Wednesday, February 29, 2012

Early diphtheria-tetanus-pertussis vaccination associated with higher female mortality and no difference in male mortality/ Arch Disease Childhood

Peter Aaby's group from Statens Serum Institute, Denmark, has been studying the effects of many vaccines in African children for many years.  The group has found some similar results in the past.  The fact that they continue to see the same effect (huge increases in death rates in young vaccinated female infants, increases not seen in unvaccinated females) is extremely troubling, and calls into question the rationale for early female DPT vaccinations in countries with already high mortality rates.

From the original article:  Early diphtheria-tetanus-pertussis vaccination associated with higher female mortality and no difference in male mortality in a cohort of low birthweight children: an observational study within a randomised trial:

What is already known on this topic

  • Live vaccines such as measles vaccine and Bacille Calmette-Guerin have non-specific beneficial effects in areas with high mortality.
  • Previous studies from several low-income African countries have suggested that inactivated vaccines, including diphtheria-tetanus-pertussis (DTP), may have non-specific negative effects for survival of girls.
  • WHO sponsored studies which have found a beneficial effect of DTP have major methodological problems.

What this study adds

  • Adjusted for nutritional status, DTP vaccinated children, particularly girls, had threefold higher mortality between 2 and 6 months of age.
  • Nutritional status was a strong predictor of mortality among boys but not girls.
  • There is a continuing contradiction between studies of DTP from low-income countries and current policy.

    "Adjusting for mid upper arm circumference (a surrogate measure of nutritional status), the overall effect for DTP vaccinated children was 2.62 (95% CI 1.34 to 5.09); the death rate ratio was 5.68 (95% CI 1.83 to 17.7) for girls and 1.29 (95% CI 0.56 to 2.97) for boys (p=0.023, homogeneity test). While anthropometric indices were a strong predictor of mortality among boys, there was little or no association for girls."

    [If these adjustments are accurate, it seems both girls and boys died at higher than expected rates.--Nass]

Common toxic exposures can affect future generations/PLOS

This story was reported today in Science News, and the scientific publication from which the story was derived also came out today in PLOS. The concept is troubling:  toxic materials we encounter in everyday life may seriously scar our progeny generations later.  Although this research was performed for the Army, using toxics encountered by military personnel, the toxic exposures were also those faced by civilians.  Exposures to incinerator fumes (dioxins), the linings of tin cans (bis-phenol-A) and insect repellents all affected rat offspring.

Back in 2009, I wrote about birth defect rates after anthrax vaccine, and noted that the rate of major birth defects was about 3.0% in the US population overall.  But the rate is higher in the military:  in  offspring of military women who did not receive anthrax vaccine prior to pregnancy, the birth defect rate is 3.85--4.0%.  In female military servicemembers  who received anthrax vaccine before or during their pregnancies, the birth defect rate rises to 4.5--4.7%.

Why is the birth defect rate higher for offspring of military mothers who did not receive anthrax vaccine than for civlian moms?  This report hints at an answer.  Exposure to toxic materials is widespread in the military and almost impossible to avoid, although less than in years past.
Pollutants long gone, but disease carries on
Certain chemicals cause epigenetic changes that foster illness in rats’ offspring
Exposure to certain pollutants early in a rat’s pregnancy can foster disease in her offspring during their adulthood as well as in subsequent generations, a new study shows. A wide range of pollutants elicited such lasting effects, despite future generations never encountering the triggering pollutant.
Some chemicals tested led to premature puberty among great-granddaughters, with an increased risk of disease in reproductive tissues. In some tests, the chemicals disrupted ovarian function, something that in humans could lead to infertility or premature menopause. And another chemical exposure caused premature death of sperm-forming cells in the great-grandsons, researchers report online February 28 in PLoS ONE.
Rather than altering genes, the tested pollutants altered chemical switches that regulate genes, reports Michael Skinner and his colleagues at Washington State University in Pullman. These epigenetic switches can lock a gene on or off...

In the new work, Skinner worked with the Army, which funded the study, to identify pollutants to which troops would probably be exposed. They settled on dioxins (spewed by burning materials or the defoliant Agent Orange); the insect deterrents DEET and permethrin; the plastic ingredients bisphenol A and phthalates; and jet fuel (often sprayed onto dirt for dust control). “I tried to pick classes of compounds that were across the whole [pollutant] spectrum — everything from hydrocarbons down to an endocrine disruptor like bisphenol A,” Skinner says.
The exposures used were relatively high, but not high enough to cause fetal deaths or signs of toxicity in either exposed rat moms or their pups. Yet “all promoted epigenetic transgenerational changes,” Skinner says. This suggests that epigenetic changes that get passed down through the generations are not some unique quirk of any one chemical, he says; he now suspects most pollutants have the potential to do this...

Tuesday, February 28, 2012

Metal on Metal Hips release two probable carcinogens and fail at rates 300% plus higher than other hip materials/ BMJ

One million Americans have received faulty hips, which continue to be promoted by manufacturers according to the British Medical Journal. The cobalt and chromium they release into local and distant tissues destroy muscle and bone and cause so-called genotoxicity, which may translate into cancer.  Definitely worth a read of the whole article, but excerpts are posted below:
Hundreds of thousands of patients around the world may have been exposed to toxic substances after being implanted with poorly regulated and potentially dangerous hip devices, a BMJ/ BBC Newsnight investigation reveals this week. Despite the fact that these risks have been known and well documented for decades, patients have been kept in the dark about their participation in what has effectively been a large uncontrolled experiment. 
This isn’t the unlucky failure to spot the misdemeanours of one rogue company or the occasional unforeseen breakdown of a small number of devices. It is the inability to prevent a whole class of failing hip implant from being used in hundreds of thousands of people globally—a class of implant that the usually reticent National Joint Registry of England and Wales described recently as a “cause for concern.”1 2 The implants concerned are “metal on metal”—the head at the top and the lining of the cup it fits into are made of cobalt-chromium alloy rather than ceramic or polyethylene—and there are models for both total hip replacement and hip resurfacing...
Hundreds of thousands of patients around the world may have been exposed to toxic substances after being implanted with poorly regulated and potentially dangerous hip devices, a BMJ/ BBC Newsnight investigation reveals this week. Despite the fact that these risks have been known and well documented for decades, patients have been kept in the dark about their participation in what has effectively been a large uncontrolled experiment. 
The manufacturers were aware of the potential for genotoxicity. The BMJ and Newsnight have seen a DePuy internal memo from July 2005, that says: “In addition to inducing potential changes in immune function, there has been concern for some time that wear debris may be carcinogenic. The mechanism is not known and only 24 local malignancies have been reported in patients with joint replacements. Also worrying is the possibility of distant effects. One study suggested a threefold risk of lymphoma and leukaemia 10 years after joint replacement. The metal to metal total hip appears to be quite promising and in the laboratory the data is (sic) definitely in its favour. However, the ultimate test is the long term human experience...” 

Sunday, February 26, 2012

Linking side effects that develop many years after an exposure to the exposure

Over the past two weeks, several people asked me about illnesses they developed a number of years after exposures to the Gulf War, to anthrax vaccine, and to other toxic products.  Because this is an extremely complex subject, and a recurring issue, I thought I should address it in the blog, rather than try to discuss it separately with each person who approached me.

Here are the big questions embodied by the issues raised, imho:
  1. Did the exposure cause (or perhaps contribute to) the illness?
  2. Is there is a convincing way to link the original exposure to an illness that only became known many years later?
  3. What kinds of compensation might the person be eligible for?
Some illnesses are known to only be caused by specific exposures, but they are a small minority of illnesses.  An example:  eosinophilia myalgia syndrome, caused by a contaminant in the supplement L-Tryptophan, manufactured by the Showa Denko company of Japan.  This happened to be an early product made from genetically engineered bacteria.  It was a new illness caused by a new toxicant.  This is a very rare occurrence.

Some illnesses are related to a toxic exposures, but not everyone with the illness is known to have been exposed.  Parkinson's disease is much more common in farmers and others exposed to pesticides, but also occurs in the absence of a pesticide exposure.   This probably reflects the general idea that illnesses are due to an interaction between exposures, genetic predispositions, and other factors, such as nutritional state.

Both the VA and wikipedia list the illnesses that have been assigned, over time, as due to Agent Orange (contaminated with the dioxin TCDD) for purposes of a VA disability rating and medical treatment.  Congress granted veterans the "presumption" of disability if they served in Vietnam and developed a designated illness. 

This VA benefit is distinct from an initial settlement of $180 million made by the manufacturers of Agent Orange and attorneys for a Vietnam Veteran class action in 1984. 

Per wikipedia:
In 1991, the US Congress enacted the Agent Orange Act, giving the Department of Veterans Affairs the authority to declare certain conditions 'presumptive' to exposure to Agent Orange/dioxin, making these veterans who served in Vietnam eligible to receive treatment and compensation for these conditions.[63] The same law required the National Academy of Sciences to periodically review the science on dioxin and herbicides used in Vietnam to inform the Secretary of Veterans Affairs about the strength of the scientific evidence showing association between exposure to Agent Orange/dioxin and certain conditions.[64]
Through this process, the list of 'presumptive' conditions has grown since 1991, and currently the U.S. Department of Veterans Affairs has listed prostate cancer, respiratory cancers, multiple myeloma, type II diabetes, Hodgkin's disease, non-Hodgkin's lymphoma, soft tissue sarcoma, chloracne, porphyria cutanea tarda, peripheral neuropathy, chronic lymphocytic leukemia, and spina bifida in children of veterans exposed to Agent Orange as conditions associated with exposure to the herbicide. This list now includes B cell leukemias, such as hairy cell leukemia, Parkinson's disease and ischemic heart disease, these last three having been added on August 31, 2010.
Note that diseases were still being added to this list as recently as 18 months ago, for exposures that occurred 40-50 years earlier!

My point is that it can take a long time to identify a statistical relationship and make a causality assessment between an exposure and an illness.  And it can take a long time to develop a related illness after exposure.  In the case of Agent Orange (and probably related herbicides) the connections were only made because of federal legislation that asked the National Academy of Sciences to keep looking into possible connections.

Similar legislation does not exist for most other exposures.  So potential connections are not being made.  And the scientific research that might be used to make them may be sponsored by the manufacturer of the putative toxic substance, with the goal of obscuring a relationship.  For example, despite overwhelming evidence to the contrary, Showa Denko tried to blame overuse of L-tryptophan, rather than a contaminant, for cases of eosinophilia myalgia syndrome.

So it all comes down to politics.  Did Congress face enough pressure to investigate the potential linkage?  Was legislation passed to provide some type of compensation?  Was a viable mechanism set up to review the medical literature in order to identify any linkage?

In the case of illnesses meeting the definition of Gulf War syndrome, if you were physically in the Gulf, and later developed the condition, veterans are eligible for disability benefits and care.

In the case of anthrax vaccine, Congress has provided no remedy for vaccine-related injuries.  There as yet exist no standards for what constitutes an anthrax vaccine injury.  It is difficult or impossible to perform the necessary studies in an unbiased manner, as the Defense Department will not share its data.  And since only soldiers currently receive anthrax vaccine, there is no other modern data.  The Gulf War studies maybe confounded by multiple other exposures, and suffer from the long time that elapsed between the exposures and the self-reports of vaccinations and injuries.

Unless and until the US public demands access to the scientific data it paid for, I see no remedy for this state of affairs.

Wednesday, February 15, 2012

In Sweden, 5.4 million swine flu jabs saved six lives/ The Local

An estimated five lives were saved in Sweden by swine flu shots--while 170 Swedish children have developed narcolepsy as a result, and no one has any information on how many other severe side effects were due to the vaccine.  (Sarcoidosis, for example:  see below.)  Add in the cost of the vaccinations (about $100 million was spent by Sweden for the vaccine and its administration) and the vaccine program is shown to be "public health in reverse" -- a medical intervention was given to the public, resulting in reduced overall health. And the money wasted could not be spent on other, beneficial public health measures.

Selling drugs and vaccines is not the same as selling baseballs or underwear.  Drugs can kill or maim.  In the era of patent medicines, sloppy manufacturing sometimes did--thus the Food, Drug and Cosmetic Act was established, to protect the public from dangerous medicinal products.
"[T]he bill ... was ultimately enhanced and passed in the wake of a therapeutic disaster in 1937. A Tennessee drug company marketed a form of the new sulfa wonder drug that would appeal to pediatric patients, Elixir Sulfanilamide. However, the solvent in this untested product was a highly toxic chemical analogue of antifreeze; over 100 people died, many of whom were children. The public outcry not only reshaped the drug provisions of the new law to prevent such an event from happening again, it propelled the bill itself through Congress. FDR signed the Food, Drug, and Cosmetic Act on 25 June 1938.
But since 9/11, Congress has voted in provisions for expedited approvals of drugs and vaccines for emergencies, or non-emergent potential emergencies. [Anthrax vaccine's manufacturer, for example, was relieved of liability for adverse reactions through the end of 2015, simply because the vaccine might be needed for an emergency.] Both FDA and DHHS' Assistant Secretary for Preparedness and Response, with input from the Secretary of Homeland Security, have several different means by which unlicensed or even untested drugs and vaccines can be approved for use.

The method that is used the most is a waiver of liability for both manufacturers, professionals administering the drug or vaccine and government program planners: those who approved use of the untried product. This allows manufacturers to get the product on the market with very abbreviated testing. It saves an enormous amount (think $hundreds of millions) that would normally be spent on clinical trials. Sometimes the government performs most of those trials, saving the manufacturer more money, after the product is approved.
A total of six lives were saved by Sweden's massive swine flu vaccination programme, according to a new report, despite 60 percent of the Swedish population getting vaccinated.
In Sweden, 60 percent of the population was vaccinated against the swine flu in 2009.

A tally carried out by the European Centre for Disease Prevention and Control (ECDC) after the pandemic had passed found Sweden ended up with a death rate of 0.31 fatalities per 100,000 people.

In Germany, where only eight percent of the population was vaccinated, the fatality figures were the same.

And in Poland, which didn't have any vaccination programme at all, the death rate was only 0.47 per 100,000 , the Svenska Dagbladet (SvD) newspaper reports.

“We concluded that six fatalities were avoided by the mass vaccination programme,” Lisa Brouwers of the Swedish Institute for Communicable Disease Control (Smittskyddsinstitutet) told the newspaper.

In addition, Sweden has documented 168 cases of vaccine-related side effects, compared to only 29 in Germany.

“I feel stupid. What disappoints me most is that it was important that everyone in Sweden was vaccinated. The problem is that you don't get any sort of help afterwards,” 27-year-old Ida Andersson told the Aftonbladet newswpaper.

Andersson suffers from the sarcoidosis in her lungs, inflammation of the face, and abnormal drowsiness attributed to having been vaccinated against the swine flu.

“I don't know if I'll be sick for the rest of my life or if I'll ever get better,” she said.

So far, no explanation of the results of vaccination programmes in different countries has been carried out yet.

“The ECDC is still investigating and doesn't have any answers yet,” Johan Giesecke, head researcher at the Swedish agency, told SvD.

Sweden's own National Board of Health and Welfare (Socialstyrelsen) is also carrying out a review of the swine flu vaccination programme which has yet to be completed.

Lars-Olof Kalling, former head of the Swedish Institute for Communicable Disease Control, thinks one explanation to the differences between countries may be that the flu was so mild that the vaccinations didn't make much of a difference.

Effectiveness of vaccine against pandemic influenza/ BMJ

If you read the second post below this one, you will see evidence from several countries that suggests a previous seasonal flu vaccine may actually increase the risk of getting flu, and may worsen one's short and long-term immune response to a newer flu vaccine.

As if that wasn't enough reason to avoid getting routine flu vaccinations, it seems flu vaccine may actually increase your risk of getting flu in the first two weeks after flu vaccination!  That was a Danish finding in a study including 80,000 swine flu-vaccinated people under age 65 who were thought to be at increased risk from a flu infection.  The study is of high quality, published in the BMJ Jan 25.
An increased risk of laboratory confirmed H1N1 infection was observed during the first 1-7 days after receiving the pandemic vaccine, with vaccine effectiveness estimates of −112% (95% confidence interval −187% to −56%) [Negative effectiveness means you have an enhanced chance of getting flu] compared with those who did not receive either the pandemic or the seasonal influenza vaccines. In the following 8-14 days, no significant effectiveness from the pandemic vaccine was observed, and effectiveness was 49% (10% to 71%) more than 14 days after receiving the vaccine (table 2⇓). Those who received only the 2009-10 seasonal influenza vaccine had an increased risk of laboratory confirmed H1N1 infection compared with those who were not vaccinated (hazard ratio 2.31, 95% confidence interval 1.65 to 3.23; table 2)...
Did the vaccine keep people out of the hospital?  In other words, did they have a milder illness as a result of vaccination?
An increased risk of H1N1 related admission to hospital was observed during the first 1-7 days after receiving the pandemic vaccine, with vaccine effectiveness estimates of −258% (95% confidence interval −464% to −127%) compared with those who did not receive either the pandemic or the seasonal vaccines... 

Those who received only the 2009-10 seasonal influenza vaccine had an increased risk of H1N1 related hospital admission (hazard ratio 2.55, 95% confidence interval 1.38 to 4.70; table 2)...
If you got only the seasonal flu vaccine, you were 2.5 times more likely to be admitted to hospital with swine flu than if you received no flu vaccine at all!  And if you happened to get the swine flu vaccine, you were 2.6 times as likely to wind up in the hospital in the week after vaccination as people who got no flu vaccine at all!

How could this be, you might ask.  It isn't hard to theorize why:
"... one group of researchers suggested that repeated immunisations effectively block the robust, complex, and cross protective immunity afforded by previous infection. This might be a possible explanation for the Canadian findings and also a possible explanation for the finding in the present study..."
Given these facts, I have a hard time with public 'health' officials who want to force Americans to get yearly flu vaccines. 

Monday, February 13, 2012

Narcolepsy caused by swine flu vaccine: 170 Swedish children affected, according to health minister

Narcolepsy has been in the news the past 10 days.  Severe disabilities in 31 affected Irish children were reported; 70-100 Finnish children were reported with the disorder after receiving Pandemrix; 86 Norwegian claims have been made; now 170 Swedish children are affected, according to Sweden's health minister.  A Swedish study found the relative risk of narcolepsy to be 6.6 after receiving Pandemrix swine flu vaccine.  (It is unclear if this was in all age groups or only children.)  A year ago, WHO said cases were reported from 12 countries.  But WHO advisors have not changed their position: they still recommend people get vaccinated anyway, saying the benefits outweigh the relatively small risk.
Families of children in Sweden suffering from narcolepsy caused by vaccination for the swine flu can expect some form of compensation, Swedish health minister Göran Hägglund said on Sunday.
... According to Hägglund, the state will compensate those affected by narcolepsy caused by the swine flu vaccine.

“Yes, there will be some form of compensation for the roughly 170 children who've been affected,” the health minister told Sveriges Radio (SR).

However, Hägglund refused to specify how much the compensation might be or what form it might take.

“Our lawyers are looking into what's the best way to shape the compensation. This is a terrible situation which no one anticipated.”

... Previously, the families were told they would receive a one-time compensation of 50,000 kronor ($7,340) and that their needs would be assesssed again when they turned 18.

When Sweden agreed to purchase the drug from GlaxoSmithKline, the contract stipulated that the company would be free of responsibility to cover costs associated with any side effects.  
And in Norway:
Nordic medical experts highlighted a possible narcolepsy-Pandemrix link last year. Narcolepsy causes excessive sleepiness and frequent sleep attacks, sometimes without warning.
National Administrative body Norsk Patienskadeerstatning (NPE) now reports it has upheld damages claims regarding three children aged between 8 and 15 that they more than likely have developed the disorder because of the vaccine.
Assistant NPE director Rolf Gunnar Jørstad says each case is to be individually assessed. Compensation sums will vary according to symptoms’ scale, duration in years, as well as the degree they affect each child’s everyday life.
He tells NRK, “Unfortunately, there is reason to believe this is a disorder they may have to live on with. We’ll have to follow the individual child’s actual development, but could be talking about significant amounts of damages if the symptoms are lasting and comprehensive, at least a million kroner, or maybe more.”
Approximately 598,000 children and youths aged 6 months to 19 years out of roughly 2.2 million Norwegians were vaccinated with Pandemrix under the 2009-2010 mass vaccination programme.
The NPE has received 86 cases in total so far regarding various medical issues relating to the swine flu vaccine. Under a third have been processed. 7 complaints have been upheld and 18 have been rejected, most commonly because of no proven relation between the vaccine and problems.

Sunday, February 12, 2012

Mandatory Flu Vaccinations: Points to Consider/ New Research

1.  A significant number of healthcare workers (HCW) are already immune to new flu strains, due to exposures from previous years, crossover immunity, and high levels of exposure.  Thus a Spanish study found that 25% of its healthcare workers were already immune to swine flu prior to the 2009 epidemic.  Vaccinating those with preexisting immunity may increase the risk of autoimmune reactions.

2.  Prior year vaccinations may actually increase one's risk of getting sick from flu, according to studies by Danika Skowronski and other Canadian researchers: 
"... Because of limitations in study design and because they represented unexpected findings, we interpreted the results of this outbreak investigation as a paradoxical signal of possible concern-thought-provoking but inconclusive and warranting further evaluation. Canadian investigators thus embarked on a series of confirmatory studies using more rigorous methods and laboratory-confirmed outcomes through the summer of 2009, each of which corroborated findings from this initial outbreak investigation. In combination, these showed 1.4–2.5 fold increased risk of medically attended, laboratory-confirmed pH1N1 illness among prior 2008–2009 TIV recipients [17]. An additional Canadian study using the linked Manitoba immunization registry and administrative databases has also shown similar findings of increased risk [4] (Dr Carole Beaudoin, Public Health Agency of Canada, personal communication). Thus, in Canada, 6 observational studies based on different methods and settings, including the current outbreak investigation, consistently showed increased risk of pH1N1 illness during the spring and summer of 2009 associated with prior receipt of the 2008–2009 TIV [4, 17]"
One reason may be that if you were previously vaccinated, you were less likely to develop a high antibody titre to a newer flu vaccine, according to researchers in Portugal.  Consistent with these findings, the Dutch found a poorer response to adjuvanted swine flu vaccine in HCW who were vaccinated yearly for flu.

The Dutch researchers found that after being vaccinated for swine flu,  antibody against swine flu persisted in 72% of health care workers who did not receive annual flu vaccinations, but in only 44% of those who got yearly flu shots. 

HCW vaccinated yearly may therefore be at higher risk of disease when a serious influenza outbreak hits, as they are likely to mount a poorer response to vaccination than someone who is more vaccine-naive.

3.  A recently published meta-analysis from Hong Kong of healthcare worker flu vaccinations and subsequent illness failed to show the vaccinations gave the healthcare workers any benefit:
"No evidence can be found of influenza vaccinations significantly reducing the incidence of influenza, number of ILI [influenza-like illnesses] episodes, days with ILI symptoms, or amount of sick leave taken among vaccinated HCWs.
There is insufficient data to assess the adverse effects after vaccination. There is no definitive conclusion on the effectiveness of influenza vaccinations in HCWs because of the limited number of related trials. Further research is necessary to evaluate whether annual vaccination is a key measure to protect HCWs against influenza infection and thus increase their confidence in the vaccine. In the mean time, the direction of promoting influenza vaccination to HCWs can be shifted from staff protection to patient protection, with accurate information to address concerns and misconceptions."
4.  How do you determine if a vaccine is "safe"?  A study from Perth, Australia of vaccinated healthcare workers found that 1.3% of those who received seasonal flu vaccine sought medical attention for an adverse event temporally related to vaccination.  That seems like a high rate for seeking medical attention; yet to the study author, it indicated the vaccine was safe.

What were the side effects due to this seasonal flu vaccine?  A low rate of developing narcolepsy (a serious, lifelong disability) in adjuvanted swine flu vaccine recipients indicates to most people that the vaccine was not safe.  Without knowing the precise type of side effects (and usually no one is looking for them very hard) it is impossible to assess safety from numbers such as % seeking medical attention.

In a Korean study, 11% of military healthcare workers reported fatigue after swine flu vaccine and 7% reported muscle pain.  A whopping 32% had some type of systemic reaction.  Being military, the participation rate was high; these are probably more reliable data than in most other studies.

A Japanese study of HCW receiving swine flu vaccine found that 1.3% had a severe adverse event within 7 days of vaccination, and 23% reported some type of systemic reaction.  In Thailand, fatigue and malaise affected 24% of HCW after swine flu vaccination.

Note that the Koreans, Japanese and Australians got a vaccine that was very similar to that used in Finland and elsewhere in Europe, where it caused narcolepsy.  None of these studies were designed to identify persisting adverse events such as narcolepsy.  And the European narccolepsy cases were predominantly in the 5-20 year age group, generally outside the healthcare worker age range, which would cause them to be missed in any event.

I would conclude that vaccine safety remains uncertain, and that the range of long-terms effects from adjuvanted swine flu vaccine is probably not yet known.  Will it ever be?

Mandatory vaccinations for healthcare workers continue to be pushed--and then they will be for everyone

On February 8, a federal government vaccine advisory group (NVAC) made five recommendatios to increase healthcare worker flu vaccinations.  Members have significant conflicts of interest, such as Marie McCormick, who has chaired many IOM committees on vaccine safety and efficacy.  As reported by CIDRAP:
... The NVAC's recommendations urge US hospitals to establish comprehensive infection control programs that include education on how to prevent flu transmission and integrate flu vaccination programs into existing flu prevention and occupational health programs. The recommendations also press federal health officials to continue efforts to standardize methods on how to measure healthcare worker flu vaccination rates.
If those three steps don't push the healthcare worker vaccination levels to the national goal, NVAC suggests that healthcare employers strongly consider mandatory flu vaccination policies. A fifth recommendation calls for new and better flu vaccines...

From NPR
... Consumer and business groups met in Washington Feb 1 to show their support for a recommendation from the National Business Group on Health that hospitals require all health care workers to be vaccinated annually against the flu.
"We believe that patients have the right to assume that health care personnel, themselves, will take all reasonable measures to reduce and avoid transmission of preventable diseases including the flu," said Helen Darling, president and CEO of the NBGH. "I think we, as people, assume that after all, they're our caretakers and we look to them for care and treatment."
  The NBGH is a nonprofit representing more than 300 large employers, including 68 of the Fortune 100.   Its statement urged hospitals to "require annual flu vaccination of all employees as a condition of employment unless employees can demonstrate medical contraindications (with physician documentation) or religious objections."
... Among other groups supporting the proposal there were Consumer Reports and the American Hospital Association. Dr. Don Wright, deputy assistant secretary for health care quality at the Department of Health and Human Services, said at the briefing that the agency will be publishing data by next year on hospitals that have vaccinated employees as part of their efforts to reduce hospital-acquired infections.
... Even within the government, there are conflicting views. In a letter to the National Vaccine Program Office last month, Jordan Barab, deputy assistant secretary for the Department of Labor's Occupational Safety and Health Administration, said his organization supports the goal of the HHS' Healthy People 2020 initiative to get 90 percent of health care personnel vaccinated. But "we are troubled that some have tried to convert the goal into a mandate," he wrote.
... Hospitals that report their employee vaccination data will receive a bonus payment, Wright said, and already well over 95 percent of hospitals are doing that. Wright said in an interview later that HHS is not "endorsing any one method [of boosting vaccination rates] over another. Our goal is to get the rate of vaccinations up, so the jury is still out on the best way to do that."
But do vaccinations really make sense?  Flu shots are newly compounded each year, and in many years they do not provide protection against circulating strains.  For example, in 2009 the seasonal flu vaccine had more takers than the swine flu vaccine, yet no flu strains circulated that were in the vaccine.  CDC still recommended the seasonal vaccine throughout that flu season, even when it was clear there would be no exposure to seasonal flu strains.  How many side effects occurred from those (approx.) 90 million US vaccinations?  What were the costs to administer the vaccine after it became clear it would be of no benefit?  How many were harmed once it became clear the vaccinations were unnecessary?  What happened to "First, Do No Harm"?

Flu is transmitted by coughing and sneezing.  Healthcare workers should not be working with patients if they are coughing and might transmit any of multiple respiratory infections. 

Most institutions have policies that prevent staff working while infectious (actively coughing), as does my hospital.

There is no evidence that vaccinated healthcare workers reduce flu deaths in patients.

Mild flu and very little this year--only 3 deaths in US children since last April have been associated with flu/CDC

Influenza-Associated Pediatric Mortality

Thanks to CDC for these weekly influenza stats

Click on map to launch interactive tool

Thursday, February 9, 2012

Merck's Crooked HPV Marketing to Doctors: "Strategies to combat the spread of HPV infection"

Thank retired Colonel John Grabenstein, Merck Vaccine's King of Spin, for the following marketing technique, which detours around all FDA regulations about what companies can tell doctors regarding their products.  

If the issue was stopping the spread of HPV, then CONDOMS would be the most effective strategy.

Here's the strategy Merck used, delivered to my email today so I could learn how to talk patients into this vaccine:

*  Get your vaccine recommended by CDC's advisory committee (ACIP) for all 11 through 21 year old boys to prevent the dread disease GENITAL WARTS

*  Hire a "communications company" to "sponsor" a program about your product for doctors.  In this case:
Health Education Alliance, Inc. (HEA) specializes in the development and implementation of educational activities that integrate key clinical data and educational messages.
*  Since the program is not coming directly from Merck, it can make any claims it wants for the product, and absolutely no one can be blamed:
Statements and opinions expressed herein are those of the faculty and not necessarily those of the editor(s), publisher, CME sponsor, or Merck & Co., Inc. The editor(s) and publisher disclaim any responsibility or liability for such material and do not guarantee, warrant, or endorse any product or service communicated in this educational activity. These materials may discuss therapeutic products that have not been approved by the U.S. Food and Drug Administration and/or off-label uses of approved products. A qualified healthcare professional should be consulted before using any therapeutic product discussed. Viewers of this program should verify all information and data before treating patients or employing any therapies described in this educational activity.
The program early on has a "vignette" that indicates the vaccine is close to 100% effective for two strains causing 70% of cervical cancers, and that the immunity is very long-lasting.  These claims are questionable--Nass

(We have been told--in the fine print--not to believe what has been communicated!)

*  Blatantly, the fine print admits (under "Click here to view program"):
Note: one or more of the speakers may discuss unapproved or “off-label” usage of a commercial product or device.
*  Merck's communications company hired marionettes who teach at medical and nursing schools (but also happen to be on Merck's advisory boards) to "write" presentations about Merck's vaccine (except the materials they "wrote" have been copyrighted by the communications company, not the puppet professors) 
Copyright © 2011 Health Education Alliance, Inc. All rights reserved. No part of this educational activity may be reproduced...
*  Merck's puppets tell doctors they have the answer to a life-threatening condition... which requires rooting out the "barriers to vaccination":
With life threatening consequences such as cervical, anal, penis, and various head and neck cancers, clinicians need to be able to recognize barriers to vaccination, understand current clinical evidence, and to effectively communicate/counsel their patients about the clinical evidence, safety and efficacy of available vaccines.
*  A For-Profit, second-rate journal (owned by Elsevier) was paid to stand behind these marketing materials for your vaccine, packaged as if it was unbiased information.  A University (Purdue) was paid to provide additional cover.

*  The journal claimed the program was "peer-reviewed" and therefore meets the highest standards of medical journalism.

*  Doctors were given free continuing education credits for watching the presentations

*  Just in case there is any question at all about liability... such as not telling the truth about side effects and lack of demonstrated cancer prevention--doctors are required to *click* that they have reviewed the faculty disclosures, before they can view the program!   So if a doctor then uses the product off-label and problems ensue, it is the doctor's fault, because the doctor should have known the program was biased!

Wonder if the FDA will shut this educational activity down?

Friday, February 3, 2012

My submission to the Presidential Commission for the Study of Bioethical Issues

Public Commentary -- for meeting on February 2-3, 2012
Presidential Commission for the Study of Bioethical Issues
1425 New York Avenue NW, Suite C–100
Washington, DC 20005
Re:  Pediatric anthrax vaccine trial
Dear Members of the Presidential Commission for the Study of Bioethical Issues:
In this statement, I want to share with you the evidence that underlies my conviction that the proposed trial of anthrax vaccine in children represents an experiment whose risks far outweigh any possible benefits.
My name is Meryl Nass, M.D., and I have been involved in the study of anthrax and bioterrorism for the past 23 years.  I wrote one of the first reviews of the current vaccine.[1]  I have spoken about anthrax vaccine before 3 Congressional committees and 2 Institute of Medicine committees.  Apart from the clinicians at the military Vaccine Healthcare Centers network and Deployment Health Clinical Center, I have probably treated more servicemembers who became ill and/or disabled following anthrax inoculations than anyone in the US. These servicemembers have developed a range of disorders, which most often resemble the Gulf War syndrome—fibromyalgia—chronic fatigue syndrome pattern.  I invite you to contact physicians at the military centers noted above for additional information on anthrax vaccine safety.  I have remained engaged with this issue because I have met so many people whose health was destroyed by this vaccine.
The US human anthrax vaccine has been in development from the 1950s to the 2000s. There have been many changes to its manufacturing process over 60 years.  The Department of Health, Education and Welfare requested the manufacturer to conduct a human efficacy study in workers occupationally exposed to anthrax at the time of licensure
in 1969[2] (this is normally required prior to licensure) but there is no evidence the study was ever done.
All US human anthrax vaccines were named “Anthrax Vaccine Adsorbed” or AVA until 2002.  Subsequently, anthrax vaccine has been named “Biothrax.”

Vaccine effectiveness
The only direct human efficacy study for a US anthrax vaccine was conducted in the 1950s at 4 goat hair mills by Philip Brachman, MD et al. for the Army and CDC.[3]  Workers at these mills were exposed to imported anthrax spores in the course of their work.  The study used two vaccines that were very different from those used in 1970 or today.[4]  Brachman’s study demonstrated efficacy for cutaneous anthrax but not inhalation anthrax, although this distinction was disputed four decades later.  It is an important distinction, because route of exposure can be a critical determinant of vaccine efficacy.  Two other bioterrorism vaccines (plague[5] and Venezuelan equine encephalitis[6]) yielded evidence of protection from infection transmitted by insect bites, but protection for exposure via inhalation was lacking. There is a further important distinction:  deliberate use of anthrax for bioterrorism is likely to expose victims to orders of magnitude more spores than were inhaled in mills. 
At the time of Brachman’s study, neither of the two subjects who had received a placebo vaccine and were believed to develop inhalation anthrax had positive evidence of anthrax infection by culture, serology or pathologic examination, making the diagnosis of anthrax questionable.  One of the two recovered, which was unusual for inhalation anthrax.  Brachman himself wrote, “When inhalation anthrax is considered, the limited experience with this form of the disease makes the data less significant in showing effectiveness of the vaccine.” [7]
Later vaccine studies have used surrogate markers to infer immunity, although for anthrax vaccine this approach is fraught with uncertainty. No surrogate markers have been validated in humans; there is no clear relationship between antibody levels and survival rates in animals.[8] [9] Probably only a subset of measured antibodies are protective, but the understanding of this is at an early stage.[10]  Toxin neutralizing antibodies have been thought to better represent immunity than simple antibody levels.[11]  However, a recent study of sera from anthrax-vaccinated subjects found that only 46% of the 200 subjects had toxin neutralizing antibodies greater than unvaccinated controls, and only 20.5% of the subjects had greater than 50% in vitro toxin neutralization.[12]  In other words, the measurable degree of immunity was weak in most vaccinated subjects.

Vaccine Safety
In terms of safety, the Brachman trial only looked for adverse events up to 48 hours after subjects were vaccinated.  There were no obvious safety issues. Later versions of the vaccine have had a variety of safety evaluations.  The quality of these studies has varied considerably.  Many involved Colonel John Grabenstein, PhD, RPh, who oversaw the military vaccine program.
Each study that he supervised claimed a high degree of vaccine safety. However, Dr. Grabenstein, who is a member of the National Biodefense Science Board, had and continues to have a financial conflict of interest in propagating the claim that the vaccine is safe.  Dr. Grabenstein has been a consultant for several vaccine companies and is currently a scientist at Merck Vaccine, which produced anthrax vaccine for the US government in the 1960s and is today a major US vaccine manufacturer.
For example, a 1998-2000 study was designed to use active surveillance for long-term side effects and to determine their duration, according to principal investigator Colonel Glenn Wasserman.[13]  But when the study was published in 2003, with Colonel Grabenstein as second author, information on prolonged or late onset adverse events was not disclosed.  Eleven women who had been vaccinated while pregnant, mentioned by Wasserman in oral presentations, failed to be mentioned in the published paper.  Half the subjects were lost to follow-up by the end of the study.  The exit questionnaire was not designed to capture specific information about vaccine-related adverse events and their duration, and did not mention anthrax vaccine.  The paper claimed that only local reactions could be linked to vaccinations, dismissing vaccine causality for other reactions without explanation.  And although “women in the immunized cohort were more likely to report that their general health was “poor or fair” (6.6%) compared with the unimmunized cohort (1.5%) (RR 4.4; 95% CI 1.3-15.1)” the report concluded, “The findings of this study support the relative reactogenicity [local side effects] of AVA immunization but do not reveal any serious adverse events or effects on health.”[14]
A 2001 unpublished Navy study of women vaccinated for anthrax during pregnancy revealed a small but statistically significant increase in birth defects.  The research results led to several actions, according to the IOM[15]:
  • FDA changed the pregnancy warning in the vaccine label to category D, indicating evidence of fetal harm, in 2002.  (The Navy study was not published until 2008,[16] after expanding the original database, which diluted the fetal effect somewhat.  I wrote a commentary on it.[17] )
  • CDC added a pregnancy warning to the informed consent document for its 2001 IND trial of post-exposure anthrax vaccinations. 
  • The Assistant Secretary of Defense for Health Affairs issued a memorandum and press release requiring all military services to check for pregnancy before administering anthrax vaccinations. 
FDA closed the anthrax vaccine manufacturing plant in 1998 due to manufacturing problems, finding “the manufacturing process for anthrax vaccine is not validated.”[18]  Despite sale of the plant and a rebuild of the anthrax vaccine facility, the new plant continued to fail FDA inspections and was not allowed to open.  The Defense Department’s stock of vaccine was almost entirely consumed by mid 2001.  However, following the anthrax letters attack in late 2001, DHHS Secretary Tommy Thompson announced to the country that the plant would be relicensed.  In January 2002 FDA issued a new license with a new vaccine label.
The new label provided a higher systemic adverse event rate (5-35%) than the prior label (0.2%).  It also noted, without using the term “Gulf War,” that illnesses meeting CDC’s case definition for Gulf War illness[19] had been reported.[20]  It may be of interest that some
survivors of inhalation and cutaneous anthrax reported similar, lingering medical problems, “such as chronic fatigue, inability to concentrate and joint pain.”[21]
In 2007, a Government Accountability Office report noted, “Officials from the VHC (Vaccine Healthcare Centers) Network and CDC estimate that between 1 and 2 percent of immunized individuals may experience severe adverse events, which could result in disability or death."[22]  The report made clear, in a page 3 footnote, that it was addressing issues related only to anthrax vaccine.  The Assistant Secretary of Defense for Health Affairs concurred with the report’s findings.
CDC conducted a multicenter trial of Biothrax in 1563 subjects, 83% of whom received anthrax vaccine, between 2002 and 2007.  Two hundred twenty-nine serious adverse event reports were filed with the federal Vaccine Adverse Event Reporting System during the 43-month trial.  About 12% of subjects experienced a serious[23] adverse event.  But only a preliminary report on the first seven months and first 1000 subjects in the trial was published,[24] in 2008.  There has been no final report, nor any publicly available accounting of these adverse events.
Simultaneously in 1998, the US, UK, Canada and Australia began vaccinating troops deploying to the Gulf region with anthrax vaccine.  Within several years, the UK, Canada and Australia ended their anthrax vaccinations of troops.  Only the US persisted with them.
Federal District Judge Emmett Sullivan pulled the vaccine’s license in 2004 due to failures in the licensure process, including inadequate evidence of efficacy.[25] [26]  One year later, after a required review, FDA issued a reapproval for the vaccine (without more data) and the new license was upheld in court.
Hundreds of Israeli troops were given (both US and Israeli) anthrax vaccines in experiments beginning in the 1990s, funded by the US.[27]  Dozens are said to remain ill.  Sixty-four have sued for information about the trials and to get their medical care compensated.[28]  A report by the Israeli Medical Association, which recently investigated the trial, said, “No scientific justification was found for the experiment, scientific background was lacking, the experiment's design and execution did not suit its goals, and no result would have justified those goals. Also, conventional guidelines were not followed, risks and possible side effects were not thoroughly investigated, and a follow-up mechanism to keep track of participating soldiers was not set up.”[29]
According to Les Baillie, PhD, former head of anthrax vaccine research at Porton Down, UK, “…concerns over the toxicity of the current vaccines have driven the development of second-generation products.”[30] (emphasis added)
That the current vaccine is unsatisfactory is tacitly acknowledged by the Defense Department and other federal agencies, which continue to fund work to develop a more effective and safer anthrax vaccine. For example, US Army researchers at USAMRIID published a 2012 study of an entirely new candidate vaccine that uses the anthrax capsule, rather than the currently used ‘protective antigen,’ as its primary immunizing agent.[31]

Vaccine Necessity

Anthrax vaccine is not an emergency treatment for anthrax exposure.  It takes 2 or 3 vaccine doses, administered over 28 days, before what is thought to be a sufficient immune response is generated at about day 40. 
True emergency treatments for anthrax exposure include antibiotics, monoclonal antibodies and anti-anthrax antisera, all of which have been stockpiled by the US government.  These treatments are likely to be more effective than vaccination, even after day 40, due to the questionable levels of immunity evoked by the vaccine.  Antibiotics were 100% successful at preventing anthrax in those who received them prior to the onset of clinical disease, following exposure to the anthrax letters in 2001.
The current justification for post-exposure anthrax vaccine is the need for late immunity if inhaled spores germinate in the lungs after antibiotics are stopped.  This is a tenuous theory, based on limited animal data of anthrax deaths 2-3 months after a deliberate exposure.  However, a prolonged antibiotic course is more likely to be effective than vaccination with Biothrax.
Another justification for vaccination after exposure is to allow people to inhabit an area contaminated with anthrax spores. But given the expected  illnesses/deaths of many animals and some humans living in an area with a high level of spore contamination (for no antibiotic or vaccine is 100% protective in everyone) the theory that humans would want to remain in such areas is tenuous.
A third justification for vaccination is the possibility that anthrax used in an attack could be antibiotic resistant.  True:  but it can also be made vaccine resistant, as demonstrated by a Soviet scientist who came to work for NIH.[32]
The anthrax vaccine is not licensed for those under 18, nor for those over age 65.  No studies to test the efficacy, safety and dosing of the vaccine in the elderly have been proposed.  Yet in light of historically poor efficacy of influenza vaccine in those over 65, a high potency flu vaccine (containing 5 times more antigen than standard vaccines) was approved for elders two years ago.  How will the elderly be dosed with anthrax vaccine?  Shouldn’t those over 65, who can provide informed consent, be tested to determine dosing, before children?  However, given the lack of a reliable surrogate marker for the current vaccine, how valid will any tests of dosing be?
Despite questions about the utility of post-exposure vaccinations, the vaccine’s manufacturer has sold nearly two billion dollars’ worth of Biothrax to the federal government to be stockpiled for civilian use, post-exposure.  This stockpile is in addition to vaccine sold to the military for pre-exposure use.  Questions have been raised about the very high profit margin for these sales, said to be on the order of 300%.[33] 
The vaccine manufacturer, Emergent Biosolutions, has had on its payroll a former head of the Joint Chiefs of Staff, a former Secretary of DHHS, a former assistant secretary of DHHS, a former Assistant Secretary of Defense for Health Affairs, a former US Surgeon General, a former Army Surgeon General, and others who had responsibility for biodefense procurement in their former roles in government.
Vaccine Ethics
In 2001 CDC offered anthrax vaccinations to children after possible exposure to the anthrax letters.  To my knowledge there were no takers.  In 2005 the NIH proposed a trial of anthrax vaccine in 100 healthy children. Senator Bingaman, chairman of the Senate Health, Education, Labor and Pensions committee, noted as part of a detailed critique sent to DHHS Secretary Leavitt:
The Institute of Medicine's report Ethical Conduct of Clinical Research Involving Children (2004), which I requested as part of the "Best Pharmaceuticals for Children Act of 2002" (P.L. 107-109), points out, "...when proposed research involves a minor increase over minimal risk and does not offer the prospect of
direct benefit, the research must be limited to children with a disorder or condition and must be expected (among other criteria) to generate vital knowledge about the disorder or condition" (45 CFR 46.406; 21 CFR 50.53).
The IOM report adds, "For research that involves a control group of healthy children (and the anthrax study is to include healthy children) without a disorder or condition and without prospect of direct benefit from the research, the research procedures for that group would have to involve no more than minimal risk."
Subpart A of the HHS regulation defines "minimal risk" as meaning "that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests" (45 CFR46.102(i); 21 CFR 50.53(k)).[34] 
The NIH withdrew the proposed trial ten days later.[35] 
The Code of Federal Regulations (46.407) is clear regarding the protection of underage human subjects.  Their participation in research must only occur if “the research presents a reasonable opportunity to further the understanding, prevention, or alleviation of a serious problem affecting the health or welfare of children.”  The language of the regulation does not indicate that a serious potential problem would meet this standard.
Furthermore, 46.407 requires the assent of both parents and children.  A true informed consent, in which the serious outstanding questions about efficacy, safety and necessity were explained to families and understood by them, would result in few, if any, subjects volunteering for the vaccine study.
An IRB, if made aware of the questions about efficacy, safety and necessity, could not ethically approve such a trial.  However, the US government and manufacturer have successfully obfuscated the facts surrounding anthrax vaccine for soldiers. Given this history, the facts will no doubt be concealed from an IRB reviewing a protocol for a pediatric trial of Biothrax.
Anthrax vaccinations are mandatory for all soldiers deploying to the Afghan, Gulf or Korean theaters of operation.  Since 1998, approximately 3 million soldiers have received a required course of anthrax inoculations.  Soldiers are a vulnerable group in our society, required to accept vaccines and other medical treatments ordered by the military, exposed to noxious agents, frequently placed in harms’ way, and soldiers come predominantly from the poorer strata of society.
Will the children selected for a proposed anthrax vaccine trial come with a similar demography?  Whose children will be used to test a vaccine that will provide them no benefit, but a certain risk of harm?
Harvard professor Jerry Avorn, MD wrote:  “The design of the Tuskegee experiment was so loathsome that its legacy became a touchstone for medical researchers all over the world.  If a question of potential harm to patients arose in the design or conduct of a clinical trial, someone might underscore an objection by warning, “We don’t want another Tuskegee.”’[36]
The decision your Commission makes will determine whether anthrax vaccine research on children takes place, research intended to expand the anthrax vaccine license to those under 18.  Will your Commission approve another Tuskegee?  Please consider the many complex issues surrounding the use of the current anthrax vaccine, and make a determination that meets our highest ethical and legal standards.
Thank you very much for your attention.  I would be happy to provide additional information or documents at any time.
Sincerely yours,
Meryl Nass, M.D.

Nass M. Anthrax Vaccine:  Model of a response to the biologic warfare threat.  Infectious Disease Clinics of North America 1999; 13(1):187-208.
Pittman M., Memorandum to S. Gibson, Assistant Director for Licenses and Inspections, NIH. February 10, 1969.
Brachman PS, Gold H, Plotkin SA, Fekety FR, Werrin M and Ingraham NR. Field Evaluation of a Human Anthrax Vaccine. Am J Public Health 1962; 52(4): 632-645.
GAO T-NSIAD-99- 148, "Medical Readiness: Safety and Efficacy of the Anthrax Vaccine" (Apr 29, 1999).
CDC, "Prevention of Plague: Recommendations of the Advisory Committee on Immunization Practices (ACIP)", MMWR, Dec 13, 1996 / 45 (RR-14); 1-15
[6] Jahrling PB and Stephenson EH. Protective efficacies of live attenuated and formaldehyde-inactivated Venezuelan Equine Encephalitis virus vaccines against aerosol challenge in hamsters. J Clin Microbiology 1984; 19: 429-31.
[7] Brachman, op. cit.
[8] Nass, op. cit.
[9] Turnbull PCB. Anthrax vaccines: past, present and future. Vaccine 1991 Aug; 9(8):533-9.
[10] Crowe SR, Ash LL, Engler RJM, Ballard JD, Harley JB, Farris AD, and James JA. Select human anthrax protective antigen (PA) epitope-specific antibodies provide protection from lethal toxin challenge. J Infect Dis. 2010; 202: 251–260.
[11] Ngundi MM, Meade BD, Lin T-L, Tang W-J, and Burns DL. Comparison of Three Anthrax Toxin Neutralization Assays. Clin Vaccine Immunol 2010; 17(6): 895-903. 
[12] Crowe SR et al. op.cit.
[13] Wasserman G. Tripler Army Medical Center Survey. First Annual Department of Defense Conference for Biological Warfare Defense Immunizations. May 26, 1999. Fort Detrick, Maryland. Transcript.
Wasserman GMGrabenstein JDPittman PRRubertone MVGibbs PPWang LZGolder LG. Analysis of adverse events after anthrax immunization in US Army medical personnel. J Occup Environ Med. 2003 Mar;45(3):222-33
National Research Council. The Anthrax Vaccine:  Is it Safe? Does it Work? Washington, DC: The National Academies Press, 2002. Pages 171-2
Ryan MAK, Smith TC, Sevick CJ et al. Birth Defects among Infants Born to Women Who Received Anthrax Vaccine in Pregnancy. Am. J. Epidemiol 2008. 168(4): 434-442.
[18] FDA Inspection Report of Michigan Biologics Products Institute for February 4-20, 1998. Obtained through FOIA request to FDA.
[19] Fukuda K, Nisenbaum R, Stewart G et al. Chronic multisymptom illness affecting Air Force veterans of the Gulf War. JAMA 1998; 280: 981-8.
January 2002 anthrax vaccine label: “Infrequent reports were also received of multisystem disorders defined as chronic symptoms involving at least two of the following three categories:  fatigue, mood-cognition, musculoskeletal system.”
Center for Counterproliferation Research. Working Paper:  Anthrax in America. A chronology and analysis of the fall 2001 attacks. November 2002. Page 12. The paper cites: William J. Broad and Denise Grady, “Science Slow to Ponder Ills that Linger in Anthrax Victims,” The New York Times, 16 September 2002, p. A1; Shelley Emling, “Anthrax Victims Feel Forgotten in 9/11 Honors,” The Atlanta Journal-Constitution, 29 September 2002, p. 15A; Deborah Sharp, “Survivors Still Wrestle With Pain, Fatigue, and Shortness of Breath,” USA Today, 1 October 2002, p. 4A.
GAO-07-787R DOD’s Healthcare Centers Network
Marano M, Plikaytis BD, Martin SW et al. Effects of a Reduced Dose Schedule and Intramuscular Administration of Anthrax Vaccine Adsorbed on Immunogenicity and Safety at 7 Months. JAMA 2008; 300(13): 1532-1543.
[30] Baillie L. Is new always better than old? The development of human vaccines for anthrax. Hum Vaccine 2009 Dec; 5(12):806-16.
[31] Chabot DJ, Joyce J, Caulfield M, Cook J, Hepler R, Wang S, Vietri NJ, Ruthel G, Shoop W, Pitt L, Leffel E, Ribot W, Friedlander AM. Efficacy of a capsule conjugate vaccine against inhalational anthrax in rabbits and monkeys. Vaccine 2012 Jan 20;30(5):846-52.
[32] Pomerantsev APStaritsin NAMockov YuVMarinin LI. Expression of cereolysine AB genes in Bacillus anthracis vaccine strain ensures protection against experimental hemolytic anthrax infection. Vaccine 1997 Dec; 15(17-18): 1846-50.
Center for American Progress. (Scott Lilly). Getting Rich on Uncle Sucker:  Should the federal government strengthen efforts to fight profiteering? October 2010.
[36] Avorn J. Powerful Medicines: The benefits, risks and costs of prescription drugs. Borzoi (Alfred A Knopf) 2004. NYC. Page 32.