Sweden confirms swine flu vaccine and narcolepsy

Saturday, 30 March 2013

The swine flu vaccine Pandemrix has a direct link to causing narcolepsy, especially among the younger people who were vaccinated, a new Swedish study revealed on Tuesday.

The Swedish Medical Products Agency (Läkemedelsverket) ordered the massive study to determine if the vaccine had any connection to narcolepsy after dozens of reported cases of young people coming down with the affliction after receiving a swine flu jab.

The study, which took place between October 2009 and the December 2011, compared 3.3 million vaccinated Swedes with 2.5 million who were not vaccinated.

“We can see that over the whole study period we have 126 cases of those vaccinated getting narcolepsy,” Ingemar Person, professor behind the study, said in a statement on Tuesday.

“There were 20 cases among those not vaccinated. We’re talking about a threefold increase in risk.”

The risk was found to be highest among the youngest people who took the vaccines. For those under the age of 21, the risk of contracting narcolepsy was three times higher for those who were vaccinated with Pandemrix, whereas those aged between 21 and 30 had double the risk.

Those vaccinated over the age of 40 had the same risk as those who didn’t, according to the study.

Person added that it was “very difficult” to determine whether there was any connection with other sicknesses or diseases from taking the vaccine.

http://macedoniaonline.eu/content/view/23020/54/

Increased risk of sleep disorder in children who received swine flu vaccine : Up to 16-fold increased risk

Contact: Emma Dickinson edickinson@bmjgroup.com 44-020-738-36529 BMJ-British Medical Journal

Results consistent with findings from Finland and Sweden, but may still be overestimated

The results are consistent with previous studies from Finland and Sweden and indicate that the association is not confined to Scandinavian populations. However, the authors stress that the risk may still be overestimated, and they call for longer term monitoring of the cohort of children and adolescents exposed to Pandemrix to evaluate the exact level of risk.

In 2009, pandemic influenza A (H1N1) virus spread rapidly, resulting in millions of cases and over 18,000 deaths in over 200 countries. In England the vaccine Pandemrix was introduced in October 2009. By March 2010, around one in four (24%) of healthy children aged under 5 and just over a third (37%) aged 2-15 in a risk group had been vaccinated.

In August 2010 concerns were raised in Finland and Sweden about a possible association between narcolepsy and Pandemrix. And in 2012 a study from Finland reported a 13-fold increased risk in children and young people aged 4-19.

But a lack of reported cases in other countries led to speculation that any possible association might be restricted to these Scandinavian populations.

Narcolepsy is a chronic disorder of excessive daytime sleepiness, often accompanied by sudden muscle weakness triggered by strong emotion (known as cataplexy). To evaluate the risk after vaccination in England, a team of researchers reviewed case notes for 245 children and young people aged 4-18 from sleep centres and child neurology centres across England.

Of these, 75 had narcolepsy (56 with cataplexy) with onset after 1 January 2008. Eleven had been vaccinated before onset of symptoms; seven within six months.

After adjusting for clinical conditions, vaccination at any time was associated with a 14-fold increased risk of narcolepsy, whereas vaccination within six months before onset was associated with a 16-fold increased risk.

In absolute numbers, this means that one in 52,000 to 57,500 doses are associated with narcolepsy, say the authors.

They write: “The increased risk of narcolepsy after vaccination with ASO3 adjuvanted pandemic A/H1N1 2009 vaccine indicates a causal association, consistent with findings from Finland. Because of variable delay in diagnosis, however, the risk might be overestimated by more rapid referral of vaccinated children.”

While further use of this vaccine for prevention of seasonal flu seems unlikely, they say their findings “have implications for the future licensure and use of AS03 adjuvanted pandemic vaccines containing different subtypes such H5 or H9.”

And they conclude: “Further studies to assess the risk, if any, associated with the other A/H1N1 2009 vaccines used in the pandemic, including those with and without adjuvants, are also needed to inform the use of such vaccines in the event of a future pandemic.”

Insight: Evidence grows for narcolepsy link to GSK swine flu shot : Doctors are fearful of having their reputations ruined by reporting possible links

By Kate Kelland, Health and Science Correspondent | Reuters – 8 mins ago

STOCKHOLM (Reuters) – Emelie is plagued by hallucinations and nightmares. When she wakes up, she’s often paralyzed, unable to breathe properly or call for help. During the day she can barely stay awake, and often misses school or having fun with friends. She is only 14, but at times she has wondered if her life is worth living.

Emelie is one of around 800 children in Sweden and elsewhere in Europe who developed narcolepsy, an incurable sleep disorder, after being immunized with the Pandemrix H1N1 swine flu vaccine made by British drugmaker GlaxoSmithKline in 2009.

Finland, Norway, Ireland and France have seen spikes in narcolepsy cases, too, and people familiar with the results of a soon-to-be-published study in Britain have told Reuters it will show a similar pattern in children there.

Their fate, coping with an illness that all but destroys normal life, is developing into what the health official who coordinated Sweden’s vaccination campaign calls a “medical tragedy” that will demand rising scientific and medical attention.

Europe’s drugs regulator has ruled Pandemrix should no longer be used in people aged under 20. The chief medical officer at GSK’s vaccines division, Norman Begg, says his firm views the issue extremely seriously and is “absolutely committed to getting to the bottom of this”, but adds there is not yet enough data or evidence to suggest a causal link.

Others – including Emmanuel Mignot, one of the world’s leading experts on narcolepsy, who is being funded by GSK to investigate further – agree more research is needed but say the evidence is already clearly pointing in one direction.

“There’s no doubt in my mind whatsoever that Pandemrix increased the occurrence of narcolepsy onset in children in some countries – and probably in most countries,” says Mignot, a specialist in the sleep disorder at Stanford University in the United States.

30 MILLION RECEIVED PANDEMRIX

In total, the GSK shot was given to more than 30 million people in 47 countries during the 2009-2010 H1N1 swine flu pandemic. Because it contains an adjuvant, or booster, it was not used in the United States because drug regulators there are wary of adjuvanted vaccines.

GSK says 795 people across Europe have reported developing narcolepsy since the vaccine’s use began in 2009.

Questions about how the narcolepsy cases are linked to Pandemrix, what the triggers and biological mechanisms might have been, and whether there might be a genetic susceptibility are currently the subject of deep scientific investigation.

But experts on all sides are wary. Rare adverse reactions can swiftly develop into “vaccine scares” that spiral out of proportion and cast what one of Europe’s top flu experts calls a “long shadow” over public confidence in vaccines that control potential killers like measles and polio.

“No-one wants to be the next Wakefield,” said Mignot, referring to the now discredited British doctor Andrew Wakefield who sparked a decades-long backlash against the measles, mumps and rubella (MMR) shot with false claims of links to autism.

With the narcolepsy studies, there is no suggestion that the findings are the work of one rogue doctor.

Independent teams of scientists have published peer-reviewed studies from Sweden, Finland and Ireland showing the risk of developing narcolepsy after the 2009-2010 immunization campaign was between seven and 13 times higher for children who had Pandemrix than for their unvaccinated peers.

“We really do want to get to the bottom of this. It’s not in anyone’s interests if there is a safety issue that needs to be addressed,” said GSK’s Begg.

LIFE CHANGED

Emelie’s parents, Charles and Marie Olsson, say she was a top student who loved playing the piano, taking tennis lessons, creating art and having fun with friends. But her life started to change in early 2010, a few months after she had Pandemrix. In the spring of 2010, they noticed she was often tired, needing to sleep when she came home from school.

But it wasn’t until May, when she began collapsing at school, that it became clear something serious was happening.

As well as the life-limiting bouts of daytime sleepiness, narcolepsy brings nightmares, hallucinations, sleep paralysis and episodes of cataplexy – when strong emotions trigger a sudden and dramatic loss of muscle strength.

In Emelie’s case, having fun is the emotional trigger. “I can’t laugh or joke about with my friends anymore, because when I do I get cataplexies and collapse,” she said in an interview at her home in the Swedish capital.

Narcolepsy is estimated to affect between 200 and 500 people per million and is a lifelong condition. It has no known cure and scientists don’t really know what causes it. But they do know patients have a deficit of a brain neurotransmitter called orexin, also known as hypocretin, which regulates wakefulness.

Research has found that some people are born with a variant in a gene known as HLA that means they have low hypocretin, making them more susceptible to narcolepsy. Around 25 percent of Europeans are thought to have this genetic vulnerability.

When results of Emelie’s hypocretin test came back in November last year, it showed she had 15 percent of the normal amount, typical of heavy narcolepsy with cataplexy.

The seriousness of her strange new illness has forced her to contemplate life far more than many other young teens: “In the beginning I didn’t really want to live any more, but now I have learned to handle things better,” she said.

TRIGGERS?

Scientists investigating these cases are looking in detail at Pandemrix’s adjuvant, called AS03, for clues.

Some suggest AS03, or maybe its boosting effect, or even the H1N1 flu itself, may have triggered the onset of narcolepsy in those who have the susceptible HLA gene variant.

Angus Nicoll, a flu expert at the European Centre for Disease Prevention and Control (ECDC), says genes may well play a part, but don’t tell the whole story.

“Yes, there’s a genetic predisposition to this condition, but that alone cannot explain these cases,” he said. “There was also something to do with receiving this specific vaccination. Whether it was the vaccine plus the genetic disposition alone or a third factor as well – like another infection – we simply do not know yet.”

GSK is funding a study in Canada, where its adjuvanted vaccine Arepanrix, similar to Pandemrix, was used during the 2009-2010 pandemic. The study won’t be completed until 2014, and some experts fear it may not shed much light since the vaccines were similar but not precisely the same.

It all leaves this investigation with far more questions than answers, and a lot more research ahead.

WAS IT WORTH IT?

In his glass-topped office building overlooking the Maria Magdalena church in Stockholm, Goran Stiernstedt, a doctor turned public health official, has spent many difficult hours going over what happened in his country during the swine flu pandemic, wondering if things should have been different.

“The big question is was it worth it? And retrospectively I have to say it was not,” he told Reuters in an interview.

Being a wealthy country, Sweden was at the front of the queue for pandemic vaccines. It got Pandemrix from GSK almost as soon as it was available, and a nationwide campaign got uptake of the vaccine to 59 percent, meaning around 5 million people got the shot.

Stiernstedt, director for health and social care at the Swedish Association of Local Authorities and Regions, helped coordinate the vaccination campaign across Sweden’s 21 regions.

The World Health Organization (WHO) says the 2009-2010 pandemic killed 18,500 people, although a study last year said that total might be up to 15 times higher.

While estimates vary, Stiernstedt says Sweden’s mass vaccination saved between 30 and 60 people from swine flu death. Yet since the pandemic ended, more than 200 cases of narcolepsy have been reported in Sweden.

With hindsight, this risk-benefit balance is unacceptable. “This is a medical tragedy,” he said. “Hundreds of young people have had their lives almost destroyed.”

PANDEMICS ARE EMERGENCIES

Yet the problem with risk-benefit analyses is that they often look radically different when the world is facing a pandemic with the potential to wipe out millions than they do when it has emerged relatively unscathed from one, like H1N1, which turned out to be much milder than first feared.

David Salisbury, the British government’s director of immunization, says “therein lies the risk, and the difficulty, of working in public health” when a viral emergency hits.

“In the event of a severe pandemic, the risk of death is far higher than the risk of narcolepsy,” he told Reuters. “If we spent longer developing and testing the vaccine on very large numbers of people and waited to see whether any of them developed narcolepsy, much of the population might be dead.”

Pandemrix was authorized by European drug regulators using a so-called “mock-up procedure” that allows a vaccine to be authorized ahead of a possible pandemic using another flu strain. In Pandemrix’s case, the substitute was H5N1 bird flu.

When the WHO declared a pandemic, GSK replaced the mock-up’s strain with the pandemic-causing H1N1 strain to form Pandemrix.

GSK says the final H1N1 version was tested in trials involving around 3,600 patients, including children, adolescents, adults and the elderly, before it was rolled out.

The ECDC’s Nicoll says early warning systems that give a more accurate analysis of a flu strain’s threat are the best way to minimize risks of this kind of tragedy happening in future.

Salisbury agrees, and says progress towards a universal flu vaccine – one that wouldn’t need last-minute changes made when a new strain emerged – would cuts risks further.

“Ideally, we would have a better vaccine that would work against all strains of influenza and we wouldn’t need to worry about this ever again,” he said. “But that’s a long way off.”

With scientists facing years of investigation and research, Emelie just wants to make the best of her life.

She reluctantly accepts that to do so, she needs a cocktail of drugs to try to control the narcolepsy symptoms. The stimulant Ritalin and the sleeping pill Sobril are prescribed for Emelie’s daytime sleepiness and night terrors. Then there’s Prozac to try to stabilize her and limit her cataplexies.

“That’s one of the things that makes me feel most uncomfortable,” she explains. “Before I got this condition I didn’t take any pills, and now I have to take lots – maybe for the rest of my life. It’s not good to take so many medicines, especially when you know they have side effects.”

(Reporting by Kate Kelland; Editing by Will Waterman)

http://news.yahoo.com/insight-evidence-grows-narcolepsy-gsk-swine-flu-shot-070212916–finance.html

 

Swine flu vaccine linked to child narcolepsy: EU Confirmation

By Agence France-Presse Saturday, September 22, 2012 1:15 EDT

vaccine.istock

A swine flu vaccine used in 2009-10 is linked to a higher risk of the sleeping disorder narcolepsy in children and teens in Sweden and Finland, the European Centre for Disease Prevention and Control said Friday.

The EU agency studied the effects of the Pandemrix vaccine on children in eight European countries after Sweden and Finland reported higher incidences of narcolepsy among children who were inoculated with the vaccine during the swine flu pandemic in 2009 and 2010.

“The case-control study found an association between vaccination with Pandemrix and an increased risk of narcolepsy in children and adolescents (five to 19 years of age) in Sweden and Finland,” the ECDC said.

“The overall number of new cases of narcolepsy being reported after September 2009 was much higher in Sweden and Finland … compared with the other countries participating in the study,” it said.

In the six other countries — Britain, Denmark, France, Italy, The Netherlands and Norway — no link was found based on a strict statistical analysis, which tried to address media bias.

However, other confirmatory analyses did identify an increased risk, the report said.

The report included several recommendations for further study to try to distinguish between true vaccine effects and media attention.

An ECDC spokesman said that while the study did not quantify the increased risk compared with non-vaccination, national studies showed the risk of developing narcolepsy after taking Pandemrix, which is produced by British drug company GlaxoSmithKline, was around one in 20,000 for children and adolescents.

Narcolepsy is a chronic nervous system disorder that causes excessive drowsiness, often causing people to fall asleep uncontrollably, and in more severe cases to suffer hallucinations or paralysing physical collapses called cataplexy.

In Finland, 79 children aged four to 19 developed narcolepsy after receiving the Pandemrix vaccine in 2009 and 2010, while in Sweden the number was close to 200, according to figures in the two countries.

Both countries recommended their populations, of around five and 10 million respectively, to take part in mass vaccinations during the swine flu scare. Pandemrix was the only vaccine used in both countries.

Meanwhile, a recent study in the medical journal The Lancet said that between five and 17 people in Finland aged 0-17 are estimated to have died as a direct result of the 2009-10 swine flu pandemic, while the same number for Sweden was nine to 31.

In the past year, the Finnish and Swedish governments have both agreed to provide financial compensation for the affected children after their own national research showed a link between the inoculation and narcolepsy

Department defends indemnity deal with producers of swine flu vaccine

The Irish Times – Friday, April 20, 2012

THE DEPARTMENT of Health has defended its decision to sign an indemnity deal with the producers of a swine flu vaccine that is associated with an increase in the rate of sleeping disorders among children.

A report commissioned by the department and published yesterday concluded that an increase in narcolepsy among young people since 2009 is associated with the vaccine Pandemrix.

Narcolepsy is a disorder typically characterised by excessive sleepiness, sudden loss of muscle tone and hallucinations.

It found the risk of narcolepsy was 13 times higher among children and adolescents who received the vaccine than those who hadn’t.

At least 24 young people who received the vaccine in Ireland have received a diagnosis of narcolepsy. However, authorities are aware of other potential cases which have yet to be confirmed.

The young people affected range from five to 19 years old and all received the Pandemrix swine flu vaccine. Among those affected are students due to sit State exams such as the Junior and Leaving Certificate this year.

In all, health authorities administered more than 900,000 doses of this vaccine in 2009 and 2010.

The use of Pandemrix is no longer recommended in Ireland and GPs have been advised to return any remaining stocks. This year’s seasonal flu vaccine does not contain Pandemrix.

At a press conference yesterday, the department’s chief medical officer Dr Tony Holohan said he regretted the fact that some young people had developed a disorder associated with the vaccine.

However, he said the decision to push ahead with a mass vaccination campaign as the “right decision at the time” and it had helped to lessen the effects of the swine flu pandemic which was responsible for the deaths of 30 people.

Dr Holohan said the Government, along with other jurisdictions, had no option but to sign an indemnity deal in order to get access to sufficient quantities of the vaccine.

He said the Health Service Executive and other State agencies were working to meet the needs of children.

On the issue of compensation, he said the Minister for Health was drawing up proposals for Cabinet for the further support of those affected, but would not comment further on the issue.

A campaign group established by families of children affected by the disorder, meanwhile, expressed frustration yesterday at the speed of the State’s response to their children’s needs.

Sufferers of Unique Narcolepsy Disorder represents about 35 children it believes have been affected in Ireland. The group’s chair, Mary Fitzpatrick, called on the Government to follow the Finnish government’s moves to compensate children and meet their ongoing needs.

Adjuvanted flu vaccine associated with child narcolepsy in Finland

A sudden increase in narcolepsy in Finnish children at the beginning of 2010 was likely related to the Pandemrix vaccine used in response to the H1N1 2009 flu pandemic, according to two reports published Mar. 28 in the open access journal PLoS ONE.

The authors of the studies, led by Markku Partinen of the Helsinki Sleep Clinic and Hanna Nohynek of the National Institute for Health and Welfare in Finland, found that the average annual incidence of narcolepsy between 2002 and 2009 among children younger than 17 was 0.31 per 100,000, and in 2010, this incidence was about 17 times higher, at 5.3 cases per 100,000. In contrast, the incidence rate for adults over 20 was essentially unchanged over that same time period.

To further evaluate the potential connection between the vaccine and narcolepsy, the researchers collected vaccination and childhood narcolepsy data for children born between January 1991 and December 2005.

They found that the narcolepsy incidence for vaccinated individuals within this age group was 9.0 per 100,000 people, as compared to just 0.7 per 100,000 for unvaccinated individuals – almost 13 times lower.

Together, these results provide compelling evidence that the Pandemrix vaccine, used in 2009 and 2010 in association with the H1N1 flu pandemic, contributed to narcolepsy in patients between the age of 4 and 19 in Finland, the authors conclude.