Failure of artemether-lumefantrine therapy in travellers returning to Belgium with Plasmodium falciparum malaria: an observational case series with genomic analysis.

Autor:	Pierreux J; Infectious Diseases Department, Saint-Pierre University Hospital, Université Libre de Bruxelles, Brussels 1000, Belgium., Bottieau E; Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp 2000, Belgium., Florence E; Department of General Internal Medicine and Infectious Diseases, University Hospital of Antwerp, Antwerp 2000, Belgium., Maniewski U; Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp 2000, Belgium., Bruggemans A; Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp 2000, Belgium., Malotaux J; Department of General Internal Medicine and Infectious Diseases, Ghent University Hospital, Ghent 9000, Belgium., Martin C; Infectious Diseases Department, Saint-Pierre University Hospital, Université Libre de Bruxelles, Brussels 1000, Belgium., Cox J; Department of Infectious Diseases and Immunity, Jessa Hospital, Hasselt 3500, Belgium.; Faculty of Medicine and Life Sciences, University of Hasselt, Hasselt 3500, Belgium., Konopnicki D; Infectious Diseases Department, Saint-Pierre University Hospital, Université Libre de Bruxelles, Brussels 1000, Belgium., Guetens P; Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp 2000, Belgium., Verschueren J; Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp 2000, Belgium., Coppens J; Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp 2000, Belgium., Van Esbroeck M; Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp 2000, Belgium., Mutsaers M; Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp 2000, Belgium., Rosanas-Urgell A; Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp 2000, Belgium.
Jazyk:	angličtina
Zdroj:	Journal of travel medicine [J Travel Med] 2024 Apr 06; Vol. 31 (3).
DOI:	10.1093/jtm/taad165
Abstrakt:	Background: Failure of artemisinin-based combination therapy is increasingly reported in patients with Plasmodium falciparum malaria in sub-Saharan Africa. We aimed to describe the clinical and genomic characteristics of recent cases of P. falciparum malaria failing artemether-lumefantrine in Belgium. Methods: Travel-related cases of malaria confirmed at the national reference laboratory of the Institute of Tropical Medicine, Antwerp, Belgium, were reviewed. All cases for which attending clinicians reported persistence (beyond Day 3 post-treatment initiation, i.e. early failure) or recrudescence (from Day 7 to 42, i.e. late failure) of P. falciparum parasites despite adequate drug intake were analysed. Both initial and persistent/recurrent samples were submitted to next generation sequencing to investigate resistance-conferring mutations. Results: From July 2022 to June 2023, eight P. falciparum cases of failure with artemether-lumefantrine therapy were reported (early failure = 1; late failure = 7). All travellers were returning from sub-Saharan Africa, most (6/8) after a trip to visit friends and relatives. PfKelch13 (PF3D7_1343700) mutations associated with resistance to artemisinin were found in two travellers returning from East Africa, including the validated marker R561H in the patient with early failure and the candidate marker A675V in a patient with late failure. Additional mutations were detected that could contribute to decreased susceptibility to artemisinin in another three cases, lumefantrine in six cases and proguanil in all eight participants. Various regimens were used to treat the persistent/recrudescent cases, with favourable outcome. Conclusion: Within a 12-month period, we investigated eight travellers returning from sub-Saharan Africa with P. falciparum malaria and in whom artemether-lumefantrine failure was documented. Mutations conferring resistance to antimalarials were found in all analysed blood samples, especially against lumefantrine and proguanil, but also artemisinin. There is a pressing need for systematic genomic surveillance of resistance to antimalarials in international travellers with P. falciparum malaria, especially those experiencing treatment failure. (© International Society of Travel Medicine 2023. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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