Influenza: the year in review, and looking forward

Influenza season is wrapping up here in the United States, and it seems so far that the 2006-7 season was pretty typical. The first cases of the disease were reported in late October, and cases were sporadic throughout November and early December. After increasing a bit in mid-late December of 2006, outbreaks declined slightly in January, and then picked up again later that month, increasing again in February before falling again, and continuing to do so in March. Early reports suggest that the vaccine matched the circulating strains pretty well, and that most of the isolates which were subtyped were serotype H1 influenza A viruses. Via the CDC, we can see the influenza outbreak and types of virus in the figure below:

What about H5N1? And pandemic influenza in general? More on that after the jump.


You may recall news about surveillance for H5N1 in wild birds in Alaska and beyond here in the United States. Though a few low-pathogenicity H5N1 avian viruses were detected in Michigan, Maryland, and Pennsylvania, no highly pathogenic H5N1 isolates (or other highly pathogenic avian virus serotypes) were found in Alaskan waterfowl.

However, overseas, H5N1 continues its march. 2006 ended with a total of 115 cases of H5N1 diagnosed worldwide (79 of them fatal). This is up from 2005's 98 cases (and 45 deaths). So far in 2007, we've seen 22 cases (and 12 deaths). The virus is also spreading into new geographic areas. There has been a lot of trouble this season with birds in Nigeria; it appears that the virus is spreading there along poultry trade routes, and has caused outbreaks in several areas of the country. Additionally, this season saw Nigeria's first human case of avian influenza, a fatality in their largest city, Lagos. Of course, the virus also doesn't recognize geographic borders, and has recently been reported in Bangladesh and Saudi Arabia, after taking its first human victim in Laos. It's also returned to Europe, and caused England's first poultry outbreak of the virus. However, there is a bit of good news: so far this season, the spread of the virus doesn't appear to be as extensive as during the 2005-6 season, where it spread throughout Asia, Europe, and even parts of Africa. However, the downside of this is that many outbreaks are likely still going unrecognized, so we don't truly know the extent of the virus' spread.

Other avian strains

While H5N1 has been the topic of much discussion on pandemic influenza, I mentioned here that we can't be certain that H5N1 will be the next pandemic influenza virus, citing outbreaks of H9N2 and H7N7 viruses in recent years. Well, since then, H9N2 has caused another human infection in Hong Kong, in a 9-month-old girl. Like previous H9N2 cases, her symptoms were fairly mild, and there has been no evidence of spread. However, it should serve as a reminder that just targeting H5N1 is bad policy; we need something in place that will allow us to respond to any virus with pandemic potential.

Pandemic consequences

And if we don't have a working response plan in place? Obviously, we leave ourselves open to the potential for a lot of human life lost, and a lot of suffering from those who contract the pandemic virus. However, new reports have again emphasized that an influenza pandemic will impact much more than just our physical health. The research suggests that a severe pandemic (1918-type scale) could cost the US alone up to $638 billion, and plunge the economy into a deep recession:

If rates of illness and death matched those of 1918--when one third of the population fell ill and 2.5% of those who were sickened died--US production of goods and services could shrink 5.5% in a year, according to an analysis released by the Trust for America's Health (TFAH).

But the pain would not be spread evenly across the country. States whose economies depend on tourism and entertainment would be hit hardest, with losses as large as 8% of their economic production, the group said. But areas that depend on other sectors--from agriculture and finance to real estate and government--might hold their losses to half that much.

So, Iowa might be OK--but sorry for those of you in tourist-y states. However (and I've not read the report yet, so they may address this), I wonder if they factor in any potential losses to agriculture in that. Iowa is a huge swine-producing state, and even if a future pandemic virus doesn't evolve in swine, it could possibly infect them (again, like was the case in 1918). If we have a big swine flu epidemic here concurrent with a human epidemic, there's going to be a lot of economic hardship. But I digress...

"Businesses, governments, schools and other sectors could all face serious disruptions," said Jeff Levi, PhD, executive director of the TFAH, a nonpartisan group that has published several reports on pandemic preparedness.

While the analysis released today focuses on the impact of a pandemic on the US economy, the consequences would ripple worldwide, Levi said in a briefing for reporters: "In today's global economy, almost every aspect of commerce relies directly or indirectly on an interconnected, worldwide network of workers, products and services. A major shock to this network could have serious negative consequences on trade and commerce worldwide."

So that, very briefly, is where we stand on influenza. I think the media steam is waning a bit (probably a good thing; at least it means an audience for scientifically inaccurate mini-series about influenza is drying up), and this year's influenza season was fairly mundane as influenza goes. However, the pandemic threat remains, as does our overall lack of preparedness should one occur. It does appear, at least, that some politicians are waking up to the potential disaster that pandemic influenza represents; whether they'll continue to do something about it if it drops lower on the media's radar, though, is anyone's guess.

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Proc Natl Acad Sci U S A. 2007 Mar 29;
Simultaneous amino acid substitutions at antigenic sites drive influenza A hemagglutinin evolution.

Shih AC, Hsiao TC, Ho MS, Li WH.

Institute of Information Science, Institute of Biomedical Sciences, and Genomics Research Center, Academia Sinica, Nankang, Taipei 115, Taiwan.

The HA1 domain of HA, the major antigenic protein of influenza A viruses, contains all of the antigenic sites of HA and is under continual immune-driven selection. To resolve controversies on whether only a few or many residue sites of HA1 have undergone positive selection, whether positive selection at HA1 is continual or punctuated, and whether antigenic change is punctuated, we introduce an approach to analyze 2,248 HA1 sequences collected from 1968 to 2005. We identify 95 substitutions at 63 sites from 1968 to 2005 and show that each substitution occurred very rapidly. The rapid substitution and the fact that 57 of the 63 sites are antigenic sites indicate that hitchhiking plays a minor role and that most of these sites, many more than previously found, have undergone positive selection. Strikingly, 88 of the 95 substitutions occurred in groups, and multiple mutations at antigenic sites sped up the fixation process. Our results suggest that positive selection has been ongoing most of the time, not sporadic, and that multiple mutations at antigenic sites cumulatively enhance antigenic drift, indicating that antigenic change is less punctuated than recently proposed.

By Pete Dunkelberg (not verified) on 02 Apr 2007 #permalink