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isirv-AVG publications

Links are provided to the online publications, where available (please note that a subscription may be required to obtain the full text of some articles).

3rd AVG Conference:  Influenza and Other Respiratory Virus Infections: Advances in Clinical Management

adobe pdf icon2   Overview of the 3rd iSiRV-Antiviral Group Conference – advances in clinical management Aeron C. Hurt, David S. Hui, Alan Hay, Frederick G. Hayden. Influenza Other Respir Viruses 2015 Jan; 9(1): 20-31

IRV Journal Volume 7, Supplement 3, 2013

2nd AVG Conference:  Severe Influenza: Burden, Pathogenesis and Management

adobe pdf icon2   Antivirals in the 2009 pandemic – lessons and implications for future strategies Deeva Berera, Maria Zambon 
adobe pdf icon2   Detection and management of antiviral resistance for influenza viruses Guy Boivin 
adobe pdf icon2   Viral–bacterial interactions–therapeutic implications Jane C. Deng
adobe pdf icon2   Advances in antivirals for non-influenza respiratory virus infections Frederick G. Hayden 
adobe pdf icon2   Adjunctive therapies and immunomodulating agents for severe influenza David S. C. Hui, Nelson Lee
adobe pdf icon2   Second isirv antiviral group conference: overview Hurt et al
adobe pdf icon2   Influenza prevention and treatment in transplant recipients and immunocompromised hosts Michael G. Ison 
adobe pdf icon2   Influenza vaccines: an Asia–Pacific perspective Lance C. Jennings
adobe pdf icon2   Ventilatory strategies and supportive care in acute respiratory distress syndrome Andrew M. Luks

adobe pdf icon2   Influenza encephalopathy and related neuropsychiatric syndromes Masashi Mizuguchi

IRV Journal Volume 7, Supplement 1, 2012 

1st AVG Conference:   Influenza Antivirals: Efficacy and Resistance 

adobe pdf icon2  Neuraminidase inhibitors for influenza: a review and public health perspective in the aftermath of the 2009 pandemic Charles R. Beck et al   
adobe pdf icon2  Modeling the global transmission of antiviral-resistant influenza viruses Dennis L. Chao 
adobe pdf icon2  Consequences of resistance: in vitro fitness, in vivo infectivity, and transmissibility of oseltamivir-resistant influenza A viruses Elena A. Govorkova
adobe pdf icon2  Newer influenza antivirals, biotherapeutics and combinations Frederick G. Hayden
adobe pdf icon2  Clinical use of approved influenza antivirals: therapy and prophylaxis Michael G. Ison 
adobe pdf icon2  Influenza neuraminidase inhibitors: antiviral action and mechanisms of resistance Jennifer L. McKimm-Breschkin
adobe pdf icon2  Assays for monitoring susceptibility of influenza viruses to neuraminidase inhibitors Margaret Okomo-Adhiambo, Tiffany G.Sheu, Larisa V.Gubareva 
adobe pdf icon2  Overview of the conference: Influenza Antivirals: Efficacy and Resistance, Rio de Janeiro 2011 Noel Roberts, Meera Chand 
adobe pdf icon2  Influenza antivirals: efficacy and resistance Marilda Siqueira, Alan Hay 
adobe pdf icon2  Antivirals in seasonal and pandemic influenza—future perspectives Michael W. Wathen, Mario Barro, Rick A. Bright
adobe pdf icon2  Surveillance for antiviral resistance Maria C. Zambon
adobe pdf icon2  An Overview of Antiviral Drug Resistance Data presented at Options for the Control of Influenza VII. Hong Kong. September 2010.
adobe pdf icon2  Neuraminidase Inhibitor Susceptibility Network (2009). Surveillance for neuraminidase-inhibitor-resistant influenza viruses in Japan, 1996-2007Antiviral Ther. 2009 14 (6): 751-761.
adobe pdf icon2  Neuraminidase Inhibitor Susceptibility Network (2007). Monitoring of neuraminidase inhibitor resistance among clinical influenza virus isolates in Japan during the 2003–2006 influenza seasonsWkly Epidemiol Rec. Apr;82(17):141-52.
adobe pdf icon2  Monto AS, McKimm-Breschkin JL, Macken C, Hampson AW, Hay A, Klimov A, Tashiro M, Webster RG, Aymard M, Hayden FG, Zambon M (2006). Detection of influenza viruses resistant to neuraminidase inhibitors in global surveillance during the first 3 years of their useAntimicrob Agents Chemother. Jul;50(7):2395-402.
adobe pdf icon2  Hayden F, Klimov A, Tashiro M, Hay A, Monto A, McKimm-Breschkin J, Macken C, Hampson A, Webster RG, Amyard M, Zambon M (2005). Neuraminidase inhibitor susceptibility network position statement: antiviral resistance in influenza A/H5N1 virusesAntivir Ther.;10(8):873-7. Review. Erratum in: Antivir Ther. 2006;11(1):130.
adobe pdf icon2  Neuraminidase Inhibitor Susceptibility Network (2005). Use of influenza antivirals during 2003-2004 and monitoring of neuraminidase inhibitor resistanceWkly Epidemiol Rec. Apr 29;80(17):156.
adobe pdf icon2  McKimm-Breschkin J, Trivedi T, Hampson A, Hay A, Klimov A, Tashiro M, Hayden F, Zambon M (2003). Neuraminidase sequence analysis and susceptibilities of influenza virus clinical isolates to zanamivir and oseltamivirAntimicrob Agents Chemother. 47(7):2264-72.
adobe pdf icon2  Wetherall, N. T., T. Trivedi, J. Zeller, C. Hodges-Savola, J. L. McKimm- Breshkin, M. Zambon, and F. G. Hayden (2003). Evaluation of neuraminidase enzyme assays using different substrates to measure susceptibility of influenza virus clinical isolates to neuraminidase inhibitors: report of the Neuraminidase Inhibitor Susceptibility NetworkJ. Clin. Microbiol. 41:742–750.
adobe pdf icon2  Zambon, M., and F. G. Hayden (2001). Position statement; global neuraminidase inhibitor susceptibility network (NISN)Antivir. Res. 49:147–156.

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The predecessor organisation to the isirv Antiviral Group, NISN (the Neuraminidase Inhibitor Susceptibility Network) published a number of scientific papers on the detection and surveillance of neuraminidase inhibitor resistance.


Key Publications on Antiviral Resistance


The scientific papers listed below are a selection of recent and key papers on neuraminidase inhibitor resistance and closely related topics. Links are provided to the online publications, where available (please note that a subscription may be required to obtain the full text of some articles).

It is not possible to provide a comprehensive list in this rapidly emerging area of scientific research.  If you believe there are any significant omissions, please contact us with the details.



Management of influenza infection with antiviral drugs
Moscona A (2008).  Medical management of influenza infection. Annu Rev Med. 2008;59:397-413.

Sugaya N, Tamura D, Yamazaki M, Ichikawa M, Kawakami C, Kawaoka Y, Mitamura K (2008). Comparison of the clinical effectiveness of oseltamivir and zanamivir against influenza virus infection in children. Clin Infect Dis. Aug 1;47(3):339-45.
Hota S, McGeer A (2007).  Antivirals and the control of influenza outbreaks. Clin Infect Dis. Nov 15;45(10):1362-8. Epub 2007 Oct 11.

McGeer A, Green KA, Plevneshi A, Shigayeva A, Siddiqi N et al (2007). Antiviral therapy and outcomes of influenza requiring hospitalization in Ontario, Canada. Clin Infect Dis. Dec 15;45(12):1568-75.
Sander B, Hayden FG, Gyldmark M, Garrison LP Jr (2006). Post-exposure influenza prophylaxis with oseltamivir: cost effectiveness and cost utility in families in the UK. Pharmacoeconomics. 24(4):373-86.
Moscona A (2005).  Neuraminidase inhibitors for influenza.  N Engl J Med. Sep 29; 353(13):1363-73.

Monto A. S (2003). The role of antivirals in the control of influenza. Vaccine 21:1796–1800.

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Clinical implications of NAI resistance

Dharan NJ, Gubarcva LV, Meyer JJ, et al. Infections with oseltamivir-resistant influenza A(H1N1) virus in the United States. JAMA (2009);301(10): 1034-1041.

This study compares people infected with oseltamivir-resistant and oseltamivir-susceptible strains of H1N1 during the 2007-08 season in the USA. The authors found no differences in patient characteristics, symptoms, or severity of illness but report that four patients infected with resistant strains died.

Gooskens J, Jonges M, Claas ECJ, et al. Morbidity and mortality associated with nosocomial transmission of oseltamivir-resistant influenza A(H1N1) virus. JAMA (2009);301(10): 1042-46.

This paper describes an outbreak of resistant H1N1 infections in four patients in a Dutch hospital in February 2008. Three immunocompromised patients became ill after exposure to a patient who was sick with a resistant H1N1 strain. Genetic analysis showed that the viruses all matched, indicating that there was person-to-person in the hospital.

Lackenby A, Thompson CI, Democratis J. The potential impact of neuraminidase inhibitor resistant influenza. Curr Opin Infect Dis. 2008 Dec;21(6):626-38.
van der Vries E, van den Berg B, Schutten M (2008). Fatal oseltamivir-resistant influenza virus infection. N Engl J Med. 2008 Sep 4;359(10):1074-6.
McKimm-Breschkin JL. (2005). Management of influenza virus infections with neuraminidase inhibitors: detection, incidence, and implications of drug resistance. Treat Respir Med. 4:107-116.
McKimm-Breschkin J. L (2000). Resistance to influenza viruses to neuraminidase inhibitors—a review. Antivir Res. 47:1–17.
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Methods of NAI resistance detection
Lackenby A, Democratis J, Siqueira MM, Zambon MC (2008). Rapid quantitation of neuraminidase inhibitor drug resistance in influenza virus quasispecies. Antivir Ther. 13(6):809-20.
Deyde VM, Okomo-Adhiambo M. Sheu TG, Wallis TR, Fry A, Dharan N, Klimov AI, Gubareva LV (2008). Pyrosequencing as a tool to detect molecular markers of resistance to neuraminidase inhibitors in seasonal influenza A viruses. Antivir Res 2008 Oct 7. (Epub ahead of print).
Tisdale M, Daly J, Gor D (2001). Methods for determining resistance to neuraminidase inhibitors.  International Congress Series 1219: 879–886.
Mechanisms of NAI resistance and characterisation of NAI resistant viruses
Barrett S, Mohr PG, Schmidt PM, McKimm-Breschkin JL (2011). Real Time Enzyme Inhibition Assays Provide Insights into Differences in Binding of Neuraminidase Inhibitors to Wild Type and Mutant Influenza Viruses. PLoS ONE 6(8): e23627. Doi:10.1371/journal.pone.0023627.
Mohr PG, Geyer H, McKimm-Breschkin JL (2011). Mixed influenza A and B infections complicate the detection of influenza viruses with altered sensitivities to neuraminidase inhibitors. Antivir Res. Jul; 91(1):20-2. Epub 2011 Apr 23. Summary of publication.

Ferraris O, Lina B (2008). Mutations of neuraminidase implicated in neuraminidase inhibitors resistance.  J Clin Virol. Jan;41(1):13-9.

Ho HT, Hurt AC, Mosse J, Barr I (2007). Neuraminidase inhibitor drug susceptibility differs between influenza N1 and N2 neuraminidase following mutagenesis of two conserved residues. Antiviral Res. Dec;76(3):263-6. Epub 2007 Aug 27.

Yen H-L, Hoffmann E, Taylor G, Monto A.S, Webster R.G, Govorkova E.A (2006). Importance of neuraminidase active-site residues to the neuraminidase inhibitor resistance of influenza viruses. J Virol. 80 (17): 8787-8795.
Abed Y, Baz M, Boivin G (2006). Impact of neuraminidase mutations conferring influenza resistance to neuraminidase inhibitors in the N1 and N2 genetic backgrounds. Antivir Ther. ;11(8):971-6.

Hurt AC, Iannello P, Jachno K, Komadina N, Hampson AW, Barr IG, McKimm-Breschkin JL(2006). Neuraminidase inhibitor-resistant and -sensitive influenza B viruses isolated from an untreated human patient. Antimicrob Agents Chemother. May;50(5):1872-4.

Yen H-L, Herlocher L.M, Hoffmann E, Matrosovich M.N, Monto A.S, Webster R.G, Govorkova E.A (2005). Neuraminidase inhibitor–resistant influenza viruses may differ substantially in fitness and transmissibility. Antimicrob Agents Chemother. 49 (10): 4075-4084.

Mishin VP, Hayden FG, Gubareva LV (2005). Susceptibilities of antiviral-resistant influenza viruses to novel neuraminidase inhibitors. Antimicrob Agents Chemother. 49(11):4515-20.
Cheam AL, Barr IG, Hampson AW, Mosse J, Hurt AC (2004). In vitro generation and characterisation of an influenza B variant with reduced sensitivity to neuraminidase inhibitors. Antiviral Res. Sep;63(3):177-81.
Gubareva LV, Webster RG, Hayden FG (2001). Comparison of the activities of zanamivir, oseltamivir, and RWJ-270201 against clinical isolates of influenza virus and neuraminidase inhibitor-resistant variants. Antimicrob Agents Chemother. 45(12):3403-8.
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Surveillance for NAI resistance: community isolates
Hauge SH, Dudman S, Borgen K, Lackenby A, Hungnes O (2009).  Emergence and efficient spread of oseltamivir resistant influenza A(H1N1) viruses in Norway in 2007-08. Emerg Infect Dis. 15(2): 155-62.
Stephenson I, Democratis J, Lackenby A, McNally T, Smith J, Pareek J, Ellis J, Bermingham J, Nicholson K, Zambon MC (2009).  Neuraminidase inhibitor resistance following treatment of acute influenza A and B in children with oseltamivir. Clin Infect Dis.15;48(4):389-96.
Besselaar TG, Naidoo D, Buys A, Gregory V, McAnerney J, Manamela JM, et al. (2008). Widespread oseltamivir resistance in influenza A viruses (H1N1), South Africa [letter]. Emerg Infect Dis. 14(11):1809-10.
Hurt AC, Barr IG. Influenza viruses with reduced sensitivity to the neuraminidase inhibitor drugs in untreated young children (2008). Commun Dis Intell. Mar; 32(1):57-62.

Sheu TG, Deyde VM, Okomo-Adhiambo M, Garten RJ, et al (2008).  Surveillance for neuraminidase inhibitor resistance among human influenza A and B viruses circulating worldwide from 2004 to 2008. Antimicrob Agents Chemother. 52(9):3284-92.
Lackenby A, Hungnes O, Dudman SG, Meijer A, Paget WJ, Hay AJ, Zambon MC (2008). Emergence of resistance to oseltamivir among influenza A(H1N1) viruses in Europe. Euro Surveill.  Jan 31;13(5). pii: 8026.
Meijer A, Lackenby A, Hay A, Zambon M (2007). Influenza antiviral susceptibility monitoring activities in relation to national antiviral stockpiles in Europe during the winter 2006/2007 season. Euro Surveill. Apr 1;12(4):E3-4.
Aoki FY, Boivin G, Roberts N (2007). Influenza virus susceptibility and resistance to oseltamivir. Antivir Ther. 2007;12(4 Pt B):603-16.
Hurt AC, Barr IG, Hartel G, Hampson AW (2004). Susceptibility of human influenza viruses from Australasia and South East Asia to the neuraminidase inhibitors zanamivir and oseltamivir. Antiviral Res. Apr; 62(1):37-45.
 Surveillance for NAI resistance: avian and animal influenza viruses
Yun NE, Linde NS, Zacks MA, Barr IG, Hurt AC et al (2008). Injectable peramivir mitigates disease and promotes survival in ferrets and mice infected with the highly virulent influenza virus, A/Vietnam/1203/04 (H5N1). Virol. Apr 25;374(1):198-209.
Ilyushina, NA, Hay A, Yilmaz N , Boon AC, Webster RG, and Govorkova EA (2008). Oseltamivir-Ribavirin Combination Therapy for Highly Pathogenic H5N1 Influenza Virus Infection in Mice. Antimicrob Agents Chemother, 52 (11):3889-3897.
Boltz DA, Ilyushina NA, Arnold CS, Babu YS, Webster RG, Govorkova EA (2008). Intramuscularly administered neuraminidase inhibitor peramivir is effective against lethal H5N1 influenza virus in mice. Antiviral Res., 80:150-157.
Boltz DA, Rehg JE, McClaren JL, Webster RG, and Govorkova EA (2008). Oseltamivir prophylactic regimens prevent H5N1 influenza morbidity and mortality in a ferret model. Journal Infec Dis., 197:1315–1323, 2008.
McKimm-Breschkin JL, Selleck P, Usman TB, Johnson M. (2007) Reduced Sensitivity of influenza A (H5N1) to Oseltamivir. Emerg Infect Dis. 13:1354-1357.
Yen H-L, Ilyushina NA, Salomon R, Hoffmann E, Webster RG,  Govorkova EA (2007). Neuraminidase inhibitor–resistant recombinant A/Vietnam/1203/04 (H5N1) influenza viruses retain their replication efficiency and pathogenicity in vitro and in vivo. J Virol, 81(22): 12418-12426.
Govorkova EA, Ilyushina NA, Boltz DA, Douglas A, Yilmaz N, Webster RG (2007). Efficacy of oseltamivir therapy in ferrets inoculated with different clades of H5N1 influenza virus. Antimicrob Agents Chemother, 51 (4):1414-1424.
Ilyushina NA, Hoffmann E, Salomon R, Webster RA, Govorkova EA (2007). Amantadine-oseltamivir combination therapy for H5N1 influenza virus infection in mice. Antivir Ther, 12: 363-370.
Yen H-L, Monto AS, Webster RG, Govorkova EA (2005).  Virulence may determine the necessary duration and dosage of oseltamivir treatment for highly pathogenic A/Vietnam/1203/04 influenza virus in mice. J Infect Dis. 192 (4): 665-672.
Govorkova EA , Leneva IA, Goloubeva OG, Bush K, Webster RG (2001). Comparison of the efficacy of RWJ-270201, zanamivir, and oseltamivir against H5N1, H9N2, and other avian influenza viruses. Antimicrob Agents Chemother 45: 2723-2732. 
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