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This Year’s Flu Season Marked by Vaccine Mismatch in the U.S. and Antiviral Resistance in Europe

By Eric Toner, M.D., February 14, 2008

As the seasonal flu epidemic gets into full swing across the U.S., the CDC is reporting that this year’s flu epidemic is more severe than those of the last two years. The CDC also reports that there is a mismatch between this year’s vaccine and two of the predominant circulating strains of flu virus,1 while from Europe, there are reports of an unexpected, and so far unexplained, emergence of H1N1 virus with a mutation associated with decreased sensitivity to oselatamivir.2,3

U.S. Flu Season More Severe

CDC data from the week ending February 2 indicate that 48 of the 51 jurisdictions (all 50 states plus the District of Columbia) are reporting regional or widespread flu outbreaks. A sudden jump in mortality attributed to pneumonia and flu, along with increased physician visits for influenza-like illness over the two weeks prior (January 20-February 2), indicate that this season is more severe than the last two.1

Vaccine Mismatch in the U.S.

Antigenic typing of flu isolates shows that, like last year, A/H1N1 is the predominant strain nationally (see Table 1, below). However, both A/H3N2 and Influenza B are increasing in frequency and are now predominant in some regions. In the Mid Atlantic region, half of the isolates have been Influenza B for the last 4 weeks, while in the North Central region, H3N2 has been the most frequent isolate. This is significant because 87% of this year’s H3N2 isolates are the Brisbane strain, which was not included in this year’s vaccine, and 93% of the influenza B isolates belong to the Yamagata lineage, also not included in this year’s vaccine.1 This means that the vaccine does not match 43% of flu isolates in this country.

Table 1: Frequency of influenza isolates by strain

Strain# of isolates/out of 197Included
in vaccine?

101 (51%) 

     A/ Solomon Island (H1N1)

97 (49%)



53 (27%) 

     A/Wisconsin (H3N2)

6 (3%)


     A/Brisbane (H3N2)

46 (23%)



43 (22%) 


3 (1%) 



 40 (20%)


The degree of cross-protection from these strains afforded by this year’s vaccine is uncertain. H3N2/Brisbane is a recent variant that evolved from H3N2/Wisconsin, which is included in the current vaccine, so some degree of cross-protection is likely. On the other hand, B/Yamagata has been co-circulating with the vaccine strain B/Victoria for many years and there is little cross-reactivity between the two strains.4

Oseltamivir Resistance in Europe

At the same time, reports from Europe2,3 indicate that 20% (151/755) of H1N1 isolates contain a neuraminidase mutation (H274Y) that has been associated with decreased sensitivity to oseltamivir. In Europe, 80% of the isolates are influenza A, and 98% of those are H1N1. This incidence of oseltamivir resistance is surprising because oseltamivir is not commonly used in Europe to treat seasonal influenza.

In Norway and France, this mutation has been found in 63% and 39% of isolates, respectively. In Norway, none of the patients from whom resistant viruses were isolated had been treated with or had known contact with anyone who had been treated with oseltamivir.5 The resistant viruses are sensitive to zanamivir and amantadine.1 In the U.S., the CDC reports that 8% of H1N1 isolates carry this mutation (4.5 % of all influenza viruses tested).


Because of the mismatch between the vaccine and two of the predominant circulating strains, clinicians may be seeing a greater than normal number of patients who have flu despite having been vaccinated. If antiviral treatment is clinically warranted, the neuraminidase inhibitors oseltamivir and zanamivir remain the drugs of choice, as the vast majority of both A and B influenza viruses in the U.S. are still sensitive to these medications.


  1. Centers for Disease Control and Prevention. FluView weekly influenza surveillance report: 2007-2008 influenza season week 5, ending February 2, 2008. weekly/index.htm. Accessed February 13,2008.

  2. European Influenza Surveillance Scheme. Medium levels of influenza activity in most European countries. Weekly Electronic Bulletin. Issue Number 252. February 8, 2008. =252&bulletin=252. Accessed February 13, 2008

  3. European Centre for Disease Prevention and Control. Oseltamivir resistance in human seasonal influenza Type A/H1N1 isolates in Europe. Health_topics/influenza/antivirals_table.html. Accessed February 13, 2008.

  4. Schnirring L. CDC says influenza B strain doesn't match vaccine. Center for Infectious Disease Research and Policy (CIDRAP). February 8, 2008. cidrap/content/influenza/ general/news/feb0808flu.html. Accessed February 13,2008.

  5. Zambon M, Hay A, Paget J. Antiviral drug resistance of influenza viruses in Europe–winter 2007-2008. European Influenza Surveillance Scheme. Accessed February 13, 2008.