| Title: |
Prevalence and characterization of piperaquine, mefloquine and artemisinin derivatives triple-resistant Plasmodium falciparum in Cambodia |
| Authors: |
Mairet-Khedim, Mélissa; Roesch, Camille; Khim, Nimol; Srun, Sreynet; Bouillon, Anthony; Kim, Saorin; Ke, Sopheakvatey; Kauy, Chhayleang; Kloeung, Nimol; Eam, Rotha; Khean, Chanra; Kul, Chanvong; Chy, Sophy; Leang, Rithea; Ringwald, Pascal; Barale, Jean-Christophe; Witkowski, Benoit |
| Contributors: |
Microbiologie structurale - Structural Microbiology (Microb. Struc. (UMR_3528 / U-Pasteur_5)); Institut Pasteur Paris (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité); Malaria Translational Research Unit (MTRU); Institut Pasteur du Cambodge; Pasteur Network (Réseau International des Instituts Pasteur)-Pasteur Network (Réseau International des Instituts Pasteur)-Institut Pasteur Paris (IP)-Université Paris Cité (UPCité); Malaria Molecular Epidemiology (MMEU); Pasteur Network (Réseau International des Instituts Pasteur)-Pasteur Network (Réseau International des Instituts Pasteur); National Center for Malariology; Ministry of Health Phnom Penh; Organisation Mondiale de la Santé / World Health Organization Office Genève, Suisse (OMS / WHO); This study was funded by the Bill & Melinda Gates Foundation and Global Fund/UNOPS through WHO and by the Institut Pasteur Department of International Affairs. M.M.K. was supported by the 5% initiative (MIVS-ACT, grant #15SANIN211). |
| Source: |
ISSN: 0305-7453. |
| Publisher Information: |
CCSD; Oxford University Press (OUP) |
| Publication Year: |
2023 |
| Subject Terms: |
[SDV]Life Sciences [q-bio] |
| Description: |
International audience ; Background In early 2016, in Preah Vihear, Northern Cambodia, artesunate/mefloquine was used to cope with dihydroartemisinin/piperaquine-resistant Plasmodium falciparum parasites. Following this policy, P. falciparum strains harbouring molecular markers associated with artemisinin, piperaquine and mefloquine resistance have emerged. However, the lack of a viable alternative led Cambodia to adopt artesunate/mefloquine countrywide, raising concerns about a surge of triple-resistant P. falciparum strains. Objectives To assess the prevalence of triple-resistant parasites after artesunate/mefloquine implementation countrywide in Cambodia and to characterize their phenotype. Methods For this multicentric study, 846 samples were collected from 2016 to 2019. Genotyping of molecular markers associated with artemisinin, piperaquine and mefloquine resistance was coupled with phenotypic analyses. Results Only four triple-resistant P. falciparum isolates (0.47%) were identified during the study period. These parasites combined the pfk13 polymorphism with pfmdr1 amplification, pfpm2 amplification and/or pfcrt mutations. They showed significantly higher tolerance to artemisinin, piperaquine and mefloquine and also to the mefloquine and piperaquine combination. Conclusions The use of artesunate/mefloquine countrywide in Cambodia has not led to a massive increase of triple-resistant P. falciparum parasites. However, these parasites circulate in the population, and exhibit clear resistance to piperaquine, mefloquine and their combination in vitro. This study demonstrates that P. falciparum can adapt to more complex drug associations, which should be considered in future therapeutic designs. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/36508338; PUBMED: 36508338; PUBMEDCENTRAL: PMC9890270 |
| DOI: |
10.1093/jac/dkac403 |
| Availability: |
https://pasteur.hal.science/pasteur-04132691; https://pasteur.hal.science/pasteur-04132691v1/document; https://pasteur.hal.science/pasteur-04132691v1/file/dkac403.pdf; https://doi.org/10.1093/jac/dkac403 |
| Rights: |
http://creativecommons.org/licenses/by-nc/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.D561ECA2 |
| Database: |
BASE |