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Open Access Research

Electrocardiographic study in Ghanaian children with uncomplicated malaria, treated with artesunate-amodiaquine or artemether-lumefantrine

George O Adjei1*, Collins Oduro-Boatey2, Onike P Rodrigues2, Lotte C Hoegberg3, Michael Alifrangis3, Jorgen A Kurtzhals3 and Bamenla Q Goka2

Author Affiliations

1 Centre for Tropical Clinical Pharmacology & Therapeutics, University of Ghana Medical School, College of Health Sciences, University of Ghana, Accra, Ghana

2 Department of Child Health, University of Ghana Medical School, College of Health Sciences, University of Ghana, Accra, Ghana

3 Centre for Medical Parasitology at Department of International Health, University of Copenhagen and Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark

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Malaria Journal 2012, 11:420  doi:10.1186/1475-2875-11-420

Published: 17 December 2012

Abstract

Background

Several anti-malarial drugs are associated with adverse cardiovascular effects. These effects may be exacerbated when different anti-malarials are used in combination. There has been no report yet on the potential cardiac effects of the combination artesunate-amodiaquine.

Methods

Electrocardiographic (ECG) intervals in Ghanaian children with uncomplicated malaria treated with artesunate-amodiaquine (n=47), were compared with that of children treated with artemether-lumefantrine (n=30). The ECG measurements were repeated one, two, three, seven and 28 days after treatment. The ECG intervals of artesunate-amodiaquine treated subjects were correlated with plasma concentrations of desethylamodiaquine (DEAQ), the main metabolite of amodiaquine.

Results

The mean ECG intervals were similar in both groups before treatment. After treatment (day 3), ECG intervals changed significantly from baseline in all subjects, but there were no differences between the two treatment groups. A significantly higher proportion of children treated with artesunate-amodiaquine developed sinus bradycardia compared with artemether-lumefantrine treated subjects (7/47 vs 0/30; χ2 p=0.03). Subjects who developed bradycardia were significantly older, and had higher DEAQ concentrations than those who did not develop bradycardia. The proportion of subjects with QTc interval prolongations did not differ significantly between the groups, and no relationship between prolonged QTc intervals and DEAQ levels were observed. No clinically significant rhythm disturbances were observed in any of the subjects.

Conclusion

Artesunate-amodiaquine treatment resulted in a higher incidence of sinus bradycardia than artemether-lumefantrine treatment in children with uncomplicated malaria, but no clinically significant rhythm disturbances were induced by combining artesunate with amodiaquine. These findings, although reassuring, may imply that non-amodiaquine based artemisinin combination therapy may be preferable for malaria treatment in patients who are otherwise at risk of cardiac effects.

Keywords:
Malaria; Combination therapy; Cardiotoxicity; Children; Ghana