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Maria Zambon - One of the best experts on this subject based on the ideXlab platform.
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Evaluation of influenza virus Antiviral Susceptibility testing in Europe: results from the first external quality assessment exercise.
Journal of Clinical Virology, 2013Co-Authors: Catherine Thompson, Angie Lackenby, Adam Meijer, R S Daniels, J W Mccauley, D Pereyaslov, Eeva Broberg, Maria ZambonAbstract:Abstract Background The first Antiviral Susceptibility testing external quality assessment (EQA) was held for European influenza reference laboratories during winter 2010/11. Objectives To assess European network influenza Antiviral Susceptibility testing capability and provide participants with an independent performance evaluation. Study design The EQA panel contained ten coded specimens of inactivated human influenza A and B viruses with reduced Susceptibility to neuraminidase inhibitors (NAI), or adamantanes. Twenty-four laboratories from 19 member states of the WHO European region analysed the panel using phenotypic (determination of 50% inhibitory concentration (IC 50 ) values by neuraminidase (NA) enzyme inhibition assay) and/or genotypic methods. Results All 24 laboratories returned genotypic data for A(H1N1)pdm09 influenza virus, 18 (75%) for former seasonal A(H1N1), 16 (67%) for A(H3N2) and 15 (63%) for influenza B virus, correctly identifying NAI or adamantane reduced Susceptibility-associated substitutions in the NA (mean 84%; range 52–100%) or M2 (mean 85%; range 73–94%), respectively. Thirteen laboratories (54%) returned phenotypic NAI Susceptibility data. Despite inter-laboratory and inter-assay IC 50 value variation, all 13 laboratories correctly identified oseltamivir reduced Susceptibility/resistance in pure preparations of A(H1N1) oseltamivir-resistant viruses. However, only 11 (85%) identified oseltamivir reduced Susceptibility/resistance in a mixture of A(H1N1)pdm09 oseltamivir-sensitive/-resistant viruses. Furthermore, 3 laboratories (23%) considered oseltamivir-sensitive influenza B virus reduced susceptible/resistant. Conclusions Detection of NA-H275Y in A(H1N1) viruses was achieved by most laboratories. IC 50 values and interpretation thereof varied for a sensitive/resistant virus mixture and for influenza B virus. The results of this exercise will assist harmonisation of Antiviral Susceptibility testing, interpretation and reporting within the European network through targeted training.
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Emergence of resistance to oseltamivir among influenza A(H1N1) viruses in Europe.
Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin, 2008Co-Authors: A Lackenby, Olav Hungnes, Susanne Gjeruldsen Dudman, Adam Meijer, W J Paget, Alan J. Hay, Maria ZambonAbstract:Surveillance of the Antiviral Susceptibility of influenza viruses circulating in Europe has been established since 2004 through the European Union-funded European Surveillance Network for Vigilance against Viral Resistance (VIRGIL), in collaboration with the European Influenza Surveillance Scheme (EISS), the World Health Organization (WHO) and national influenza centres. Results from analysis of early winter (November 2007 - January 2008) A(H1N1) virus isolates has revealed that a significant proportion, approximately 14% of these European strains (see Table), are resistant to oseltamivir (Tamiflu), the most widely used anti-influenza drug, but retain sensitivity to zanamivir (Relenza) and amantadine/rimantadine. .
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influenza Antiviral Susceptibility monitoring activities in relation to national Antiviral stockpiles in europe during the winter 2006 2007 season
Eurosurveillance, 2007Co-Authors: Adam Meijer, Angie Lackenby, Alan J. Hay, Maria ZambonAbstract:Due to the influenza pandemic threat, many countries are stockpiling Antivirals in the hope of limiting the impact of a future pandemic virus. Since resistance to Antiviral drugs would probably significantly alter the effectiveness of Antivirals, surveillance programmes to monitor the emergence of resistance are of considerable importance. During the 2006/2007 influenza season, an inventory was conducted by the European Surveillance Network for Vigilance against Viral Resistance (VIRGIL) in collaboration with the European Influenza Surveillance Scheme (EISS) to evaluate Antiviral Susceptibility testing by the National Influenza Reference Laboratories (NIRL) in relation to the national Antiviral stockpile in 30 European countries that are members of EISS. All countries except Ukraine had a stockpile of the neuraminidase inhibitor (NAI) oseltamivir. Additionally, four countries had a stockpile of the NAI zanamivir and three of the M2 ion channel inhibitor rimantadine. Of 29 countries with a NAI stockpile, six countries'; NIRLs could determine virus Susceptibility by 50% inhibitory concentration (IC50) and in 13 countries it could be done by sequencing. Only in one of the three countries with a rimantadine stockpile could the NIRL determine virus Susceptibility, by sequencing only. However, including the 18 countries that had plans to introduce or extend Antiviral Susceptibility testing, the NIRLs of 21 of the 29 countries with a stockpile would be capable of Susceptibility testing appropriate to the stockpiled drug by the end of the 2007/2008 influenza season. Although most European countries in this study have stockpiles of influenza Antivirals, Susceptibility surveillance capability by the NIRLs appropriate to the stockpiled Antivirals is limited.
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Programme of the Community Network of Reference Laboratories for Human Influenza to improve Influenza Surveillance in Europe.
Vaccine, 2006Co-Authors: Adam Meijer, Olav Hungnes, Sylvie Van Der Werf, Caroline Brown, Brunhilde Schweiger, Martine Valette, Maria ZambonAbstract:All laboratories participating in the Community Network of Reference Laboratories for Human Influenza in Europe (CNRL) co-ordinated by the European Influenza Surveillance Scheme (EISS) should be able to perform a range of influenza diagnostics. This includes direct detection, culture, typing, subtyping and strain characterisation of influenza viruses, diagnostic serology and the creation of archives for clinical specimens and virus isolates. To improve the capacity and quality of the laboratories of the CNRL and to increase the consistency in performance among all 25 European Union countries plus Norway, Romania, and Switzerland, five task groups were set up in February 2005. These task groups developed work programmes in the areas of virus isolation, antibodies, molecular virology, quality control assessment and Antiviral Susceptibility testing. This report outlines the programmes and the results achieved in the first half-year of operation of the task groups. The action plans are challenging and it is expected that these efforts will lead to considerable improvements in the performance of the laboratories and in the standardisation of methods employed in Europe with regard to routine influenza surveillance and early warning for emerging viruses.
Adam Meijer - One of the best experts on this subject based on the ideXlab platform.
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Guidance for clinical and public health laboratories testing for influenza virus Antiviral drug Susceptibility in Europe
Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology, 2013Co-Authors: Francisco Pozo, Angie Lackenby, R S Daniels, Eeva Broberg, Vincent Enouf, Bruno Lina, Helena Rebelo De Andrade, Athanasios Kossyvakis, Adam MeijerAbstract:Abstract Two classes of Antiviral drugs are licensed in Europe for treatment and prophylaxis of influenza; the M2 ion-channel blockers amantadine and rimantadine acting against type A influenza viruses only and the neuraminidase enzyme inhibitors zanamivir and oseltamivir acting against type A and type B influenza viruses. This guidance document was developed for but not limited to the European Union (EU) and other European Economic Area (EEA) countries on how and when to test for influenza virus Antiviral drug Susceptibility. It is aimed at clinical and influenza surveillance laboratories carrying out Antiviral drug Susceptibility testing on influenza viruses from patients suspected of harbouring viruses with reduced Susceptibility or for the monitoring of the emergence of such among circulating viruses, respectively. Therefore, the guidance should not be read as a directive or an algorithm for treatment. Monitoring for emergence of influenza viruses with reduced drug Susceptibility in hospitalized cases is crucial for decision making on possible changes to Antiviral treatment. Therefore, it is important to test for Antiviral Susceptibility in certain patient groups, such as patients treated with influenza Antiviral drugs. It is also important to determine the frequency of viruses with natural (not related to drug use) reduced Susceptibility among community and hospitalized cases, as this knowledge is essential for making empirical Antiviral treatment decisions. Furthermore, testing of specimens from community influenza patients is needed to determine the frequency of viruses with reduced Susceptibility and good viral fitness that are readily transmissible, as they may become dominant among circulating viruses. Phenotypic neuraminidase enzyme inhibition assays are recommended to determine the level of inhibition of the neuraminidase enzyme by Antiviral drugs as a measure of drug Susceptibility of the virus. Genotypic assays are recommended to identify amino acid substitutions in the neuraminidase and M2 ion-channel proteins that have been associated with reduced Antiviral Susceptibility previously. By 2012 all circulating seasonal influenza A(H1N1)pdm09 and A(H3N2) viruses were naturally resistant to the M2 ion-channel blockers, so priority should be given to testing for neuraminidase inhibitor Susceptibility.
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Evaluation of influenza virus Antiviral Susceptibility testing in Europe: results from the first external quality assessment exercise.
Journal of Clinical Virology, 2013Co-Authors: Catherine Thompson, Angie Lackenby, Adam Meijer, R S Daniels, J W Mccauley, D Pereyaslov, Eeva Broberg, Maria ZambonAbstract:Abstract Background The first Antiviral Susceptibility testing external quality assessment (EQA) was held for European influenza reference laboratories during winter 2010/11. Objectives To assess European network influenza Antiviral Susceptibility testing capability and provide participants with an independent performance evaluation. Study design The EQA panel contained ten coded specimens of inactivated human influenza A and B viruses with reduced Susceptibility to neuraminidase inhibitors (NAI), or adamantanes. Twenty-four laboratories from 19 member states of the WHO European region analysed the panel using phenotypic (determination of 50% inhibitory concentration (IC 50 ) values by neuraminidase (NA) enzyme inhibition assay) and/or genotypic methods. Results All 24 laboratories returned genotypic data for A(H1N1)pdm09 influenza virus, 18 (75%) for former seasonal A(H1N1), 16 (67%) for A(H3N2) and 15 (63%) for influenza B virus, correctly identifying NAI or adamantane reduced Susceptibility-associated substitutions in the NA (mean 84%; range 52–100%) or M2 (mean 85%; range 73–94%), respectively. Thirteen laboratories (54%) returned phenotypic NAI Susceptibility data. Despite inter-laboratory and inter-assay IC 50 value variation, all 13 laboratories correctly identified oseltamivir reduced Susceptibility/resistance in pure preparations of A(H1N1) oseltamivir-resistant viruses. However, only 11 (85%) identified oseltamivir reduced Susceptibility/resistance in a mixture of A(H1N1)pdm09 oseltamivir-sensitive/-resistant viruses. Furthermore, 3 laboratories (23%) considered oseltamivir-sensitive influenza B virus reduced susceptible/resistant. Conclusions Detection of NA-H275Y in A(H1N1) viruses was achieved by most laboratories. IC 50 values and interpretation thereof varied for a sensitive/resistant virus mixture and for influenza B virus. The results of this exercise will assist harmonisation of Antiviral Susceptibility testing, interpretation and reporting within the European network through targeted training.
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Emergence of resistance to oseltamivir among influenza A(H1N1) viruses in Europe.
Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin, 2008Co-Authors: A Lackenby, Olav Hungnes, Susanne Gjeruldsen Dudman, Adam Meijer, W J Paget, Alan J. Hay, Maria ZambonAbstract:Surveillance of the Antiviral Susceptibility of influenza viruses circulating in Europe has been established since 2004 through the European Union-funded European Surveillance Network for Vigilance against Viral Resistance (VIRGIL), in collaboration with the European Influenza Surveillance Scheme (EISS), the World Health Organization (WHO) and national influenza centres. Results from analysis of early winter (November 2007 - January 2008) A(H1N1) virus isolates has revealed that a significant proportion, approximately 14% of these European strains (see Table), are resistant to oseltamivir (Tamiflu), the most widely used anti-influenza drug, but retain sensitivity to zanamivir (Relenza) and amantadine/rimantadine. .
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Emergence of oseltamivir resistant influenza A (H1N1) viruses in the Netherlands during the winter 2007/2008.
2008Co-Authors: Adam Meijer, Frederika Dijkstra, Gé Donker, R. Van Beek, Marcel Jonges, M A B Van Der Sande, Charles A. Boucher, M. P. G. Koopmans, A.d.m.e. Osterhaus, Guus F. RimmelzwaanAbstract:Background: Continuous monitoring of influenza Antiviral Susceptibility has become more important since the introduction of the neuraminidase inhibitors (NAI) in 1999, in addition to the existing adamantane M2 channel inhibitors (M2I). Since the 2005/2006 winter season the Dutch National Influenza Centre (ErasmusMC and RIVM) systematically monitors the Antiviral Susceptibility of influenza viruses derived from patients with influenza like illness or acute respiratory infection who consult a general practitioner of the influenza sentinel network (coordinated by NIVEL). Only sporadically viruses with a lower Susceptibility for the NAI were found in the Netherlands in the winter seasons 2005/2006 and 2006/2007, whilst an increasing proportion of A(H3N2) viruses were found resistant to M2I. Methods: During the 2007/2008 season, influenza viruses detected in clinical specimens from sentinel and non-sentinel (through hospital and peripheral laboratories) patients were tested for Antiviral Susceptibility. Fifty percent inhibitory concentrations (IC50s) for the NAIs oseltamivir and zanamivir were determined using a fluorescent inhibition assay. Sequencing of the neuraminidase (NA) gene and the M2 ion channel gene was used to identify mutations previously associated with Antiviral resistance to NAI and M2I respectively. To determine the possible impact of oseltamivir resistant A(H1N1) viruses on the severity of disease, basic descriptive variables and information on symptoms, complications and exposure to Antivirals were collected. Results: A(H1N1) influenza viruses (91% of all subtyped influenza A viruses) dominated the first part of the 2007/2008 winter season followed by type B viruses from week 9/2008 onward (Figure 1). By the end of March 2008, 132 isolates [119 A( H1N1), 1 A(H3N2), 12 B] were analyzed for Antiviral resistance. Resistant strains were only detected among the A(H1N1) viruses from sentinel and non-sentinel sources; 33 (28%) were found resistant and contained the H274Y substitution in the neuraminidase that has been associated with oseltamivir resistance previously. None of the oseltamivir resistant viruses tested for zanamivir and amantadine Susceptibility were resistant to these Antivirals. Further analysis of A(H1N1) viruses for which the NA nucleotide sequence was available showed that the resistant viruses (n=28) had glycine (G) at position 354, whereas the sensitive viruses (n=75) had aspartic acid (D) at that position. This substitution does not have known association with oseltamivir resistance. By four-week period, the proportion resistant viruses increased from 0% in weeks 40-51/2007 to 14% in weeks 52/2007-3/2008, 34% in weeks 4-7/2008 and 35% in weeks 8-11/2008. For a break down by week see Figure 1. Basic descriptive variables were available for all 119 patients with A(H1N1) virus and clinical data for 30 (all sentinel patients). The proportion resistant strains among viruses from sentinel and non-sentinel patients was not significantly different, 20% and 30% respectively (X2=1.196, p=0.274). Furthermore, no differences (p>0.05) were found between patients infected with oseltamivir resistant or sensitive virus with respect to age, gender, symptoms, complications or death. None of the 30 patients for which clinical data were available used oseltamivir prior to virus isolation. Conclusions Similar to many countries in Europe and worldwide, oseltamivir resistant A(H1N1) influenza viruses started to spread in the Netherlands during the 2007/2008 winter season with an overall prevalence of 28% among 119 A(H1N1) viruses analyzed by March 2008. Based on the current data, no differences in clinical impact between resistant and sensitive viruses were found. The analysis will be repeated when more data become available. Acknowledgements: We thank all patients and their general practitioners or hospital physicians for providing information and specimens for investigation, the Dutch virologists for sending non-sentinel virus isolates to the NIC, and the Dutch Society for Clinical Virology for their help in designing the clinical study among non-sentinel patients.
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influenza Antiviral Susceptibility monitoring activities in relation to national Antiviral stockpiles in europe during the winter 2006 2007 season
Eurosurveillance, 2007Co-Authors: Adam Meijer, Angie Lackenby, Alan J. Hay, Maria ZambonAbstract:Due to the influenza pandemic threat, many countries are stockpiling Antivirals in the hope of limiting the impact of a future pandemic virus. Since resistance to Antiviral drugs would probably significantly alter the effectiveness of Antivirals, surveillance programmes to monitor the emergence of resistance are of considerable importance. During the 2006/2007 influenza season, an inventory was conducted by the European Surveillance Network for Vigilance against Viral Resistance (VIRGIL) in collaboration with the European Influenza Surveillance Scheme (EISS) to evaluate Antiviral Susceptibility testing by the National Influenza Reference Laboratories (NIRL) in relation to the national Antiviral stockpile in 30 European countries that are members of EISS. All countries except Ukraine had a stockpile of the neuraminidase inhibitor (NAI) oseltamivir. Additionally, four countries had a stockpile of the NAI zanamivir and three of the M2 ion channel inhibitor rimantadine. Of 29 countries with a NAI stockpile, six countries'; NIRLs could determine virus Susceptibility by 50% inhibitory concentration (IC50) and in 13 countries it could be done by sequencing. Only in one of the three countries with a rimantadine stockpile could the NIRL determine virus Susceptibility, by sequencing only. However, including the 18 countries that had plans to introduce or extend Antiviral Susceptibility testing, the NIRLs of 21 of the 29 countries with a stockpile would be capable of Susceptibility testing appropriate to the stockpiled drug by the end of the 2007/2008 influenza season. Although most European countries in this study have stockpiles of influenza Antivirals, Susceptibility surveillance capability by the NIRLs appropriate to the stockpiled Antivirals is limited.
Angie Lackenby - One of the best experts on this subject based on the ideXlab platform.
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Virological self-sampling to monitor influenza Antiviral Susceptibility in a community cohort
The Journal of antimicrobial chemotherapy, 2013Co-Authors: Angie Lackenby, Catherine Thompson, Alex J. Elliot, Cassandra Powers, Nick Andrews, Joanna Ellis, Alison Bermingham, Monica Galiano, S. Large, H. DurnallAbstract:OBJECTIVE: To perform Antiviral Susceptibility monitoring of treated individuals in the community during the 2009 influenza A(H1N1) pandemic in England. PATIENTS AND METHODS: Between 200 and 400 patients were enrolled daily through the National Pandemic Flu Service (NPFS) and issued with a self-sampling kit. Initially, only persons aged 16 and over were eligible, but from 12 November (week 45), self-sampling was extended to include school-age children (5 years and older). All samples received were screened for influenza A(H1N1)pdm09 as well as seasonal influenza [A(H1N1), A(H3N2) and influenza B] by a combination of RT-PCR and virus isolation methods. Influenza A(H1N1)pdm09 RT-PCR-positive samples were screened for the oseltamivir resistance-inducing H275Y substitution, and a subset of samples also underwent phenotypic Antiviral Susceptibility testing by enzyme inhibition assay. RESULTS: We were able to detect virus by RT-PCR in self-taken samples and recovered infectious virus enabling further virological characterization. The majority of influenza A(H1N1)pdm09 RT-PCR-positive NPFS samples (n = 1273) were taken after oseltamivir treatment had begun. No reduction in phenotypic Susceptibility to neuraminidase inhibitors was detected, but five cases with minority quasi-species of oseltamivir-resistant virus (an H275Y amino acid substitution in neuraminidase) were detected. CONCLUSIONS: Self-sampling is a useful tool for community surveillance, particularly for the follow-up of drug-treated patients. The virological study of self-taken samples from the NPFS provided a unique opportunity to evaluate the emergence of oseltamivir resistance in treated individuals with mild illness in the community, a target population that may not be captured by traditional sentinel surveillance schemes.
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Guidance for clinical and public health laboratories testing for influenza virus Antiviral drug Susceptibility in Europe
Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology, 2013Co-Authors: Francisco Pozo, Angie Lackenby, R S Daniels, Eeva Broberg, Vincent Enouf, Bruno Lina, Helena Rebelo De Andrade, Athanasios Kossyvakis, Adam MeijerAbstract:Abstract Two classes of Antiviral drugs are licensed in Europe for treatment and prophylaxis of influenza; the M2 ion-channel blockers amantadine and rimantadine acting against type A influenza viruses only and the neuraminidase enzyme inhibitors zanamivir and oseltamivir acting against type A and type B influenza viruses. This guidance document was developed for but not limited to the European Union (EU) and other European Economic Area (EEA) countries on how and when to test for influenza virus Antiviral drug Susceptibility. It is aimed at clinical and influenza surveillance laboratories carrying out Antiviral drug Susceptibility testing on influenza viruses from patients suspected of harbouring viruses with reduced Susceptibility or for the monitoring of the emergence of such among circulating viruses, respectively. Therefore, the guidance should not be read as a directive or an algorithm for treatment. Monitoring for emergence of influenza viruses with reduced drug Susceptibility in hospitalized cases is crucial for decision making on possible changes to Antiviral treatment. Therefore, it is important to test for Antiviral Susceptibility in certain patient groups, such as patients treated with influenza Antiviral drugs. It is also important to determine the frequency of viruses with natural (not related to drug use) reduced Susceptibility among community and hospitalized cases, as this knowledge is essential for making empirical Antiviral treatment decisions. Furthermore, testing of specimens from community influenza patients is needed to determine the frequency of viruses with reduced Susceptibility and good viral fitness that are readily transmissible, as they may become dominant among circulating viruses. Phenotypic neuraminidase enzyme inhibition assays are recommended to determine the level of inhibition of the neuraminidase enzyme by Antiviral drugs as a measure of drug Susceptibility of the virus. Genotypic assays are recommended to identify amino acid substitutions in the neuraminidase and M2 ion-channel proteins that have been associated with reduced Antiviral Susceptibility previously. By 2012 all circulating seasonal influenza A(H1N1)pdm09 and A(H3N2) viruses were naturally resistant to the M2 ion-channel blockers, so priority should be given to testing for neuraminidase inhibitor Susceptibility.
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Evaluation of influenza virus Antiviral Susceptibility testing in Europe: results from the first external quality assessment exercise.
Journal of Clinical Virology, 2013Co-Authors: Catherine Thompson, Angie Lackenby, Adam Meijer, R S Daniels, J W Mccauley, D Pereyaslov, Eeva Broberg, Maria ZambonAbstract:Abstract Background The first Antiviral Susceptibility testing external quality assessment (EQA) was held for European influenza reference laboratories during winter 2010/11. Objectives To assess European network influenza Antiviral Susceptibility testing capability and provide participants with an independent performance evaluation. Study design The EQA panel contained ten coded specimens of inactivated human influenza A and B viruses with reduced Susceptibility to neuraminidase inhibitors (NAI), or adamantanes. Twenty-four laboratories from 19 member states of the WHO European region analysed the panel using phenotypic (determination of 50% inhibitory concentration (IC 50 ) values by neuraminidase (NA) enzyme inhibition assay) and/or genotypic methods. Results All 24 laboratories returned genotypic data for A(H1N1)pdm09 influenza virus, 18 (75%) for former seasonal A(H1N1), 16 (67%) for A(H3N2) and 15 (63%) for influenza B virus, correctly identifying NAI or adamantane reduced Susceptibility-associated substitutions in the NA (mean 84%; range 52–100%) or M2 (mean 85%; range 73–94%), respectively. Thirteen laboratories (54%) returned phenotypic NAI Susceptibility data. Despite inter-laboratory and inter-assay IC 50 value variation, all 13 laboratories correctly identified oseltamivir reduced Susceptibility/resistance in pure preparations of A(H1N1) oseltamivir-resistant viruses. However, only 11 (85%) identified oseltamivir reduced Susceptibility/resistance in a mixture of A(H1N1)pdm09 oseltamivir-sensitive/-resistant viruses. Furthermore, 3 laboratories (23%) considered oseltamivir-sensitive influenza B virus reduced susceptible/resistant. Conclusions Detection of NA-H275Y in A(H1N1) viruses was achieved by most laboratories. IC 50 values and interpretation thereof varied for a sensitive/resistant virus mixture and for influenza B virus. The results of this exercise will assist harmonisation of Antiviral Susceptibility testing, interpretation and reporting within the European network through targeted training.
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the potential impact of neuraminidase inhibitor resistant influenza
Current Opinion in Infectious Diseases, 2008Co-Authors: Angie Lackenby, Catherine I Thompson, Jane DemocratisAbstract:Purpose of reviewNeuraminidase inhibitor resistant influenza virus has recently emerged, and circulated, in untreated persons. Influenza virus evolution is causing Antiviral Susceptibility to change. We review the latest research in this rapidly moving field.Recent findingsOseltamivir-resistant infl
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influenza Antiviral Susceptibility monitoring activities in relation to national Antiviral stockpiles in europe during the winter 2006 2007 season
Eurosurveillance, 2007Co-Authors: Adam Meijer, Angie Lackenby, Alan J. Hay, Maria ZambonAbstract:Due to the influenza pandemic threat, many countries are stockpiling Antivirals in the hope of limiting the impact of a future pandemic virus. Since resistance to Antiviral drugs would probably significantly alter the effectiveness of Antivirals, surveillance programmes to monitor the emergence of resistance are of considerable importance. During the 2006/2007 influenza season, an inventory was conducted by the European Surveillance Network for Vigilance against Viral Resistance (VIRGIL) in collaboration with the European Influenza Surveillance Scheme (EISS) to evaluate Antiviral Susceptibility testing by the National Influenza Reference Laboratories (NIRL) in relation to the national Antiviral stockpile in 30 European countries that are members of EISS. All countries except Ukraine had a stockpile of the neuraminidase inhibitor (NAI) oseltamivir. Additionally, four countries had a stockpile of the NAI zanamivir and three of the M2 ion channel inhibitor rimantadine. Of 29 countries with a NAI stockpile, six countries'; NIRLs could determine virus Susceptibility by 50% inhibitory concentration (IC50) and in 13 countries it could be done by sequencing. Only in one of the three countries with a rimantadine stockpile could the NIRL determine virus Susceptibility, by sequencing only. However, including the 18 countries that had plans to introduce or extend Antiviral Susceptibility testing, the NIRLs of 21 of the 29 countries with a stockpile would be capable of Susceptibility testing appropriate to the stockpiled drug by the end of the 2007/2008 influenza season. Although most European countries in this study have stockpiles of influenza Antivirals, Susceptibility surveillance capability by the NIRLs appropriate to the stockpiled Antivirals is limited.
Elsa B. Damonte - One of the best experts on this subject based on the ideXlab platform.
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changes in Antiviral Susceptibility to entry inhibitors and endocytic uptake of dengue 2 virus serially passaged in vero or c6 36 cells
Virus Research, 2014Co-Authors: Eliana G. Acosta, Luana Érica Piccini, Laura B. Talarico, Viviana Castilla, Elsa B. DamonteAbstract:The aim of the present study was to analyze the influence of virus origin, mammalian or mosquito cell-derived, on Antiviral Susceptibility of DENV-2 to entry inhibitors and the association of this effect with any alteration in the mode of entry into the cell. To this end, ten serial passages of DENV-2 were performed in mosquito C6/36 cells or monkey Vero cells and the Antiviral Susceptibility of each virus passage to sulfated polysaccharides (SPs), like heparin and carrageenans, was evaluated by a virus plaque reduction assay. After serial passaging in Vero cells, DENV-2 became increasingly resistant to SP inhibition whereas the Antiviral Susceptibility was not altered in virus propagated in C6/36 cells. The change in Antiviral Susceptibility was associated to a differential mode of entry into the host cell. The route of endocytic entry for productive Vero cell infection was altered from a non-classical clathrin independent pathway for C6/36-grown virus to a clathrin-mediated endocytosis when the virus was serially propagated in Vero cells. Our results show the impact of the cellular system used for successive propagation of DENV on the initial interaction between the host cell and the virion in the next round of infection and the relevant consequences it might have during the in vitro evaluation of entry inhibitors.
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Changes in Antiviral Susceptibility to entry inhibitors and endocytic uptake of dengue-2 virus serially passaged in Vero or C6/36 cells.
Virus research, 2014Co-Authors: Eliana G. Acosta, Luana Érica Piccini, Laura B. Talarico, Viviana Castilla, Elsa B. DamonteAbstract:The aim of the present study was to analyze the influence of virus origin, mammalian or mosquito cell-derived, on Antiviral Susceptibility of DENV-2 to entry inhibitors and the association of this effect with any alteration in the mode of entry into the cell. To this end, ten serial passages of DENV-2 were performed in mosquito C6/36 cells or monkey Vero cells and the Antiviral Susceptibility of each virus passage to sulfated polysaccharides (SPs), like heparin and carrageenans, was evaluated by a virus plaque reduction assay. After serial passaging in Vero cells, DENV-2 became increasingly resistant to SP inhibition whereas the Antiviral Susceptibility was not altered in virus propagated in C6/36 cells. The change in Antiviral Susceptibility was associated to a differential mode of entry into the host cell. The route of endocytic entry for productive Vero cell infection was altered from a non-classical clathrin independent pathway for C6/36-grown virus to a clathrin-mediated endocytosis when the virus was serially propagated in Vero cells. Our results show the impact of the cellular system used for successive propagation of DENV on the initial interaction between the host cell and the virion in the next round of infection and the relevant consequences it might have during the in vitro evaluation of entry inhibitors.
Elena A Govorkova - One of the best experts on this subject based on the ideXlab platform.
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Susceptibility of avian influenza viruses of the n6 subtype to the neuraminidase inhibitor oseltamivir
Antiviral Research, 2012Co-Authors: Terri D Stoner, Jasmine Turner, Nicholas J Negovetich, Elena A Govorkova, Sharon Frase, David E Stallknecht, Patrick Seiler, Scott Krauss, Robert G. WebsterAbstract:Abstract Avian influenza viruses are a source of genetic material that can be transmitted to humans through direct introduction or reassortment. Although there is a wealth of information concerning global monitoring for Antiviral resistance among human viruses of the N1 and N2 neuraminidase (NA) subtypes, information concerning avian viruses of these and other NA subtypes is limited. We undertook a surveillance study to investigate the Antiviral Susceptibility of avian influenza N6 NA viruses, the predominant subtype among wild waterfowl. We evaluated 73 viruses from North American ducks and shorebirds for Susceptibility to the NA inhibitor oseltamivir in a fluorescence-based NA enzyme inhibition assay. Most (90%) had mean IC50 values ranging from 50.0 nM. Susceptibility to oseltamivir remained stable among all isolates collected over approximately three decades (P ⩽ 0.74). Two isolates with I222V NA substitution had moderately reduced Susceptibility to oseltamivir in vitro (IC50, 30.0 and 40.0 nM). One field sample was a mixed population containing an avian paramyxovirus (APMV) and H4N6 influenza virus, as revealed by electron microscopy and hemagglutination inhibition assays with a panel of anti-APMV antisera. This highlights the importance of awareness and careful examination of non-influenza pathogens in field samples from avian sources. This study showed that oseltamivir-resistant N6 NA avian influenza viruses are rare, and must be tested both phenotypically and genotypically to confirm resistance.
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Fitness of neuraminidase inhibitor-resistant influenza A viruses
Current opinion in virology, 2011Co-Authors: Tatiana Baranovich, Robert G. Webster, Elena A GovorkovaAbstract:Antiviral drugs are important components for the control of influenza. The key question is whether Antiviral use or natural virus evolution will lead to the emergence of drug-resistant virus with comparable or superior fitness to drug-susceptible counterpart. Currently, neuraminidase (NA) inhibitors (NAIs) are the first choice for influenza prevention and treatment. In this article we will review complex process of the risk assessment for the fitness of NAIs-resistant seasonal H1N1 and H3N2, pandemic 2009 H1N1, and highly pathogenic H5N1 influenza A viruses: identification of Antiviral Susceptibility, degree of functional NA loss, molecular markers of resistance, and evaluation of replicative ability in vivo, virulence and transmissibility in animal studies (mouse, ferret, and guinea pig models).
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Antiviral Susceptibility of Avian and Swine Influenza Virus of the N1 Neuraminidase Subtype
Journal of virology, 2010Co-Authors: Terri D Stoner, Nicholas J Negovetich, David E Stallknecht, Scott Krauss, Rebecca M. Dubois, Dennis A. Senne, Marie Gramer, Seth R. Swafford, Thomas J. Deliberto, Elena A GovorkovaAbstract:Influenza viruses of the N1 neuraminidase (NA) subtype affecting both animals and humans caused the 2009 pandemic. Anti-influenza virus NA inhibitors are crucial early in a pandemic, when specific influenza vaccines are unavailable. Thus, it is urgent to confirm the Antiviral Susceptibility of the avian viruses, a potential source of a pandemic virus. We evaluated the NA inhibitor susceptibilities of viruses of the N1 subtype isolated from wild waterbirds, swine, and humans. Most avian viruses were highly or moderately susceptible to oseltamivir (50% inhibitory concentration [IC50], 50 nM) but were sensitive to the NA inhibitors zanamivir and peramivir. Oseltamivir Susceptibility ranged more widely among the waterbird viruses (IC50, 0.5 to 154.43 nM) than among swine and human viruses (IC50, 0.33 to 2.56 nM). Swine viruses were sensitive to oseltamivir, compared to human seasonal H1N1 isolated before 2007 (mean IC50, 1.4 nM). Avian viruses from 2007 to 2008 were sensitive to oseltamivir, in contrast to the emergence of resistant H1N1 in humans. Susceptibility remained high to moderate over time among influenza viruses. Sequence analysis of the outliers did not detect molecular markers of drug-resistance (e.g., H275Y NA mutation [N1 numbering]) but revealed mutations outside the NA active site. In particular, V267I, N307D, and V321I residue changes were found, and structural analyses suggest that these mutations distort hydrophobic pockets and affect residues in the NA active site. We determined that natural oseltamivir resistance among swine and wild waterbirds is rare. Minor naturally occurring variants in NA can affect Antiviral Susceptibility.