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Increased Risk of Early Vomiting among Infants and Young Children Treated with Dihydroartemisinin-Piperaquine Compared with Artemether-Lumefantrine for Uncomplicated Malaria

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  • Department of Medicine, San Francisco General Hospital, University of California, San Francisco, California; Centre for Drug Candidate Optimisation, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia; Infectious Diseases Research Collaboration, Kampala, Uganda; Global AIDS Program, Centers for Disease Control and Prevention, Atlanta, Georgia; Makerere University School of Medicine, Kampala, Uganda; Department of Medicine, University of Washington, Seattle, Washington

Artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP) are highly efficacious antimalarial therapies in Africa. However, there are limited data regarding the tolerability of these drugs in young children. We used data from a randomized control trial in rural Uganda to compare the risk of early vomiting (within one hour of dosing) for children 6–24 months of age randomized to receive DP (n = 240) or AL (n = 228) for treatment of uncomplicated malaria. Overall, DP was associated with a higher risk of early vomiting than AL (15.1% versus 7.1%; P = 0.007). The increased risk of early vomiting with DP was only present among breastfeeding children (relative risk [RR] = 3.35, P = 0.001) compared with children who were not breastfeeding (RR = 1.03, P = 0.94). Age less than 18 months was a risk factor for early vomiting independent of treatment (RR = 3.27, P = 0.02). Our findings indicate that AL may be better tolerated than DP among young breastfeeding children treated for uncomplicated malaria.

Author Notes

*Address correspondence to Taylor G. Sandison, Fred Hutchinson Cancer Research Center, Clinical Research, University of Washington, Box 358080, Seattle, WA 98195-8080. E-mail: tgsand@u.washington.edu

Financial support: Children in this study were enrolled in programs supported by the U.S. President's Emergency Plan for AIDS Relief and by Cooperative Agreement Number U62P024421 from the Department of Health and Human Services/Centers for Disease Control and Prevention, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Global AIDS Program. This study was also supported by the Doris Duke Charitable Foundation. Grant Dorsey is a recipient of a Clinical Scientist Development Award, and Taylor G. Sandison was supported through the Puget Sound Partners in Global Health and National Institutes of Health/National Institute of Allergy and Infectious Disease grant K23-AI082553. Dihydroartemisinin-piperaquine study drugs were provided free of charge by Holleypharm (Chiongging City, People's Republic of China).

Disclosure: None of the authors have any conflicts of interest. The corresponding author had full access to all data in the study and takes final responsibility for the decision to submit the paper for publication.

Authors' addresses: Darren Creek, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, CA, and Centre for Drug Candidate Optimisation, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia, E-mail: darrencreek@gmail.com. Victor Bigira, Emmanuel Arinaitwe, Humphrey Wanzira, Abel Kakuru, and Moses R. Kamya, Infectious Diseases Research Collaboration, Kampala, Uganda, E-mails: vbigira@gmail.com, emmy3md@yahoo.com, wanzirah@yahoo.com, abelkakuru@gmail.com, and mkamya@infocom.co.ug. Jordan Tappero, Global AIDS Program, Centers for Disease Control and Prevention, Atlanta, GA, E-mail: jwt0@cdc.gov. Grant Dorsey, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, CA, E-mail: gdorsey@medsfgh.ucsf.edu. Taylor G. Sandison, Department of Medicine, University of Washington, Seattle, WA, E-mail: tgsand@u.washington.edu.

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