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I don't know how many of you have caught this or done the math, but the case fatality rate (CFR) from swine flu has actually increased, at both global levels and within the United States.

The published global CFR in late June was plugging along at .002, while the US CFR was at .0045.  Now, the US CFR is .0056, and the global CFR is at .0045.  So the world has caught up with America in terms of its death rate, and the figure of .0045 places this pandemic squarely within the HHS Category Two pandemic status.  But the threshold to Category 3 status is .0051.  For the past two weeks, the US CFR has exceeded the Category 3 benchmark.  Like the hurricane that spawned this HHS analogy, those winds -- and deaths -- have to be sustained.  The next few weeks will tell us if we are seeing a drop in the CFR, or if the numbers are holding steady.  That may also signal the waning of the pandemic's first wave.

These death numbers do not sound large until you look at large numbers.  If the current CFR holds, by the end of the pandemic, we could be looking at over 400,000 dead in the United States alone.  In Florida, for example, the final death toll could reach 30,000. 

This is probably why the WHO has chosen its words very carefully when describing this pandemic as "moderate" and not as "mild."

How is this possible, you ask?  Swine H1 is "mild," the public health authorities are telling us!  You are even hearing the words "no worse than seasonal flu" mentioned!

I would answer this way:  First, read Dr. Kawaoka's analysis of swine flu in today's/tomorrow's papers.  Second, re-read my blog about totally botched risk communication, and Google/read Dr. Sandman's similar remarks about recent botched risk communication.  Third, remember we are in the beginning stages of a global health crisis that will take at least eighteen months to finally play out. 

Pandemics are not for institutions with ADD, nor are they for institutions who like quick resolutions at the end of a 60-minute show.  Nor are they for institutions who demand happy endings, unless you count the conclusion itself as happy.  They are slow, historic, and life-changing events.  We should treat them and respect them as such.

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