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The Management of Patients with Severe Malaria

Severe malaria is a global problem, claiming at least 1 million lives annually. Few adequately powered clinical studies have been directed at improving the management of severe malaria over the years, but this situation is slowly changing. The antimalarial treatment of severe disease is being transformed by the development and deployment of the water-soluble artemisinin derivative artesunate. Parenteral artesunate is now the treatment of choice in low-transmission areas and in the 2nd and 3rd trimesters of pregnancy, and research is underway into whether it should replace quinine as the treatment of choice in African children. Development of good manufacturing practice (GMP) formulations should make parenteral artesunate more widely available in the near future. The development of artesunate suppositories offers another exciting prospect, the ability to treat patients with severe disease in remote rural settings, delaying the evolution of disease and buying them time to reach a health care facility. No adjunctive therapy has been shown to improve the outcome of severe malaria, but most studies have been underpowered. Future trials of interventions shown to be promising in pilot studies should be large and adequately powered. This will require multi-center designs and necessitate close collaboration between groups, as well as agreement on the research agenda. We suggest a list of candidate interventions for debate.

Received January 19, 2007. Accepted for publication October 1, 2007.

Acknowledgments: We thank Professor Nicholas White for helpful discussions.

^* Address correspondence to Nicholas Day, Wellcome Trust–Mahidol University–Oxford Tropical Medicine Programme, Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Road, Bangkok, 10400, Thailand. E-mail: nickd{at}tropmedres.ac

Authors’ addresses: Nicholas Day and Arjen M. Dondorp, Wellcome Trust–Mahidol University–Oxford Tropical Medicine Programme, Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Road, Bangkok, 10400, Thailand, Telephone: +66 2 3549172, Fax: +66 2 3549169 and Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, University of Oxford, Oxford, U.K, E-mail: nickd{at}tropmedres.ac.

N.D. and A.D. are funded by the Wellcome Trust.

¹ On June 21, 2007, the U.S. FDA approved an Investigational New Drug protocol that will allow the Centers for Disease Control and Prevention to make intravenous artesunate available to clinicians who request it for patients who have severe malaria.

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				J. G. Breman, M. S. Alilio, and N. J. White Defining and Defeating the Intolerable Burden of Malaria III. Progress and Perspectives Am J Trop Med Hyg, December 1, 2007; 77(6_Suppl): vi - xi. [Full Text] [PDF]