Artesunate for Malaria in Travelers, Europe | CDC EID

EID Journal Home > Volume 17, Number 5–May 2011

Volume 17, Number 5–May 2011
Synopsis
Intravenous Artesunate for Severe Malaria in Travelers, Europe
Thomas Zoller, Thomas Junghanss, Annette Kapaun, Ida Gjørup, Joachim Richter, Mats Hugo-Persson, Kristine Mørch, Behruz Foroutan, Norbert Suttorp, Salih Yürek, and Holger Flick

Author affiliations: Charité Universitätsmedizin, Berlin, Germany (T. Zoller, N. Suttorp, S. Yürek, H. Flick); Universitätsklinikum Heidelberg, Heidelberg, Germany (T. Junghanss, A. Kapaun); The State University Hospital, Copenhagen, Denmark (I. Gjørup); Universitätsklinikum Düsseldorf, Düsseldorf, Germany (J. Richter); Hospital of Helsingborg, Helsingborg, Sweden (M. Hugo-Persson); Haukeland University Hospital, Bergen, Norway (K. Mørch);

Suggested citation for this article


Abstract
Multicenter trials in Southeast Asia have shown better survival rates among patients with severe malaria, particularly those with high parasitemia levels, treated with intravenous (IV) artesunate than among those treated with quinine. In Europe, quinine is still the primary treatment for severe malaria. We conducted a retrospective analysis for 25 travelers with severe malaria who returned from malaria-endemic regions and were treated at 7 centers in Europe. All patients survived. Treatment with IV artesunate rapidly reduced parasitemia levels. In 6 patients at 5 treatment centers, a self-limiting episode of unexplained hemolysis occurred after reduction of parasitemia levels. Five patients required a blood transfusion. Patients with posttreatment hemolysis had received higher doses of IV artesunate than patients without hemolysis. IV artesunate was an effective alternative to quinine for treatment of malaria patients in Europe. Patients should be monitored for signs of hemolysis, especially after parasitologic cure.


Infection with Plasmodium falciparum malaria remains a major risk for European travelers returning from malaria-endemic areas. World Health Organization (WHO) guidelines recommend intravenous (IV) artesunate as first-line therapy for severe malaria (1). However, quinine is still the primary treatment for severe non–multidrug-resistant P. falciparum malaria in Europe (2) because IV artesunate is not registered for this indication, and the only commercially available product is not manufactured according to good manufacturing practice. Quinine has several adverse effects (e.g., cardiotoxicity, hypotension, hypoglycemia, and cinchonism), has a narrow therapeutic range, and must be administered 3×/d by rate-controlled infusion (3,4). In experienced hands, adverse effects can be minimized, but a major proportion of patients still experience moderate-to-severe side effects.

The efficacy and safety of artemisinins and their derivatives in oral, rectal, and intramuscular dosage forms have been widely studied (5–11). When administered intravenously, these drugs are useful for treatment of severe malaria because of their rapid parasite clearance, apparent absence of clinically relevant side effects, and simplicity of administration (e.g., by bolus injection). Since 1992, several studies in Asia (5,6,8–10) and a recent study of children in Africa (11) have shown better, or at least equivalent, survival rates for patients with severe malaria treated with artesunate than for those treated with quinine. This finding applies particularly to patients with severe malaria and hyperparasitemia (10).

Systematic data are not available for safety and efficacy of IV artesunate for treatment of severe P. falciparum malaria outside disease-endemic areas. In the United States, use of IV artesunate is monitored by the Centers for Disease Control and Prevention (Atlanta, GA, USA) under an investigational new drug protocol (12). In Europe, artesunate manufactured by the Guilin Pharmaceutical Factory No. 2 (Shanghai, People's Republic of China), which was used in all major trials of artesunate in Southeast Aia and Africa (9–11), is used. TropNetEurop (www.tropnet.net/about/contents/about_tropnet.htmla), a European surveillance network for tropical diseases, has been collecting data on artesunate use since 2005 (13).

Severe malaria is rare outside disease-endemic regions. Thus, the limited numbers of patients in industrialized countries makes it difficult to conduct trials with sufficient statistical power to reproduce the survival benefit for IV artesunate observed in Southeast Asia (10). Nonetheless, these patients may benefit from the lower cardiotoxicity of artesunate than that of quinine and, because of more rapid parasite clearance, from reduction of time spent in intensive care units, in-hospital treatment, decreased use of exchange transfusion, and secondary complications. This finding is relevant for increased numbers of older persons who travel abroad to malaria-endemic areas, despite relevant cardiac or other medical conditions associated with a several-fold increased risk for complications and death caused by severe malaria (14). We report data for 25 patients with severe malaria who were treated with IV artesunate in 7 treatment centers in areas to which malaria was not endemic.

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Artesunate for Malaria in Travelers, Europe | CDC EID


Suggested Citation for this Article
Zoller T, Junghanss T, Kapaun A, Gjørup I, Richter J, Hugo-Persson M, et al. Intravenous artesunate for severe malaria in travelers, Europe. Emerg Infect Dis [serial on the Internet]. 2011 May [date cited].
http://www.cdc.gov/EID/content/17/5/771.htm


DOI: 10.3201/eid1705.101229


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Thomas Zoller, Medizinische Klinik mit Schwerpunkt Infektiologie und Pneumologie, Augustenburger Platz 1, 13353 Berlin, Germany; email: thomas.zoller@charite.de