tetano
Editor, Senior Moderator
The Journal of Infectious Diseases 2010;201:656?658
This article is in the public domain, and no copyright is claimed.
0022-1899/2010/20105-0005
DOI: 10.1086/650465
EDITORIAL COMMENTARY
Current Challenges in the Risk Assessment of Neuraminidase Inhibitor‐Resistant Influenza Viruses
Larisa V. Gubareva and
Alicia M. Fry
Influenza Division, National Center for Respiratory Infectious Diseases and Immunization, Coordinated Center for Infectious Diseases, Centers for Diseases Control and Prevention, Atlanta, Georgia
Received 12 August 2009; accepted 12 August 2009; electronically published 25 January 2010.
*
(See the article by Baz et al, on pages 740?745.)
Reprints or correspondence: Dr Larisa Gubareva, 1600 Clifton St NE, CDC, MS G16, Atlanta, GA 30333 (LGubareva@cdc.gov).
In this issue of the Journal, Baz et al [1] present data on the replicative fitness and virulence of seasonal influenza A(H1N1) viruses and their oseltamivir‐resistant variants. The sudden emergence and global spread of oseltamivir‐resistant variants of seasonal influenza A(H1N1) viruses carrying the substitution His→Tyr at position 274 (275 by N1 numbering) in the drug‐targeted neuraminidase (NA) were hallmarks of the 2007?2008 influenza season. The viruses continued to circulate during the next season and increased in prevalence to become the predominant circulating influenza virus strain in several countries. Moreover, there have been rare reports of the acquisition of the H275Y mutation by the pandemic novel influenza A(H1N1) virus (previously referred to as swine‐origin influenza H1N1) that emerged in the spring of 2009. H275Y is the NA mutation that is most frequently associated with oseltamivir resistance in the N1 subtype. The emergence of drug‐resistant viruses that retain replicative fitness is a significant obstacle in the effective management of influenza virus infections and poses a threat to pandemic strategies to reduce morbidity and mortality when vaccine is either not available or in limited supply. There is a need to better understand virological and clinical correlates of viral fitness and the methods used to assess viral fitness. The results of previous in vivo studies indicated that mutations conferring resistance to NA inhibitors (NAIs) often lead to a loss of viral fitness [2?5]. This is in contrast with the results of Baz and colleagues, which suggest that the viral fitness and virulence of oseltamivir‐resistant influenza A(H1N1) viruses were unimpaired compared with those of oseltamivir‐susceptible viruses. The conclusions drawn by Baz and colleagues are consistent with the available (although somewhat limited) epidemiological information [6?9]. Nevertheless, it is essential to analyze in more detail the experiments and experimental design that led to these conclusions.
...
full article
http://www.journals.uchicago.edu/doi/full/10.1086/650465?prevSearch=h1n1&searchHistoryKey=
This article is in the public domain, and no copyright is claimed.
0022-1899/2010/20105-0005
DOI: 10.1086/650465
EDITORIAL COMMENTARY
Current Challenges in the Risk Assessment of Neuraminidase Inhibitor‐Resistant Influenza Viruses
Larisa V. Gubareva and
Alicia M. Fry
Influenza Division, National Center for Respiratory Infectious Diseases and Immunization, Coordinated Center for Infectious Diseases, Centers for Diseases Control and Prevention, Atlanta, Georgia
Received 12 August 2009; accepted 12 August 2009; electronically published 25 January 2010.
*
(See the article by Baz et al, on pages 740?745.)
Reprints or correspondence: Dr Larisa Gubareva, 1600 Clifton St NE, CDC, MS G16, Atlanta, GA 30333 (LGubareva@cdc.gov).
In this issue of the Journal, Baz et al [1] present data on the replicative fitness and virulence of seasonal influenza A(H1N1) viruses and their oseltamivir‐resistant variants. The sudden emergence and global spread of oseltamivir‐resistant variants of seasonal influenza A(H1N1) viruses carrying the substitution His→Tyr at position 274 (275 by N1 numbering) in the drug‐targeted neuraminidase (NA) were hallmarks of the 2007?2008 influenza season. The viruses continued to circulate during the next season and increased in prevalence to become the predominant circulating influenza virus strain in several countries. Moreover, there have been rare reports of the acquisition of the H275Y mutation by the pandemic novel influenza A(H1N1) virus (previously referred to as swine‐origin influenza H1N1) that emerged in the spring of 2009. H275Y is the NA mutation that is most frequently associated with oseltamivir resistance in the N1 subtype. The emergence of drug‐resistant viruses that retain replicative fitness is a significant obstacle in the effective management of influenza virus infections and poses a threat to pandemic strategies to reduce morbidity and mortality when vaccine is either not available or in limited supply. There is a need to better understand virological and clinical correlates of viral fitness and the methods used to assess viral fitness. The results of previous in vivo studies indicated that mutations conferring resistance to NA inhibitors (NAIs) often lead to a loss of viral fitness [2?5]. This is in contrast with the results of Baz and colleagues, which suggest that the viral fitness and virulence of oseltamivir‐resistant influenza A(H1N1) viruses were unimpaired compared with those of oseltamivir‐susceptible viruses. The conclusions drawn by Baz and colleagues are consistent with the available (although somewhat limited) epidemiological information [6?9]. Nevertheless, it is essential to analyze in more detail the experiments and experimental design that led to these conclusions.
...
full article
http://www.journals.uchicago.edu/doi/full/10.1086/650465?prevSearch=h1n1&searchHistoryKey=