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As you know, I have been kvetching recently about the potential for a hybrid (or maybe "hybird," as I originally typed, in error but perhaps a Freudian slip?), avian/human flu virus to emerge from somewhere other than here.

Today, respected researcher Dr. Yoshihiro Kawaoka of the University of Wisconsin-Madison (left) has issued a paper where he postulates that such an occurrence is not only possible -- he has done it. 

Let's read the release and then talk.  From the University of Wisconsin-Madison press release:

VIRUS HYBRIDIZATION COULD CREATE PANDEMIC BIRD FLU

MADISON - Genetic interactions between avian H5N1 influenza and human seasonal influenza viruses have the potential to create hybrid strains combining the virulence of bird flu with the pandemic ability of H1N1, according to a new study.

In laboratory experiments in mice, a single gene segment from a human seasonal flu virus, H3N2, was able to convert the avian H5N1 virus into a highly pathogenic form. The findings are reported the week of Feb. 22 in the online early edition of the Proceedings of the National Academy of Sciences.

"Some hybrids between H5N1 virus and seasonal influenza viruses were more pathogenic than the original H5N1 viruses. That is worrisome," says Yoshihiro Kawaoka, a virologist at the University of Wisconsin-Madison and senior author of the new study.

The H5N1 bird flu virus has spread worldwide through bird populations and has caused 442 confirmed human cases and 262 deaths, according to the World Health Organization. To date, however, bird flu has not been able to spread effectively between people.

"H5N1 virus has never acquired the ability to transmit among humans, which is why we haven't had a pandemic. The worry is that the pandemic H1N1 virus may provide that nature in the background of this highly pathogenic H5N1 virus," says Kawaoka, a professor of pathobiological sciences at the UW-Madison School of Veterinary Medicine.

Two viruses infecting a single host cell can swap genetic material, or reassort, creating hybrid strains with characteristics of each parent virus.

Before the current study, hybrid viruses generated in lab studies had always been less virulent than parent strains. However, the new findings raise concerns that H5N1 and pandemic H1N1 viruses could reassort in individuals exposed to both viruses and generate an influenza strain that is both highly virulent and contagious.

The increased virulence seen in the new study seems to arise from one of the eight genes in the viral genome, called PB2, which is known to affect how well the bird flu virus grows in mammalian hosts, including humans. When tested in mice, the human virus version of PB2 swapped into H5N1 converted the avian virus to a highly pathogenic form.

The researchers say surveillance of viral populations is critical to monitor the potential emergence of highly pathogenic viral variants due to reassortment of avian and human influenza viruses. Their results, including identification of the PB2 segment as a key to enhanced virulence, offer information likely to be useful in the event of a pandemic caused by a hybrid avian-human influenza strain.

"With the new pandemic H1N1 virus, people sort of forgot about H5N1 avian influenza. But the reality is that H5N1 avian virus is still out there," Kawaoka says. "Our data suggests that it is possible there may be reassortment between H5 and pandemic H1N1 that can create a more pathogenic H5N1 virus."

The work was funded by the U.S. National Institutes of Health, the Japan Society for the Promotion of Science, the Ministry of Education, Culture, Sports, Science and Technology of Japan, and the Japan Science and Technology Agency. (bold mine)

Dr. Kawaoka's research is getting a lot of attention, including a recent grant from the Bill and Melinda Gates Foundation.  What is so interesting about Dr. Kawaoka's recent experiments is that he targeted PB2, the segment which few know enough about to be decisive.  Dr. Kawaoka and his research team have taken a human PB2 gene segment and spliced it to H5N1 bird flu.  The result is a more lethal and even more virulent virus than the parent H5N1 strain!

Dr. Kawaoka and his staff have now, and pretty conclusively, named PB2 as the gene segment responsible for lethality in humans.  In prepping for this blog, I stumbled across a blogsite by the name of Monotreme's Blog, and how I never saw it before now is a mystery to me.  Anyway, this blog has an interesting confirmation of Kawaoka's discovery.  But it turns things in a different direction than an avian/swine hybrid doomsday virus.  From Monotreme's Blog entry of December 2, 2009:

The PB2 gene is reported to be key in the adaptation of a virus that infects birds to one that infects humans. In particular, it has been reported that the amino acid at position 627 is critical for this adaptation (Van Hoeven et al. 2009). Viruses that infect birds typically have a glutamic acid (E) in this position. Flu A viruses that are fully adapted to humans usually have a lysine (K) at this position. This same position in PB2 appears to be key in determining the lethality of flu viruses (Hatta et al. 2001). In the 1918 pandemic and H5N1 viruses, a lysine in this position is associated with a higher level of lethality. The presence of a lysine at position 627 appears to permit flu viruses to replicate in both the lungs and nose and thus spread more easily from person to person.

It is possible, perhaps likely, that as pandemic H1N1 adapts to humans, a mutation will occur that will create a lysine in position 627 in this virus. If so, will the virus become more virulent? At this point, it is difficult to say. On the one hand, “seasonal” flu viruses that are not considered particularly lethal have a lysine at position 627. On the other hand, a change from glutamic acid, when the virus is infecting birds, to a lysine, when the virus is starts to infect humans, is associated with much greater virulence. How to reconcile these apparently contradictory facts? It may be that the change to a lysine is initially associated much greater virulence due to interactions with other proteins. As the virus moves through the human population immune responses are triggered. Thus, a year or two after a pandemic begins, the virus comes under selection to escape immune system detection. This selection may result in the preferential propagation of new versions of other proteins which no longer interact with PB2 to create a more lethal virus. In this scenario, a mutation at position 627 from gluatamic acid to lysine will initially create a more lethal virus, but, as the virus is “tamed” by the immune system selection, this mutation will utlimately be insufficient to sustain a high degree of lethality.

Given that human-adapted flu A viruses tend to have a lysine at position 627, it seems likely that the new pandemic H1N1 will eventually lose its “avian” glutamic acid and acquire a lysine at this position. There have already been sporadic instances of this. If/when this occurs in a strain that spreads widely, it would not be surprising if it becomes more lethal.

Kawaoka's research has taken Monotreme's (and others') speculation and turned it into fact.  

Monotreme offers a theory that immune responses in humans will ultimately steer this lysine-altered virus toward a less lethal path in order for it to evade antibody detection and eradication.  But how long will that process take, and how many lives would be impacted by the virus in the meantime, are only known to God.

In the meantime, bird flu continues to buck the tradition of flu viruses during a pandemic.  this virus refuses to go away.  Just today, comes word of two more Egyptians struck down with H5N1 bird flu.

Now I am going to make a statement, and I want you to read it and absorb it.

There have been more Egyptians hit by H5N1 bird flu thus far in 2010 than there are Americans who have tested positive for H1N1 or H3N2 seasonal influenza.

Bird flu continues to spread again, in defiance of tradition and in defiance of all governments' attempts to eradicate it.  As the H1N1v pandemic continues to strike and spread in Asia, the potential for dual infection with H5 and H1 simultaneously increases.  How many cross-infections does it take to achieve some sort of viral critical mass?

Only one. 

My last blog focused on the return of H5N1 avian influenza in humans in 2009.  Just scroll down to read it... I'll wait.

OK, welcome back.  What is happening is a veritable explosion of bird flu across Asia and the Middle East in 2010.  We have over 400 residents of West Bengal (India) under Tamiflu blankets; human cases seemingly every third day in Egypt, and at one point we had three confirmed cases in one day; and a quite sudden acceleration of H5N1 in poultry and wild birds across most of southeast Asia. 

Now Indonesia, a nation which has thankfully turned away from insanity with the appointment of a new health minister. is back in the timely reporting category.  Hey, anything was better than the last two years under Supari!  They could have had a zombie epidemic and the rest of the world could have been blissfully unaware -- until the undead came down Broadway.  And speaking of zombies -- where the Sam Hill is that World War Z movie?  Brad Pitt and Plan B, don't make me come down there and read you the Zombie Riot Act.  Why do you think Zombieland was such a financial success?   And a bit of movie trivia -- Zombieland's central character (right) was named Tallahassee, by the way.

But I digress.  Anyway, Indonesia has now reported two confirmed human H5N1 cases.  One case is in West Java, and one is in Jakarta.  Regrettably, the West Java case -- a 25-year old of unknown gender -- died.  I am sure that if you go to www.flutrackers.com, you will find plenty of stories about the deaths. 

And just this morning, news of a third Indonesian bird flu patient arrives via proMED.  This patient, a woman in Lampung, accompanies a huge die-off of birds in the province.

While this is taking place, the Western press is reporting about the roasting of public health officials over regarding what some misguided souls proclaim to be a "false pandemic" of H1N1v.  As the public health officers of the civilized world circle the wagons in the West, swine flu continues to insinuate itself throughout Asia.  Ans as it does what the flu does, it will absolutely have multiple opportunities to rub elbows with bird flu in towns and villages.  It has already had multiple opportunities with each and every confirmed human H5N1 case since April of 2009. 

Everyone is asking him/herself, "What virus was shed by those who are testing positive for bird flu?  Who might have walked into a cloud of H5N1 particles expunged by someone?  And what if that person, in turn, also acquires H1N1v swine flu?  Deep in the lungs of those dual-flu victims, what terrible reassortment experiments might be churning?  And what is the form and substance of that mutation, if it survives?"

Wait, you ask.  Why should swine flu mix with bird flu?  Recall that swine flu is only one-third swine.  It is also one-third human, and one-third avian.  Look at the number of flocks of turkeys all over the world that have acquired swine flu.  (interesting that I can only recall turkey flocks having acquired H1N1v).

For these flocks to have acquired a human strain of flu surely must tell us that H1N1v retains enough of an avian genetic footprint that direct infection from humans to birds is not just possible -- it has happened.  Numerous times.

Follow my logic here.  If birds can catch swine flu from humans, then it means swine flu retains enough of its bird ancestry that reassortment with bird flu is absolutely possible.  All it takes is enough exposure, in enough hosts, all over the world, to cook a strain that can both infect humans and kill in greater numbers than swine flu.

Sure, the swine flu pandemic was not what we were fearing.  But let's finish the sentence.

The swine flu pandemic was not what we were fearing -- yet.  We have a long, long way to go.

I just got a news story in my Google Alerts folder.  Opening it and clicking on the accompanying link, I was shown something I had not seen in ages and ages -- namely, the WHO statistics for H5N1 bird flu for 2009.

Now, you know how fond I am of saying that influenza plays "King of the Mountain."  That image of children trying to topple the reigning King at the top of the dirt pile (growing up in southern Florida, with all its construction and fill dirt, that game was enormously popular) is exactly what I try to convey with regards to flu strains.

Pandemic viruses play that game quite well.  In fact, I have not bothered to even get my seasonal flu shot yet, because I believed that there would be no seasonal flu until very late in the season.  based on the stats I have been getting from various flu sources, I was right on the money.

So there is virtually no seasonal flu, anywhere in the world, save for some Influenza B that I recently read was either in China or Japan.

But there is one flu strain that keeps on trucking, unabated by events that combine to make seasonal flu virtually nonexistent.  And that is H5N1 bird flu.

It can be argued, possibly successfully, that H5N1 isn't seen in people enough for swine flu to even care about it.  H1N1v just casts a look over its shoulder at H5N1 and ignores it.

But I was really, really surprised to find that 2009 was a pretty good year, or a pretty bad year, depending on whether you are a researcher or the virus itself.  Globally, there were 72 cases of H5N1 in humans, with 32 deaths.  That is still a 44.4% case fatality rate, or CFR. The two extremes for CFR were Egypt, with 39 reported human cases and 4 deaths, for a 10% CFR; and Indonesia, with 20 reported cases and 19 deaths, a whopping 95% CFR.  Of course Indonesia has just gotten over years of governmental madness courtesy of their former health minister.  This somewhat refreshing reporting of cases may skew the CFR heavier, as certainly more human bird flu cases must have been encountered and just not reported.  Or reported and covered up.  Who knows?

In fact, the year 2009 shaped up as the fourth-worst year for human H5N1 cases on record, surpassed by (in order) 2006, 2005 and 2007 in terms of the sheer number of confirmed human cases. From 2008 to 2009, confirmed reported human bird flu cases jumped by 63% while deaths stabilized.

In 2010, we already are reading about more accounts of bird flu in poultry, in all the usual spots.  This recent news, when combined with the 2009 data, should make us all more concerned than ever that a hybrid virus is more than just hypothetically possible.  A glance at the WHO chart also shows us that the areas of the world where human H5N1 cases proliferate are also areas where the H1N1v virus is just beginning to make its inroads. China has recently announced it expects a constant flow of H1N1v human cases throughout 2010.  China had 7 reported human bird flu cases in 2009, its third-highest year on record and the highest number since 2006.

Indeed, in those areas where H5N1 is assumed to be endemic, human cases are on par with previous years.  For example, Egypt's 2009 human bird flu total (39) was 500% higher than 2008's (8).  Vietnam's 5 cases was not statistically different than the previous two years.  And in each and every one of those nations, H1N1v insinuates itself further and deeper rural villages and farms. 

In the midst of all this, we read news reports accusing the WHO of generating a "fake pandemic".  What are these people ingesting?   A key indicator of a pandemic (you know, other than a genetically novel virus)  is a rising of pediatric mortality.  Pediatric mortality in 2009 was three or five times the running average for a normal flu season, according to different sources.  Our own CDC now says upwards of 11,000 Americans died of swine H1.  The overwhelming majority of them were under age 55.  And this virus is far from finished. 

To its credit, the WHO fired back to the flat-Earthers who claimed that the raising of the pandemic level to Phase Six was inspired by the drug companies, and some even claim this virus was genetically engineered.  These are the same drug companies who do not make a lot of money from vaccines.  To even insinuate that drug companies make huge sums of money from vaccines is to show a colossal lack of understanding about how drug companies make their fortunes.  Vaccines represent a huge downside financial risk to their bottom lines, precisely for the reasons we are seeing and reading about today.  Stories abound regarding this nation and that nation trying to renegotiate its vaccine buying agreements in an effort to reduce its purchases.  It is a wonder that drug companies even make vaccines anymore.

But that is a rant best saved for another time.  I wanted to close this blog by saying that we need to watch Asia and Egypt like a hawk.  Because H5N1 had a very good year on the books in 2009.  It continues to be productive and it has not read the memo that it is supposed to roll over and play dead while swine flu takes center stage.