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  3. Artemisinin resistance-associated gene mutations in Plasmodium falciparum: A case study of severe malaria from Mozambique

Artemisinin resistance-associated gene mutations in Plasmodium falciparum: A case study of severe malaria from Mozambique

  • Travel Med Infect Dis. 2023 Dec 29:57:102684. doi: 10.1016/j.tmaid.2023.102684.
Daniela Casanova 1,  Vitória Baptista 2,  Magda Costa 1,  Bruno Freitas 3,  Maria das Neves Imaculada Pereira 3,  Carla Calçada 3,  Paula Mota 4,  Olena Kythrich 4,  Maria Helena Jacinto Sarmento Pereira 1,  Nuno S Osório 3,  Maria Isabel Veiga 5
Affiliations

Affiliations

  • 1 Internal Medicine Department, Hospital Senhora da Oliveira, 4835-044, Guimarães, Portugal.
  • 2 Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar, 4710-057, Braga, Portugal; ICVS/3B's─PT Government Associate Laboratory, 4806-909, Guimarães/ Braga, Portugal; Microelectromechanical Systems Research Unit (CMEMS-UMinho), School of Engineering, University of Minho, Campus de Azurém, 4800-058, Guimarães, Portugal.
  • 3 Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar, 4710-057, Braga, Portugal; ICVS/3B's─PT Government Associate Laboratory, 4806-909, Guimarães/ Braga, Portugal.
  • 4 Clinical Pathology Department, Hospital Senhora da Oliveira, 4835-044, Guimarães, Portugal.
  • 5 Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar, 4710-057, Braga, Portugal; ICVS/3B's─PT Government Associate Laboratory, 4806-909, Guimarães/ Braga, Portugal; Clinical Academic Center-Braga (2CA-Braga), 4710-243, Braga, Portugal. Electronic address: [email protected].
PMID: 38159875 DOI: 10.1016/j.tmaid.2023.102684
Abstract

Background: The effectiveness of artemisinin-based combination therapies (ACT) in treating Plasmodium falciparum, is vital for global malaria control efforts, particularly in sub-Saharan Africa. The examination of imported cases from endemic areas holds implications for malaria chemotherapy on a global scale.

Method: A 45-year-old male presented with high fever, dry cough, diarrhoea and generalized muscle pain, following a two-week trip to Mozambique. P. falciparum Infection with hiperparasitemia was confirmed and the patient was treated initially with quinine and doxycycline, then intravenous artesunate. To assess drug susceptibility, ex vivo half-maximal inhibitory concentration assays were conducted, and the isolated P. falciparum genome was deep sequenced.

Results: The clinical isolate exhibited elevated ex vivo half-maximal inhibitory concentration values to dihydroartemisinin, lumefantrine, mefloquine and piperaquine. Genomic analysis identified a I416V mutation in the P. falciparum Kelch13 (PF3D7_1343700) gene, and several mutations at the Kelch13 interaction candidate genes, pfkics (PF3D7_0813000, PF3D7_1138700, PF3D7_1246300), including the ubiquitin carboxyl-terminal hydrolase 1, pfubp1 (PF3D7_0104300). Mutations at the drug transporters and genes linked to next-generation antimalarial drug resistance were also present.

Conclusions: This case highlights the emergence of P. falciparum strains carrying mutations in artemisinin resistance-associated genes in Mozambique, couple with a reduction in ex vivo susceptibility to ACT drugs. Continuous surveillance of mutations linked to drug resistance and regular monitoring of drug susceptibility are imperative to anticipate the spread of potential resistant strains emerging in Mozambique and to maintain effective malaria control strategies.

Keywords

Artemisinin-based combination therapy; Imported malaria; Molecular markers; Mozambique; Resistance.

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