Treatment outcome of intravenous artesunate in patients with severe malaria in the Netherlands and Belgium

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.

Comparison of artesunate and quinine in the treatment of severe Plasmodium falciparum malaria at Kassala hospital, Sudan

“…Likewise, it has been observed previously that fever clearance time and parasite clearance time (16.0 and 22.4 hours, respectively) were shorter when intramuscular artemether was compared with quinine in the treatment of Sudanese children with severe P. falciparum malaria in eastern Sudan [10]. The mean parasite clearance time shown in this study was relatively shorter than the results (68 hours) obtained from other studies in Southeast Asia [14] and a parasite clearance time of 29.5 hours that was reported among non-immunized European travelers [15]. Interestingly, while Praygod et al, in their review of twelve trials (1,524 patients), found no significant difference in parasite clearance time or fever clearance time between one parenteral artemisinin derivative (artemether, β-arteether/artemotil, or artesunate) and quinine [16]; however, Sinalr et al observed the superiority of parenteral artesunate over quinine for the treatment of severe malaria in both adults and children and in different regions of the world in their recent review.…”

Postartesunate delayed hemolysis is a predictable event related to the lifesaving effect of artemisinins

“…1 Compared with quinine, AS further reduces mortality resulting from severe malaria by 22.5% to 35% 2,3 and induces fewer adverse cardiac events or hypoglycemic episodes. [2][3][4][5] However, delayed anemic episodes were recently reported in 20% to 25% of travelers with severe malaria treated with AS, [6][7][8][9][10][11][12] a high, and possibly overestimated, proportion. All of these patients survived, but 60% of them required transfusions.…”

“…All of these patients survived, but 60% of them required transfusions. [6][7][8][9][10][11][12] Hence, although it does not jeopardize the lifesaving effect of AS, post-AS anemia does complicate patient management. Furthermore, being currently unpredictable, this delayed post-AS hemolysis and anemia require close monitoring for all patients with severe malaria treated with AS, although it will occur in only 20% to 25% of them.…”

“…Most episodes have included a marked extravascular hemolysis component with high lactate dehydrogenase (LDH) and low plasma haptoglobin. [6][7][8][9][10][11][12] Conversely, intense, acute intravascular hemolysis (as in blackwater fever) has been equally infrequent in quinine-and in AStreated patients. 2,3 The search for conventional causes or markers of immune-mediated or drug-induced hemolytic anemia, such as glucose-6-phosphate dehydrogenase deficiency or the direct antiglobulin test, has been generally inconclusive so far.…”

“…2,3 The search for conventional causes or markers of immune-mediated or drug-induced hemolytic anemia, such as glucose-6-phosphate dehydrogenase deficiency or the direct antiglobulin test, has been generally inconclusive so far. 6,9,12 Post-AS delayed hemolysis (PADH) has attracted attention because it often occurs well after resolution of malaria-related symptoms and at least several days after complete parasite clearance. 6 Erythrocyte loss during post-AS hemolysis is therefore not directly related to active infection or to the presence of parasites.…”