Sunday, September 08, 2024

Because Shift Happens

Antigenic `Shift' or Reassortment 


#18,296

Influenza co-infections in humans - or in any other susceptible host (birds, pigs, cattle, etc.) - are a concern because - while rare - it can allow two (or more) influenza viruses to swap genetic material (reassort) producing a hybrid virus (see graphic at top of blog).

A novel pandemic virus might emerge solely from the wild, but an `easier' route would be for an avian or swine virus to reassort with an already `human-adapted' seasonal flu virus, producing a pandemic inducing hybrid. 

While most of these reassortments are evolutionary failures, twice in my lifetime (1957 & 1968) a reassortment between seasonal flu and an avian flu virus - likely in a human host - produced a pandemic virus. 
  • The first (1957) was H2N2, which According to the CDC `. . . was comprised of three different genes from an H2N2 virus that originated from an avian influenza A virus, including the H2 hemagglutinin and the N2 neuraminidase genes.'
  • In 1968 a novel H3N2 virus emerged (a reassortment of 2 genes from a low path avian influenza H3 virusand 6 genes from H2N2which supplanted H2N2 - killed more than a million people during its first year - and continues to spark yearly epidemics more than 50 years later.
Note: The 2009 H1N1 pandemic - although it was a triple-reassortment containing some avian-origin genetic contributions - emerged from swine. 

This is the reason why yearly flu vaccination is strongly recommended for people who raise pigs or work with poultry, and the CDC is now pushing for the vaccination in dairy workers

Occupational exposure to H5N1 has - at least in the United States - been the primary route of infection, but Friday's announcement of an unrelated case in Missouri is a reminder that past performance is no guarantee of future results. 

Only one outlier so far is encouraging, but an absence of evidence is not evidence of absence. Particularly when we see reports of sick dairy workers who go untested, and most states relying on voluntary testing of livestock.

Although it is possible that this Missouri infection was a singular event - miraculously picked up (albeit, belatedly) by limited  surveillance - past studies strongly suggest we would be lucky to detect 1 in 10 (or even 100) novel flu cases.  

  • During the opening weeks of China's H7N9 outbreak in 2013, in Lancet: Clinical Severity Of Human H7N9 Infection, we saw estimates that the number of `symptomatic' cases was likely anywhere between 10 and 200 times higher than reported.
  • A little over a year ago, we looked at a study from the UK HSA (see UK Novel Flu Surveillance: Quantifying TTD) that estimated the TTD (Time To Detect) a novel H5N1 virus in the community via passive surveillance could take weeks, and the virus might only be picked up after hundreds or possibly even thousands of infections.

While no one can say with any certainty what happens next with HPAI H5, one thing we can do as individuals to lower the chances of a bad outcome (both personally & for society as a whole) is to get the seasonal flu vaccine this fall. 

Granted, the seasonal flu shot is not expected to provide any protection against the H5N1 virus, but it can help reduce the chances of an individual being simultaneously infected with novel and seasonal flu.

It is admittedly not a perfect solution, since the seasonal flu shot is far better at preventing serious illness than preventing infection. But it is a readily available tool - and given that co-infection might produce more severe illness than seasonal flu alone - having the seasonal vaccine on board may lessen its impact. 

And while seasonal vaccine doesn't protect against avian H5N1, it is conceivable (but far from certain) that it might provide some degree of protection against an H5/Seasonal reassortment.  

There are plenty of other advantages to getting the seasonal flu vaccine, of course. A few past blogs include:

Nature: Severe Influenza in Pregnancy Linked to Neurodevelopmental Disorders in Offspring

Pediatrics: Maternal Flu Vaccination Extends Protection To Infants

PloS One: Early Risk of Acute Myocardial Infarction Following Hospitalization for Severe Influenza

CDC: Another Study Linking Severe Influenza To Heart Damage

Sometime the next 30 days I'll roll up my sleeve to get my 19th seasonal flu shot in as many years. In all of that time I've only caught the flu once (summer 2009), before the pandemic H1N1 vaccine was released. 

While I recognize it probably only provides my age group with 30%-40% protection, given the long list of things that can go wrong during or following flu infection, I'll take whatever advantage I can get.

And if, perchance, it prevents a pandemic-inducing reassortment with HPAI H5 (not that we'll ever know), so much the better.