Sunday, November 02, 2014

A `Drift’ In A Sea Of Influenza Viruses


P&I Mortality Surveillance by Week & Year - CDC


# 9278


There is always a degree of folly attached to trying to predict the kind of flu season we will have ahead.  The variability in influenza severity can be easily demonstrated by the wide range in the CDC’s mortality estimates, as described in the  August 27, 2010 MMWR report entitled Thompson MG et al. Updated Estimates of Mortality Associated with Seasonal Influenza through the 2006-2007 Influenza Season. MMWR 2010; 59(33): 1057-1062.


CDC estimates that from the 1976-1977 season to the 2006-2007 flu season, flu-associated deaths ranged from a low of about 3,000 to a high of about 49,000 people.


In other words, even across a span of three decades without seeing an influenza pandemic, there was as much as a 12-fold difference in mortality between flu seasons.  


Over the past several years, we’ve seen a huge spread in severity as well, with the 2011-12 flu season perhaps the mildest in three decades (see  2011-2012 Flu Season Draws to a Close), while the following year (2012-13) was deemed moderate-to-severe


Surprisingly, both were H3N2  dominated seasons, which tend to produce more severe flu seasons – particularly among the elderly (see MMWR Influenza Activity — United States, 2012–13 Season and Composition of the 2013–14 Influenza Vaccine) – proving that `rules of thumb’ don’t always work.


Last year we saw the `return’ of the H1N1 strain – which never really went away, but had been dominated by H3N2 since the 2009 pandemic ended. 


As is common with H1N1 strains, younger people were more severely impacted than we normally see with H3N2 (see Influenza Activity — United States, 2013–14 Season and Composition of the 2014–15 Influenza Vaccines), prompting a CDC HAN Advisory On Early pH1N1 Influenza Activity to be issued in late December.


As far as vaccines are concerned, the 2009 H1N1 component has remained remarkably antigenically stable since it emerged more than five years ago.  We keep expecting to see it drift away from its original form, but so far, it hasn’t.

Less stable have been the H3N2 viruses, which continue to drift and form antigenically diverse clades, which constantly bump shoulders as they seek susceptible hosts. The most recent ECDC: Influenza Characterization – Sept 2014 describes 7 distinct genetic groups detected since 2009, making vaccine strain selection more problematic.


Since the fall 2014 vaccines strains were selected last February, surveillance has begun to detect a rise in the number of antigenically drifted H3N2 isolates, prompting the WHO to recommend a strain change for next year’s Southern Hemisphere vaccine formulation from an A/Texas/50/2012 (H3N2)-like virus to an A/Switzerland/9715293/2013 (H3N2)-like virus.


According to the CDC’s latest FluView report – while this new, drifted H3N2 strain has begun to show up in North America, for now, this year’s vaccine strain (A/Texas/50/2012(H3N2)) remains dominant  among the limited number of H3N2 viruses tested.


CDC has antigenically characterized 10 influenza A (H3N2) viruses collected since October 1, 2014. This is the first antigenic characterization data available for H3N2 viruses collected in the United States since October 1, 2014.

  • Seven (70%) of the 10 influenza A (H3N2) viruses tested have been characterized as A/Texas/50/2012-like. This is the influenza A (H3N2) component of the 2014-2015 Northern Hemisphere influenza vaccine. Three (30%) H3N2 viruses were antigenically similar to A/Switzerland/9715293/2013, the H3N2 virus selected for the 2015 Southern Hemisphere influenza vaccine.

Additionally, early surveillance suggests we may be looking at an H3N2-centric flu season.


Influenza A (H3N2), 2009 influenza A (H1N1), and influenza B viruses have all been identified in the U.S. this season. During the week ending October 25, 237 (74.1%) of the 320 influenza-positive tests reported to CDC were influenza A viruses and 83 (25.9%) were influenza B viruses. Of the 82 influenza A viruses that were subtyped, 96% were H3 viruses and 4% were 2009 H1N1 viruses.


Again, flu seasons don’t always end up the way they start out. 


But for now, it looks as if we may be looking at a flu season dominated by H3N2, and with two antigenically divergent clades in circulation.  One `covered’ by the this year’s vaccine, and the other – well, probably not so much.


None of which is to suggest that this year’s flu vaccine isn’t worth getting (I’ve already gotten mine), or that a mismatched vaccine offers no protection against an antigenically divergent virus.   The CDC explains:


What if there is a mismatch between circulating viruses and the vaccine viruses?

A “mismatch” is said to occur when the viruses in the vaccine are significantly different from those circulating in the community. In years when the vaccine strains are not well matched to circulating strains, vaccine effectiveness can be reduced. However, even when the viruses in the vaccine and circulating viruses are not well matched, a vaccine may still offer some protection against circulating viruses.

For example, in a study among persons 50-64 years of age during the 2003-04 influenza season, when the vaccine strains were not optimally matched, inactivated influenza vaccine effectiveness against laboratory-confirmed influenza was 60% among persons without high-risk conditions, and 48% among those with high risk conditions. However, vaccine effectiveness was 90% against laboratory-confirmed influenza hospitalization (Herrera, et al Vaccine 2006). A study in children during the same year found vaccine effectiveness of about 50% against medically diagnosed influenza and pneumonia without laboratory confirmation (Ritzwoller, Pediatrics 2005). Still, in some years when vaccine and circulating strains were not well-matched, no vaccine effectiveness may be able to be demonstrated (Bridges, JAMA 2000). It is not possible in advance of the influenza season to predict how well the vaccine and circulating strains will be matched, and how that may affect vaccine effectiveness. For more information, see Vaccine Effectiveness - How Well Does the Flu Vaccine Work?


Although a partially mismatched vaccine, and an H3 heavy year may suggest a severe flu season ahead, how all of this will play out, is unknown. Which is why the CDC issues a mid-season and end-of-season reports rather than a forecast.


As I’ve written here often , flu vaccines are considered very safe – and most years provide a moderate level of protection against influenza. Their VE (vaccine effectiveness) can vary widely between flu shot recipients, and is often substantially reduced among those older than 65 or with immune problems.


While the vaccine can’t promise 100% protection, it – along with practicing good flu hygiene (washing hands, covering coughs, & staying home if sick) – remains your best strategy for avoiding the flu (and other viruses) this winter.

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