Bovine Spongiform Encephalopathy (BSE) in the United Kingdom and Creutzfeldt Jakob Disease (CJD) in the United States -------------------------------------------------------------------------------- What is BSE? BSE is a progressive neurological disorder of cattle which results from infection by an unconventional transmissible agent. As of September 1997, more than 168,000 cases of BSE were confirmed in Great Britain in more than 34,000 herds. The epidemic peaked in January 1993 at almost 1,000 new cases per week. The outbreak may have resulted from the feeding of scrapie-containing sheep meat-and-bone meal to cattle. There is a strong evidence and general agreement that the outbreak was amplified by feeding rendered bovine meat-and- bone meal to young calves. The nature of the transmissible agent is unknown. Currently the most accepted theory is that the agent is a modified form of a normal cell surface component known as prion protein, a pathogenic form of the protein that is both less soluble and more resistant to enzyme degradation than the normal form. Is BSE occurring in the United States? According to the Animal and Plant Health Inspection Services of the United States Department of Agriculture, BSE has not been detected in the United States, despite active surveillance efforts for several years. As of September 30, 1997, 6,263 bovine brain specimens have been examined by an ongoing BSE surveillance system in the United States and no evidence of BSE was seen. Further, to prevent BSE from entering the United States, severe restrictions were placed on the importation of live ruminants and certain ruminant products from countries where BSE was known to exist. Recently, these restrictions were extended to include importation of ruminants and certain ruminant products from all European countries. Is BSE a food-borne hazard in the United States? As indicated above, BSE has not been shown to exist in the United States. Thus, it is extremely unlikely that BSE would be a foodborne hazard in this country. Because the use of ruminant tissue in ruminant feed was probably a necessary factor responsible for the BSE outbreak in the United Kingdom and because of the current evidence for a possible transmission of BSE to humans, the Food and Drug Administration (FDA) instituted a mammalian-to-ruminant feed ban in June 1997 that became fully effective as of October 1997. Is BSE a food-borne hazard in the United Kingdom? The statement from the Spongiform Encephalopathy Advisory Committee (SEAC) of the United Kingdom on March 20, 1996 indicated that SEAC was concerned that before November 1989, when a ban preventing inclusion of specified offals in human food was placed, that BSE might have been a foodborne hazard in the United Kingdom. It is this possible hazard that SEAC indicated might account for the 10 new variant CJD cases in the United Kingdom described on April 6, 1996 in the medical literature (Lancet 1996;347:921- 5). If indeed this hazard did exist, the control measures already instituted in the United Kingdom would have greatly reduced that risk today. Because of the SEAC statement, BSE control measures in the United Kingdom are being tightened even further. SEAC has indicated that milk and milk products are unlikely to pose any risk for human exposure to the BSE agent. Is there any monitoring of the incidence of CJD in the United States? Yes. The possibility that BSE can spread to humans has focused increased attention on the desirability of national CJD surveillance. Today, the Centers for Disease Control and Prevention (CDC) monitors the trends and current incidence of CJD in the United States by analyzing death certificate information from U.S. multiple-cause-of-death data, compiled by the National Center for Health Statistics, CDC. These data indicate that the annual CJD death rates in the United States from 1979 through 1995 have been relatively stable ranging between 0.8 cases per million in 1980 and 1.1 cases per million in 1987. In addition, CJD deaths in persons aged <30 years in the United States remains extremely rare (<5 cases per billion per year). In contrast, in the United Kingdom, at least 13 of the 23 patients who died with new variant CJD were in this young age group. What is the new variant form of CJD that the experts in the United Kingdom believe might be related to the BSE outbreak in cattle? In contrast to the classic form of CJD, the new variant form in the United Kingdom affects younger persons (median age at onset: 28 years), has atypical clinical features, with prominent psychiatric or sensory symptoms at the time of clinical presentation, with delayed onset of neurologic abnormalities, including ataxia within weeks or months, dementia and myoclonus late in the illness, a duration of illness of at least six months, and a diffusely abnormal non-diagnostic electroencephalogram. The characteristic neuropathologic profile of new variant CJD includes, in both the cerebellum and cerebrum, numerous kuru-type amyloid plaques surrounded by vacuoles and prion protein accumulation at high concentration, indicated by immunohistochemical analysis. The typical spongiform changes are most evident in the basal ganglia and thalamus with sparse distribution throughout the cerebral cortex. Is there evidence directly linking this newly recognized variant of CJD to BSE exposure? There is a strong epidemiologic and laboratory evidence for a causal association between new variant CJD and BSE. The absence of confirmed cases of new variant CJD in other geographic areas free of BSE supports a causal association. In addition, the interval between the most likely period for the initial exposure of the population to potentially BSE contaminated food (1984-1986) and onset of initial new variant CJD cases (1994-1996) is consistent with known incubation periods for CJD. An experimental study reported in June 1996 showed that three cynomologus macaque monkeys inoculated with brain tissue obtained from cattle with BSE had clinical and neuropathological features strikingly similar to new variant CJD (Nature 1996;381:743-4). A study published in 1996 indicated that a Western blot analysis of infecting prions obtained from 10 new variant CJD patients and BSE-infected animals had similar molecular characteristics that were distinct from prions obtained from patients with other types of CJD (Nature 1996;383:685-90). Most recently, interim results of an ongoing experimental study involving inoculation of a panel of inbred mice with the agents causing BSE and new variant CJD substantially increased the strength of the scientific evidence for a causal association between new variant CJD and BSE (Nature 1997;389:498-501). Has CDC initiated increased surveillance efforts to determine whether the newly recognized variant of CJD occurs in the United States? Yes. In addition to the ongoing review of national CJD mortality data, CDC conducted active CJD surveillance in its four established Emerging Infections Program areas (Minnesota; Oregon; Connecticut; and the San Francisco Bay area, California) and in a metropolitan Atlanta site during April and May 1996. In 1996, with the support of the Council of State and Territorial Epidemiologists, CDC initiated an ongoing follow-up review of clinical and neuropathology records of CJD decedents aged <55 years who are identified through the national mortality data analysis. Also in 1996, the American Association of Neuropathologists (AANP), in collaboration with CDC, alerted its members about the new variant CJD neuropathology and requested reports of any such cases regardless of the clinical diagnosis or age of the patient. These surveillance efforts have not detected evidence of the occurrence of new variant CJD in the United States. From CDC.GOV Creutzfeldt-Jacob disease Definition: A brain disorder involving rapid decrease of mental function and movement abnormalities caused by damage to the tissues of the brain from a viral-like organism (a transmissible protein called a prion). Causes, incidence, and risk factors: Creutzfeldt-Jakob disease is an organic brain syndrome caused by a viral-type organism. The disorder is rare, occurring in about 2 out of 1,000,000 people. It usually first appears in mid-life, beginning between ages 20 and 68, with the average age at onset of symptoms being around age 50. Cases have occurred in adolescents who have received growth hormone derived from cadavers, despite the production process, which is intended to kill all bacterial and viral material in the product. The causative agent, or prion, is thought to have been transmitted in the growth hormone (extracted from the pituitary of cadavers), which explains the abnormally early appearance of the disease. Cadaver derived growth hormone has been replaced by synthetically manufactured growth hormone and contagion is no longer a problem. Once symptoms appear there is rapid progression of the disorder with progressive loss of brain function. The lesion and deterioration of function is similar to that of senile dementia/Alzheimer's type, but is distinguished by its very rapid course. There may be a familial tendency to acquire the disorder. Early symptoms include personality changes and changes in coordination. Extreme dementia is accompanied by muscle tremors and rigid posture. The virus associated with Creutzfeldt-Jakob disease is contagious to humans and primates. Risks include exposure to the virus, directly or indirectly through contact with contaminated equipment or tissues (especially corneal transplant). Other risks include a family history of dementia. Creutzfeldt-Jacob disease may be related to several other diseases also thought to be caused by prions, including kuru (seen in New Guinea headhunters), scrapie (seen in sheep) and bovine spongiform encephalitis (seen in cows). Treatment: There is no known cure for Creutzfeldt-Jacob disease. Custodial care may be required early in the course of the disease. Medications may be needed to control aggressive behaviors. These include sedatives, antipsychotics, and others. The need to provide a safe environment, control aggressive or agitated behavior, and meet physiologic needs may require monitoring and assistance in the home or in an institutionalized setting. This may include in-home care or institutionalization. Family counseling may help in coping with the changes required for home care. Visiting nurses or aides, volunteer services, homemakers, adult protective services, and other community resources may be helpful in caring for the person with Creutzfeldt-Jacob disease. Behavior modification may be helpful in some cases for controlling unacceptable or dangerous behaviors. This consists of rewarding appropriate or positive behaviors and ignoring inappropriate behaviors (within the bounds of safety). Reality orientation, with repeated reinforcement of environmental and other cues, may help reduce disorientation. Legal advice may be appropriate early in the course of the disorder, to form advance directives, power of attorney, and other legal actions that may make it easier to make ethical decisions regarding the care of an individual with Creutzfeldt-Jacob disease. Expectations (prognosis): The outcome is usually very poor. Complete dementia commonly occurs within 6 months or less, with the person becoming totally incapable of self care. The disorder is fatal in a short time, usually within 7 months, but a few people survive as long as 1 or 2 years after diagnosis of the disorder. The cause of death is usually infection, heart failure, or respiratory failure. Complications: infection heart failure respiratory failure loss of ability to function or care for oneself loss of ability to interact with others side effects of medications used to treat the disorder (see the specific medication) Calling your health care provider: Creutzfeldt-Jacob disease is not an emergency disorder, but early diagnosis and treatment may make the symptoms easier to control. from adam.com Creutzfeldt-Jakob Disease Fact Sheet -------------------------------------------------------------------------------- Index: What is Creutzfeldt-Jakob Disease? What are the Symptoms of the Disease? How is CJD Diagnosed? How is the Disease Treated? What Causes Creutzfeldt-Jakob Disease? How is CJD Transmitted? How Can People Avoid Spreading the Disease? What Research is Taking Place? How Can I Help Research? Where Can I Get Help? (last updated 2-14-00) -------------------------------------------------------------------------------- Return to NINDS Publications Page or NINDS Homepage -------------------------------------------------------------------------------- What is Creutzfeldt-Jakob Disease? Creutzfeldt-Jakob disease (CJD) is a rare, degenerative, invariably fatal brain disorder. It affects about one person in every one million people worldwide and about 200 people in the United States. CJD usually appears in later life and runs a rapid course. Typically, onset of symptoms occurs about age 60, and about 90 percent of patients die within 1 year. In the early stages of disease, patients may have failing memory, behavioral changes, lack of coordination and visual disturbances. As the illness progresses, mental deterioration becomes pronounced and involuntary movements, blindness, weakness of extremities, and coma may occur. There are three major categories of CJD: In sporadic CJD, the disease appears even though the person has no known risk factors for the disease. This is by far the most common type of CJD and accounts for at least 85 percent of cases. In hereditary CJD, the person has a family history of the disease and/or tests positive for a genetic mutation associated with CJD. About 5 to 10 percent of cases of CJD in the United States are hereditary. In acquired CJD, the disease is transmitted by exposure to brain or nervous system tissue, usually through certain medical procedures. There is no evidence that CJD is contagious through casual contact with a CJD patient. Since CJD was first described in 1920, fewer than 1 percent of cases have been acquired CJD. CJD belongs to a family of human and animal diseases known as the transmissible spongiform encephalopathies (TSEs). Spongiform refers to the characteristic appearance of infected brains, which become filled with holes until they resemble sponges under a microscope. CJD is the most common of the known human TSEs. Other human TSEs include kuru, fatal familial insomnia (FFI), and Gerstmann-Straussler-Scheinker disease (GSS). Kuru was identified in people of an isolated tribe in Papua New Guinea and has now almost disappeared. Fatal familial insomnia and GSS are extremely rare hereditary diseases, found in just a few families around the world. Other TSEs are found in specific kinds of animals. These include bovine spongiform encephalopathy (BSE), which is found in cows and often referred to as "mad cow" disease; scrapie, which affects sheep; and mink encephalopathy. Similar diseases have occurred in elk, deer, and exotic zoo animals. -------------------------------------------------------------------------------- What are the Symptoms of the Disease? The first symptoms of Creutzfeldt-Jakob disease typically include dementia — personality changes together with impaired memory, judgment, and thinking — and problems with muscular coordination. People with the disease also may experience insomnia, depression, or unusual sensations. CJD does not cause a fever or other flu-like symptoms. As the illness progresses, the patients’ mental impairment becomes severe. They often develop involuntary muscle jerks called myoclonus, and they may go blind or lose bladder control. They eventually lose the ability to move and speak and enter a coma. Pneumonia and other infections often occur in these patients and can lead to death. There are several known variants of CJD. These variants differ somewhat in the symptoms and course of the disease. For example, a variant form of the disease (nv-CJD or v-CJD), described in Great Britain and some other parts of Europe, begins primarily with psychiatric symptoms, affects younger patients than other types of CJD, and has a longer than usual duration from onset of symptoms to death. Another variant, called the panencephalopathic form, occurs primarily in Japan and has a relatively long course, with symptoms often progressing for several years. Scientists are trying to learn what causes these variations in symptoms. Some symptoms of CJD can be similar to symptoms of other progressive neurological disorders, such as Alzheimer’s or Huntington’s disease. However, CJD causes unique changes in brain tissue which can be seen at autopsy. It also tends to cause more rapid deterioration of a person’s abilities than Alzheimer’s disease or most other types of dementia. -------------------------------------------------------------------------------- How is CJD Diagnosed? There is currently no single diagnostic test for CJD. When a doctor suspects CJD, the first concern is to rule out treatable forms of dementia such as encephalitis (inflammation of the brain) or chronic meningitis. A neurological examination will be performed or the doctor may seek consultation with other physicians. Standard diagnostic tests will include a spinal tap to rule out more common causes of dementia and an electroencephalogram (EEG) to record the brain’s electrical pattern, which can be particularly valuable because it shows a specific type of abnormality in CJD. Computerized tomography of the brain can help rule out the possibility that the symptoms result from other problems such as stroke or a brain tumor. Magnetic resonance imaging (MRI) brain scans also can reveal characteristic patterns of brain degeneration that can help diagnose CJD. The only way to confirm a diagnosis of CJD is by brain biopsy or autopsy. In a brain biopsy, a neurosurgeon removes a small piece of tissue from the patient’s brain so that it can be examined by a neuropathologist. This procedure may be dangerous for the patient, and the operation does not always obtain tissue from the affected part of the brain. Because a correct diagnosis of CJD does not help the patient, a brain biopsy is discouraged unless it is needed to rule out a treatable disorder. In an autopsy, the whole brain is examined after death. Both brain biopsy and autopsy pose a small, but definite, risk that the surgeon or others who handle the brain tissue may become accidentally infected. Special surgical and disinfection procedures can minimize this risk. A fact sheet with guidance on these procedures is available from the NINDS. Scientists are working to develop laboratory tests for CJD. One such test, developed at NINDS, is performed on a person’s cerebrospinal fluid and detects a protein marker that indicates neuronal degeneration. This can help diagnose CJD in people who already show the clinical symptoms of the disease. This test is much easier and safer than a brain biopsy. The false positive rate is about 5 to 10 percent. Scientists are working to develop this test for use in commercial laboratories. There have been reports of other ways of diagnosing the disease, including tonsil biopsies, which may lead to other tests. -------------------------------------------------------------------------------- How is the Disease Treated? There is no treatment that can cure or control Creutzfeldt-Jakob disease. Researchers have tested many drugs, including amantidine, steroids, interferon, acyclovir, antiviral agents, and antibiotics. However, none of these treatments has shown any consistent benefit. Current treatment for CJD is aimed at alleviating symptoms and making the patient as comfortable as possible. Opiate drugs can help relieve pain if it occurs, and the drugs clonazepam and sodium valproate may help relieve myoclonus. During later stages of the disease, changing the person’s position frequently can keep him or her comfortable and helps prevent bedsores. A catheter can be used to drain urine if the patient cannot control bladder function, and intravenous fluids and artificial feeding also may be used. -------------------------------------------------------------------------------- What Causes Creutzfeldt-Jakob Disease? Some researchers believe an unusual "slow virus" or another organism causes CJD. However, they have never been able to isolate a virus or other organism in people with the disease. Furthermore, the agent that causes CJD has several characteristics that are unusual for known organisms such as viruses and bacteria. It is difficult to kill, it does not appear to contain any genetic information in the form of nucleic acids (DNA or RNA), and it usually has a long incubation period before symptoms appear. In some cases, the incubation period may be as long as 40 years. The leading scientific theory at this time maintains that CJD and the other TSEs are caused not by an organism but by a type of protein called a prion. Prions occur in both a normal form, which is a harmless protein found in the body’s cells; and in an infectious form, which causes disease. The harmless and infectious forms of the prion protein are nearly identical, but the infectious form takes a different folded shape than the normal protein. Sporadic CJD may develop because some of a person’s normal prions spontaneously change into the infectious form of the protein and then alter the prions in other cells in a chain reaction. Once they appear, abnormal prion proteins stick together and form fibers and/or clumps called plaques that can be seen with powerful microscopes. Fibers and plaques may start to accumulate years before symptoms of CJD begin to appear. It is still unclear what role these abnormalities play in the disease or how they might affect symptoms. About 5 to 10 percent of all CJD cases are inherited. These cases arise from a mutation, or change, in the gene that controls formation of the normal prion protein. While prions themselves do not contain genetic information and do not require genes to reproduce themselves, infectious prions can arise if a mutation occurs in the gene for the body’s normal prions. If the prion gene is altered in a person’s sperm or egg cells, the mutation can be transmitted to the person’s offspring. Several different mutations in the prion gene have been identified. The particular mutation found in each family affects how frequently the disease appears and what symptoms are most noticeable. However, not all people with mutations in the prion gene develop CJD. This suggests that the mutations merely increase susceptibility to CJD and that other, still-unknown factors also play a role in the disease. -------------------------------------------------------------------------------- How is CJD Transmitted? While CJD can be transmitted to other people, the risk of this happening is extremely small. CJD cannot be transmitted through the air or through touching or most other forms of casual contact. Spouses and other household members of sporadic CJD patients have no higher risk of contracting the disease than the general population. However, direct or indirect contact with brain tissue and spinal cord fluid from infected patients should be avoided to prevent transmission of the disease through these materials. In a few very rare cases, CJD has spread to other people from grafts of dura mater (a tissue that covers the brain), transplanted corneas, implantation of inadequately sterilized electrodes in the brain, and injections of contaminated pituitary growth hormone derived from human pituitary glands taken from cadavers. Doctors call these cases that are linked to medical procedures iatrogenic cases. Since 1985, all human growth hormone used in the United States has been synthesized by recombinant DNA procedures, which eliminates the risk of transmitting CJD by this route. The appearance of a new variant of CJD (nv-CJD or v-CJD) in several younger than average people in Europe has led to concern that BSE can be transmitted to humans through consumption of contaminated beef. Although laboratory tests have shown a strong similarity between the prions causing BSE and v-CJD, there is no direct proof to support this theory. Furthermore, BSE has never been found in the United States, and importing of cattle and beef from countries with BSE has been banned in the United States since 1989 to reduce the risk that it will occur in this country. Many people are concerned that it may be possible to transmit CJD through blood and related blood products such as plasma. Some animal studies suggest that contaminated blood and related products may transmit the disease, although this has never been shown in humans. If there are infectious agents in these fluids, they are probably in very low concentrations. Scientists do not know how many abnormal prions a person must receive before he or she develops CJD, so they do not know whether these fluids are potentially infectious or not. They do know that, even though millions of people receive blood transfusions each year, there are no reported cases of someone contracting CJD from a transfusion. Even among hemophiliacs, who sometimes receive blood plasma concentrated from thousands of people, there are no reported cases of CJD. This suggests that, if there is a risk of transmitting CJD through blood or plasma, it is extremely small. -------------------------------------------------------------------------------- How Can People Avoid Spreading the Disease? To reduce the already very low risk of CJD transmission from one person to another, people should never donate blood, tissues, or organs if they have suspected or confirmed CJD, or if they are at increased risk because of a family history of the disease, a dura mater graft, or other factor. Normal sterilization procedures such as cooking, washing, and boiling do not destroy prions. Caregivers, health care workers, and undertakers should take the following precautions when they are working with a person with CJD: Wash hands and exposed skin before eating, drinking, or smoking. Cover cuts and abrasions with waterproof dressings. Wear surgical gloves when handling a patient’s tissues and fluids or dressing the patient’s wounds. Avoid cutting or sticking themselves with instruments contaminated by the patient’s blood or other tissues. Use disposable bedclothes and other cloth for contact with the patient. If disposable materials are not available, regular cloth should be soaked in undiluted chlorine bleach for an hour or more, then washed in a normal fashion after each use. Use face protection if there is a risk of splashing contaminated material such as blood or cerebrospinal fluid. Soak instruments that have come in contact with the patient in undiluted chlorine bleach for an hour or more, then use an autoclave (pressure cooker) to sterilize them in distilled water for at least one hour at 132 - 134 degrees Centigrade. A fact sheet listing additional precautions for healthcare workers and morticians is available from the NINDS. -------------------------------------------------------------------------------- What Research Is Taking Place? Many researchers are studying CJD. They are examining whether the transmissible agent is, in fact, a prion, and trying to discover factors that influence prion infectivity and how the disorder damages the brain. Using rodent models of the disease and brain tissue from autopsies, they are also trying to identify factors that influence susceptibility to the disease and that govern when in life the disease appears. They hope to use this knowledge to develop improved tests for CJD and to learn what changes ultimately kill the neurons so that effective treatments can be developed. from www.ninds.nih.gov