Bovine Spongiform Encephalopathy in the United States — An Epidemiologist's View
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《新英格兰医药杂志》
On December 9, 2003, a nonambulatory ("downer") dairy cow was slaughtered in Washington State, and because the animal's condition was attributed to complications from calving, the animal was judged to be fit for human consumption (designated as "inspected and passed" by the U.S. Department of Agriculture ). Samples taken from this animal tested positive for bovine spongiform encephalopathy (BSE, also known as mad cow disease) on December 22; the USDA diagnosis was subsequently confirmed by the British world reference laboratory. The international response to the announcement of this result on December 23 was strong and swift, with bans being imposed immediately on U.S. beef and cattle by Japan, Mexico, South Korea, and other countries. Although it has now been confirmed that the infected cow was imported from Alberta, Canada, in 2001, the bans have remained in place.
A rational interpretation of the potential risks posed by BSE in North America must be grounded in the findings of long-term studies of the epidemics of BSE and new-variant Creutzfeldt–Jakob disease in Europe; these studies have focused particularly on Britain — the country that has been the most affected, with more than 179,000 confirmed clinical cases of BSE.1,2 The disease was first identified in England in 1986, and the recycling of infection through the inclusion of bovine protein in cattle feed was soon identified as the process driving the epidemic. The key measure that brought the British BSE epidemic under control was the ban, introduced in 1988, on feeding tissues from one ruminant animal to other ruminant animals. However, because of the long delay between infection and the onset of clinical signs of disease (five years, on average), the annual incidence of clinical cases did not peak until 1992 (Figure). This ban targeted ruminant animals in general, rather than cattle in particular, because scrapie, a BSE-like disease that affects sheep, has long been endemic in Britain.
Figure. Incidence of Bovine Spongiform Encephalopathy and New-Variant Creutzfeldt–Jakob Disease in Great Britain.
The epidemic of bovine spongiform encephalopathy (BSE) in Britain peaked in 1992, four years after the introduction of the ban on feeding tissues of one ruminant animal to other ruminant animals. The associated human disease, new-variant Creutzfeldt–Jakob disease, was not identified until 1996, seven years after a ban was introduced in Britain on the use in food for humans of specified offal from cattle (the brain, spinal cord, spleen, thymus, tonsils, and intestines of cattle six months of age or older). In the United States, the brains of cattle younger than 30 months of age may still be used in food produced for human consumption.
The identification in 1996 of a new variant of Creutzfeldt–Jakob disease in humans in association with BSE prompted authorities to strengthen many existing BSE-control measures (for example, the British ban on ruminant feed was extended to feed including any mammalian meat or bone meal) and to introduce new measures (for example, a British ban on the consumption of cattle older than 30 months of age). Although most of the estimated 4 million cattle that were infected over the course of the BSE epidemic in Britain3 were slaughtered for consumption, to date only 145 (definite or probable) cases of new-variant Creutzfeldt–Jakob disease have been identified in British patients, only 6 of whom remain alive. The decrease in the incidence of new-variant Creutzfeldt–Jakob disease in Britain since the peak of the epidemic in 2000 (when there were 28 cases) has dramatically decreased the uncertainty surrounding the likely size of the primary epidemic involving the known susceptible genotype (with homozygosity for methionine at codon 129 of the prion protein gene).4 A small number of additional cases have been reported in other countries (Ireland, France, Italy, Canada, and the United States). The only affected U.S. resident, whose probable case of new-variant Creutzfeldt–Jakob disease was identified in 2002, was a 22-year-old woman who had moved from the United Kingdom to Florida in 1992.
Although a ban on ruminant feed was introduced in the United States in 1997 as a precaution in response to the identification of new-variant Creutzfeldt–Jakob disease, there is still a risk of cross-contamination from other livestock feed. Specifically, materials from deer and elk may be used in feed for nonruminant animals in the United States, unless the deer or elk are known to be positive for chronic wasting disease, a BSE-like disease in cervids. Although the Food and Drug Administration (FDA) recommended in September 2003 that deer and elk from areas where chronic wasting disease is endemic no longer be used for any animal feed, the nonbinding nature of this recommendation would allow materials from animals with unidentified chronic wasting disease to be included in feed for nonruminant animals, resulting in a potential risk of cross-contamination of cattle. Similar risks were minimized in Britain in 1996 with the extension of the feed ban to include the feeding of mammalian meat or bone meal to any farmed livestock, including fish and horses.
The small-scale active surveillance program for BSE that was initiated by the USDA in 1990 has now been expanded, and about 20,000 brains from U.S. cattle were tested for abnormal prion protein in each of the past two years. Since no cases of BSE had been detected in the United States until December 2003, this testing program has been considerably more limited than the programs implemented in Europe. Except in the United Kingdom, European cattle older than 30 months of age may be used for human consumption only if the particular animal tests negative for BSE; in the United Kingdom, such use is banned completely (although the British ban, enacted in 1996, will probably be replaced by testing for the disease).3 As controls become more stringent, it becomes increasingly unlikely that cattle younger than 30 months of age will be infected with BSE; even if these younger animals were infected, they would typically be in the earlier stages of disease, and unfortunately, the currently available tests, although highly sensitive and specific for clinical disease, are less likely to detect infection at these early stages.
The protection of public health is best served by avoiding the transmission of BSE within the cattle population through well-enforced feed bans that keep potentially infectious material (whether it is infected with BSE, scrapie, or chronic wasting disease) away from cattle. There is some speculation that spontaneous cases of BSE might occur at a very low rate, similar to the rate of sporadic Creutzfeldt–Jakob disease that occurs in human populations worldwide. Even so, an effective feed ban would avert cattle-to-cattle transmission and the amplification of infectiousness within the cattle population.
Bans limiting the meat and meat products used for human consumption work in parallel with measures aimed at preventing the infection of cattle. The U.S. regulations designed to prevent cattle-to-human transmission have been strengthened in response to the recently detected case, with additional bovine tissues and all downer cattle being banned from use in food for human consumption. (As of January 12, the USDA has prohibited the use, in food for humans, of skull, brain, trigeminal ganglia, eyes, vertebral column, spinal cord, and dorsal root ganglia of cattle 30 months of age or older and the small intestines of all cattle. Tonsils from all U.S. cattle had already been banned from use in the human food supply.) Furthermore, any apparently healthy U.S. cattle targeted at slaughter for BSE-surveillance testing will no longer be marked as "inspected and passed" until confirmation is received that the animal has tested negative for BSE. Although this latter measure certainly reduces the overall risk of human exposure to meat from BSE-infected animals, its effect is limited to those cattle that are selected for BSE testing (which currently number about 20,000 annually, accounting for less than 0.1 percent of the 36 million U.S. cattle that are slaughtered each year).
The possibility of secondary human-to-human transmission of new-variant Creutzfeldt–Jakob disease was anticipated, and concern about it has prompted precautionary measures, in Britain and other countries, aimed at preventing blood-borne transmission. In 1999, after considering, on the one hand, the potential risks posed by the blood-borne transmission of new-variant Creutzfeldt–Jakob disease and, on the other hand, the reduction in the blood supply due to additional restrictions on blood donors, the FDA recommended that donations from persons who had resided in the United Kingdom for a total of six months or more between 1980 and 1996 be deferred. A recent case has highlighted the risk associated with blood transfusion: a patient in Britain who died of new-variant Creutzfeldt–Jakob disease in 2003 had received blood from a donor who had also died of the disease; the donor had not become symptomatic until 1999, three years after the blood donation had been made. It has been pointed out that both persons could have acquired the disease independently, by eating meat or meat products from BSE-infected cattle. However, a blood-transfusion link between 2 of 145 independently infected persons is so unlikely that the case can be viewed as very strong evidence of transfusion-related transmission.
The big question being posed to officials and scientists — "Is U.S. beef safe?" — cannot, of course, be answered with 100 percent certainty. Although USDA testing has been targeted at downer cattle, which are considered to be at increased risk of BSE, skeptics would argue that the testing of only a small proportion of slaughtered cattle could leave some BSE-infected animals undetected. Further reassurance could be gained by expanding the testing program to include complete sampling of all downer cattle and those that are found dead, as well as a great proportion of cattle that are slaughtered while apparently healthy. Statistically robust epidemiologic analysis, taking into account the ages and risk category (apparently healthy or having increased risk) of the cattle that are tested and allowing the test sensitivity to depend on the stage of disease, could provide policymakers and the public with the best-case and worst-case scenarios on the basis of the available data. However, the diagnosis to date of roughly 150 cases of new-variant Creutzfeldt–Jakob disease worldwide — as compared with the roughly 200,000 cases of clinical BSE that have been confirmed throughout Europe — indicates that cattle-to-human transmission has been rare even with exposure to relatively large epidemics of BSE.
Thus, the available evidence suggests that if the current control measures are well enforced, then the risk, if any, from U.S. cattle, is very low, although further regulation to limit exposure to material from cervids infected with chronic wasting disease would further reduce the potential risk of cervid-to-cattle transmission. Consumers need not be overly anxious about the risks they may have incurred by consuming beef, but they should press authorities to test more cattle, to strengthen the regulations on feed production, and to extend the ban on brain and spinal cord in food for human consumption to include cattle younger than 30 months of age.
Source Information
From the Department of Infectious Disease Epidemiology, Imperial College, London.
References
BSE: homepage. London: Department for Environment, Food and Rural Affairs (DEFRA), 2003. (Accessed January 16, 2004, at http://www.defra.gov.uk/animalh/bse/index.html.)
Anderson RM, Donnelly CA, Ferguson NM, et al. Transmission dynamics and epidemiology of BSE in British cattle. Nature 1996;382:779-788.
Ferguson NM, Donnelly CA. Assessment of risk posed by bovine spongiform encephalopathy in Cattle in Great Britain and the impact of potential changes to current control measures. Proc R Soc Lond B Biol Sci 2003;270:1579-1584.
Monthly Creutzfeldt-Jakob disease statistics. London: Department of Health, 2004. (Accessed January 16, 2004, at http://www.doh.gov.uk/cjd/index.htm)(Christl A. Donnelly, Sc.D)
A rational interpretation of the potential risks posed by BSE in North America must be grounded in the findings of long-term studies of the epidemics of BSE and new-variant Creutzfeldt–Jakob disease in Europe; these studies have focused particularly on Britain — the country that has been the most affected, with more than 179,000 confirmed clinical cases of BSE.1,2 The disease was first identified in England in 1986, and the recycling of infection through the inclusion of bovine protein in cattle feed was soon identified as the process driving the epidemic. The key measure that brought the British BSE epidemic under control was the ban, introduced in 1988, on feeding tissues from one ruminant animal to other ruminant animals. However, because of the long delay between infection and the onset of clinical signs of disease (five years, on average), the annual incidence of clinical cases did not peak until 1992 (Figure). This ban targeted ruminant animals in general, rather than cattle in particular, because scrapie, a BSE-like disease that affects sheep, has long been endemic in Britain.
Figure. Incidence of Bovine Spongiform Encephalopathy and New-Variant Creutzfeldt–Jakob Disease in Great Britain.
The epidemic of bovine spongiform encephalopathy (BSE) in Britain peaked in 1992, four years after the introduction of the ban on feeding tissues of one ruminant animal to other ruminant animals. The associated human disease, new-variant Creutzfeldt–Jakob disease, was not identified until 1996, seven years after a ban was introduced in Britain on the use in food for humans of specified offal from cattle (the brain, spinal cord, spleen, thymus, tonsils, and intestines of cattle six months of age or older). In the United States, the brains of cattle younger than 30 months of age may still be used in food produced for human consumption.
The identification in 1996 of a new variant of Creutzfeldt–Jakob disease in humans in association with BSE prompted authorities to strengthen many existing BSE-control measures (for example, the British ban on ruminant feed was extended to feed including any mammalian meat or bone meal) and to introduce new measures (for example, a British ban on the consumption of cattle older than 30 months of age). Although most of the estimated 4 million cattle that were infected over the course of the BSE epidemic in Britain3 were slaughtered for consumption, to date only 145 (definite or probable) cases of new-variant Creutzfeldt–Jakob disease have been identified in British patients, only 6 of whom remain alive. The decrease in the incidence of new-variant Creutzfeldt–Jakob disease in Britain since the peak of the epidemic in 2000 (when there were 28 cases) has dramatically decreased the uncertainty surrounding the likely size of the primary epidemic involving the known susceptible genotype (with homozygosity for methionine at codon 129 of the prion protein gene).4 A small number of additional cases have been reported in other countries (Ireland, France, Italy, Canada, and the United States). The only affected U.S. resident, whose probable case of new-variant Creutzfeldt–Jakob disease was identified in 2002, was a 22-year-old woman who had moved from the United Kingdom to Florida in 1992.
Although a ban on ruminant feed was introduced in the United States in 1997 as a precaution in response to the identification of new-variant Creutzfeldt–Jakob disease, there is still a risk of cross-contamination from other livestock feed. Specifically, materials from deer and elk may be used in feed for nonruminant animals in the United States, unless the deer or elk are known to be positive for chronic wasting disease, a BSE-like disease in cervids. Although the Food and Drug Administration (FDA) recommended in September 2003 that deer and elk from areas where chronic wasting disease is endemic no longer be used for any animal feed, the nonbinding nature of this recommendation would allow materials from animals with unidentified chronic wasting disease to be included in feed for nonruminant animals, resulting in a potential risk of cross-contamination of cattle. Similar risks were minimized in Britain in 1996 with the extension of the feed ban to include the feeding of mammalian meat or bone meal to any farmed livestock, including fish and horses.
The small-scale active surveillance program for BSE that was initiated by the USDA in 1990 has now been expanded, and about 20,000 brains from U.S. cattle were tested for abnormal prion protein in each of the past two years. Since no cases of BSE had been detected in the United States until December 2003, this testing program has been considerably more limited than the programs implemented in Europe. Except in the United Kingdom, European cattle older than 30 months of age may be used for human consumption only if the particular animal tests negative for BSE; in the United Kingdom, such use is banned completely (although the British ban, enacted in 1996, will probably be replaced by testing for the disease).3 As controls become more stringent, it becomes increasingly unlikely that cattle younger than 30 months of age will be infected with BSE; even if these younger animals were infected, they would typically be in the earlier stages of disease, and unfortunately, the currently available tests, although highly sensitive and specific for clinical disease, are less likely to detect infection at these early stages.
The protection of public health is best served by avoiding the transmission of BSE within the cattle population through well-enforced feed bans that keep potentially infectious material (whether it is infected with BSE, scrapie, or chronic wasting disease) away from cattle. There is some speculation that spontaneous cases of BSE might occur at a very low rate, similar to the rate of sporadic Creutzfeldt–Jakob disease that occurs in human populations worldwide. Even so, an effective feed ban would avert cattle-to-cattle transmission and the amplification of infectiousness within the cattle population.
Bans limiting the meat and meat products used for human consumption work in parallel with measures aimed at preventing the infection of cattle. The U.S. regulations designed to prevent cattle-to-human transmission have been strengthened in response to the recently detected case, with additional bovine tissues and all downer cattle being banned from use in food for human consumption. (As of January 12, the USDA has prohibited the use, in food for humans, of skull, brain, trigeminal ganglia, eyes, vertebral column, spinal cord, and dorsal root ganglia of cattle 30 months of age or older and the small intestines of all cattle. Tonsils from all U.S. cattle had already been banned from use in the human food supply.) Furthermore, any apparently healthy U.S. cattle targeted at slaughter for BSE-surveillance testing will no longer be marked as "inspected and passed" until confirmation is received that the animal has tested negative for BSE. Although this latter measure certainly reduces the overall risk of human exposure to meat from BSE-infected animals, its effect is limited to those cattle that are selected for BSE testing (which currently number about 20,000 annually, accounting for less than 0.1 percent of the 36 million U.S. cattle that are slaughtered each year).
The possibility of secondary human-to-human transmission of new-variant Creutzfeldt–Jakob disease was anticipated, and concern about it has prompted precautionary measures, in Britain and other countries, aimed at preventing blood-borne transmission. In 1999, after considering, on the one hand, the potential risks posed by the blood-borne transmission of new-variant Creutzfeldt–Jakob disease and, on the other hand, the reduction in the blood supply due to additional restrictions on blood donors, the FDA recommended that donations from persons who had resided in the United Kingdom for a total of six months or more between 1980 and 1996 be deferred. A recent case has highlighted the risk associated with blood transfusion: a patient in Britain who died of new-variant Creutzfeldt–Jakob disease in 2003 had received blood from a donor who had also died of the disease; the donor had not become symptomatic until 1999, three years after the blood donation had been made. It has been pointed out that both persons could have acquired the disease independently, by eating meat or meat products from BSE-infected cattle. However, a blood-transfusion link between 2 of 145 independently infected persons is so unlikely that the case can be viewed as very strong evidence of transfusion-related transmission.
The big question being posed to officials and scientists — "Is U.S. beef safe?" — cannot, of course, be answered with 100 percent certainty. Although USDA testing has been targeted at downer cattle, which are considered to be at increased risk of BSE, skeptics would argue that the testing of only a small proportion of slaughtered cattle could leave some BSE-infected animals undetected. Further reassurance could be gained by expanding the testing program to include complete sampling of all downer cattle and those that are found dead, as well as a great proportion of cattle that are slaughtered while apparently healthy. Statistically robust epidemiologic analysis, taking into account the ages and risk category (apparently healthy or having increased risk) of the cattle that are tested and allowing the test sensitivity to depend on the stage of disease, could provide policymakers and the public with the best-case and worst-case scenarios on the basis of the available data. However, the diagnosis to date of roughly 150 cases of new-variant Creutzfeldt–Jakob disease worldwide — as compared with the roughly 200,000 cases of clinical BSE that have been confirmed throughout Europe — indicates that cattle-to-human transmission has been rare even with exposure to relatively large epidemics of BSE.
Thus, the available evidence suggests that if the current control measures are well enforced, then the risk, if any, from U.S. cattle, is very low, although further regulation to limit exposure to material from cervids infected with chronic wasting disease would further reduce the potential risk of cervid-to-cattle transmission. Consumers need not be overly anxious about the risks they may have incurred by consuming beef, but they should press authorities to test more cattle, to strengthen the regulations on feed production, and to extend the ban on brain and spinal cord in food for human consumption to include cattle younger than 30 months of age.
Source Information
From the Department of Infectious Disease Epidemiology, Imperial College, London.
References
BSE: homepage. London: Department for Environment, Food and Rural Affairs (DEFRA), 2003. (Accessed January 16, 2004, at http://www.defra.gov.uk/animalh/bse/index.html.)
Anderson RM, Donnelly CA, Ferguson NM, et al. Transmission dynamics and epidemiology of BSE in British cattle. Nature 1996;382:779-788.
Ferguson NM, Donnelly CA. Assessment of risk posed by bovine spongiform encephalopathy in Cattle in Great Britain and the impact of potential changes to current control measures. Proc R Soc Lond B Biol Sci 2003;270:1579-1584.
Monthly Creutzfeldt-Jakob disease statistics. London: Department of Health, 2004. (Accessed January 16, 2004, at http://www.doh.gov.uk/cjd/index.htm)(Christl A. Donnelly, Sc.D)