Treatment of imported severe malaria with artesunate instead of quinine - more evidence needed?

Treatment of severe malaria requires prompt administration of safe and fast acting anti-malarials. While approximately 4% of all imported malaria cases progress to severe malaria, the overall mortality rate of imported Plasmodium falciparum malaria in Europe is 0,4% [1]. Until recently, quinine was the only option for parenteral therapy. Two large multinational randomized controlled unblinded trials (RCTs) have been conducted to compare intravenous quinine versus artesunate in malaria-endemic countries in Southeast Asia (SEAQUAMAT) and in sub-Saharan Africa (AQUAMAT) [2,3]. The evidence from these and some smaller trials supports the choice of artesunate over quinine in the treatment of severe malaria in endemic regions. But is this evidence sufficient to finally implement this anti-malarial in the treatment of imported severe malaria in non-endemic countries?First, is it of concern that none of the existing trials has been performed as a double blind comparative study? This appears to be less important with respect to effectiveness as the end-point of the two large studies was mortality. However, some limitations regarding outcomes such as adverse events or (neurologic) sequelae remain and from a regulatory perspective this may well be of concern.Second, can the existing evidence from endemic countries be generalized to imported severe malaria in industrialized, non-endemic, countries? Clinical manifestations, supportive intensive medical care and patient characteristics differ in endemic versus non-endemic countries. In particular, the following limitations have to be addressed: i) most evidence has been obtained from children while the great majority of patients with imported severe malaria are adults, ii) quinine monotherapy was used which does not completely reflect the often used combination of quinine with doxycycline or clindamycin in imported severe malaria, iii) the study population included a large variety of individuals from Southeast Asia, India and Afr