scholarly journals Emergence of Plasmodium vivax Resistance to Chloroquine in French Guiana

2019 ◽  
Vol 63 (11) ◽  
Author(s):  
Lise Musset ◽  
Christophe Heugas ◽  
Richard Naldjinan ◽  
Denis Blanchet ◽  
Pascal Houze ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Therapeutic Efficacy ◽  
French Guiana ◽  
Gene Copy Number ◽  
Chloroquine Resistance ◽  
World Health ◽  
Gene Copy ◽  
Content Type ◽  
Gene Copy Number Variation ◽  
Health Organization

ABSTRACT In South America, Plasmodium vivax resistance to chloroquine was recently reported in Brazil and Bolivia. The objective of this study was to collect data on chloroquine resistance in French Guiana by associating a retrospective evaluation of therapeutic efficacy with an analysis of recurrent parasitemia from any patients. Patients with P. vivax infection, confirmed by microscopy and a body temperature of ≥37.5°C, were retrospectively identified at Cayenne Hospital between 2009 and 2015. Follow-up and treatment responses were performed according to the World Health Organization protocol. Parasite resistance was confirmed after dosage of a plasma concentration of chloroquine and microsatellite characterization. The pvmdr1 and pvcrt-o genes were analyzed for sequence and gene copy number variation. Among the 172 patients followed for 28 days, 164 presented adequate clinical and parasitological responses. Eight cases of treatment failures were identified (4.7%; n = 8/172), all after 14 days. The therapeutic efficacy of chloroquine was estimated at 95.3% (95% confidence interval [CI], 92.5 to 98.1%; n = 164/172). Among the eight failures, five were characterized: two cases were true P. vivax chloroquine resistance (1.2%; 95% CI, 0 to 2.6%; n = 2/172), and three cases were found with subtherapeutic concentrations of chloroquine. No particular polymorphism in the Plasmodium vivax pvmdr1 and pvcrt-o genes was identified in the resistant parasites. This identified level of resistance of P. vivax to chloroquine in French Guiana does not require a change in therapeutic recommendations. However, primaquine should be administered more frequently to limit the spread of resistance, and there is still a need for a reliable molecular marker to facilitate the monitoring of P. vivax resistance to chloroquine.

scholarly journals Discordant Temporal Evolution ofPfcrtandPfmdr1Genotypes and Plasmodium falciparum In Vitro Drug Susceptibility to 4-Aminoquinolines after Drug Policy Change in French Guiana

2012 ◽  
Vol 56 (3) ◽  
pp. 1382-1389 ◽  
Author(s):  
Eric Legrand ◽  
Joséphine Yrinesi ◽  
Marie-Thérèse Ekala ◽  
Julie Péneau ◽  
Béatrice Volney ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Drug Policy ◽  
French Guiana ◽  
Target Genes ◽  
Gene Copy Number ◽  
Drug Susceptibility ◽  
Gene Copy ◽  
Poor Correlation ◽  
Content Type

ABSTRACTAnalysis of the evolution of drug target genes under changing drug policy is needed to assist monitoring ofPlasmodium falciparumdrug resistance in the field. Here we genotypePfcrtandPfdmr1of 700 isolates collected in French Guiana from 2000 (5 years after withdrawal of chloroquine) to 2008, i.e., the period when the artemether-lumefantrine combination was progressively introduced and mefloquine was abandoned. Gene sequencing showed fixation of the 7G8-typePfcrtSMVNT resistance haplotype and near fixation of the NYCDYPfdmr1haplotype.Pfdmr1gene copy number correlated with 50% inhibitory concentrations of mefloquine and halofantrine (r= 0.64 and 0.47, respectively,n= 547); its temporal changes paralleled changes inin vitromefloquine susceptibility. However, the molecular parameters studied did not account for the regainedin vitrosusceptibility to chloroquine and showed a poor correlation with susceptibility to artemether, lumefantrine, or quinine. Identification of novel markers of resistance to these antimalarials is needed in this South American area.

scholarly journals Genomic analyses of Staphylococcus aureus clonal complex 45 isolates does not distinguish nasal carriage from bacteraemia

2020 ◽  
Vol 6 (8) ◽  
Author(s):  
Chandler Roe ◽  
Marc Stegger ◽  
Berit Lilje ◽  
Thor Bech Johannesen ◽  
Kim Lee Ng ◽  
...  
Keyword(s):  
Type Species ◽  
Clonal Complex ◽  
Gene Copy Number ◽  
Nasal Carriage ◽  
Gene Copy ◽  
Genomic Features ◽  
Content Type ◽  
Link Type ◽  
Gene Copy Number Variation ◽  
Number Variation

Staphylococcus aureus is a colonizing opportunistic pathogen and a leading cause of bloodstream infection with high morbidity and mortality. S. aureus carriage frequency is reportedly between 20 and 40 % among healthy adults, with S. aureus colonization considered to be a risk factor for S. aureus bacteraemia. It is unknown whether a genetic component of the bacterium is associated with S. aureus bacteraemia in comparison to nasal carriage strains. Previous association studies primarily focusing on the clinical outcome of an S. aureus infection have produced conflicting results, often limited by study design challenged by sample collections and the clonal diversity of S. aureus . To date, no study has investigated whether genomic features separate nasal carriage isolates from S. aureus bacteraemia isolates within a single clonal lineage. Here we have investigated whether genomic features, including single-nucleotide polymorphisms (SNPs), genes, or kmers, distinguish S. aureus nasal carriage isolates from bacteraemia isolates that all belong to the same clonal lineage [clonal complex 45 (CC45)] using whole-genome sequencing (WGS) and a genome-wide association (GWA) approach. From CC45, 100 isolates (50 bacteraemia and 50 nasal carriage, geographically and temporally matched) from Denmark were whole-genome sequenced and subjected to GWA analyses involving gene copy number variation, SNPs, gene content, kmers and gene combinations, while correcting for lineage effects. No statistically significant association involving SNPs, specific genes, gene variants, gene copy number variation, or a combination of genes was identified that could distinguish bacteraemia isolates from nasal carriage isolates. The presented results suggest that all S. aureus nasal CC45 isolates carry the potential to cause invasive disease, as no core or accessory genome content or variations were statistically associated with invasiveness.

scholarly journals No evidence of amplified Plasmodium falciparum plasmepsin II gene copy number in an area with artemisinin-resistant malaria along the China–Myanmar border

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Fang Huang ◽  
Biraj Shrestha ◽  
Hui Liu ◽  
Lin-Hua Tang ◽  
Shui-Sen Zhou ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Molecular Markers ◽  
Therapeutic Efficacy ◽  
Copy Number ◽  
Copy Number Variants ◽  
Gene Copy Number ◽  
Artemisinin Resistance ◽  
World Health ◽  
Gene Copy ◽  
Synonymous Mutations

Abstract Background The emergence and spread of artemisinin resistance in Plasmodium falciparum poses a threat to malaria eradication, including China’s plan to eliminate malaria by 2020. Piperaquine (PPQ) resistance has emerged in Cambodia, compromising an important partner drug that is widely used in China in the form of dihydroartemisinin (DHA)-PPQ. Several mutations in a P. falciparum gene encoding a kelch protein on chromosome 13 (k13) are associated with artemisinin resistance and have arisen spread in the Great Mekong subregion, including the China–Myanmar border. Multiple copies of the plasmepsin II/III (pm2/3) genes, located on chromosome 14, have been shown to be associated with PPQ resistance. Methods The therapeutic efficacy of DHA-PPQ for the treatment of uncomplicated P. falciparum was evaluated along the China–Myanmar border from 2010 to 2014. The dry blood spots samples collected in the efficacy study prior DHA-PPQ treatment and from the local hospital by passive detection were used to amplify k13 and pm2. Polymorphisms within k13 were genotyped by capillary sequencing and pm2 copy number was quantified by relative-quantitative real-time polymerase chain reaction. Treatment outcome was evaluated with the World Health Organization protocol. A linear regression model was used to estimate the association between the day 3 positive rate and k13 mutation and the relationship of the pm2 copy number variants and k13 mutations. Results DHA-PPQ was effective for uncomplicated P. falciparum infection in Yunnan Province with cure rates > 95%. Twelve non synonymous mutations in the k13 domain were observed among the 268 samples with the prevalence of 44.0% and the predominant mutation was F446I with a prevalence of 32.8%. Only one sample was observed with multi-copies of pm2, including parasites with and without k13 mutations. The therapeutic efficacy of DHA-PPQ was > 95% along the China–Myanmar border, consistent with the lack of amplification of pm2. Conclusion DHA-PPQ for uncomplicated P. falciparum infection still showed efficacy in an area with artemisinin-resistant malaria along the China–Myanmar border. There was no evidence to show PPQ resistance by clinical study and molecular markers survey. Continued monitoring of the parasite population using molecular markers will be important to track emergence and spread of resistance in this region.

Genetic variability of CYP2D6, CYP3A4 and CYP3A5 among the Egyptian population

2021 ◽  
Author(s):  
Thuraya M Mutawi ◽  
Mohamed M Zedan ◽  
Raida S Yahya ◽  
Mahmoud M Zakria ◽  
Mamdouh R El-Sawi ◽  
...  
Keyword(s):  
Genetic Variability ◽  
Copy Number Variation ◽  
Copy Number ◽  
Middle Eastern ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Allelic Variants ◽  
Gene Copy Number Variation ◽  
Number Variation ◽  
Study Participants

Aim: This study investigated major allelic variants of CYP2D6, CYP3A4 and CYP3A5 in Egyptians, an Arabic population for which there is little information regarding these important pharmacogenes. Patients & methods: CYP2D6*2, *4, *5, *10, *41 and gene copy number variation, as well as CYP3A4*22 and CYP3A5*3 were determined with commercially available TaqMan assays in 145 healthy study participants. Results: The CYP2D6 alleles identified suggest that the prevalence of poor metabolizers is low as none were found among the 145 subjects investigated. The frequency for CYP3A5 nonexpressers was 74.5% and the CYP3A4*22 allele frequency was low at 2.0%. Conclusion: These preliminary findings indicate that pharmacogene variation in Egyptians is different from those of other Middle Eastern/Arabic populations and warrants further investigation.

scholarly journals Nosocomial Outbreak of Carbapenemase-Producing Proteus mirabilis With Two Novel Salmonella Genomic Island 1 Variants Carrying Different blaNDM–1 Gene Copies in China

2022 ◽  
Vol 12 ◽  
Author(s):  
Lang Yang ◽  
Hong He ◽  
Qichao Chen ◽  
Kaiying Wang ◽  
Yanfeng Lin ◽  
...  
Keyword(s):  
Proteus Mirabilis ◽  
Copy Number ◽  
Genomic Island ◽  
Gene Copy Number ◽  
Carbapenem Resistance ◽  
Multidrug Resistant ◽  
Gene Copy ◽  
Nosocomial Outbreak ◽  
Gene Copy Number Variation ◽  
Gene Copies

NDM-1-producing multidrug-resistant Proteus mirabilis brings formidable clinical challenges. We report a nosocomial outbreak of carbapenem-resistant P. mirabilis in China. Six P. mirabilis strains collected in the same ward showed close phylogenetic relatedness, indicating clonal expansion. Illumina and MinION sequencing revealed that three isolates harbored a novel Salmonella genomic island 1 carrying a blaNDM–1 gene (SGI1-1NDM), while three other isolates showed elevated carbapenem resistance and carried a similar SGI1 but with two blaNDM–1 gene copies (SGI1-2NDM). Four new single nucleotide mutations were present in the genomes of the two-blaNDM–1-harboring isolates, indicating later emergence of the SGI1-2NDM structure. Passage experiments indicated that both SGI variants were stably persistent in this clone without blaNDM–1 copy number changes. This study characterizes two novel blaNDM–1-harboring SGI1 variants in P. mirabilis and provides a new insight into resistance gene copy number variation in bacteria.

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