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Updated: May 3, 2026

Quadruple-Checkerboard: A Modification of the Three-Dimensional Checkerboard for Studying Drug Combinations
Published on: July 24, 2021
Artemisinin combination therapy can result in clinical failure if oral therapy is not directly observed
Wilson W Chan1, Divya Virmani2, Dylan R Pillai3
1Calgary Laboratory Services, University of Calgary, Calgary, Alberta ; Department of Pathology & Laboratory Medicine, University of Calgary, Calgary, Alberta.
Abstract:
Intravenous artesunate therapy is the first-line therapy for severe malaria, and is highly efficacious when used in combination with an oral partner drug such as doxycycline or atovaquone-proguanil. However, treatment failure occurs routinely with artesunate monotherapy due to the very short half-life of this drug. In North America, experience with artesunate is limited. With the pressure to discharge patients early, administration of the essential oral partner drug is often left to the discretion of the patient. Thus, treatment failure may be commonplace if nonadherence is a factor, as was observed in the case described in the present report.
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