Friday, September 30, 2011

Narcolepsy and Swine Flu Vaccine: Is this the vaccine we use today?/ BBC

From the BBC:  Link between narcolepsy and flu vaccine investigated 
Health officials are investigating a link between narcolepsy and the Pandemrix vaccine in two people who were treated for swine flu.
Northern Ireland's Chief Medical Officer has confirmed to the BBC, that Northern Ireland had become the latest country to report suspected cases of the sleeping disorder.
Dr Michael McBride said the vaccine was used during the flu pandemic of 2009.
"Let's be clear - this is not the vaccine that we use today," he added...
Let's be clearer in this blog.  The trivalent vaccine used today does include the swine flu (H1N1) hemagglutinin antigen --the main immunizing ingredient in swine flu vaccines.  According to the FDA, the 2011-2012 vaccine's "A/California/7/09 (H1N1)-like virus is the pandemic (H1N1) 2009 influenza virus."  In the UK and many countries, but not the US, the swine flu vaccine used in 2009-10 also contained a novel adjuvant; in the UK this was ASO3.  It is of interest that in one important study, most, but not all cases of post-vaccination narcolepsy were associated with the ASO3-adjuvanted vaccine, while other cases were associated with the plain vaccine...which contained the same ingredients as are found in the current flu vaccine.  So far, neither ASO3 adjuvant nor hemagglutinin antigen has been implicated as "the" cause of the narcolepsy outbreak.  Certainly, the European Medicines Agency has no clue, below:
In the past six months, the number of narcolepsy cases in Beijing in China, and Scandinavian countries including Finland has risen significantly...
With concern growing about the potential side effects of Pandemrix, the vaccine used during the pandemic flu in 2009, the European Medicines Agency completed a review of the drug in July 2011. 
It concluded that the benefits of Pandemrix continued to outweigh its risks, but that it may only be used in people under 20 if the recommended annual seasonal vaccine was not available and if immunization against H1N1 was still needed.  [Would the person who calculated this crazy risk - benefit analysis please stand up?---Nass] 

Wednesday, September 28, 2011

US Food and Drug Administration lashes pharmaceutical giant CSL over lab practices/ The Australian

for video click here
Despite the report below, CSL is one of six flu vaccine manufacturers licensed to sell flu vaccine in the US in 2011.  The CSL vaccine, Afluria, is labelled for use over 5 years old.  However, the CDC's Advisory Committee on Immunization Practises recommends that Afluria not be used in children aged 6 months through 9 years, because of "increased reports of febrile reactions in this age group."  Why use it at all, when Australia had 9 times the expected rate of febrile seizures from Afluria in early 2010?  Or are the other five brands equally problematic?  Here are the brands and lots released for use by FDA so far this season.

Febrile seizures in small children may not be the only problem with the vaccine.  One must also balance the risk of getting flu, and the benefit from vaccination.  In the US, approximately 100 children die from flu yearly, half of whom have underlying chronic illnesses.  There are about 80 million US children, so yearly deaths from flu are slightly more than one in a million.  It appears that about 64 per million vaccinated children developed narcolepsy in Ireland.  About 90% of new child narcolepsy cases in Finland were due to vaccination. 

UPDATE Oct. 19:  CSL accused of not reporting seizures during its flu vaccine's clinical trial.
SECRET audits by the powerful US Food and Drug Administration have revealed a multitude of manufacturing flaws at Australia's biggest pharmaceutical company, CSL. The FDA's 2010 and 2011 audits, released to The Australian yesterday after a Freedom of Information request, cite a string of "objectionable conditions and practices" used by CSL to make vaccines.
The FDA allegations - which CSL said yesterday had been or were in the process of being resolved - include the failure of laboratory staff to wear masks while dispensing and mixing vaccines, "deficient" tests to check whether viruses were properly split to prevent side-effects and "inadequate" investigations into product failures.
The FDA documents reveal that CSL took six months to start investigating the cause of mysterious dark particles in the national stockpile of swine flu vaccine.
The most recent audit, in March, branded as "inadequate" CSL's investigation of febrile fits among children immunised with Fluvax, its seasonal flu vaccine.
Eleven months after Fluvax was banned for young children, the FDA audit discovered CSL had not compiled an investigations report or even designated anyone to be in charge of the investigation.
Australia's pharmaceutical regulator, the Therapeutic Goods Administration, refused to release the findings of its own audits into CSL.
And CSL insisted the FDA audits contained "observations only" rather than any final determination of compliance.
CSL, the privatised Commonwealth Serum Laboratories, has also been under fire this week after being forced to ration supplies of penicillin in its role as sole Australian supplier of the medicine.
The FDA audit findings form the basis of a "warning letter" the US regulator sent to CSL in June, threatening to revoke its US licence if it failed to address outstanding issues.
This year's audit described as "inadequate" CSL's investigation into the high rate of fever and convulsions among children given the Fluvax shot last year. "There was limited analysis of the manufacturing process to determine why there was a substantial increase of adverse-event reports of fever and convulsions in the 2010 southern hemisphere influenza season in comparison to previous seasons. "There was no evaluation of testing of raw material and potential impact on manufacturing," it said.
The audit found 15 lots of a key ingredient in CSL's flu vaccines, the detergent sodium taurodeoxycholate, failed an "identity test" but were used regardless.
The detergent is used to split the flu viruses used to make vaccines to minimise side-effects.
The Medical Journal of Australia reported last week that CSL was "one of only a few manufacturers globally" to use the ingredient.
The FDA audit also criticised CSL's "inadequate" investigation into the cause of dark particles that appeared in multi-dose vials of vaccines against swine and seasonal flu, produced for the US market in 2009.
"The investigation is ongoing and a root cause has not been determined," its report said.
It also noted that CSL had manufactured products "outside the validated processes" without determining if they would remain stable until their expiry date.
It cited a "formulation error" discovered in July last year, when not enough swine flu virus was used in the vaccine against seasonal flu.
The FDA inspectors raised the problem of black particles in multi-dose vials during an inspection of the Parkville laboratory in April last year.
The same discolouration had been detected in Australia's stockpile of swine flu vaccine, Panvax, for which the federal government paid CSL $131 million of taxpayer funds. Half the stockpile - 10 million doses - had to be destroyed after passing their use-by date last year, while the paediatric version was withdrawn early because the medication lost potency before the expiry date.
The FDA's 2010 audit found CSL's supplier of rubber stoppers had told the company they could react with the mercury in multi-dose vials and should not be used.
The TGA said it agreed with the FDA findings, but it refused to release its own audits.
UPDATE:  from the Australian Broadcasting Corporation

Sunday, September 11, 2011

Health problems linger for survivors of the anthrax attacks/PA's Courier Times

The following article talks about an important finding, which I mentioned back in a 2002 NY Times interview:  the people who developed inhalation anthrax (or cutaneous anthrax that became generalized) were likely to suffer from the identical symptoms as those who became very ill after anthrax vaccinations.  These symptoms have now lingered for ten years in those who got the disease anthrax, and for ten years or more in those I have treated for anthrax vaccine exposures.  The symptoms are fatigue, impaired cognition, psychological problems and muscle/joint pains.  Perhaps not coincidentally, these symptoms also define Gulf War Syndrome.  Many of my patients have developed hormone deficiencies as well (both Gulf War and anthrax vaccine-injured patients) and it appears from the article that research physician Mary Wright at NIH is finding hormonal problems in her anthrax survivors as well.

How can you explain why people who got the vaccine have a similar chronic illness as those who caught the disease?  I don't believe any research has been published on this interesting fact, but it isn't hard to speculate.  This is particularly important for several reasons:  people who are cured of anthrax may never become well, unlike those who recover from most other infectious diseases.  What is fundamentally different about anthrax infection in this regard?  Furthermore, many monkeys who were given anthrax vaccine, then exposed to anthrax, actually got the disease but survived.  (See the July 18, 2000 Washington Post article by Tom Ricks, "Anthrax Shots' Effects Challenged:  Army Disputes Expert Who Reviewed Vaccine Tests.")

If people get the same level of protection afforded by the vaccine as the monkeys did, it may not prevent them developing chronic illness, although it may prevent their death. That doesn't speak well for the vaccine, and suggests a better vaccine is needed: both to be more effective at preventing anthrax, in addition to being more safe.

The licensed human anthrax vaccine, produced by Emergent BioSolutions, contains many anthrax proteins and other anthrax molecules produced during bacterial fermentation, and one or more of these probably cause[s] the symptoms, or cause[s] some type of deregulation that not only causes the symptoms, but allows them to persist, apparently forever.  The persistence of these symptoms--after the disease is long gone--is another issue crying out for study.
In the 10 years since 17 people survived the deadly anthrax attacks that terrorized the nation in the weeks following 9/11, little recent information is known about their health.
But the National Institute of Health has quietly monitored the health of seven of the those survivors, including Falls resident Patrick O’Donnell. The group represents the largest pool of anthrax survivors U.S. researchers have studied.
The ongoing study will provide the first comprehensive data on the long-term health effects of anthrax exposure, the project’s head researcher said recently.
“No one has ever documented followup in anthrax survivors,” said Dr. Mary Wright, the principal investigator with the NIH’s National Institute of Allergy and Infectious Disease.
Before 2001, the last reported U.S. anthrax case occurred in 1976, and it was reported two years later, according to the NIH. The only previous anthrax studies were 50 years old and contained little data about long-term effects or possible complications.
In fall 2001, 22 people in the U.S. were exposed to anthrax through tainted letters sent through the U.S. mail. Five died. Many of those affected were U.S. Postal Service workers, who either inhaled anthrax spores or were exposed to it through skin contact.
NIAD is the only research agency that is following the health of anthrax attack survivors, a project that started in February 2002.
The study participants include two with inhaled exposure, and all but one are regularly tested and evaluated every one to two years, Wright said. The testing includes neuropsychological, blood and hormone level tests. The study will continue as long as the participants are willing. And one survivor, a woman who has not recently participated, can return at any time, Wright said.
The most recently released information about the health of the survivors came in 2004. It was based on a one-year followup study of 15 of the 17 survivors conducted by the Centers for Disease Control and Prevention. That study used medical interviews, standardized self-administered questionnaires, and a review of available medical records.
The study found that eight of the participants hadn’t returned to work more than a year after the attacks, all were under psychiatric care, and most reported symptoms ranging from chronic cough, fatigue and memory problems to depression, anxiety and hostility. Eight survivors also reported moderate to severe joint problems and decreased physical functioning.
But diagnostic tests performed on six of the eight patients showed no signs of immune or inflammatory disorders or other common medical explanations for the symptoms.
Nearly nine years later, Wright says her data shows the survivors who were the sickest in 2001 continue to experience the most persistent symptoms, including memory trouble and chronic fatigue. These survivors either inhaled anthrax or had it enter their bloodstream after they contracted the skin form.
The sickest patients also have had the most difficulty returning to work. Though some have returned, they can’t perform at the same level as before, Wright said. Those with less severe symptoms appear to have returned to their regular lives.
Wright added that researchers know some survivors will develop common age-related medical problems, but there likely will be no way to prove a cause-effect relationship with the anthrax exposure.
“We are hoping what we learn, once we publish, is if there are new cases, including natural cases, that they can learn from this experience and monitor some of these variables, like hormone levels and memory testing and offer some support to folks,” Wright said.
O’Donnell, now 45 and a U.S. postal worker, was the 12th of the 22 anthrax attack victims. Four coworkers also were exposed and survived.
He returned to his job at the Hamilton, N.J., office in 2005, where he continued to work a “modified schedule” through Workers’ Compensation, according to a recent post on the PostalWorker News Blog, which isn’t affiliated with the U.S. Postal Service.
The Courier Times was unsuccessful in attempts to reach O’Donnell for comment.
O’Donnell came in contact with one of the tainted envelopes, a letter addressed to then Senate Majority Leader Thomas Daschle, while working overtime on Columbus Day 2001. Normally, he didn’t sort first-class mail.
Five days later, O’Donnell noticed a welt-like sore on his neck where he had nicked himself shaving the day he worked the overtime. He was treated at an emergency room for a suspected spider bite and released. The next morning, though, O’Donnell woke to find his neck had swelled to 27 inches around. The welt was now a pus-filled boil and a softball-size lump protruded from his chest.
He returned to the emergency room, where doctors confirmed he had an anthrax infection, triggering emergency infectious disease protocols. After five days in isolation with antibiotic treatments, O’Donnell was released.
O’Donnell last spoke to the newspaper in 2008, after he attended a private FBI briefing discussing Bruce Ivins, the late Army scientist the government said was responsible for the anthrax attacks. At the time, O’Donnell complained of symptoms that he believed were the lingering effects of the anthrax — stuffy head, achy joints, throbbing headaches, insomnia and panic attacks.
In an Aug. 6 post on the PostalWorker blog, O’Donnell wrote that he still suffers severe post traumatic stress disorder, which a doctor has diagnosed. He said his condition has been worsened because he continues to work at a postal center 300 yards from the building where he was exposed to anthrax and he’s required to sort and throw away waste mail.
He added that his repeated requests for a job transfer closer to home have gone nowhere.
“Without having been through this experience, it has been impossible for others, including U.S. Post officials, to comprehend the mental and physical toll I face each day driving back and forth to work and seeing the postal facility, a constant reminder of this terrible, near-fatal exposure I suffered,” O’Donnell’s post said. “This has proven to be no help whatsoever in me trying to obtain closure and getting on with my life. I just want to spend my last years of service at a facility with a less stressful, remindful environment.”
The USPS cannot comment on employee claims without the employee’s written permission, spokesman Ray Daiutolo said.
But Daiutolo said that if an injured worker disagrees with the offered position, that employee can provide supporting documentation to the Office of Workers’ Compensation Programs, which makes the final decision.
If an employee is returned to duty in a “suitable position” and subsequently experiences a worsening of his/her condition or has a change in work tolerances, that employee has the right to submit a claim for recurrence, Daiutolo added.

Thursday, September 1, 2011

Probe on narcolepsy–H1N1 vaccine link finds genetic risk factor/ CIDRAP

Sep 1, 2011 (CIDRAP News) – A final report from Finnish health officials on the link between the 2009 H1N1 Pandemrix vaccine and narcolepsy confirmed the link, finding a greater risk than their earlier estimate and identifying a genetic risk factor in all patients.
In a statement on the findings today, a task force from Finland's National Institute for Health and Welfare also said an immunologic study found that one quarter of those who experienced narcolepsy after vaccination had antibodies that bound to the AS03 adjuvant component of the Pandemrix vaccine, which they said is a preliminary finding that requires more investigation.
Today's report put the increased risk of narcolepsy with vaccination at 6 cases per 100,000 people, which amounts to a 12.7-fold greater risk than in those who had not been vaccinated. The task force's first estimate in a January preliminary report was a nine times greater risk.
Some countries, mostly Nordic, have reported a link between the vaccine and narcolepsy in young people. Pandemrix, made by GlaxoSmithKline (GSK), is one of the 2009 H1N1 vaccines used in Europe during the pandemic.
In July the European Medicines Agency (EMA), in issuing its final review on the link, recommended a labeling change that limits the vaccine's use to protecting children and teens from the 2009 H1N1 virus when seasonal flu vaccine isn't available.
Finnish officials haven't found an increased risk in children younger than 4 or among adults older than 19.
In reporting the genetic findings in vaccinated patients who had narcolepsy, the task force said the risk factor for the condition is strongly linked to genetic factors that regulate immune responses. "Narcolepsy is considered an immune-mediated disease," they wrote.
Antibody tests found that less than 10% of those who had narcolepsy had been infected with the 2009 H1N1 virus, which led the group to conclude that infection with the strain doesn't appear play a significant role or show a combined effect with Pandemrix vaccination and narcolepsy onset.
The task force said so far Finland and Sweden are the only countries that have confirmed the link between Pandemrix and narcolepsy, though Norway and France have reported higher-than-expected numbers of cases. It added that several studies on the link are under way in countries that used considerable amounts of Pandemrix and Arepanrix, another GSK pandemic vaccine made in Canada that included the same adjuvant.
As of Aug 25, Finnish health officials had received reports of 98 narcolepsy cases in people who had been vaccinated with Pandemrix, and 79 were in patients between ages 4 and 19 years old. The condition was associated with cataplexy, a sudden and transient loss of muscle tone, in 78 cases.
Despite the limited number of unexpected and unfortunate narcolepsy cases, Finnish officials said the overall benefits of the vaccine still outweigh the risks.
They added that research teams in Finland and other countries are exploring the immunogenetics, pathogenesis, and clinical course of narcolepsy.
GSK spokeswoman Jennifer Armstrong told CIDRAP News that the Finnish data are similar to what officials reported earlier this year. She said Glaxo is committed to patient safety and is working closely with the EMA and other regulatory groups.
"Further information from ongoing studies is still needed in order to gain additional insight into the cause of the reported cases of narcolepsy," Armstrong said. "In addition, GSK has committed to conduct further research into any potential association between Pandemrix and narcolepsy and will seek independent expert advice on this research activity, as agreed with the EMA."