Giuseppe
Emeritus
[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]
The Neuraminidase Inhibitor Oseltamivir is Effective against A/Anhui/1/2013 (H7N9) Influenza Virus in a Mouse Model of Acute Respiratory Distress Syndrome
Tatiana Baranovich 1,a, Andrew J. Burnham 1,a, Bindumadhav M. Marathe 1, Jianling Armstrong 1, Yi Guan 2,3,4, Yuelong Shu 5, Joseph Malik Sriyal Peiris 6,7, Richard J. Webby 1,8, Robert G. Webster 1,8 and Elena A. Govorkova 1
Author Affiliations: 1 Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee 38105-3678; 2 Joint Influenza Research Centre [Shantou University Medical College (SUMC)/University of Hong Kong (HKU)], Shantou University, Shantou, PR China; 3 State Key Laboratory of Emerging Infectious Diseases (HKU-Shenzhen Branch), Shenzhen Third People's Hospital, Shenzhen, PR China; 4 State Key Laboratory of Emerging Infectious Diseases/Centre of Influenza Research, School of Public Health, The University of Hong Kong, Hong Kong SAR, PR China; 5 National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Key Laboratory for Medical Virology, National Health and Family Planning Commission, Beijing, PR China; 6 Centre of Influenza Research, School of Public Health, Li Ka Shing Faculty of Medicine, HKU, Pokfulam, Hong Kong; 7 HKU-Pasteur Pole, School of Public Health, Li Ka Shing Faculty of Medicine, HKU, Pokfulam, Hong Kong; 8 Department of Pathology, University of Tennessee, Memphis, Tennessee 38105
Correspondence: Elena A. Govorkova, Department of Infectious Diseases, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105-3678 (elena.govorkova@stjude.org).
a Authors contributed equally to this work.
J Infect Dis. (2013) - doi: 10.1093/infdis/jit554 - First published online: October 16, 2013
Abstract
Background.
High mortality and uncertainty about the effectiveness of neuraminidase inhibitors (NAIs) in humans infected with A (H7N9) influenza viruses are public health concerns.
Methods.
Susceptibility of N9 viruses to NAIs was determined in a fluorescence-based assay. The NAI oseltamivir (5, 20, or 80 mg/kg/day) was administered to BALB/c mice twice daily starting 24, 48, or 72 hours after A/Anhui/1/2013 (H7N9) virus challenge.
Results.
All 12 avian N9 and 3 human H7N9 influenza viruses tested were susceptible to NAIs. Without prior adaptation, A/Anhui/1/2013 (H7N9) caused lethal infection in mice that was restricted to the respiratory tract and resulted in pulmonary edema and acute lung injury with hyaline membrane formation, leading to decreased oxygenation, all characteristics of human acute respiratory distress syndrome. Oseltamivir at 20 and 80 mg/kg protected 80% and 88% of mice when initiated after 24 hours, and the efficacy decreased to 70% and 60%, respectively, when treatment was delayed by 48 hours. Emergence of oseltamivir-resistant variants was not detected.
Conclusions.
H7N9 viruses are comparable to currently circulating influenza A viruses in susceptibility to NAIs. Based on these animal studies, early treatment is associated with improved outcomes.
Received August 5, 2013. Revision received August 28, 2013. Accepted August 30, 2013.
© The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
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The Neuraminidase Inhibitor Oseltamivir is Effective against A/Anhui/1/2013 (H7N9) Influenza Virus in a Mouse Model of Acute Respiratory Distress Syndrome
Tatiana Baranovich 1,a, Andrew J. Burnham 1,a, Bindumadhav M. Marathe 1, Jianling Armstrong 1, Yi Guan 2,3,4, Yuelong Shu 5, Joseph Malik Sriyal Peiris 6,7, Richard J. Webby 1,8, Robert G. Webster 1,8 and Elena A. Govorkova 1
Author Affiliations: 1 Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee 38105-3678; 2 Joint Influenza Research Centre [Shantou University Medical College (SUMC)/University of Hong Kong (HKU)], Shantou University, Shantou, PR China; 3 State Key Laboratory of Emerging Infectious Diseases (HKU-Shenzhen Branch), Shenzhen Third People's Hospital, Shenzhen, PR China; 4 State Key Laboratory of Emerging Infectious Diseases/Centre of Influenza Research, School of Public Health, The University of Hong Kong, Hong Kong SAR, PR China; 5 National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Key Laboratory for Medical Virology, National Health and Family Planning Commission, Beijing, PR China; 6 Centre of Influenza Research, School of Public Health, Li Ka Shing Faculty of Medicine, HKU, Pokfulam, Hong Kong; 7 HKU-Pasteur Pole, School of Public Health, Li Ka Shing Faculty of Medicine, HKU, Pokfulam, Hong Kong; 8 Department of Pathology, University of Tennessee, Memphis, Tennessee 38105
Correspondence: Elena A. Govorkova, Department of Infectious Diseases, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105-3678 (elena.govorkova@stjude.org).
a Authors contributed equally to this work.
J Infect Dis. (2013) - doi: 10.1093/infdis/jit554 - First published online: October 16, 2013
Abstract
Background.
High mortality and uncertainty about the effectiveness of neuraminidase inhibitors (NAIs) in humans infected with A (H7N9) influenza viruses are public health concerns.
Methods.
Susceptibility of N9 viruses to NAIs was determined in a fluorescence-based assay. The NAI oseltamivir (5, 20, or 80 mg/kg/day) was administered to BALB/c mice twice daily starting 24, 48, or 72 hours after A/Anhui/1/2013 (H7N9) virus challenge.
Results.
All 12 avian N9 and 3 human H7N9 influenza viruses tested were susceptible to NAIs. Without prior adaptation, A/Anhui/1/2013 (H7N9) caused lethal infection in mice that was restricted to the respiratory tract and resulted in pulmonary edema and acute lung injury with hyaline membrane formation, leading to decreased oxygenation, all characteristics of human acute respiratory distress syndrome. Oseltamivir at 20 and 80 mg/kg protected 80% and 88% of mice when initiated after 24 hours, and the efficacy decreased to 70% and 60%, respectively, when treatment was delayed by 48 hours. Emergence of oseltamivir-resistant variants was not detected.
Conclusions.
H7N9 viruses are comparable to currently circulating influenza A viruses in susceptibility to NAIs. Based on these animal studies, early treatment is associated with improved outcomes.
Received August 5, 2013. Revision received August 28, 2013. Accepted August 30, 2013.
© The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
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