Oct 18, 2012 (CIDRAP News) – Federal health officials are inviting the public to weigh in on whether research on H5N1 avian influenza viruses, including strains modified in the lab to make them more transmissible, is risky enough to require new safety regulations and precautions.

The Department of Health and Human Services (HHS) wants to know if people think H5N1 should be designated an HHS special agent, which means that medical labs handling it would have to register with the agency and meet special requirements for physical security and personnel screening and training.

The department also has asked for comments on whether special safety and containment measures are needed for research involving H5N1 strains with increased transmissibility in mammals. The request follows the publication earlier this year of two controversial studies describing genetically modified H5 strains that were capable of aerosol transmission in ferrets.

HHS published its request for comments yesterday in a 16-page Federal Register notice. The public has 60 days to comment.

Highly pathogenic avian influenza (HPAI) H5N1 viruses are already listed as select agents in the US Department of Agriculture's (USDA's) province of the Select Agent Program, which means that labs that handle them must register with the USDA's Animal and Plant Health Inspection Service (APHIS) and meet related security and screening requirements. But the viruses are not on HHS's select agent list.

Oversight by APHIS "focuses on the threat to animal health and safety," the HHS notice says. "Listing influenza viruses that contain an HA [hemagglutinin] from the goose/Guangdong/1/96 lineage [the first highly pathogenic H5N1 isolate identified] as an HHS select agent will ensure that the focus of regulation will also be on the potential impact of these viruses on human health as well as agriculture."

The notice notes that certain other agents, such as Bacillus anthracis, which causes anthrax, are on both the USDA and HHS select agent lists. Adding H5N1 to the HHS list "may help to ensure that HPAI strains that have the greatest potential for major direct effects on human health will be regulated with a focus on protection of human health," it states.

The request for comments follows a determination by a federal interagency committee that H5N1 viruses may pose a severe threat to human health and safety, according to the notice. The finding came from the Centers for Disease Control and Prevention's Intragovernmental Select Agents and Toxins Technical Advisory Committee (ISATTAC), which includes members from various HHS and USDA agencies and the departments of Homeland Security and Defense.

That committee considered "the data showing transmissibility of genetically modified H5N1 viruses among ferrets," along with the virus's virulence and the low level of immunity in the population.

The panel also recognized that H5N1 research could lead to better preparedness for pandemic flu and therefore said the risks inherent in research must be weighed against any negative effects that new restrictions might have on legitimate research, according to the notice.

HHS is asking for opinions not only on H5N1 as a possible select agent, but also on whether it should be a "Tier 1" select agent, a new category for agents thought to pose the greatest risk of misuse leading to major harm. Tier 1 agents require additional precautions, such as greater physical security and "personal reliability" screening for staff who work with them.

Both the USDA and HHS recently revised their lists of select agents. The USDA kept H5N1 on its list but did not designate the virus as a Tier 1 agent. HHS put several agents in the Tier 1 category, including Ebola and Marburg viruses and the agents that cause smallpox, plague, anthrax, and botulism, among others.

"The final determination of whether or not to designate this particular lineage of H5N1 HPAI as Tier 1 would be a collaborative process between HHS and USDA," the Federal Register notice says. "HHS and USDA would continue to work closely together whether or not both HHS and USDA designate these viruses as Tier 1 Select Agents."

Further questions in the HHS notice include:

  • Should special safety and biocontainment measures be considered when working with diagnostic specimens suspected of containing HPAI H5N1?
  • Should even more stringent precautions be used when working with HPAI H5 strains that have increased transmissibility in mammals?

In response to queries from CIDRAP News, comments from groups and researchers likely to be affected by an HHS move to make H5N1 a select agent suggest there's a lot of uncertainty about the implications of the HHS notice.

Chris N. Mangal, MPH, director of public health preparedness and response at the Association of Public Health Laboratories, said, "APHL has concerns about HPAI H5 viruses being included on the new tier 1 list of select agents. These viruses are already regulated by the US Department of Agriculture. In the coming weeks, APHL will be gathering more information from member public health laboratories to better address the questions posed in the Oct 17 Federal Register notice."

Richard J. Webby, PhD, whose lab at St. Jude Children's Research Hospital in Memphis studies H5N1 viruses and is registered with the USDA Select Agent Program, commented, "To be honest it's not entirely clear what the impact of such a decision would be on operations here but it's something that we are of course investigating fully now." Webby directs the World Health Organization Collaborating Center for Studies on the Ecology of Influenza in Animals and Birds, which is at St. Jude.

John J. Treanor, MD, a veteran flu and flu vaccine researcher at the University of Rochester, commented, "I don't work directly with H5 viruses in the lab, but I am sure that this [issue] will be quite controversial. It is probably a consequence of the earlier issues related to the ferret studies. It's a tough call—increasing restrictions will without any doubt make it more difficult to study H5 viruses and if the new regulations required specialized facilities that are not readily available, could substantially reduce research in this area.

"On the other hand, H5 viruses are potentially very dangerous. I would see a question—do H5 viruses pose greater danger in the form of natural emergence of H5 as an epidemic in humans, in which case increasing containment requirements is counterproductive, or do H5 viruses pose a danger to humans primarily because of possible accidental release, in which case increased containment is very important."

See also:

Oct 17 HHS Federal Register notice

Oct 10 CIDRAP News story "Changes in select agent rules concern public health labs"

Jun 21 CIDRAP News story "Fouchier study reveals changes enabling airborne spread of H5N1 virus"

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