It is safe to say I am very far behind on that promised blog regarding the construction of this swine H1N1 virus. But that's not a bad thing, because I have stumbled across a new Wiki dedicated to sharing information on the construction of this new virus. It is titled "Human/Swine A/H1N1 Influenza Origins and Evolution," and is located at: http://tree.bio.ed.ac.uk/groups/influenza/ . 

A note of caution: It is for professional influenza researchers, but is also great fun for influenza geeks who have at least a passing knowledge of the structure of influenza and how it picks up its polymorphisms. It is also important to have some sort of working knowledge of the structure of the flu virus itself. If you know what HA, NA and MP stand for, you re aready to proceed. Otherwise, you might want to hit Google and get smart on the influenza virus' composition before proceeding there.

Laypeople can see, at first glance, one big amazing point; namely, influenza picks up genetic markers like seasoned travelers used to put destination stickers on their luggage, or like Russian generals put ribbons on their chests. The diversity of genetic markers and their initial points of discovery (A/New York, A/Texas, A/Florida, etc.) point to the diversity of genes that make up the most facsinating virus on the planet.

I found this Wiki through an NPR article that I found by stumbling upon the Twittersite of Helen Branswell. I have been a huge fan (how cliche) of Ms. Branswell's work ever since I dove head-first into this topic some three years ago. She writes for the Canadian Press and I consider her one of the top two infectious disease reporters on the planet. Her Twitter address is @CP_Branswell and I encourage you to follow her Tweets. She'll make you smarter in no time!

Intrepid reader,

Last week, I blogged about the possibilities of swine H1N1 to graft other genes onto its genetic construction. I have mentioned my concern that swine H1N1 could, in fact, easily pick up the amino acid combo which, in the aggregate, represents the Tamiflu Resistance Gene.

I also alluded to the potential for swine H1N1 to take a victory lap around the world and reassort with our old friend H5N1. Now I mentioned this only in passing. The reason should be obvious: A number of persons believe this whole H1N1 thing is either a gross overreaction by public health professionals, and/or a ploy by the Obama Administration to advance its public health agenda.

It is neither, although every time I hear an Obama official even mention health care "homes" in the same breath as H1N1, I cringe, because they need to put the Rahm Emanuel playbook down ("Rule 1: Never allow a crisisto go to waste") during this entire evolving event.  It is important to know that the Obama Administration is essentially running the Bush playbook on the management of this epidemic, and they have acknowledged as much and have been publicly grateful for its existence. So far, I have not seen any major mistakes, mea culpas or blown calls in the response to this unfolding situation out of Washington, excepting the Vice-President-in-charge-of-embarrassing-gaffes and soon to be Lame Duck, Joe Biden.  And even he was saying what everyone else was thinking, I suppose.  Still, as a recovering politician myself, I am amazed at this guy's lack of an "internal quip governor" (think NASCAR restrictor plate) and how Obama allowed him to get on the ticket. 

But I digress.  Back to the issue at hand, namely reassortment.  Bloggers have been understandably reluctant to stray too far into joining swine H1N1 with avian H5N1.  But when the world's leading influenza expert -- the "Pope of Influenza," Dr. Robert G. Webster of St. Jude in Memphis -- comes out and says what everyone else in Flublogia is thinking, I think it warrants a good blog.

Dr. Webster has dedicated his entire adult life to the understanding of influenza. He has learned much, but each answer generates a whole new set of questions. He, Edwin Kilbourne, John Oxford, and the late Graeme Laver stand as the true giants of modern influenza research. Upon their footpaths walk Kawaoka, Peiris, Webby (like Peiris, a protege of Webster) and others.

Kawaoka has taken some ribbing from this Blogger in the past, but let me assure you he knows his stuff and the world is a better place with him and all his skills on board.

When Webster talks, or even speculates, it is by definition informed, and we should do the old E. F. Hutton commercial and listen. Today, an AP article -- one of the best-researched I have read in quite some time -- speaks of the opportunity for swine H1N1 to reassort with avian H5N1 and produce -- something.  One treat is that it quotes from three of the best-known names on the influenza front, which is always fun.

I will give the article and its link later. What I want to talk about now is the situation in Egypt, and why the Egyptian government made the controversial move to slaughter all its pigs virtually overnight. Something feels Biblical in that decision, you know. It was met with hostility and violent demonstrations across the nation. Only Christians eat pork there, and the hogs slaughtered were destined only for Egyptian Christian dinnertables.

But I believe the Egyptian government had its own experience and that of Indonesia on its mind when it made the decision. The Egyptian government has been looking for a reason to wipe out the hog population since 2008, because there was and is growing concern that Egyptian pigs had become reservoirs for H5N1. Search "Egypt" on my blogsite to find everything of consequence that has happened in that country, flu-wise, since 2006. I'll wait. Especially read my January, 2008 blog here. It has a pretty graphic, too.

OK, welcome back. You should have seen the blog post fromEgyptian blogger Zeinobia, whose blog from January 2008 -- yes, I said January 2008 -- was an eerie foreshadowing of our current situation.

Short form: The Egyptian government is scared to death that H1N1 will come around and reassort with H5N1, which they believe to possibly be endemic in their pig population.  And if you look at the continuing increase in suspected and confirmed Egyptian H5N1 human bird flu cases, I think you'd agree there is much to be concerned about.

Likewise, the situation in Indonesia and in China also involoves informed speculation on behalf of animal and human influenza researchers that H5N1 may have made a small foothold in the hog populations there. Especially Indonesia, which remains Bird Flu Central for human cases and potential pandemic explosion, despite the competition from ongoing Egyptian human infections. Researchers already know that some 20% of the stray cat population in Indonesia has H5N1 antibodies. Likewise, some hogs in Indonesia have tested positive for H5N! antibodies. From the Website FluWiki, from2006:

Cat H5N1 sequences in Indonesia are apparently more similar to H5N1 sequences from humans than either are to H5N1 sequences from birds. What is the most logical interpretation of these results? I submit that there may be a mammalian reservoir for H5N1 in Indonesia and other countries and that H5N1 is under selection to adapt to mammals in this reservoir. Further, at least some of the human cases may be due to mammal-to-human infections. (See also Dr. Jeremijenko’s post at 23:14 in this thread, and here and here). In the recent large cluster of human cases in Indonesia, no infections of poultry were found in close proximity to the village where the outbreak occured. However, pigs with antibodies to H5N1 were found in this region reference. H5N1 infections in pigs would be particularly worrisome as these animals could serve as mixing vessels for the formation of a human-adapted H5N1 strain. (bold mine)

That is what everyone is worried about. That is the Elephant in the Room. That is why no one in Geneva, Atlanta or anywhere else is overreacting about this swH1H1 epidemic.

Now it is time to bring in the AP story. Here it is, in its entirety.

Top flu expert warns of a swine flu-bird flu mix

By MARGIE MASON, AP Medical Writer Margie Mason, Ap Medical Writer 2hrs29minsago

MEXICO CITY – Bird flu kills more than 60 percent of its human victims, but doesn't easily pass from person to person. Swine flu can be spread with a sneeze or handshake, but kills only a small fraction of the people it infects.

So what happens if they mix?

This is the scenario that has some scientists worried: The two viruses meet — possibly in Asia, where bird flu is endemic — and combine into a new bug that is both highly contagious and lethal and can spread around the world.

Scientists are unsure how likely this possibility is, but note that the new swine flu strain — a never-before-seen mixture of pig, human and bird viruses — has shown itself to be especially adept at snatching evolutionarily advantageous genetic material from other flu viruses.

"This particular virus seems to have this unique ability to pick up other genes," said leading virologist Dr. Robert Webster, whose team discovered an ancestor of the current flu virus at a North Carolina pig farm in 1998.

The current swine flu strain — known as H1N1 — has sickened more than 2,300 people in 24 countries. While people can catch bird flu from birds, the bird flu virus — H5N1 — does not easily jump from person to person. It has killed at least 258 people worldwide since it began to ravage poultry stocks in Asia in late 2003.

The World Health Organization reported two new human cases of bird flu on Wednesday. One patient is recovering in Egypt, while another died in Vietnam — a reminder that the H5N1 virus is far from gone.

"Do not drop the ball in monitoring H5N1," WHO Director-General Margaret Chan told a meeting of Asia's top health officials in Bangkok on Friday by video link. "We have no idea how H5N1 will behave under the pressure of a pandemic."

Experts have long feared that bird flu could mutate into a form that spreads easily among people. The past three flu pandemics — the 1918 Spanish flu, the 1957-58 Asian flu and the Hong Kong flu of 1968-69 — were all linked to birds, though some scientists believe pigs also played a role in 1918.

Webster, who works at St. Jude's Children's Research Hospital in Memphis, Tenn., said bird flu should be a worry now. Bird flu is endemic in parts of Asia and Africa, and cases of swine flu have already been confirmed in South Korea and Hong Kong.

"My great worry is that when this H1N1 virus gets into the epicenters for H5N1 in Indonesia, Egypt and China, we may have real problems," he told The Associated Press. "We have to watch what's going on very diligently now."

The U.S. Centers for Disease Control and Prevention are extraordinarily busy trying to understand the swine flu virus itself, and haven't had time to break off staff to look at the possibility of a swine flu-bird flu mix, spokesman Dave Daigle said.

Malik Peiris, a flu expert at Hong Kong University, said the more immediate worry is that swine flu will mix with regular flu viruses, as flu season begins in the Southern Hemisphere. It is unclear what such a combination would produce.

But he said there are indications that scenario is possible. Peiris noted that the swine flu virus jumped from a farmworker in Canada and infected about 220 pigs. The worker and the pigs recovered, but the incident showed how easily the virus can leap to a different species.

"It will get passed back to pigs and then probably go from pigs to humans," Peiris said. "So there would be opportunities for further reassortments to occur with viruses in pigs."

He said so far bird flu hasn't established itself in pigs — but that could change.

"H5N1 itself has not got established in pigs," he said. "If that were to happen and then these two viruses were both established in pigs in Asia, that would be quite a worrying scenario."

Michael Osterholm, an infectious disease specialist at the University of Minnesota who has advised the U.S. government on flu preparations, said while flu experts are discussing the scenario, he has yet to see specific evidence causing him to think it will happen.

"Everything with influenza is a huge guessing game because Mother Natureholds all the rules, and we don't even know what they are, so anything's possible," he said. "We don't have any evidence that this particular reassortment is that much more likely to pick up H5N1 than any other reassortment out there."

"We don't have to put these things together," he added. "This is not chocolate and peanut butter running into each other in the dark hallway."

But there is in fact discussion of putting them together — in a high-security laboratory — to see what a combination would look like, according to Webster. Similar tests have been done at the CDC mixing bird flu and seasonal human flu, resulting in a weak product, he said.

Daigle, the CDC spokesman, said the agency wants to look at the question in the future.

Webster has done groundbreaking work on both swine and bird flus in his 40-year career, and has followed the evolution of the current swine flu strain from a virus that sickened a handful of people who worked with North Carolina hogs into a bug that has spread from person to person around the world.

He is closely involved in the global effort to analyze what the virus might do next. It has killed 42 people in Mexico and two in Texas, but so far has not proven very deadly elsewhere, leading to some criticism that the World Health Organization's warnings of a potential pandemic have been overblown.

Webster said underestimating the swine flu virus would be a huge mistake.

"This H1N1 hasn't been overblown. It's a puppy, it's an infant, and it's growing," he said. "This virus has got the whole human population in the world to breed in — it's just happened. What we have to do is to watch it, and it may become a wimp and disappear, or it may become nasty."

___

AP Medical Writer Maria Cheng in London contributed to this report.

So there you go.  I hope wimp, but no one knows what it will do eventually.  However, it is this worry that, I believe, has led the Egyptian government to do what it could not do last year; namely, slaughter the mixing vessels of influenza.  They do not want the Next Pandemic to start on their doorstep.  In that regard, and now knowing what you know, let me ask you:  Have they made the correct decision?

Here are the links, basically the same story.

http://news.yahoo.com/s/nm/20090504/ts_nm/us_flu_who_pandemic

http://www.foxnews.com/story/0,2933,518780,00.html

No one is saying when the alert level will be raised.  My guess is when we see some community transmission outside of North America, especially in Europe and Asia.  Also if we see more cases south of the Equator, where their flu season just began.

OK, we have had a couple of days in which to charge our batteries, refresh and reflect on the events of the past ten days on swine flu, or H1N1, or PC FLU fluffy bunny slippers, or whatever you want to call it.

Here's the quick catchup, and where we will probably go from here:

The situation in Mexico appears to be abating.  Fewer cases and much lower mortality. 

Cases in the United States and elsewhere are increasing.  This is technically true, but the reality is that cases are being confirmed that were first swabbed over a week ago.  So it would be natural and not surprising that the number of cases would increase. These cases are days to a week old by now.

The real issue is this:  Just how deep is this "widespread" flu epidemic?

Flu can best be described using the visual of that old classic shampoo commercial.  You know:  "And they tell two friends, and so on and so on..." as the screen continues to show little squares of faces, Brady Bunch-style. This increase of shampoo-happy faces carries on in the mind of the viewer.

So it is with influenza.  To paraphrase the commercial:  "You'll infect two friends, and they'll infect two friends, and so on and so on..." 

The problem is, we are unsure if we are seeing that "and so on" infection from swine H1N1.  We are seeing human-to-human, maybe even human-to-human-to-human.  But are we seeing the type of sustained community infection patterns that would signify the true start of a pandemic?  And are we seeing this on other continents?

So this is clearly a widespread infection.  But how deep is it?  How well can the virus sustain its ability to infect?  Early indications are maybe not so well, but sustained testing -- and eliminating that testing backlog accurately but quickly -- will answer that question.

Even if we are not seeing sustained community outbreaks, we are not out of the woods by a long shot.  And it is not just if this disease decides to take a victory lap around the world.  I would remind everyone of the prime theory of the late Dr. R. Edgar Hope-Simpson; namely, that a pandemic candidate needs to seed the planet with asymptomatic cases prior to the seminal event that triggers a true pandemic.

With the Internet, rapid testing and other 21st century capabilities (including bloggers, of course!), something that would have never even been a blip on the radar -- not even in 1968 -- can be detected in a reasonable timeframe and dealt with before it is Too Late.

Despite these advances, it is surprising and alarming to listen to certain people in the media talk in one moment about "this response was SO overblown" then alternately asking "Why did it take so long for the Mexican government and the WHO to respond?" 

One genetic change in the 1918 virus made it a killer of tens of millions of people. ONE CHANGE.  That is why organizations and agencies are moving in the ways they are moving.  And what a marvelous opportunity to go to school on this event; to test plans to see what works, what is workable and what clearly is not; and what to tweak and what to abandon.

We don't get these opportunities very often, and we should take advantage of them whenever possible.

Back to the woods:  We're clearly not out of them yet.  The virus has moved to some nations in the Southern Hemisphere, which is having its regularly-scheduled influenza season now.  This means that swine H1N1 will have multiple opportunities to recombine with its seasonal counterpart H1N1, and also reassort with a multitude of oither flus, including seasonal H3N2 -- and H5N1.  So vigilance must be exercised and the course of this situation will be measured not in news cycles.  It will be measured in weeks or months.

Remember, this virus will do one of two things:  It will either burn itself out, or it will go pandemic.  And even if it appears to burn out, it could come back in the fall.  That is one reason why public health authorities are making the decisions they are making.

So settle in, and don't get wrapped around the axle of expecting this to resolve itself on a 24-hour news cycle.  Because we are weeks away from knowing the real scope and more importantly, the depth of this new virus. 

We ain't gonna know anytime soon. 

The news stories are starting to come out of Washington, DC; Baltimore; and soon Sarasota (and that is rare to have that small retirement city mentioned in the same breath with two of the Big Cities on the East Coast!) that states just don't have enough Tamiflu to go around.

And here in sunny Florida, where we did not avail ourselves of the now-expired Federal coupon offer to buy Tamiflu at cheaper prices, people are openly questioning whether the state should, indeed, buy more.

I have a better idea. First, let me set some background.

I do not know if Roche can take enough plants offline, recommission them and start making Tamiflu again in any quantity. recall that Roche made a huge capital investment in more Tamiflu plants in 2005 and 2006, only to see global demand for Tamiflu abate as the concern evaporated regarding a bird flu pandemic. Roche then recommissioned the lion's share of these facilities to make other drugs instead.

Roche also made a huge breakthrough around that time, namely being able to synthesize the key ingredient of the antiviral drug: Something only found in Chinese star anise. Shikimic Acid. According to Wikipedia, Star Anise, under the influence of shimikic acid, fought Iron Man and Wolverine before being brought down by Captain America, who is now his old sidekick Bucky, the Winter Soldier.

No, that's not right. Damn that Wikipedia!  Anyway,Janapese star anise is right out; only Chinese star anise will work. So Chinese farmers began doing what American farmers have been doing with corn; plowing under all other crops to make the big cash (cow) crop. Chinese farmers were making the kind of money American farmers were making! BIG money from star anise, because it also took a long time to reap the fruit.

But then Roche spoiled the party by synthesizing shikimic acid, and now it can be mass-produced more cheaply. Roche will have to recommission those gleaming Tamiflu plants and also begin re-licensing other drug makers to make Tamiflu under license.

Or will they? Roche has been burned by the world's governments once already. I doubt if Roche will be as willing a corporate partner (meaning ready to heavily discount Tamiflu) as they were in 2006 and 2007. And maybe they shouldn't.

The other X-Factor (so you see a pattern here? Wolverine? X-Factor?) is the dreaded Tamiflu Resistance Gene, or the combination of mutations to neuraminidase of gene segments R292K, N294S, and H274Y. Widespread circulations of this set of anti-Tamiflu genes have rendered Tamiflu virtually useless against the non-swine H1N1 that is our seasonal bug.

In fact, a Scientific American article of March, 2009 coincidentally reminded readers of the presence of this gene set. Here's the most striking passage:

A whopping 98 percent of this year's circulating H1N1 flu strains are immune to Tamiflu, compared with only 12 percent during the 2007-2008 flu season. (bold mine)

"We don’t know what's physically happened to the virus to cause it to transmit more rapidly, but something has and even more so this year," says study author Nila Dharan, a fellow in the Centers for Disease Control and Prevention's (CDC) Epidemic Intelligence Service, which studies major disease outbreaks. Dharan tells ScientificAmerican.com that a spontaneous (natural) genetic mutation – and not overuse of Tamiflu — is to blame. She notes that additional structural changes to the virus (that scientists don’t completely understand) have enhanced the resistant strain's ability to grow and infect people.

The trend is alarming enough that Department of Health and Human Services (HHS) officials have been huddling for the past week to consider whether to adjust the composition of the federal pandemic flu drug stockpile, of which 40 million treatment courses (80 percent) is Tamiflu, says Robin Robinson, director of the Biomedical Advance Research and Development Authority(BARDA), an HHS arm that manages the stockpile.

I guaran-damn-tee you that in the back/front of every single influenza researcher's mind on this planet is the knowledge that these mutations could, at any time, by reassortment or recombination, get into the present swine H1N1. Mutations have already been seen in H5N1 avian flu, but not in large numbers.

But the movement from 12% to 98% in seasonal H1N1 is striking. And where those mutations first appeared is absolutely head-scratching. Rather than link you to all the blogs I have made on Tamiflu resistance, just search this Blogsite for the words "Tamiflu resistance." You'll read everything from the presence of Tamiflu in the water supply of Sweden to the lack of resistance in the most-prescribed Tamiflu nation on earth -- Japan.

OK, now let's assume you are a policymaker. Here are the facts:

• You are broke, out of money, laying off workers, cutting services.
• You have a pandemic-in-the-brewing called swine H1N1. Or H1H1 influenza A. Or "fluffy bunny slippers," according to this insane "let's not-p-off-the-pork-people" White House PC-silliness. Hey, let's just call this "PC FLU?"

But I digress.

• You also know you don't have enough Tamiflu to really get the job done.
• And there is this as-widespread-as-Jonas-Brothers-fever anti-Tamiflu gene that is found in 98% of all seasonal H1N1 flu this past season.
• Did I mention your state is broke?

I have a solution. Back in World War II, largely in the pacific, Corpsmen and medics were stretched to the limit on penicillin. They did not have enough to treat everyone with an infection.

Miraculously, they did have this relatively new anti-gout medicine called Probenecid. They knew one of the side effects of Probenecid was that people didn't pee as much as normal. So someone in some battlefield MASH unit said "What the Hell, let's see if it works," and co-administered Probenecid with penicillin.

And danged if it didn't work! The co-administration of Probenecid with penicillin stretched the effective supply of penicillin by a factor of 2.

A few years ago, people with long memories and concern over Tamiflu stocks began speculating about the effectiveness of Tamiflu and Probenecid. I have written about this many time before, but the definitive blog on the subject in my inventory is this shoulda-won-a-Pulitzer story:

Killing two birds with one stone

A portion of Roche's study of the use of probenecid in 2002 comes from the blogsite Smart Economy, and the story can be found at: http://smarteconomy.typepad.com/smart_economy/2005/11/smart_wartime_t.html.

Dr. Michael Greger, a person whom I communicate with occasionally, wrote in his seminal work Bird Flu: A Virus of our own Hatching:

Roche found that probenicid doubled the time that Tamiflu spent circulating in the human bloodstream, effectively halving the dose necessary to treat someone with the flu. Since probenicid is relatively safe, cheap, and plentiful, joint administration could double the number of people treated by current global Tamiflu stores. “This is wonderful,” exclaimed David Fedson, former medical director of French vaccine giant Aventis Pasteur. “It is extremely important for global public health because it implies that the stockpiles now being ordered by more than 40 countries could be extended, perhaps in dramatic fashion.”2495

So let's review:

• Probenecid is safe.
• It keeps the medicine in the body longer.
• It will effectively double our supply of Tamiflu overnight.
• It will free up Relenza for use exclusively by police, fire, EMT, emergency room staff, and otehr first responders.
• It will reduce the incidence of painful gout in Tamiflu takers.
• It will reduce the amount of Tamiflu that makes its way into the groundwater, thereby making it the "green" solution.

In short, the co-administration of Tamiflu with Probenecid is a solution that bears very close, careful scrutiny. 

Always glad to help.