The Experts below are selected from a list of 23715 Experts worldwide ranked by ideXlab platform

Frederick G Hayden - One of the best experts on this subject based on the ideXlab platform.

  • Antiviral Resistance during the 2009 influenza a h1n1 pandemic public health laboratory and clinical perspectives
    Lancet Infectious Diseases, 2012
    Co-Authors: Aeron C. Hurt, Frederick G Hayden, Tawee Chotpitayasunondh, Nancy J Cox, R S Daniels, Alicia M Fry, Larisa V Gubareva, David Hui, Olav Hungnes
    Abstract:

    Influenza A H1N1 2009 virus caused the first pandemic in an era when neuraminidase inhibitor Antiviral drugs were available in many countries. The experiences of detecting and responding to Resistance during the pandemic provided important lessons for public health, laboratory testing, and clinical management. We propose recommendations for Antiviral susceptibility testing, reporting results, and management of patients infected with 2009 pandemic influenza A H1N1. Sustained global monitoring for Antiviral Resistance among circulating influenza viruses is crucial to inform public health and clinical recommendations for Antiviral use, especially since community spread of oseltamivir-resistant A H1N1 2009 virus remains a concern. Further studies are needed to better understand influenza management in specific patient groups, such as severely immunocompromised hosts, including optimisation of Antiviral treatment, rapid sample testing, and timely reporting of susceptibility results.

  • emerging influenza Antiviral Resistance threats
    The Journal of Infectious Diseases, 2011
    Co-Authors: Frederick G Hayden, Menno D De Jong
    Abstract:

    Antiviral Resistance in influenza may not only develop during treatment but also sometimes transmit widely to replace susceptible strains in the absence of drug pressure. This transmission is exemplified by the global spread of adamantane-resistant A(H3N2) viruses since 2003, oseltamivir-resistant seasonal A(H1N1) viruses since 2007, and adamantane-resistant pandemic A(H1N1) viruses in 2009, events that emphasize the unpredictability of influenza viruses and the increasing challenges of clinical management of influenza, especially given the current paucity of therapeutic choices. Three articles in this issue of The Journal of Infectious Diseases extend these observations, describing the plasticity of seasonal A(H1N1) viruses in developing dual adamantane-oseltamivir Resistance [1], the effects on drug susceptibility and viral fitness of various neuraminidase (NA) mutations in pandemic A(H1N1) viruses [2], and the risk of nosocomial spread of oseltamivir-resistant pandemic A(H1N1) virus [3]. Together, these findings illustrate that single reassortment events or mutations can lead to the emergence of transmissible variants of pandemic 2009 or seasonal A(H1N1) viruses unresponsive to most, if not all, of our currently available drugs. This raises multiple questions regarding patient management and preparations for future influenza outbreaks.

  • Antiviral Resistance in influenza viruses implications for management and pandemic response
    The New England Journal of Medicine, 2006
    Co-Authors: Frederick G Hayden
    Abstract:

    Resistance to amantadine has been detected at an extraordinarily high frequency in isolates of influenza A virus. Dr. Frederick Hayden discusses the implications of Resistance to Antiviral agents for the current clinical management of influenza and for planning for a possible pandemic.

  • neuraminidase inhibitor susceptibility network position statement Antiviral Resistance in influenza a h5n1 viruses
    Antiviral Therapy, 2005
    Co-Authors: Frederick G Hayden, Alan W Hampson, Michele Amyard, Arnold S. Monto, Jennifer L Mckimmbreschkin, Alexander Klimov, Masato Tashiro, Catherine A. Macken, Robert G. Webster, Maria Zambon
    Abstract:

    The emerging epidemic of H5N1 avian influenza virus with spillover into the human population in Asia has provoked intense concern globally about the potential of these particularly pathogenic viruses to evolve with the capacity for human-to-human transmission with a consequent pandemic. The availability of Antiviral drugs with activity against influenza A viruses and the recognition of drug-resistant variants to these drugs prompted the following report by a select group of the global experts - members of the Neuraminidase Inhibitor Susceptibility Network - on the best use of the available drugs, both for prophylaxis and treatment. The editors of Antiviral Therapy are pleased to be able to provide this document in an expeditious manner.

  • special article neuraminidase inhibitor susceptibility network position statement Antiviral Resistance in influenza a h5n1 viruses
    2005
    Co-Authors: Frederick G Hayden, Alan W Hampson, Alexander Klimov, Masato Tashiro, Catherine A. Macken, Robert G. Webster, Alan J Hay, Arnold Monto, Jennifer Mckimm, Maria Zambon
    Abstract:

    Division of Infectious Disease and International Health, Department of Internal Medicine, University of Virginia School of Medicine, Charlottesville, VA, USA Chief, Strain Surveillance Section, CDC, Atlanta, USA National Institute of Infectious Diseases, Tokyo, Japan MRC National Institute for Medical Research, London, UK University of Michigan School of Public Health, MI, USA CSIRO Division of Health Sciences and Nutrition, Melbourne, Australia Los Alamos National Laboratory, New Mexico, USA WHO Collaborating Centre for Influenza Reference & Research, Melbourne, Australia St Jude Children's Research Hospital, Memphis, TN, USA Universite Claude Bernard, Lyon, France Health Protection Agency, London, UK

Guy Boivin - One of the best experts on this subject based on the ideXlab platform.

  • Antiviral Resistance in herpes simplex virus and varicella zoster virus infections diagnosis and management
    Current Opinion in Infectious Diseases, 2016
    Co-Authors: Jocelyne Piret, Guy Boivin
    Abstract:

    Purpose of review Aciclovir (ACV) is the first-line drug for the management of herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections. Long-term administration of ACV for the treatment of severe infections in immunocompromised patients can lead to the development of drug Resistance. Furthermore, the emergence of isolates resistant to ACV is increasingly recognized in immunocompetent individuals with herpetic keratitis. This review describes the mechanisms involved in drug Resistance for HSV and VZV, the laboratory diagnosis and management of patients with infections refractory to ACV therapy. Recent findings Genotypic testing is more frequently performed for the diagnosis of infections caused by drug-resistant HSV or VZV isolates. Molecular biology-based systems for the generation of recombinant viruses have been developed to link unknown mutations with their drug phenotypes. Fast and sensitive methods based on next-generation sequencing will improve the detection of heterogeneous viral populations of drug-resistant viruses and their temporal changes during Antiviral therapy, which could allow better patient management. Novel promising compounds acting on targets that differ from the viral DNA polymerase are under clinical development. Summary Antiviral drug Resistance monitoring for HSV and VZV is required for a rational use of Antiviral therapy in high-risk populations.

  • systematic review of influenza Resistance to the neuraminidase inhibitors
    BMC Infectious Diseases, 2011
    Co-Authors: Kristian Thorlund, Guy Boivin, Tahany Awad, Lehana Thabane
    Abstract:

    Antivirals play a critical role in the prevention and the management of influenza. One class of Antivirals, neuraminidase inhibitors (NAIs), is effective against all human influenza viruses. Currently there are two NAI drugs which are licensed worldwide: oseltamivir (Tamiflu®) and zanamivir (Relenza®); and two drugs which have received recent approval in Japan: peramivir and laninamivir. Until recently, the prevalence of Antiviral Resistance has been relatively low. However, almost all seasonal H1N1 strains that circulated in 2008-09 were resistant to oseltamivir whereas about 1% of tested 2009 pandemic H1N1 viruses were found to be resistant to oseltamivir. To date, no studies have demonstrated widespread Resistance to zanamivir. It seems likely that the literature on Antiviral Resistance associated with oseltamivir as well as zanamivir is now sufficiently comprehensive to warrant a systematic review. The primary objectives were to systematically review the literature to determine the incidence of Resistance to oseltamivir, zanamivir, and peramivir in different population groups as well as assess the clinical consequences of Antiviral Resistance. We searched MEDLINE and EMBASE without language restrictions in September 2010 to identify studies reporting incidence of Resistance to oseltamivir, zanamivir, and peramivir. We used forest plots and meta-analysis of incidence of Antiviral Resistance associated with the three NAIs. Subgroup analyses were done across a number of population groups. Meta-analysis was also performed to evaluate associations between Antiviral Resistance and clinical complications and symptoms. We identified 19 studies reporting incidence of Antiviral Resistance. Meta-analysis of 15 studies yielded a pooled incidence rate for oseltamivir Resistance of 2.6% (95%CI 0.7% to 5.5%). The incidence rate for all zanamivir Resistance studies was 0%. Only one study measured incidence of Antiviral Resistance among subjects given peramivir and was reported to be 0%. Subgroup analyses detected higher incidence rates among influenza A patients, especially for H1N1 subtype influenza. Considerable heterogeneity between studies precluded definite inferences about subgroup results for immunocompromised patients, in-patients, and children. A meta-analysis of 4 studies reporting association between oseltamivir-Resistance and pneumonia yielded a statistically significant risk ratio of 4.2 (95% CI 1.3 to 13.1, p = 0.02). Oseltamivir-Resistance was not statistically significantly associated with other clinical complications and symptoms. Our results demonstrate that that a substantial number of patients may become oseltamivir-resistant as a result of oseltamivir use, and that oseltamivir Resistance may be significantly associated with pneumonia. In contrast, zanamivir Resistance has been rarely reported to date.

Mahima Swamy - One of the best experts on this subject based on the ideXlab platform.

  • Intestinal intraepithelial lymphocyte activation promotes innate Antiviral Resistance
    2016
    Co-Authors: Mahima Swamy, James Chettle, Delphine Goubau, Probir Chakravarty, Peter Staeheli, George Ramsay, Caetano Reis E Sousa, Barbara A. Blacklaws, Jonathan L. Heeney, Adrian C. Hayday
    Abstract:

    Unrelenting environmental challenges to the gut epithelium place particular demands on the local immune system. In this context, intestinal intraepithelial lymphocytes (IEL) compose a large, highly conserved Tcell compartment, hypothesized to provide a first line of defence via cytolysis of dysregulated intestinal epithelial cells (IEC) and cytokine-mediated re-growth of healthy IEC. Here we show that one of the most conspicuous impacts of activated IEL on IEC is the functional upregulation of Antiviral interferon (IFN)-responsive genes, mediated by the collective actions of IFNs with other cytokines. Indeed, IEL activation in vivo rapidly provoked type I/III IFN receptor-dependent upregulation of IFN-responsive genes in the villus epithelium. Consistent with this, activated IEL mediators protected cells against virus infection in vitro, and pre-activation of IEL in vivo profoundly limited norovirus infection. Hence, intraepithelial T cell activation offers an overt means to promote the innate antivira

  • intestinal intraepithelial lymphocyte activation promotes innate Antiviral Resistance
    Nature Communications, 2015
    Co-Authors: Mahima Swamy, James Chettle, Tanel Mahlakõiv, Delphine Goubau, Lucie Abelerdorner, Probir Chakravarty
    Abstract:

    Unrelenting environmental challenges to the gut epithelium place particular demands on the local immune system. In this context, intestinal intraepithelial lymphocytes (IEL) compose a large, highly conserved T cell compartment, hypothesized to provide a first line of defence via cytolysis of dysregulated intestinal epithelial cells (IEC) and cytokine-mediated re-growth of healthy IEC. Here we show that one of the most conspicuous impacts of activated IEL on IEC is the functional upregulation of Antiviral interferon (IFN)-responsive genes, mediated by the collective actions of IFNs with other cytokines. Indeed, IEL activation in vivo rapidly provoked type I/III IFN receptor-dependent upregulation of IFN-responsive genes in the villus epithelium. Consistent with this, activated IEL mediators protected cells against virus infection in vitro, and pre-activation of IEL in vivo profoundly limited norovirus infection. Hence, intraepithelial T cell activation offers an overt means to promote the innate Antiviral potential of the intestinal epithelium.

Alexander L Greninger - One of the best experts on this subject based on the ideXlab platform.

  • evaluation of genotypic Antiviral Resistance testing as an alternative to phenotypic testing in a patient with dock8 deficiency and severe hsv 1 disease
    The Journal of Infectious Diseases, 2020
    Co-Authors: Amanda M Casto, Alexander L Greninger, Sean C Stout, Rangaraj Selvarangan, Alexandra F Freeman, Brandon D Newell, Erin D Stahl, Atif A Ahmed, Dwight E Yin
    Abstract:

    Antiviral Resistance frequently complicates the treatment of herpes simplex virus (HSV) infections in immunocompromised patients. Here we present the case of an adolescent boy with dedicator of cytokinesis 8 (DOCK8) deficiency, who experienced recurrent infections with resistant HSV-1. We used both phenotypic and genotypic methodologies to characterize the Resistance profile of HSV-1 in the patient and conclude that genotypic testing outperformed phenotypic testing. We also present the first analysis of intrahost HSV-1 evolution in an immunocompromised patient. While HSV-1 can remain static in an immunocompetent individual for decades, the virus from this patient rapidly acquired genetic changes throughout its genome. Finally, we document a likely case of transmitted Resistance in HSV-1 between the patient and his brother, who also has DOCK8 deficiency. This event demonstrates that resistant HSV-1 is transmissible among immunocompromised persons.

  • phenotypic and genotypic Antiviral Resistance testing of hsv 1 causing recurrent cutaneous lesions in a patient with dock8 deficiency
    bioRxiv, 2019
    Co-Authors: Amanda M Casto, Sean C Stout, Rangaraj Selvarangan, Alexandra F Freeman, Brandon D Newell, Erin D Stahl, Alexander L Greninger
    Abstract:

    Abstract Antiviral Resistance frequently complicates treatment of herpes simplex virus (HSV) infections in immunocompromised patients. Here we review the case of an adolescent boy with dedicator of cytokinesis 8 (DOCK8) deficiency, who experienced recurrent infections with resistant HSV-1. We used both phenotypic and genotypic methodologies to characterize the Resistance profile of HSV-1 in the patient and conclude that genotypic testing outperformed phenotypic testing. We also present the first analysis of intrahost HSV-1 evolution in an immunocompromised patient. While HSV-1 can remain static in an immunocompetent individual for decades, the virus from this patient rapidly acquired genetic changes throughout its genome.

  • limited marginal utility of deep sequencing for hiv drug Resistance testing in the age of integrase inhibitors
    Journal of Clinical Microbiology, 2018
    Co-Authors: Ronit R Dalmat, Negar Makhsous, Gregory Pepper, Amalia Magaret, Keith R Jerome, Anna Wald, Alexander L Greninger
    Abstract:

    HIV drug Resistance genotyping is a critical tool in the clinical management of HIV infections. Although Resistance genotyping has traditionally been conducted using Sanger sequencing, next-generation sequencing (NGS) is emerging as a powerful tool due to its ability to detect low-frequency alleles. However, the clinical value added from NGS approaches to Antiviral Resistance testing remains to be demonstrated. We compared the variant detection capacity of NGS versus Sanger sequencing methods for Resistance genotyping in 144 drug Resistance tests (105 protease-reverse transcriptase tests and 39 integrase tests) submitted to our clinical virology laboratory over a four-month period in 2016 for Sanger-based HIV drug Resistance testing. NGS detected all true high-frequency drug Resistance mutations (>20% frequency) found by Sanger sequencing, with greater accuracy in one instance of a Sanger-detected false positive. Freely available online NGS variant callers HyDRA and PASeq were superior to Sanger methods for interpretations of allele linkage and automated variant calling. NGS additionally detected low-frequency mutations (1 to 20% frequency) associated with higher levels of drug Resistance in 30/105 (29%) protease-reverse transcriptase tests and 4/39 (10%) integrase tests. In clinical follow-up of 69 individuals for a median of 674 days, we did not find a difference in rates of virological failure between individuals with and without low-frequency mutations, although rates of virological failure were higher for individuals with drug-relevant low-frequency mutations. However, all 27 individuals who experienced virological failure reported poor adherence to their drug regimen during the preceding follow-up time, and all 19 who subsequently improved their adherence achieved viral suppression at later time points, consistent with a lack of clinical Resistance. In conclusion, in a population with low Antiviral Resistance emergence, NGS methods detected numerous instances of minor alleles that did not result in subsequent bona fide virological failure due to Antiviral Resistance.

  • limited marginal utility of deep sequencing for hiv drug Resistance testing in the age of integrase inhibitors
    bioRxiv, 2018
    Co-Authors: Ronit R Dalmat, Negar Makhsous, Gregory Pepper, Amalia Magaret, Keith R Jerome, Anna Wald, Alexander L Greninger
    Abstract:

    Abstract HIV drug Resistance genotyping is a critical tool in the clinical management of HIV infections. Although Resistance genotyping has traditionally been conducted using Sanger sequencing, next-generation sequencing (NGS) is emerging as a powerful tool due to its ability to detect lower frequency alleles. However, the value added from NGS approaches to Antiviral Resistance testing remains to be demonstrated. We compared the variant detection capacity of NGS versus Sanger sequencing methods for Resistance genotyping of 144 drug Resistance tests (105 protease-reverse transcriptase tests and 39 integrase tests) submitted to our clinical virology laboratory over a four-month period in 2016 for Sanger-based HIV drug Resistance testing. NGS detected all true high frequency drug Resistance mutations (>20% frequency) found by Sanger sequencing, with greater accuracy in one instance of a Sanger-detected false positive. Freely available online NGS variant callers Hydra and PASeq were superior to Sanger methods for interpretations of allele linkage and automated variant calling. NGS additionally detected low frequency mutations (1-20% frequency) associated with higher levels of drug Resistance in 30/105 (29%) of protease-reverse transcriptase tests and 4/39 (10%) of integrase tests. Clinical follow-up of 69 individuals for a median of 674 days found no difference in rates of virological failure between individuals with and without low frequency mutations, although rates of virological failure were higher for individuals with drug-relevant low frequency mutations. However, all 27 individuals who experienced virological failure reported poor adherence to their drug regimen during preceding follow-up time, and all 19 who subsequently improved their adherence achieved viral suppression at later time points consistent with a lack of clinical Resistance. In conclusion, in a population with low Antiviral Resistance emergence, NGS methods detected numerous instances of minor alleles that did not result in subsequent bona fide virological failure due to Antiviral Resistance. Importance Genotypic Antiviral Resistance testing for HIV is an essential component of the clinical microbiology and virology laboratory. Next-generation sequencing (NGS) has emerged as a powerful tool for the detection of low frequency sequence variants (allele frequencies

Peter Staeheli - One of the best experts on this subject based on the ideXlab platform.

  • the discovery of the Antiviral Resistance gene mx a story of great ideas great failures and some success
    Annual Review of Virology, 2018
    Co-Authors: Otto Haller, Heinz Arnheiter, Jovan Pavlovic, Peter Staeheli
    Abstract:

    The discovery of the Mx gene–dependent, innate Resistance of mice against influenza virus was a matter of pure chance. Although the subsequent analysis of this Antiviral Resistance was guided by straightforward logic, it nevertheless led us into many blind alleys and was full of surprising turns and twists. Unexpectedly, this research resulted in the identification of one of the first interferon-stimulated genes and provided a new view of interferon action. It also showed that in many species, MX proteins have activities against a broad range of viruses. To this day, Mx research continues to flourish and to provide insights into the never-ending battle between viruses and their hosts.

  • the discovery of the Antiviral Resistance gene mx a story of great ideas great failures and some success
    Annual Review of Virology, 2018
    Co-Authors: Otto Haller, Heinz Arnheiter, Jovan Pavlovic, Peter Staeheli
    Abstract:

    The discovery of the Mx gene–dependent, innate Resistance of mice against influenza virus was a matter of pure chance. Although the subsequent analysis of this Antiviral Resistance was guided by st...

  • Intestinal intraepithelial lymphocyte activation promotes innate Antiviral Resistance
    2016
    Co-Authors: Mahima Swamy, James Chettle, Delphine Goubau, Probir Chakravarty, Peter Staeheli, George Ramsay, Caetano Reis E Sousa, Barbara A. Blacklaws, Jonathan L. Heeney, Adrian C. Hayday
    Abstract:

    Unrelenting environmental challenges to the gut epithelium place particular demands on the local immune system. In this context, intestinal intraepithelial lymphocytes (IEL) compose a large, highly conserved Tcell compartment, hypothesized to provide a first line of defence via cytolysis of dysregulated intestinal epithelial cells (IEC) and cytokine-mediated re-growth of healthy IEC. Here we show that one of the most conspicuous impacts of activated IEL on IEC is the functional upregulation of Antiviral interferon (IFN)-responsive genes, mediated by the collective actions of IFNs with other cytokines. Indeed, IEL activation in vivo rapidly provoked type I/III IFN receptor-dependent upregulation of IFN-responsive genes in the villus epithelium. Consistent with this, activated IEL mediators protected cells against virus infection in vitro, and pre-activation of IEL in vivo profoundly limited norovirus infection. Hence, intraepithelial T cell activation offers an overt means to promote the innate antivira