BSE: New tests on the horizon


While German officials discuss lifting the age at which cattle should be tested for bovine spongiform ecephalopathy (BSE) from 24 months to the EU-approved 30 months, one researcher - who has developed a novel test - argues the age should be lowered.

BioMedNet, News, 24. Dezember 2003


BMN241203 - The process of BSE testing in cattle is far from perfect. Only slaughtered animals can be tested, and to prove that an animal is infected, it takes time before sufficient prion material has accumulated in the brain and can be detected. Because of this, the EU age limit for BSE testing is 30 months. In some countries, including Germany, it is 24 months.

This could mean that younger cattle infected with BSE might not be discovered. However, after millions of tests in three years, only two infected animals younger than 30 months (both 28 months) have been identified. So Germany's health experts are considering raising the age limit in line with EU recommendations.

But Bertram Brenig, director of the Institute of Veterinary Medicine at Göttingen University in Germany, claims raising the age limit would be taking the wrong direction. After a few cases of infected cattle in Japan and France where infected animals were younger than the existing limit of 24 months, much younger animals must be tested, he demands.

To solve the dilemma of tests that are not able to detect BSE in younger cattle, he offers a new kind of blood test with, he claims, two advantages: the test detects BSE in younger cattle, and animals do not need to be killed first. Furthermore, he says, one positive test in a herd would no longer mean killing the entire cattle cohort (all animals born in the year before and in the year after the positive tested animal was born).

Once the test has been in place for two years, Brenig predicts, "Numbers of BSE cases will have reduced significantly."

Instead of scanning the brains of dead cattle for prion proteins, Brenig's test investigates a marker in the animals' blood called microvesicular associated RNA. "These nucleic acids was first recognized in the serum of veterans suffering from Gulf War Syndrome and reflect sub-clinical changes to individuals exposed to toxic events," he told BioMedNet News. Nobody knows how, but it is thought that the host genome responds to a toxic event, in part, by expressing and releasing nucleic acids that differ from normal status: "The detection of these non-normal status nucleic acid profiles is the basis of the living test," he said. Similar nucleic acid traces have also been found in some cancer cases. Brenig and his colleagues have patented their BSE test in the US.

"It sounds interesting, but his test is not authorized by the EU," says Thomas Mettenleiter, director of the Federal Research Center for Viral Diseases of Animals, at the Isle of Riems in the Baltic Sea. He agrees that a test for living animals would be useful, but thinks 24 months as a minimum age would be enough. "After the two cases in Japan, I think it's better not to lift the age limit to 30 months," he said. Asked about the case in France, he replied: "This was an untypical case of BSE concerning its prion pattern, as we also have one in Italy, but this has nothing to do with untypical age."

Even one of the two cases in Japan seems not to show that tests for younger cattle are needed, says Konrad Beyreuther, a molecular biologist from Heidelberg University who is also minister of state in Baden-Wuerttemberg with responsibility for BSE. Beyreuther advocates raising the age limit from 24 months to 30 months. Although the regular BSE test on this young animal in Japan showed an infection with BSE, further tests did not confirm the finding. And the prion test was not repeated. Thus, doubts remain about the result.

But even if there was a need to test younger cattle, Brenig's peers doubt that his test will hold what he promises. "There are no articles where he presented his results," says Michael Beekes of the Robert Koch Institute in Berlin. Beekes' team has just published promising results on their own blood test for BSE in living animals. They describe their postmortem serum analysis in the December issue of Analytical Chemistry. Their test works by comparing serum spectra of different cattle. The team reached as far as 96% sensitivity and specificity of BSE detection.

Mettenleiter agrees with Beekes: "Nothing is validated, nothing is known about the test´s reliability." But Brenig remains defiant. "We have presented results on two congresses, one in May in the US, and one in October at the International Prion Conference in Munich. Furthermore have we described our method in a magazine called New Food," he said. (New Food is a business magazine for the food and drink industry and is not a peered reviewed scientific journal.)

Brenig´s peers also accuse him of testing too few animals and not using blinded tests, though he says that he has carried out blind analysis and has submitted data on six BSE-positive animals for publication in a peer reviewed journal.

But six animals are not sufficient to authorize a BSE-test-alternative for Europe. Brussels demands tests of at least 200 animals. "We know that, but if you keep in mind that in Germany there were only around 280 cases of BSE in the last three years, you could imagine our problems," said Brenig. "Even in Britain or elsewhere we can´t get enough blood samples."

In addition, he says, at the start of his research he thought six animals would be enough: "Our study design was geared to the initial design for testing the first BSE tests, and six animals were enough then." However, Beekes´ team at the Robert Koch Institute has serum samples from 249 confirmed BSE cases from the Veterinary Laboratories Agency in Weybridge, UK.

With insufficient samples, Brenig´s team changed its strategy. Instead of offering an alternative to the present BSE test for individual cattle, which has to be authorized by the EU, he and his team plan to market a risk test for whole populations in 2004. "This will be comparable to scrapie tests in sheep to build up herds with a low risk for scrapie," he said. Cattle will then be classified into several groups based on differences in RNA patterns. Michael Beekes, by contrast, is much more cautious. Referring to his own test, he said: "[We] will have to do a lot of work before one could say the test is reliable."

BioMedNet, News, 24. Dezember 2003

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