Abstract

BackgroundIntravenous (IV) artesunate is the treatment of choice for severe malaria. In Europe, however, no GMP-manufactured product is available and treatment data in European travellers are scarce. Fortunately, artesunate became available in the Netherlands and Belgium through a named patient programme. This is the largest case series of artesunate treated patients with severe malaria in Europe.MethodsHospitalized patients treated with IV artesunate between November 2007 and December 2010 in the Netherlands and Belgium were retrospectively evaluated. Patient characteristics, treatment and clinical outcome were recorded on a standardized form and mortality, parasite clearance times and the occurrence of adverse events were evaluated.ResultsOf the 68 treated patients, including 55 with severe malaria, two patients died (2/55 = 3.6%). The mean time to 50% parasite clearance (PCT50), 90% and 99% were 4.4 hours (3.9 - 5.2), 14.8 hours (13.0 - 17.2), and 29.5 hours (25.9 - 34.4) respectively. Artesunate was well tolerated. However, an unusual form of haemolytic anaemia was observed in seven patients. The relationship with artesunate remains uncertain.ConclusionsData from the named patient programme demonstrate that IV artesunate is effective and well-tolerated in European travellers lacking immunity. However, increased attention needs to be paid to the possible development of haemolytic anaemia 2-3 weeks after start of treatment.Treatment of IV artesunate should be limited to the period that IV treatment is required and should be followed by a full oral course of an appropriate anti-malarial drug.

Highlights

  • Intravenous (IV) artesunate is the treatment of choice for severe malaria

  • Parasite clearance time (PCT)50%, PCT90%, and PCT99% were defined as the time to obtain a 50%, 90%, and 99% reduction in parasite burden after start of artesunate treatment

  • One patient died of an iatrogenic complication (IV catheter related haemorrhage) 4 days after complete parasite clearance; the other succumbed to a suspected lung embolism 8 days after parasite clearance (Table 4). 42 (62%) patients were admitted to the ICU with a median ICU stay of 2 days

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Summary

Introduction

Intravenous (IV) artesunate is the treatment of choice for severe malaria. In Europe, no GMP-manufactured product is available and treatment data in European travellers are scarce. Artesunate became available in the Netherlands and Belgium through a named patient programme. This is the largest case series of artesunate treated patients with severe malaria in Europe. Intravenous (IV) quinine or a mixture of four cinchona alkaloids (Quinimax)® were, for many years, the only available drugs in Europe for the treatment of imported severe malaria. In the US, where quinine is not available, quinidine was used for this indication. Semi-synthetic derivatives of artemisinin were developed with even higher intrinsic activity than the parent compound. The water-soluble sodium artesunate was developed for IV administration

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