The results of this retrospective follow-up study indicate that parasite clearance is more rapid for adult travellers with severe falciparum malaria when they are treated with artesunate than with quinine. Manual exchange transfusion does not significantly contribute to parasite clearance. These conclusions were drawn irrespective of the analysis method used to estimate parasite clearance. The parasite clearance times associated with artesunate and quinine found in the present study in largely non-immune travellers are compatible with those found in field trials in endemic regions . Currently, there is no evidence for artesunate resistance in returning travellers, which may be due that the majority of P. falciparum infections was acquired in Africa where artesunate resistance has not been described yet  opposed to emerging artesunate resistance in South East Asia .
Since its introduction in 1974 , ET has remained a controversial adjunct therapy for the treatment of severe malaria. Exchange transfusion has successfully been used as an adjunct therapy in malaria patients for rapid reduction of parasite burden in patients with hyperparasitaemia, improvement of the rheological characteristics of blood and removal of toxic byproducts. On the other hand, its efficacy has never been properly demonstrated in a sufficiently powered randomized controlled trial. In a meta-analysis comparing severe malaria patients who received either adjunct ET or anti-malarial chemotherapy alone, no difference in survival rates was found, although patients who received exchange transfusion were more critically ill and had significantly higher parasitaemia levels . Furthermore, ET may come with significant health risks such as fluid overload, hypotension, cerebral hemorrhage, febrile and allergic reactions, metabolic disturbances and transmissible infections . However, with the use of a standardized but foremost isovolumetric manual exchange protocol these adverse events were rarely observed .
It should be noted that the parasite clearance times may completely differ for exchange procedures using automated erythrocytapheresis. Whereas in a manual ET procedure approximately half of the blood volume is exchanged in 5 hours with an anticipated 40% reduction of parasite load in case of an isovolumetric exchange , an entire blood volume can be exchanged in 1.5 hours with automated erythrocytapheresis . In addition, automated erythrocytapheresis may have further advantages over manual exchange procedures in terms haemodynamic stability, preservation of plasma and cellular components, efficiency and speed. However, it would only be easily available in specialized centers. In contrast, manual exchange procedures can be executed without delay once a diagnosis of severe disease has been made, even in hospitals without direct access to automated RBC exchange.
Irrespective of the exchange procedure applied, exchanging blood only removes circulating parasite stages from the circulation; a large proportion of parasitized RBCs may not be exchanged as long as they remain sequestered in the microvasculature of vital organs. In addition, exchange procedures may have additional advantages over automated RBC exchange by removing the burden of toxins and other products arising from the parasite and host response. This may explain the beneficial effect of plasma exchange in severe malaria observed in some reports . Moreover, and probably underestimated, as compared to healthy subjects, parasitized RBCs but also uninfected RBCs are considerably less deformable in severe malaria . Replacing less deformable RBCs by fresh RBC is a biologically plausible explanation for potential beneficial effects of exchange transfusion. Although there is currently no consensus in treatment protocol in terms of indication and volume to be exchanged, exchange transfusion was usually initiated in patients with hyperparasitaemia (either >30% or > 10% in the presence of other severe complications). Since the rapid reduction of parasite burden is mostly attributable to anti-malarial treatment, in particular artesunate, ET should not be installed for reasons of aiding in parasite clearance, at least not with manual exchange transfusion procedures.
This study is based on a single-centre experience with standardized procedure and well-equipped intensive care facilities. It has the advantage of standardized and uniform procedures but the disadvantage of a relatively small sample size. The treatment protocol reserves ET for the most severely ill patients with hyperparasitaemia and/or organ damage and this may have led to selection bias with diminishing effect modification. However, within the treatments groups subjected to ET (groups III and IV), there were no differences at baseline between artesunate and quinine treated patients and this suggest that a proper comparison is allowed. A prospective comparative trial in industrialized non-endemic countries is deemed not feasible because the number of eligible patients suffering from severe imported P. falciparum malaria is small, and to obtain a meaningful outcome, even in a multicentre-based study, it would require many years. It is not expected that high-level of evidence will become available soon. Since this study focused on parasite clearance alone, no conclusions can be drawn on other proposed beneficial mechanisms of exchange transfusion like removal of parasite toxins and improvement of haemorrheology.