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Simplified artesunate regimen is non-inferior to WHO-recommended malaria treatment


In African children, a 3-dose intramuscular (i.m.) artesunate regimen is non-inferior to the WHO-recommended regimen for the treatment of severe malaria, according to a trial published this week in PLOS Medicine. The trial, conducted by Peter Kremsner at Eberhard Karls Universität Tübingen, Tübingen, Germany and Hôpital Albert Schweitzer, Lambaréné, Gabon, and colleagues, did not show non-inferiority of a similar 3-dose intravenous (i.v.) regimen.

WHO recommends that patients with severe malaria be given a 5-dose i.m. or i.v. regimen of artesunate at the time of admission (0 hours) and at 12, 24, 48, and 72 hours. In resource-limited settings, administering five doses on schedule can be challenging. In this open-label, non-inferiority randomized controlled trial, the researchers investigated the efficacy of three-dose i.m. and i.v. artesunate at 0, 24, and 48 hours. Among the 1,002 children who received per-protocol regimens, 78% in the three-dose i.m. group had ?99% parasite clearance at 24 hours compared to 79% in the five-dose i.m. group, a result that met a preset criterion for non-inferiority. The three-dose i.v. regimen did not meet the non-inferiority criterion. Combined with the results of several secondary analyses, these findings provide evidence that a three-dose i.m. artesunate regimen may be used for treatment of severe malaria in African children.

The study's open-label design may limit the accuracy of its findings. Due to practical constraints, the primary endpoint was parasite clearance at 24 hours rather than survival. Further studies are needed to clarify whether treatment with artesunate or the malaria infection itself was responsible for the delayed anemia observed in 22% of participants. The authors state, "Simplifying [artesunate] usage with a once daily i.m. regimen in severe malaria is supported by our results, but because delayed anemia is common, patients should be monitored for this complication."


Trial registration: PACTR201102000277177

Research Article


The study was funded by (; CT.2004.31070.001) and Federal Ministry of Education and Research (BMBF grant 01KA1011). Additional support was received by Central African Network on Tuberculosis, HIV/AIDS and Malaria; CANTAM, German Center for Infection Research (DZIF), Deutsche Forschungsgemeinschaft (DFG; http://www.dfg.degrant; KE 1629/1-1) and Robert Bosch Stiftung (Stuttgart, Germany). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests:

GK, BM, CK, SB, and TE report grants from European and Developing Countries Clinical Trials Partnership and Bundesministerium für Building und Forschung Deutschland for the conduct of the study. SK reports grants from European and Developing Countries Clinical Trials Partnership for the conduct of the study, personal fees from Merck Serono and shareholder at QuantuMDx. AAA, JFZ, ABH, TET, YC, AL, MK, MKBA, DPMM, TA, DA, JS, BRO, GAO, AW, KAB, UO, FSI, CRN, PN, MK, and SI report grant from European and Developing Countries Clinical Trials Partnership for the conduct of the study. MS, MG, and RK report grants from DFG and Robert Bosch Stiftung for the conduct of the study. TPV and CN report grant from Deutsche Forschungsgemieinschaft for the conduct of the study. SK is a member of the Editorial Board of PLOS Medicine.


Kremsner PG, Adegnika AA, Hounkpatin AB, Zinsou JF, Taylor TE, Chimalizeni Y, et al. (2016) Intramuscular Artesunate for Severe Malaria in African Children: A Multicenter Randomized Controlled Trial. PLoS Med 13(1): e1001938. doi:10.1371/journal.pmed.1001938

Author Affiliations:

Institut für Tropenmedizin, Eberhard Karls Universität Tübingen, Tübingen, Germany

Centre de Recherches Médicales de Lambaréné, Hôpital Albert Schweitzer, Lambaréné, Gabon

Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi

Department of Parasitology Mycology, Faculty of Medicine, Université des Sciences de la Santé, Libreville, Gabon

Department of Physiology, University of Science and Technology, School of Medical Sciences, Kumasi, Ghana

Departments of Child Health and Medicine, Komfo Anokye Teaching Hospital, Kumasi, Ghana

Centre for Clinical Research, Kenya Medical Research Institute, Kisumu, Kenya

Medical Research Council Laboratories, Fajara, The Gambia

Centre for Geographic Medicine Research-Coast, Kenya Medical Research Institute, Kilifi, Kenya

Dr. Margarete Fischer-Bosch-Institut für Klinische Pharmakologie, Stuttgart, Germany

Eberhard Karls Universität Tübingen, Tübingen, Germany

Abteilung Klinische Pharmakologie, Universitätsklinikum Tübingen, Tübingen, Germany

Institute for Infection and Immunity, St George's, University of London, London, United Kingdom



Professor Sanjeev Krishna
St. George's, University of London
Institute of Infection and Immunity
Cranmer Terrace
London, London SW17 ORE
+44 (020) 8725 5836
Twitter: @ProfSKrishna

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