Tracking oseltamivir-resistance in New Zealand influenza viruses during a medicine reclassification in 2007, a resistant-virus importation in 2008 and the 2009 pandemic

Hall, Richard J.; Peacey, Matthew; Ralston, Jacqui; Joux, Danielle J de; Bocacao, Judy; Nicol, Mackenzie; Ziki, Molly; Gunn, Wendy; Wang, Jing; Huang, Q Sue

doi:10.5365/wpsar.2012.3.3.002

Cited by 2 publications

(3 citation statements)

References 15 publications

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“…A recent study conducted in New Zealand revealed all 2009 seasonal Influenza A (H1N1) viruses to be resistant to Oseltamivir with the IC 50 values between 305 nM to 7912 nM. Similar study conducted in Thailand reported IC 50 values between 165.76 nM to 840.77 nM [4,28]. The Oseltamivir-resistant isolate obtained from Mumbai also displayed extremely high IC 50 value of 1261 nM which was similar to 2009 seasonal Influenza A (H1N1) viruses circulating in New Zealand and Thailand.…”

Section: Discussionmentioning

confidence: 87%

“…Antiviral agents confer significant prophylactic and therapeutic benefits during seasonal Influenza outbreaks and unexpected Influenza pandemics [3]. The development and occurrence of antiviral drug resistance in human Influenza viruses has been extensively studied over the last decade [4]. Initial analysis of Influenza A (H1N1) pdm 09 revealed that the virus was resistant to the Adamantanes class of drugs that inhibit the M2 ion channel [5].…”

Section: Introductionmentioning

confidence: 99%

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Oseltamivir Resistant Influenza A (H1N1) Virus Infection in Mumbai, India

Gohil¹,

Kothari²

2015

J Antivir Antiretrovir

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Objectives:Oseltamivir is an important antiviral agent approved for treatment of infections caused by Influenza virus. The emergence of an Oseltamivir resistant seasonal Influenza A (H1N1) virus in 2007 in Norway and pandemic Influenza A (H1N1) virus in 2009 [Influenza A (H1N1) pdm 09] is of major concern. This study aimed for examining antiviral drug resistance of Influenza A viruses circulating during 2009 Influenza season in Mumbai.Methods: Nasopharyngeal swabs positive for Influenza A virus were inoculated on Madin-Darby canine kidney cell line for virus isolation. Molecular analysis of neuraminidase gene and matrix gene was carried out to detect known mutations contributing to resistance. Resistance to neuraminidase was assayed using a commercially available chemiluminescence based NA-Star assay kit.Results: Genotypically, a total of 47 isolates of Influenza A (H1N1) pdm 09 isolates were observed to harbor mutations known to confer resistance to Adamantane. However, no known mutations conferring resistance to neuraminidase (NA) inhibitors were detected. Resistance to Oseltamivir was observed in a single isolate of seasonal Influenza A (H1N1) isolate with an extremely high IC 50 value of 1261 nM. Conversely, the isolate was sensitive to Adamantane. Phylogenetic analysis revealed that NA gene of this Oseltamivir-resistant isolate from Mumbai was antigenically related to human A (H1N1) A/Brisbane/59/2007 vaccine strain. Conclusions:Surveillance on drug susceptibility of circulating strains in Mumbai helped us to identify Oseltamivir resistance in seasonal Influenza virus. The study highlights the importance of continual surveillance on Influenza in India to ensure that antiviral prescribed by clinicians is effective when treating patients for Influenza infections.

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Section: Discussionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Oseltamivir Resistant Influenza A (H1N1) Virus Infection in Mumbai, India

Gohil¹,

Kothari²

2015

J Antivir Antiretrovir

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“…However, the virus can acquire resistance to NIs by developing single point mutations (Ferraris and Lina, 2008). The ability of the virus to develop resistance against NIs depends upon enzyme mutations, and therefore, it is important to monitor the sensitivity of new influ-enza strains to NI drugs (Hall et al, 2009;Hall et al, 2012). The existing methods for testing viral resistance to a particular antiviral drug are time-consuming, and results can vary with methods (Okomo-Adhiambo et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

A surface plasmon resonance assay for measurement of neuraminidase inhibition, sensitivity of wild-type influenza neuraminidase and its H274Y mutant to the antiviral drugs zanamivir and oseltamivir

et al. 2015

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Antiviral resistance is currently monitored by a labelled enzymatic assay, which can give inconsistent results because of the short half-life of the labelled product, and variations in assay conditions. In this paper, we describe a competitive surface plasmon resonance (SPR) inhibition assay for measuring the sensitivities of wild-type neuraminidase (WT NA) and the H274Y (histidine 274 tyrosine) NA mutant to antiviral drugs. The two NA isoforms were expressed in High-five™ (Trichoplusia ni) insect cells. A spacer molecule (1,6-hexanediamine (HDA)) was conjugated to the 7-hydroxyl group of zanamivir, and the construct (HDA-zanamivir) was immobilized onto a SPR sensor chip to obtain a final immobilization response of 431 response units. The immobilized HDA-zanamivir comprised a bio-specific ligand for the WT and mutant proteins. The effects of the natural substrate (sialic acid) and two inhibitors (zanamivir and oseltamivir) on NA binding to the immobilized ligand were studied. The processed SPR data was analysed to determine 50% inhibitory concentrations (IC50-spr ), using a log dose-response curve fit. Although both NA isoforms had almost identical IC50-spr values for sialic acid (WT = 5.5 nM; H274Y mutant = 3.25 nM) and zanamivir (WT = 2.16 nM; H274Y mutant = 2.42 nM), there were significant differences between the IC50-spr values obtained for the WT (7.7 nM) and H274Y mutant (256 nM) NA in the presence of oseltamivir, indicating that oseltamivir has a reduced affinity for the H274Y mutant. The SPR inhibition assay strategy presented in this work could be applied for the rapid screening of newly emerging variants of NA for their sensitivity to antiviral drugs.

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Tracking oseltamivir-resistance in New Zealand influenza viruses during a medicine reclassification in 2007, a resistant-virus importation in 2008 and the 2009 pandemic

Abstract: No evidence was found to suggest that increased access to oseltamivir has promoted resistance. A probable importation event was documented for the global 2008 oseltamivir-resistant seasonal A(H1N1) virus nine months after it was first reported in Europe in January 2008.

Cited by 2 publications

References 15 publications

Oseltamivir Resistant Influenza A (H1N1) Virus Infection in Mumbai, India

Oseltamivir Resistant Influenza A (H1N1) Virus Infection in Mumbai, India

A surface plasmon resonance assay for measurement of neuraminidase inhibition, sensitivity of wild-type influenza neuraminidase and its H274Y mutant to the antiviral drugs zanamivir and oseltamivir

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