Neuraminidase inhibitor susceptibility surveillance of influenza viruses circulating worldwide during the 2011 Southern Hemisphere season.

Abstract

BACKGROUND:

Neuraminidase (NA) inhibitors (NAIs) are currently the only antivirals effective against influenza infections due to widespread resistance to M2 inhibitors.

METHODS:

Influenza A and B viruses (n = 1079) collected worldwide between April 01, 2011, and September 30, 2011, were assessed for susceptibility to FDA-approved NAIs, oseltamivir and zanamivir, and investigational peramivir, using the fluorescent-based NA-Fluor™ Influenza Neuraminidase Assay Kit. A subset of viruses (n = 98) were tested for susceptibility to the investigational NAI, laninamivir.

RESULTS:

Influenza A(H1N1)pdm09 viruses (n = 326) were sensitive to all NAIs, except for two (0.6%) with H275Y (N1 numbering; H274Y in N2 numbering) substitution, which exhibited elevated IC50 s for oseltamivir and peramivir, and a third with previously unreported N325K substitution, exhibiting reduced susceptibility to oseltamivir. Influenza A(H3N2) viruses (n = 407) were sensitive to all NAIs. Influenza B viruses (n = 346) were sensitive to all NAIs, except two (0.6%) with H273Y (N1 numbering; H274Y in N2 numbering) substitution, exhibiting reduced susceptibility to oseltamivir and peramivir, and one with previously unreported G140R and N144K substitutions, exhibiting reduced susceptibility to oseltamivir, zanamivir, and peramivir. All influenza A and B viruses were sensitive to laninamivir. It is unknown whether substitutions N325K, G140R, and N144K were present in the virus prior to culturing because clinical specimens were unavailable for testing.

CONCLUSIONS:

This study summarizes NAI susceptibility of influenza viruses circulating worldwide during the 2011 Southern Hemisphere (SH) season, assessed using the NA-Fluor™ Kit. Despite low resistance to NAIs among tested influenza viruses, constant surveillance of influenza virus susceptibility to NAIs should be emphasized.

• Authors: Margaret Okomo-Adhiambo, Katrina Sleeman, Colleen Lysén, Ha T Nguyen, Xiyan Xu, Yan Li, Alexander I Klimov, Larisa V Gubareva
• Journal: Influenza and other respiratory viruses (Influenza Other Respir Viruses) Vol. 7 Issue 5 Pg. 645-58 (Sep 2013) ISSN: 1750-2659 [Electronic] England
• PMID: 23575174 (Publication Type: Journal Article)
• Copyright: © 2013 John Wiley & Sons Ltd.

Chemical References

• Acids, Carbocyclic
• Antiviral Agents
• Cyclopentanes
• Enzyme Inhibitors
• Guanidines
• Pyrans
• Sialic Acids
• Oseltamivir
• laninamivir
• Neuraminidase
• Zanamivir
• peramivir

Topics

• Acids, Carbocyclic
• Africa
• Antiviral Agents (pharmacology)
• Cyclopentanes (pharmacology)
• Drug Resistance, Viral
• Enzyme Inhibitors (pharmacology)
• Global Health
• Guanidines (pharmacology)
• Humans
• Influenza A Virus, H1N1 Subtype (drug effects, genetics, isolation & purification)
• Influenza A Virus, H3N2 Subtype (drug effects, genetics, isolation & purification)
• Influenza B virus (drug effects, genetics, isolation & purification)
• Influenza, Human (drug therapy, virology)
• Neuraminidase (antagonists & inhibitors)
• Oceania
• Oseltamivir (pharmacology)
• Pyrans
• Seasons
• Sentinel Surveillance
• Sialic Acids
• South America
• Zanamivir (analogs & derivatives, pharmacology)