Patrick S. Twomey, MD; Bryan L. Smith, MD; Cathy McDermott, RN, MPH; Anne Novitt-Moreno, MD; William McCarthy, PhD; S. Patrick Kachur, MD; Paul M. Arguin, MD
Disclaimer: The views expressed in the article are that of the authors and do not necessarily represent the views of the U.S. Army or the Centers for Disease Control and Prevention.
Acknowledgment: The authors thank Aarti Agarwal, Veronica Baechler, Melissa Briggs, John T. Brooks, Cristina Cardemil, Kevin R. Clarke, Gregory Deye, Tarayn A. Fairlie, Nan Guo, Julie Gutman, Keren Z. Landman, Sheryl Lyss, Monica E. Parise, Janet Ransom, Alexander Rowe, Isaac See, Katherine Tan, and Andrew Terranella.
Disclosures: Dr. Smith is a full-time U.S. Army product manager responsible for the development of intravenous artesunate. Dr. Novitt-Moreno reports an army contract with the U.S. Army Medical Research and Materiel Command. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M15-0910.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer.
Reproducible Research Statement:Study protocol: Available at www.cdc.gov/malaria/artesunate.html. Statistical code and data set: Not available.
Requests for Single Reprints: Patrick S. Twomey, MD, U.S. Army Medical Materiel Development Activity, 1430 Veterans Drive, Fort Detrick, MD 21702; e-mail, email@example.com.
Current Author Addresses: Drs. Twomey, Smith, and McCarthy; and Ms. McDermott: U.S. Army Medical Materiel Development Activity, 1430 Veterans Drive, Fort Detrick, MD 21702.
Dr. Novitt-Moreno: Fast-Track Drugs and Biologics, 5 Paramus Court, North Potomac, MD 20878.
Drs. Kachur and Arguin: Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333.
Author Contributions: Conception and design: P.S. Twomey, B.L. Smith, C. McDermott, A. Novitt-Moreno, W. McCarthy, S.P. Kachur, P.M. Arguin.
Analysis and interpretation of the data: P.S. Twomey, B.L. Smith, C. McDermott, A. Novitt-Moreno, S.P. Kachur, P.M. Arguin.
Drafting of the article: P.S. Twomey, C. McDermott, A. Novitt-Moreno, P.M. Arguin.
Critical revision of the article for important intellectual content: P.S. Twomey, B.L. Smith, C. McDermott, S.P. Kachur, P.M. Arguin.
Final approval of the article: P.S. Twomey, B.L. Smith, C. McDermott, S.P. Kachur, P.M. Arguin.
Provision of study materials or patients: B.L. Smith.
Statistical expertise: W. McCarthy.
Obtaining of funding: B.L. Smith.
Administrative, technical, or logistic support: B.L. Smith, C. McDermott, S.P. Kachur.
Collection and assembly of data: P.S. Twomey, B.L. Smith, C. McDermott, S.P. Kachur, P.M. Arguin.
Quinidine gluconate, the only U.S. Food and Drug Administration–approved treatment for life-threatening malaria in the United States, has a problematic safety profile and is often unavailable in hospitals.
To assess the safety and clinical benefit of intravenous artesunate as an alternative to quinidine.
Retrospective case series.
102 patients aged 1 to 72 years (90% adults; 61% men) with severe and complicated malaria. Patients received 4 weight-based doses of intravenous artesunate (2.4 mg/kg) under a treatment protocol implemented by the Centers for Disease Control and Prevention between January 2007 and December 2010. At baseline, 35% had evidence of cerebral malaria, and 17% had severe hepatic impairment. Eligibility required the presence of microscopically confirmed malaria, need for intravenous treatment, and an impediment to quinidine.
Clinical and laboratory data from each patient's hospital records were abstracted retrospectively, including information from baseline through a maximum 7-day follow-up, and presented before a physician committee to evaluate safety and clinical benefit outcomes.
7 patients died (mortality rate, 6.9%). The most frequent adverse events were anemia (65%) and elevated hepatic enzyme levels (49%). All deaths and most adverse events were attributed to the severity of malaria. Patients' symptoms generally improved or resolved within 3 days, and the median time to discharge from the intensive care unit was 4 days, even for patients with severe liver disease or cerebral malaria. More than 100 concomitant medications were used, with no documented drug–drug interactions.
Potential late-presenting safety issues might occur outside the 7-day follow-up.
Artesunate was a safe and clinically beneficial alternative to quinidine.
Office of the Surgeon General, Department of the U.S. Army.
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Twomey PS, Smith BL, McDermott C, Novitt-Moreno A, McCarthy W, Kachur SP, et al. Intravenous Artesunate for the Treatment of Severe and Complicated Malaria in the United States: Clinical Use Under an Investigational New Drug Protocol. Ann Intern Med. 2015;163:498-506. doi: 10.7326/M15-0910
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Published: Ann Intern Med. 2015;163(7):498-506.
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