Scott McPherson's Web Presence

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.

This afternoon, I challenged and questioned the World Health Organization's decision to move its pandemic doomsday clock from Phase 4 to Phase 5.

Then, on my drive home, I heard a familiar voice on my radio. I immediately recognized it as Dr. Margaret Chan, the head of the WHO. Later, I found out that it was Chan who personally made the decision -- and takes the responsibility -- for moving the world to One Stroke from Midnight.

I absolutely support Dr. Chan, because she is getting to be an old hand at these things.

A history lesson is in order for the newbies who are coming to this Website. Dr. Chan is a dual Canadian and Chinese citizen. I am confident that distinction has literally saved her life at least once.

In June of 1997, Dr. Chan was the public health secretary of the City of Hong Kong when the city was handed over to the Communist Chinese by the British government. Barely six months later, Hong Kong citizens began dying from a sudden outbreak of a new and novel strain of influenza. At first, Chan was told -- ordered -- by the Communist handlers to ignore the situation and to downplay it however possible. At first, she did this. But it was soon apparent that this novel virus was moving with devastating efficiency from person to person.

This virus was then typed. It was an avian flu that jumped the species barrier and began infecting humans directly. It was moving quickly and she recognized that drastic action was necessary. So, in direct conflict with her new Communist bosses, she disclosed the existence of H5N1 -- H5N1 -- and ordered the culling -- the destruction -- of all commercial poultry in the city.

Amazingly, her handlers stood down, the Hong Kong government moved quickly, and an H5N1 avian flu pandemic was averted.  That original human strain of H5N1 was moving person-to-person and she stopped it in its tracks with her actions.

Next came the beginning of 2003. In neighboring Guangdong province on the mainland, and an area under direct Communist control, people were getting sick and dropping dead of a strange and deadly virus that moved far more quickly than influenza. Initially, she was unable to even inquire into the affairs of a neighboring province.  The Communists had settled in, and they had established a ridiculous and centralized reporting infrastructure that meant everything went through Beijing.  Eventually, she felt compelled to act, again risking dismissal, imprisonment (or worse) from her bosses. 

The virus would eventually be known as Sudden Acute Resipratory Syndrome, or SARS. Her actions help save lives and she helped beat back the disease.

Some have been critical of Dr. Chan's handling of the SARS crisis. Those criticisms usually revolve around the delayed quarantine of E block of the Amoy Gardens apartment complex within the city.

Let me set the record straight on this.  Hong Kong's residents were and are very independent.  Amoy Gardens block E was a 33-story, 8-units per floor apartment complex.  It took Dr. Chan several days before it was decided by the authorities that she even had the authority to quarantine an entire apartment building.  Then, many residents attempted to break quarantine.  Eventually, the government was able to convince the residents to evacuate the building and move to different accommodations, because reinfection with SARS was possible via the sewage system of the building.  Once the residents were moved, the outbreak ended.

One only needs to read former Time editor Karl Taro Greenfield's superb - and I mean superb - chronicle of the SARS epidemic, titled "China Syndrome - the True Story of the 21st Century's First Great Epidemic" to appreciate both the restrictions placed upon Dr. Chan by the Communist bureaucracy and her resourcefulness in overcoming those obstacles.

Decisions made in these situations are similar to battlefield decisions, and events move very, very rapidly. I am sure some decisions hang heavily on her to this day.  But she has never shirked away from her duty.

In 2003, the WHO brought in Dr. Chan to become director of the Department for Protection of the Human Environment. She rose to the position of Director General in November 2006, following the sudden and tragic death of her predecessor, South Korea's Lee Jong-wook, who died in late May, 2006 after he underwent surgery to remove a blood clot on his brain.  Her direct experience with H5N1 and SARS got her the assignment.

So as far as pandemics go, this ain't her first rodeo.  She has stared down two pandemic candidates and helped beat them back.  She has seen both diseases up close and personal.  So if Dr. Chan felt compelled to make the call and push the button and take us to Phase 5, I am not qualified to question her decision.  I am with her all the way.

No one alive has the experience she does to make that call.  No one else has the blend of medical, scientific and political knowledge necessary to make that call.  She is unique among her peers and the world is fortunate to have her where she is. 

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Just in:  We are at Phase 5.

Everyone who has read this blogsite for any duration of time knows of my quest to get the WHO to raise the pandemic threat level from 3 to 4.

Two days ago, and for a wildly different reason, the WHO has seen fit to do just that.  Now there is speculation that the WHO is about to raise that pandemic threat level again, to Phase 5.

I think that is a bad idea.  I will wait while you pick up your jaw from the floor.

OK, let's talk.

It took a mammoth event to get the WHO off the schnide in the first place.  Now, with the pandemic alert level at 4 of 6, I think we should let that level sink in a bit.  The WHO cannot be seen as crying wolf, especially if there is no evidence that the virus is causing massive, exponential infections beyond those unfortunates who recently traveled to Mexico.

We will see evidence of these expanded infections quickly if they are to come.  Evidence of expanded infections would mean the virus is causing widespread infections.  I don't mean an infection or two in a town that does not go beyond a person or a family.  I mean infections that go from 5 to 100 in a couple of days.

A lack of same would mean this virus may have temporarily lost some of its bluster.  "Temporarily" could be a few days, a few weeks or the virus could lay dormant until the late summer or early fall -- just like 1918.

I just don't think we are seeing the groundswell (yet) in cases that would signify a raising to Phase 5.  If -- and I mean IF -- the WHO raises the threat level, it could be because there are so many nations reporting a pocket of cases in a number of countries.  But there is so much surveillance going on now that evidence of a rapid expansion of cases beyond those people who recently traveled to Mexico would be quickly forthcoming.

 We are also not seeing an exponential increase in Mexican cases.  If this virus was lethal, we would see a continuing acceleration of extreme respiratory distress, and an increase in deaths.  In the past two days, these Mexican cases haveapparently slowed down.  This is decidedly good news and we all certainly hope that  this trend continues.

Everyone is prepositioning assets in the field.  We have anecdotal evidence of increased Federal activity right here in Florida, and I am certain other states have similar initiatives underway.  Everyone is on alert and on their guard.  So let's let Phase 4 do its thing -- what it was designed to do -- and get everyone moving to prepare for Phases 5 and 6.  Tell people what to buy and how to recognize infection.  But let's not pull that Phase 5 trigger unless and until the number of follow-on cases have justified the acceleration.

Of course, there is always the possibility that things are afoot that no one knows about.  But I do not think that anyone knows enough about this virus at this point that would justify a move to Phase 5.  Scientists and researchers are having trouble why this virus has changed its business model to sicken humans, when there are no apparent major changes to be seen in either the HA or NA strands. 

One more thing:  because of the Guillain-Barre side effect problems back in 1976, the government and vaccine makers had better make damn sure there is nothing in that syrup to prompt the kind of anomaly that occurred in 1976.  And putting it in the trivalent fall cocktail makes a hell of a lot of sense. 

Phase 5 is the equivalent of the Department of Homeland Security going to Code Red.  In both cases, the only next available step is "Holy *#&#!"

Phase 5 triggers a number of corporate and government responses, and they all cost money and effort.  Let's not move to Phase 5 unless there is demonstrable, defensible evidence that this virus is causing massive infections growing out of those limited number of clusters.  It is a huge move and should not be taken lightly. 

The statement that just came out of Houston clarified the circumstances surrounding the first death in the United States of a person due to swine influenza.  Initial news reports said the child was Mexican and the family took the child to the US for treatment.

Wrong.

The child was Mexican, but the family was visiting relatives in Brownsville, Texas when the child suddenly became very ill.  The child wound up in Houston and died there.

This disclosure will, as you can imagine, create far more questions than answers.  This child was shedding virus all the while he was here.  Let's watch and learn.