Experiments suggest a 1918-like flu virus could rise again

Avian influenza viruses with components similar to those in the 1918 pandemic flu virus still circulate in nature, and genetic engineering experiments suggest it would take only a few mutations to turn them into a human threat, according to a team of scientists led by Yoshiro Kawaoka, DVM, PhD, of the University of Wisconsin.

Writing in Cell Host & Microbe, Kawaoka and colleagues say their studies have shown "the global prevalence of avian influenza virus genes whose proteins differ by only a few amino acids from the 1918 pandemic influenza virus, suggesting that 1918-like pandemic viruses may emerge in the future." The genes are found in viruses circulating in wild ducks, according to a University of Wisconsin press release.

To assess the risk, the team used reverse genetics to generate a virus with gene segments encoding proteins very similar to those of the 1918 virus. They found that this virus was more pathogenic in mice and ferrets than a natural avian flu virus, causing flu-like symptoms, but not as pathogenic as the 1918 virus.

In further experiments, they found that seven amino-acid changes in this virus's polymerase and hemagglutinin proteins gave it the ability to spread in ferrets via respiratory droplets, the report says. It adds that the findings suggest "that the potential exists for a 1919-like pandemic virus to emerge at any time from the avian virus gene pool."

Kawaoka said that knowing which avian flu virus genes to look for can help scientists predict the likelihood of an emerging strain of pandemic flu, according to the release.

The experiments were conducted under biosafety level 3 precautions, the second-highest safety level. The press release says the manuscript was reviewed by the National Institute of Allergy and Infectious Diseases, in keeping with US policy on "dual-use research of concern" (DURC).

The researchers found that blood serum from people vaccinated with the current seasonal flu vaccine reacted with the 1918-like virus, suggesting that the vaccine could be protective against it. Also, the authors say the viruses used in the study are likely to be "highly susceptible" to the antiviral drug oseltamivir.

Other scientists not involved in the research weren't so reassuring. In a story in The Guardian today, Simon Wain-Hobson, PhD, a virologist at the Pasteur Institute in Paris, said, "It's madness, folly. It shows profound lack of respect for the collective decision-making process we've always shown in fighting infections."

Harvard epidemiologist Marc Lipsitch, PhD, commented, "This is a risky activity, even in the safest labs. Scientists should not take such risks without strong evidence that the work could save lives, which this paper does not provide." Lipsitch co-wrote a commentary last month in PLoS Medicine calling for safer alternatives to DURC.
Jun 11 Cell Host & Microbe abstract
Jun 11 University of Wisconsin press release
Jun 11 Guardian story
May 22 CIDRAP News story on Lipsitch DURC commentary

Study shows potential for ocular-only influenza infection

Ferrets experimentally infected with either avian or human influenza strains through only the eyes readily transmitted the virus to other ferrets, and those inoculated with low levels of H5N1 avian flu via that route died, according to a study today in the Journal of Virology.

Researchers in the Influenza Division of the Centers for Disease Control and Prevention (CDC) first inoculated 11 ferrets via aerosol to the eyes with H5N1 viruses at various doses and for exposure times from 2 to 30 minutes. Only 1 of those ferrets survived, and the experiment showed that H5N1 via the ocular route can be fatal to ferrets even when administered for 2 minutes and at doses as low as 10 plaque-forming units.

The investigators then inoculated ferrets with H7N3, H7N7, and H7N9 avian flu strains, as well as with pre-pandemic H1N1 and variant H3N2 human strains. They found that, with all strains, the infected ferrets shed virus for prolonged periods and were able to transmit influenza by either direct contact or via respiratory droplets.

The authors conclude, "Ocular-only exposure to virus-containing aerosols constitutes a valid exposure route for a potentially fatal respiratory infection . . . In the absence of eye protection, the human ocular surface remains vulnerable to infection with aerosolized respiratory viruses."
Jun 11 J Virol study

Federal settlement to cover woman's flu vaccine claims

A Philadelphia law firm announced yesterday that it had negotiated a settlement worth up to $11.6 million to pay for ongoing medical costs of a 24-year-old former nurse's aide who had symptoms 3 weeks after getting a flu shot in 2010 that were later diagnosed as Guillain-Barre syndrome (GBS), the Morning Call, a newspaper based in Allentown, Penn., reported yesterday.

The settlement will be paid by the National Vaccine Injury Compensation (NVIC) program, a federal program designed to handle claims related to seasonal flu vaccines and routine childhood immunizations.

The woman received the vaccine at work in October 2010. Though Lehigh Valley Hospital, where she worked, now requires employees to be vaccinated against influenza, the requirement was not in place when the woman was immunized, and the facility was not named as a defendant. She has been in a hospital or nursing homes for nearly 4 years and cannot walk, feed, or clothe herself.

The settlement, negotiated by attorneys Lawrence Cohan and David Carney, also provides the woman with more than $1 million in lost wages, pain, suffering, and other expenses, according to the report.

Carney told the Morning Call that the case was clear: The woman was previously healthy, and symptom onset closely match medical literature reports for GBS caused by flu vaccine, and there was no other explanation for her illness. Studies have suggested that there is a negligible risk of developing GBS after getting the flu vaccine, but health officials have said the health risks from flu outweigh the vaccine risk. Studies have also suggested that flu infection is a likely risk factor for GBS.
Jun 10 Morning Caller story