# 6971
Pandemrix was the adjuvanted pandemic H1N1 flu shot developed by GlaxoSmithKline (GSK) and distributed to more than 30 countries beginning in the fall of 2009. This vaccine included a squalene-based component called AS03, used as a adjuvant.
Adjuvants are additives that are used to increase the immune response to a vaccine. Their use can allow the `stretching’ of the vaccine supply, as shots can contain a smaller amount of antigens.
While they have been used in Europe and in Canada, adjuvanted flu vaccines have not been licensed for use in the United States.
Roughly a year after the vaccine was deployed, we began to see reports of an unusual rise in the number of children in Finland (a country where Pandemrix was used) diagnosed with a rare neurological disorder called narcolepsy.
For early coverage of this story, you may wish to revisit Finland Suspends Use of Pandemrix Vaccine and EMA To Review Pandemrix Vaccine, both of which I wrote in August of 2010.
Despite some conflicting and incomplete data the European Medicines Agency issued a statement in July of 2011 recommending:
In persons under 20 years of age Pandemrix to be used only in the absence of seasonal trivalent influenza vaccines, following link to very rare cases of narcolepsy in young people.
Finland also convened a Narcolepsy Task Force (see Finland: Task Force Report On Pandemrix-Narcolepsy Link) that confirmed an association – as yet unexplained – between receipt of the vaccine and an increase in narcolepsy in children between the ages of 4 and 19.
In September of 2012, the ECDC released a 164 page technical report called Narcolepsy In Association With Pandemic Influenza Vaccination in which the summary found:
The case–control study confirms an association between vaccination with Pandemrix® and an increased risk of narcolepsy in children and adolescents (5 to 19 years of age) in Sweden and Finland that originally reported on this issue (signalling countries). No such association was found in adults in these two countries.
Fast forward to yesterday, and we have a press release from the HPA on a study – just published in the BMJ - that has also found a link between the Pandemrix vaccine and childhood narcolepsy in the UK.
First a link to the study, then some excerpts from the HPA release.
Risk of narcolepsy in children and young people receiving AS03 adjuvanted pandemic A/H1N1 2009 influenza vaccine: retrospective analysis
BMJ 2013; 346 doi: http://dx.doi.org/10.1136/bmj.f794 (Published 26 February 2013)
Cite this as: BMJ 2013;346:f794
Conclusion 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 unproven, the authors raise the possibility that the adjuvanted vaccine – rather than directly causing narcolepsy – might have accelerated the process in children who would eventually have gone on to develop the disorder.
A significant dip in the `background rate’ of narcolepsy over the next few years in countries that saw a spike after 2009 ASO3 vaccination would help give this theory more weight.
A paucity of safety trials on children, and the public’s memories of the 1976 Swine Flu vaccine debacle, led the HHS to decide not to allow adjuvants in the pandemic flu vaccines deployed in the United States, despite urging by the global community.
The HPA has put together the following summary.
Pandemic flu vaccination linked to narcolepsy in UK children
27 February 2013
Health Protection Agency (HPA) scientists have found evidence of an association between Pandemrix flu vaccination and narcolepsy in children in England, according to the findings of a study published in the British Medical Journal. These findings are consistent with previous studies from Finland and Sweden which identified a similar association.
In collaboration with researchers from Papworth and Addenbrooke’s hospitals in Cambridge, the study looked at 75 children aged between four and 18 who were diagnosed with narcolepsy from January 2008 and who attended sleep centres across England. Eleven of these children had been vaccinated with Pandemrix before their symptoms began, seven of these within six months. This suggests a risk of narcolepsy following vaccination with Pandemrix of around one in every 55,000 doses of the vaccine.
The Pandemrix vaccine was recommended for use in children at risk of serious complications from influenza during the pandemic flu outbreak in 2009/10. It was also used occasionally in children during the 2010/11 flu season. Since July 2011 the use of Pandemrix in people under the age of 20 across Europe has been restricted.
Although prior to this study, there was no evidence to suggest an association in the UK, on the basis of the findings from Finland the HPA launched an in depth study in February 2011 with narcolepsy experts across England. This investigated whether there was evidence of an association between narcolepsy and Pandemrix as used in the UK.
Lead author Professor Liz Miller, a consultant epidemiologist with the HPA, said: "These findings suggest there is an increased risk in children of narcolepsy after Pandemrix vaccination and this is consistent with findings from studies in other European countries. However, this risk may be overestimated by more rapid referral of vaccinated cases. Long term follow up of people exposed to Pandemrix is needed before we can fully establish the extent of the association.
“Our findings have implications for the future licensing and use of adjuvanted pandemic vaccines. Further studies to assess the possible risk associated with other 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.”
Study co-author Dr John Shneerson, consultant physician from the Respiratory Support and Sleep Centre at Papworth Hospital in Cambridge, said: “Narcolepsy is thought to be due to a loss of function of a small group of cells in one of the sleep centres in the brain, as a result of an abnormal reaction of the body’s immune system. Pandemrix may have triggered an immune reaction against the sleep centre cells in those children who were genetically predisposed to develop narcolepsy. This study has been important in helping to shed light on the mechanism of how narcolepsy can develop.”
Narcolepsy is a chronic neurological disorder caused by the brain's inability to control sleep, particularly REM (dream) sleep. It leads to excessive daytime sleepiness usually accompanied by sudden episodes of muscle weakness triggered by strong emotions such as laughter – this is known as cataplexy. Narcolepsy has a genetic component but this has to be triggered by other factors in order for the condition to appear. 20,000 people in the UK are through to have narcolepsy - drug treatment and lifestyle measures are usually effective in relieving the symptoms.
Ends
The exact mechanism behind this Pandemrix-Narcolepsy link remains a medical mystery. Our understanding of this neurological disorder is very limited, as well.
The absolute risk of a child developing narcolepsy from the Pandemrix flu shot appears appears to be about 1 in 55,000. The authors warn that:
`Our findings have implications for the future licensing and use of adjuvanted pandemic vaccines’.
While a handful of countries had reported increases in post-vaccination narcolepsy, the link between the AS03 adjuvanted vaccine and childhood narcolepsy in the UK has not, until now, been quantified.
This study found the increased risk was similar to that previously reported from Finland.
