WASHINGTON — Despite a critical report from another agency and a fair amount of political pressure, the Department of Homeland Security (DHS) remains committed to the Manhattan, Kan., site it chose for building a new national bio-defense research laboratory and says it won’t re-open the site-selection process.

As part of the 2010 government appropriations bill, Congress asked the Government Accountability Office (GAO) to conduct a separate study on DHS’s recommendation to move the Level-3 laboratory at Plum Island, N.Y., to Kansas. The study was to evaluate whether it would be safe to conduct research into foot-and-mouth disease (FMD) at a mainland site for the first time, rather than on the offshore island where it’s been handled for decades in an aging facility.

GAO concluded that DHS, with input from the U.S. Department of Agriculture (USDA), didn’t adequately assess the bio-security and economic risks of building the new Level-4 National Agro and Bio-Defense Facility (NABF) in Midwestern farm country, near livestock operations, where a release of the FMD pathogen by a tornado, terrorist act or other means reportedly could have a much greater economic and disease impact than in offshore New York.

Such an event on Plum island could have a $31 million economic impact, compared to a $1 billion impact in Kansas, the GAO report says, citing another study. “Given the significant limitations in DHS’s analyses that we found, the conclusion that FMD work can be done as safely on the mainland as on Plum Island is not supported,” the GAO report says.

DHS defends its choice

But DHS shot back, in a 30-page response in July, that the GAO study didn’t respond to what Congress asked. Instead of evaluating whether FMD research “can be done safely on the mainland,” the GAO instead chose to evaluate whether the research “can be done as safely on the mainland as on Plum Island.”

DHS says its own environmental-impact study took into account the GAO’s point that the water barrier around Plum Island would provide an extra layer of protection in the event of an accidental release of the FMD pathogen, but it called that scenario “extremely unlikely,” adding that “while the study of contagious diseases anywhere is not without risk, modern bio-containment technology makes the likelihood of an accidental release of a pathogen extremely low, and … has eliminated the need for locating animal-disease research on an island as was done decades ago.”

GAO should not dismiss the fact that FMD research is being performed safely on the mainland in several other countries, DHS says in its response. And it points out that there are already five BSL-4 (highest level) facilities currently operating in the United States in populated areas (Centers for Disease Control and Prevention and Georgia State University, both in Atlanta; U.S. Army Medical Research Institute of Infectious Diseases at Ft. Detrick, Md.; University of Texas Medical Branch in Galveston; and Southwest Foundation for Biomedical Research in San Antonio, Texas).

In his own formal response to the GAO report, Bradley Buswell, DHS Under Secretary for Science and Technology, noted strong public opposition to building a BSL-4 research lab on Plum Island but strong support for Kansas and the other locations DHS considered in Texas, North Carolina, Mississippi and Georgia.

But U.S. Rep. Tim Bishop (D-N.Y.), responding to GAO’s report, calls the recommendation to phase out Plum Island “essentially a rush job” and wants DHS Secretary Janet Napolitano “to revisit the decision” as well as the decision to build the Kansas facility.

“This (GAO) study underscores the validity of why Plum Island was originally chosen,” Bishop says. “I’m sobered by this report. … We still have time to correct this.”

Napolitano, however, says the decision to move the lab to Kansas was properly researched and should go forward.

A group of Texas business and bioscience experts sued DHS in a federal court over the decision to locate the NABF in Kansas, but a judge dismissed the suit in July, saying it was based on hypothetical claims and thus not “ripe” for judicial review, although the suit could be re-filed later.

Kansas officials say the county in Texas where some lobbyists had wanted to bring the NABF is more tornado-prone than Kansas, and presents a hurricane risk as well. And Tom Thornton, president of the Kansas Bioscience Authority, the group that helped land the facility at the Kansas State University site, says conducting FMD research in Kansas is no different or more dangerous than conducting research in human diseases at the CDC in Atlanta.

Kansas officials expect construction of the $560 million to $650 million NABF to start in July 2010, although Congress hasn’t yet appropriated any construction funds. The facility is expected to create 1,500 jobs and pump some $3.5 billion into the local economy when it opens in about 2015.

Hong Kong’s health authorities announced Wednesday [27 Jul 2009] that a new variant of the H3N2 seasonal influenza virus has been found in the city. The Brisbane strain has been the prevalent circulator of H3N2 in the past year, and the new variant is its direct descendent, said Thomas Tsang, controller of Hong Kong’s Center for Health Protection (CHP). “However, it has some genetic changes distinguishing it from the old Brisbane strain,” he said. He said it is normal for viruses to go through changes, adding that overseas health authorities, including those in Canada, Britain and Australia, had also found the new variant.

Tsang said although vaccines provided for the northern hemisphere may not be a direct match for this new variant, they will still provide some protection against it. Noting that vaccines will be widely available in Hong Kong in a month, Tsang appealed to high-risk groups, such as those with chronic diseases, the elderly and children, to get flu shots.

According to the CHP, H3N2 accounts for 43 percent of flu viruses circulating in Hong Kong, while A/H1N1 accounts for 49 percent.

By Carol D. Leonnig
Washington Post Staff Writer
Monday, July 27, 2009

The Department of Homeland Security relied on a rushed, flawed study to justify its decision to locate a $700 million research facility for highly infectious pathogens in a tornado-prone section of Kansas, according to a government report.

The department’s analysis was not “scientifically defensible” in concluding that it could safely handle dangerous animal diseases in Kansas — or any other location on the U.S. mainland, according to a Government Accountability Office draft report obtained by The Washington Post. The GAO said DHS greatly underestimated the chance of accidental release and major contamination from such research, which has been conducted only on a remote island off the United States.

DHS staff members tried quietly last week to fend off a public airing of the facility’s risks, agency correspondence shows. Department officials met privately with staff members of a congressional oversight subcommittee to try to convince them that the GAO report was unfair, and to urge them to forgo or postpone a hearing. But the House Energy and Commerce Committee’s oversight and investigations subcommittee, chaired by Rep. Bart Stupa (D-Mich.), decided otherwise. It plans to hold a hearing Thursday on the risk analysis, according to two sources briefed on the plans.

The criticism of DHS’s site selection comes as the proposed research lab, the National Bio and Agro-Defense Facility (NBAF), was expected to win construction funding in the congressional appropriations process.

“Drawing conclusions about relocating research with highly infectious exotic animal pathogens from questionable methodology could result in regrettable consequences,” the GAO warned in its draft report. DHS’s review was too “limited” and “inadequate” to decide that any mainland labs were safe, the report found. GAO officials declined to comment on the findings.

The new developments started another round of accusations that politics steered DHS’s decision in January to build the proposed lab in Manhattan, Kan. Critics of the choice argue that a Kansas contingent of Republican Senators Sam Brownback and Pat Roberts and then-Gov. Kathleen Sebelius, a Democrat, aggressively lobbied DHS to pick their state. Records show that a DHS undersecretary and his site selection committee met frequently with the senators, one of whom is a member of an appropriations subcommittee that helps set DHS funding.

A Texas consortium that hoped to lure the DHS facility to San Antonio argues that the agency has wasted millions of dollars trying to justify its choice, and said the GAO’s findings show that the selection method was “preposterous.”

“They call it ‘Tornado Alley’ for a reason,” said Michael Guiffre, an attorney for the consortium. “This really boils down to politics at its very worst and public officials who are more concerned about erecting some gleaming new research building than thinking about what’s best for the general public.”

DHS officials and Kansas leaders say the selection system, which began in late 2006, was always fair and open. Brownback has noted that George W. Bush was president in mid-January when his home state of Texas lost the competition.

“The process involved a transparent six-year process, run by career civil servants and punctuated with multiple public meetings near each finalist location,” DHS spokesman Matthew Chandler said.

The DHS lab would replace and expand upon the mission of a federal research facility on a remote island on the northern tip of Long Island, N.Y. Critics of moving the operation to the mainland argue that a release could lead to widespread contamination that could kill livestock, devastate a farm economy and endanger humans. Along with the highly contagious foot-and-mouth disease, NBAF researchers plan to study African swine fever, Japanese encephalitis, Rift Valley fever and other viruses.

GAO’s draft report said the agency’s assessment of the risk of accidental release of toxins on mainland locations, including Kansas, was based on “unrepresentative accident scenarios,” “outdated modeling” and “inadequate” information about the sites. The agency’s analysis of the economic impact of domestic cattle being infected by foot-and-mouth disease played down the financial losses by not considering the worst-case scenario.

The agency noted that the United Kingdom’s outbreak of foot-and-mouth disease in 2001, which resulted from an accidental release at a biological research laboratory south of London. Six million sheep, cattle and pigs were slaughtered to stop the contamination, and the country’s agriculture market, comparatively a fraction of the U.S. market, lost $4.9 billion.

DHS had cited a foot-and-mouth disease facility in Winnipeg, Manitoba, as evidence that doing this research on the mainland is safe. But GAO said that is illogical: The NBAF would have a less sophisticated method for containing releases than the Winnipeg lab, it said, but would handle as many as 10 times the number of animals.

Selecting a spot for the lab has been rife with political battling and vigorous lobbying from five states that were finalists. Though the general public repeatedly voiced concern about the safety of such research, elected leaders were seeking the $3.5 billion jolt that the facility was expected to bring to its host’s economy.

Critics of the selection of Kansas note that DHS Undersecretary Jay Cohen and others met often with the state’s senators. Brownback said this month that he had helped add $36 million to a Senate bill to build the Kansas facility, and that he would work for the same in the House.

“We fought hard for this funding, and I’m glad my colleagues in the Senate realized the significant role this facility will play in researching emerging diseases that could endanger our food supply,” he said on his Web site.

In recent days, DHS science officials involved in choosing the Manhattan site, adjoining Kansas State University, told Secretary Janet Napolitano’s top staff members that GAO exceeded its authority in reviewing the agency’s risk assessment, according to internal correspondence shared with The Post.

Chandler confirmed that agency staff members told the Energy and Commerce subcommittee staff members in their meeting last Monday that DHS would prefer not to have a hearing now. DHS officials were not trying to avoid discussing the issue during the appropriations process, Chandler said, but wanted to avoid wasting the agency’s and committee’s time until they saw the final GAO report.

“This has nothing to do with politics,” Chandler said. “This is about logical reasoning . . . and was in the interest of everyone’s time.”

Two Canadian Food Inspection Agency [CFIA] inspectors appear to have contracted swine flu while investigating an outbreak of the new virus in pigs on an Alberta farm in late April [2009], the agency confirmed on 21 July 2009.

The cases appear to be the first report of people catching the new H1N1 virus from pigs.

While the pandemic virus is of swine origin, it was found in people first. Pigs are not currently believed to be playing a role in ongoing transmission of the virus.

The agency said in emailed answers to questions that it’s impossible to say with 100 per cent certainty that the inspectors were infected by the animals. But the infections took place in the early days of the swine flu outbreak, when few cases were being reported in Canada.  It’s known that the men did not use proper safety techniques while in the barn, apparently removing the N-95 respirators that covered their noses and mouths because they were hot. “We conducted a review of the situation and determined that CFIA protocols for personal protection were not fully observed in this case,” the agency’s email said.

The agency said it doesn’t intend to change protocols for conducting this type of investigation because its existing protocols, if complied with, would have been adequate to protect the workers.

“Supervisors are being asked to ensure inspection staff have received the appropriate training and understand the procedures before being assigned to the investigation.”

The Alberta pig farm incident was the first report ever of this new virus being found in pigs. The source of the infection in the pigs remains a mystery and the handling of the case has been anything but smooth.

Officials at first identified a carpenter who worked briefly on the farm while ill with flu-like symptoms as being the source of the infection. But the man, who had recently returned from a trip to Mexico, was later told tests showed he was never infected with the new virus.

There were reports that members of the farm family were also sick shortly before the pigs started showing symptoms. But samples taken from them were not adequate to confirm or dismiss them as possible sources of the infection. Officials now admit they’ll likely never know how the virus was introduced into the herd.

Argentina recently reported two more cases of person-to-pig transmission of the new virus.

Influenza experts are not surprised the virus can infect pigs and pass back from them to people. But they worry that if this type of ping-ponging occurs, it will drive the viruses to mutate.

It’s impossible to predict what the outcome of that type of evolution would be, but it could undermine the effectiveness of swine flu vaccine currently being developed for people.

Earl Brown, an expert in influenza virus evolution, called the trend towards increasing interspecies transmission of flu viruses “disquieting.” “When it was in Alberta, you had this virus of swine origin … and then you had the question: Well, is it now a human flu or is it a swine flu? And it’s clear that it’s both,” said Brown, a virologist at the University of Ottawa. He said there has been rapid evolution of flu viruses in pigs in recent years, as well as cases of avian influenza viruses, including the dangerous H5N1 virus, jumping into people.

In the influenza world, pigs are described as the mixing vessel, because they can be infected with both bird viruses and human viruses — giving rise to hybrids that they can pass back to people. “You just don’t want the pig to be the conduit for all these adapted viruses they’ve got from birds,” Brown said.

“I think the general trend is not good but this particular virus, you know it’s still an open book at to whether it’s going to tone down, or it’s going to become more like a seasonal flu fast, or if it’s going to ramp up. We really can’t predict and we’re just watching and trying to read the numbers.”

Whether speaking of a 58-year-old man or a 38-year-old woman, or a little boy of 9, officials announcing swine flu deaths are almost always quick to note “underlying health  conditions” may have contributed to the fatal outcome. Asthma, heart disease, diabetes, maybe even obesity are among the conditions used to help explain why swine flu infection is hospitalizing and killing younger people, people who would be expected to make a full recovery from seasonal flu.

It could create the impression that only the sickly are dying from the new H1N1 flu virus — a claim no one is making. To the contrary, many, including the World Health Organization, say between one-third and one-half of swine flu deaths have occurred in people who were previously healthy. But how healthy is previously healthy? The answer depends on who you ask.

Dr Anand Kumar is a critical care specialist who has been treating swine flu cases in embattled intensive care units (ICU) in several Winnipeg hospitals. He says a small portion of the ICU patients look like flu’s typical victims, people with health conditions know to be badly exacerbated by a bout of influenza. But more are younger and — until they got sick — healthier than flu patients hospitals typically see during a regular influenza season. “For the most part, these young, relatively healthy people aren’t marathon runners or anything like that,” he admits. “They’re normal people…. If you asked them ‘Are you healthy?’ they’d say ‘Yeah, pretty healthy.”‘

Dr Michael Gardam, head of infectious disease prevention and control for Ontario’s public health agency, believes the constant refrain of “underlying conditions” bespeaks a sort of wishful thinking, an attempt to explain away the unusual age range of the people the new virus is sending to hospital or to the morgue. “That’s the story that I think people haven’t really registered,” says Gardam. “We’re clinging to these ‘Oh, they had underlying illness, therefore it’s OK.”‘ “But … I would argue that the 30-year-old with mild asthma — how big of an  underlying illness is that compared to again the 80-year-old person with bad lung disease from smoking, who’s got heart disease? That’s the usual group that unfortunately gets really sick with flu, not this healthy adult group.” You’ll find little argument that this virus, at this time, is causing more severe disease in people far younger than those normally hospitalized and killed by flu or its complications in a typical flu season.

“This is not a disease of older adults. There’s no question,” says Dr. Allison McGeer, an influenza expert with Toronto’s Mount Sinai Hospital. “For people under 50, this is a significantly more severe disease than seasonal flu. For people over 50, it’s much better,” she notes. But are the people under 50 who are being badly hit by the virus specimens of perfect health or are many of them already shaded by the broad umbrella known as “pre-existing health conditions?” How you view a condition like asthma — seen in 41 per cent of the hospitalized cases in New York City — may influence how you answer that question. “A lot of that is about labelling people,” McGeer admits. “Half of me doesn’t want you to think you’re diseased if you have asthma, and the other half of me wants you to get your flu vaccine because you’re at increased risk.” “How do you walk that line?”

Year in and year out, public health authorities get plenty of evidence many people who have some health issues plunk themselves firmly on the “healthy” side of the divide. Scans of people with asthma, diabetes and other conditions, and women who are pregnant forego the flu shots public health officials urge them to get, suggests Dr Scott Harper, an influenza expert with New York City’s Department of Health. New York City has had one of the biggest swine flu outbreaks to date. As of Tuesday [16 Jun 2008], more than 700 New Yorkers have been hospitalized with swine flu and 23 people in the city have died from infections. With those kinds of numbers, one might expect to see patterns emerge. But Harper says in fact the department believes that many of the health conditions known for years to increase the risk posed by flu are being seen in the people suffering serious disease with swine flu. “The majority of deaths that are being seen have well recognized underlying health risks,” he insists. “Those that don’t may have and we just haven’t seen them yet. And then we may also find new risk factors, but they have not yet been adequately described analytically to be able to say it’s a legitimate risk factor.”

One such potential new risk factor is obesity. An early study from the US Centers for Disease Control suggested it may be contributing to poor outcomes in people who contract the new H1N1. The WHO is concerned about that possibility. “Obesity is now a huge global problem,” says Dr Nikki Shindo, an expert with the WHO’s global influenza program. “And if obesity is a risk factor, then I would be very much worried about some of the populations that are living with obese conditions.” Four of the people who died in New York City were obese. Still, Harper says it’s too soon to say whether that’s a risk factor in and of itself, or if some of the things that go hand-in-hand with obesity — like early heart disease, like diabetes – — are the real risk factors. Teasing out that answer will be tough but necessary, he says, noting that knowing who is truly at the most risk from this virus will dictate who stands where in the queue for swine flu vaccine once it becomes available and who should get priority access to antiviral drugs.

A GAO report issued on May 22, 2008 (GAO-08-821T, HIGH-CONTAINMENT BIOSAFETY LABORATORIES, DHS Lacks Evidence to Conclude that Foot-and-Mouth Disease Research Can be Done Safely on the U.S. Mainland reviews the background of foot and mouth disease (FMD) research in the U.S. and elsewhere. This report questions the basis for the Department of Homeland Security (DHS) support for the movement of FMD virus and research from the current location at Plum Island Animal Disease Research Center (PIADC) to the newly announced National Bio and Agro-Defense Facility (NBAF) site managed by Kansas State University. In the GAO report, concern was raised regarding a study where DHS relied on a secondary study that the United States of Agriculture (USDA) commissioned and that a contractor conducted in May 2002. This study examined the question of whether it is technically feasible to conduct exotic disease research and diagnostics, including FMD and rinderpest, on the U.S. mainland with adequate biosafety and biosecurity to protect U.S. agriculture? Some significant problems existed in the conduct of this study. Nonetheless, DHS continues to cite to this study as supporting the closing of PIADC, and being the basis of support for the $450 million facility funded to Kansas State University. Various concerns are raised by GAO regarding this USDA study and the readership of this blog is encouraged to read the report in detail and the GAO criticisms.

At the heart of the debate is the question as to what existing laws and statutes govern the site for FMD research in the United States? DHS assumed control of PIADC on June 1, 2003 based on authority granted by the Homeland Security Act of 2002. On January 30, 2004 DHS was instructed by Homeland Security Presidential Directive / HSPD-9 (Defense of United States Agriculture and Food) to undertake several actions to protect United States agriculture and food systems, and improve infrastructure to both natural and intentional acts which would erode U.S. agriculture. DHS has identified PIADC as “reaching the end of its life cycle”, and as lacking critical capabilities to continue as the primary facility for such work. DHS initiated actions to replace PIADC which was judged as antiquated using the following authority, specifically clause (24), cited from HSPD-9.

Research and Development (numbers in parenthesis are paragraph markings as appearing in HSPD-9)

(23) The Secretaries of Homeland Security, Agriculture, and Health and Human Services, the Administrator of the Environmental Protection Agency, and the heads of other appropriate Federal departments and agencies, in consultation with the Director of the Office of Science and Technology Policy, will accelerate and expand development of current and new countermeasures against the intentional introduction or natural occurrence of catastrophic animal, plant, and zoonotic diseases. The Secretary of Homeland Security will coordinate these activities. This effort will include countermeasure research and development of new methods for detection, prevention technologies, agent characterization, and dose response relationships for high-consequence agents in the food and the water supply.

(24) The Secretaries of Agriculture and Homeland Security will develop a plan to provide safe, secure, and state-of-the-art agriculture biocontainment laboratories that research and develop diagnostic capabilities for foreign animal and zoonotic diseases.

(25) The Secretary of Homeland Security, in consultation with the Secretaries of Agriculture and Health and Human Services, shall establish university-based centers of excellence in agriculture and food security.

The above citation is very important at several levels. Nowhere in HSPD-9 is FMD mentioned directly. However, DHS states authoritatively that FMD virus and research will be housed at the NBAF. The Secretary of Agriculture is directed to assist DHS in plans to upgrade biocontainment and diagnostic capabilities without reference to other legal obligations. Most importantly, nowhere in HSPD-9 is it mentioned that PIADC should be closed and research relocated. This brings us to the point of asking: what exactly is the authority conveyed through a Presidential Directive? These documents are referred to in different ways in Presidential Directives depending on the administration occupying the Executive Office. From the White House briefing room we cite: “PRESIDENTIAL ACTIONS In this section you will find official actions by the President that have a significant impact on how the federal government functions but do not require legislation or Congressional approval . . . ”

Herein is the problem and this problem was referenced, but not detailed, by the GAO study. FAD research and the legal justification to establish and maintain PIADC is well documented in 21 USC 113a. United States Code (U.S.C.) is a compilation and codification of the general and permanent federal law of the United States. Specifically 21 USC 113a states:

“The Secretary of Agriculture is authorized to establish research laboratories, including the acquisition of necessary land, buildings, or facilities, and also the making of research contracts under the authority contained in section 427i(a) of title 7, for research and study, in the United States or elsewhere, of foot-and-mouth disease and other animal diseases which in the opinion of the Secretary constitute a threat to the livestock industry of the United States: Provided, that no live virus of foot-and-mouth disease may be introduced for any purpose into any part of the mainland of the United States (except coastal islands separated therefrom by water navigable for deep-water navigation and which shall not be connected with the mainland by any tunnel) unless the Secretary determines that it is necessary and in the public interest for the conduct of research and study in the United States (except at Brookhaven National Laboratory in Upton, New York) and issues a permit under such rules as the Secretary shall promulgate to protect animal health, except that the Secretary of Agriculture may transport said virus in the original package across the mainland under adequate safeguards, and except further, that in the event of outbreak of foot-and-mouth disease in this country, the Secretary of Agriculture may, at his discretion, permit said virus to be brought into the United States under adequate safeguards.”

The above is literally the law of the land, and violations of this law are punishable through an assortment of penalties including Contempt of Congress. Returning to the topic, where exactly did DHS assume precedent to establish and award the NBAF contract? From the prior discussion the legal precedent is very clear – - only the Secretary of Agriculture or Congress can allow FMD virus to be moved from PIADC onto the mainland. This was established by law in 1949, and this law is still on the books and in effect. With reference to the Secretary of Agriculture, two questions arise. With the erosion of authority over FMD virus research, does USDA, or DHS, assume the obligations of indemnification should FMD escape biocontainment and damage U.S. agriculture? What is the consequence of actions by the current Secretary of Agriculture on binding commitments made by future Secretaries of Agriculture? Should plans for NBAF proceed and the existing PIADC be razed on the basis of “reaching the end of its life cycle”, and as lacking critical capabilities to continue as the primary facility for such work just to have a future Secretary of Agriculture reverse the decision, the ugly reality emerges of “what options exist”? In short, none! And, US agriculture will lack a FMD research program which could assist in vaccine development should this FAD occur at some time in the future.

This leaves open the question of: why has the U.S. Congress not been proactive in the award of the NBAF facility contract, and why is Congress not diligent in the enforcement of existing U.S. Code? Without bias, we assume that FMD research is suitably placed at PIADC consistent with existing law. Moreover, infrastructure upgrades could revitalize this facility, possibly at a fraction the cost of a site based on the mainland. NBAF is currently funded at an estimated cost of $450 million, which is considerable. However, an estimated loss of $1 billion could occur to the economy of the State of Kansas should FMD virus escape containment and impact the State. The latter figure was derived from a Kansas State University publication (Pendell et al., The Economic Impacts of a Foot-and-Mouth Disease Outbreak: A Regional Analysis. J. Agricultural and Applied Economics, 39:19-33. 2007).

In conclusion, a key question remains unanswered – - why is this blog the only source asking these questions?

The following is [1] a statement of the research program of the United States Department of Agriculture (USDA) Agricultural Research Service (ARS), and [2] the outcome of a study of the cross-reactivity of serum samples from US pigs against the new swine origin 2009 H1N1 influenza virus (S/O H1N1). The results of this analysis indicate that pre-existing immunity induced by swine influenza viruses circulating in the US may not protect pigs against the new S/O H1N1 influenza virus presently circulating in people.

Soon after the emergence of the H1N1 virus in April 2009, ARS scientists at the National Animal Disease Center in Ames, Iowa began research using virus samples provided by the Centers for Disease Control and Prevention (CDC). The 1st step was to evaluate whether current US H1N1 swine influenza vaccines can protect pigs from infection with the 2009 H1N1 influenza virus circulating in people. This research study also evaluated whether pre-existing titers in pigs previously infected with endemic H1N1 swine influenza viruses circulating in the US could protect against the 2009 H1N1 influenza virus.

Classical swine influenza virus infections are enzootic among pigs in North America. Sporadic cases of human infection with swine influenza virus have been reported in the United States and elsewhere. Worldwide, more than 50 human cases of swine influenza virus infection, mostly due to classical swine influenza virus, have been documented in the past 35 years, with the greatest risk of infection among people with occupational exposure to live pigs.

Experts believe pigs can act as a “mixing vessel” for the reassortment of avian, swine and human influenza viruses and might play an important role in the emergence of novel influenza viruses that could be capable of causing a human pandemic similar to the virus in the current outbreak.

Between the 1930s and the 1990s, the most commonly circulating swine influenza virus among pigs — classical swine influenza A, known as H1N1 — underwent little change.

However, by the late 1990s, multiple strains and subtypes of triple reassortant swine influenza viruses — whose genomes include combinations of avian, human and swine influenza virus gene segments — had emerged and became predominant among North American pigs. The 2009 H1N1 influenza virus is also a triple reassortent, but its lineage is different than the H1N1 influenza viruses currently circulating in US pigs.

Background:
The genetic makeup of swine influenza viruses is identical to other influenza A viruses and consists of 8 segments of RNA that code for different proteins. Influenza viruses have the ability to exchange these segments, creating new genetically different viruses. Two major surface glycoproteins (proteins with a carbohydrate attached) called hemagglutinin (H) and neuraminidase (N) are how influenza A viruses are identified. These glycoproteins also determine the host range, antigenicity and the pathogenicity of the viruses. The hemagglutinin and neuraminidase proteins are important targets for diagnostics and are used to designate the subtype of the virus.

Currently, 16 different hemagglutinins and 9 neuraminidases have been identified. The majority of these viral subtypes are found in waterfowl, with only a few combinations being found in humans and swine.

Swine influenza virus (SIV) is one of the primary causes of respiratory disease in growing pigs and can lead to major economic losses. Currently, only H1N1, H1N2, and H3N2 subtypes are circulating in the US swine population.

Pigs have long been considered a potential source for new and novel influenza viruses that infect humans, as they have receptors on their cells that bind both mammalian and avian influenza viruses, increasing the opportunity for the exchange of genetic segments of the virus.

Previously, CDC has reported about one case of human infection with a swine influenza virus every one to 2 years.

Recent ARS research results: 2009 H1N1 influenza virus: ARS researchers tested serum samples from pigs previously infected with US swine influenza viruses or vaccinated with commercial vaccines to determine whether US commercial swine herds are susceptible to the new swine origin (S/O) H1N1 influenza virus. They found that there was limited cross reactivity against the new S/O H1N1 influenza virus. This suggests that pre-existing immunity induced by swine influenza viruses previously circulating in the US may not protect pigs against the new S/O H1N1 influenza virus presently circulating in people. Importantly, vaccines currently used to protect pigs on US swine farm operations against swine influenza viruses may not be effective against the new S/O H1N1 influenza virus.

If and when a pandemic of H1N1 swine flu hits, vaccines might be the world’s best hope for softening the blow. But major uncertainties cloud the prospects for vaccines against the new  strain. No pandemic vaccine yet exists, and it is unclear how much vaccine would have to be available, and by what time, to have any impact. Should manufacturers halt the production of seasonal influenza vaccine to focus on a pandemic version, and if so, when? And is there any way to ensure that people around the world have an equal chance to get the new vaccine?

These topics have been the subject of frantic, almost daily discussions among scientists, vaccine manufacturers, regulatory agencies, and the World Health Organization (WHO) over the past few weeks. But so far, there are few concrete answers, in part because no one knows just how severe a threat the new virus poses, or how difficult it will be to mass-produce a vaccine. One thing is certain, however: There won’t be nearly enough vaccine to protect all the world’s citizens, and the question of who has first dibs could get ugly, says David Fedson, a former pharma executive and influenza vaccine expert living in France.

Almost all seasonal flu vaccine is made using a clunky, 50-year-old process, in which companies adapt the virus to multiply in hens’ eggs, grow the virus in eggs, then purify the  key antigens needed to make vaccine—the hemagglutinin and neuraminidase molecules that stick out from the virus’s surface. In all, the process takes more than 5 months. This is also how at least the vast majority of a pandemic vaccine will be made, because promising alternative production strategies won’t be ready in time.

Immediately after isolating the new H1N1 strain, the U.S. Centers for Disease Control and Prevention and other labs began producing a “seed stock” of virus, which will be given to manufacturers in a few weeks for vaccine production. But how much pandemic vaccine will they be able to produce once they get going? A study funded by the Bill and Melinda Gates Foundation, whose main outcomes were announced in February, gives an indication. The study, carried out by Adam Sabow of the consulting company Oliver Wyman, in collaboration with WHO and the International Federation of Pharmaceutical Manufacturers & Associations, showed that all manufacturers combined can currently produce some 680 million doses of seasonal flu vaccine per year—a number that is expected to grow to at least 1.4 billion by 2014.

It’s not easy to translate that figure into doses of pandemic vaccine. The number depends, among other things, on how successfully scientists can make the new virus grow in eggs, how much antigen is needed for an adequate vaccine response, and whether a so-called adjuvant can reduce the amount of antigen needed per shot. But Sabow’s study concluded that in the most likely scenario, the world’s vaccinemakers combined could produce almost 2.5 billion doses of pandemic vaccine in the first year.

Assuming, as many scientists do, that two shots would be needed for adequate protection— as opposed to one for seasonal vacine—that means there would be enough for 1.2 billion people, less than 20% of the world’s population, that first year. The study was based on the assumption of a pandemic of H5N1 avian influenza, but the figures are not expected to be vastly different for swine flu.

Achieving that output assumes, however, that vaccine manufacturers immediately stop their production of seasonal vaccine, which they are now making for 2009–10, and go full-bore on a pandemic vaccine—a very unlikely scenario. In reality, WHO has to weigh the risk of a shortage of seasonal vaccine, and the increased risk of disease and death that would ensue, against the threat posed by the new strain. For the moment, the new virus doesn’t appear to be highly virulent, but that could change over time. After a relatively mild first wave in the spring of 1918, the Spanish flu returned with a vengeance in the fall.

“It’s a devilish dilemma,” says Jaap Venema, global project director influenza at vaccine producer Solvay in the Netherlands. At a press briefing last week, WHO vaccine expert Marie-Paule Kieny said the agency is in close contact with manufacturers; some are further along with their seasonal production than others, and those might switch first to pandemic vaccines while others do so later.

How to ensure equitable distribution of the vaccine is trickier still. Since the threat of an avian influenza pandemic became urgent 6 years ago, a few developing nations have been fighting hard to ensure they will have access to vaccines if a pandemic strikes. Indonesia even went so far as to refuse participation in WHO’s system for virus sharing in an attempt to wrest hard guarantees from the agency. WHO responded with a plan to increase production capacity in the developing world, which is now home to some 13% of the global vaccine production capacity—but the plan is still in its infancy. To ensure equal access, WHO Director-General Margaret Chan has called for “international solidarity,” and Kieny says WHO is already talking to donors and major global health funders about ways to buy vaccine for the world’s poorest.

But there are some major obstacles. Several countries already have first dibs on any pandemic vaccine. In 2006, for instance, the Dutch government signed a contract with Solvay  guaranteeing that it gets the first 16 million doses of a pandemic vaccine to protect its own population. Other governments have signed similar deals, Kieny says, so “the books  of the manufacturers are already quite full.”

In addition, the governments of the countries with a flu vaccine plant in their territories will be under tremendous political pressure to protect their own populations first, Fedson predicts. “You don’t need a contract,” he says; “all you need is an army” to prevent the vaccine from going across the border. Thus, even rich countries like Sweden and Spain that lack a vaccine plant could find themselves empty-handed, he says.

Unfortunately, there are few alternatives for the moment. Most flu vaccine manufacturers are working to replace the antiquated chicken-egg technology with a cell-based method, in which the vaccine virus is grown in mammalian cells. This has several advantages: Manufacturers are less dependent on the supply of chicken eggs—which is difficult to increase quickly and can become vulnerable during bird flu outbreaks—and it could shave 10 weeks from the 22 weeks now needed to make influenza vaccine using eggs.

But although more practical and cleaner, cell-based vaccines don’t promise a major boost in production capacity. Moreover, success with the technique has been slow to come, despite more than $1.5 billion in U.S. Department of Health and Human Services contracts to several companies to fund clinical trials of cell-based vaccines and scale up manufacturing. “The cell-based vaccines are coming, but we’re not going to see them for this pandemic,” says influenza expert Arnold Monto of the University of Michigan School of Public Health in Ann Arbor. Other recombinant vaccines that could truly lead to an explosion in production capacity are even further down the road, says John Treanor of the University of Rochester’s School of Medicine and Dentistry in New York state.

That means that, at least for now, the world is still dependent on chicken eggs.

Assessing the Severity of an Influenza Pandemic

The major determinant of the severity of an influenza pandemic, as measured by the number of cases of severe illness and deaths it causes, is the inherent virulence of the virus. However, many other factors influence the overall severity of a pandemic’s impact.

Even a pandemic virus that initially causes mild symptoms in otherwise healthy people can be disruptive, especially under the conditions of today’s highly mobile and closely interdependent societies. Moreover, the same virus that causes mild illness in one country can result in much higher morbidity and mortality in another. In addition, the inherent
virulence of the virus can change over time as the pandemic goes through subsequent waves of national and international spread.

Properties of the virus

An influenza pandemic is caused by a virus that is either entirely new or has not circulated recently and widely in the human population. This creates an almost universal vulnerability to infection. While not all people ever become infected during a pandemic, nearly all people are susceptible to infection.

The occurrence of large numbers of people falling ill at or around the same time is one reason why pandemics are socially and economically disruptive, with a potential to temporarily overburden health services.  The contagiousness of the virus also influences the severity of a pandemic’s impact, as it can increase the number of people falling ill and needing care within a short time frame in a given geographical area. On the positive side, not all parts of the world, or all parts of a country, are affected at the same time.

The contagiousness of the virus will influence the speed of spread, both within countries and internationally. This, too, can influence severity, as very rapid spread can undermine the capacity of governments and health services to cope.

Pandemics usually have a concentrated adverse impact in specific age groups. Concentrated illnesses and deaths in a young, economically productive age group will be more disruptive to societies and economies than when the very young or very old are most severely affected, as seen during epidemics of seasonal influenza.

Population vulnerability

The overall vulnerability of the population can play a major role. For example, people with underlying chronic conditions, such as cardiovascular disease, hypertension, asthma, diabetes, rheumatoid arthritis, and several others, are more likely to experience severe or lethal infections. The prevalence of these conditions, combined with other factors such as
nutritional status, can influence the severity of a pandemic in a significant way.

Subsequent waves of spread

The overall severity of a pandemic is further influenced by the tendency of pandemics to encircle the globe in at least 2, sometimes 3, waves. For many reasons, the severity of subsequent waves can differ dramatically in some or even most countries.

A distinctive feature of influenza viruses is that mutations occur frequently and unpredictably in the 8 gene segments, and especially in the hemagglutinin gene. The emergence of an inherently more virulent virus during the course of a pandemic can never be ruled out.

Different patterns of spread can also influence the severity of subsequent waves. For example, if schoolchildren are mainly affected in the 1st wave, the elderly can bear the brunt of illness during the 2nd wave, with higher mortality seen because of the greater vulnerability of elderly people.

During the previous century, the 1918 pandemic began mild and returned, within 6 months, in a much more lethal form. The pandemic that began in 1957 started mild, and returned in a somewhat more severe form, though significantly less devastating than seen in 1918. The 1968 pandemic began relatively mild, with sporadic cases prior to the 1st wave, and remained mild in its 2nd wave in most, but not all, countries.

Capacity to respond

Finally, the quality of health services influences the impact of any pandemic. The same virus that causes only mild symptoms in countries with strong health systems can be  devastating in other countries where health systems are weak, supplies of medicines, including antibiotics, are limited or frequently interrupted, and hospitals are crowded, poorly equipped, and understaffed.

Assessment of the current situation

To date, the following observations can be made, specifically about the H1N1 virus, and more generally about the vulnerability of the world population. Observations specific to H1N1 are preliminary, based on limited data in only a few countries.

The H1N1 virus strain causing the current outbreaks is a new virus that has not been seen previously in either humans or animals. Although firm conclusions cannot be reached at present, scientists anticipate that pre-existing immunity to the virus will be low or non-existent, or largely confined to older population groups.

H1N1 appears to be more contagious than seasonal influenza. The secondary attack rate of seasonal influenza ranges from 5 per cent to 15 per cent. Current estimates of the secondary attack rate of H1N1 range from 22 per cent to 33 per cent.

With the exception of the outbreak in Mexico, which is still not fully understood, the H1N1 virus tends to cause very mild illness in otherwise healthy people. Outside Mexico, nearly all cases of illness, and all deaths, have been detected in people with underlying chronic conditions.

In the 2 largest and best documented outbreaks to date, in Mexico and the United States of America, a younger age group has been affected than seen during seasonal epidemics of influenza. Though cases have been confirmed in all age groups, from infants to the elderly, the youth of patients with severe or lethal infections is a striking feature of these early outbreaks.

In terms of population vulnerability, the tendency of the H1N1 virus to cause more severe and lethal infections in people with underlying conditions is of particular concern.

For several reasons, the prevalence of chronic diseases has risen dramatically since 1968, when the last pandemic of the previous century occurred. The geographical distribution of these diseases, once considered the close companions of affluent societies, has likewise shifted dramatically. Today, WHO estimates that 85 per cent of the burden of chronic diseases is now concentrated in low- and middle-income countries. In these countries, chronic diseases show an earlier average age of onset than seen in more affluent parts of the world.

In these early days of the outbreaks, some scientists speculate that the full clinical spectrum of disease caused by H1N1 will not become apparent until the virus is more widespread. This, too, could alter the current disease picture, which is overwhelmingly mild outside Mexico.

Apart from the intrinsic mutability of influenza viruses, other factors could alter the severity of current disease patterns, though in completely unknowable ways, if the virus continues to spread.

Scientists are concerned about possible changes that could take place as the virus spreads to the southern hemisphere and encounters currently circulating human viruses as the normal influenza season in that hemisphere begins.

The fact that the H5N1 avian influenza virus is firmly established in poultry in some parts of the world is another cause for concern. No one can predict how the H5N1 virus will behave under the pressure of a pandemic. At present, H5N1 is an animal virus that does not spread easily to humans and only very rarely transmits directly from one person to another.

Introduction

In light of the H1N1 (formerly known as swine flu) virus outbreak, consumers should have an understanding of the influenza virus from a pork producer perspective, and the steps that US swine producers routinely utilize to keep pigs healthy.

Influenza background from the pork industry perspective

• Pork producers have occasionally battled an influenza virus that is transmitted among pigs. Pig influenza within a swine herd generally presents as a relatively mild respiratory disease and treatment is initiated in consultation with the herd veterinarian.

• Very rarely, swine influenza can be transmitted from pigs to humans (zoonotic transmission).

• Although rare, the Centers for Disease Control reports several past cases where an influenza virus originating in swine passed from human to human.

• It appears as if pigs can be infected from humans who are shedding the current H1N1 virus, as evidenced by a case in Canada.

Many routine practices employed by US swine producers prevent, not only swine influenza, but other diseases as well.

• Most animals are housed in like-aged groups to reduce disease transfer from older pigs to younger pigs. Buildings are temperature-controlled and scientifically designed to keep pigs clean, safe and protected from predators, disease and extreme weather.

• Producers utilize all-in-all out production where a building is completely emptied, washed, and disinfected between groups of pigs. This practice serves as a further measure to break disease cycles on pig farms.

• As part of the National Pork Board’s Pork Quality Assurance (PQA) program, pork producers develop and follow a herd health plan in cooperation with a licensed veterinarian. The herd health plan may include influenza vaccine among other disease prevention vaccinations. Most US pork packers require producers to maintain PQA certification.

• Producers practice biosecurity to prevent diseases from traveling into or out of a facility. In the event of a disease outbreak, pigs confined in an enclosed building are much easier to quarantine than are pigs housed in the open.

Conclusion

Contemporary swine production practices and biosecurity measures are well suited to reduce the spread of diseases, including the current H1N1 influenza virus. Confined production greatly reduces the opportunity for conventional and zoonotic disease transfer because of limited animal-to-animal and animal-to-human contact, and serves as an effective disease isolation mechanism when diseases do occur.