Plasmodium vivax multidrug resistance-1 gene polymorphism in French Guiana

Faway, Émilie; Musset, Lise; Volney, Béatrice; Casteras, Jessica; Caro, Valérie; Ménard, Didier; Briolant, Sébastien; Legrand, Eric

doi:10.1186/s12936-016-1595-9

Cited by 20 publications

(21 citation statements)

References 45 publications

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“…Increased pvmdr1 copy number was associated with reduced sensitivity to MFQ in some studies [31][32][33]73]. Like in P. falciparum [74], pvmdr1 amplification was also rare at the China-Myanmar border and only detected in three isolates (3/64).…”

Section: Discussionmentioning

confidence: 91%

“…Whereas some studies reported the association of the pvmdr1 substitutions Y976F with CQR P. vivax in vitro [27], others did not find such an association [28][29][30]. Some studies have found that an increase in pvmdr1 gene copy number was correlated with increased susceptibility to CQ, but perhaps reduced susceptibility to MFQ [31][32][33]. In a study from Brazil, higher expression levels of pvcrt-o and pvmdr1 were shown to confer CQ resistance in P. vivax [34].…”

Section: Plos Neglected Tropical Diseasesmentioning

confidence: 97%

“…Given the potential contribution of pvmdr1 copy number variation to altered susceptibility to CQ and MFQ [31][32][33], the copy number of the pvmdr1 gene was determined by real-time PCR. For the 62 samples where pvmdr1 copy number was successfully determined, 95.2% of the parasite isolates had one copy, whereas 3 (4.8%) isolates had two copies of the pvmdr1 gene.…”

Section: Plos Neglected Tropical Diseasesmentioning

confidence: 99%

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Ex vivo susceptibilities of Plasmodium vivax isolates from the China-Myanmar border to antimalarial drugs and association with polymorphisms in Pvmdr1 and Pvcrt-o genes

Zhang

et al. 2020

PLoS Negl Trop Dis

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Background Vivax malaria is an important public health problem in the Greater Mekong Subregion (GMS), including the China-Myanmar border. Previous studies have found that Plasmodium vivax has decreased sensitivity to antimalarial drugs in some areas of the GMS, but the sensitivity of P. vivax to antimalarial drugs is unclear in the China-Myanmar border. Here, we investigate the drug sensitivity profile and genetic variations for two drug resistance related genes in P. vivax isolates to provide baseline information for future drug studies in the China-Myanmar border. Methodology/Principal findings A total of 64 P. vivax clinical isolates collected from the China-Myanmar border area were assessed for ex vivo susceptibility to eight antimalarial drugs by the schizont maturation assay. The medians of IC 50 (half-maximum inhibitory concentrations) for chloroquine, mefloquine, pyronaridine, piperaquine, quinine, artesunate, artemether, dihydroartemisinin were 84.2 nM, 34.9 nM, 4.0 nM, 22.3 nM, 41.4 nM, 2.8 nM, 2.1 nM and 2.0 nM, respectively. Twelve P. vivax clinical isolates were found over the cutoff IC 50 value (220 nM) for chloroquine resistance. In addition, sequence polymorphisms in pvmdr1 (P. vivax multidrug resistance-1), pvcrt-o (P. vivax chloroquine resistance transporter-o), and difference in pvmdr1 copy number were studied. Sequencing of the pvmdr1 gene in 52 samples identified 12 amino acid substitutions, among which two (G698S and T958M) were fixed, M908L were present in 98.1% of the isolates, while Y976F and F1076L were present in 3.8% and 78.8% of the isolates, respectively. Amplification of the pvmdr1 gene was only detected in 4.8% of PLOS NEGLECTED TROPICAL DISEASES

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Section: Discussionmentioning

confidence: 91%

Section: Plos Neglected Tropical Diseasesmentioning

confidence: 97%

Section: Plos Neglected Tropical Diseasesmentioning

confidence: 99%

See 1 more Smart Citation

Ex vivo susceptibilities of Plasmodium vivax isolates from the China-Myanmar border to antimalarial drugs and association with polymorphisms in Pvmdr1 and Pvcrt-o genes

Zhang

et al. 2020

PLoS Negl Trop Dis

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“…[16][17][18][19] More recent studies show the presence of P. vivax isolates harboring CQ-resistant mutations in French Guiana and Brazil. 20,21 Reported cases of TF with CQ alone in South America suggest that it is necessary to monitor the clinical and parasitological response to the drug because of a possible unrecognized emergence of resistant P. vivax strains in Colombia, although the extent of the threat to national malaria control efforts remains to be determined. In Colombia, the initial studies between 1998 and 2011 found a 100% ACPR to CQ alone in patients with malaria vivax monoinfection [22][23][24][25][26] ; one study reported an 11% rate of TFs in 2001, defined by the authors as "clinical drug resistance" 27 ; and one study addressed P. vivax in vitro susceptibility to various drug regimens between 2010 and 2012.…”

Section: Introductionmentioning

confidence: 99%

Chloroquine–Primaquine Therapeutic Efficacy, Safety, and Plasma Levels in Patients with Uncomplicated Plasmodium vivax Malaria in a Colombian Pacific Region

Mesa-Echeverry

Niebles-Bolivar

Tobón-Castaño

2019

The American Journal of Tropical Medicine and Hygiene

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In Colombia, published studies for the treatment of uncomplicated Plasmodium vivax malaria with chloroquine-primaquine (CQ-PQ) are scarce. The aim of the study was to evaluate the therapeutic efficacy and safety profile of this combination. A clinical trial was performed in adults with uncomplicated P. vivax malaria using the 28-day World Health Organization validated protocol. Patients received supervised antimalarial treatment and the primary efficacy end point was the clinical and parasitological response. Safety was assessed through adverse events surveillance, and plasma levels of antimalarial drugs were measured. A total of 77 patients were included. Adequate clinical and parasitological response rate diagnosed by thick blood smear examination was achieved in 72 of 73 patients (98.6%) with a complete 28-day follow-up. There were two parasitological therapeutic failures (TFs) (2.9%) on day 28, established by polymerase chain reaction among 68 patients, one of them with a positive film. No adverse events were detected. After completing the antimalarial treatment, all patients reached adequate plasma concentrations of CQ and desethylchloroquine (DECQ), with medians of 302.9 and 104.0 ng/mL, respectively. Uncomplicated P. vivax malaria treatment with CQ-PQ standard treatment was effective and safe in the study population; TFs were not associated with low plasma levels of CQ and DECQ.

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“…Previous studies in Southeast Asia have shown that P. vivax isolates with pvmdr1 ( P. vivax multidrug-resistant gene 1) gene amplification were characterized by increased susceptibility to chloroquine but decreased susceptibility to mefloquine (Imwong et al, 2008 ; Suwanarusk et al, 2008 ). Nevertheless, the role of pvmdr1 in conferring resistance to chloroquine is still elusive and controversial (Faway et al, 2016 ). Although number of pvmdr1 gene copies correlated with mefloquine use history, in vivo data showing a direct relationship between mefloquine resistance and pvmdr1 gene amplification form mefloquine-treated patients are needed (Khim et al, 2014 ).…”

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confidence: 99%