H5N1 facts, not fear

Peter Palese and Taia Wang have written a compelling article that uses scientific facts to address the controversy over publication of research involving transmission of avian influenza H5N1 in ferrets. In response to calls in the media to destroy the viruses, curtail the research, and protect the public from frightening research, they write that “fear needs to be put to rest with solid science and not speculation”.

The authors begin with the facts: they indicate that the object of ferret-to-ferret passage of avian H5N1 influenza virus was to determine whether sustainable aerosol transmission could be achieved in this animal model. The finding that transmission in ferrets is conferred by a small number of mutations emphasizes the need for continued surveillance of H5 viruses and development of vaccines and antivirals.

Are these studies relevant to humans?

Ferrets are quite susceptible to infection with influenza viruses. However, it is not clear that all virus strains that replicate in and transmit between ferrets necessarily do so in humans. Ferrets are also more likely than humans to have disseminated, multiorgan influenza disease including neurological sequelae….one cannot directly extrapolate from the data to make predictions about humans.

Under the heading ‘fear’, they address the heart of this controversy, the notion that the fatality rate for human H5 infections is greater than 50%:

…in order for a case to be confirmed by WHO, a person must have an acute, febrile respiratory illness with known H5 exposure in the 7 days preceding and have molecular confirmation of H5 infection by a WHO approved laboratory. This definition does not allow for asymptomatic infections and essentially requires that a person actively seek medical help at a hospital that is equipped to draw samples and ship them to an approved laboratory….it seems unlikely that even a small fraction of the total number of infected cases has been accounted for under the WHO surveillance system.

They also review seroevidence in humans for H5 infections:

Of the 10 largest studies of which we are aware…eight report rates ranging from 0.2% to 5.6%….even if only a low percentage of the rural population is asymptomatically/subclinically infected, the case fatality rate that is offered by the WHO – and that is driving this controversy – is likely orders of magnitude too high.

The authors believe that selection of these papers for redaction by the National Science Advisory Board for Biosecurity appears arbitrary, considering what has been published on influenza in the past:

In 2005, the complete sequences for the 1918 pandemic influenza virus were published…in 2006, both Science and Nature published reports of specific mutations that enable the H5 viral hemagglutinin to bind human, rather than avian tissues. In 2012, a report from the CDC that bears striking resemblance, in principle, to the works by Fouchier and Kawaoka was already published in Virology: it describes mutations in an H5N1 virus that confer airborne transmissibility between ferrets.

Finally the address the question: Could the data from these two papers realistically be used to generate an H5N1 biologic weapon?

The answer is simply no.

Everyone should read this article, including anyone who is concerned about the safety of the H5N1 experiments; biosecurity analysts who do not seem to understand the underlying science; and science writers who propagate misinformation about the virus.

TWiV Special: Dr. Peter Palese

twiv_aa_2001On a special episode of the podcast “This Week in Virology”, Vincent speaks with Dr. Peter Palese, noted influenza expert, about the origin and pandemic potential of the new H1N1 influenza virus.

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Why swine flu isn’t so scary

Peter Palese has written an excellent opinion piece for the Wall Street Journal on why swine flu is not that scary. His arguments may bring some comfort for those readers of virology blog who are worried about the impact of the new influenza H1N1 strain. Even if you are not worried, the scientific basis for his arguments are compelling and answer some of the many questions I have been receiving in the past week. I can’t think of anyone’s opinion on influenza virus that I value more – and it’s not just because I did my Ph.D. research in his laboratory. He’s an outstanding scientist with balanced, well-informed opinions. Herewith are some excerpts from his piece.

First, Palese reviews the concerns about the new H1N1 viruses:

1. The swine virus belongs to the same H1N1 group as did the 1918 pandemic virus.
2. The swine virus is readily transmitted from human to human.  At this point, swine virus isolates have been reported on four continents.  The avian H5N1 virus (another virus with pandemic potential) was never proven to readily transmit from person to person; rather, humans were probably infected directly from chickens and these infections required large quantities of virus.
3. The swine virus shows an unusual robustness in emerging outside the normal seasonal period for the virus.  Influenza viruses are rarely isolated at the end of April in the northern hemisphere, and winter hasn’t yet started in New Zealand, where several isolates have already been reported.
4. Mutations and/or acquisition of genes derived from other human or animal influenza viruses could make the swine virus into something much more virulent than it is now.  Mutations and acquisition of genes are natural processes for influenza viruses against which there are no man-made interventions.  Furthermore, these processes (and the extent to which they could enhance virulence) cannot be predicted.

Next, he argues why we should be optimistic:

1. In 1976 there was a an outbreak of an H1N1 swine virus in Fort Dix, New Jersey, which showed human to human transmission but did not go on to become a highly virulent pandemic strain.
2. The presently circulating swine virus is most likely not more virulent than the other seasonal strains we have experienced over the last several years.
3. The current swine virus lacks an important molecular signature (the protein PB1-F2) which was present in the 1918 virus and in the highly lethal H5N1 chicken viruses.  If this virulence marker is necessary for an influenza virus to become highly pathogenic in humans or in chickens, then the current swine virus doesn’t have what it takes to become a major killer.
4. Since people have been exposed to H1N1 viruses over many decades, we likely have some cross-reactive immunity against the swine H1N1 virus. While it may not be sufficient to prevent becoming ill, it may very well dampen the impact of the virus on mortality.  I would postulate that by virtue of this “herd immunity” even a 1918-like H1N1 virus could never have the horrific effect it had in the past.  The most likely outcome is that the current swine virus will become another (fourth) strain of regular seasonal influenza.
5. The landscape of vaccines and anti-influenza drugs has dramatically improved over what it was just a few years ago.  Based on what we know of the structure and sequence of the swine virus, these FDA-approved drugs and FDA-licensed vaccines (modified to include the swine strain) would be highly effective against this new virus.  Also, present technologies as well as manufacturing capacities will allow us to make sufficient quantities of a swine virus vaccine for the winter 2009-10 season in this country.

In closing, he notes that we have a vastly improved infrastructure to deal with novel emerging diseases:

The preparedness plans developed against the H5N1 influenza threat dramatically improved overall surveillance (we would probably not have learned so fast about the swine virus were it not for these improved capabilities).  Major advances have been initiated by our government to develop new and improved manufacturing processes and exciting new vaccine and antiviral approaches are also in the pipeline, and they show promise of tipping the balance in favor of humans against a devious virus.  For example, universal influenza vaccines (one long-lasting vaccine against all strains) and broadband antivirals are being developed in our academic laboratories and in innovative small biotech companies.  This work has been primarily funded by the NIH and the CDC and it will pay off by diminishing the future impact of influenza on the health of our citizens and on the economy of our country.  It is prudent to prepare against swine influenza, but equally important to keep a balanced outlook and an awareness of our current capabilities.

Coming from such a well-informed and experienced source, these arguments are compelling. Please pass them on to anyone you know who might be worried by the recent emergence of the new influenza H1N1 virus.

Futures in Biotech on influenza

futures-in-biotechI joined host Dr. Marc Pelletier on the TWiT podcast ‘Futures in Biotech’ to interview influenza virologist Dr. Peter Palese, professor and chair of microbiology at the Mount Sinai School of Medicine in New York. We talk about influenza and why Dr. Palese revived a virus that killed 50 million people.

Download Futures in Biotech 40: Virus Reborn or subscribe to the podcast in iTunes.