Oseltamivir-Resistant Pandemic (H1N1) 2009 Virus, Mexico

Ramirez-Gonzalez, Jose Ernesto; González-Durán, Elizabeth; Alcantara-Perez, Patricia; Wong-Arámbula, Claudia; Olivera-Díaz, Hiram; Cortez-Ortiz, Iliana; Barrera-Badillo, Gisela; Nguyen, Ha; Gubareva, Larisa V.; López-Martı́nez, Irma; Díaz-Quiñonez, José Alberto; Fernández, Miguel Ángel Lezana; Gatell-Ramírez, Hugo López; Villalobos, José Ángel Córdova; Hernández-Ávila, Mauricio; Alpuche-Aranda, Celia

doi:10.3201/eid1702.100897

Cited by 19 publications

(12 citation statements)

References 11 publications

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“…The isolation of oseltamivir-resistant strains of the pandemic influenza virus (H1N1) has been reported with increasing frequency. The situation of oseltamivir-resistant strains in Thailand displays a similar prevalence to that observed in other countries (WHO, 2010; Ujike et al, 2011; Ramirez-Gonzalez et al, 2011; Duwe et al, 2011; Yang et al, 2010; Harvala et al, 2010; Chen et al, 2009). In this study showed that the number of patients infected by oseltamivir resistant strains was higher in the course of the second (0.24%) and third (0.61%) waves than during the first (0%) outbreak.…”

Section: Discussionsupporting

confidence: 68%

Detection of oseltamivir sensitive/resistant strains of pandemic influenza A virus (H1N1) from patients admitted to hospitals in Thailand

Payungporn¹,

Poomipak²,

Makkoch³

et al. 2011

Journal of Virological Methods

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Oseltamivir has been used widely for prophylaxis or treatment during outbreaks of the pandemic influenza virus (H1N1) in several countries. The aim of this study was to develop a real-time RT-PCR (reverse transcription-polymerase chain reaction) to be applied for detection and monitoring of the oseltamivir resistant strains of this virus during three outbreaks (May, 2009 to October, 2010) in Thailand. The real-time RT-PCR assay for detecting H275Y proved highly specific for the pandemic influenza virus (H1N1) as no cross-amplification was detected with other respiratory viruses or human total RNA. The assay was also highly sensitive with a detection limit as low as 100 copies/μL for both wild-type and resistant strains. The performance of the assay was evaluated in terms of amplification efficiency (100%). The results obtained by real-time RT-PCR were in complete agreement with direct nucleotide sequencing. However, real-time RT-PCR provided more detail on the relative quantities of ratios between resistant and sensitive strains in each individual. The results revealed that four of 1,288 (0.31%) patients were infected with the oseltamivir resistant strain. The number of patients infected by resistant strains was higher during the third (0.61%) and second (0.24%) waves than during the first (0%) outbreak. In conclusion, the real-time RT-PCR assay for H275Y detection is advantageous because it is specific, sensitive, and provides quantitative data. And it would be useful for large-scale testing and monitoring of oseltamivir resistant strains of the pandemic influenza A virus (H1N1).

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Section: Discussionsupporting

confidence: 68%

Detection of oseltamivir sensitive/resistant strains of pandemic influenza A virus (H1N1) from patients admitted to hospitals in Thailand

Payungporn¹,

Poomipak²,

Makkoch³

et al. 2011

Journal of Virological Methods

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“…The finding of three cases harboring this mutation in the same location suggests frequent transmission of this viral haplotype. The first published report of a H275Y mutation in Mexico documented a case that occurred in January, 2010 [36], few months after the one reported here (November, 2009). Intriguingly, data mining of retrieved NA sequences from the IVR revealed that the H275Y mutation appeared in Mexico since May, 2009.…”

Section: Discussionmentioning

confidence: 63%

Using High-Throughput Sequencing to Leverage Surveillance of Genetic Diversity and Oseltamivir Resistance: A Pilot Study during the 2009 Influenza A(H1N1) Pandemic

et al. 2013

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BackgroundInfluenza viruses display a high mutation rate and complex evolutionary patterns. Next-generation sequencing (NGS) has been widely used for qualitative and semi-quantitative assessment of genetic diversity in complex biological samples. The “deep sequencing” approach, enabled by the enormous throughput of current NGS platforms, allows the identification of rare genetic viral variants in targeted genetic regions, but is usually limited to a small number of samples.Methodology and Principal FindingsWe designed a proof-of-principle study to test whether redistributing sequencing throughput from a high depth-small sample number towards a low depth-large sample number approach is feasible and contributes to influenza epidemiological surveillance. Using 454-Roche sequencing, we sequenced at a rather low depth, a 307 bp amplicon of the neuraminidase gene of the Influenza A(H1N1) pandemic (A(H1N1)pdm) virus from cDNA amplicons pooled in 48 barcoded libraries obtained from nasal swab samples of infected patients (n = 299) taken from May to November, 2009 pandemic period in Mexico. This approach revealed that during the transition from the first (May-July) to second wave (September-November) of the pandemic, the initial genetic variants were replaced by the N248D mutation in the NA gene, and enabled the establishment of temporal and geographic associations with genetic diversity and the identification of mutations associated with oseltamivir resistance.ConclusionsNGS sequencing of a short amplicon from the NA gene at low sequencing depth allowed genetic screening of a large number of samples, providing insights to viral genetic diversity dynamics and the identification of genetic variants associated with oseltamivir resistance. Further research is needed to explain the observed replacement of the genetic variants seen during the second wave. As sequencing throughput rises and library multiplexing and automation improves, we foresee that the approach presented here can be scaled up for global genetic surveillance of influenza and other infectious diseases.

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“…M2 inhibitors are effective only against type A viruses, and drug resistance is widespread (4). Neuraminidase inhibitors, which are effective against type A and type B viruses, are also confronting drug-resistant viruses (5)(6)(7)(8). Novel antiviral drugs with different targets are required to treat patients infected with drug-resistant viruses.…”

Section: Introductionmentioning

confidence: 99%

Cyclosporin A Inhibits the Propagation of Influenza Virus by Interfering with a Late Event in the Virus Life Cycle

et al. 2013

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Oseltamivir-Resistant Pandemic (H1N1) 2009 Virus, Mexico

Cited by 19 publications

References 11 publications

Detection of oseltamivir sensitive/resistant strains of pandemic influenza A virus (H1N1) from patients admitted to hospitals in Thailand

Detection of oseltamivir sensitive/resistant strains of pandemic influenza A virus (H1N1) from patients admitted to hospitals in Thailand

Using High-Throughput Sequencing to Leverage Surveillance of Genetic Diversity and Oseltamivir Resistance: A Pilot Study during the 2009 Influenza A(H1N1) Pandemic

Cyclosporin A Inhibits the Propagation of Influenza Virus by Interfering with a Late Event in the Virus Life Cycle

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