ACT is a very effective and safe treatment in the management of imported uncomplicated malaria. Besides producing more rapid parasite clearance, its use in patients admitted with uncomplicated malaria reduces the period of hospitalization compared to classic treatments that were used previously, resulting in healthcare savings.
The management of imported malaria is still a challenge for many healthcare professionals in non-endemic zones. P. falciparum is the species most frequently involved, and also the one which most results in morbidity and/or mortality in travellers (tourists and expatriates), as well as in foreigners who return home to visit friends and family [3–5]. The use of artemisinin derivatives has been spreading, various articles have been published showing the superior results of these drugs compared to other treatments; indeed, their use has been recommended as a first-line drug in the main national and international guidelines [18–20]. Quinine is now relegated to a second-line treatment for cases where contraindications exist, or because of the unavailability of ACT or atovaquone–proguanil; likewise in complicated malaria treatment given within the first trimester of pregnancy due to the possibility of teratogenicity [7, 18–20].
Most studies concerning imported malaria have been carried out on patients with complicated malaria [11, 12] with artesunate being the most-commonly used drug for intravenous treatment. Besides producing faster parasite clearance and ending fever, it has a better safety profile (posing predominantly less risk of severe hypoglycaemia), shortens hospitalization and has recently been shown to reduce the length of time in ICU, above all in patients with more elevated parasitaemia . No reduction in mortality has been demonstrated given the few patients who died in the studies thus making such analysis impossible, although with the solid evidence obtained in endemic regions, it would be unethical to carry out clinical trials with this objective in mind.
In the case of uncomplicated malaria caused by P. falciparum, the general recommendation is hospital admittance and oral treatment for at least 24–48 h , with the aim of observing the clinical evolution and tolerance to the drugs. Very few studies have been carried out with ACT in non-endemic zones. Hatz et al.  concluded that treatment with artemether–lumefantrine is safe and efficacious in those patients. A prospective observational multicentre study (MALTHER) compared the various treatment regimens for imported uncomplicated malaria in Europe . There were a total of 18 different regimens although the most used were atovaquone–proguanil, quinine and artemether–lumefantrine. Compared to other regimens, quinine was associated with the highest non-completion rate, more secondary effects and the most days of hospitalization. In contrast, the artemether–mefloquine combination was linked to the fastest parasite clearance and cessation of fever. Regarding the period of hospitalization, the use of quinine was associated with longer hospital stays. In this study, unlike the MALTHER study, dihydroartemisinin–piperaquine was used as the ACT, the only drug of its type commercially available in Spain and presumably the main drug used in the majority of Spanish hospitals; this combination has also been demonstrated to be efficacious and safe both in endemic countries as well as in Europe [16, 22]. In addition, as belonging to just one centre, the two groups of patients compared were much more homogenous thus avoiding, to a large extent, any bias derived from variations in clinical practice between healthcare sites or in different countries.
The overall average hospital stay for patients in our study was 2.88 days. The fact that most of the patients are immigrants has probably contributed to a slightly longer stay to that recommended. The language barrier that exists with many of these patients, as well as the problems concerning frequent follow-up visits to the healthcare centres, often for economic or work-related reasons, means that it is common their doctors feel more comfortable keeping them admitted to hospital until they are sure of good treatment tolerance and response. The rapid parasite clearance and the markedly shorter treatment regimen using ACT are probably the factors that most influence the length of stay.
Atovaquone–proguanil is another medication recommended as a first-line treatment for uncomplicated malaria from P. falciparum [18–20]; however, the parasite clearance rate is longer than with ACT and the adverse effects, above all gastrointestinal, are similarly more frequent . Furthermore, ACT has a very good profile in relation to possible Plasmodium resistance.
With regard to possible adverse reactions, the compounds derived from artemisinin have shown good tolerance and have a good safety profile [23, 24]. The most frequent adverse effects are: Type 1 hypersensitivity at the cutaneous level; a long QTc interval in the ECG; and, at the gastrointestinal level, nausea, vomiting and diarrhoea, although often this can be clinically confused with the malaria itself . Cases have also been described of raised transaminase levels or hepatitis. This was only observed in one patient; and although there were no important consequences and the condition ceased after only a few days, it did result in more days spent in hospital.
The most severe adverse effect of artemisinin derivatives however is delayed haemolytic anaemia [25–28]. This is produced by the “pitting” mechanism, in which the parasitized erythrocytes, after being cleared of parasites by the spleen, are resealed and returned to the blood stream, but with a reduced lifespan of 1–3 weeks . This lysis process occurs on average 2 weeks after the drug is administered, and in some cases can require a blood transfusion. Although this has mainly been seen in patients with complicated malaria (with elevated parasitaemia) treated with artesunate, it has also been described in patients treated with intramuscular artemether and oral artemether–lumefantrine . As far as it is known, no case has been reported in relation to dihydroartemisinin–piperaquine. In this study, the Hb levels were higher even in the group treated with ACT at 7 and 28 days. This is probably because in patients with uncomplicated malaria, delayed haemolysis is the exception; in fact, the more rapidly the parasitaemia disappears and the ACT-treated patients recover, the more rapid the accompanying recovery of the basal hemoglobin levels as well.
With regard to pregnancy, there is insufficient information about the safety and efficacy of many anti-malarials, especially in the first trimester. Consequently, the only drugs considered safe are quinine, chloroquine, clindamycin and proguanil. Artemisinin-derived drugs are safe and efficacious in the second and third trimesters, in that they have been demonstrated not to be teratogenic [29, 30].
The limitations present in this study come from the fact that it is a retrospective work.
Furthermore, given the characteristics of the population that is the object of the study, the results may only be strictly extrapolated to African immigrants treated with two treatment regimens, one which has already passed to second-line use (quinine sulfate–doxycycline) and the other, an ACT (dihydroartemisinin–piperaquine), which is a first-line treatment. New prospective studies will need to be carried out to evaluate if any differences exist in terms of safety, efficacy and healthcare costs between the ACT-based treatments and, for example, atovaquone–proguanil, which is also a fixed combination over the same period (3 days in total). Moreover, with atovaquone–proguanil, ample experience has been gathered in non-endemic regions and it has a proven safety record.