Plasmodium vivax multidrug resistance-1 gene polymorphism in French Guiana.
BACKGROUND
Plasmodium vivax malaria is a major public health problem in French Guiana. Some cases of resistance to chloroquine, the first-line treatment used against P. vivax malaria, have been described in the Brazilian Amazon region. The aim of this study is to investigate a possible dispersion of chloroquine-resistant P. vivax isolates in French Guiana. The genotype, polymorphism and copy number variation, of the P. vivax multidrug resistance gene-1 (pvmdr1) have been previously associated with modification of the susceptibility to chloroquine.


METHODS
The pvmdr1 gene polymorphism was evaluated by sequencing and copy number variation was assessed by real-time PCR, in P. vivax isolates obtained from 591 symptomatic patients from 1997 to 2013.


RESULTS
The results reveal that 1.0% [95% CI 0.4-2.2] of French Guiana isolates carry the mutations Y976F and F1076L, and that the proportion of isolates with multiple copies of pvmdr1 has significantly decreased over time, from 71.3% (OR = 6.2 [95% CI 62.9-78.7], p < 0.0001) in 1997-2004 to 12.8% (OR = 0.03 [95% CI 9.4-16.9], p < 0.0001) in 2009-2013. A statistically significant relationship was found between Guf-A (harboring the single mutation T958M) and Sal-1 (wild type) alleles and pvmdr1 copy number.


CONCLUSIONS
Few P. vivax isolates harboring chloroquine-resistant mutations in the pvmdr1 gene are circulating in French Guiana. However, the decrease in the prevalence of isolates carrying multiple copies of pvmdr1 might indicate that the P. vivax population in French Guiana is evolving towards a decreased susceptibility to chloroquine.
Laboratoire de Parasitologie, Institut Pasteur de la Guyane, Cayenne, French Guiana.|URPhyM-NARILIS, University of Namur, Namur, Belgium.
Emilie
E
Faway
Laboratoire de Parasitologie, Institut Pasteur de la Guyane, Cayenne, French Guiana.|National Reference Center for Malaria, Institut Pasteur de la Guyane, Cayenne, French Guiana.|World Health Organization Collaborating Center for Surveillance of Antimalarial Drug Resistance, Institut Pasteur de la Guyane, Cayenne, French Guiana.
Lise
L
Musset
Laboratoire de Parasitologie, Institut Pasteur de la Guyane, Cayenne, French Guiana.|National Reference Center for Malaria, Institut Pasteur de la Guyane, Cayenne, French Guiana.|World Health Organization Collaborating Center for Surveillance of Antimalarial Drug Resistance, Institut Pasteur de la Guyane, Cayenne, French Guiana.
Stéphane
S
Pelleau
Laboratoire de Parasitologie, Institut Pasteur de la Guyane, Cayenne, French Guiana.|National Reference Center for Malaria, Institut Pasteur de la Guyane, Cayenne, French Guiana.|World Health Organization Collaborating Center for Surveillance of Antimalarial Drug Resistance, Institut Pasteur de la Guyane, Cayenne, French Guiana.
Béatrice
B
Volney
Laboratoire de Parasitologie, Institut Pasteur de la Guyane, Cayenne, French Guiana.|National Reference Center for Malaria, Institut Pasteur de la Guyane, Cayenne, French Guiana.
Jessica
J
Casteras
Environment and Infectious Risks unit, Genotyping of Pathogens Pole, Institut Pasteur, Paris, France.
Valérie
V
Caro
Malaria Molecular Epidemiology Unit, Institut Pasteur in Cambodia, Phnom Penh, Cambodia.|Malaria Translational Research Unit, Institut Pasteur in Cambodia, Phnom Penh, Cambodia.
Didier
D
Menard
Laboratoire de Parasitologie, Institut Pasteur de la Guyane, Cayenne, French Guiana.|Direction Interarmées du Service de Santé, Cayenne, French Guiana.|Institut de Recherche Biomédicale des Armées, Brétigny sur Orge, France.
Sébastien
S
Briolant
Laboratoire de Parasitologie, Institut Pasteur de la Guyane, Cayenne, French Guiana. eric.legrand@pasteur.fr.|National Reference Center for Malaria, Institut Pasteur de la Guyane, Cayenne, French Guiana. eric.legrand@pasteur.fr.|World Health Organization Collaborating Center for Surveillance of Antimalarial Drug Resistance, Institut Pasteur de la Guyane, Cayenne, French Guiana. eric.legrand@pasteur.fr.|Malaria Translational Research Unit, Institut Pasteur, Paris, France. eric.legrand@pasteur.fr.|Genetics and Genomics of Insect Vectors Unit, Institut Pasteur, Paris, France. eric.legrand@pasteur.fr.
Eric
http://orcid.org/0000-0003-4725-0712
E
Legrand
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D000962:Antimalarials / Q000494:pharmacology; D002648:Child; D002675:Child, Preschool; D002738:Chloroquine / Q000494:pharmacology; D004351:Drug Resistance; D005260:Female; D005616:French Guiana; D018628:Gene Dosage; D005838:Genotype; D006801:Humans; D007223:Infant; D016780:Malaria, Vivax / Q000469:parasitology*; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D020125:Mutation, Missense; D010966:Plasmodium vivax / Q000235:genetics* / Q000302:isolation & purification*; D011110:Polymorphism, Genetic; D015800:Protozoan Proteins / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D055815:Young Adult
D000962:Antimalarials; D002738:Chloroquine; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D015800:Protozoan Proteins; C541684:Mdr1 protein, Plasmodium vivax