Bovine Spongiform Encephalopathy Risk Research Articles

The risk of accidental transmission of transmissible spongiform encephalopathy: identification of emerging issues

The transmissible spongiform encephalopathies (TSEs), thought to be caused by prions, are fatal neurodegenerative disorders of humans and animals. Despite their rarity, human prion diseases have received prominence because the consumption of prion-contaminated meat from cattle with bovine spongiform encephalopathy (BSE) is thought to be responsible for the emergence of variant Creutzfeldt–Jakob disease (vCJD) in humans. Clinical criteria for the diagnosis of vCJD is now available. Recent, more startling evidence suggests that the clinical presentation of vCJD may vary and that patients may present as classical (sporadic) CJD or may have subclinical infection and be apparently healthy. These patients may still pose a risk of iatrogenic transmission through surgical or medical (blood transfusion) procedures. The aim of future work is to develop preclinical screening tests for the identification of infected but still healthy individuals. The future course of vCJD is still uncertain. Modelling studies to predict the cases of vCJD depend on the date of origin of BSE and time of infection, which is, at best, only approximated. As the number of cases of BSE in the UK declines, the risk of BSE in other countries from imported cattle or meat and bone meal from the UK has been increasing. It is also recognized that other animal species (farmed, domestic and wild animals) other than cows are susceptible to TSEs. The possibility of interspecies transmission of TSEs and the global presence of the disease suggests a need for a co-ordinated worldwide risk management approach to eradicate TSEs.

Descriptive spatial analysis of BSE in western France.

The spatial heterogeneity of Bovine Spongiform Encephalopathy (BSE) was analysed on the 84 cases confirmed in western France (WF) between August and December 2000, when both the Mandatory Reporting System and an active surveillance on cattle at risk were running. Ninety-four percent of these cases were born between June 1993 and June 1996, and we analysed the location at birth. One disease mapping and two clustering methods (Scan of Kulldorff and the method of Besag and Newell) were used. In order to attenuate the contrasts artificially created by the standard disease mapping method (over-dispersion), we estimated the Standard Incidence Ratio (SIR) with a Bayesian method (Poisson-Gamma model) allowing a smoothing of the estimators. The geographical location of interest was the "canton", that divided the total area into 526 geographical units. The background population (2.6 million cattle) was obtained from the Agricultural Census 2000. We tested the hypothesis of a homogenous spatial distribution of the BSE risk where the expected number of BSE cases per unit area was obtained by applying the overall BSE rate in WF to each "canton", standardised on the type of breed, dairy versus beef suckler. The SIR ranged from 0.80 to 2.18 and the spatial distribution of BSE cases was significantly heterogeneous. Two spatial clusters were detected with the spatial scan statistics of Kulldorff and the method of Besag and Newell (18 to 20 observed BSE-cases per cluster with a radius of 45 km) centred on the "département" of Côtes-d'Armor and Mayenne. Another cluster was detected with the method of Besag and Newell (9 observed BSE-cases) in the "département" of Finistère. The results proved that the risk of BSE is linked to the geographical location in the area of the study.

European Union's rapid TSE testing in adult cattle and sheep: implementation and results in 2001 and 2002.

After the discovery of variant Creutzfeldt-Jakob disease (vCJD), scientific advances quickly led to post-mortem tests to identify late-stage bovine spongiform encephalopathy (BSE) disease. These were first used in Switzerland in 1999 for active BSE surveillance of a) fallen and emergency-slaughter bovines (risk stock) and b) 5% sample of routinely slaughtered cattle over 30 months of age. In 1999 and 2000, Switzerland's estimated 103 BSE positives per 1000000 adult cattle put it in the same BSE risk classification as UK and Portugal. In July 2000, the European Union's Scientific Steering Committee published its methodology (and first vetted results) for geographical BSE risk (GBR) assessment in cattle. Member states with no BSE cases found themselves, on rational assessment, classified as GBR III (BSE likely but not confirmed, or confirmed at a lower level). Because of Europe's thus highly assessed BSE risks, active BSE surveillance of adult cattle in all member states began in January 2001 using one of three validated post-mortem tests. Implementation was variable across member states in January to March 2001 but, where operational, active surveillance was typically achieved for around 13300 routinely slaughtered and 1000 risk stock per month per 1000000 adult cattle; BSE positive rates were 60 and 600 per 1000000 routinely slaughtered and risk cattle, respectively. By the second half of 2001, active BSE surveillance was operating reasonably in most member states, although anomalies persisted. Performance and results for July to December 2001 and for January to June 2002 are considered in detail. The BSE positive rate decreased substantially in UK, Portugal and Ireland between semesters, whereas Spain's rates increased for both routinely slaughtered and risk bovines. Based on 1450000 routinely slaughtered and 135000 risk stock as standard, France could have expected 153 BSE positives in July to December 2001 (109 in January to June 2002); Italy 154 (67); and Germany only 39 (48). When sample-based surveillance data were scaled up and combined with clinical BSE cases, Great Britain's BSE positives were estimated at around 400 per 1000000 adult cattle in 2002 compared with over 1000 per 1000000 adult cattle in 2000. Age distributions for cattle subject to active BSE surveillance have been underexploited. The major transmissible spongiform encephalopathy (TSE) which affects sheep and goats is scrapie. Passive surveillance of scrapie is associated with substantial under-reporting. Susceptibility to scrapie depends strongly on sheep genotype; but resistance to scrapie does not necessarily confer resistance of sheep to BSE. Because of uncertainty about the true prevalence of scrapie-infected adult sheep and concern that BSE in sheep may be missed, the European Union pre-empted its planned evaluation of rapid post-mortem TSE tests in sheep by requiring the rapid TSE testing of small ruminants from April 2002 with one of the three cattle-validated tests. Basic requirements for active TSE surveillance in sheep were: random sample of 6000 fallen sheep and of 60000 routinely slaughtered adult native sheep to be tested per member state by end March 2003. Lower surveillance targets were set for countries with under 1000000 adult sheep. Adequately to map scrapie-susceptible genotypes and identify resistant genotypes, a random sample of 500 routinely slaughtered native adult sheep was to be genotyped, together with each TSE rapid test positive adult sheep and two sets of three suitably sampled controls. By the end of August 2002, when 41% of the initial surveillance time had elapsed, only 20% of the European joint target for routinely slaughtered adult sheep had been completed, but that for fallen sheep was exceeded. Except in Ireland, the upper 95% confidence bound on TSE prevalence exceeded 500 per 1000000 routinely slaughtered adult sheep in reporting-compliant countries with more than 1000000 adult sheep. The UK, Greece, Italy and France were likely to approach the goal of 100 TSE rapid test positives on completion of their assigned first-year surveillance target for sheep. Results from the recommended genotyping of TSE positive adult sheep and controls for use in inferring differential TSE-positive susceptibility by genotype are awaited. Only by genotyping 5000-50000 TSE-positive adult sheep, a massive undertaking even on the European scale, will it become clear whether scrapie resistance is relative rather than absolute. This paper details Europe's quantitative evolution in TSE surveillance.

Can ε-Aminocaproic Acid Balance the Off-Pump Bleeding Advantage?

Background: Aprotinin improved the control of bleeding in patients undergoing surgery with cardiopulmunary bypass, but its use was halted because of the risk of bovine spongiform encephalopathy. We then started to use ε-aminocaproic acid and the results in the control of bleeding were satisfactory. To assess its effectiveness in the control of postoperative bleeding precisely, we compared the results for patients operated on for myocardial revascularization on-pump and treated with ε-aminocaproic acid with those for patients who decidedly bleed less: off-pump patients. Methods: Two groups of patients who had had either on- or off-pump double aortocoronary bypass surgery were retrospectively reviewed for postoperative bleeding. These two almost homogeneous group had two grafts only: left anterior descending and circumflex arteries operated on with cardiopulmonary bypass and treated with the ε-aminocaproic acid, and left anterior descending and right coronary arteries operated on off-pump. Results: Postoperative bleeding through chest drainage at 4 h was 265 ± 91.7 mL in the off-pump group and 328.4 ± 131.4 mL in the on-pump group ( p = 0.004). But at 24 h it was 671.6 ± 311.5 mL in the off-pump group and 827.8 ± 514.4 mL in the on-pump group ( p = 0.07). Conclusions: ε-Aminocaproic acid is effective in controlling postoperative bleeding in patients operated on for myocardial revascularization with the aid of cardiopulmonary bypass.

Perceived Risk of Bovine Spongiform Encephalopathy and Dietary Behavior

The German BSE crisis in early 2001 can be considered as a natural experiment with strong behavioral consequences. The present study investigated psychological and other factors associated with reduced meat consumption compared to the first months of the previous year. As expected, all types of meat, with the exception of poultry and game, were eaten less often. The effect was strongest in beef, where almost half of the sample reported reduced meat consumption. As predicted by the health belief model, perceived threat was associated with subjective vulnerability. It was not, however, strongly associated with perceived seriousness of BSE, probably due to the ubiquitous public discussion of the topic. Reduced beef consumption has three to four times more frequent in the event of subjective threat.

Perceived risk of bovine spongiform encephalopathy and dietary behavior.

The German BSE crisis in early 2001 can be considered as a natural experiment with strong behavioral consequences. The present study investigated psychological and other factors associated with reduced meat consumption compared to the first months of the previous year. As expected, all types of meat, with the exception of poultry and game, were eaten less often. The effect was strongest in beef, where almost half of the sample reported reduced meat consumption. As predicted by the health belief model, perceived threat was associated with subjective vulnerability. It was not, however, strongly associated with perceived seriousness of BSE, probably due to the ubiquitous public discussion of the topic. Reduced beef consumption has three to four times more frequent in the event of subjective threat.

An exploration of risk factors for bovine spongiform encephalopathy in ruminant production systems in the tropics.

The epidemic of bovine spongiform encephalopathy (BSE) in Europe in the late Twentieth Century required the interplay of two sets of factors, which now provide reference points for assessment of the BSE risk throughout the world. One set of factors consisted of the presence of infective agent in cattle or some other ruminant. The second set consisted of transmission and amplification of the disease, made possible through a particular feeding system that allowed persistent and habitual feeding of meat-and-bone meal (MBM) derived from cattle. The authors explore the ruminant production systems of three representative countries in South-East Asia against the background of factors required for the manifestation of BSE. The results can be extended to other countries in sub-tropical and tropical regions where similar, non-industrial ruminant production systems operate. In short, the lack of a nutritionally or economically rational niche for MBM as a source of dietary protein or nitrogen in many ruminant production systems removes the hazard of BSE.

Can ε-aminocaproic acid balance the off-pump bleeding advantage?

Background: Aprotinin improved the control of bleeding in patients undergoing surgery with cardiopulmunary bypass, but its use was halted because of the risk of bovine spongiform encephalopathy. We then started to use ε-aminocaproic acid and the results in the control of bleeding were satisfactory. To assess its effectiveness in the control of postoperative bleeding precisely, we compared the results for patients operated on for myocardial revascularization on-pump and treated with ε-aminocaproic acid with those for patients who decidedly bleed less: off-pump patients. Methods: Two groups of patients who had had either on- or off-pump double aortocoronary bypass surgery were retrospectively reviewed for postoperative bleeding. These two almost homogeneous group had two grafts only: left anterior descending and circumflex arteries operated on with cardiopulmonary bypass and treated with the ε-aminocaproic acid, and left anterior descending and right coronary arteries operated on off-pump. Results: Postoperative bleeding through chest drainage at 4 h was 265±91.7 mL in the off-pump group and 328.4±131.4 mL in the on-pump group ( p=0.004). But at 24 h it was 671.6±311.5 mL in the off-pump group and 827.8±514.4 mL in the on-pump group ( p=0.07). Conclusions: ε-Aminocaproic acid is effective in controlling postoperative bleeding in patients operated on for myocardial revascularization with the aid of cardiopulmonary bypass.

How the surveillance system may bias the results of analytical epidemiological studies on BSE: prevalence among dairy versus beef suckler cattle breeds in France.

Until recently, epidemiological studies on Bovine Spongiform Encephalopathy (BSE) were based on Mandatory Reporting Systems (MRS) of clinically suspect bovines only, but rapid diagnostic tests were validated in 1999 and are used for targeted surveillance in Switzerland, France and other countries, as a complementary and secondary tool. Data on 30491 cattle issued from a French pilot program targeted at cattle having died on the farm, subjected to euthanasia or sent for emergency slaughter, did not show any significant difference in BSE risk between dairy and beef suckler breeds. The data also revealed that part of the clinical cases of BSE escaped the MRS, which permitted to detect more dairy than beef suckler affected cattle compared to the targeted surveillance in the same period (from August to December 2000) and region (Bretagne, Pays de la Loire and Basse Normandie regions). Analyzing together the data of the targeted surveillance and mandatory reporting system programs with a non-conditional logistic regression, we found that the odds of a dead cow being a BSE case among all dead cattle was 3.2 times higher for dairy breeds compared to beef suckler breeds. This confirmed British findings but points out to the fact that considering either MRS or targeted surveillance data alone may possibly create biases in epidemiological studies on BSE.

BSE – Epidemiology and Transmission Mechanisms in Animal Production Systems

In 1986, a new clinical disease in cattle was recognized in the UK. It was classified as a progressive neurological condition in cattle similar to scrapie of sheep and goats, and was named bovine spongiform encephalopathy (BSE). Epidemiological studies on clinical cases diagnosed in 1986 and 1987 highlighted the increased risk of BSE on farms that had fed cattle concentrates containing meat-andbone meal (MBM). The addition of MBM to cattle concentrate feed at that time was common practice in the UK and other countries (but with varying percentages). As a consequence, the use of MBM in ruminant feed was banned in the UK in 1988. This ban resulted in a significant reduction of new infections in cattle born after this ban, thereby highlighting the importance of controlling this exposure route. Further studies in the UK and other countries confirmed that BSE is predominantly, if not exclusively, transmitted by inclusion of ruminant CNS material - brain or spinal cord from BSE-infected cattle - in cattle rations. BSE cases born after these MBM bans (denoted BAB cases) documented the presence of other infection routes besides routine inclusion of MBM in cattle concentrates. Cross-contamination of cattle feed with feed produced for pigs and poultry, and cross-exposure of cattle to pig or poultry feed on mixed-species farms were identified as additional infection routes. The Scientific Steering Committee (SSC) of the European Commission listed several risk factors for BSE propagation including the structure and intensity of the cattle population and other livestock populations, production and use of ruminant-derived meat-and-bone meal (including feed bans), the use of specified risk material (SRM) and carcasses (including SRM bans) and the rendering industry (structure, technology, rendering parameters). Prevention of these known and suspected feed-related routes of BSE transmission has resulted in a decline in the number of new infection in subsequent birth cohorts in several countries. Due to the long incubation time of BSE, however, it takes several years until the effectiveness of implemented measures to prevent new BSE infections can be assessed. BSE is a food-transmitted disease, and exposure to the infectious agent is strongly associated with the cattle feed production and management practices within specific cattle production systems. The disease can be controlled by changes in these feed production systems and cattle farming practices, however, it will take time for countries that have detected domestic BSE cases to completely eliminate all circulating BSE infectivity.

Application of systems analysis in modelling the risk of bovine spongiform encephalopathy (BSE)

Bovine spongiform encephalopathy (BSE), widely known as “mad cow disease”, has virtually crippled the British livestock industry. Even though, no cases of BSE have been reported in the United States (US), a similar epidemic in the US would be catastrophic. The added concern for the risk of introduction of the human disease called variant Creutzfeldt‐Jacob disease that has been linked to eating meat of BSE infected cattle compounds the risk of BSE. Systems dynamics models based on the underlying transmission pathways of BSE can help to anticipate the spread of this disease in different cattle populations and assist in the evaluation of potential risk mitigations for preventing its introduction or controlling its spread if it was introduced. With this in mind, an age and health status structured systems dynamics model was developed. By making assumptions and setting up feasible scenarios, the model can be used to examine potential prevalence and incidences rates of BSE; the effect of mitigations including changes in feeding habits or rendering processes and/or other policies and regulations designed to prevent the introduction of BSE. The systems dynamics simulation model enabled us to create virtual experiments whose real‐world analogues would otherwise be expensive, dangerous, or even impossible to carryout.

Prions, BSE and food

Biochemical and biophysical properties of prions including possible inactivation methods are reviewed. Possible molecular markers of transmissible spongiform encephalopathy (TSE) and mechanisms behind infectivity and correlation with clinical symptoms are discussed. The risk of Bovine Spongiform Encephalopathy (BSE) for humans i.e. variant Creutzfeldt–Jakob Disease (cCJD) is addressed in detail. The consequences of the emergence of the new cCJD and the lack of information on the infectivity of cCJD at the clinical stage of the disease in relation to the need to reconsider the biological concepts currently used in microbiology.

Risks of bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease in the United States.

Risks of bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease in the United States.

Big decisions based on small numbers: Lessons from BSE

Summary The epidemic of bovine spongiform encephalopathy (BSE) has been the most expensive disaster ever to have befallen farming in the UK. It is believed to have led to a new form of spongiform encephalopathy in humans and as yet there is no way of knowing how many people will die of this disease. In order to curtail the BSE epidemic major decisions had to be made, often on the basis of inadequate scientific data. These data may have been derived from experiments using small sample numbers. Here we review some examples of where this has happened, sometimes with a beneficial outcome and sometimes with a misleading outcome. The identification of BSE as a new disease depended on precise neuropathological observation of a small number of cases rather than the obvious occurrence of large numbers of sick animals. Similarly, the recognition that BSE may have led to disease in humans was based on the neuropathological and clinical picture of new variant Creutzfeldt‐Jakob disease (CJD) rather than on an increase in the number of cases of CJD in the UK. Early in the BSE epidemic the possibility that disease could be maternally transmitted from cow to calf was raised, mainly because of a belief that such transmission occurs in scrapie disease of sheep. But, we argue, the evidence for maternal transmission of scrapie, collected in the 1960s, was based on small numbers and is inadequate. Subsequent research has shown a very substantial genetic component in scrapie and epidemiological data show no excess risk in the offspring of affected ewes relative to the risk in the offspring of affected rams. An experiment to determine whether maternal transmission occurs in BSE was flawed and was unable to distinguish between maternal transmission and genetic susceptibility to environmental contamination. An assessment of the risk of BSE to humans depends on determining the levels of infectivity in tissues and transmissibility across species. Data on both of these are deficient, so it is not possible to predict how many people in the UK or elsewhere will become affected with new variant CJD in the next fifty years. The assessment of whether BSE could be transmitted to sheep and whether sheep therefore pose a risk to humans is hampered by a serious lack of evidence about the epidemiology of scrapie in the UK and elsewhere. The UK has paid a heavy price for the BSE epidemic but lessons should be learned from the experience. Every country should have a Specified Offals Ban even if it has no cases of BSE because, by the time it has, it will be too late. Furthermore, the occasional case of BSE should not be regarded as insignificant since it may be the harbinger of an epidemic in the making.

A genetic interpretation of heightened risk of BSE in offspring of affected dams.

An analysis is presented of the results of a cohort study designed to test whether or not the aetiological agent of bovine spongiform encephalopathy (BSE) in cattle can be transmitted maternally (vertically) from dam offspring. Various genetic models are fitted to the data under the assumption that the results could be explained entirely by genetic predisposition to disease (as opposed to maternal transmission) given exposure of offspring of diseased and unaffected dams to contaminated cattle feed. The analyses suggest that the results could be explained by the hypothesis of genetic predisposition, provided a large difference exists in the susceptibility of resistant and susceptible hosts, and explore the range of genotypic parameters and frequencies consistent with the limited currently available data. The results presented are broadly robust, even under the scenario that a portion of the observed maternally enhanced risk of BSE is due to a low level of maternal transmission in late incubation stage dams.

The risk of bovine spongiform encephalopathy ('mad cow disease') to human health

The risk of bovine spongiform encephalopathy ('mad cow disease') to human health

Analysis of the Bovine Spongiform Encephalopathy Maternal Cohort Study: Evidence for Direct Maternal Transmission

SUMMARY In an initial exploratory analysis of the bovine spongiform encephalopathy (BSE) maternal cohort study data we demonstrate several confounding effects in the study design. Given these effects, we assess a variety of statistical models to determine the relative contributions of direct maternal transmission of the aetiological agent of BSE and of genetic susceptibility to the observed maternally enhanced risk of BSE in the offspring of affected dams. To control for the substantial between-herd variation in the risk of exposure to the BSE agent, it is essential that analyses take into account the matched pair structure of the data. Maternal exposure is estimated to be most important in animals born within 150 days of disease onset in their dams. The analysis of a full survival likelihood model indicates that the hypothesis of maternal transmission with no genetic variation in susceptibility fits the data significantly better than the hypothesis of genetically variable susceptibility with no maternal transmission. However, models incorporating both maternal transmission and genetically variable susceptibility fit the data significantly better than pure maternal transmission models. Although genetic susceptibility cannot be excluded as the cause of the cohort study results in the absence of detailed genotyping, the analysis of these study data suggest that low level maternal transmission of BSE is, at least in part, responsible for the significantly enhanced risk of BSE in the offspring of affected dams. Similar results indicating significant maternal transmission in the later stages of the dam incubation period are obtained from the independent analysis of data on the dam–offspring relationships among confirmed BSE cases.

A matter for debate: the risk of bovine spongiform encephalopathy to humans posed by blood transfusion in the UK.

If human infection with bovine spongiform encephalopathy (BSE) were to occur, donated peripheral blood from humans that might have become infected from eating adequate quantities of food containing BSE should, until evidence is available to the contrary, be assumed to contain the human form of the disease. The chance of disease transfer to a blood recipient in 1995, which might in turn cause clinical disease with an incubation period of 20 years, is calculated. Transfusion is calculated to be a potential cause of a maximum of only 0.2% of clinical cases of Creutzfeldt-Jakob disease (CJD) in the UK population if the BSE epidemic were to spread to humans. Prospective epidemiological techniques would be unlikely to demonstrate any such minor contribution that blood transfusion might make to CJD incidence.

Risk assessment and surveillance for bovine spongiform encephalopathy (BSE) in Argentina

An assessment was made of the risks of bovine spongiform encephalopathy (BSE) occurring in Argentina. Most of the factors associated with the origin and development of the BSE epidemic in the UK are essentially absent. For example, Argentina's large sheep and cattle industries are based on low-cost production systems using grass. Concentrated feeds are not used for sheep, rarely for beef cattle and to a comparatively modest extent for dairy cows. Particularly important are the facts that scrapie (and BSE) has never been reported in Argentina—very small amounts of waste tissues from sheep are rendered to produce meat and bone meal (MBM)—and MBM is not used in concentrated feeds for cattle. We conclude that Argentina has an exceptionally low risk of BSE due to scrapie. There is a very small risk of BSE having been introduced via live animals imported from countries with BSE, but this could only give rise to isolated cases because MBM is not fed to cattle. A surveillance programme has been carried out based largely on a histological examination of brains from three categories of old dairy cows: animals reported on the suspicion of having neurological disease; animals in poor condition at slaughter; healthy animals randomly selected in the abattoir. No evidence of transmissible spongiform encephalopathy was seen in several sections from each of a total of 1019 brains. We conclude that, for most practical purposes, Argentina may be considered to be free from BSE.

Risk of human exposure to bovine spongiform encephalopathy

Recent reports of prion disease developing in four dairy farmers and two teenagers in Britain have raised renewed concerns about the potential health risk of bovine spongiform encephalopathy to humans. Documented transmission of bovine spongiform encephalopathy to non-human primates indicates that such concerns are not without foundation.1 Although prions are not conventional pathogens, many of the basic principles governing microbial pathogenesis seem to apply to the infectious forms of prion diseases. In this context human risk of infection after exposure to bovine spongiform encephalopathy can be considered in terms of the size of the infecting inoculum, the potential routes of entry into the host, and factors of host susceptibility. Infectivity in human prion diseases is concentrated primarily in neural (brain, spinal cord, eye) and lymphoreticular (liver, spleen, lymph nodes) tissues.2 Human brain material has been estimated to contain 103-105 infectious units per gram of tissue,2 and bioassay in mice has shown brain material from cattle with bovine spongiform encephalopathy to contain 105-106 infectious units per gram.3 In both human prion diseases and bovine spongiform encephalopathy, infectivity is not found in skeletal muscle, adipose tissue, or body fluids (blood, saliva, urine, faeces, semen, milk).2 3 4 5 Fortunately, with …