Tuesday, September 29, 2009

Monday, September 28, 2009

Study prompts [Canadian] provinces to rethink flu plan/Globe and Mail

Article by Patrick White:

A "perplexing" Canadian study linking H1N1 to seasonal flu shots is throwing national influenza plans into disarray and testing public faith in the government agencies responsible for protecting the nation's health.  Distributed for peer review last week, the study confounded infectious-disease experts in suggesting that people vaccinated against seasonal flu are twice as likely to catch swine flu.  The paper is under peer review, and lead researchers Danuta Skowronski of the British Columbia Centre for Disease Control and Gaston De Serres of Laval University must stay mum until it's published.

Met with intense early skepticism both in Canada and abroad, the paper has since convinced several provincial health agencies to announce hasty suspensions of seasonal flu vaccinations, long-held fixtures of public-health planning.  "It has confused things very badly," said Dr. Ethan Rubinstein, head of adult infectious diseases at the University of Manitoba. "And it has certainly cost us credibility from the public because of conflicting recommendations. Until last week, there had always been much encouragement to get the seasonal flu vaccine."

On Sunday Quebec joined Alberta, Saskatchewan, Ontario and Nova Scotia in suspending seasonal flu shots for anyone under 65 years of age. Quebec's Health Ministry announced it would postpone vaccinations until January, clearing the autumn months for health professionals to focus on vaccinating against H1N1, which is expected to be the more severe influenza strain this season.  "By the time the H1N1 wave is over, there will be ample time to vaccinate for seasonal flu," Dr. Rubinstein said.

B.C. is expected to announce a similar suspension during a press conference Monday morning.  Other provinces, including Manitoba, are still pondering a response to the research.  New Brunswick is a lone hold-out, announcing last week it would forge ahead with seasonal flu shots for all residents in October, as originally planned.

So far, the study's impact is confined to Canada. Researchers in the U.S., Britain and Australia have not reported the same phenomenon. Marie-Paule Kieny, the World Health Organization's director of vaccine research, said last week the Canadian findings were an international anomaly and could constitute a "study bias."

An international panel is currently scrutinizing the research data. "The review process has been expedited, so we're hoping for a response within days," said Roy Wadia, spokesman for the B.C. Centre for Disease control.

Dr. Rubinstein, who has read the study, said it appears sound.  "There are a large number of authors, all of them excellent and credible researchers," he said. "And the sample size is very large - 12 or 13 million people taken from the central reporting systems in three provinces. The research is solid."

The vaccine suspensions do not apply for people over 65. Seniors are considered more susceptible to severe seasonal flu symptoms. At the same time, they carry antibodies from a 1957 pandemic that seem to neutralize the current version of H1N1.

Even if the statistical link is proven, the medical link between seasonal flu shots and H1N1 remains ysterious. One hypothesis suggests seasonal flu vaccine preoccupies the cells that would otherwise produce antibodies against H1N1.  But, according to Dr. Rubinstein, the research shows that people who received the seasonal shot during the 2007-08 flu season remained vulnerable to swine flu well into 2009 - an interval that should provide most immune systems ample restoration time.  "We don't understand the mechanism," Dr. Rubinstein said. "At the present time it is quite perplexing."

Saturday, September 26, 2009

Most parents won't have kids get H1N1 flu shots, study finds/LA Times

From the LATimes:

In a poll of 1,678 U.S. parents conducted by the University of Michigan's C.S. Mott Children's Hospital, 40% said they would get their children immunized against the H1N1 virus -- even as 54% indicated they would get their kids vaccinated against regular seasonal flu.

Hospitals and States Mandating Swine Flu Vaccinations Don't Get It: They will be on the Hook for all Liability for Injured Recipients

A domino effect is cascading through the country, as officials rush to impose vaccination mandates on citizens (Massachusetts) and health care employees (New York), as well as mandate influenza (seasonal +/-swine) vaccinations in many other healthcare systems and hospitals.  Many state laws are written such that in a declared emergency, vaccination or, alternatively, quarantine are required.  The tsunami mandating vaccinations (see WaPo article) is occurring in a vacuum of information about the incidence and impact of the diseases citizens will be forcibly protected against, and the effectiveness and safety of mandated vaccines.  Meantime, the institutions mandating the vaccinations appear clueless about the massive liability for vaccine injuries they are assuming as a result of these mandates.

1)  Low disease incidence of seasonal influenza viruses

Currently (this week) only 1% of circulating influenza viruses in the United States are of the "seasonal" type.  Seasonal flu outbreaks usually start late in the season:  November at the earliest.  It takes 7-10 days to develop  a strong immune response.  Vaccine recipients who are elderly or have weak immune systems have a rapid decline in antibody levels over the few months following vaccination.  It makes no sense to vaccinate these people early in the season, as they may lose vaccine protection before flu season is over.

And since only 1% of currently circulating flu viruses will be covered by the seasonal vaccine, it hardly makes sense to use that vaccine at all, at this point in time.  If such viruses increase in the population as time passes, vaccinations could be started later.  (Those with good memories may recall that seasonal vaccinations are normally offered in October and November.)

2)  Uncertain swine flu vaccine effectiveness and adverse effects

Swine flu vaccine generates good antibody levels, but we still don't know how well it prevents influenza disease.  Nor do we know how safe it is, since pretty much all the experts agree that until millions receive a vaccine, it is impossible to accurately identify its adverse effects. 

Now, a story out of British Columbia's Center for Disease Control indicates that people who have received flu vaccine in a previous year may be more susceptible to developing swine flu (the disease).  Odd as this sounds at first, it is a fact that receiving certain animal vaccines increased susceptibility to the disease the vaccine was designed to prevent.  Such vaccines were taken off the market.

UPDATE:  Most of Canada's provinces have suspended seasonal flu shots for those under 65 due to this study, since it suggests last season's flu shot enhances susceptibility to swine flu infection.  Apparently Canada fears this year's seasonal flu shot may do so as well.  But those over 65 are more susceptible to seasonal flu, and less susceptible to swine flu, than younger age groups, so they are the appropriate target group for seasonal flu vaccine. 

We need to wait to learn if this finding (higher risk of swine flu associated with prior vaccination) is borne out by other studies, but it does offer a reminder that vaccinations can have unanticipated effects that are a lot more serious than a sore arm. By the way,  CSL's swine flu "vaccine triggered [systemic] side-effects including headache, myalgia, fever and nausea in more than 60 per cent of trial participants."

From Bloomberg:
“This is the biggest mass vaccination we have done in world history and we are doing it on data so far which shows this virus is not a lot worse than seasonal influenza,” said Peter Collignon, director of infectious diseases at the Australian National University’s medical school. “There is a real worry that the fear makes us do things out of proportion to the risk."
“If this was causing 1 or 2 percent mortality and spreading quickly, I would be the first person up there with my arm,” Collignon said. As it is, “I will put my arm up next February or March when I have seen more data.”

Swine flu killed 170 people in Australia, and the epidemic peaked there in July:  a far cry from predictions of many thousands of deaths.  Now Australia plans to start swine flu vaccinations; but it is likely most of the population is already immune as a result of widespread exposure.  (When Australians enrolled in swine flu vaccine trials, 30% of subjects were found to be immune already.) 

3)  Workplaces and states that mandate swine flu vaccinations don't have liability waivers

But everyone else involved in the swine flu vaccination process does have a liability waiver:  this includes manufacturers, distributors, medical professionals who administer the vaccine and government program planners who worked on the vaccination program.  Read it in the Federal Register of June 25, 2009.

It says that licensed individuals authorized to prescribe, administer and dispense the vaccine have liability waivers, but there are no other "qualified persons" (pursuant to section 319F-3[i][8][B]) who are given this immunity, (such as employers of these persons, or states).  Unless there has been a new government declaration extending immunity to these entities since June 25, of which I am unaware, hospitals, other health care institutions and states appear to be inviting lawsuits as a result of employee or state mandates they are issuing.

Since the newly created federal compensation program for swine flu vaccine injuries has both a low payment cap and prohibits access to the U.S. legal system, the occurrence of employee mandates virtually guarantees that any vaccine injuries suffered by employees will result in lawsuits against employers, the only "deep pocket" left liable.

It appears that some employers may have already dug themselves a hole by issuing blanket mandates, since some states guarantee vaccine exemptions on the basis of religious beliefs or union contracts.

4.  Vaccine Mandates, Exemptions and Legal Implications

See this Congressional Research Service report on state provisions for vaccine exemptions.  And this book chaper by Malone KM and Hinman AR, page 273 (current in 2001) for discussion on vaccine exemptions, constitutionality of mandates, and list of 48 states with religious exemptions and 15 with philosophic vaccine exemptions.  Also see this 2008 ACLU Report by Annas G, Mariner WK and Parmet WE, titled "Pandemic Preparedness: The Need for a Public Health--Not a Law Enforcement/National Security--Approach."  It "examines the relationship between civil liberties and public health in contemporary U.S. pandemic planning and makes a series of recommendations for developing a more effective, civil liberties-friendly approach."  An excerpt:  
"It is worth noting that federal legislation has given vaccine manufacturers immunity
for the vaccines they produce in response to a public health emergency. The CDC has also called for broad immunity statutes to protect “first responders” and unlicensed health professionals who respond to emergencies.  These proposals are viewed as a form of “Good Samaritan” statute, but should be resisted in the pandemic setting for at least three reasons:
(1) almost all of the people and corporations covered are not volunteers, but are doing a job that they have been trained for and are being paid for and should be accountable and responsible for their actions
(2) negligent Samaritans are no good—they harm rather than help;  and
(3) immunity [from liability] encourages negligent and intentional violations of individual rights that breeds public distrust."

Friday, September 25, 2009

FDA Admits Improper Medical Device Approval--and it plans to fix its process/NYT

Important article by Gardiner Harris about the new, improving FDA:
The Food and Drug Administration said Thursday that four New Jersey congressmen and its own former commissioner unduly influenced the process that led to its decision last year to approve a patch for injured knees, an approval it is now revisiting...

The agency has never before publicly questioned the process behind one of its approvals, never admitted that a regulatory decision was influenced by politics, and never accused a former commissioner of questionable conduct.

“The message here is that there were problems with the integrity of F.D.A.’s decision-making process that have solutions,” Dr. Joshua Sharfstein, the agency’s principal deputy commissioner, said in a conference call with reporters...

The F.D.A.’s report said that its Office of Legislation began receiving calls from members of Congress in December 2007 complaining about its review of the device, and the office’s director “described the pressure from the Hill as the most extreme he had seen.”

...On Wednesday, the agency asked the Institute of Medicine to review the entire process by which the agency approves the vast majority of medical devices. The agency report was deeply critical of its device approval process and said that confusion over basic rules and how to resolve differences among reviewers was rife. For decades, most medical devices have received only cursory reviews of their safety and efficacy from the agency.  For equipment like bed pans and shower curtains, experts agree that quick appraisals are appropriate. But the medical device industry is producing more and more complex machinery like pacemakers and stents.

In January, the Government Accountability Office concluded that it was long past time that the agency demanded that manufacturers prove that all complex devices are safe and effective before being approved for sale.
UPDATE:  Here is a sampling of how the game worked, according to the Washington Post.  The device manufacturer paid $300,000 to one of its lobbyists, Michael H. Hutton, who happened to be the former chief of staff of New Jersey Senator Robert Menendez.  (Menendez happens to be a Cuban American who is used to employing hardline tactics to enforce Cuba policies he favors.)  The lobbyist then "contributed nearly $40,000 to Menendez and three other Democrats"--obscuring the source of the funds, which really originated with the device manufacturer.  It seems almost fitting that a Senator with "kneecap-breaking" propensities got a device approved for knee injuries, which resulted in the need for re-operations on the knee since the device was ineffective.

Thursday, September 24, 2009

Physical interventions to interrupt or reduce the spread of respiratory viruses: systematic review/BMJ

From Jefferson T et al. in this week's BMJ: 
The disparity in effectiveness between the high profile of influenza vaccines and antivirals and the low profile of physical interventions is striking. Public health recommendations are almost completely based on the use of vaccines and antivirals despite the lack of strong evidence.1 Vaccines work best in those who are universally considered least to need them10—namely, healthy adults...
Conclusions Based on the findings of this review, we recommend that handwashing programmes should be implemented nationwide, their effectiveness monitored, and their cost effectiveness evaluated. In situations of high risk of transmission, barrier measures should be implemented such as wearing gloves, gowns, and masks with a filtration apparatus, and isolation of likely cases. Most effort should be concentrated on reducing transmission from young children through regular education at school on hygiene. In addition, society should invest in more comfortable and better designed face masks and barrier apparatus, which would increase compliance with their use.

Mass vaccinations for Swine Flu: learning from hindsight

by Australian Infectious Diseases professor Peter Collignon at the ANU:

In 1976, a small group of soldiers at Fort Dix in the US were infected with a swine flu virus. It had an apparent high mortality rate and was deemed similar to the virus responsible for the great 1918-19 worldwide flu pandemic. The US government initiated an unprecedented effort to immunise every American against swine flu. More than 40 million Americans received the vaccine  — but the disease never spread to the population.

The program was marked by controversy, delay, administrative troubles, legal complications, unforeseen side effects and a progressive loss of credibility for public health authorities. One of the biggest issues was the unexpected side effect of ascending paralysis (Guillain-Barré syndrome) that complicated about one in 100,000 people vaccinated and caused 25 deaths.

In the waning days of the flu season, the incoming health secretary asked the Institute of Medicine of the National Academies to examine what happened and to extract lessons to help cope with similar future situations. The result was  The Swine Flu Affair: Decision-Making on a Slippery Disease.

From my perspective, we seem to not have learned much since then. We look to be repeating nearly all the same mistakes  — but this time on a global scale.

I quote verbatim from the summary:

   “Decision-making for the swine flu program had seven leading features.

   To simplify somewhat, they are:

       * Overconfidence by specialists in theories spun from meagre evidence.
       * Conviction fueled by a conjunction of some pre-existing personal agendas.
       * Zeal by health professionals to make their lay superiors do right.
       * Premature commitment to deciding more than had to be decided.
       * Failure to address uncertainties in such a way as to prepare for reconsideration.
       * Insufficient questioning of scientific logic and of implementation prospects.
       * Insensitivity to media relations and the long-term credibility of institutions.”

This time around, we have started from many presumptions that data now shows were wrong. Yet we have not changed our approach. The basis for rolling out a pandemic plan around the world was to be a new flu virus with mortality rates of 1% or more and by a virus that readily spreads from person to person.

While the swine flu virus spreads readily, it has a very low overall mortality rate — less than one per 100,000 of the population and likely less than seasonal flu. It is also likely that more than 10% of the population has already been infected in Australia and New Zealand. The reason this epidemic rapidly decreased after mid-July here, might be because we ran out of further susceptible hosts (as so many had already been infected and are now immune). Thus, the maximum the case fatality rate can be is one per 10,000 infections or 0.01%. Low mortality rates are also seen in data from Canada and the US during their summers.

Original projections and commentary for Australia was that we would see tens of thousands of deaths when this virus spread through an unimmunised population. These have been wrong. Federal Health had one of the lowest of these projections with 6000 deaths by the end of winter. While all deaths are regrettable, in Australia there have been about 170 associated deaths. This number of deaths is much less than the 2000-3000 estimated to occur each winter with seasonal flu here.

Thus, it is unclear to me why we are rushing out in Australia the largest-ever mass vaccination program.

This is with a vaccine that has had less than optimal safety and efficacy studies performed but for which the Government has indemnified CSL. So far the only data available on the CSL PanFlu vaccine has been from a small preliminary study published in the New England Journal of Medicine article about one week ago. It was only based on 220 people and without a comparative placebo arm group. This showed apparent good antibody responses from the vaccine (18-65 year olds). However, it also showed that a third had protective pre-existing antibodies and so were already immune.

About 50% of recipients had systemic or local side effect from the vaccine. In 1%, side effects were severe. This is a much higher rate of adverse events than seen with other inactivated vaccines such as Hepatitis B. We need to also keep in context that the vast majority of people who get swine flu only have a mild-to-moderate illness. Rolling it out in multi-dose vials also has the inherent increased risk of cross infections with bacteria and blood-borne virus infections.

We need to be sure with any vaccination program that the benefits will substantially outweigh the risks. That is not at all clear with this pandemic.

The best up-to-date data that is age-stratified is from NSW Health. It and the other Australian data show now that this flu episode is close to ending (it peaked early and unexpectedly in mid-July). The data show that this flu season has not been much worse overall than 2007 (although certain subgroups e.g. pregnant women have been over-represented in hospital and ICU admissions).

The death rate in the population was low at about 0.8 per 100,000 people.

Overall admission rates were not high either compared to seasonal influenza (17.5 but in previous years about 15 per 100,000). ICU admissions were 3.3 per 100,000 population. There are about 200,000 pregnant women at any one time in Australia. My estimate for death was about two per 100,000 pregnant women. My calculations of deaths by age group are in table 1 of the linked article.

Worldwide we are about to roll out one of the biggest and most rapid vaccine campaigns ever undertaken. Influenza vaccines are not among our most effective vaccines. Reported inactivated vaccine efficacy is 50-80%. Thus at most for every one million people vaccinated we will likely decrease the number of deaths from six to two or three people and prevent 75-120 hospital admissions and 13-22 ICU admissions.

Given the relative lack of infections we are seeing in the elderly, it appears that most people older than  60 are already immune (presumably from previous H1N1 infection). Now also probably at least 30% of 18-65 year olds are already immune and many more have been infected this winter along with those younger than  18. Thus probably much less than 50% of the Australian population may benefit from mass vaccination if H1N1 returns next winter.

We need to weigh this against the risks of vaccination. There will probably be one or two additional episodes of Guillain-Barré syndrome per million vaccine recipients. If we have a repeat of the 1976 US swine flu vaccination roll-out, then there may be 10 cases per million vaccine recipients. We also need to estimate how many bacterial and blood borne virus infections we may expect from the use of multi-use vials.

Australia is now in spring. There is no need here to rush into a mass vaccination program particularly using multi-dose vials. We need to see what happens in the northern hemisphere with the infections and the effects of vaccination.

Some targeted early vaccination in high risk groups may be appropriate in our summer (even though the virus here has substantially disappeared). However, I believe an early mass vaccination program is not appropriate unless we have data that shows the likely benefits will substantially outweigh risks for different age groups.

LI nurses to rally against mandatory swine flu vaccines/Newsday

From the Sept. 21 Newsday:
Dozens of Long Island nurses - many from Stony Brook University Medical Center - plan to rally with health care workers from across the state next week in Albany to protest a state regulation that mandates they be vaccinated for swine flu or lose their jobs.
The New York State Department of Health issued an emergency regulation in August that requires all health care workers in hospitals, public health clinics, hospices and in home health care be immunized against seasonal and swine flu. But it is the mandated swine flu shot that has angered the workers, who claim the vaccine has not been fully tested...

Tuesday, September 22, 2009

Benefit and Doubt in Vaccine Additive/NYT

With respect to squalene-containing (a.k.a. oil-in-water emulsion) adjuvants, the September 21 New York Times' Andrew Pollack has done some excellent reporting: 
...“These are products that potentially can be given to millions of healthy people,” said Dr. Jesse Goodman, chief scientist at the Food and Drug Administration. “There is not a known, specific safety danger or issue” with the adjuvants, Dr. Goodman acknowledged. “There’s just more uncertainty.”

Officials also fear that using an adjuvant would raise public fears about vaccine safety at a time when their challenge might be about to shift from procuring enough vaccine to persuading people to use it.

“If you add what the public would perceive as another unknown there, there’s a concern that people would be reluctant to get vaccinated,” said Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases....

Sunday, September 20, 2009

New York Health Care Workers Resist Flu Vaccine Rule/ NY Times

From the NY Times:
“This is just not the right flu season to take this on,” said Dr. Frieden, who previously was the New York City health commissioner.[He was responding to questions about mandatory flu vaccinations--Nass]
...Over all, virologists say, of every 100 people who faithfully get flu shots, only about 70 are fully protected every year. But even the other 30 are partly protected by previous shots and by “herd immunity” — the fewer unprotected victims a virus finds, the faster it fades out.

Saturday, September 19, 2009

IgG2 Deficiency May Underlie Cases of Life-threatening Swine Flu

from the Canadian Press:

Researchers from Melbourne, Australia tested pregnant patients with life-threatening swine flu infections for levels of antibody in different antibody subclasses.  This test is rarely done, but is used to investigate possible immune deficiencies.  Serendipitously, the researchers and treating physicians found that one class of antibody (IgG2) was low in most of the patients.  When they gave a mixture of IgGs to critically ill patients, 3 out of 4 who were expected to die, survived.

Potential treatments thus include nonspecific "gamma globulin" or IVIG treatment, as well as treating patients with antibodies or serum harvested from patients who have survived swine flu infections and generated high levels of antibodies in response.  Potentially, protective monoclonal antibodies could be produced from engineered lymphocytes in the near future.

This is how medicine is supposed to be practiced: with a desperate situation you go beyond the tried-and-true (failing) treatments, and investigate the patients more broadly and try experimental treatments.  The Australians are again on the front lines dealing with this troubling disease.

Friday, September 18, 2009

Mandating vaccinations: APIC

APIC is the Association for Professionals in Infection Control and Epidemiology.  Its President and most officers are RNs, but no particular qualifications are required for membership, apart from a $175 annual fee.  An August 31, 2009 APIC announcement says, "The association's more than 12,000 members direct infection control programs that save lives and improve the bottom line for hospitals and other healthcare facilities around the globe."
APIC's announcement further states:  "All healthcare workers, including those who are pregnant, need to be immunized against seasonal influenza and 2009 H1N1 virus when vaccines become available... Current rates of healthcare worker immunizations are appallingly low and must not be tolerated.  It's time for hospitals to require flu shots--and hold employees accountable for declining the vaccine."
Why is it so important to be immunized this year?
"Immunization will be especially critical for healthcare personnel during the 2009-2010 flu season because we will have more than one virus circulating,” said APIC 2009 President Christine J. Nutty, RN, MSN, CIC.
Pardon me, Ms. Nutty.  Do you understand the facts upon which your assertions are based?  There are multiple influenza viruses circulating every flu season, and sometimes outside the season.  That is why seasonal flu shots contain antigens from 3 different strains.  Frequently the circulating strains change mid-season.  Therefore, having more than one virus circulating is not and has never been unique or critical.  Here is the composition of this year's vaccine.

According to CDC's Anne Schuchat, 2% of currently circulating influenza virus is of the seasonal type, and 98% is swine flu.  This suggests the population should be eligible to receive swine flu vaccines, but if seasonal flu remains at 2% it would hardly be necessary to vaccinate for it.

However, the swine flu vaccines have not completed safety testing.  Nor do we know how effective they really are:  the only data available currently concern antibody levels generated, not cases of flu prevented, and even these data are not available for children and pregnant women.

Why do you want to mandate vaccines whose safety and effectiveness are not yet known? Did one of your strategic partners,  a partner in prevention or other corporate relationships suggest it?  APIC should be held accountable for providing information on where this idea for mandating vaccinations really originated, and whether, how much and by whom APIC was paid to produce and disseminate it.

Liability Shield Issued for Manufacturers: What if a Swine Flu Vaccine Causes Injury?

A notice was issued in December 2007 regarding the process for seeking compensation under the 2006 Public Readiness and Emergency Preparedness Act  (PREPA).  The DHHS Secretary Sibelius has designated the Health Resources and Services Administration (HRSA) to address adverse vaccine reactions.  HRSA created a Countermeasures Injury Compensation Program, modeled on the VICP, with the potential to compensate citizens injured by "covered countermeasures" such as swine flu vaccine.  The current appropriation for such swine flu vaccine injuries is 14 million dollars.

The precise method for proving a claim is not known yet, but will be entirely non-judicial.  A physician employee of HRSA will review claims and make a determination as to whether the injured party proved that the vaccine caused their injury.  An appeals process will exist within DHHS, but will also be entirely non-judicial.  No lawyers' fees will be paid by the program, nor will there be payments for "pain and suffering."  The amount paid for a death proven to be caused by a vaccine covered by this program is approximately $300,000. 

Approximately 20 claims were paid for smallpox vaccine injuries.  A lot more was known about smallpox vaccine adverse events going into the smallpox vaccine program in 2003.  No one knows what the process will be like for this vaccine, nor how satisfactory it will be for claimants.  Dr. Vito Caserta also told me the agency will be the "payor of last resort" and will not duplicate payments received by other means.

Effect Magnitude

Everybody knows some things are good for health and some things are bad.  Yet one rarely learns the magnitude of the positive or negative effect, making it impossible to take the logical approach, which is to balance risks and benefits as we make all sorts of choices.

For example, how much benefit will I receive if I eat organic food, compared to standard food?  How much risk (and what type?) if I drink water out of nalgene/lexan bottles containing Bisphenol A?

For some risks, epidemiologists have done a great job measuring magnitude.  In 1976, you had about a 1 in 100,000 chance of developing Guillain Barre Syndrome (GBS) in the 6-8 weeks post-vaccination.  Not a high risk:  but devastating if you are the one affected.

Were other autoimmune conditions caused by the vaccine?  We don't know, as the intensive case ascertainment performed for GBS was not performed for anything else.  GBS happened fast and got your attention; a less dramatic illness developing over a longer window of time would be less likely to be noticed.

This week's BMJ titled a news article with the claim that Swine flu vaccine is a "thousandfold" safer than the infection, say experts.  But where are the completed safety studies?  The studies in children have only been going on for 3-4 weeks, and in pregnant women for less time.  What black hole was this number pulled from?

Tuesday, September 15, 2009

Guillain Barre DEFINITELY linked to 1976 Swine Flu Vaccine

Over and over, I have seen media reports that claim, regarding the 1976 flu vaccine and Guillain Barre Syndrome (GBS): "scientists never proved whether that link was real or coincidence"--as reported in Lauran Neergard's Associated Press article Sept. 15 and again by her on September 27.  Or by Maggie Fox (Reuters) on Sept. 17: "Guillain-Barre was never definitively linked with the vaccine, but many Americans have viewed immunizations with suspicion ever since."  The NYT's Donald McNeil has now [9/27] gotten into the act, saying "Experts still disagree over whether the vaccine caused ]GBS] cases to increase that year.

(Since his and Neergard's articles on 9/27 cite the same stats from CDC, I am afraid the disinfo probably has its origins there.  Too bad.  Director Tom Frieden has been very honest, but his agency has a history of dissembling for our own good.  Hopefully he can elevate the culture of PR in Atlanta.)

UPDATE:  Now the "experts" are being trotted out (in the BMJ) to recite the mantra as well:
Robert Dingwall, director of the University of Nottingham’s Institute for Science and Society, who was speaking at a press briefing on swine flu vaccination, said that people would be more likely to get Guillain-Barré syndrome as a result of flu itself than from the vaccine. He added that the compensation claims paid out in the US would be unlikely to succeed today. "In 1976 the science was less well developed, and in the framework of the American legal system there was considerable pressure to make some payment on the basis of a possible link. Thirty years on from that it looks as if that link probably doesn’t exist and that those compensation claims probably weren’t paid appropriately," he said.

Mike Skinner, senior lecturer in virology at Imperial College in London, agreed, saying that all flu vaccines since 1976 have had an excellent safety record and that a link between Guillain-Barré syndrome and vaccination was "basically impossible at this stage to demonstrate."  [Excuse me; ten studies conducted in the late 1970s--early 1980s did prove the link.  It does not need to be restudied now when many of those affected and their physicians are dead.  One only needs to read the contemporaneous literature.  However, these experts don't seem to have done that.--Nass]
I find examples of rewriting history difficult to stomach.  When they appear to result from a deliberate media campaign, the effect is beyond nauseating.  Why is this particular mantra being repeated over and over?

Back in February 2008, before there was a swine flu pandemic, Dr. John Iskander, acting head of the CDC's Immunization Safety Office, had this to say about the link:
"A proven association between the 1976-1977 swine influenza vaccine and Guillain-Barré syndrome halted that particular national vaccination campaign."
His article was titled, Monitoring the safety of annual and pandemic influenza vaccines: lessons from the US experience, and it was published in Expert Review of Vaccines.  Here is an excerpt:
Although a great deal of safety data has been accumulated, concerns remain regarding rare, serious adverse events following immunization. A proven association between the 1976-1977 swine influenza vaccine and Guillain-Barré syndrome halted that particular national vaccination campaign. Recently, annual influenza vaccines have been associated with novel adverse events, for example, oculorespiratory syndrome in Canada. Any vaccine used against an influenza strain of pandemic potential will have an incompletely described safety profile. Thus, the challenge of influenza vaccine safety is to detect new safety concerns that may arise during seasonal campaigns, while preparing vaccine safety systems for the timely detection of adverse events in the setting of a pandemic.
The Department of Health and Human Services' Health Resources and Services Administration website expanded on Dr. Iskander's report above in March 2008:
"An NVPO (National Vaccine Program Office at CDC)--sponsored animal study at the University of Pennsylvania showed that swine flu vaccine does induce antibodies that may be related to GBS, and further studies are planned.   Non-federal scientists, looking at VAERS data, have suggested that vaccines other than influenza vaccine could be associated with GBS."
BTW, the authors of all other reviews I found in the National Library of Medicine database on the subject of vaccines and GBS agreed with the causative link between the 1976 swine flu vaccine and GBS.  If someone can show otherwise, I will be happy to post the evidence here.

4 Swine Flu vaccines licensed by FDA

An FDA Press Release today notes that vaccines made by MedImmune (the nasal spray attenuated live virus vaccine) and killed vaccines from CSL (Commonwealth Scientific Laboratories, Australia), Novartis and Sanofi Pasteur have been approved for use (licensed).

These are the vaccines made without novel adjuvants.  Based on FDA's statement that, "All four firms manufacture the H1N1 vaccines using the same processes, which have a long record of producing safe seasonal influenza vaccines," none will use cell-culture techniques.  (Novartis has developed a  cell-culture H1N1 vaccine also, which has apparently not been approved at this time.)

The vaccines have interim information on adverse effects.  Novartis' package insert states that the adverse event information provided is a copy of that used for its seasonal flu vaccine, Fluvirin.  CSL's package insert says the same:  "Adverse reactions information is based on studies conducted with seasonal trivalent influenza virus vaccine, Afluria."  Sanofi's package insert also says this.  The NEJM provides some early information from clinical trials.

Vaccine will be available in multi-dose vials with thimerosal (25 mcg/dose) and single dose vials without much thimerosal (actually, 1 mcg/dose) for children and pregnant women.  Vaccine will be free; there may be an administration fee charged.

Manufacturers of all H1N1 swine flu vaccines have been given waivers of liability by the US government for injuries caused as a result of vaccination.   According to FDA:
"FDA and CDC will closely monitor the safety of the Influenza A (H1N1) 2009 vaccines...  Efforts are underway to establish a robust network to share information in real-time.  The network will build on the well established Vaccine Adverse Event Reporting System and Vaccine Safety Datalink by integrating capabilities from the Department of Defense, the Department of Veterans Affairs, the Center for Medicare and Medicaid Services, State, Territorial, Tribal, and local public health and medical, and private sector healthcare entities.  FDA is also engaged with international regulatory partners on pharmacovigilance planning efforts.
The purpose of the collaborations is to improve our ability to identify adverse events following receipt of the 2009 H1N1 monovalent vaccines and rapidly evaluate them to determine their significance."
The 1976 swine flu vaccine was also made using standard techniques and no novel adjuvants.  Guillain Barre Syndrome occurred after vaccination, during a specified window of time, at about 8 times the baseline rate.

Improving vaccine safety monitoring is very important for understanding the safety profile of all vaccines.  Hopefully the systems put in place to monitor this vaccine will be used for all new vaccines, as well as those already licensed...since there has been virtually no active surveillance performed after vaccines are licensed.  Such systems will help answer many questions about the benefits and risks of all vaccines.

Monday, September 14, 2009

UK plans to use vaccine adjuvant if virus mutates

The UK head of immunization, Dr. David Salisbury, wrote today to the Guardian that the decision had been taken to add adjuvants to the H1N1 vaccine, if the virus mutates.  Salisbury claims this would offer cross-protection.

It might, but it might not.  Until the virus mutates you won't know.

Salisbury contends that, "the UK has robust surveillance in place for early detection of any adverse events."  Kudos for this plan.  Please let the public know what is found.

Sunday, September 13, 2009

Dr. Jesse Goodman (Deputy FDA Commissioner)'s December 2, 2008 slides note adjuvant safety questionable

On December 2-3, 2008, FDA with joint NIAID sponsorship held a public workshop
"for academics, government researchers, government regulators, vaccine clinical trial experts and industry representatives. The purpose of this workshop is to assess the scientific knowledge base regarding vaccine adjuvants and to facilitate the development of a research agenda to improve the safety and efficacy assessments of adjuvanted vaccines for the treatment and prevention of disease."
Jesse Goodman, M.D., now deputy FDA Commissioner, presented a talk that listed some adjuvant concerns.  It included the following information (slide 7):

Adjuvants: Potential Concerns/Risks

– Potentially antigen specific or non-specific potent
immune and inflammatory stimulation

– Increased reactogenicity, local +/-systemic
  • Unclear which, if any, correlate with risk of rare SAEs [serious adverse events]
 – Potential role in autoimmunity, short or long term?
  • Antigen specific (e.g. neural or cardiac antigens)
  • Auto-immune/inflamm[atory] disease, e.g. SLE [systemic lupus erythematosus], “idiopathic”
– Are there plausible risks to [childrens'] developing immune

--Reassuring observations to date:
  • Even strong TLR/PRR signaling likely similar to natural
    infection (caveat w/ recent UK CD28 agonist trial)
  • No strong evidence to date of major problems with
    compounds being most actively considered – but limited
    numbers w/ controls, long term active follow-up, or in children
It might be interesting to inquire of Dr. Goodman whether these concerns still hold, and if not, what data have become available to mitigate them.

Saturday, September 12, 2009

85 Million Doses of Swine Flu Vaccine Should be Available in October

With 45 million doses expected October 15, and 20 million vaccine doses available weekly thereafter, 85 million high-risk Americans will be able to receive their single needed swine flu vaccination during October.  By the end of November, another 80 million (lower risk) Americans could be vaccinated. That will probably cover everyone who wants to be vaccinated.

It is very fortunate that the killed vaccine generates a strong antibody response with only one dose,  in the absence of novel adjuvants.

However, some experts are expert at finding reasons why we need those adjuvants, despite this good news.  According to the NY Times, epidemiologists fear many millions will develop swine flu before sufficient vaccine is available.  And the Baltimore Sun interviewed a local doctor conducting a swine flu vaccine trial.

Using an adjuvant - a substance with an oil and water base that is added to the vaccine - could mean having four times as much vaccine supply, Wilbur Chen, of U. Maryland's Center for Vaccine Development, said. But adjuvants, used with flu vaccines in Europe, are not licensed for flu vaccines here. Federal approval would require an emergency declaration by the Food and Drug Administration.

Still,  Chen thinks studying adjuvants now could prove helpful later in the flu season or in future years.

"Depending how bad H1N1 gets, we may want to stretch out our vaccine supply even further," he said. "This study still addresses a critical issue that is important for public health planning as we get into the flu season."

Friday, September 11, 2009

G-7 and Mexico choose pregnant women but omit kids under 5 for earliest vaccinations/AP

Associated Press

In accord with what we've learned from the mortality data, the G-7 plus Mexico group chose to omit children, but include pregnant women, in the group most at risk of death or severe illness from swine flu infection: those who should be offered vaccination first.

Wedded to its earlier pronouncements, however, CDC continues to say children under 5 are at high risk, despite data on children it published in the MMWR just seven days ago that indicate otherwise.  These children will likely be encouraged to receive early swine flu vaccinations in the US, but not in the rest of the G-7 or Mexico.

Data on the benefits from seasonal flu vaccination in this age group are also hard to come by.

Tuesday, September 8, 2009

Expert group recommendations: limitations of prediction based on insufficient data

If you convene an expert group to issue a set of recommendations, they will be issued.  What the groups' report may omit is an explanation of the sufficiency of the data.  Nor will their report provide an idea of how statistically likely the conclusions are to be right or wrong.  Historically, the experts usually issue the recommendations that the agency that convened them most wants to hear. 

Often, the experts may come from fields other than the one they are asked to examine.  And because the field of vaccine pharmacovigilance is only now being birthed, the science of vaccine safety offers little in the way of guidance.  Thus scientific analysis of vaccination risks and benefits may receive short shrift.

Let's look at some of the WHO Strategic Advisory Group of Experts on Immunization recommendations, released July 13:

 * All countries should immunize their health-care workers as a first priority to protect the essential health infrastructure. As vaccines available initially will not be sufficient, a step-wise approach to vaccinate particular groups may be considered. SAGE suggested the following groups for consideration, noting that countries need to determine their order of priority based on country-specific conditions: pregnant women; those aged above 6 months with one of several chronic medical conditions; healthy young adults of 15 to 49 years of age; healthy children; healthy adults of 50 to 64 years of age; and healthy adults of 65 years of age and above. [Currently, this list looks reasonable.  However, it should be made clear, as some UK advisories have done, that pregnant women should only be vaccinated when in the second or third trimester.  Update Sept. 10NIH knows better than to test the vaccine in the first trimester of pregnancy.  Under-5 children have had a low illness burden, at least in the US.--Nass]
    * Since new technologies are involved in the production of some pandemic vaccines, which have not yet been extensively evaluated for their safety in certain population groups, it is very important to implement post-marketing surveillance of the highest possible quality. In addition, rapid sharing of the results of immunogenicity and post-marketing safety and effectiveness studies among the international community will be essential for allowing countries to make necessary adjustments to their vaccination policies. [The experts credulously assume that postmarketing surveillance will suffice for the lack of premarketing safety assessment; yet this method is of little value for recipients given the vaccine simultaneously throughout the world, en masse.  Furthermore, postmarketing surveillance barely exists in much of the developing world.  Postmarketing surveillance was enhanced for the 1976 swine flu vaccine program, resulting in the program ending after only 10 weeks, which seems extremely efficient to me.  Yet 45 million Americans were vaccinated before the data were adequate to halt the program.  Enhanced surveillance is being initiated for Guillain Barre in the US now.--Nass]
    * In view of the anticipated limited vaccine availability at global level and the potential need to protect against "drifted" strains of virus, SAGE recommended that promoting production and use of vaccines such as those that are formulated with oil-in-water adjuvants and live attenuated influenza vaccines was important. [We have not seen significant drifted strains, and whether low-risk individuals even need vaccine is questionable.  Yet two untested methods of vaccination are espoused, justified by a false sense of the pandemic's severity and urgency.--Nass]

CDC's MMWR published "early release" H1N1 vaccine recommendations on August 21.   The MMWR lists ACIP's July 29, 2009 "Initial Target Groups" for vaccination, which comprise more than 50% of the US population, and are virtually identical to the WHO/SAGE targeted groups.  [Despite CDC data suggesting lower illness burden in infants, and Cochrane Collaboration data indicating lack of effectiveness of seasonal vaccination in this age group, children 6 months-4 years are a priority group for H1N1 vaccines.--Nass]  The document acknowledges that if oil-in-water emulsion adjuvants are used, they will require issuance of an Emergency Use Authorization.

The President's Council on Science and Technology projected a "worst case" but "plausible" scenario of up to 1.8 million hospitalizations, filling of more than half the nation's ICU beds and up to 90,000 US deaths.  The Council urged that vaccine production be accelerated.  Reportedly, the Council based its predictions on prior pandemics, particularly those of 1957 and 1968.  But since prior pandemics have had a wide range of behaviors, it is difficult to base predictions on them.  CDC spokespeople immediately played down these estimates.

Health Workers Under Pressure to Get Flu Shots/AP

From the Associated Press:
Roughly half of health workers skip the immunizations, raising two concerns: If doctors and nurses get sick, who will treat what could be millions of Americans reeling from seasonal or swine flu? And could infected health workers make things worse by spreading flu to patients?

New York, the first state to be hard-hit by swine flu, is requiring all health workers to get immunized against both types of flu. Other states are weighing whether to follow suit.
But shots for all health workers may not be an easy sell.

Fewer than half of them got flu vaccinations last year, according to a Centers for Disease Control and Prevention survey of about 1,000 workers...

"...If health care workers have concerns about the safety and efficacy of a vaccine that has been around for decades, I'm sure they're going to have those same concerns about a vaccine that we've never used before," said Dr. Gregory Poland, a Mayo Clinic vaccine specialist.
...Some large hospitals have adopted rules requiring employees to get flu shots. Loyola University Medical Center near Chicago and Charleston Area Medical Center in West Virginia recently joined a handful of hospitals that have made seasonal flu shots mandatory for all workers. Some also plan to include swine flu. Several infectious disease groups support required flu vaccination for health workers.
...Dr. Joyce Lammert, Virginia Mason's chief of medicine, said if testing shows the new vaccine is safe and effective, and if supplies are adequate, the hospital will make that mandatory, too.
"We feel that getting immunized is so important," Lammert said. "In some ways, I'm glad H1N1 is out there. It raises awareness of the seriousness of the disease."
From the Sept. 8 Guardian: Dr. Crippen:  Just don't try giving me the swine flu vaccine  

Monday, September 7, 2009

Cervarix, containing ASO4, up for FDA consideration (again)

Thanks to Merrill Goozner:

FDA's Vaccines and Related Biological Products Advisory Committee meets on Tuesday, September 9. It will consider the safety and efficacy of an HPV vaccine for girls from GlaxoSmithKline called Cervarix.  In an earlier post, I noted that the safety of Cervarix (which includes the squalene-containing adjuvant ASO4) was controversial.  No US vaccines contain this type of novel adjuvant.  Here is some safety information:
the pivotal trials submitted to the FDA showed a disturbing if not statistically significant increase in spontaneous abortions in the three months after the young women were given the vaccine -- 11.6 percent versus 5 percent in the sham vaccine group. Glaxo's discussions with the FDA about conducting a large post-approval trial to gauge whether this was vaccine-related will undoubtedly be a major topic of discussion at Tuesday's advisory committee meeting.

Scientists Move Closer To A Safer Anthrax Vaccine/ Science Daily

Finally, a series of logical experiments were done by Drs. Nareen Abboud and Arturo Casadevall to see what small peptides might stimulate immunity to anthrax.  Two were found:  one is five and the other six amino acids long.   Each is immunogenic and protected macrophages from anthrax toxin. Their efficacy and safety in other models is still unknown, but the approach is promising.

Sunday, September 6, 2009

Swine H1N1 progenitors/ Lancet

The Lancet's H1N1 Flu Resource Center includes this interesting article on the provenance of the swine flu virus.  CDC submitted a first set of completed coding sequences (8 gene segments) for the 2009 swine flu virus to GenBank on April 27, 2009.

Drs. Hong Zhang and Ling Chen of Zunyi Medical College, China, compared the gene segments to other influenza virus sequences in GenBank.  Six gene segments probably came from swine viruses circulating between 1999 and 2001 in the US, and two segments possibly originated from swine viruses circulating in Europe between 1985 and 1998.  Where, when and how they recombined and formed the current reassortment H1N1 viruses are "important questions," according to the authors, who note:
The [future] prevention and control of the worldwide spread of pandemic influenza will need improved animal and human surveillance, early detection and differentiation of causative viruses.
A July NEJM article on the history of this swine flu virus provides additional information, and concludes similarly, highlighting the:
critical need for deeper understanding of zoonotic viruses, including in vivo studies of pathogenesis in animals, field epidemiologic studies, and surveillance in animal populations, along with the development of computational models.

Saturday, September 5, 2009

Thinking about infections and immunity

I think I have had influenza twice, based on my symptom pattern and the fact I was exposed to flu cases.  But every winter I care for flu patients, so I have probably been exposed to flu viruses repeatedly each season.  But I generally stay well.  Why?

For each infectious disease, an "infectious dose" has been calculated.  This refers to the number of microorganisms it takes, roughly, to cause infection in a healthy person.  Ten bacteria are thought to be enough to cause a case of tularemia, while an estimated fifty thousand spores are needed to cause a case of inhalation anthrax.

So it is likely I got less than my infectious dose of flu viruses, repeatedly:  small amounts that were quickly destroyed by my immune system.  An infectious illness could be said to be an event characterized by exposure to a sufficient number of microorganisms to overwhelm immune protection.

Thinking about flu virus exposures that are insufficient to cause infection, one wonders whether they are enough to produce immunity.  Maybe one or several of these exposures, over a period of time, serve as immune "boosters" to prevent subsequent disease when exposed to a larger amount.  Is this the explanation for why I stay well?

If so, maybe instead of injecting attenuated (weakened) viruses, killed viruses or parts of viruses using standard vaccines, we could instead give people very tiny, repeated doses of live virulent viruses that could be inhaled.  Live viruses produce a more long-lasting and stronger immunity than killed viruses, in general.  (OTOH, inhaled, attenuated Flumist vaccine virus is less effective than killed vaccine in most adults.)  By using the same route for this new form of vaccination as the route of infection, we would likely produce stronger immunity at the most important sites.  Finally, we would avoid an injection, which bypasses our body's mucosal defenses, inserting materials like mercury, aluminum and formaldehyde deep into the body.  Our mucosae exist to keep them out.

Maybe using appropriate infection control measures for H1N1 prevents some of us from getting the tiny exposures that lead to natural immunity, which might be more effective at preventing infection than a "killed" vaccine.  Or maybe tiny, repeat exposures are common for health professionals, but don't often occur in the general population.  Would repeated, controlled exposures to tiny doses be safe and efficacious?  It would be useful to know.

US and World Swine Flu Statistics/Xinhua and CDC

Xinhua, September 5, 2009:

Total US swine flu deaths are at 593; this is confirmed by CDC.  Total US hospitalizations are 9,079.  California has had 144 deaths.

New cases at 165 US universities totalled 1,640 last week.  No college students have died.

WHO reported total global deaths of 2,837.

The MMWR mortality in children report came out Sept. 4.  Thirty-six swine flu-associated pediatric deaths (under age 18) occurred in the US through Aug. 8.  Two-thirds (67%) had one or more "high risk medical conditions," and of these "92% were neurodevelopmental disorders."  Nine of these also had chronic lung disease.  Only 7 (19% of the deaths) were in children under 5 years of age.

For those 10 cases with culture results, all 6 children over 5 years of age who died, and had no  pre-existing medical conditions, were found to have had secondary bacterial infections.  This suggests that treating secondary infections aggressively will prevent deaths, especially in previously healthy children.

Of 31 deaths for which antiviral data were available, 19 (61%) received antiviral drugs, only 4 of whom received it within 2 days of illness onset.  These data are insufficient to assess their efficacy.

Friday, September 4, 2009

Emory, Grady make seasonal flu shots mandatory; Interesting legal conundrum for institutions mandating swine flu vaccinations

The Atlanta Journal Constitution tells us that Atlanta's large public hospital, Grady Memorial, is requiring that seasonal flu shots be given to all employees.
"Several factors led Emory officials to make taking the seasonal flu vaccine mandatory — protecting patients and providing a safe environment for workers; the fact that the seasonal flu and swine flu will be circulating at the same time; and the successful implementation of mandatory flu vaccinations in other healthcare systems."
But the LA Times describes research by Daniel Perez et al. at University of Maryland, where ferrets were coinfected with both swine and 2 seasonal flu viruses.   They found "the pandemic virus, commonly known as swine flu, grows much faster than seasonal flu viruses and is thus less likely to exchange genetic material with them."  Only the swine flu virus spread between the animals.  Co-circulation caused no specific problems.
"Grady officials said similar mandates could follow for health care workers to take the swine flu vaccine, which is expected to be available in mid-October."
Given the liability shield issued for swine flu vaccine through the Public Readiness and Emergency Preparedness Act, mandatory swine flu vaccinations could open a legal can of worms.  Employers that mandate vaccines will assume all liability for any injuries to employees that result, since manufacturers, those giving injections and government officials have all been given immunity from any liability by the Act.

Swine flu death estimate lowered/ BBC

The BBC reports:
  •  The UK has lowered its worst-case scenario estimate of possible swine flu-related deaths from 65,000 to 19,000.
  •  Seventy people have died so far in the UK, while 6,000 to 8,000 die yearly from seasonal flu.  
  •  Advisors have now agreed that the swine flu death rate is lower than previously thought, likely to be 0.1% of cases. [However, with an estimated 110,000 new cases in the UK during the first week of August alone, the mortality rate is clearly less than 0.1%--Nass]
  •  The number of new cases continues to decrease, week by week, down to an estimated 4,500 cases last week.  

H1N1: Avoid "the boy who cried wolf" effect

From the LA Times blog:
Since the outbreak this spring of the novel H1N1, public health officials have treated the new so-called swine flu as if it were a replay of the devastating 1918 Spanish flu, which claimed tens of millions of victims and was particularly devastating to people who were otherwise young and healthy...

What’s wrong with preparing for the worst-case scenario? Plenty, Doshi writes. The SARS panic prompted involuntary quarantines, travel restrictions, and led to at least $18 billion in economic losses. In the end, the number of people affected by the response to the virus was much greater than the number of people infected by it.
The blog discusses a BMJ article by Peter Doshi, which notes:
... pandemic preparedness strategies have largely considered only type 1 (catastrophic) epidemics. Public health responses not calibrated to the threat may be perceived as alarmist, eroding the public trust and resulting in people ignoring important warnings when serious epidemics do occur.
Calibrating public health preparedness

Swine flu clinics have been arranged for public schools in Maine.  Governor Baldacci has declared a swine flu emergency.  (I have not yet learned what the implications are for Maine when such an emergency is declared, but it may trigger provisions of the Model State Emergency Health Powers Act, as passed by the legislature.

Sept. 8 Update: Governor Baldacci's office said he declared an emergency to protect school H1N1 vaccination clinics from liability.  But the federal government already protected them with a PREP Act Emergency Declaration in June.

The last time the US initiated a school immunization program was in 1962, when students lined up to swallow a pink drop of attenuated polio virus placed on a sugar cube.  The Sabin oral vaccine we received was quite effective.  But there continued to be reversions to virulence of Sabin's viruses (which may be shed in the stool for years after vaccination), and for more than a decade recently, the only polio cases in the US were due to viruses derived from vaccine strains.  As a result, Sabin's polio vaccines are no longer used in the US. 

This brings up two points.  First, why are we setting a precedent for school-based vaccinations for a relatively mild disease, when the US has managed well with its usual vaccination strategies over the last 47 years?  (Despite sensational media reports, only 12 healthy children have died after developing swine flu in the US, through August 8.  Most of these cases had secondary bacterial pneumonias.  Approximately 350 adults had swine flu-associated deaths during the same period.  The disease doesn't target children as strongly as the media made it appear.) 

Second, the Sabin saga demonstrates that adverse vaccine effects are difficult to predict in advance.  You simply cannot calibrate the risk from a new vaccine until it has been given to millions of people.

Just as the punishment should fit the crime, let's calibrate our response to swine flu to fit the degree of threat, based on the available data, keeping in mind the many unknowns and maintaining flexibility of response.

UPDATE Sept. 3:  President Obama on Tuesday requested an additional $2.7 billion "in emergency H1N1 flu funding to buy vaccines, antiviral drugs and to make other preparations for an immunization campaign in the fall," Roll Call reports (Dennis, 9/2). "The money is on top of $1.8 billion the administration earmarked in July for tackling the virus" and is part of funds that have already been appropriated, Reuters writes(9/3).

Thursday, September 3, 2009

CDC Director Frieden: No Adjuvant

From today's Bloomberg News

Kudos to Dr. Frieden, who said, perhaps in response to front page news that Novartis' (squalene-adjuvanted) swine flu vaccine would require only one dose (after initial testing in 100 subjects):
“We don’t anticipate that we’ll be using adjuvanted vaccine in most of the scenarios that we anticipate now, though that could change...”  
 Controversial in U.S.
Adjuvants are controversial because some studies show they cause immune disorders in mice. The U.S. Health and Human Services Department declared a public health emergency over swine flu in April, giving the Food and Drug Administration the power to allow the use of unapproved medical products including adjuvants.

The U.S. never had to consider the risks of adjuvants in flu shots because the vaccines have “worked so tremendously well” without the additives, said Lone Simonsen, research director in the department of global health at George Washington University in Washington, in July. Flu vaccines with adjuvants have been used safely “for years” in Italy and Spain, Simonsen said.

The U.S. has been slow to approve the use of adjuvants because of safety concerns, and for fear of giving Americans an excuse to avoid getting the shots, said John Treanor, a University of Rochester researcher, in July as well.

Wednesday, September 2, 2009

Caring for patients

It's September.  Kids are back in school.  A federal panel predicted a worst-case scenario of 90,000 Americans dead from complications of swine flu ten days ago.

CDC's Clinician Guidance:  Identifying and Caring for Patients is still dated May 4 and fails to provide any guidance based on study of the pandemic's characteristics.

It still says, "Complications:  There is insufficient information to date about clinical complications of this novel influenza A (H1N1) virus infection."

It still says, "The duration of shedding with novel influenza A (H1N1) virus is unknown."

Ironically, HHS has teamed up with Sesame Street to teach children to wash their hands and cough into their sleeves.  Excellent strategies to prevent spread.

But part of my job involves taking care of very sick people with swine flu, in the hospital, and CDC/HHS shows no signs of giving me guidance to do that job.  When will clinicians and the public be informed of the basics about this pandemic?

UPDATE:  In an apparent attempt to close the H1N1 knowledge gap, the British medical journal The Lancet has created a web collection of updating information and papers on the H1N1 flu.

UPDATE #2:  The CDC'S Sept. 4 MMWR (MORBIDITY AND MORTALITY WEEKLY REPORT) does have information on deaths in children related to H1N1.  The Sept. 4. NY Times also provides useful information on the report.