|Trends & Perspectives|
With the discovery of a bovine spongiform encephalopathy (BSE)–positive cow in Washington state last December 23rd, the United States lost its BSE-free status. The loss of several U.S. beef importing partners, a fall in domestic beef prices, and a decline in consumer confidence followed.
Part of USDA’s plan to eradicate BSE is an increase in surveillance testing. The question now is, even with this increase, will its surveillance program be wide enough to truly reveal the prevalence of the disease among U.S. cattle and provide customers with reasonable assurance of a safe food supply?
On February 9th, USDA ended its search for cattle exposed to the same feed as the BSE-infected cow. The agency had failed to locate 11 of the 25 cows that were likely to have eaten the potentially infectious feed. In addition, what happened to much of the 10,410 pounds of beef, consisting of the meat from the BSE-infected cow mixed in with the meat from 19 other cows, is unknown. Given the two-week span of time between slaughter and recall, officials say that it is likely that some of the meat was eaten. USDA said the infectious parts of the cow, including the brain and spinal cord, were removed before processing.
Such end-of-the-line protection methods as using recalls are evidently not entirely effective, as it is likely that some of the missing, and possibly infectious, beef was eaten. An increase in diagnostic testing, coupled with USDA’s newly implemented “test-and-hold” policy, should prevent meat from tested cows from being processed until test results come back negative.
The gold standard technique, and the only test used by USDA, for identifying the BSE agent is immunohistochemistry (IHC). However, rapid tests have proven to be very effective as well. According to Mary Jo Schmerr, PhD, research chemist, respiratory and neurologic disease research at USDA’s National Animal Disease Center, “the screening tests probably are just about as accurate as immunohistochemistry. There’s one test that’s a Western blot test, which can also be used as a gold standard.”
Although extremely accurate, IHC testing requires highly skilled technicians and veterinarians, lengthy sample preparation that results in the generation of toxic waste materials, and a test turnaround time of several days. In regard to the IHC test, Schmerr says, “that technology is really not a surveillance technique, which is what the U.S. government is using it for right now.”
Similarly reliable, far more rapid, and less costly tests are available and have been approved for use in the European Union, Japan, and Canada for years, so one wonders why USDA has not already made such tests a part of its surveillance program. Sources at USDA’s Animal and Plant Health and Inspection Service attribute the agency’s lack of licensed rapid BSE tests to the fact that the United States previously had BSE-free status, and therefore consideration of such testing was not necessary. During the second week in January, USDA called for submission of rapid tests for review.
In addition to considering alternate testing techniques, USDA demonstrated its willingness to review its BSE testing policy by appointing an international panel of experts to review and assess the agency’s BSE surveillance measures. The panel’s findings will, presumably, have a strong impact on the way in which USDA conducts its surveillance in the future. During a technical briefing on BSE on January 26th, Ron DeHaven, DVM, chief veterinary officer at the USDA, said, “We are evaluating our risk and will certainly rely very heavily on the recommendations from the international review team . . . with regard to additional enhancements to our overall [BSE surveillance] program and measures.”
In its report, this review team stated that implementation of rapid testing will be an important part of improving USDA’s surveillance program. In the report, the panel stated that it “recommends the adoption of rapid immunodiagnostic assays as the primary screening tests for active surveillance . . . [and recommends] that a number of laboratories throughout the country be governmentally approved to conduct screening tests as part of the national surveillance program.” Several major IVD manufacturers have submitted their rapid tests to USDA for review.
Bio-Rad Laboratories (Hercules, CA) has submitted its TeSeE (formerly Platelia) BSE test to USDA for review. The test was developed in collaboration with the French atomic energy administration, the Commissariat à l’Energie Atomique (CEA; Paris). The test relies on enzyme-linked immunosorbent assay (ELISA) technology, and is priced competitively with the other rapid tests on international markets. The company claims that its test is the most widely used in Europe and Japan.
According to BioRad, the test was quickly adopted as the standard in Japan when a cow with visible BSE symptoms tested negative using another rapid test, but tested positive with the Bio-Rad test. News of the test’s accuracy quickly spread, and, according to Brad Crutchfield, vice president of the Life Science Division of Bio-Rad, “In the second round of testing [in the European Union, the second-generation BSE tests] were all compared against the Bio-Rad test because our test is considered the world standard. It is the most heavily used by now.”
Abbott Laboratories’ ELISA-based BSE test was developed by Enfer Scientific (Newbridge, Kildare, Ireland). However, Abbott representatives believe that the company’s greatest advantage, when it comes to testing for the BSE agent, comes from Abbott’s extensive experience with blood testing.
Rhonda Luniac, a spokesperson for Abbott said, “Although the [BSE] testing technology is quite different because you’re working with a different sample and different storage materials, there are similarities in the processes, as far as tracking, holding, testing, and releasing. We see numerous parallels between the screening of the nation’s beef and the protection of the blood supply.” Regarding its decision to select the Enfer test over others, Luniac said, “as the world’s largest testing facility of bovine and ovine tissues for the detection of TSE, Enfer Scientific possesses vast experience within the food and agriculture industry.”
Beckman Coulter (Fullerton, CA) licensed a BSE test from InPro (San Francisco). This Conformation-Dependent Immunoassay (CDI-5) sets itself apart from the first generation of BSE tests in that it relies on a detection technique that does not destroy any of the disease-causing forms of the prion protein. As such, company representatives have voiced an intention to develop a similar test for live animals. Anne M. Warde, a spokesperson for Beckman, said, “in line with our strategy is the possibility that the technology may be developed for use in other neurodegenerative disorders such as Alzheimer’s, Parkinson’s disease and Lou Gehrig’s Disease.”
In opting to license the CDI-5 test over other tests, the company was also drawn to the association with Stanley B. Prusiner, MD, Nobel Prize– winning professor of neurology and biochemistry at the University of California, San Francisco, who developed the test. The CDI-5 test works by comparing the antigen-antibody binding affinities of prions in their native state with those of their unfolded state.
Roche (Basel, Switzerland) has licensed the Check Western by Prionics (Zurich, Switzerland). According to Roche, “a breakthrough of the test is that its performance is not impeded when partly or fully degraded tissue samples are used, [is] as typically occurring in surveillance programs focusing on downer cattle.”
These tests may allow for more BSE testing to take place, and in a shorter amount of time than is required for the IHC test. According to Schmerr, “you can take a brain sample and report back to the attending veterinarian, and a tech can move the carcasses as they’re passed. That can be done within 12 hours so the [beef processing] lines can move forward.”
BSE testing in the United States has been limited to a small segment of the cattle population because, according to Jim Rogers, spokesperson for the USDA’s Animal and Plant Health Inspection Service, the purpose of BSE testing in the United States has been “surveillance [testing] to determine whether or not there is prevalence of BSE in a livestock population.”
Until now, the BSE surveillance program in the United States has focused on screening “downer cattle,” or cattle that are unable to walk at the time of slaughter, as such a condition is one symptom of BSE. “A higher-risk population such as downers, dead stock, animals that show clinical signs of neurological or central nervous system disease, that’s the pool of animals most likely to have the disease, so that’s why we test there,” says Rogers.
However, a cow can be infected with the BSE agent for two to three years before showing any outward symptoms of disease. In fact, there is some question about whether the BSE-infected cow found in Washington was, in fact, a downer. Although Secretary of Agriculture Ann M.Veneman says that the BSE-positive cow was a downer, Dave Louthan, the cattle hand who slaughtered the cow, has made statements to the contrary, saying that the cow was “a perfectly good walking cow.”
According to Louthan, the fact that the cow was tested for BSE was just a fluke. She arrived at the slaughterhouse in a trailer containing many downers, and although she was standing, she was stubborn about exiting the trailer. As is the procedure with downers, she was slaughtered in the trailer, and therefore processed along with the downers. “If I’d took the time to run her around to the pens, we’d never have known that cow had mad cow. She’d have gone right in,” he said.
Only 10% of the 200,000 downer cattle slaughtered in 2003 were tested for BSE. When looking at the entire population of 35 million cattle that were slaughtered for consumption last year, this figure amounts to one tenth of one percent of cattle having been tested. When asked whether the USDA testing policy has been sufficient to determine the prevalence of BSE-infected cows in the United States, Rogers said, “we were actually testing four to seven times higher than the rate [the OIE guidelines] require. Our testing goal was actually only 12,500.”
Once the BSE-positive cow was found, USDA pledged to double the number of cows that it tests for BSE, which would lead to an increase in testing from 20,000 cows to 40,000. According to some, this amount of testing is not enough to truly determine the prevalence of the disease. “I think that probably the [USDA] policy will move toward testing more animals. They have already said that they will test twice as many, but they need to increase that number,” says Schmerr.
“Looking at the numbers statistically: if they test 20,000 animals of a population of roughly about 200,000– 300,000 [downer] cattle and they find one [BSE-positive cow] in 20,000, then you can just do the mathematics, and find that there’s probably a few more [BSE-positive cows] in that population [of downers]. It’s difficult to know [the true prevalence of BSE] though, unless the testing actually is performed on a large number of animals. I’m talking about testing approximately a million so that we could get some kind of statistical analysis of how many really are positive in that [U.S.] population.”
Some would go so far as to request that all U.S. cattle be tested. Japan, the number-one importer of American beef, has put a ban on the import of all beef from the United States until USDA agrees to match Japan’s policy of testing all slaughtered cows. Congressman George Miller (D-CA) plans to introduce a bill requiring that USDA test all cattle bound for human consumption.
Experts, such as Schmerr, believe that testing all cattle might be too costly and unnecessary. However, a far broader base of testing is certainly doable, and necessary to assess the prevalence of the disease. Japan tests all cows, UK tests all cows over 24 months, and continental Europe tests all cows over 30 months. “The logistics of all of the slaughterhouses [in the United States] would probably have to be changed a little bit, about the way that they hold the carcasses after the animals are slaughtered. I think that we’ll still have to [make these modifications] because, even if we test 100,000 animals, the capacity to test by the current IHC test isn’t there. It’s going to eventually happen,” says Schmerr.
The USDA-appointed panel of experts agrees that the increase in testing is necessary, stating, “the surveillance program in the USA must be significantly extended in order to measure the magnitude of the [BSE] problem.” The panel “recommends testing of all cattle [in high BSE-risk populations, including cows that appear to be sick, die on the farm, or are unable to walk at slaughter], older than 30 months, and strengthening of the passive surveillance system.”
If, as the panel recommends, all downers were tested for BSE, then at least 200,000 cows would need to be tested. In addition, the panel said, “testing of a random sample of healthy slaughter cattle over 30 months should be strongly considered.”
Even if USDA tested all downers arriving at the slaughterhouses, there is some suspicion that cases of BSE may be missed when cows that are ill or die on the farms are not tested for BSE. Caroline Smith DeWaal, food safety director for the Center for Science in Public Interest (Washington, DC) said, “all downer cattle on ranches must be tested, to ensure that ranchers don’t try to hide evidence of the disease.” In addition, the expert panel noted that financial incentives may need to be offered to ranchers in order to persuade them to test fallen, and potentially ill, cattle that die on the ranch.
USDA has said that it is taking the experts’ findings into consideration. Findings related to BSE prevalence in other countries seem to strongly support the panel’s recommendations. Other countries with a positive BSE status have found that the disease prevalence can be as high as one in 14,000. In addition, among those cows that test positive, more than half show no symptoms.
However, it may be some time before any significant action will be taken by USDA to increase testing. In his budget proposal for FY 2005, President George Bush requested $17 million, enough for testing only 40,000 cattle for BSE, and $5 million for advanced research and development of BSE testing technologies.
In addition to the rapid tests under consideration by USDA, a great effort is being made to develop a test that can be performed on a live animal. However, it is very difficult to detect the disease-causing mutant form of the prion in the blood.
Companies with blood tests in development include Q-RNA (New York City), the Robert Koch Institute (Berlin), and GeneThera (Wheat Ridge, CO). USDA has also been working on such tests. “I myself have developed a test that needs a lot more work to make it more robust, but it detects the prion in the blood. The sample preparation is difficult because you are trying to concentrate things like five to ten thousand times. And when you do that, you end up with problems with nonspecific binding, and so there are many things that need to be worked on,” said Schmerr.
When asked about viable new technologies that can be applied to developing a test, Schmerr said, “there are some tests and techniques out there that are pretty promising, that may work. There’s a test called the SIFT; that stands for scanning for intensely fluorescent targets. And there’s some work being done with ultrasound, and some work being done with a technology called Fourier transform IR (FTIR).”
Unfortunately, a fundamental opposition of interests within various USDA departments may hamper the strengthening of the U.S. surveillance system via the adoption of rapid tests and development of blood tests. According to Schmerr, “The Department of Agriculture has basically been given two charges, which are to be a cheerleader for the cattle industry and also the charge for food safety. It’s very difficult to do both because a lot of times there’s a direct conflict with the interests of one over the other.”
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