It is always flu season somewhere in the world. As Australia’s flu season comes to a close, we are getting ready for ours in the Northern Hemisphere. This is a good time to start thinking about getting the flu vaccine, and as always there is a lot of flu vaccine news to sort through.

Mark Crislip has already reviewed the evidence for the efficacy of the seasonal flu vaccine. Like most questions in medicine, the evidence is deceptively complex, and Mark does an excellent job of sorting through it, so I won’t repeat it here.

This year the H1N1 pandemic flu virus will be incorporated into the seasonal flu vaccine, so there will not be two separate vaccines as there was last year. H1N1 remains the dominant strain of seasonal flu, and as predicted the pandemic has simply been incorporated into the seasonal flu pattern.

Here are some updates on flu vaccine news – first the good news:

Flu Vaccine Efficacy

Two recent studies demonstrate the efficacy of the flu vaccine in improving outcomes. Mark Crislip discussed two weeks ago a recent study that shows that the flu vaccine (but not the pneumococcal vaccine) is associated with a decreased risk of heart attack. This makes sense as getting the flu can be a significant physiological strain and can plausibly provoke a heart attacks in those who are susceptible. This study emphasizes the importance of getting the seasonal flu vaccine early in the flu season.

Another recent study looked at the effect of maternal flu vaccination while pregnant and the subsequent risk of flu for their infant children. Angelia Eick et al studied 1169 mother-infant pairs among Navajo and White Mountain Apache Indian reservations and found that getting the seasonal flu vaccine while pregnant was associated with increase anti-flu antibodies up to 2-3 months old and a 41% reduction in the risk of flu in the first 6 months. This is important because young infants are generally not given the flu vaccine – they depend upon passive antibodies from the mother.

These two studies add to the body of evidence that clearly demonstrates that the flu vaccine is effective in preventing the flu and reducing morbidity. The media, however, also like to report about every flu vaccine side effect scare, whether legitimate or not.

H1N1 Vaccine and Narcolepsy

Over the summer it was reported that there were a cluster of cases of narcolepsy in Finland and Sweden. Narcolepsy is a sleep disorder characterized by excessive sleepiness. It is caused by a combination of genetics and environment, and can be triggered by infections with high fever. The appearance of narcolepsy in about a dozen children and adults was thought to perhaps be associated with the Pandemrix flu vaccine, and Finland promptly suspended use of this brand of flu vaccine. The possible association was widely reported – but the follow up investigation was not.

Sweden’s Medical Products Agency (MPA) investigated a possible association between narcolepsy and the flu vaccine, specifically Pandemrix, and found no association.

The agency’s report said six narcolepsy cases in Stockholm were in children, two of whom had not received the Pandemrix vaccine, according to the YLE report. Of 10 narcolepsy cases reported in adults, half had received the vaccine.

The CDC did their own review of the vaccine adverse events reporting system (VAERS) and found no pattern of reports that would be concerning for a link between vaccines and narcolepsy.

It is perfectly reasonable, as part of the precautionary principle, to take apparent clusters of diseases and investigate them to see if they are real or are just statistical clusterings (as Carl Sagan said – “randomness is clumpy”). It is also reasonable, and this happens often, to suspend use of a drug or medical product until a potential risk can be investigated. So there really was nothing unusual about the narcolepsy episode. Most apparent clusters like this turn out not to be real, and so it is no surprise that this was the case with narcolepsy.

The more difficult problem is the media response to these episodes. I would not say that such cases should not be reported, but rather that special care should be taken to put such reports into a reasonable context and to not prematurely and unnecessarily fear-monger. Further, when later investigations find that there was no risk, that should be given equal reporting – perhaps even more, as it is more difficult to quell fears than to stoke them. In addition, there is a subculture that is anti-science-based medicine, and also anti-vaccine. Such episode are exploited for propaganda purposes. It is likely that narcolepsy will now be added to the list of fears used against vaccines by such groups.

Flu Vaccine and Convulsions in Australia

Recently in Australia there has been a real cluster of fever and seizures in children who had received a particular brand of flu vaccine, the Fluvax. New Scientist reports:

Last week the Australian Department of Health and Ageing reported that flu vaccination was “causally related” to fever and convulsions in 99 Australian children this year. Of those, 74 had no other possible cause, and Fluvax had been given to all 66 of those where the vaccine’s name was known, CSL says it is trying to identify the problem.

Unlike the narcolepsy episode, this appears to be a real cluster, and the association with a particular brand of flu vaccine statistically solid. Fever with flu vaccine is a known risk, and in young children a high fever can sometimes trigger what is called a febrile seizure. Febrile seizures, while scary for the parents, are most often benign and to not result in any permanent damage or long term seizure risk. Rarely, however, there are neurological complications.

The baseline risk of febrile seizures from the flu vaccine is about 1.4 per 10,000 doses. This is much less than what would be expected from the flu itself, and so getting the vaccine actually decreases the risk of developing febrile seizures. The Fluvax, however, was associated with a 50 fold increase in risk of febrile seizures from that normally associated with the flu vaccine. Even with this increased risk there was still more statistical benefit than risk from this vaccine, especially since the H1N1 flu (which is included in this year’s seasonal vaccine) had such a high mortality rate (1% of those children admitted to the hospital with confirmed H1N1 flu in Australia died.

But of course this is an unacceptable side effect from the Fluvax, and since it is dramatically greater than other brands there must be something wrong with this particular batch. It is not yet known what that is. This is precisely the reason for careful post-marketing surveillance of drugs and vaccines – if unexpected side effects emerge then steps can be taken to quickly remove the offending agent from the market until the risks can be sorted out.

The same company that makes Fluvax, CSL, also makes a product for the Northern Hemisphere called Afluria. The CDC is recommending that this brand not be given to children under 5 years old, as other brands are also available. It is not known if Afluria carries the same increased risk as Fluvax, but again this is a reasonable application of the precautionary principle.

Conclusion

This latest evidence supports what is already known about the seasonal flu vaccine – it works, but it is not without risk. All medical interventions have risk and it is important to always consider risk vs benefit. When considered in this context, the evidence clearly shows that the benefit of receiving the flu vaccine far outweighs the small risk. The flu is a serious illness and preventing it carries significant benefit.