mBio: Taubenberger et al. On the 1918 Spanish Flu

Credit CDC PHIL

 

 

# 6549

 

mBio, the American Society for Microbiology’s online, open access journal, has published a long and fascinating review this morning on what we’ve learned over the past 15 years about the 1918 H1N1 `Spanish Flu’ pandemic virus, written by some of the biggest experts in the field.

 

At this point, I’ll just step aside and invite you to read:

 

 

Reconstruction of the 1918 Influenza Virus: Unexpected Rewards from the Past

 

Jeffery K. Taubenberger, David Baltimore, Peter C. Doherty, Howard Markel, David M. Morens, Robert G. Webster and Ian A. Wilson

 

doi:10.1128/mBio.00201-12

 

Highly recommended.

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PNAS: Virulence & Transmissibility Of H1N2 Influenza Virus In Ferrets

 

 

 

# 6547

 

Timing is, as they say, everything.

 

And coming on the heels the announcement 10 days ago of three human infections with a swine-origin H1N2 influenza (see Minnesota Reports Swine H1N2v Flu), a study that appears today in PNAS is certainly well timed.

 

The study, conducted at Chungbuk National University South Korea examined viruses circulating in Korean swine (H1N2 & H3N2), and found - for the most part - they were not particularly pathogenic in ferrets.

 

The exception was a triple reassortant H1N2 virus dubbed Sw/1204, that had picked up two notable mutations, and it not only transmitted efficiently, it also caused severe (even fatal) disease in the test animals.

 

The study, is called:

 

Virulence and transmissibility of H1N2 influenza virus in ferrets imply the continuing threat of triple-reassortant swine viruses

Philippe Noriel Q. Pascua, Min-Suk Song, Jun Han Lee, Yun Hee Baek, Hyeok-il Kwon, Su-Jin Park, Eun Hye Choi, Gyo-Jin Lim, Ok-Jun Lee, Si-Wook Kim, Chul-Joong Kim, Moon Hee Sung, Myung Hee Kim, Sun-Woo Yoon, Elena A. Govorkova, Richard J. Webby, Robert G. Webster, and Young-Ki Choi

 

Ed Yong, writing for Nature has the details  on this paper:

 

Need for flu surveillance reiterated

Study of Korean pigs finds virus with pandemic potential.

Ed Yong 10 September 2012

 

 

One to the two mutations discussed in this paper is hemagglutinin (HA) (Asp-225-Gly) – also known as D225G – which is something we’ve looked at a number of times in the past.

 

This mutation involves a single amino acid change in the HA gene at position 225 (H3 numbering) from aspartic acid (D) or Asp to glycine (G), and was first linked to more severe pandemic flu by Norwegian Scientists in 2009.

 

The evidence for the D222G/N  amino acid substitution driving increased virulence, and deep lung infection, has been mixed, however. A few earlier blogs include:

 

Eurosurveillance: Debating The D222G/N Mutation In H1N1

Study: Receptor Binding Changes With H1N1 D222G Mutation

WER Review: D222G Mutation In H1N1

 

The second mutation, called NA-315 (serine to asparagine the in neuraminidase) isn’t as well studied, but is believed to assist the virus in breaking out of infected cells after replicating.

 

As Ed Yong mentions in his article - viruses often have multiple amino acid changes – and we are really just beginning to understand the ramifications of these different genetic combinations. 

 

Whether this particular virus ever ends up posing a public health threat is impossible to say, but it does illustrate these swine reassortant viruses aren’t always mild in mammals.

 

New strains of influenza come about from reassortment; the swapping of genetic material between two different flu strains in a common host. We tend to focus on swine, simply because they are highly susceptible to a variety of influenza viruses, and have a history of producing reassorted viruses.  

 

 

The pandemic virus that emerged in the spring of 2009 was the end product of several influenza strains that had kicked around the world’s swine population for many years, trading bits of genetic material back and forth, until they produced a version capable of jumping to humans.

 

But any host (human, swine, avian, or other mammal) could produce a reassorted virus.

 

For more on the flu risks from swine reassortments, I continue to heartily recommend Helen Branswell’s terrific piece in SciAm  from late 2010 called Flu Factories.

Flu Factories

The next pandemic virus may be circulating on U.S. pig farms, but health officials are struggling to see past the front gate

By Helen Branswell  | December 27, 2010 |

 

And for some of my earlier looks at swine influenza, you may wish to revisit:

 

H3N2v: When Pigs Flu

You Say You Want An Evolution?

The (Swine) Influenza Reassortment Puzzle

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Revisiting The H5N1 CFR Debate

 

 

Source – WHO as of 6/7/12

 

 

 

# 6401

 

One of the more contentious aspects of the H5N1 research debate of the past 8 months has been the argument over the `real’ CFR (Case Fatality Ratio) of the H5N1 virus in humans.

 

The `official’ number – a fatality rate of roughly 60% – is derived from the total known human infections by the virus (606 as of June 7th, 2012), and the total number of fatalities within that group (357)

 

Critics point out that only the sickest of the sick would end up in a testing environment, and that many mild cases would recover and never be counted.

 

The numbers, they maintain, are badly skewed.

 

Last February (see Science: Peter Palese On The CFR of H5N1) the journal Science published a meta-analysis by  Taia T. Wang,  Michael K. Parides &  Peter Palese, that argued that we are likely missing a great many H5N1 infections (perhaps millions), and that the virus is far less lethal than has been assumed in the past.

 

That argument was countered by CIDRAP director Michael T. Osterholm and Nick Kelley in an mBio  article, where they found little serological evidence to suggest that we are missing `millions’ of uncounted H5N1 infections (see mBio: Mammalian-Transmissible H5N1 Influenza: Facts and Perspective).

 

Today, we’ve a new response to the Palese meta-analysis appearing in the journal Science. One with a remarkable pedigree; attached you’ll find some of the biggest names in influenza research:

 

 

Comment on “Seroevidence for H5N1 Influenza Infections in Humans: Meta-Analysis”

Science 22 June 2012:
Vol. 336 no. 6088 p. 1506
DOI: 10.1126/science.1221434

Maria D. Van Kerkhove, Steven Riley,Marc Lipsitch, Yi Guan, Arnold S. Monto, Robert G. Webster, Maria Zambon, Angus Nicoll, J. S. Malik Peiris, Neil M. Ferguson

Abstract

A better understanding of the severity of H5N1 in humans is needed. Wang et al. (Brevia, 23 March 2012, p. 1463; published online 23 February 2012) over interpret the results of seroprevalence studies and take too little account of underlying uncertainties. Although the true risk of death from H5N1 infection will likely be lower than the 60% of reported laboratory-confirmed cases, there is little evidence of millions of missed infections.

 

Their entire rationale may be read here, and it strongly counters the assessment presented by Wang et al. in the original paper.

 

Dueling opinion pieces, regardless of the credentials of those involved, can’t really settle this argument. What we need are more, and better, seroprevalence studies in places where the H5N1 virus is endemic to come to any firm conclusions.

 

While most researchers accept that the 60% CFR number is probably far too high, as the authors of today’s article caution, in the absence of compelling data to the contrary:

 

“The precautionary principle dictates that we continue to assume that natural H5N1 infection in humans carries a high risk of death”

 

A policy I would certainly endorse.

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Robert Webster on The Bird Flu Threat

 

 

# 5848

 

 

I know Crof already posted excerpts last night, but the interview and bird flu backgrounder with Dr. Robert G. Webster that appeared yesterday in The Guardian is certainly worthy of further mention. 

 

Webster, as most of you know, is one of the world’s most acclaimed virologists, and is the head of the virology department of St Jude Children's Research Hospital in Memphis.

 

 

Robert Webster: 'We ignore bird flu at our peril'

With the UN issuing renewed warnings and a Hollywood disaster movie stoking our fears, bird flu is back in the news. We meet the man who first warned of a pandemic 50 years ago – and who is worried again now

 

Like many flu observers, Webster finds the evolution of the H5N1 virus in Egypt of particular concern.

 

Egypt has reported the greatest number of human infections over the past couple of years, and the virus has shown signs it may be slowly adapting more towards human physiology (see PLoS: Human-Type H5N1 Receptor Binding In Egypt).

 

While Webster’s greatest concern is with the H5N1 bird flu virus – mostly due to its high lethality - he acknowledges that other pandemic flu threats exist, and mentions the H9N2 avian virus which is widespread across much of Asia.

 

Earlier this summer (see PNAS: Reassortment Potential Of Avian H9N2) we looked at some of the ways that this avian virus could reassort into a more easily transmitted pathogen.

 

Last week, another virologist with impeccable credentials – Professor John Oxford, Scientific Director of Retroscreen Virology Ltd. and a Professor of Virology at St Bartholomew’s and the Royal London Hospital – expressed his own pandemic concerns in a online webinar (see Webinar: John Oxford On Pandemic Preparedness).

 

And 3 weeks ago, in Professor Peter Doherty On Bird Flu, we looked at his worries on the possibility that the H5N1 virus might one day swap genes (reassort) with the H1N1 virus and produce an easily transmitted, highly virulent flu strain.

 

And indeed, just last Friday we saw research (see Study: Reassorted H1N1-H5N1 Produced Virulent Strain) where a laboratory-created reassortant virus with genes taken from the H5N1 and H1N1 virus produced a highly transmissible and virulent strain.

 

Of course, while the world was waiting for bird flu, in 2009 a Swine flu virus unexpectedly sparked a global pandemic. We were fortunate that it wasn’t any more severe than it was, but it illustrates that there are many ways a pandemic can evolve.

 

 

 

Detections of  trH3N2 swine flu viruses in Pennsylvania and Indiana over the past month are a fresh reminder of the need for establishing better global surveillance of humans, and of farm animals, in order to detect the next emerging influenza virus before it can spread widely.

 

There is a chance, albeit it small, that a limited outbreak could be stopped if detected early enough. 

 

That was done successfully in Hong Kong in 1997 when the H5N1 virus first emerged.

 

While it is always possible that the next pandemic will spring directly from the wild, the odds favor that it will come from a farm – where large numbers of animals intermingle, swap viruses, and come in daily contact with humans.

 

For more on the reassortment potential of avian, swine, and human flu viruses, you can’t do better than  Helen Branswell’s excellent Scientific American article from last December called Flu Factories, or her SciAm Podcast interview.

 

And for good measure, a sampling of a few of my earlier blogs on reassortment:

 

Review: Evolution & Adaptation Of The 2009 pdmH1N1 Virus

You Say You Want An Evolution?

EID Journal: Co-Infection By Influenza Strains

EID Journal: Swine Flu Reassortants In Pigs

If You’ve Seen One Triple Reassortant Swine Flu Virus . . .

 

 

Although we could get lucky and go years - or even decades - before the next pandemic emerges, another one could just as easily start tomorrow.

 

As Dr. Webster points out, we ignore these risks at our own peril.

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The Hong Kong Flu Conference

 

 

 

# 4870

 

Robert Webster Warns of Complacency

 

 

Friday marked the beginning of a 5-day International Options For The Control of Influenza (VII) conference being held in Hong Kong.

 

Organized this year by such notables as Dr. Malik Peiris, Dr. Yi Guan, and Dr. Gavin Smith of the University of Hong Kong, the roster of speakers is a veritable who’s who in the world of influenza research.

 

Conference Program

 

During the first morning session attendees heard from such familiar names as Malik Peiris, York Chow, Kennedy Shortridge, Daniel Jernigan, Sherif Zaki and perhaps the most famous of all, Dr. Robert Webster.

 

Robert G. Webster is regarded as the father of influenza virology, having correctly posited 5 decades ago that human flu's are derived from avian flu strains.

 

Webster holds the Rose Marie Thomas Chair in Virology at St. Jude Children's Research Hospital, and is also a fellow of the Royal Society of London, the Royal Society of Medicine and the Royal Society of New Zealand, and a member of the National Academy of Sciences of the United States.

 

Now in his late-70s, Dr. Webster continues his research at St. Judes Research Hospital, which has been named one of  six Centers of Excellence for Influenza Research and Surveillance funded by the National Institute of Allergy and Infectious Diseases (NIAID), a part of the National Institutes of Health.

 

Today the Associated Press is carrying a story out of this influenza conference which includes some sideline comments from Dr. Webster and others. 

 

Expert warns of complacency after swine flu fizzle

By MIN LEE (AP)

 

In it Webster is quoted as saying, "We may think we can relax and influenza is no longer a problem. I want to assure you that that is not the case."

 

Webster also predicted that the next pandemic could easily arise from a virus that moves from waterfowl to swine, and then to humans.

 

A prime candidate he fears is H5N1 -  although he cautions that we can’t say when - or if – that might happen.

 

You’ll find other quotes from Webster, along with statements by Malik Peiris and the head of WHO’s global influenza program, Sylvie Briand on future pandemic threats, and on the pandemic just past.  

 

Follow the link to read the article in its entirety.

 

Hopefully the next few days will provide us with a stream of reports out of this conference.

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