Testimony Before the Committee on Appropriations United States Senate CDC’s Role in Monitoring for Transmissible Spongiform Encephalopathies
Statement of Julie L. Gerberding, M.D., M.P.H. Director Centers for Disease Control and Prevention U.S. Department of Health and Human Services
Good morning, Mr. Chairman and Members of the Committee. I am Dr. Julie L. Gerberding, Director of the Centers for Disease Control and Prevention (CDC). Thank you for the invitation to participate in this timely hearing on a critical public health issue: bovine spongiform encephalopathy (BSE) and its potential impact on human health. In my testimony today, I will describe CDC’s surveillance activities for Creutzfeldt-Jakob disease (CJD), variant CJD which is believed to have resulted from consumption of BSE-contaminated cattle products, and the possible occurrence of chronic wasting disease in humans.
Transmissible Spongiform Encephalopathies
Bovine Spongiform Encephalopathy (BSE)–Cattle BSE is a progressive, fatal neurologic disorder of cattle and is classified as one of the transmissible spongiform encephalopathies (TSEs), a group of diseases of animals and humans believed to be caused by abnormally folded proteins called prions. BSE was first identified in the United Kingdom in 1986 where it had been causing a large outbreak among cattle. Although controversy exists about the origin of BSE, there is general agreement among scientists that feeding cattle meat-and-bone meal produced from rendered carcasses of BSE-infected cattle is the primary route of BSE spread and greatly amplified the BSE outbreak. Since 1986, BSE cases have been identified in 20 European countries, Japan, Israel, Canada, and in December 2003 in an imported cow in the U.S. state of Washington.
Chronic Wasting Disease (CWD)–Deer and Elk Another animal TSE that is prevalent in the United States which could potentially pose a public health threat is chronic wasting disease (CWD) of deer and elk. The endemic occurrence of CWD for several decades has been reported in a contiguous area in northeastern Colorado and southeastern Wyoming. Since 2000, new foci of CWD among free ranging deer and elk were reported in Illinois, Nebraska, New Mexico, South Dakota, Utah, Wisconsin, and non-endemic portions of Colorado and Wyoming. No human cases of CWD have been identified.
Creutzfeldt-Jakob Disease (CJD)–Humans
In contrast, strong epidemiologic and laboratory evidence indicates that the BSE agent has been transmitted to humans via consumption of BSE-contaminated cattle products, causing a newly recognized variant form of CJD. The occurrence of the first 10 variant CJD cases and their possible causal link with BSE was first announced in the United Kingdom in 1996, about 9 years after the identification of BSE. Since then, as of February 2004, a total of 156 variant CJD cases have been identified worldwide; 146 of these were reported from the United Kingdom, 6 from France, and 1 each from Canada, Ireland, Italy, and the United States. Except for the variant CJD cases in France and Italy, all the other cases, including the cases in Canada and the United States, are believed to have acquired variant CJD as a result of exposure to BSE in the United Kingdom. The number of variant CJD cases reported to date is relatively small compared with an estimated 1 million or more cattle infected with BSE in the United Kingdom alone, indicating that a “species barrier” provides substantial but incomplete protection to humans against development of variant CJD.
The variant form differs from what is termed the “classic form” of CJD which also occurs in humans. Classic CJD is the most common TSE in the human population. It primarily occurs in a sporadic form with no recognizable pattern of transmission but also as a familial disease resulting from inheritable defective genes. It has also been associated with receipt of contaminated human growth hormone and dura mater and corneal grafts and with exposure to contaminated neurosurgical equipment. The variant form differs from the classic form of CJD also in the age distribution of affected patients, duration of illness, clinical manifestation and course, and most importantly the pathologic lesions in the brain and biochemical characteristics of the agent. Characteristically, variant CJD patients are unusually young with over half of the patients dying before 30 years of age and over 98% before 55 years of age. In contrast, classic CJD commonly develops in patients in their sixth and seventh decade of life, and about 90% of classic CJD patients die at 55 years of age or older. Patients with variant CJD often have prominent behavioral or psychiatric manifestations and painful sensory symptoms, with neurologic signs such as involuntary movements and gait disturbances being delayed for several months after illness onset. The typical electroencephalographic findings observed in classic CJD patients are absent in patients with variant CJD. A characteristic MRI finding, demonstrated in over 75% of variant CJD patients, is considered to be very supportive of a variant CJD diagnosis in the appropriate clinical context.
In addition to selectively affecting younger people, the occurrence of variant CJD seems to be limited to a segment of the general population that have a particular genetic profile. Studies have indicated that only about one-third of the general population falls under this category of BSE susceptibility. Although the diagnosis of variant CJD or classic CJD can often be strongly suspected on the basis of clinical manifestations and radiologic and electroencephalographic studies, confirmatory diagnosis of both of these diseases requires testing of brain tissue obtained after a brain autopsy or biopsy.
CDC Role
CDC’s primary role related to BSE is to monitor for the occurrence of variant CJD possibly resulting from exposure to BSE within the United States or due to travel to other countries such as the United Kingdom where more cases of BSE have been identified. CDC also investigates CJD cases or clusters in which a plausible external source of infection is suspected. A foundation of CDC’s disease surveillance and outbreak investigation activities is its relationship with and support of state and local health departments that are often the first to encounter newly emerging human diseases or changes in the epidemiology of recognized human diseases. These relationships complement those that CDC maintains with health care providers and other healthcare institutions and are designed to maximize the likelihood that a sentinel event will be detected, whether in an expected or an unexpected location.
CJD Surveillance
After the identification of variant CJD in the United Kingdom in 1996, CDC enhanced its CJD surveillance activities to monitor the occurrence of the disease in the United States and monitor the emergence of other new forms of the disease among the U.S. population. CDC utilizes multiple surveillance mechanisms to track the occurrence of human TSEs. These mechanisms include: 1) periodic review of national mortality database; 2) investigation of individuals who have died from CJD and are under 55 years of age; 3) establishment and support of the National Prion Disease Pathology Surveillance Center; 4) active collaborative surveillance of TSEs in special populations (e.g., recipients of human growth hormone); and 5) investigation of patients suspected with a TSE reported to CDC by health care providers (e.g., suspected variant CJD cases).
One of the major ways by which CDC monitors the occurrence of CJD is through periodic review of the national multiple cause-of-death data compiled by the National Center for Health Statistics. Review of death certificate data enables CDC to more efficiently monitor any changes in the epidemiology of CJD in the United States. Because patients with CJD invariably die of the disease and usually within 1 year of illness onset, death certificate surveillance of CJD can be used to estimate the incidence of the disease. Through analysis of death certificate data, CDC determined that the rate and characteristics of CJD deaths identified in the United States during 1979 through 2001 were stable over time and were not at an unexpected level. During the 23-year surveillance period, 5473 deaths attributed to CJD were identified in the United States. The average annual age adjusted CJD death rate during 1979-2001 was 1.06 cases per million population. The CJD death rate has been relatively stable during the surveillance period particularly after 1985. Most cases of CJD in the United States occur in persons in their sixth and seventh decade of life, and unlike in the United Kingdom, where the occurrence of variant CJD resulted in an appreciable increased occurrence of the disease in persons less than 30 years of age, no such increase has been identified in the United States.
To effectively monitor the possible occurrence of variant CJD, CDC routinely investigates the illnesses of suspected or physician-diagnosed CJD patients under 55 years of age by reviewing their clinical and pathologic records. This investigation is conducted in collaboration with state and local health departments and takes advantage of the differences in age distribution of variant CJD from that of classic CJD patients by targeting the age group known to be at an increased risk of BSE transmission. Patients who have died of CJD before 55 years of age are identified from multiple sources, including review of mortality data and reports by clinicians and state and local health departments. To date, CDC has completed review of the clinical or pathologic records of 185 CJD patients under 55 years of age who died since 1994, and none of the patients have evidence of variant CJD.
In addition, during 1996 and 1997, in collaboration with the American Association of Neuropathologists, CDC established the National Prion Disease Pathology Surveillance Center which is located at the Division of Neuropathology of Case Western Reserve University in Cleveland, Ohio. CDC continues to support and monitor the activities of this pathology center. In fiscal year 2003, CDC provided approximately $2.5 million to support the activities of the center. The pathology surveillance center makes available state-of-the-art human TSE diagnostic services to U.S. physicians and state and local health departments. It periodically contacts neurologists and pathologists across the United States informing them about the need to arrange for autopsy of suspected CJD cases and urging them to utilize the free services provided by the center. During its existence since 1996, the center has examined brain tissues from over 1200 patients but did not identify any domestically acquired variant CJD case in the United States. Slightly over half of the cases examined by the center are confirmed with a TSE, most of them with sporadic CJD. Through analysis of brain tissues of patients suspected with TSEs, the center continues to define and characterize the normal background occurrence of human TSEs to help recognize any emerging forms of the disease. It specifically searches for the occurrence of variant CJD and any other form of TSE with potential link with CWD of deer and elk. In addition, the pathology surveillance center with support from CDC and the Food and Drug Administration (FDA) conducts applied laboratory research by developing appropriate animal models to characterize the susceptibility of humans to infection by the CWD agent.
CDC’s multi-pronged surveillance mechanisms have not identified domestically acquired variant CJD in the United States. In 2002, CDC reported the occurrence of the first variant CJD case in the United States in a 22-year-old British woman who is a resident of Florida. The patient was born in the United Kingdom and raised there during the BSE outbreak and is believed to have acquired variant CJD from consumption of BSE-infected cattle products in her native country. This patient is still alive, and is receiving medical care in Florida.
The major challenge to CDC’s national surveillance of CJD and other emerging forms of the diseases is lack of autopsy brain specimens in some cases of CJD. Because availability of brain specimens permits confirmation of the diagnosis and allows for effective monitoring of newly emerging forms of the disease such as variant CJD, CDC places a high priority in increasing the number of autopsies in suspected and physician-diagnosed patients with TSEs. To understand the problems associated with lack of autopsies, CDC recently collaborated with the California State Department of Health Services and the New York State Department of Health on a survey of neurologists and pathologists to determine the barriers for autopsy performance in CJD patients. The survey findings indicate that cost of autopsy, infection control concerns by pathologists, and lack of family consent may be some of the barriers to autopsy performance. CDC is collaborating with state and local health departments, the National Prion Disease Pathology Surveillance Center, and the national Creutzfeldt-Jakob Disease Foundation to address these autopsy barriers and increase the number of brain specimens available for effective surveillance of emerging forms of human TSEs. The increasing number of brain specimens referred to the National Prion Disease Pathology Surveillance Center during the last several years may indicate some improvement in the number of suspected CJD cases that are being autopsied. However, some challenges still remain.
CWD Investigations
To monitor the possible transmission of CWD to humans, CDC has investigated several CJD case clusters among hunters who consumed deer and elk meat. One such investigation, published in 2001, included an investigation of three unusually young patients aged 28 to 30 years of age with CJD who consumed deer or elk meat they harvested from the wild or provided by a family member. Our investigation of the three cases did not provide any convincing evidence for a causal link between CWD and the CJD illness in the patients. Recently, CDC also investigated the illnesses of three hunters who participated in wild game feasts and subsequently died of neurologic illnesses. The wild game feasts were regularly held in a cabin in Wisconsin and were hosted by one of the decedents who was a lifelong hunter and consumed venison frequently. Clinical and pathologic investigation of the illnesses of the three patients indicated that two of the patients did not die of a TSE illness. The one patient confirmed with CJD had an illness consistent with other classic CJD patients with no history of venison consumption. In addition, this patient was unlikely to have consumed CWD-infected venison because venison and other game that was served during the feasts did not originate from known CWD-endemic areas, and the man participated in the feasts only once. Although CDC’s investigations to date have not identified strong evidence for a causal link between CWD and human illness, the conversion of human prion protein to the disease causing form by CWD-associated prions has been demonstrated in a cell-free experimental study performed at a National Institute of Health laboratory. This finding and the transmission of BSE to humans indicate that humans may not be completely protected from infection by the CWD agent. To monitor for this possibility, CDC is collaborating with the Wyoming Department of Health and the Colorado Department of Public Health and Environment to determine any unusual increase in the number of human TSEs among hunters who hunted deer and elk in areas where CWD was known to be endemic for several decades.
Acquired TSEs
In collaboration with other government and private institutions, CDC also conducts several follow up studies of special populations deemed to be at a potentially increased risk of developing acquired TSEs. One of these studies was initiated in the 1980s to monitor the occurrence of CJD among patients known to have received cadaveric-derived human growth hormone. Before 1985, this hormone was derived from pituitary glands obtained from human cadavers and was inadvertently contaminated when pituitary glands from donors who had died of CJD were included in the batch processing. As of February 2004, a total of 26 human growth hormone-associated CJD cases have been identified among about 8000 recipients included in the follow-up study. A second follow-up study that is being conducted in collaboration with the American Red Cross relates to the possible transmission of CJD to patients known to have received blood components obtained from donors who, subsequent to their donation, died of CJD. As of February 2004, 331 recipients of blood components obtained from 25 “CJD donors” were enrolled in the follow-up study. Although some of the recipients died of the underlying condition that led them to receive blood, none of the 116 recipients who were followed for at least 5 years developed CJD. The median follow-up time was 9½ years, and in some cases, the follow up lasted for over 20 years.
Conclusion
In summary, two animal TSEs are believed to potentially pose a risk to the U.S. population. One of these, BSE of cattle with documented evidence of transmission to humans, has now been detected in Canada and the United States. Although the measures taken by the U.S. Department of Agriculture are expected to reduce the risk of exposure of the U.S. population to BSE, there is a possibility that domestically acquired variant CJD may appear in the United States. However, this possibility is believed to be extremely small. Another animal TSE that could pose a risk to the U.S. population is CWD of deer and elk. Although the occurrence of CWD seems to be geographically limited to certain areas of the United States, recent evidence suggests that new foci of infection may have emerged. An ongoing concern exists about the possibility that human exposure to the CWD agent may increase with the increasing spread of the disease to new geographic areas. CDC will continue working with our partners to conduct and enhance surveillance mechanisms to monitor the occurrence of classic CJD in the United States and to monitor the occurrence of emerging forms of the disease, including variant CJD and CWD in humans.
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