Friday, November 25, 2011

Pseudo Pandemics And Viral Interlopers



# 5978



With the recent detections of a novel trH3N2 virus (see MMWR dispatch) among a handful of people across four states, today seems like a opportune time to look back at some viral contenders that threatened . . . but failed to produce a full blown pandemic.


Given that surveillance and testing methods have improved over the years, it is possible (perhaps even likely) that similar novel influenza viruses have briefly emerged in the past and simply gone undetected.





But interspersed between the pandemics of 1918, 1957, 1968 and 2009 we are aware of at least four other influenza strains that could have sparked a pandemic, but didn’t.


One was extremely mild and widespread, another extremely virulent but geographically limited and short lived, the third disappeared mysteriously, and the fourth affected mostly children and adolescents.



The first example comes from shortly after the end of WWII with what would become known as the `pseudo-pandemic’ or vaccine failure of 1947.


In 1943, the US military – fearing that crowded ships and barracks could give rise to a reprise of the 1918 pandemic – commissioned Dr. Thomas Francis of the University of Michigan and his protégé Jonas Salk to come up with a viable influenza vaccine.  


Within a year a vaccine based on the 1934 and 1943 flu strains was in wide use in the military, and for several years the Francis/Salk vaccine worked well. 


But in 1947, a new variant of the H1N1 virus appeared on military bases – first in Japan – and quickly spread from there infecting hundreds of millions around the globe (see 2002 PNAS article).


While it produced a generally mild illness, and few excess deaths, this new strain apparently had drifted enough antigenically to evade both the vaccine and community immunity acquired from earlier strains.


1947 is little remembered today, except for the lesson it taught us; that vaccines must be updated each year to take into account antigenic drift (or newly emerging flu strains).


Four years later, a far more ominous viral strain made an appearance on the global stage, during what was an otherwise mild and unremarkable 1950-51 flu season. 


This outbreak is commonly called the Liverpool Flu.


For about six weeks, a highly virulent influenza erupted in Liverpool, England and then spread across the UK and to Canada – that for a time was as deadly as the 1918 pandemic.




This startling graphic comes from the March 16th, 1951 Proceedings of The Royal Society of Medicinepage 19 – and shows in detail the tremendous spike in influenza deaths in early 1951 over the (admittedly, unusually mild) 1948 flu season. 


The CDC's EID Journal  has a stellar account of this 1951 event, and is very much worth reading.


Viboud C, Tam T, Fleming D, Miller MA, Simonsen L. 1951 influenza epidemic, England and Wales, Canada, and the United States. Emerg Infect Dis [serial on the Internet]. 2006 Apr [date cited].



This aberrant strain never spread much beyond the UK and eastern Canada, and died out as the flu season came to a close. Thankfully, it did not return the following year. 


What made it so virulent, and why it failed to return the following year, remains a medical mystery.


The 1957 and 1968 pandemics – while mild in comparison to the Spanish Flu of 1918 – followed.


In February of 1976, a young recruit at Ft. Dix, New Jersey fell ill and died within 24 hours. The virus went on to infect more than 200 soldiers and caused severe respiratory disease in 13 of them. It circulated on the base for nearly a month.


The virus was isolated and dubbed A/New Jersey/76 (Hsw1N1). How it arrived on the base was unknown. While the death rate was very low, this virus appeared to easily transmissible among humans.


And the fear was, it might develop a higher mortality rate as it mutated.


This led to the swine flu pandemic scare of 1976, which I chronicled several years ago in Deja Flu, All Over Again


The feared swine flu pandemic never materialized, and for reasons we cannot explain, the virus simply disappeared.


But a year later, we did see an epidemic, at least among children, with the return of the H1N1 virus after a 20 year absence.


The 1918 H1N1 virus, and its descendents, monopolized the world’s influenza scene for nearly 40 years until the H2N2 strain appeared in 1957, and replaced it. Another replacement occurred in 1968, when the H3N2 strain supplanted H2N2.


It appeared that in the normal scheme of things, only one major Influenza A strain could circulate at a time.


But that theory was turned on its head when, in 1977, H1N1 resurfaced. How and why it returned is a mystery, although many believe it was the result of an accidental release from a Russian or Chinese research laboratory (see Vince Racaniello’s  Origin of current influenza H1N1 virus).


It was dubbed the `Russian Flu’, and quickly spread among the under-20-somethings who had no immunity. 


But this time things were different. It didn’t replace or drive out the existing (H3N2) virus.


The two strains (H3N2 and H1N1) co-circulated, and since then having two main `A’ strains in circulation (along with some `B’ viruses) has become the norm.


The reason most commonly given is that older people were less affected by the returning H1N1 virus – since those born before 1957 had previous exposure – and so they remained a reservoir of the H3N2 virus.


The seasonal H1N1 virus was supplanted in 2009 by the arrival of the  pandemic H1N1 virus, which, while no longer a pandemic strain, co-circulates today with H3N2.


None of this tells us what will become of the trH3N2 virus we are currently watching, or any of the other novel strains that we’ve seen jump to humans over the past few years.


But it does provide some perspective.


It shows that new, emerging influenza viruses can appear - and even transmit efficiently among humans –and still fail to spark a global pandemic. These viral interlopers can sometimes simply run out of steam and die out, for no discernable reason. 


And even if one spreads globally – as we saw in 1947 – it can turn out to be exceedingly mild.


Of course, the opposite can be true. The pandemics of 1918, 1957, 1968, and 2009 show us that.


The bottom line is that influenza viruses are notoriously unpredictable. They certainly deserve our attention and respect.


Whether trH3N2 becomes a contender, or ends up a footnote in the history of influenza, is something we will have to wait to see.


But with a wide constellation of viruses out there, constantly evolving, looking for new hosts and an evolutionary advantage, the smart money is on being prepared.

Because, regardless of its source, pandemics happen.


It’s just a matter of time.