Artemisinin resistance-associated gene mutations in Plasmodium falciparum: A case study of severe malaria from Mozambique
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 glo...
Published in: | Travel Medicine and Infectious Disease |
---|---|
Main Authors: | , , , , , , , , , , |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
Elsevier
2024
|
Subjects: | |
Online Access: | https://doi.org/10.1016/j.tmaid.2023.102684 https://doaj.org/article/629d0bdfd2bf44d092a344d4175f3f0c |
id |
ftdoajarticles:oai:doaj.org/article:629d0bdfd2bf44d092a344d4175f3f0c |
---|---|
record_format |
openpolar |
spelling |
ftdoajarticles:oai:doaj.org/article:629d0bdfd2bf44d092a344d4175f3f0c 2024-02-11T10:01:38+01:00 Artemisinin resistance-associated gene mutations in Plasmodium falciparum: A case study of severe malaria from Mozambique Daniela Casanova Vitória Baptista Magda Costa Bruno Freitas Maria das Neves Imaculada Pereira Carla Calçada Paula Mota Olena Kythrich Maria Helena Jacinto Sarmento Pereira Nuno S. Osório Maria Isabel Veiga 2024-01-01T00:00:00Z https://doi.org/10.1016/j.tmaid.2023.102684 https://doaj.org/article/629d0bdfd2bf44d092a344d4175f3f0c EN eng Elsevier http://www.sciencedirect.com/science/article/pii/S1477893923001448 https://doaj.org/toc/1873-0442 1873-0442 doi:10.1016/j.tmaid.2023.102684 https://doaj.org/article/629d0bdfd2bf44d092a344d4175f3f0c Travel Medicine and Infectious Disease, Vol 57, Iss , Pp 102684- (2024) Imported malaria Molecular markers Resistance Artemisinin-based combination therapy Mozambique Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2024 ftdoajarticles https://doi.org/10.1016/j.tmaid.2023.102684 2024-01-21T01:35:56Z 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. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Travel Medicine and Infectious Disease 57 102684 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Imported malaria Molecular markers Resistance Artemisinin-based combination therapy Mozambique Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
spellingShingle |
Imported malaria Molecular markers Resistance Artemisinin-based combination therapy Mozambique Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Daniela Casanova Vitória Baptista Magda Costa Bruno Freitas Maria das Neves Imaculada Pereira Carla Calçada Paula Mota Olena Kythrich Maria Helena Jacinto Sarmento Pereira Nuno S. Osório Maria Isabel Veiga Artemisinin resistance-associated gene mutations in Plasmodium falciparum: A case study of severe malaria from Mozambique |
topic_facet |
Imported malaria Molecular markers Resistance Artemisinin-based combination therapy Mozambique Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
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. |
format |
Article in Journal/Newspaper |
author |
Daniela Casanova Vitória Baptista Magda Costa Bruno Freitas Maria das Neves Imaculada Pereira Carla Calçada Paula Mota Olena Kythrich Maria Helena Jacinto Sarmento Pereira Nuno S. Osório Maria Isabel Veiga |
author_facet |
Daniela Casanova Vitória Baptista Magda Costa Bruno Freitas Maria das Neves Imaculada Pereira Carla Calçada Paula Mota Olena Kythrich Maria Helena Jacinto Sarmento Pereira Nuno S. Osório Maria Isabel Veiga |
author_sort |
Daniela Casanova |
title |
Artemisinin resistance-associated gene mutations in Plasmodium falciparum: A case study of severe malaria from Mozambique |
title_short |
Artemisinin resistance-associated gene mutations in Plasmodium falciparum: A case study of severe malaria from Mozambique |
title_full |
Artemisinin resistance-associated gene mutations in Plasmodium falciparum: A case study of severe malaria from Mozambique |
title_fullStr |
Artemisinin resistance-associated gene mutations in Plasmodium falciparum: A case study of severe malaria from Mozambique |
title_full_unstemmed |
Artemisinin resistance-associated gene mutations in Plasmodium falciparum: A case study of severe malaria from Mozambique |
title_sort |
artemisinin resistance-associated gene mutations in plasmodium falciparum: a case study of severe malaria from mozambique |
publisher |
Elsevier |
publishDate |
2024 |
url |
https://doi.org/10.1016/j.tmaid.2023.102684 https://doaj.org/article/629d0bdfd2bf44d092a344d4175f3f0c |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Travel Medicine and Infectious Disease, Vol 57, Iss , Pp 102684- (2024) |
op_relation |
http://www.sciencedirect.com/science/article/pii/S1477893923001448 https://doaj.org/toc/1873-0442 1873-0442 doi:10.1016/j.tmaid.2023.102684 https://doaj.org/article/629d0bdfd2bf44d092a344d4175f3f0c |
op_doi |
https://doi.org/10.1016/j.tmaid.2023.102684 |
container_title |
Travel Medicine and Infectious Disease |
container_volume |
57 |
container_start_page |
102684 |
_version_ |
1790597435358183424 |