This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Contact me when this article is cited  Related Content  • Related articles  • Similar articles in JAMA  Topic Collections  • Viral Infections  • Infectious Diseases, Other  • H1N1 Influenza  • Drug Therapy  • Drug Therapy, Other  • Infectious Diseases  • Alert me on articles by topic  Social Bookmarking   What's this?

Jairo Gooskens, MD; Marcel Jonges, MSc; Eric C. J. Claas, PhD; Adam Meijer, PhD; Peterhans J. van den Broek, MD, PhD; Aloys C. M. Kroes, MD, PhD

JAMA. 2009;301(10):1042-1046. Published online March 2, 2009 (doi:10.1001/jama.2009.297).

Context  The sudden emergence and rapid spread of oseltamivir-resistant influenza A(H1N1) viruses with neuraminidase (NA) gene H274Y amino acid substitution is the hallmark of global seasonal influenza since January 2008. Viruses carrying this mutation are widely presumed to exhibit attenuated pathogenicity, compromised transmission, and reduced lethality.

Objective  To investigate nosocomial viral transmission in a cluster of patients with influenza A(H1N1) virus infection.

Design, Setting, and Patients  Descriptive outbreak investigation of 2 hematopoietic stem cell transplant recipients and an elderly patient who developed hospital-acquired influenza A virus infection following exposure to an index patient with community-acquired H274Y-mutated influenza A(H1N1) virus infection in a medical ward at a Dutch university hospital in February 2008. The investigation included a review of the medical records, influenza virus polymerase chain reaction and culture, phenotypic oseltamivir and zanamivir susceptibility determination, and hemagglutinin chain 1 (HA₁) gene and NA gene sequence analysis.

Main Outcome Measure  Phylogenetic relationship of patient cluster influenza A(H1N1) viruses and other 2007-2008 seasonal influenza A(H1N1) viruses.

Results  Viral HA₁ and NA gene sequence analysis from the 4 patients revealed indistinguishable nucleotide sequences and phylogenetic clustering of H274Y-mutated, oseltamivir-resistant influenza A(H1N1) virus, confirming nosocomial transmission. Influenza virus pneumonia (3 patients) and attributable mortality (2 patients) during active infection was observed in patients with lymphocytopenia at onset.

Conclusion  Seasonal oseltamivir-resistant influenza A(H1N1) viruses with NA gene H274Y mutation are transmitted and retain significant pathogenicity and lethality in high-risk patients.

Author Affiliations: Departments of Medical Microbiology (Drs Gooskens, Claas, and Kroes) and Infectious Diseases (Dr van den Broek), Center of Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands; and Section of Virology, National Institute for Public Health and the Environment, Bilthoven, the Netherlands (Mr Jonges and Dr Meijer).

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

RELATED ARTICLES

Infections With Oseltamivir-Resistant Influenza A(H1N1) Virus in the United States
Nila J. Dharan, Larisa V. Gubareva, John J. Meyer, Margaret Okomo-Adhiambo, Reginald C. McClinton, Steven A. Marshall, Kirsten St. George, Scott Epperson, Lynnette Brammer, Alexander I. Klimov, Joseph S. Bresee, Alicia M. Fry, and for the Oseltamivir-Resistance Working Group
JAMA. 2009;301(10):1034-1041.
ABSTRACT | FULL TEXT  

The Evolution of Influenza Resistance and Treatment
David M. Weinstock and Gianna Zuccotti
JAMA. 2009;301(10):1066-1069.
EXTRACT | FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Oseltamivir-Resistant Influenza A Virus
JWatch General 2009;2009:4-4.
FULL TEXT  

Influenza: Problems with Prevention and Treatment
JWatch Infect. Diseases 2009;2009:1-1.
FULL TEXT  

The Evolution of Influenza Resistance and Treatment
Weinstock and Zuccotti
JAMA 2009;301:1066-1069.
FULL TEXT