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The WHO has just declared that it does not see a mass-produced swine flu vaccine until next year at the earliest. First, the whole news story.  Then, my usually concise and brilliant commentary.

WHO: No licensed swine flu vaccine til end of year

By MARIA CHENG – 4 hours ago

LONDON (AP) — A fully licensed swine flu vaccine might not be available until the end of the year, a top official at the World Health Organization said Monday, in a report that could affect many countries' vaccination plans.

But countries could use emergency provisions to get the vaccines out quicker if they decide their populations need them, Marie-Paule Kieny, director of WHO's Initiative for Vaccine Research, said during a news conference.

The swine flu viruses currently being used to develop a vaccine aren't producing enough of the ingredient needed for the vaccine, and WHO has asked its laboratory network to produce a new set of viruses as soon as possible.

So far, the swine flu viruses being used are only producing about half as much "yield" to make vaccines as regular flu viruses.

Last week, WHO reported nearly 95,000 cases of swine flu worldwide including 429 deaths. Most people who get the virus only experience mild symptoms and don't need treatment to get better.

In a presentation to WHO's vaccines advisory group last week, Kieny said a lower-producing vaccine would significantly delay the timeline for vaccines. That could complicate many Western countries' plans to roll out vaccines in the fall.

British Health Minister Andy Burnham promised that vaccines would start arriving in the U.K. in August — and predicted the country could see up to 100,000 cases a day by the end of that month.

Before countries can start any mass swine flu vaccination campaigns, the vaccines need to be vetted by regulatory authorities for safety issues. That means testing the vaccines in a small number of humans first, which can take weeks or months.

"I think it will be a very significant challenge to have vaccines going into peoples' arms in any meaningful number by September," said Michael Osterholm, director of the Center for Infectious Diseases Research and Policy at the University of Minnesota. "At this point, it is still is an issue of when will it be available, who will get it, and what will be the dose?"

Kieny said many of those questions remain unanswered at the moment. But she said WHO's vaccine advisory group recommended that health care workers receive the first swine flu shots since they are on the front lines of the global outbreak.

On Monday, British health authorities said a family doctor died over the weekend after contracting swine flu.

WHO's vaccine experts recommend that countries decided that certain groups should get the vaccine first — like pregnant women, people with chronic respiratory problems or obesity, children, and possibly young to middle-aged adults, who have been disproportionately affected by the virus.

The decision to start vaccinating people against swine flu — which so far remains a mild virus in most people — will ultimately be a gamble, since there will be limited data on any vaccine. Until millions of people start receiving the shots, experts will not know about rare and potentially dangerous side effects.

The public health community may still be scarred by the U.S.' disastrous 1976 swine flu vaccination campaign, which was abruptly stopped after hundreds of people reported developing Guillain-Barre syndrome, a paralyzing disorder, after getting the flu vaccine. (bold mine)

Several drugmakers are currently considering using adjuvants, ingredients used to stretch a vaccine's active ingredient, which could allow for many more vaccine doses. But little or no data exists on the safety of vaccines with adjuvants in populations including children and pregnant women. And in the U.S., there are no licensed flu vaccines that use adjuvants.

Copyright © 2009 The Associated Press. All rights reserved.

I bolded the reference to 1976 because it is relevant.  In 1976, several people contracted Guillain-Barre syndrome and died.  As a result, the vaccine was pulled from production.  And yet, when A/Victoria broke out in early 1977 at a nursing home in Miami, the only vaccine available was the bivalent swine flu shot.  They broke it out and never saw a statistically significant rise in Guillain-barre, even though it was the same vaccine!  Why has never been determined.

Haste makes waste.  A hastily-manufactured vaccine can bring its own batch of problems and issues.  And now we  see where this virus simply does not like to be cultured.  Not "cultured" as in Shakespeare, although I suspect we will see Shakespearian tragedies and heroism before this pandemic is finished.  I mean "cultured" as in grown in a Petri dish, or in this case grown in chicken eggs.

The first doses of swine flu vaccine that rolls off anyone's assembly line will be directed at first responders and medical personnel.  Doctors, nurses, police and fire and EMS/EMTs will be the first to get the shots.  So will National Guard troops, I suspect.  Then will come the high-risk groups, beginning with anyone from age 5 to 50.  Then will also concurrently come persons with high risk factors, such as HIV, lupus, diabetes, cancer patients on chemotherapy, persons with other auto-immune disorders, persons with COPD, and so on.

And as of today, it is highly doubtful if any of these shots will come before the first of the year.  With the pandemic's first wave still underway and its second wave forecast for autumn, that means we will be well into the second wave before any vaccine hits the masses.

In the sensational book Good to Great, author Jim Collins speaks of the Stockdale Paradox.  The late Admiral Jim Stockdale was a Vietnam POW.  How did he get through several grueling years as a captive?  By always having hope, but not having false hope.  He knew he eventually would be released or rescued, but he never latched onto transient, false hope as some of his fellow POWs did.  He never bought into "We're going home by Christmas!  Did you hear?" or "I heard the armistice is close at hand!" Admiral Stockdale simply kept going, day to day, resolved his situation would improve, yet never pinning his belief on false hope.  This apparent paradox of hoping without hoping also needs to be our mantra as the fall approaches and things turn decidedly for the worse.  We do what Momma taught us.  We cover our cough or sneeze with our sleeve; we wash our hands thoroughly; and we keep a respectable distance from strangers.

So don't pin your hopes on a vaccine that might not come until the pandemic's second wave has returned.  Focus on the things you know work and share those things with others.  Eventually, there will be a vaccine.  But do what needs to be done until (and during and after) that time.

University of Wisconsin-Madison virologist Dr. Yoshihiro Kawaoka is also a professor at the University of Tokyo. He is one of the world's top influenza and infectious disease researchers and, quite frankly, someone you better listen to.

Veteran readers of this blog know I have mentioned him from time to time, and have sometimes been critical of him. But that does not diminish my massive respect for him, nor does it diminish his formidable intellect and talent.  He's one of the best we've got ("we" being the Human Race).

He has just released a new study that the entire world needs to read and absorb. The new study was funded by grants from the U.S. National Institutes of Health, and the Japanese Ministry of Education, Culture, Sports, Science and Technology. Funding sources like these do not come easily and must be won with extremely hard work and superb science.

So do I have your attention? Good.

Dr. Kawaoka says the current swine H1N1, or H1N1v, or whatever it is we are supposed to call our resident pandemic virus, is reminiscent of the 1918 Spanish flu. Quoting directly from the press release:

In contrast with run-of-the-mill seasonal flu viruses, the H1N1virus exhibits an ability to infect cells deep in the lungs, where it can cause pneumonia and, in severe cases, death. Seasonal viruses typically infect only cells in the upper respiratory system.

"There is a misunderstanding about this virus," says Kawaoka, a professor of pathobiological sciences at the UW-Madison School of Veterinary Medicine and a leading authority on influenza. "People think this pathogen may be similar to seasonal influenza. This study shows that is not the case. There is clear evidence the virus is different than seasonal influenza."

The ability to infect the lungs, notes Kawaoka, is a quality frighteningly similar to those of other pandemic viruses, notably the 1918 virus, which killed tens of millions of people at the tail end of World War I. There are likely other similarities to the 1918 virus, says Kawaoka, as the study also showed that people born before 1918 harbor antibodies that protect against the new H1N1 virus.

And it is possible, he adds, that the virus could become even more pathogenic as the current pandemic runs its course and the virus evolves to acquire new features. It is now flu season in the world's southern hemisphere, and the virus is expected to return in force to the northern hemisphere during the fall and winter flu season.

Dr. Kawaoka's study mentions in elaborate detail the methodology used to acquire this evidence:

To assess the pathogenic nature of the H1N1 virus, Kawaoka and his colleagues infected different groups of mice, ferrets and non-human primates - all widely accepted models for studies of influenza - with the pandemic virus and a seasonal flu virus. They found that the H1N1 virus replicates much more efficiently in the respiratory system than seasonal flu and causes severe lesions in the lungs similar to those caused by other more virulent types of pandemic flu.

"When we conducted the experiments in ferrets and monkeys, the seasonal virus did not replicate in the lungs," Kawaoka explains. "The H1N1 virus replicates significantly better in the lungs."

The new study was conducted with samples of the virus obtained from patients in California, Wisconsin, the Netherlands and Japan.

OK, the short form:  Swine H1N1v is replicating deep in the lungs of victims, as did the 1918 pandemic virus (and as does H5N1 bird flu).   Kawaoka claims that the virus has every ability to become even deadlier as it wins its King of the Mountain excursion across the Southern Hemisphere.  Over 90% of all influenza in the Southern Hemisphere is swine H1, meaning the pandemic strain has officially won the  competition. What spoils of war will this flu acquire as it assimilates other, defeated flus?

To say I am disappointed in the overall US response to the current swine H1, or A/H1N1v, or whatever the Hell we are supposed to call our pandemic of 2009, is to state things mildly.  And we have had failures on every front imaginable:  Risk communication, surveillance, sampling, and community response.

First, let me take the most recent CDC report I could find.  Dated 10 July 2009, the CDC report on pandemic H1N1 states that out of 37,246 cases, 211 persons have died.  The previous week, out of 33,902 reported or suspected cases, 170 have died.  This equals a case fatality rate of .005.  Statistically, it is in line with the .0045 I spoke of a little over two weeks ago.

But it is also consistent, which means that .0045, or .005, is not an abberation.

Meanwhile (and I TOLD YOU SO back on June 11th), the WHO has recommended to its major members that it stop swabbing each and every single case solely for the purpose of counting swine flu cases.  I said to take that approach over a month ago; the WHO moves a little more slowly, but it has been moving in exactly the same direction as what I have recommended since the first outbreaks began.

The WHO is recommending that other member nations continue to swab to determine spread in nations that previously have not experienced many cases.  They are also recommending swabbing in order to detect any mutations in the virus itself, specifically Tamiflu resistance and any changes in PB.

But our reporting methodology still relies upon human beings.  And those humans right now are exhausted, overworked, and tired.  Let me give you a glaring example of a hole in reporting:  the State of Florida.

Florida's Department of Health had the legislative equivalent of a shotgun wedding with previously-run county health departments a few years ago.  The marriage has gone pretty well, considering the scattershot states of being these health departments were in.  Post-9/11 funding and training has moved things along, and the October, 2001 anthrax attacks here in Florida also moved mountains.

But look at the swine flu surveillance report dated 4 July 2009.  Of Florida's 67 counties, nineteen did not report anything -- good, bad or ugly -- pertaining to swine flu.  These counties included Brevard, home of Cocoa Beach and Cape Canaveral; Lee, home of Ft. Myers; Charlotte, home of Punta Gorda (OK, maybe not so big); and rural Gadsden, which had already reported a swine flu case!

The total population in all the nonreporting counties alone exceeds 1,400,000 people. That makes the non-reporting counties of Florida larger than 11 states and on par with the states of Nebraska and Idaho.  Now, of course this does not mean these counties had cases, nor does it mean they did not have cases.  We do know for a fact that earlier, Lee and Brevard have had multiple confirmed cases. 

The point is that we are in the beginning of a flu pandemic, and we cannot get 19 counties to report their status?  What is wrong with these people?   How can we get an accurate count of anything if 19 counties are not reporting?

This is going on everywhere, I suspect.  But it does not affect the attack rate nor does it affect CFR.  If similar attack rates are happening elsewhere, they are probably happening in similar counties, reporting or not.  Swabbing or not.  And I have to suspect that with haphazard reporting comes - haphazard explanations of death.

"Oh yes, Mrs. MacGillicuddy.  She was 63 years old and had a bad heart.  It just gave out on her.  Yes, she said she felt bad.  Feverish, even.  But her heart killed her, poor thing."

It takes just one of those events in a third of the counties in America to reach alarming numbers of swine flu-related deaths.

A Danish patient has the distinction of being the first known, apparently-documented case of Tamiflu-resistant swine H1N1.

That's a mouthful.

It is being dutifully reported across the globe, and no doubt shares of Roche are tumbling.

I hope none of you bought Roche heavily, right? Because you knew this day would come. I predicted it back in April, on this blogsite. And it was not too Nostradamian, admittedly. You see, in 2006-07, Tamiflu-resistant seasonal H1N1 was around 4% of all samples tested. the following season, 2007-08, it had climbed to 10%. And this past season, seasonal H1N1 was 97% Tamiflu-resistant.

Tamiflu resistance has cropped up from time to time in areas hit by human H5N1 bird flu infections. So it was not a stretch to imagine that Tamiflu resistance would occur.

Nor is it too surprising that Denmark would be the first occurrence. Recall (search "Norway" or "Sweden" on this site) that Scandinavia has a far higher proportion to Tamiflu resistance than other nations. Denmark ain't that far away from Scandinavia, as the migrating bird flies.  Here's what I wrote, back in January, 2008:

Normally, you would expect Tamiflu-resistant H1N1 influenza to show up in areas where Tamiflu is prescribed. But that is not the case here! There are no known cases of H1N1 with the H274Y mutation in Japan, where Tamiflu is habitually overprescribed;and 70% of H1N1 is showing Tamiflu resistance in distant Norway, where Tamiflu is rarely, if ever, prescribed. Quite a conundrum.

Dr. (Henry) Niman believes that Tamiflu-resistant H1N1 with the H274Y mutation has already been detected in these US isolates:

ISDN282211 A/Hawaii/21/2007 H1N1
ISDN282224 A/Hawaii/28/2007 H1N1
ISDN282222 A/Hawaii/28/2007 H1N1
CY027037 A/Kansas/UR06-0104/2007 H1N1
ISDN282240 A/Minnesota/23/2007 H1N1
ISDN263890 A/Texas/31/2007 H1N1

Norway's seasonal H1N1 was 70% Tamiflu-resistant in late 2007. That's when ours was 4% resistant. If we are to assume our doctrine/dogma that wild birds and globalization and travel move virus mutations, then at least in this one Danish patient, H1N1 has recombined with its seasonal cousin and has conferred Tamiflu resistance. If it has happened once, it has already happened dozens of times. The simple question is: Will this mutation hold?

I expect so. Tamiflu is a weapon of unknown duration and potency in this fight.Use it or lose it. Here;s the Reuters story (with a tip of the cap to Mike Coston at Avian Flu Diary:)

http://www.reuters.com/article/healthNews/idUSTRE55S3UM20090629

By now, alert reader, you know the details. The entire world is engulfed with swine flu.  Even though the WHO dragged its feet in the final days before the Phase 6 declaration, we all knew this virus had achieved pandemic status.

But in this nation, the press, with the exception of the New York Times and local newspapers, has for the most part ignored the story since early June's pandemic declaration. So let's catch up on recent events:

• More people died in this country last week from swine flu than died in all of April and May combined.
• Same thing happened last week.
• Deaths in this country are doubling every week.
• It is spreading deeper into corners and pockets of America where it was not before.
• The Muscular Dystrophy Association has cancelled every single one of its MDA kids' summer camps, coast-to-coast. Other organizations are following suit.
• The average age of a dead American from swine influenza is 37.
• The CDC is telling us this virus is moving faster than the 1957 or 1968 pandemics did. Understandable, with quick, easy air travel and interstate highways. But so far, it is not moving with the ease of seasonal flu. So far.

What is difficult to gauge is just how we should categorize this pandemic from a "Saffir-Simpson" standpoint.  Drs. Fukuda and Chan of the WHO says this is a "moderate" pandemic. That would place it in the range of 1957's H2N2 pandemic, which killed 70,000 Americans and around 2 million worldwide. (If the 1957 pandemic hit today, it would kill 122,000 Americans).

A moderate pandemic would also nest 2009's swine H1 pandemic into high Category 1 or low Category 2 status on the US charts.   As you have seen from the charts I have published before, the case fatality rate from a Category 1 pandemic is up to 90,000 deaths. A Category 2 pandemic is anywhere from 90,000 to 450,000 deaths.

The case fatality rate from swine H1 is currently .0045, or .45%. That means that for every 2000 people who get sick from swine H1, 9 will die. Extrapolating this rate out over the probable three pandemic waves, we could see as many as 400,000 Americans die from swine H1.

There, first time in print. Unchecked, and at the current rate of fatality, some 400,000 US residents could die. And most of them would be under age 50.

Can you imagine what devastation that would cause to young families? To the economy? To the economic future of the Republic?  Is it any wonder, then, that the US government has arranged for some 600 million doses of swine flu vaccine, to be administered in two shots for each American at three week intervals?

Well, two shots spaced three weeks apart for anyone under age 50.  For those of us carrying AARP cards, we get one shot -- one shot, Vasily -- and one shot only.  At least that's the current thinking.  Nice to know that neither 1946 nor 1951, when subtracted from 2009, equals 50.  As you know, those were the last two aberrant outbreaks of H1N1 that caused either a partial pandemic or increased fatalities.  So the CDC should limit jabs to one for anyone ages 64 and older. that covers anyone who went through both 1946 and 1951.

Now the public health people would quickly say, "Wait! We think a million Americans have been exposed to swine flu! And only 127 have died, based on positive test results. Your projections are WAY out of line! And you're inciting panic!"

Am I?

First, let's take that "one million Americans" stat. I absolutely agree that at least one million Americans have been exposed to the virus. But in what quantity (titer) of virus? How many particles?

We know that a normal flu season will only infect up to a fifth of Americans. Why only a fifth is a matter of continual speculation. It is probably a combination of vaccination successes, cleanliness, partial immunity, and damn good genes. There is a growing community in the scientific and public health fields that believes some people are genetically doomed to always catch the flu, while others are genetically predisposed to never catch it. Most of the rest of us are constantly in the middle.

Pandemic calculations are different. The US government's own pandemic projections indicate 90 million infected, 45 million presenting serious illness, and then factor in the appropriate Case Fatality Rate (CFR). This is opposed to the 5% to 20% who gets seasonal flu every year, according to the CDC. Roughly 36,000 to 40,000 people annually die from seasonal flu. A CFR of .001.

But last year, the CDC only tested less than a quarter of a million people for flu, even though some 60 million may have been infected.From the CDC Website:

During September 30, 2007 – May 17, 2008, World Health Organization (WHO) and National Respiratory and Enteric Virus Surveillance System (NREVSS) collaborating laboratories in the United States tested 225,329 specimens for influenza viruses.

And another statistic:  In the 2007-08 flu season, only 83 deaths were reported of children ages 18 and under from influenza.  Eighty-three hardcore, confirmed pediatric deaths out of 36,000 estimated seasonal deaths from flu.

So the figure of 36,000 people annually dying from flu is an old stat that has pretty much entered the lexicon as fact. But certainly not every single one of those 36,000 people were tested for flu! Else the CFR for seasonal flu would be around 16%.  So the experts at CDC have algorithms to determine such things.

OK so far?  Let's continue.

The estimate of 36,000 deaths annually from seasonal flu is based on extrapolating the numbers of infected and looking at the CFR of those who tested positive and died, and then reapplying that CFR to the overall guesstimate of infected. And you really never know how it all turned out until it all turns out.

The calculations are really no different with pandemic flu. We've earlier mentioned the equations.  Let's do the calculations together:

• According to the CDC, one million Americans have been infected with swine H1.
• That means 330,000 Americans (nearly one-third) have become ill, even mildly so.
• That means 165,000 people have been seriously ill enough to (hopefully) stay home.
• That means an estimated 1,485 Americans have potentially died from swine flu or its complications to date.

How many Americans have died from pneumonia, or from other life-threatening complications, and were never diagnosed with swine H1? What are the chances that, from late March until today, that over a thousand Americans have died from swine H1 and those deaths have gone undetected and unrecorded?

I'd say, pretty damn good. Look at the massive, gaping holes in surveillance. Look at the people who have not been swabbed. Look at the immuno-compromised in this nation.

I would speculate that a significant number of deaths from pneumonia since March 2009, and many MRSA-related deaths, and significant numbers of death from "respiratory complications" since mid-March could, in actuality, have been swine flu-related.  As of last week, we have 127 documented deaths from some 27,717 confirmed or probable cases.  We know that 99% of all influenza A being typed in America today -- right this minute -- is testing positive for the pandemic strain. From the CDC:

During week 24 (June 14-20, 2009), influenza activity decreased in the United States, however, there were still higher levels of influenza-like illness than is normal for this time of year.

• Three thousand two hundred eighty-six (41.9%) specimenstested by U.S. World Health Organization (WHO) and National Respiratory and Enteric Virus Surveillance System (NREVSS) collaborating laboratories and reported to CDC/Influenza Division were positive for influenza.
• Over 99% of all subtyped influenza A viruses being reported to CDC were pandemic influenza A (H1N1) viruses. (bold mine)

OK, so we have 127 confirmed swine H1 deaths. Subtract 127 from 1,484 and we have 1,357 deaths. We have, according to the Census Bureau via Wikipedia:

The U.S. Census Bureau lists 3,140 counties or county-equivalent administrative units in total. There are on average 62 counties per state.

It would take less than one death in half the counties in America to reach that number. What are the odds that one pneumonia-related death, or one MRSA-related death, has occurred in each county in the United States since the inception of this swine H1 outbreak/epidemic/pandemic?

Pretty daggum good, I would say.

At the 2000 U.S. Census, only 16.7% of U.S. counties had more than 100,000 inhabitants. That would make 525 counties (let's round up in case some county had 90,000 people). What are the chances that each of these 525 counties had, say, three people die of pneumonia since late March that went untyped? And even if they only had one apiece in the past three months, that would leave the remaining thousand cases to be spread over some 2,600 counties, parishes, etc.

Not to mention the possibility that many swine H1 deaths may have been mistakenly attributed to seasonal flu.  I have great difficulty in believing that only 2 persons have died in Florida from swine influenza. Not when you look at the figures coming out of Latin America and you realize Miami is the gateway to Latin America -- not to mention Orlando's Disney World. 

Miami-Dade County has over two million residents.  It has reported, to date, 305 positive swine flu cases.  Yet only one death-- a 9-year old child -- has been reported?  Ridiculous.  Florida has recorded 941 cases, yet it has documented only two deaths from swine H1.  Using the nationwide CFR, Florida should have experienced 4 deaths.  Using New York's CFR, it should have 10 deaths.  Do the numbers yourself.  Check the CDC H1N1 Website and see your state's results.

This is probably as much a function of the diligence of state and local health departments to test suspected influenza cases as anything else.  New York has a higher CFR because they have been looking for the virus and they had a good health commissioner.  So good, he now runs the CDC, promoted by Obama in the middle of New York's problems. 

I think you can see where I am taking you.  We are missing many deaths.  You cannot speculate that we have a million swine flu cases without a concurrent speculation that we are missing many, many deaths.  And as I have just proven, it takes less than one death per county over two months to fill in those gaps in surveillance.  This is the danger in trying to look so closely at the actual number of positive swabs that you miss the Big Picture. 

That Big Picture includes monitoring large employers for signs of absenteeism.  It includes enlisting Chambers of Commerce and the US Department of Labor to check employee absenteeism.  It means coordinating with governments at the local and state level as well as the Federal government to monitor absenteeism on a daily basis.

Keep swabbing and keep testing, absolutely.  But do not solely rely upon swabs to tell you who is sick.  And do not tell me, or anyone else, that we only have 127 dead from swine H1 so far in this nation. 

Effect Measure has a sensational piece regarding the current state of the flu pandemic. It includes references to risk communication expert Dr. Peter Sandman, who was very kind in his praise of one of my recent blogs.  It concludes this way:

Public health authorities up north are counting on having some advance warning on how bad things can get by seeing what is going on in the southern hemisphere. But the virus may not give anyone that luxury. Countries like Australia, Argentina and Chile are already getting hammered and the virus seems to be increasing in places in the north at the same time. In other words, we have yet to take the measure of this virus.

Whatever that measure turns out to be, I feel pretty confident that "mild" won't be a word to describe it.

My good friend Mike Coston has also weighed in on the topic.  Both Revere at Effect Measure and Mike reference the piece by Helen Branswell of the Canadian Press.  Helen's work is always superior, and her article is spot-on perfect. Read her piece (you just passed the link).

Get set to get absolutely hammered this fall.