Mad cow disease: back in the headlines

April 2001

After a seemingly quiet year in 2000, mad cow disease, aka bovine spongiform encephalopathy (BSE), was back in the headlines with a vengeance starting early in 2001, and has persisted to this day. After apparently being largely confined to the United Kingdom, there is now widespread recognition of BSE virtually throughout Western Europe. This has had profound effects on the European cattle industry, in addition to what the British cattle industry has been through (now further decimated by foot-and-mouth disease). In addition, there are renewed concerns in the United States about the safety of blood donations from individuals who have lived in Europe, and increasing concerns about possible importation of BSE into this country.

Regarding the safety of the U.S. blood supply: in 1999, the FDA banned blood donation by people who had spent six months or more in the United Kingdom from 1980 to 1996. This period was believed to be the “at-risk” period for eating BSE-infected British beef. Earlier this year, however, and based on the recognition of BSE-infected cattle in many countries in Europe, an FDA advisory committee recommended extending that ban to people who have spent 10 years or more since 1980 in several other countries, France, Portugal and Ireland. Recall that there is not a shred of epidemiologic evidence suggesting that bloodborne transmission has occurred. On the other hand, there is a theoretical risk that it could occur, and since it is impossible to completely rule out such a possibility, the proposed extension of the ban seems to be a conservative and cautious judgment.

How safe are we?

Just how safe are we in this country, from both BSE and its likely human expression, new variant Creutzfeld-Jakob disease (nvCJD)? It is important to be aware of the extent of the “safety net” that has been established.

Responsibility for safety of the food supply falls principally on two government agencies, the U.S. Department of Agriculture (USDA) and the FDA. No British beef has been imported into the United States since 1985, and importation of live cows from BSE-infected countries was banned in 1989. Did these steps interdict the possible importation of BSE? Unfortunately, the answer is “no,” since high-risk European beef products continue to be imported into the United States. Such products include gelatin, collagen, semen and albumin; these products are used to manufacture cosmetics and vaccines. Although some vaccines currently in use were made with imported serum albumin, the risk is believed to be vanishingly small, and lots currently in production do not use imported albumin products. However, dietary supplements used in this country may still contain a variety of imported bovine tissues, including brain! Thus, exclusion of BSE-contaminated beef from the United States is incomplete at best, and applies only if the tissue is destined to be used in food and medicines.

For these and other reasons, close surveillance is also maintained on the U.S. cattle supply. Here individual farmers, USDA inspectors, and veterinarians form the “front line” of surveillance, looking for odd behaviors, or the more alarming signs of uncoordination, unusually aggressive behavior, or wasting. Once the suspect animal dies or is killed, samples of brain tissue are harvested, examined, and if BSE is suspected, the samples sent to the USDA laboratory in Ames, Iowa. If the diagnosis were to be confirmed, the sample would be sent by courier to the Central Veterinary Laboratory in England; this laboratory is considered virtually a world reference lab, since it has by far the most expertise in BSE diagnosis. In the past decade, the USDA laboratory has processed almost 12,000 cattle brain specimens, and has found no evidence of BSE. Note, however, that in the United States, a test of brain tissue is not required for cattle to enter the human food supply.

There is another theoretical risk to the U.S. food supply, and that is a transmissible encephalopathy that is expanding in populations of deer and elk in the western part of the country, referred to as chronic wasting disease. Could people who eat deer and elk meat be at risk of nvCJD, or already have the clinical disease? Thus far, at least, all the evidence is negative, and most experts doubt that this is a significant threat, although it is, again, a theoretical possibility.

In addition, a National Prion Disease Pathology Surveillance Center has been established at Case Western Reserve University, charged with examination of neural tissue from people who have died with unusual neurologic conditions manifested by dementia and loss of motor control. With more than 500 brain samples examined so far, almost 300 had classical CJD, and others had brain tumors or conditions that mimicked CJD. No cases were seen with the unique and diagnostic neurohistopathology of nvCJD.

All this, of course, is quite reassuring, though not totally so. There will always be the lingering concern that — maybe — it could happen here. The consequences for the U.S. cattle industry would be catastrophic. Even absent cases of either BSE or nvCJD in this country, there are very complicated international logistics, political sensitivities, and perhaps worst of all, enormous scientific uncertainties, especially regarding transmissibility.

For the time being, the “Holy Grail” for those working with the transmissible spongiform encephalopathies must surely be improved diagnostic methodologies. The “gold standard” tests are direct histologic examination of brain tissue, and the standard test to determine transmissibility is a mouse cerebral inoculation test. Obviously, neither or these are simple, rapid or cheap. Substantial progress is being made in the development of new rapid tests to detect the abnormal brain prion, and these may eventually replace the mouse inoculation test; even these newer and more rapid tests, however, still require brain tissue. The ideal test, of course, would be a rapid screening test that could be run on serum or saliva, and although much work is being done to achieve that goal, there is nothing yet on the horizon.

Space does not permit extensive discussion of the resistance to destruction that characterizes the abnormal prions of CJD and nvCJD; the hospital infection control community is already familiar with this issue, and these patients pose some of the most perplexing problems in nosocomial infection control. Perhaps the most aggravating of these problems is our inability to judge whether the apparent lack of nosocomial transmission results from effective infection control practices, or simply because there was little or no risk of transmission in the first place! However, in a recent development, French and English investigators reported that they successfully adapted the BSE agent to primates, and that infected mouse brain homogenates given intravenously (not intracerebrally, as typically administered) successfully transmitted the disease to macaques. Although this does not speak to the issue of bloodborne transmission, it does establish that transmission can occur via the IV route. (PNAS. 2001; 98: 4142-47.)

I would commend to interested readers a review of these issues by Paul Brown and his colleagues, in the Jan-Feb 2001 issue of Emerging Infectious Diseases. It is also available online at: www.cdc.gov/ncidod/eid/vol7no1/brown.htm.