WASHINGTON, July 13 (UPI) -- The U.S. Department of Agriculture in late 2002 warned against using the same mad cow disease test the agency now is using in its expanded surveillance program for the deadly disorder, United Press International has learned.
The USDA said governments should not authorize the test, which is manufactured by Bio-Rad Laboratories in Hercules, Calif., because it can give false positives -- results that are ruled negative on follow-up testing -- and "will cause loss of consumer confidence in beef and beef products," the agency wrote in a letter to the World Organization for Animal Health in Paris.
The OIE, as it is known by its French initials, establishes international standards for animal disease issues.
The USDA recommended countries employ a different test manufactured by the Swiss firm Prionics -- a test the agency has licensed but has not yet put into use. The USDA's reason for the delay is the Prionics test, which has not yielded a false positive in more than 20 million tests in Europe, still must pass through the agency's validation procedures.
Concerns about false positives with the Bio-Rad test became a reality recently during the first month of the USDA's expanded surveillance plan, launched June 1 in response to the only confirmed U.S. case of mad cow last December. The agency reported two preliminary positive results, which caused concern among the public and havoc in the cattle futures markets until both were ruled negative on follow-up testing several days later.
So far, seven of the 12 state laboratories participating in the USDA's mad cow surveillance plan are using the Bio-Rad test and the remaining five are expected to opt for the test when they begin testing operations.
Experts on testing and mad cow disease have suggested one reason the USDA might have opted for Bio-Rad is the same reason it advised against it in 2002: its potential to yield false positives.
By releasing preliminary positives -- or inconclusives, as the USDA has deemed them -- that are later ruled negative, the agency could desensitize markets, consumers and foreign trading partners to real positive cases when and if they occur, the sources said.
"Bio-Rad was approved as a way of getting people used to a possible case if there ever was one," a veterinarian with expertise in mad cow disease told UPI.
"They (USDA officials) know it has a high false positive rate ... The more inconclusives they have, the easier it is to 'mix something up' and have all negative tests," said the veterinarian, who requested anonymity.
The veterinarian's comments were echoed by other experts in this field, who also declined to be named.
USDA spokeswoman Julie Quick did not respond to UPI's question of whether this was the agency's intended strategy. However, John Clifford, USDA's chief veterinary officer, acknowledged at a recent news conference that release of the inconclusive results could have that affect.
"We want to minimize the impacts upon the markets," Clifford said. "We feel like that after we get this information out there a couple of times that hopefully it will continue to minimize that impact."
To date, more than 15,000 cows have been tested under the surveillance plan and USDA officials have said they expect many more false positives as the agency seeks to conduct thousands of mad cow tests per week over the next 12 to 18 months.
Mad cow disease is otherwise known as bovine spongiform encephalopathy or BSE. Officials have said they also expect to find additional BSE cases.
Consumer groups and some members of Congress expressed concern about the USDA's decision to use the Bio-Rad test after the two false positives.
Sen. Conrad Burns, R-Mont., recently sent a letter to Agriculture Secretary Ann Veneman urging her "to seriously consider the reliability of your tests and to rigorously evaluate BSE screening tests used internationally that may offer more accurate results."
The concern to consumers is people can contract an incurable brain disorder called variant Creutzfeldt Jakob disease from eating meat infected with the mad cow pathogen. More than 150 people worldwide have become infected, but none of the cases has been linked to U.S. beef.
"Why are we using Bio-Rad instead of Prionics if they are as bad as the (USDA) would have us believe with all these 'inconclusives?'" asked Terry Singletary, coordinator of CJD Watch, an advocacy group for patients and family members. His mother died of a rare form of CJD called Heidenhain Variant, which has not been linked with mad cow disease.
"Do they really want to find all the cases, or are we just playing a (public relations) game?" asked Singletary, who has been sharply critical of the USDA's approach to mad cow. "How many more are we going to expose to this deadly pathogen?"
Brad Crutchfield, Bio-Rad's vice president, said the science and experience with his company's test in Europe establishes its soundness and reliability. Bio-Rad has yielded false positives only once every 300,000 tests, he said, adding that the false positives will decrease as the U.S. labs acquire more experience.
"The issue has nothing to do with the test, it has to do with the notification process," Crutchfield said, referring to the USDA's decision to notify the public of inconclusive results before they were confirmed or ruled out with confirmatory tests.
Heads of several state labs contacted by UPI said the agency allowed them to choose among five licensed rapid tests, including Bio-Rad's. However, outside testing experts said it was curious that all the labs chose the same test.
"It is slightly peculiar that it went all to one supplier for no other reason than you would want different tests because they give different results," said Roger Rosedale, chairman of Microsens Biotechnologies, a company in London that manufactures technology used in tests for detecting mad cow disease and similar disorders. One of Microsens' clients is Idexx Laboratories, which makes a competing mad cow test to Bio-Rad and Prionics.
At the time the labs were making their choices, the USDA said Bio-Rad was the only test the agency had "field tested," which apparently is a prerequisite for putting the tests into use.
The Bio-Rad test "was the only one that had been field tested, so that's limiting," said USDA's Quick. So although the USDA had licensed the other rapid tests, they may not have been available for use even if the laboratories had selected them.
The department also purchased the equipment needed to run the Bio-Rad test for the labs, some of which otherwise would not have been able to afford the machinery due to budget constraints.
A source with an American company that manufactures tests for detecting animal disease said it was unusual for the USDA to approve a test and then require field testing. Field trials are usually done before approval, the source said.
"With other tests, if you get USDA approval, you're all set," the source said. "This is something new."
Asked why the USDA was not using the Prionics Check test, as it had recommended in the 2002 OIE letter, Quick said it is still being "field tested." In the letter, however, the agency did not cite the need for a field test or validation procedure.
"Certain tests, such as the rapid tests, may not give an accurate picture of the BSE situation in a country or zone," the USDA wrote. "It is well known that certain rapid tests such as the Enfer and Bio-Rad tests have recorded false positive BSE results. For BSE-free countries or zones, the use of rapid BSE tests that give false positive results will cause loss of consumer confidence in beef and beef products."
A better approach would be to use the Prionics Check test, the agency wrote.
"For BSE free countries or zones, the use of histopathology, immunohistochemistry and the Prionics 'check' immunoblot test would provide a definitive diagnosis of a BSE suspect case," the letter stated.
Quick insisted the agency's statement was not intended to recommend against the Bio-Rad test. Instead, she said, it was meant to recommend that countries not simply rely on rapid screening tests as a way to confirm a case of mad cow disease.
No other testing experts UPI contacted interpreted the statement that way and Quick, who acknowledged she was not familiar with the technical details of the tests, declined to make Clifford or other USDA officials available to discuss the issue or offer clarification.
The USDA's decision not to release the samples from the two inconclusives for verification by outside labs has also come under question. The agency used a test called immunohistochemistry, or IHC, to determine the animals were not infected with mad cow, but experts said this is not always a foolproof test and it can miss cases.
Markus Moser, Prionics' chief executive officer and a molecular biologist, noted that Germany was considered BSE-free when using the IHC test. When officials there began using the Prionics rapid test in 2000, he said, they found several cases and so far have detected more than 300 infected animals.
Stuart Wilson, Microsens' scientific director and a molecular pathologist, noted in a document he recently prepared on false positives that there have been instances when Bio-Rad was used more than a few months before the animals would have developed symptoms. The test results were correctly positive, but IHC incorrectly ruled them negative.
"In a cow that you don't know is infected or not, it can always appear IHC positive (or negative) simply by changing the IHC timing," Wilson wrote in the document.
"This was one of the biggest problems with investigating tonsils in asymptomatic humans in the United Kingdom," the document said, referring to a recent study that indicated as many as 3,800 people in England may be unwittingly incubating vCJD.
In the December mad cow case, the USDA had the results confirmed by the Weybridge laboratory in the United Kingdom, which is one of the three mad cow disease testing reference laboratories recognized by the OIE. The other two are in Switzerland and Japan.
"It must by definition create doubt if they're not allowing any other ... OIE reference laboratory have access to them," Rosedale said. "It's not to suggest (the USDA) guys are not competent, but why would they not release it?"
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Steve Mitchell is UPI's Medical Correspondent. E-mail [email protected]
