A simplified intravenous artesunate regimen for severe malaria

A simplified intravenous artesunate regimen for severe malaria

Peter Gottfried Kremsner, Terrie Taylor, Saadou Issifou, Maryvonne Kombila, Yamikani Chimalizeni, Kondwana Kawaza, Marielle K. Bouyou Akotet, Mattias Duscha, Benjamin Mordmüller, Katrin Kösters, Alexander Humberg, R. Scott Miller, Peter Weina, Stephan Duparc, Jörg Möhrle, Jürgen F. J. Kun, Tim Planche, Paktiya Teja-Isavadharm, Julie Anne Simpson, Carsten Köhler and Sanjeev Krishna



We compared a conventional empirically derived regimen with a simplified regimen for parenteral artesunate in severe malaria.


This was a randomized, double-blind, placebo-controlled comparison to assess the noninferiority of a simplified 3-dose regimen (given at 0, 24, and 48 hours) compared with the conventional 5-dose regimen of intravenous artesunate (given at 0, 12, 24, 48, and 72 hours) in African children with Plasmodium falciparum malaria with a prespecified delta of 0.2. The total dose of artesunate in each group was 12 mg/kg. The primary end point was the proportion of children clearing ≥ 99% of their admission parasitemia at 24 hours. Safety data, secondary efficacy end points, and pharmacokinetics were also analyzed.


In 171 children (per protocol), 78% of the recipients (95% confidence interval [CI], 69%-87%) in the 3-dose group achieved ≥ 99% parasite clearance 24 hours after the start of treatment, compared with 85% (95% CI, 77%-93%) of those receiving the conventional regimen (treatment difference, -7.2%; 95% CI, -18.9% to 4.4%). Dihydroartemisinin was cleared slightly more slowly in those children receiving the higher 3-dose regimen (7.4 vs 8.8 L/h for a 13-kg child; P 5 .008).


Pharmacodynamic analysis suggests that 3 doses of artesunate were not inferior to 5 doses for the treatment of severe malaria in children.

View the full article on The Journal of Infectious Diseases website