Evidence grows for narcolepsy link to GSK swine flu shot

Insight: Evidence grows for narcolepsy link to GSK swine flu shot



By Kate Kelland, Health and Science Correspondent

STOCKHOLM |
Tue Jan 22, 2013 7:26am EST

(Reuters) - Emelie Olsson 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 any more, 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 Organisation (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."
Source:-
http://www.reuters.com/article/2013/01/22/us-narcolepsy-vaccine-pandemrix-idUSBRE90L07H20130122