Giuseppe
Emeritus
Rapid Selection of a Transmissible Multidrug-Resistant Influenza A/H3N2 Virus in an Immunocompromised Host. (J Infect Dis., abstract, edited)
[Source: US National Library of Medicine, (LINK). Edited.]
J Infect Dis. 2010 Mar 29. [Epub ahead of print]
Rapid Selection of a Transmissible Multidrug-Resistant Influenza A/H3N2 Virus in an Immunocompromised Host.
Memoli MJ, Hrabal RJ, Hassantoufighi A, Jagger BW, Sheng ZM, Eichelberger MC, Taubenberger JK. - Viral Pathogenesis and Evolution Section, Laboratory of Infectious Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, and 2Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland.
Background.
The overall impact of influenza virus infection in immunocompromised patients is largely unknown. Antigenic drift and genetic variations during prolonged influenza infection have been demonstrated. In this report we describe a multidrug-resistant H3N2 influenza virus isolated from an immunocompromised patient after 5 days of therapy.
Methods.
Multiple nasal wash samples were collected from an infected patient, and viral isolates were characterized. Sensitivity to antiviral agents was evaluated. Fitness and transmissibility were assessed in ferrets and tissue culture.
Results.
An in-frame 4-amino acid deletion emerged in the neuraminidase (NA) gene of an H3N2 virus after 5 days of oseltamivir therapy. No other changes in the NA or hemagglutinin genes were noted. Drug sensitivity assays revealed resistance to oseltamivir (>10-fold increase in 50% inhibitory concentration [IC(50)]) and reduction in sensitivity to zanamivir (3-7-fold increase in IC(50) or 50% effective concentration). No change in fitness or transmissibility was observed.
Conclusions.
An in-frame NA gene deletion was rapidly selected for in an immunocompromised patient, resulting in decreased sensitivity of the isolate to available NA inhibitors without a change in fitness or transmissibility. This finding has implications for our understanding of the emergence of antiviral resistance and treatment of patients with influenza A infection, especially those who are immunocompromised.
PMID: 20350163 [PubMed - as supplied by publisher]
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[Source: US National Library of Medicine, (LINK). Edited.]
J Infect Dis. 2010 Mar 29. [Epub ahead of print]
Rapid Selection of a Transmissible Multidrug-Resistant Influenza A/H3N2 Virus in an Immunocompromised Host.
Memoli MJ, Hrabal RJ, Hassantoufighi A, Jagger BW, Sheng ZM, Eichelberger MC, Taubenberger JK. - Viral Pathogenesis and Evolution Section, Laboratory of Infectious Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, and 2Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland.
Background.
The overall impact of influenza virus infection in immunocompromised patients is largely unknown. Antigenic drift and genetic variations during prolonged influenza infection have been demonstrated. In this report we describe a multidrug-resistant H3N2 influenza virus isolated from an immunocompromised patient after 5 days of therapy.
Methods.
Multiple nasal wash samples were collected from an infected patient, and viral isolates were characterized. Sensitivity to antiviral agents was evaluated. Fitness and transmissibility were assessed in ferrets and tissue culture.
Results.
An in-frame 4-amino acid deletion emerged in the neuraminidase (NA) gene of an H3N2 virus after 5 days of oseltamivir therapy. No other changes in the NA or hemagglutinin genes were noted. Drug sensitivity assays revealed resistance to oseltamivir (>10-fold increase in 50% inhibitory concentration [IC(50)]) and reduction in sensitivity to zanamivir (3-7-fold increase in IC(50) or 50% effective concentration). No change in fitness or transmissibility was observed.
Conclusions.
An in-frame NA gene deletion was rapidly selected for in an immunocompromised patient, resulting in decreased sensitivity of the isolate to available NA inhibitors without a change in fitness or transmissibility. This finding has implications for our understanding of the emergence of antiviral resistance and treatment of patients with influenza A infection, especially those who are immunocompromised.
PMID: 20350163 [PubMed - as supplied by publisher]
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