Sunday, May 20, 2018

J.I.D.: Population Serologic Immunity To H2N2 For Pandemic Risk Assessment


While we watch H7N9 and an assortment of avian H5 viruses for signs of developing pandemic capabilities, the known history of influenza pandemics going back more than 125 years is of a repeating pattern of H1, H2, and H3 viruses;  H2, H3, H1, H2, H3, H1 . . . .
Meaning - if that pattern were to persist - we should be looking for an H2 virus as our next pandemic contender.
Patterns - particularly short term patterns (and 130 years of influenza history qualifies as `short term') - tend to deceive, and there are also a number of non-influenza pandemic contenders (MERS, SARS, etc.) in the wings.  
So I wouldn't bet the farm on any one pathogen winning the pandemic sweepstakes.
But H2 influenza does remain in the back of a lot of researcher's heads as a likely candidate.  H2 appears to have produced a pandemic in the early to mid  1890s, and returned again in 1957 - roughly 60 years later.

Similarly, H3 viruses unleashed two pandemics (1900 and 1968) roughly 68 years apart, while H1N1 causing the great 1918 pandemic only to return in the pseudo-pandemic of 1977, 59 years later.

We are now 60 years since H2N2 last emerged as a pandemic strain.  It disappeared from the human population 11 years later (1968), and so anyone born after that has never been exposed to it.

But, as 2009's H1N1 pandemic showed us, previous exposure to an H1N1 virus didn't guarantee immunity, and so those of us over 50 could easily be affected as well.
Add in enough antigenic drift, and any acquired immunity can be overrun.
H2N2 (and other H2 subtypes) have continued to be reported in the wild - in both swine and wild birds - making its return, if not assured, at least possible.

In 2011, after the furor over the 2009 H1N1 pandemic had finally died down, some researchers suggested it might make sense to add an H2N2 component to the seasonal vaccine to head off the `next' pandemic (see Nature: A Preemptive H2N2 Vaccine Strike?).
While it sparked some academic discussions, this controversial proposal never went anywhere, the consensus being it was impossible to pick the `next' pandemic subtype with any confidence. 
In 2012, in H2N2: What Went Around, Could Come Around Again, we looked at a study conducted by scientists working at St. Jude Children's Research Hospital - published in the Journal of Virology - that concluded that H2N2 could well pose a threat to humanity once again.
A press release on this research warned:
1950s pandemic influenza virus remains a health threat, particularly to those under 50
St. Jude Children's Research Hospital scientists report that avian H2N2 influenza A viruses related to 1957-1958 pandemic infect human cells and spread among ferrets; may aid identification of emerging threats.
In 2015, we saw (so far, failed) predictions from Russian virologist Vladimir Blinov (see When H2N2 Predictions Go Viral) that H2N2 would return in 2017 as a pandemic strain.

Also in 2015, we saw a study published in The Journal Of Veterinary Medical Science, which detailed the finding of H2N2 in Siberian Muskrats (see H2N2: Everything Old Is Flu Again), perhaps sparking concerns over its return in Russia's virological circles. 
Should H2N2 re-emerge, it would find a largely susceptible global population, with some countries - particularly in the developing world, where populations run much younger - at even greater risk.
Providing us with a snapshot of the likely immunity (or lack, thereof) to H2N2 in the United States and Hong Kong, we have a new study published in the Journal of Infectious Diseases which finds the remaining vestiges of community immunity insufficient to block the pandemic spread of the virus.

First the link and abstract, after which I'll return with a postscript.

Population Serologic Immunity to human and avian H2N2 viruses in the United States and Hong Kong for Pandemic Risk Assessment
T M Babu R Perera J T Wu T Fitzgerald C Nolan B J Cowling S Krauss J T Treanor M Peiris

The Journal of Infectious Diseases, jiy291,

Published: 12 May 2018

Influenza A pandemics cause significant mortality and morbidity. H2N2 viruses have caused prior pandemic, and are circulating in avian reservoirs. The age-related frequency of current population immunity to H2 viruses was evaluated.


Hemagglutinin inhibition (HAI) assays against historical human and recent avian influenza A (H2N2) viruses were performed across age groups in Rochester, NY and Hong Kong, China. The impact of existing cross-reactive HAI immunity on the effective reproductive number(R) was modeled.


150 individual sera from Rochester and 295 from Hong Kong were included. 85% born in Rochester and Hong Kong before 1968 had HAI titers >1:40 against A/Singapore/1/57, and over 50% had titers >1:40 against A/Berkeley/1/68.
The frequency of titers ≥1:40 to avian H2N2 A/Mallard/England/727/06 and A/Mallard/Netherlands/14/07 in subjects born before 1957 was 62% and 24%.

There were no H2 HAI titers >1:40 in individuals born after 1968. These levels of seroprevalence reduce the initial R of A/Singapore/1/1957 or A/Berkeley/1/68 by 15%-20%. A basic reproductive number (R0) of the emerging transmissible virus less than 1.2 predicts a preventable pandemic.

Population immunity to H2 viruses is insufficient to block epidemic spread of H2 virus. An H2N2 pandemic would have lower impact in those born before 1968.

In 1977, a year after the feared H1N1 `swine flu' pandemic failed to materialize (see my account Deja Flu, All Over Again),  H1N1 did return after a 20 year absence, in what was dubbed the `Russian Flu' (suspected to have escaped from a Russian or Chinese lab). 
Those under 20 we're hardest hit. I was luckily 23 at the time.
As a young paramedic, it was my first `epidemic experience', and while far from a pandemic, it did slam local hospitals hard, force some ER closures, hospitals ran out of bed, and we dealt with constant ambulance diversions.
While the impact was limited and most patients recovered, in some people’s books 1977 qualifies as a `pseudo-pandemic’ year . . . at least for kids. 
H2N2 has lain dormant for far longer, and those born after 1968 appear to have little or no immunity to the influenza viruses that circulated in the mid and early 1960s.

Credit CIA World Fact Book

With the median global age just over 30, and nearly 80% of the world's population under the age of 50, should H2N2 return, it would likely find few immunological impediments to its spread.

While H7N9 or H5N6 might produce a much higher mortality rate, H2N2 has a long track record of successfully sparking pandemics, making it a virus we definitely want to watch.

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