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By Kate Kelland, Health and Science Correspondent
STOCKHOLM, Jan 22 (Reuters) - Emelie Olsson is plagued byhallucinations and nightmares. When she wakes up, she's oftenparalysed, unable to breathe properly or call for help. Duringthe day she can barely stay awake, and often misses school orhaving fun with friends. She is only 14, but at times she haswondered if her life is worth living.
Emelie is one of around 800 children in Sweden and elsewherein Europe who developed narcolepsy, an incurable sleep disorder,after being immunised with the Pandemrix H1N1 swine flu vaccinemade by British drugmaker GlaxoSmithKline in 2009.
Finland, Norway, Ireland and France have seen spikes innarcolepsy cases, too, and people familiar with the results of asoon-to-be-published study in Britain have told Reuters it willshow a similar pattern in children there.
Their fate, coping with an illness that all but destroysnormal life, is developing into what the health official whocoordinated Sweden's vaccination campaign calls a "medicaltragedy" that will demand rising scientific and medicalattention.
Europe's drugs regulator has ruled Pandemrix should nolonger be used in people aged under 20. The chief medicalofficer at GSK's vaccines division, Norman Begg, says his firmviews the issue extremely seriously and is "absolutely committedto getting to the bottom of this", but adds there is not yetenough data or evidence to suggest a causal link.
Others - including Emmanuel Mignot, one of the world'sleading experts on narcolepsy, who is being funded by GSK toinvestigate further - agree more research is needed but say theevidence is already clearly pointing in one direction.
"There's no doubt in my mind whatsoever that Pandemrixincreased the occurrence of narcolepsy onset in children in somecountries - and probably in most countries," says Mignot, aspecialist in the sleep disorder at Stanford University in theUnited States.
30 MILLION RECEIVED PANDEMRIX
In total, the GSK shot was given to more than 30 millionpeople in 47 countries during the 2009-2010 H1N1 swine flupandemic. Because it contains an adjuvant, or booster, it wasnot used in the United States because drug regulators there arewary of adjuvanted vaccines.
GSK says 795 people across Europe have reported developingnarcolepsy since the vaccine's use began in 2009.
Questions about how the narcolepsy cases are linked toPandemrix, what the triggers and biological mechanisms mighthave been, and whether there might be a genetic susceptibilityare currently the subject of deep scientific investigation.
But experts on all sides are wary. Rare adverse reactionscan swiftly develop into "vaccine scares" that spiral out ofproportion and cast what one of Europe's top flu experts calls a"long shadow" over public confidence in vaccines that controlpotential killers like measles and polio.
"No-one wants to be the next Wakefield," said Mignot,referring to the now discredited British doctor Andrew Wakefieldwho sparked a decades-long backlash against the measles, mumpsand rubella (MMR) shot with false claims of links to autism.
With the narcolepsy studies, there is no suggestion that thefindings are the work of one rogue doctor.
Independent teams of scientists have published peer-reviewedstudies from Sweden, Finland and Ireland showing the risk ofdeveloping narcolepsy after the 2009-2010 immunisation campaignwas between seven and 13 times higher for children who hadPandemrix than for their unvaccinated peers.
"We really do want to get to the bottom of this. It's not inanyone's interests if there is a safety issue that needs to beaddressed," said GSK's Begg.
LIFE CHANGED
Emelie's parents, Charles and Marie Olsson, say she was atop student who loved playing the piano, taking tennis lessons,creating art and having fun with friends. But her life startedto change in early 2010, a few months after she had Pandemrix.In the spring of 2010, they noticed she was often tired, needingto sleep when she came home from school.
But it wasn't until May, when she began collapsing atschool, that it became clear something serious was happening.
As well as the life-limiting bouts of daytime sleepiness,narcolepsy brings nightmares, hallucinations, sleep paralysisand episodes of cataplexy - when strong emotions trigger asudden and dramatic loss of muscle strength.
In Emelie's case, having fun is the emotional trigger. "Ican't laugh or joke about with my friends any more, because whenI do I get cataplexies and collapse," she said in an interviewat her home in the Swedish capital.
Narcolepsy is estimated to affect between 200 and 500 peopleper million and is a lifelong condition. It has no known cureand scientists don't really know what causes it. But they doknow patients have a deficit of a brain neurotransmitter calledorexin, also known as hypocretin, which regulates wakefulness.
Research has found that some people are born with a variantin a gene known as HLA that means they have low hypocretin,making them more susceptible to narcolepsy. Around 25 percent ofEuropeans are thought to have this genetic vulnerability.
When results of Emelie's hypocretin test came back inNovember last year, it showed she had 15 percent of the normalamount, typical of heavy narcolepsy with cataplexy.
The seriousness of her strange new illness has forced her tocontemplate life far more than many other young teens: "In thebeginning I didn't really want to live any more, but now I havelearned to handle things better," she said.
TRIGGERS?
Scientists investigating these cases are looking in detailat Pandemrix's adjuvant, called AS03, for clues.
Some suggest AS03, or maybe its boosting effect, or even theH1N1 flu itself, may have triggered the onset of narcolepsy inthose who have the susceptible HLA gene variant.
Angus Nicoll, a flu expert at the European Centre forDisease Prevention and Control (ECDC), says genes may well playa 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 wasalso something to do with receiving this specific vaccination.Whether it was the vaccine plus the genetic disposition alone ora third factor as well - like another infection - we simply donot know yet."
GSK is funding a study in Canada, where its adjuvantedvaccine Arepanrix, similar to Pandemrix, was used during the2009-2010 pandemic. The study won't be completed until 2014, andsome experts fear it may not shed much light since the vaccineswere similar but not precisely the same.
It all leaves this investigation with far more questionsthan answers, and a lot more research ahead.
WAS IT WORTH IT?
In his glass-topped office building overlooking the MariaMagdalena church in Stockholm, Goran Stiernstedt, a doctorturned public health official, has spent many difficult hoursgoing over what happened in his country during the swine flupandemic, wondering if things should have been different.
"The big question is was it worth it? And retrospectively Ihave to say it was not," he told Reuters in an interview.
Being a wealthy country, Sweden was at the front of thequeue for pandemic vaccines. It got Pandemrix from GSK almost assoon as it was available, and a nationwide campaign got uptakeof the vaccine to 59 percent, meaning around 5 million peoplegot the shot.
Stiernstedt, director for health and social care at theSwedish Association of Local Authorities and Regions, helpedcoordinate the vaccination campaign across Sweden's 21 regions.
The World Health Organisation (WHO) says the 2009-2010pandemic killed 18,500 people, although a study last year saidthat total might be up to 15 times higher.
While estimates vary, Stiernstedt says Sweden's massvaccination saved between 30 and 60 people from swine flu death.Yet since the pandemic ended, more than 200 cases of narcolepsyhave been reported in Sweden.
With hindsight, this risk-benefit balance is unacceptable. "This is a medical tragedy," he said. "Hundreds of young peoplehave had their lives almost destroyed."
PANDEMICS ARE EMERGENCIES
Yet the problem with risk-benefit analyses is that theyoften look radically different when the world is facing apandemic with the potential to wipe out millions than they dowhen 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 ofimmunisation, 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 farhigher than the risk of narcolepsy," he told Reuters. "If wespent longer developing and testing the vaccine on very largenumbers of people and waited to see whether any of themdeveloped narcolepsy, much of the population might be dead."
Pandemrix was authorised by European drug regulators using aso-called "mock-up procedure" that allows a vaccine to beauthorised ahead of a possible pandemic using another flustrain. In Pandemrix's case, the substitute was H5N1 bird flu.
When the WHO declared a pandemic, GSK replaced the mock-up'sstrain with the pandemic-causing H1N1 strain to form Pandemrix.
GSK says the final H1N1 version was tested in trialsinvolving 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 amore accurate analysis of a flu strain's threat are the best wayto minimise risks of this kind of tragedy happening in future.
Salisbury agrees, and says progress towards a universal fluvaccine - one that wouldn't need last-minute changes made when anew strain emerged - would cuts risks further.
"Ideally, we would have a better vaccine that would workagainst all strains of influenza and we wouldn't need to worryabout 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 cocktailof drugs to try to control the narcolepsy symptoms. Thestimulant Ritalin and the sleeping pill Sobril are prescribedfor Emelie's daytime sleepiness and night terrors. Then there'sProzac to try to stabilise her and limit her cataplexies.
"That's one of the things that makes me feel mostuncomfortable," she explains. "Before I got this condition Ididn't take any pills, and now I have to take lots - maybe forthe rest of my life. It's not good to take so many medicines,especially when you know they have side effects."
