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01.12.2012 | Research | Ausgabe 1/2012 Open Access

Malaria Journal 1/2012

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

Zeitschrift:
Malaria Journal > Ausgabe 1/2012
Autoren:
George O Adjei, Collins Oduro-Boatey, Onike P Rodrigues, Lotte C Hoegberg, Michael Alifrangis, Jorgen A Kurtzhals, Bamenla Q Goka
Wichtige Hinweise

Competing interests

The funding agencies had no role in the study design, collection, analysis, and interpretation of data, manuscript preparation or in the decision to submit for publication. The authors declare that they have no competing interests.

Authors’ contributions

The study was designed by GOA, BQG, OPR and JK. The clinical work was done by GOA, BQG, OPR and CO-B. The laboratory work was done by GOA, LCH, MA, and JK. The data were analysed by GOA and JK. The manuscript was drafted by GOA, and all authors contributed significantly to the final draft. All authors read and approved the final manuscript.

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.
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