The 2005 to 2006 influenza season is over

May 2006

As have so many recent influenza seasons, this was mostly an influenza A/H3N2 year. About 73% of the 629 isolates antigenically characterized by the CDC were A/H3N2 viruses.

During the course of the outbreak, however, an increasing percentage of the isolates were influenza B. During the last three weeks, over 60% of the isolates from many regions of the country were influenza B.

In the past, experts have observed such a late shift in strain predominance. When first observed over 30 years ago, it seemed to predict an influenza B epidemic the following year and was, therefore, referred to as a “herald wave.” This phenomenon was observed so frequently in the last decade, however, that much – if not all – of its predictive value has been lost.

Less excess mortality observed

It appeared to be a season somewhat milder than we have come to expect over the years. The morbidity indices used by the CDC in tracking influenza activity include hospitalization rates for children aged 0 to 4 and 5 to 17 years, the percentage of visits to U.S. sentinel providers with influenza-like illness and reports from state and territorial health officers that assess the level of influenza activity in their respective jurisdictions on a six-level scale, ranging from no activity to widespread activity. By all of these indices, the influenza season was quite modest in intensity, certainly more so than in recent years.

Somewhat more surprising were data from the single mortality index used, the influenza and pneumonia (P&I) mortality as measured in 122 U.S. cities. This has historically been a highly sensitive index of influenza activity, especially influenza A/H3N2. Influenza A/H1N1 and influenza B are much less likely to cause significant excess P&I mortality. This year, however, in a predominantly A/H3N2 year, there was simply no excess mortality at all; in fact, during most weeks the number of deaths fell below the predicted seasonal baseline.

One obvious reason, cited by a number of observers, is that the vaccine was broadly used by high-risk populations and performed admirably. And in support of that theory, the match between the wild strain and the vaccine strain – at least for the A/H3N2 component – was quite good.

Readers may recall the extensive discussions in this column last year (August 2005) of a controversial paper by Simonsen, Reichert, Viboud, et al. on the impact of influenza vaccination on seasonal mortality in the U.S. elderly population (Arch Intern Med 2005;165(3):265-272). That alone should give most of us great pause before jumping on the vaccine bandwagon as the explanation for the lack of measurable excess P&I mortality this year. I wish it were so, but one cannot conclude that from the data at hand.

The wrong B strain

For influenza B, the match between the circulating strain(s) and the vaccine strain was not nearly as good as for influenza A. This situation is a bit complicated owing to the fact that there have been two co-circulating lineages of influenza B viruses for the last 15 years or more. These are known as the B/Yamagata lineage and the B/Victoria lineage, respectively. One or the other of these strains, or their derivatives, have usually been in the ascendancy at various times and in various parts of the world, but it has been little more than an educated guessing game trying to predict which lineage would predominate nine to 12 months later in any given country.

The B strain chosen for the 2005 to 2006 vaccine was a B/Shanghai/361/2002-like virus, an updated strain in the B/Yamagata lineage. As the season evolved, it became apparent that less than one-third of the influenza B isolates this year belonged to the Yamagata lineage. Over two-thirds of B isolates belonged to the B/Victoria lineage, and therefore, vaccine recipients were poorly protected, if at all, by this year’s vaccine. That would likely matter little to adults and the elderly, who usually experience little or no morbidity or mortality from influenza B; it might matter a great deal, however, to infants and children who have had little or no previous experience with influenza B. Put bluntly, the FDA Vaccines and Related Biological Products Advisory Committee (including the writer) guessed wrong!

Unfortunately, this was of some consequence this year, for there were a number of serious influenza B infections in children, some requiring hospitalization for unusual complications like myositis.

This year, the FDA committee voted to change the B component in the vaccine to a contemporary strain in the B/Victoria lineage, B/Ohio/1/2005.

Only time will tell whether that was the correct recommendation.

That these two influenza B lineages have co-circulated for quite a long time has led to almost annual discussions among the FDA committee members about including strains from both lineages in the vaccine. This always led immediately to a dilemma. Either reduce the dose somewhat and accept a lesser degree of immunogenicity and, by inference, a lesser degree of efficacy. Or, increase the total dose from 45 mg to 60 mg of hemagglutinin by adding 15 mg of the B lineage heretofore not included and accept the fact that there would be a commensurate reduction in the total number of vaccine doses available as well as a possible increase in reactivity. The limiting factor in vaccine production is the total number of micrograms of hemagglutinin that can be produced. Increasing the quantity of hemagglutinin in each dose will necessarily reduce the number of doses available.

This issue remains a standoff. Pediatricians especially feel somewhat disenfranchised by what they perceive as inadequate vaccine coverage of influenza B.

Another issue that will hang over the 2006 to 2007 influenza season is the antiviral drug resistance of whatever strains emerge next year. This year, of course, most of the influenza A/H3N2 strains tested were resistant to amantadine and rimantadine (Flumadine, Forest). This disagreeable finding surely put even more pressure on the neuraminidase inhibitors, so there is ample reason to be grateful that this was such a relatively mild season. Next year may well be different, and it will be important to monitor the antiviral drug resistance as the 2006 to 2007 season evolves.