children.

Materials and Methods
We carried out an open-label randomized clinical trial from 1st September 2013 to 31st March 2014 at the ERH. All children aged 3 months to 15 years admitted to the hospital with slide-confirmed severe malaria to P. falciparum were recruited after informed consent was obtained from their parents. Patients were randomised into 4 groups. Those in the first group (ARTES) received parenteral artesunate at a standard dose of 2.4 mg/kg at H0, H12, H24 and then once daily; those in the second group (QLD) received a loading dose of quinine base at 16.6 mg/kg followed 8 hours later by an 8-hourly maintenance dose of 8.3 mg/kg quinine base; those in the third group (QNLD3) received 8.3 mg/kg quinine base every 8 hours without a loading dose, and those in the fourth group (QNLD2) received 12.5 mg/kg quinine base every 12 hours. All patients invariably received a minimum of 24 hours parenteral treatment, then, oral antimalarials as soon as the patient could swallow. Temperature and parasitaemia were monitored every 6 hours and the state of consciousness was monitored every 2 hours for 24 hours, then every 6 hours till normalisation. The endpoints were fever clearance time, coma resolution time, time to sit unsupported, time to eat, parasite clearance time, and parasitaemia reduction rate at H24. Direct costs during hospitalisation were recorded for each patient. Data was collected on pre-tested worksheets, introduced into Epi InfoTM version 3.5.3 software and double-checked before analysis. Analysis of variance was used to compare data in the four groups, Student t test was performed for a two-by-two comparison of the groups and a p-value less than 0.05 was considered statistically significant.

Results
One hundred and eighteen patients were enrolled in the study: 30 in ARTES arm, 28 in QLD arm, 30 in QNLD3 arm and 30 in QNLD2 arm. We recorded no major differences in baseline characteristics between the treatment groups. On analysis of endpoints, fever clearance time and parasite clearance time was significantly shorter for artesunate-treated patients than for quinine-treated patients. Parasitaemia reduction rate at H24 was also significantly higher for artesunate. Time to sit unsupported and time to eat were shorter with artesunate, but the difference was not statistically significant. Mean costs per patient during hospitalisation were evaluated at 34 625 CFA F for ARTES group, 32 250 CFA F for QLD group, 34 535 CFA F for QNLD3 group and 31 970 CFA F for QNLD2 group.

Conclusion
Fever clearance time, parasite clearance time and parasitaemia reduction rate 24 hours after onset of treatment were best in the artesunate treatment regimen arm than with any of the quinine regimens. The cost of treatment was more expensive with artesunate than with the three quinine regimens.

Recommendations
The Ministry of Public Health should ensure the availability and distribution of artesunate in all health facilities in the country; subsidize artesunate so that it could be affordable for all patients in all health facilities in the country and add it on the list of essential drugs. Health personnel should use artesunate as the first intention drug in the treatment of severe malaria in Cameroonian children as directed by the National Malaria Control Programme.
Key words: severe malaria, artesunate, quinine, efficacy, cost, children, Cameroon


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