Last year it was reported that there was a possible increase in narcolepsy, a sleep disorder characterized by excessive sleepiness, in children who had received the Pandemrix brand of H1N1 flu vaccine in Sweden, Finland, and Iceland. However a review of the data did not find a convincing connection, although concluded there was insufficient data at present and recommended further surveillance. A narcolepsy task force was formed in Finland, and now we have their preliminary report.
They conclude that the evidence suggests there is a connection:
Based on the preliminary analyses, the risk of falling ill with narcolepsy among those vaccinated in the 4-19 years age group was 9-fold in comparison to those unvaccinated in the same age group. This increase was most pronounced among those 5–15 years of age. No cases were observed among those under 4 years of age. Also, no increase in cases of narcolepsy or signs of vaccination impacting risk of falling ill with narcolepsy was observed among those above 19 years of age.
The World Health Organization (WHO) has reviewed these results and concluded:
WHO’s Global Advisory Committee on Vaccine Safety (GACVS) reviewed this data by telephone conference on 4 February 2011. GACVS agrees that further investigation is warranted concerning narcolepsy and vaccination against influenza (H1N1) 2009 with Pandemrix and other pandemic H1N1 vaccines. An increased risk of narcolepsy has not been observed in association with the use of any vaccines whether against influenza or other diseases in the past. Even at this stage, it does not appear that narcolepsy following vaccination against pandemic influenza is a general worldwide phenomenon and this complicates interpretation of the findings in Finland.
I agree with the WHO, who is basically saying that these results are intriguing, but are problematic and should be considered preliminary. They then follow with – more research is needed. Epidemiology is a complex endeavor, and there are lots of wrinkles to this data. The increased risk of narcolepsy was only seen within a certain age range. In Iceland (but not Sweden or Finland) the increase in narcolepsy was also seen in those who were not vaccinated. And further, other countries (47 in total) that also used the Pandemrix vaccine have seen no increase in narcolepsy, including Norway, the UK, Germany, and Canada.
Overall we have a very inconsistent pattern. The vaccine does not appear to be a consistent or unique risk factor for narcolepsy in these populations. The task force concludes from this that there must be another factor or factors that is combining with the vaccine to increase the risk. This is logically possible, but until this factor X is identified it remains speculation.
Narcolepsy is a neurological disorder characterized by excessive daytime sleepiness (narcoleptics sleep all night and all day), cataplexy (a tendency to lose muscle tone and collapse in response to stress), hypnagogia (hallucinations associated with a fusion of the dream state and the waking state, so-called waking dreams), and sleep paralysis (being paralyzed upon awaking from sleep). There is a strong genetic predisposition for narcolepsy. In fact it is only seen with a certain genetic type known as the (HLA) DQB1*0602 genotype.
All of the individuals who developed narcolepsy following the Pandemrix vaccine have the narcolepsy HLA type. Therefore there is the possibility that the vaccine only increases risk within this genetic populations, perhaps combined with other gene variants. Perhaps something else is also triggering the increase in Iceland, but not Finland and Sweden, to explain the rise in narcolepsy there in the unvaccinated.
Another possibility is that there is one or more confounding factors leading to the increase in narcolepsy, and the vaccines are a correlating but not causative factor.
Such is the nature of epidemiology, or observational studies. Variables are not controlled for and confounding factors are always a possibility. That does not mean that observational data is not useful or cannot be definitive – but it requires careful, thoughtful, and thorough collection and analysis of data from multiple different angles. The data we have so far from Finland is very preliminary, and generates more questions than answers. There is certainly sufficient cause for caution and further analysis. But at this point I would not be surprised by any particular outcome, since the data can be interpreted in many ways.
While there is an intriguing correlation between the Pandemrix vaccine and narcolepsy, this correlation is inconsistent – it is isolated to a few countries and to one age group and there is a rise in narcolepsy in Iceland not correlated to the vaccine. Further the cases identified so far are restricted to those with a known genetic predisposition to narcolepsy. This could mean that this population is susceptible to some factor in the vaccine, but it could also mean that they are susceptible to some other trigger, or perhaps were destined to get narcolepsy and the apparent increase in entirely an artifact of observation and reporting.
I agree with the WHO that this data should be considered preliminary – which means it is worthy of further monitoring and research, but we are not able to make any firm conclusions at this time. I would not be surprised if it turns out to be a real effect of the Pandemrix vaccine. Vaccines are not without risk, although over the decades the risks have proven to be very small and vastly outweighed by the benefits. Obviously it would be hugely useful to identify which ingredient was the culprit and exactly how it triggered narcolepsy in this population. But I would also not be surprised if this turns out to be entirely a red herring. Such is the nature of observational data.