Sunday, April 08, 2012

EID Journal: Revisiting The `Canadian Problem’



Photo Credit PHIL

# 6267



In September of 2009, just as the second wave of the H1N1 pandemic was ramping up, news of an unpublished study began to surface in Canada that suggested that those who had received a seasonal flu shot the previous year were more susceptible to the new pandemic virus than those who hadn’t.


Helen Branswell, science and medical reporter for the Canadian Press, was among the first to report on it (see Branswell On The Canadian Flu Shot Controversy).



This bombshell – which began to be known as `the Canadian problem’, sent shockwaves through public health agencies, many of whom were just days away from starting up their seasonal flu vaccination campaigns as they waited for the arrival of the H1N1 pandemic vaccine expected later in the fall.


Suddenly, there was genuine concern that with a pandemic virus on the way, that rolling out the seasonal vaccine might be the wrong thing to do.


The CDC and the World Health Organization both scrambled to look at their available data, and stated that they could find no correlation between the seasonal vaccine and susceptibility to the pandemic flu . . . but that they would continue to look.


Meanwhile, with concerns rising, a number of Canadian Provinces halted or announced delays in their seasonal flu shot campaign, even though the study had yet to be published (see Ontario Adjusts Vaccination Plan).


October saw a number of new reports and studies that failed to corroborate the (still unpublished) findings, including a study published in the BMJ (British Medical Journal) that suggested exactly the opposite - that getting the seasonal flu vaccination may be slightly protective against the swine flu  (see When Studies Collide).


By November, with no compelling corroboration of the `Canadian Problem’, Canada’s National Advisory Committee on Immunization (NACI) came out in favor of resuming seasonal flu jabs (see NACI: Canada Should Resume Seasonal Flu Vaccinations).


The controversy wasn’t over, however.


In April of 2010 these Canadian studies were finally published by PLoS Medicine. Writing for CIDRAP, Maryn McKenna   detailed their findings.


New Canadian studies suggest seasonal flu shot increased H1N1 risk

Maryn McKenna * Contributing Writer

Apr 6, 2010 (CIDRAP News) – Despite a rapidly launched range of studies, investigators in Canada are still unable to say—or to rule out—whether receiving a seasonal flu vaccination in the 2008-09 season made it more likely that Canadians would become ill from 2009 pandemic H1N1 flu.

(Continue . . .)


Other studies, however, failed to show any correlation, leaving us with a bit of a mystery on our hands. 


Fast forward to today and we’ve another study that appears ahead of print in May’s edition of the CDC’s EID Journal that looks at this supposed link, and once again, finds no evidence to support it.



Volume 18, Number 5—May 2012

No Association between 2008–09 Influenza Vaccine and Influenza A(H1N1)pdm09 Virus Infection, Manitoba, Canada, 2009

Salaheddin M. Mahmud , Paul Van Caeseele, Gregory Hammond, Carol Kurbis, Tim Hilderman, and Lawrence Elliott


We conducted a population-based study in Manitoba, Canada, to investigate whether use of inactivated trivalent influenza vaccine (TIV) during the 2008–09 influenza season was associated with subsequent infection with influenza A(H1N1)pdm09 virus during the first wave of the 2009 pandemic.


Data were obtained from a provincewide population-based immunization registry and laboratory-based influenza surveillance system.


The test-negative case–control study included 831 case-patients with confirmed influenza A(H1N1)pdm09 virus infection and 2,479 controls, participants with test results negative for influenza A and B viruses. For the association of TIV receipt with influenza A(H1N1)pdm09 virus infection, the fully adjusted odds ratio was 1.0 (95% CI 0.7–1.4). Among case-patients, receipt of 2008–09 TIV was associated with a statistically nonsignificant 49% reduction in risk for hospitalization.


In agreement with study findings outside Canada, our study in Manitoba indicates that the 2008–09 TIV neither increased nor decreased the risk for infection with influenza A(H1N1)pdm09 virus.



While the bulk of studies have shown no causal link between receipt of the seasonal vaccine and contracting the 2009 H1N1 virus, the results have not been 100% in alignment.


Leaving us with a bit of a mystery.  Why should some Canadian studies differ from those done elsewhere?


One fascinating hypothesis that might explain these disparate findings was proffered back in 2010 in the journal Eurosurveillance.


The authors suggested that infection by any influenza (or perhaps, any I-L-I) ramps up the body’s immune system for a time, making that person temporarily less susceptible to infection by another respiratory virus.


Since the pandemic arrived on the heels of the flu season in the northern hemisphere, those who received flu shot in the fall and thereby avoided illness might have been more likely to catch the pandemic strain than someone who had endured a bout of flu (and thereby acquired temporary generic immunity) over the winter.


You’ll want to read the entire paper, but I’ve included excerpts (reparagraphed for readability) from the abstract below.



Eurosurveillance, Volume 15, Issue 47, 25 November 2010


Seasonal influenza vaccination and the risk of infection with pandemic influenza: a possible illustration of non-specific temporary immunity following infection

H Kelly , S Barry, K Laurie, G Mercer

ABSTRACT (Excerpts)

We found no evidence that seasonal influenza vaccine increased the risk of, or provided protection against, infection with the pandemic virus.


Ferret experiments have suggested protection against pandemic influenza A(H1N1) 2009 from multiple prior seasonal influenza infections but not from prior seasonal vaccination.Modelling studies suggest that influenza infection leads to heterosubtypic temporary immunity which is initially almost complete.


We suggest these observations together can explain the apparent discrepant findings in Canada and Victoria. In Victoria there was no recent prior circulation of seasonal influenza and thus no temporary immunity to pandemic influenza. There was no association of seasonal influenza vaccine with pandemic influenza infection.


In Canada seasonal influenza preceded circulation of the pandemic virus. An unvaccinated proportion of the population developed temporary immunity to pandemic influenza from seasonal infection but a proportion of vaccinated members of the population did not get seasonal infection and hence did not develop temporary immunity to pandemic influenza.


It may therefore have appeared as if seasonal vaccination increased the risk of infection with pandemic influenza A(H1N1) virus.



It’s an attractive theory, and it has been suggested that this form of temporary immunity might even help explain why influenza pandemics tend to come in waves.


But it’s just a theory.


While results from today’s EID study match well with most of those in the literature, the authors warn that:


Additional epidemiologic and experimental investigations are needed to clarify the relationship between TIV use and infection with the pandemic strain.


Good science takes time.


And that means that while the evidence is currently lopsided against there being a link, more research will be needed before the `Canadian Problem’ can be fully and truly resolved.

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