Impact of the first-line treatment shift from dihydroartemisinin/piperaquine to artesunate/mefloquine on Plasmodium vivax drug susceptibility in Cambodia

Autor: Saorin Kim, Jean Popovici, Camille Roesch, Dysoley Lek, Benoit Witkowski, Melissa Mairet-Khedim
Přispěvatelé: Malaria Molecular Epidemiology (MMEU), Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Malaria Translational Research Unit (MTRU), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut Pasteur [Paris] (IP), National Center for Parasitology, Entomology and Malaria Control [Phnom Penh, Cambodia] (CNM), This study was supported by internal funding. J.P. is partly supported by the International Centers of Excellence for Malaria Research program from the National Institutes of Health, grant 1U19AI129392-0., Malaria Molecular Epidemiology, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut Pasteur [Paris]
Rok vydání: 2020
Předmět:
0301 basic medicine
medicine.medical_treatment
Plasmodium vivax
Drug Resistance
Protozoan Proteins
Artesunate
Drug resistance
0302 clinical medicine
Dihydroartemisinin/piperaquine
Chloroquine
Pharmacology (medical)
MESH: Protozoan Proteins
MESH: Plasmodium falciparum
Original Research
biology
Mefloquine
Artemisinins
MESH: Plasmodium vivax
3. Good health
Infectious Diseases
Pharmaceutical Preparations
Quinolines
MESH: Drug Resistance
MESH: DNA Copy Number Variations
Cambodia
MESH: Mefloquine
MESH: Quinolines
medicine.drug
Microbiology (medical)
DNA Copy Number Variations
MESH: Pharmaceutical Preparations
Plasmodium falciparum
030231 tropical medicine
Dihydroartemisinin
Antimalarials
03 medical and health sciences
Piperaquine
MESH: Artemisinins
parasitic diseases
Malaria
Vivax
medicine
Humans
[SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology
Pharmacology
MESH: Humans
MESH: Cambodia
MESH: Malaria
Vivax
MESH: Artesunate
biology.organism_classification
MESH: Antimalarials
Virology
030104 developmental biology
Zdroj: Journal of Antimicrobial Chemotherapy
Journal of Antimicrobial Chemotherapy, 2020, 75 (7), pp.1766-1771. ⟨10.1093/jac/dkaa092⟩
Journal of Antimicrobial Chemotherapy, Oxford University Press (OUP), 2020, 75 (7), pp.1766-1771. ⟨10.1093/jac/dkaa092⟩
ISSN: 1460-2091
0305-7453
Popis: Background Cambodia is the epicentre of the emergence of Plasmodium falciparum drug resistance. Much less is known regarding the drug susceptibility of the co-endemic Plasmodium vivax. Only in vitro drug assays can determine the parasite’s intrinsic susceptibility, but these are challenging to implement for P. vivax and rarely performed. Objectives To evaluate the evolution of Cambodian P. vivax susceptibility to antimalarial drugs and determine their association with putative markers of drug resistance. Methods In vitro response to three drugs used in the past decade in Cambodia was measured for 52 clinical isolates from Eastern Cambodia collected between 2015 and 2018 and the sequence and copy number variation of their pvmdr1 and pvcrt genes were analysed. pvmdr1 polymorphism was also determined for an additional 250 isolates collected in Eastern Cambodia between 2014 and 2019. Results Among the 52 cryopreserved isolates tested, all were susceptible to the three drugs, with overall median IC50s of 16.1 nM (IQR 11.4–22.3) chloroquine, 3.4 nM (IQR 2.1–5.0) mefloquine and 4.6 nM (IQR 2.7–7.0) piperaquine. A significant increase in chloroquine and piperaquine susceptibility was observed between 2015 and 2018, unrelated to polymorphisms in pvcrt and pvmdr1. Susceptibility to mefloquine was significantly lower in parasites with a single mutation in pvmdr1 compared with isolates with multiple mutations. The proportion of parasites with this single mutation genotype increased between 2014 and 2019. Conclusions P. vivax with decreased susceptibility to mefloquine is associated with the introduction of mefloquine-based treatment during 2017–18.
Databáze: OpenAIRE
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