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The news today brings two more cases of human infection with H7N9 avian flu, and the confirmation of the fourth death I mentioned in yesterday's blog. 

WAIT!  NEWS FLASH!  Now, according to Treyfish, veteran Flutrackers poster, China has reported 14 cases of human H7N9 infection. And one pigeon.  Five humans are dead.  The pigeon's status is uncertain.

I am only half-joking when I mention the pigeon.  As I blogged yesterday, birds appear to be unaffected by this bird flu.  Ordinarily, when a bird has bird flu, it gets very sick and then dies. 

As ESPN celebrity and former FSU player Lee Corso would say, not so fast, my friend. This bird flu is not making birds sick.  If it were, we would have seen H7N9 coming.

Now, Corso did not say that about bird flu.  I said that.

At least one of the two newly-reported cases is in Zhejiang Province.  This province has previously reported cases of H7N9 recently.  Please refer to the map of Chinese provinces I posted in a previous H7N9 blog. The location of the second new case today is not confirmed.

There is feverish (so to speak) activity taking place among those who know the genetics of influenza. These intrepid individuals have been studying the anatomy of H7N9 and sharing that data via the Internet.  The crowdsourcing of H7N9 data is most helpful and extremely important, for it allows a much greater number of qualified researchers to begin the process of dissecting this troubling new virus.

As one can imagine, samples of this new strain of H7N9 are rare.  I can only imagine the frantic process of obtaining these samples and sending them via fighter jet halfway around the world to ground transports, those transports, in turn, racing these samples to facilities such as St. Jude and Drs. Webster and Webby.  Well, that's how it would work in the movies. The reality is probably based around Fed Ex and UPS.  "Sign here for your lethal bird flu virus, Doctor Webster."

Anyway, you have eleven positive victims, and four deaths, and only so much tissue to go around.  So those lucky enough to have actually processed the samples themselves are able to post their research online.

We are a long, long way from being able to replicate things in a laboratory.  We are a long, long way from growing H7N9 in quantities sufficient to conduct any real experiments, with ferrets, birds, or any other creatures. So all we have right now are the phylogenetic charts showing the antecedents of H7N9, and where we have seen their individual component parts before. 

For example, GeneWurx, which posts to Flutrackers, says this about what they have seen:

Though H9N2 is regaled as the nearest relative on file for these internal gene segments of the H7N9 emerging zoonosis, note the highlighted areas including a fatal H5N1 human, pH1N1 in swine (with human homology) and sH3N2. These H7N9 sequences have developed from pedigrees not entirely disjunctive from human infection.

You will recall the (not so) little problem America had with its rural county fairs the past two summers.  People were petting farm animals and then winding up with swine H3N2. I really meant to blog about those cases.  Anyway, an excellent CIDRAP article from last October showed now closely related the swine H3N2 and the longtime seasonal human H3N2 were related.

The press has been running excerpts of an interview with Dr. Richard Webby, of St. Jude.  For new readers:  St. Jude has arguably the top influenza research facility in the world.  Its director, Dr. Robert Webster, is nicknamed the "Pope of Influenza."  Dr. Richard Webby works with Dr. Webster and he is also an email buddy of mine.  Dr. Webby said this to the press about H7N9:

"I think that's what's concerning about this ...This thing doesn't any longer look like a poultry virus," Webby, a swine flu expert, said in an interview.

"It really looks to me like it's adapted in a mammalian host somewhere."

If the virus is spreading in mammals, finding that source is critical to try to reduce human exposure and prevent additional cases, he said.

Also weighing in is Dr. Henry Niman.  Dr. Niman has composed an excellent map of the human cases so far, cases known and suspected.  He also is seeing the progression that Dr. Webby has seen, but he does have a rather flamboyant writing style:

The latest cases increase concerns that the presence of D225G and Q226L represents human adaption of a lethal bird flu virus that has a greater pandemic potential than H5N1.  This potention is enhanced by the presence of PB2 E627K.

Veteran readers of this Blog know that the presence of PB2 E627K signals a move away from avian proclivities and toward mammals.  These are the changes that worry researchers so much.  Also knowing that the birds are not dying means surveillance using conventional (and cheaper) methodology is out the window.  We need a better way to detect the presence of this new flu, and we need it quickly.

There is no question that, somewhere along the line, a pig -- or a human -- was the Mixing vessel that produced this new, novel and immensely troubling virus. 

Fasten your seat belt.

The H7N9 outbreak continues to grow.  This morning, both Flutrackers and Avian Flu Diary are reporting multiple Chinese stories that two new and previously unreported human H7N9 cases have been found in Hangzhou, Zhejiang Province.  Both cases have died.

The machine translation from Chinese to English can be problematic where date (well, pretty much anything else) is concerned, so it takes skill to parse correct dates from the rest of the dialogue.  Regrettably, that is a skill I lack.  But many others do, and these talented people are all located on Flutrackers.com.

There appear to be two separate dates of infection.  One apparently is the 7th of March, and the other is the 25th of March. But what is plain is that this brings a fourth province -- and third coastal province -- into the picture. By any yardstick, we have not yet defined the scope of this outbreak.  Although it appears human-to-human transmission may or may not yet be possible, and as we covered at length yesterday, H7 can and does infect humans, the cat appears to be out of the bag.

The biggest impediment to getting our arms around the scope of the crisis (yes, I consider this to be a crisis, because we have a novel strain of influenza that no one, outside a random poultry worker or hunter is immune to, and it is killing people):  It is not killing poultry.  Sentinel chickens (the proverbial canary in a coal mine), used to help detect the presence of avian influenza, may be asymptomatic carriers of the disease.  At least that is one oprevailing theory, which would also explain why and how this virus escaped surveillance and, thus, early detection. 

You always knew when H5N1 bird flu was close by:  You could follow the trail of dead and soon-to-be-dead chickens.  H7N9 is not killing chickens.  Nor, contrary to what our deepest nightmares and feelings might tell us, is it killing pigs. 

My blog of yesterday mentioned a Dr. Yin of the Bill and Melinda Gates Foundation.  Apparently Dr. Yin is the Foundation's leader in China.  And it was quite satisfying, knowing Bill and Melinda are spending funds in China, including, but not limited to, surveillance.  Dr. Yin's statement is worth paraphrasing.  He said, basically, if you don't test for H7N9, you won't find it.  But if you do test for it, you'll find it.  The inference is that there have been numerous unexplained and undiagnosed severe respiratory ailments there this season.  Retroactive testing of samples, based on Dr. Yin's inference, will yield a significant increase in the number of H7N9 human cases. 

I am hopeful that the CDC here will start looking at the number of "A (subtyping not performed)" samples still lingering around. 

Over at Computerworld, I have just delivered my first blog in over six months!  And you thought I blogged slowly over here!

Anyway, I want you to go over there and read it, because I am not supposed to post their blog over here, and vice versa.  Here's the link: http://blogs.computerworld.com/15879/dont_write_off_h1n1_pandemic_yet

The CIDRAP study I mention in the blog was authored by Cecile Viboud, a research scientist at the National Institutes of Health's Fogarty International Center, and Lone Simonsen, research professor at the Department of Global Health, George Washington University, School of Public Health and Health Services, Washington, D.C.  Another co-author is Michael T. Osterholm, PhD, MPH, director of the University of Minnesota Center for Infectious Disease Research and Policy, and publisher of CIDRAP News.  Mike is also a good friend and I am danged glad to know him.  I have also mentioned Dr. Viboud's work on this Blogsite, particularly on the 1951 "Liverpool Flu" and her discovery of how deadly that epidemic was in the UK.

The recent CIDRAP study "sought to devise an 'apples to apples' way to compare pandemic and seasonal flu mortality. To estimate the age distribution of pandemic deaths, they relied mainly on a European study of 468 laboratory-confirmed pandemic deaths, published in August 2009. It showed that more than 85% of the deaths were in people younger than 60, with an overall mean age of 37.4, as compared with an estimated mean age of 76 in those who die of seasonal flu. (bold mine)

"The team then developed an estimate of pandemic deaths, given that only a fraction of cases and deaths are laboratory tested and that final statistics will not be available for another 2 to 3 years. This task involved comparing preliminary mortality data from the CDC's 122 Cities mortality surveillance system with final mortality data from the National Center for Health Statistics for 1999 through 2006. The team also used data on deaths in non-flu-season months to estimate the number of monthly deaths that would occur in the absence of flu.

"Using these variables and the 122 Cities data for April through December 2009, the researchers estimated the (US) pandemic death toll to be between 7,500 and 44,100. The lower number is based on deaths classified as due to pneumonia and influenza (P & I). The higher number, Viboud told CIDRAP News by e-mail, is an estimate of "excess all-cause mortality, which is more inclusive as it also takes into account excess deaths from all respiratory and cardiovascular diseases that are associated with influenza infection, but may not be reported as such."

"(Dr. Viboud) added that the 'excess all-cause mortality' approach has traditionally been used to measure the impact of seasonal epidemics and for the 1957 and 1968 pandemics, while the P&I approach has been used in assessing the 1918 pandemic. The team used both approaches to allow fair comparisons with past flu seasons, she said."

The study's results were revelatory.

• More than 85% of the H1N1(2009) deaths were in people younger than 60, with an overall mean age of 37.4, as compared with an estimated mean age of 76 in those who die of seasonal flu.
• the H1N1 (2009) pandemic, so far, has taken a toll of between 334,000 and 1,973,000 years of life lost (YLL) in the United States.
• The 1968 pandemic, with 86,000 deaths and victims averaging 62.2 years old, caused 1,693,000 Years of Life Lost (YLL).
• The 1957 pandemic, with 150,600 deaths and a mean age of 64.6,caused 2,698,000 YLL.
• The 1918 pandemic, with an estimated 1,272,300 deaths and a mean age of only 27.2, exacted a toll of 63,718,000 YLL.
• An average flu season dominated by influenza A/H3N2-which generally causes more severe epidemics than other strains-causes 47,800 deaths and 594,000 YLL, with a mean age of 75.7. (bold mine)

From the CIDRAP press release:

"Thus, the authors say, the lower end of their YLL estimate for the H1N1 pandemic is comparable to the estimate for an H3N2-dominated flu season, while the upper end is greater than that for the 1968 pandemic. Those impacts, of course, are dwarfed by that of the catastrophic 1918 pandemic.

"Based on US mortality surveillance data, we conclude that the YLL burden of the 2009 pandemic may in fact be as high as for the 1968 pandemic-but that at this time the assessment is still tentative," the report states. More waves of H1N1 cases are likely to come over the next few flu seasons, and later waves could be worse, it says."

Now for the commentary you have come to expect from this Blogsite:

H1N1 is not done infecting people, not by a long shot.  And as the CIDRAP study amply demonstrates, the impact of even this "light" pandemic on the future is significant.

Need context?  In the US, losing even 300,000 years if life in younger, productive stages will affect future payments to Social Security.  Medicare.  Federal, state and local taxes. Billions lost. Try factoring that into the budget deficit equations!  Not to mention the lost buying power of those persons due to the pandemic.

And of course, it goes without saying that the emotional burden of people having lost youthful loved ones to this disease is tremendous.  Watching someone get cut down in the prime of life -- especially someone previously described as healthy -- is a trauma no one would wish on anyone except Osama Bin Laden. 

Note something that not even I knew:  The 1957 and 1968 pandemics had a much older average age at death than has (so far) the 2009 H1N1 pandemic.  No doubt this is because we have the perspective of history and the separation of decades to view the cumulative effects of 1957 and 1968.  Since this H1N1 pandemic is far from over, its ultimate average age at death is yet to be determined. But at a shade over 37 years of age, the current age at death is second only to 1918's 27 years in terms of youthful mortality.

I believe it was my buddy John Barry (what a shameless name-dropper I am!) that said in his superior book The Great Influenza, that the average age at death in the United States from 1918-1919 dropped by ten full years as a direct result of both WWI and the 1918 Spanish Flu.

And let us not forget the lingering by-product of 1918's pandemic:  Encephalitis Lethargica.  That scourge stayed with America (and the world) until it mysteriously dropped from sight around 1930.  (Re)Watch "Awakenings" to recall that terrible ordeal.

I also want to crosswalk to a recent study that shows just how antigenically similar the 1918 and 2009 H1N1 viruses are.  From Reuters, via ChinaDaily.com:

WASHINGTON - The H1N1 swine flu virus may have been new to humanity in many ways but in one key feature its closest relative was the 1918 pandemic virus, researchers reported on Wednesday.

Their findings could point to better ways to design vaccines and help explain why the swine flu pandemic largely spared the elderly.

"This study defines an unexpected similarity between two pandemic-causing strains of influenza," Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases (NIAID), said in a statement.

Two studies show an important structure called hemagglutinin is very similar in both the swine flu H1N1 and its distant cousin, the H1N1 virus that caused the 1918 pandemic. Hemagglutinin is used by viruses to infect cells and gives influenza viruses the "H" in their designations.

For one study, published in Science Translational Medicine, Chih-Jen Wei, Gary Nabel and colleagues at NIAID injected mice with a vaccine made using the 1918 influenza virus - which killed an estimated 40 million to 100 million people.

When they infected the mice with H1N1 swine flu, the vaccinated mice survived, while many unprotected mice died.

The reverse also worked - when they immunized mice using the 2009 H1N1 virus, and then infected them with the 1918 strain, the mice were protected.

"This is a surprising result," Nabel said. "We wouldn't have expected that cross-reactive antibodies would be generated against viruses separated by so many years."

The team also showed that as flu viruses circulate, they develop a kind of shield called a glycan that protects them from the body's immune system. That may allow them to become regular, seasonal visitors.

"It gives us a new understanding of how pandemic viruses evolve into seasonal strains, and, importantly, provides direction for developing vaccines to slow or prevent that transformation," Fauci said.

This type of experiment was performed in 2009, with similar results.  I believe Kawaoka did this type of work.  Webster may have done it also.  It reinforces the concern that one or two teeny little changes might really turn this virus into a nasty, nasty bug.

Policy makers, or persons who still labor under the false assumption that H1N1(2009) was a "false pandemic," would do well to examine the CIDRAP report.  Examine, and pray this virus does not mutate or evolve into anything more closely resembling its ancestor. Because it's uncomfortably close already.