Recrudescence of Plasmodium falciparum malaria imported from Sub-Saharan Africa: a report of two cases and the first detection of artemisinin resistance in Italy

Background: Artemisinin-based combination therapy for Plasmodium falciparum malaria is threatened by the emergence of partial resistance. Methods: Molecular characterization of antimalarial resistance-associated genes Pfk13, Pfcrt, Pfmdr1, Pfdhfr, Pfdhps and PfCytB was performed on blood samples collected from two patients with recurrent episodes of Results: Two severe P. falciparum malaria in Italian travelers from sub-Saharan Africa showed recrudescence after standard treatment with intravenous artesunate and oral dihydroartemisinin-piperaquine. In one case, the validated marker R561H of artemisinin partial resistance was identified. In the second patient, no Pfkelch13 mutations were detected, and the recrudescent episode was probably the consequence of low blood drug concentration administered by nasogastric tube, although the possible role of Pfkelch13-independent pathways or reduced artemisinin susceptibility cannot be ruled out. Conclusion: The first imported case of artemisinin-resistant P. falciparum in Italy from sub-Saharan Africa underscores the need for continuous surveillance and eventually adapting treatment protocols.