Mad cow disease

Mad cow disease, a relatively newly discovered malady, was first identified in Britain in 1986, when farmers noticed that their cows' behavior had changed. The cows began to shake and fall, became unable to walk or even stand, and eventually died or had to be killed. It was later determined that a variation of this fatal neurological disease, formally known as Bovine Spongiform Encephalopathy (BSE), could be passed on to humans.

It is still not known to what extent the population of Britain and perhaps other countries is at risk from consumption of contaminated meat and animal by-products. The significance of the BSE problem lies in its as yet unquantifiable potential to not only damage Britain's $7.5 billion beef industry, but also to endanger millions of people with the threat of a fatal brain disease.

A factor that stood out in the autopsies of infected animals was the presence of holes and lesions in the brains, which were described as resembling a sponge or Swiss cheese. This was the first clue that BSE was a subtype of untreatable, fatal brain diseases called transmissible spongiform encephalopathies (TSEs). These include a very rare human malady known as Creutzfeldt-Jakob Disease (CJD), which normally strikes just one person in a million, usually elderly or middle-aged. In contrast to previous cases of CJD, the new bovine-related CJD in humans is reported to affect younger people, and manifests with unusual psychiatric and sensory abnormalities that differentiate it from the endemic CJD. The BSE-related CJD has a delayed onset that includes shaky limb movements, sudden muscle spasms, and dementia.

As the epidemic of BSE progressed, the number of British cows diagnosed began doubling almost yearly, growing from some 7,000 cases in 1989, to 14,000 in 1990, to over 25,000 in 1991. The incidence of CJD in Britain was simultaneously increasing, almost doubling between 1990 and 1994 and reaching 55 cases by 1994. In response to the problem and growing public concern, the government's main strategy was to issue reassurances. However, it did undertake two significant measures to try to safeguard public health. In July 1988, it ostensibly banned meat and bone meal from cow feed, but failed to strictly enforce the action. In November 1989, a law that intended to remove those bovine body parts considered to be the most highly infective (brain, spinal cord, spleen, tonsils, intestines, and thymus) from the public food supply was passed. A 1995 government report revealed that half of the time, the law was not being adhered to by slaughterhouses. Thus, livestock—and the public—continued to be potentially exposed to BSE.

As the disease continued to spread, so did public fears that it might be transmissible to humans, and could represent a serious threat to human health. But the British government, particularly the Ministry of Agriculture, Fisheries, and Food (MAFF), anxious to protect the multibillion dollar cattle industry, insisted that there was no danger to humans. However, on March 20, 1996, in an embarrassing reversal, the government officially admitted that there could be a link between BSE and the unusual incidence of CJD among young people. At the time, 15 people had been newly diagnosed with CJD. Shocking the nation and making headlines around the world, the Minister of Health Stephen Dorrell announced to the House of Commons that consumption of contaminated beef was "the most likely explanation" for the outbreak of a new variant CJD in 10 people under the age of 42, including several teenagers. Four dairy farmers, including some with infected herds, had also contracted CJD, as had a Frenchman who died in January 1996.

British authorities estimated that some 163,000 British cows had contracted BSE. But other researchers, using the same database, put the figure at over 900,000, with 729,000 of them having been consumed by humans. In addition, an unknown number had been exported to Europe, traditionally a large market for British cattle and beef. Many non-meat products may also have been contaminated. Gelatin, made from ligaments, bones, skin, and hooves, is found in ice cream, lipstick, candy, and mayonnaise; keratin, made from hooves, horns, nails, and hair, is contained in shampoo; fat and tallow are used in candles, cosmetics, deodorants, soap, margarine, detergent, lubricants, and pesticides; and protein meal is made into medical and pharmaceutical products, fertilizer , and food additives . Bone meal from dead cows is used as fertilizer on roses and other plants, and is handled and often inhaled by gardeners.

In reaction to the government announcement, sales of beef dropped by 70%, cattle markets were deserted, and even hamburger chains stopped serving British beef. Prime Minister Major called the temporary reaction "hysteria" and blamed the press and opposition politicians for fanning it.

On March 25, 1996, the European Union banned the import of British beef, which had since 1990 been excluded from the United States and 14 other countries. Shortly afterwards, in an attempt to have the European ban lifted, Britain announced that it would slaughter all of its 1.2 million cows over the age of 30 months (an age before which cows do not show symptoms of BSE), and began the arduous task of killing and incinerating 22,000 cows a week. The government later agreed to slaughter an additional l00,000 cows considered most at risk from BSE.

A prime suspect in causing BSE is a by-product derived from the rendering process, in which the unusable parts of slaughtered animals are boiled down or "cooked" at high temperatures to make animal feed and other products. One such product, called meat and bone meal (MBM), is made from the ground-up, cooked remains of slaughtered livestock—cows, sheep, chicken, and hogs—and made into nuggets of animal feed. Some of the cows and sheep used in this process were infected with fatal brain disease. (Although MBM was ostensibly banned as cattle feed in 1988, spinal cords continued to be used.)

It is theorized that sheep could have played a major role in initially infecting cows with BSE. For over 200 years, British sheep have been contracting scrapie, another TSE that results in progressive degeneration of the brain. Scrapie causes the sheep to tremble and itch, and to "scrape" or rub up against fences, walls, and trees to relieve the sensation. The disease, first diagnosed in British sheep in 1732, may have recently jumped the species barrier when cows ate animal feed that contained brain and spinal cord tissue from diseased sheep. In 1999 the World Health Organization (WHO) implored high-risk countries to assess outbreaks of BSE-like manifestations in sheep and goat stocks. In August 2002, sheep farms in the United Kingdom demonstrated to the WHO that no increase in illnesses potentially linked to BSE occurred in non-cattle livestock. However, that same year, the European Union Scientific Steering Committee (SSC) on the risk of BSE identified the United Kingdom and Portugal as hotspots for BSE infection of domestic cattle relative to other European nations.

Scrapie and perhaps these other spongiform brain diseases are believed to be caused not by a virus (as originally thought) but rather by a form of infectious protein-like particles called prions, which are extremely tenacious, surviving long periods of high intensity cooking and heating. They are, in effect, a new form of contagion. The first real insights into the origins of these diseases were gathered in the 1950s by Dr. D. Carleton Gajdusek, who was awarded the 1976 Nobel Prize in Medicine for his work. His research on the fatal degenerative disease "kuru" among the cannibals of Papua, New Guinea, which resulted in the now-familiar brain lesions and cavities, revealed that the malady was caused by consuming or handling the brains of relatives who had just died.

In the United States, Department of Agriculture officials say that the risk of BSE and other related diseases is believed to be small, but cannot be ruled out. No BSE has been detected in the United States, and no cattle or processed beef is known to have been imported from Britain since 1989. However, several hundred mink in Idaho and Wisconsin have died from an ailment similar to BSE, and many of them ate meat from diseased "downer" cows, those that fall and cannot get up. Some experts believe that BSE can occur spontaneously, without apparent exposure to the disease, in one or two cows out of a million every year. This would amount to an estimated 150–250 cases annually among the United States cow population of some 150 million. Moreover, American feed processors render the carcasses of some 100,000 downer cows every year, thus utilizing for animal feed cows that are possibly seriously and neurologically diseased.

In June 1997, the Food and Drug Administration (FDA) announced a partial ban on using in cattle feed remains from dead sheep, cattle, and other animals that chew their cud. But the ruling exempts from the ban some animal protein, as well as feed for poultry, pigs, and pets. In March of that year, a coalition of consumer groups, veterinarians, and federal meat inspectors had urged the FDA to include pork in the animal feed ban, citing evidence that pigs can develop a form of TSE, and that some may already have done so. The coalition had recommended that the United States adopt a ban similar to Britain's, where protein from all mammals is excluded from animal feed, and some criticized the FDA's action as "totally inadequate in protecting consumers and public health."

The United States Centers for Disease Control (CDC) has reclassified CJD that is associated with the interspecies transmission of BSE disease-causing factor. The current categorization of CJD is termed new variant CJD (nvCJD) to distinguish it from the extremely rare form of CJD that is not associated with BSE contagion. According to the CDC, there have been 79 nvCJD deaths reported worldwide. By April 2002, the global incidence of nvCJD increased to 125 documented reports. Of these, most (117) were from the United Kingdom. Other countries reporting nvCJD included France, Ireland, and Italy. The CDC stresses that nvCJD should not be confused with the endemic form of CJD. In the United States, CJD seldom occurs in adults under 30 years old, having a median age of death of 68 years. In contrast, nvCJD, associated with BSE, tends to affect a much younger segment of society. In the United Kingdom, the median age of death from nvCJD is 28 years. As of April 2002, no cases of nvCJD have been reported in the United States, and all known worldwide cases of nvCJD have been associated with countries where BSE is known to exist. The first possible infection of a U.S. resident was documented and reported by the CDC in 2002. A 22-year-old citizen of the United Kingdom living in Florida was preliminarily diagnosed with nvCJD during a visit abroad. Unfortunately, the only way to verify a diagnosis with nvCJD is via brain biopsy or autopsy. If confirmed, the CDC and Florida Department of Health claim that this case would be the first reported in the United States.

The outlook for BSE is uncertain. Since tens of millions of people in Britain may have been exposed to the infectious agent that causes BSE, plus an unknown number in other countries, some observers fear that a latent epidemic of serious proportions could be in the offing. (There is also concern that some of the four million Americans alone now diagnosed with Alzheimer's disease may actually be suffering from CJD.) There are others who feel that a general removal of most infected cows and animal brain tissue from the food supply has prevented a human health disaster. But since the incubation period for CJD is thought to be 7–40 years, it will be some time before it is known how many people are already infected and the extent of the problem becomes apparent.

[Lewis G. Regenstein ]

RESOURCES

BOOKS

Rhodes, R. Deadly Feasts. New York: Simon & Schuster, 1997.

PERIODICALS

Blakeslee, S. "Fear of Disease Prompts New Look at Rendering." The New York Times, March 11, 1997.

Lanchester, J. "A New Kind of Contagion." The New Yorker, December 2, 1996.

MAD COW DISEASE.

Mad cow disease or bovine spongiform encephalopathy (BSE) was first identified in the United Kingdom in November 1986. The disease is one of a family of neurodegenerative diseases known as transmissible spongiform encephalopathies, which cause deterioration of cells in the brain and eventual death. By January 2005 more than 182,000 clinical cases of BSE had been confirmed in cattle in Great Britain, with epidemics also occurring on a smaller scale in other European countries including Northern Ireland, the Republic of Ireland, Switzerland, Portugal, and France. Worldwide cases have been confirmed as far away as Canada, the United States, and Japan. The economic impact of BSE in badly affected countries has been great, with the worldwide export ban imposed on the United Kingdom by the European Union between 1996 and 1999 having a long-lasting effect on the cattle industry in that country. In tandem, there has been a drop in consumer confidence, not only in beef products but also in the overall safety of food, triggered by other disease outbreaks caused by salmonella and other bacterial contamination. To combat this situation, the Food Standards Agency was formed as an independent food safety watchdog in 2000 to protect the public's health and consumer interests in relation to food.

BSE is thought to have originated in cattle from supplementary feed containing meat and bone meal (MBM) contaminated by a scrapie-like agent derived from sheep or cattle, although much debate continues over its origin. In the United Kingdom the disease was made notifiable in June 1988 and in July 1988 a ban on the use of ruminant-based MBM in cattle feed came into force in Great Britain. Although the ban did not prevent all infections and cases in animals born after 1988, the number of cases of BSE in Great Britain has continued to decline, demonstrating that MBM feeding practices had been the major route of transmission. However, even after stricter enforcement of the ban came into place in 1996, cases have still occurred in animals born after this time (known as Born After the Real Ban or BARBs) with more than one hundred such cases reported as of 2006. Extensive epidemiological investigations are under way for these BARB cases to identify remaining routes of transmission.

The appearance of BSE in cattle, while of veterinary, agricultural, and economic concern, was initially not thought to pose a threat to human health because of its similarity to scrapie, a disease in sheep that has been endemic in most parts of the world for more than two hundred years. This was demonstrated politically by the now-infamous picture of then–agriculture minister John Gummer feeding a hamburger to his young daughter. However this optimism was shattered in 1996 when the U.K. government announced a possible link between BSE and a new variant of Creutzfeldt-Jakob disease (vCJD) in humans. Since this time, scientific evidence in support of the hypothesis that vCJD is a direct consequence of exposure to BSE has been strengthened. In the United Kingdom alone it is estimated that more than two million infected cattle were slaughtered for human consumption, indicating widespread exposure of the population to the infectious agent. A variety of measures have been put in place to reduce exposure, including the ban on the use of high-risk materials (including the brain and spinal cord) and animals over thirty months of age in food production.

By 1 July 2005, 150 human deaths from vCJD had been reported in the United Kingdom with a further six patients with probable cases still alive. In addition cases have been reported in France, Italy, Republic of Ireland, the United States, Canada, Saudi Arabia, Portugal, and Japan. While the number of cases remains relatively small, concern has now shifted to the possibility of ongoing transmission through blood transfusions and surgical instruments given the potentially large number of people who could be harboring subclinical forms of the disease. A blood transfusion has been formally identified as the most probable source of infection for one vCJD case, and in addition signs of infection have been identified in the spleen of another patient who died from other causes but who was known to have received blood from a vCJD case. A number of measures to protect blood supplies both within the United Kingdom and elsewhere have been introduced over the past ten years, including leucodepletion of blood, which is thought to reduce the risk of transmitting infection by about 40 percent, and a ban on donors who have themselves received a blood transfusion. Transmission via surgical instruments has not been documented to date but remains a potential risk. Because of the many uncertainties about these secondary routes of transmission, the potential future scale of the outbreak is unclear. However the BSE and vCJD epidemics are likely to remain a cause for government and public concern for several years.

See alsoAgriculture; Diet and Nutrition; Public Health .

BIBLIOGRAPHY

Bruce, M. E., R. G. Will, J. W. Ironside, et al. "Transmissions to Mice Indicate that 'New Variant' CJD Is Caused by the BSE Agent." Nature 389 (1997): 498–501.

Hill, A. F., M. Desbruslais, S. Joiner, et al. "The Same Prion Strain Causes vCJD and BSE." Nature 389 (1997): 448–450.

Hilton, D. A., A. C. Ghani, L. Conyers, et al. "Prevalence of Lymphoreticular Prion Protein Accumulation in UK Tissue Samples." Journal of Pathology 203 (2004): 733–739.

Llewelyn, C. A., P. E. Hewitt, R. S. Knight, et al. "Possible Transmission of Variant Creutzfeldt-Jakob Disease by Blood Transfusion." Lancet 363 (2004): 417–421.

Peden, A., M. W. Head, D. L. Ritchie, et al. "Preclinical vCJD after Blood Transfusion in a PRNP Codon 129 Heterozygous Patient." Lancet 364 (2004): 527–529.

Statutory Instrument. "The Bovine Spongiform Encephalopathy Order 1988, no. 1039." HMSO London, 1988.

Wells, G. A., A. C. Scott, C. T. Johnson, et al. "A Novel Progressive Spongiform Encephalopathy in Cattle." Veterinary Record 121 (1987): 419–420.

Wilesmith, J. W., J. B. Ryan., and M. J. Atkinson. "Bovine Spongiform Encephalopathy: Epidemiological Studies on the Origin." Veterinary Record 128 (1991): 199–203.

Azra Ghani

Mad Cow Disease Investigation

Bovine spongiform encephalopathy (BSE, also popularly known as mad cow disease) and Creutzfeldt-Jakob disease (CJD, which occurs in humans) are ailments in which the functioning of the brain is progressively impaired.

Beginning in the 1980s in the United Kingdom, mad cow disease has been a sporadic concern in that country and others. By 1992, three cows in every 1,000 in Britain were estimated to have the disease. Then in the winter of 1997, another outbreak led to the slaughter of 100,000 cattle as a measure to stop the spread of the disease. In more recent incidents, detection of the disease in the Canadian province of Alberta in 2003 led to a ban on imports of Canadian beef to the United States. As of mid-2005, the ban is still in effect, although it is anticipated to be lifted before year's end.

The detection of mad cow disease and the determination of the extent of the disease involved a large, coordinated epidemiological (disease-tracking) and forensic science investigation.

Initially, a cow may be suspected of being infected because of behavioral changes, including loss of coordination, clumsy gait, and even the appearance of foam at the mouth (hence the origin of the mad cow moniker). Typically, the suspect cow will be removed from the herd and slaughtered. Then, examination of tissues and fluids commences. These examinations can involve microscopy of tissue sample and the use of antibodies to identify the causative agent.

Mad cow disease is associated with visually abnormal pinpoints (or plaques) in the brain, and in a changed texture of the brain tissue. These alterations are detected when the brain tissue is microscopically examined as part of an autopsy of a cow suspected of having the disease. The brain tissue, particularly in the cortex and cerebellum, becomes filled with large open spaces (vacuoles) and becomes spongy in texture. The "spongiform" part of the BSE descriptor comes from this texture characteristic.

In Canada, cattle have been tagged with an identifying code since 2001. The identifier enables the movement of cattle to be tracked from the herd (and from herd to herd) to the slaughterhouse. This enables the pattern of an illness outbreak, including mad cow disease, to be better investigated.

Mad cow disease, CJD, and maybe even other diseases such as scrapie, transmissible mink encephalopathy, fatal familial insomnia, and kuru, are thought to have a common cause, namely prions . Prions are particles that are made solely of protein. Even though they lack genetic material, they are infectious.

Mad cow disease causes a progressive neurological deterioration in cattle that is similar to the course of CJD in humans. Infected cattle are more temperamental, have problems with their posture and coordination, have progressively greater difficulty in rising off the ground and walking, produce less milk, have severe twitching of muscles, and lose weight even though their appetite is undiminished. The suspected incubation period, the time from when the animal is first infected until symptoms appear, ranges from two to eight years. After appearance of symptoms, deterioration is rapid and the animal dies or is destroyed within six months. The disease is one of a group of related diseases called transmissible spongiform encephalopathies (TSEs) in animals.

Bovine spongiform encephalopathy was confirmed as a disease of cattle in November 1996. Since then, with the exception of cases in Canada and a single case in the United States in 2004, almost all reported cases have been in cattle born in the United Kingdom. Other countries in Europe and Asia have reported BSE, but in far fewer numbers than in the U.K. As of November 2001, the total number of confirmed cases of BSE in U.K. cattle was just over 181,000. In 1993, a BSE epidemic in the U.K. peaked at almost 1,000 new cases per week. While the cause of this near-exclusivity has yet to be conclusively determined, a common practice in the United Kingdom was to feed cattle "offal," the ground up waste from the slaughter process. Cattle feed was also prepared from the ground bones and tissues of sheep, cattle, and other animals, providing a means of delivering prions from infected animals to healthy ones. The exact origin of the prions is not known. Sheep, susceptible to a similar disease called scrapie, known for many years, are considered a likely source.

Until the 1900s, scientists thought that the transmission of the BSE agent to humans did not occur. However, several post-mortem, forensic studies (autopsies and brain tissue examination) conducted in the 1990s debunked this assumption. In 1994, cases of young people (median age was 26 years) with a CJD-type disease began appearing in the U.K., often in related geographical areas. As CJD affects mostly people over age 65, and symptoms differed slightly and developed more slowly in those affected in the new outbreak, the disease was given the distinct name of variant CJD, or vCJD. An intensive investigation was launched that eventually revealed vCJD as most likely caused by eating beef from cattle infected with BSE. As of 2005, 105 cases of vCJD have been identified in young adults mostly in the U.K., with three cases occurring in France and one in Ireland. The largest number of cases occurred during 1999 (27), and has decreased to less than five cases per year afterward, suggesting that the outbreak of the disease is waning. Chances of contracting vCJD by eating beef in the U.K. are very small as of 2005, due to measures implemented more than a decade earlier (longer than the usual vCJD incubation period) to protect the food supply from BSE-infected beef.

As well, studies on mice published in 2004 have cast doubt on the previous view that the infectious agent of mad cow disease is localized exclusively in only the brain, spleen, spinal cord, and lymph tissue. Prions were additionally detected in the kidney, pancreas, and liver tissues of infected mice. This finding has profound forensic implications, since typically an investigation of mad cow disease focuses on examining samples from the brain and the other traditional locations. The presence of prions elsewhere would be overlooked. As there is no conclusive diagnostic test for variant CJD while an affected person is alive, other than a costly and invasive brain biopsy that will offer no benefit for the outcome of the disease, forensic examination of brain tissue at autopsy is the usual method of providing a definitive diagnosis of CJD and variant CJD in humans, and BSE in cattle.

see also Animal evidence; Autopsy; Prions.

mad cow disease Popular name for bovine spongiform encephalopathy (BSE)

mad cow disease Bovine spongiform encephalopathy, see BSE.