* At least 14-fold increased narcolepsy risk after Pandemrix
* Boosted vaccine may have triggered adverse immune response
* GlaxoSmithKline says determined to understand more
* Drugmaker has reports of almost 800 cases across Europe
By Kate Kelland
LONDON, Feb 27 (Reuters) - GlaxoSmithKline's Pandemrix swine flu vaccine has been linked to cases of the raresleep disorder narcolepsy in children in a scientific study inEngland that confirms similar findings elsewhere in Europe.
The vaccine, more than 30 million doses of which were givenduring the H1N1 flu pandemic in 2009-2010, contains a booster,or adjuvant, and may have triggered an adverse immune reactionin some children at higher genetic risk of narcolepsy,scientists said in new research published on Wednesday.
Researchers at Britain's Health Protection Agency (HPA) whopublished the study in the British Medical Journal said the atleast 14-fold increased risk they found had "implications forthe future licensing and use of adjuvanted pandemic vaccines".
Narcolepsy is a life-long disorder and thought to be anautoimmune disease in which patient's immune system attacks thebody's own cells. Its symptoms include frequent bouts of daytimesleepiness and in its severe forms it also causes night terrors,hallucinations and cataplexies - when strong emotions trigger asudden loss of muscle strength.
Studies in Finland, Sweden and Ireland have also found aPandemrix link to narcolepsy, and GSK says more than 800 caseslinked to the shot have been reported in Europe.
A spokesman for the British drugmaker told Reuters onWednesday: "We really want to get to the bottom of this andunderstand more about the potential role of Pandemrix in thedevelopment of narcolepsy."
He added, however, that GSK believes "the available data areinsufficient to assess the likelihood of a causal associationbetween Pandemrix and narcolepsy."
As Reuters reported earlier this month, scientistsinvestigating the link further are homing in on the vaccine'sadjuvant, a booster called AS03, and analysing whether itssuper-charging effect may have played a role.
According to the UK results, vaccination with Pandemrix atany time was associated with a 14-fold increased risk ofnarcolepsy, whereas vaccination within six months before onsetof the disease was associated with a 16-fold increased risk.
"The increased risk of narcolepsy indicates a causalassociation," said the research team led by Liz Miller, aconsultant epidemiologist with the HPA. They added, however,that because of variable delay in diagnosis, the risk may beoverestimated because vaccinated children may have been referredto specialist sleep clinics more rapidly.
Scientists said the risk translated into around one in50,000, lower than studies have found in other countries such asFinland and Sweden where Pandemrix was used more widely and therisk was around one in 16,000 to 17,000 children vaccinated.
In total, more than 30 million doses of the GSK shot weregiven in 47 mainly European countries during the H1N1 flupandemic. It was not used in the United States.
The UK study looked at 75 children aged between four and 18who were diagnosed with narcolepsy from January 2008 and whoattended sleep centres across England. Eleven of the childrenhad been vaccinated with Pandemrix before their symptoms began.
Finn stressed that Pandemrix is the only vaccine linked tothis problem: "There is nothing to suggest that it occurs afterother flu vaccines or vaccines against other diseases."
Narcolepsy is thought to be due to loss of function in cellscalled hypocretin cells in one of the brain's sleep centres.
John Shneerson, a consultant physician from the RespiratorySupport and Sleep Centre at Papworth Hospital in Cambridge whoco-led the UK study, said Pandemrix may have triggered an immunereaction against those cells, causing narcolepsy in somechildren who were genetically vulnerable.
Experts say around 25 percent of Europeans have a geneticprofile making them more susceptible. Narcolepsy has no knowncure, but specialist doctors say symptoms can be treated withdrug combinations aimed at re-regulating the sleep-wake cycle.
Glaxosmithkline (GSK)