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Influenza Update: Highlights from the 48th Annual Meeting of the Infectious Diseases Society of America

By Amesh A. Adalja, MD, October 29, 2010

The 48th annual meeting of the Infectious Diseases Society of America (IDSA) was held in Vancouver, BC, October 21-24, 2010. At least 10 sessions focused on influenza; the 2 summarized below provided important new insights gleaned from the experience with the 2009 H1N1 influenza pandemic.

Real-life Experience with the H1N1 2009 Pandemic

Robert Webster, chair of the Department of Virology and Molecular Biology at St. Jude Children’s Research Hospital, moderated a GSK-sponsored symposium entitled “Real-life Experience with the H1N1 2009 Pandemic.” He began the discussion by stating that we “haven’t seen everything H1N1 could throw at us” in terms of recombination events and drift variants, but he anticipates a quiescent period after the pandemic. In his remarks, Webster also warned that the recent H3N2 isolates could become an important player in future flu seasons, and he reiterated the dangers of H5N1 avian flu. Finally, he cautioned against developing flu fatigue while contemplating what might happen next with this virus, noting that we “can’t trust influenza.”
Other symposium participants highlighted the encouraging safety data that has accrued with GSK’s ASO3 adjuvanted pandemic vaccine, which was used in Europe and Canada.
Jennifer McKimm-Breschkin, from the Commonwealth Scientific and Industrial Research Organization in Australia, provided an overview of antiviral resistance issues with influenza. She explained that peramivir, oseltamivir, and zanamivir are derived from a parent compound known as DANA, which binds avidly to the viral neuraminidase active site. Oseltamivir includes 2 modifications from the DANA structure that require an active site conformation change for binding. This area is a site of resistance mutations (eg, H274Y). Zanamivir has 1 modification from the DANA structure and is, therefore, less susceptible to resistance, while peramivir cross-resistance occurs in oseltamivir-resistant viruses because peramivir and oseltamivir are similar in structure.  

It has been thought that resistance mutations such as the H274Y mutation would reduce the fitness of the virus and decrease transmissibility. However, as the spread of this mutation indicates, this was not the case. McKimm-Breshkin stated that in recent years, the trend with influenza viruses, prior to the H274Y mutation, had been to develop a “super-fit” neuraminidase enzyme that was then able to accommodate the cost of the mutation without compromising transmissibility.
Also noted in this session is the discovery of oseltamivir in rivers in Japan, which has raised the concern that consumption of contaminated water by aquatic birds could give rise to resistance, although there is no data confirming this phenomenon.

Secondary Bacterial Infections with Influenza

Several sessions were dedicated to the topic of bacterial infections that complicate influenza—a phenomenon that occurred in 29% to 56% of 2009 H1N1 cases, with a mortality rate ranging from 14% to 46%.
A presentation by Erika Wissinger, from Imperial College, established the mechanism of bacterial pneumonia secondary to influenza, which includes:

  • compromised epithelial barriers;
  • increased access to bacterial receptors;
  • induced apoptosis of WBCs;
  • 1000-fold increase in colony count of nasopharyngeal colonizing bacteria;
  • dampened immune response due to the action of CD200; and
  • alterations of antibacterial peptides (eg, lysozyme).

John McCullers, of St. Jude Children’s Research Hospital, presented data on strategies for treating bacterial pneumonia following influenza. He stressed the danger of using cell wall active antibiotics (vancomycin, beta-lactams), which enhance inflammation after bacterial cell lysis in aTLR-2-dependent pathway. McCullers’ data is derived from a murine model and shows that protein synthesis inhibitors—especially azithromycin—may ameliorate this complication and should be considered in the treatment of these cases.