Is the United States adequately prepared to handle an outbreak of foot-and-mouth disease? We may not be totally prepared yet, but we are much more prepared than we were several years ago, according to top officials with the USDA Animal and Plant Health Inspection Service (APHIS) and the U.S. Department of Homeland Security (DHS).

“There has been increased awareness, planning and training at the state and local levels,” says Tammy Beckham, DVM, PhD, formerly DHS deputy director for science, Plum Island Animal Disease Center (PIADC), and now with APHIS at PIADC.

DHS took over the responsibility from USDA for operating PIADC in 2003 when provisions of the Homeland Security Act of 2002 were implemented. USDA continues to work on foreign animal diseases at Plum Island.

Glen I. Garris, PhD, director of the National Veterinary Stockpile for APHIS, agrees. “I would think that we are better prepared today than we have been the last three to five years,” Garris says.

Garris cites several General Accountability Office audits that “identified issues that we have addressed that will better prepare us for an outbreak. Now, we have better relationships with sister agencies.”

Further, according to Garris, “Over the last four or five years, we have been hiring individuals to fill area emergency coordinator (AEC) positions throughout the country.” So far, there are 17 AEC positions filled in different parts of the country, Garris says. AECs are responsible for coordinating a response to a foreign animal disease between the APHIS and state and local officials.

FMD has high priority

Because it poses the greatest threat of introduction, foot-and-mouth disease (FMD) continues to be one of, if not the highest-priority foreign animal diseases (FAD) in terms of preparation and research.

Beckham points out that a large component of the agricultural portfolio for DHS is the development of FMD vaccines. “The goal is to have a vaccine for emergency use,” she says.

She explains that the current focus of this effort includes characterization of FMD vaccines that are currently in the North American FMD vaccine bank (NAFMDVB) and development of new molecular vaccines and immunomodulators.

Both of these efforts are collaborations with the USDA Agricultural Research Service (ARS) and APHIS. APHIS is responsible for maintaining the NAFMDVB, and the ARS has performed the basic research on the development of new molecular vaccines and immunomodulators.

“In a foot-and-mouth disease outbreak, it is going to be absolutely critical that we get our animals protected as soon as possible,” Beckham says.

Currently, FMD antigens are stored in the NAFMDVB at PIADC. In the event of an outbreak, these antigens would be used to produce a vaccine for use in containing it.

“Using the currently available inactivated vaccines, it is very difficult to differentiate between an infected versus a vaccinated animal,” Beckham says.

Further, she says, many of the antigens in the NAFMDVB are now being characterized for emergency use in a collaborative effort between APHIS and DHS. “One of the things we’re doing right now is evaluating antigens that are in the NAFMDVB for use in an emergency situation. How do these vaccines perform against FMD isolates that are currently circulating, and how soon do you get protection following vaccination?”

New vaccines

Meanwhile, researchers are moving ahead with their efforts to develop new genetically modified marked vaccines, which Beckham describes as “highly promising.”  These vaccines will allow differentiation between a vaccinated and infected animal.

“Researchers are currently evaluating how this new vaccine platform performs with the seven different serotypes of foot and mouth disease,” she says. “Within a serotype, you don’t always get protection from one vaccine. For instance, the A serotype of FMD has many different subtypes. Depending on the type A that is causing the outbreak, different vaccines are needed for protection.

“Currently, DHS is performing preliminary evaluations on the marked vaccines and determining their efficacy, safety and other parameters before attempting to move them into licensure mode.”

As it stands right now, the DHS Targeted Advanced Development group at PIADC is working with industry to conduct pre-licensure studies on an adenoviral platform that was developed by the ARS.

Another ongoing effort is evaluation of what Beckham describes as “immunomodulators.” Immunomodulators have the capability of protecting animals from FMD between the time they are exposed to the virus and the time they become protected from vaccine. “We know there’s a time lag between the time you vaccinate an animal and you actually get protection,” she explains. “So what we want to know is if there is a way we can get the animal protected during that time frame between the time we vaccinate and the time the serotype-specific vaccine actually gives them protection.”

Immunomodulators

Immunomodulators are not serotype specific, so they would be able to provide protection against all seroptypes of FMD very early after exposure, Beckham says. This technology is “still very much in the discovery and development phase”; therefore a definitive timeline for immunomodulator licensure and availability is not currently available, she says.

As far as availability of marked vaccines, the target is to have the first one in the pipeline by 2009, she says. “The goal of the DHS Targeted Advanced Development group and the USDA is to have the first serotype licensed and ready for National Veterinary Stockpile acquisition by 2009. This goal includes licensure of one serotype in this new marked platform, but there are an additional six serotypes that will be in the pipeline and follow a similar development and licensure pattern.”

In addition to the vaccine development efforts, DHS has funded the Foreign Animal Disease Modeling Program, Beckham says. “This program is an effort to develop both an economic and epidemiological model for foot and mouth disease to determine how foot and mouth disease might spread if it were introduced into the United States, as well as the economic implications of the spread,” she adds. “This is intended to model what would happen following an intentional introduction of FMD in the United States. The nice thing about it is that it will model on a national level so it is a large-scale model.”

Although the initial development of the model has been for an FMD outbreak, it can also be adapted to other foreign animal diseases.

Diagnostics would be another important area in the control of an FMD outbreak. Researchers have developed and are testing a new multiplexed high-throughput diagnostic test for FMD.
Although this test is still in the validation stage, it shows a lot of promise,
according to Beckham. 


RAPID DIAGNOSTIC TEST DEVELOPED FOR FOOT-AND-MOUTH DISEASE

Lawrence Livermore National Laboratory (LLNL) scientists, in partnership with the federal Homeland Security and Agriculture departments and the University of California-Davis, have developed a rapid diagnostic test that simultaneously tests for foot-and-mouth disease (FMD) and six other look-alike diseases in livestock.

This new test, which is still in the process of validation, reduces the period for diagnosing all seven diseases from days to hours and could significantly reduce costs.

In addition to the test, team researchers have made two other important advances -- in testing samples and tracking samples -- that could provide a major boost in routine agricultural disease surveillance and fighting any instances of agroterrorism.

The USDA APHIS Veterinary Services has developed a sample-tracking component and database that will allow for more rapid sample processing and accurate sample tracking, according to Tammy Beckham, DVM, PhD, former Department of Homeland Security deputy director of science at the Plum Island Animal Disease Center.

“While still in the development phase, this collaborative project will significantly enhance the future security of U.S. agriculture by providing improved technology for animal disease diagnostics,” Beckham says.

“The test provides a tool that could be used for surveillance, which would significantly enhance the nation’s capacity for early detection of foot-and-mouth disease,” says LLNL veterinarian Pam Hullinger. “Finding the first case of FMD as soon as possible is critical to minimizing the scope and impact of an outbreak.” One estimate is that the United States would lose up to $3 million in direct costs for every hour’s delay in diagnosing FMD.

The Livermore assay tests for three foreign animal diseases and four endemic diseases. Three of these are foreign animal diseases: FMD, vesicular exanthema of swine and swine vesicular disease. Four are endemic diseases: bovine viral diarrhea, bluetongue, bovine herpes-1 and the parapox virus complex.

The concept of an assay that could test for multiple livestock diseases grew out of the 2001 outbreak of FMD in the United Kingdom that caused about $5 billion in losses to the food and agriculture sector. Up to 10 million sheep, pigs and cows were slaughtered, and for several months, the nation was banned from exporting livestock and animal products that could potentially transmit the virus.

“What the U.S. veterinarians who went to England really wanted was a test for confirming FMD with a quick turnaround, so they could make a decision on how to handle the individual farms,” says Alex Ardans, director of the UC-Davis-operated California Animal Health and Food Safety Laboratory System.

The assay screens for both DNA and RNA viruses at the same time and uses 17 signatures -- unique regions of DNA or RNA -- to assist in detecting FMD and the six other diseases that resemble FMD.

Initial studies to determine the performance characteristics of the assay have been performed at LLNL, DHS’ Plum Island Animal Disease Center, National Veterinary Services Laboratory and within the National Animal Health Laboratory Network.

Beyond the assay, researchers also have developed a high-throughput, semi-automated system that permits the analysis of 1,000 animal specimen samples within a 10-hour period using two robotic workstations and two technicians.

More information may be obtained from www.llnl.gov/pao.         


LESSONS LEARNED FROM THE UNITED KINGDOM

Richard Sibley knows firsthand about foot-and-mouth disease (FMD). Sibley, a practicing veterinarian in England, was directly involved in that country’s FMD epidemic in 2001.

“I was brought into the FMD strategy group to try to create a national strategy to deal with this,” Sibley says. “I would say that the strategy was very successful, despite its critics. The world’s worst FMD outbreak was effectively brought under control within three months and eradicated within seven months of it coming in, although at a huge cost.”

In the end, Sibley says, “what we used were mathematical models, combined with traditional FMD controls with a bit of common sense attached” to contain the epidemic.

He says that there were issues in the U.K.’s FMD containment effort that U.S. veterinarians and officials can learn from. One of the things you need to do is quickly euthanize and dispose of large numbers of animals in order to stop the spread of FMD, Sibley says.

“In the United States, you will have a big problem if you are going to try to kill out some of the big farms in 24 hours, and that’s what you have to do with such an infectious disease.”

In addition to the sheer logistics of such a thing, you also will be faced with negative public reaction and, more than likely, political interference, he says.

Diagnostics also is critical when dealing with FMD, according to Sibley. “It’s absolutely critical if you are going to control this disease, you have to recognize what the disease is quickly and accurately. It takes early diagnosis. You can’t wait for lab reports. You can’t sit there waiting for some guy to come back and say we’ve confirmed this as FMD. By the time you get that, the disease has moved on. You have to run on clinical diagnosis. It’s high sensitivity but unfortunately low specificity, but it’s speedy.

“The specificity of disease diagnosis depends, unfortunately, on which vet you get, how well-educated they are and whether they’ve seen it before. You have a bit of a problem because you will have to go find someone who knows what they are looking for. Sheep are the big problem where clinical signs are very variable and sometimes minor.”

Some herds and flocks were destroyed in England based on inaccurate clinical findings, according to Sibley. “We ended up killing 600,000 cattle and 3 million sheep throughout the outbreak. A grand total of 10 million animals lost their lives in the control of this outbreak.” About 1.2 million of these died not because they were FMD-infected, but just because they “happened to be on the farm next door,” Sibley says.

The curtailment of animal movement also is an issue to be aware of, Sibley says. “Nothing moves because it’s the movement of animals which is the biggest risk of transfer of the
disease.”

What was learned in Europe was “that our modern farming systems have developed on the basis that we move animals. We have calf-rearing units, heifer-rearing units, heifers calving down, which then have to get into a milking herd. If they are calving down on a farm with no milking facilities, what do you do? If you have animals trapped in fields away from the farm on different premises that have to come back for winter housing or you’ve run out of food, what do you do?”

In England, the decisions “were made based on risk, but a lot of animals were slaughtered due to welfare considerations even if they did not have FMD,” Sibley says. “There was the livestock welfare disposal scheme. Farmers could volunteer their stock to be slaughtered on the basis of not being able to look after them any longer because of the restrictions placed on them. And that killed 1.6 million animals. There was nothing wrong with them at all. But they were suffering from the disease-control program that had been imposed upon them.”

The trouble then is you have a couple of million animals being slaughtered in a very short time. “What do you do with them? Where do they go? All sorts of theories were bandied about as to how to dispose of dead stock,” Sibley explains. “The army was called in. In one county, they commissioned a huge unused ministry of defense airfield, and it’s now a huge burial pit for sheep. Trucks brought in dead sheep and put them in the pits.”

On top of this, there were newspaper photos on the front pages and television news reports that showed burning cattle. “Of course people then get interested,” Sibley notes. “This disease is not a public health disease. It is not an issue of food safety. It’s an issue where people are interested because they see it as another failure in farming systems to deliver health and welfare to the animals that were supposedly under the care of farmers.”

Sibley says that FMD vaccination also can create problems and prolong cleanup and eradication efforts. With currently available vaccines, you can’t distinguish between vaccinated animals and animals actually carrying the virus, he says.

“Before you pull the vaccine out of the drawer, understand how you will use it, what the strategy will be and how you are going to get out of it,” he recommends.