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Biomedical subjects

J W Wilesmith

Publications and source records attributed to J W Wilesmith.

At least 37 records · Page 2Linked to original sources

Histological observations on the brains of symptomless 7-year-old cattle.

The histological changes in the brains of 506 clinically normal 7-year-old cattle, which were part of a cohort study on maternal transmission of bovine spongiform encephalopathy, are described. Vacuolation of the white matter, of unknown aetiology, located particularly in the substantia nigra, was a frequent finding. Vacuolated neurons were commonly observed in the red nucleus (64.3% of the animals) and in the habenular nucleus (50.1%). Spheroids were found in 10.8% of the brains, most frequently in the vestibular nuclei. Cellular inflammatory infiltrates in association with blood vessels occurred in 30% of the animals at various locations in the brain; their aetiology remains uncertain, but they may have reflected subclinical or latent infections. Mineralization of the wall of blood vessels, with proliferation of the intima, was observed frequently in vessels of the internal capsule and was probably associated with ageing. The description of histological findings in the brain of symptomless adult cattle in the present study provides a useful background for diagnostic bovine neuropathology.

Animals↗

Descriptive spatial analysis of the epidemic of bovine spongiform encephalopathy in Great Britain to June 1997.

This was a spatial analysis of the epidemic of bovine spongiform encephalopathy (BSE) in Great Britain, based on agricultural census data collected between 1986 and 1996 and BSE case data collected up to June 1997. Kernel smoothing techniques were used to plot the distribution of BSE-positive cattle holdings per 100 holdings per square kilometre and the distribution of confirmed BSE cases per 100 head of cattle per square kilometre. In the early stages of the epidemic reported BSE cases were scattered widely throughout Great Britain, with no clearly identifiable focus. By June 1997, a statistically significant cluster of BSE-positive holdings was identifiable in the eastern part of the South west region of England. During the epidemic the highest densities of confirmed BSE cases per 100 cattle per square kilometre occurred in the greater part of the South west region of England and within Dyfed in the south west of Wales. In Wales, a small number of holdings experienced large numbers of confirmed BSE cases. In the South west region of England a large number of holdings experienced small numbers of confirmed cases. By June 1997, the distribution of BSE-positive holdings across Great Britain was largely determined by factors that influenced the amount of recycled infectious material they were exposed to.

Animals↗

Temporal aspects of the epidemic of bovine spongiform encephalopathy in Great Britain: individual animal-associated risk factors for the disease.

The objectives of this study were first to determine the cumulative incidence of bovine spongiform encephalopathy (BSE) in the British cattle population from July 1986 to June 1997, secondly, to identify individual animal-associated risk factors that influenced the age of onset of clinical signs in confirmed BSE cases, and, thirdly, to assess the effectiveness of the measures introduced to control BSE during the epidemic. The analyses were based on the population of British cattle at risk, derived from agricultural census data collected between 1986 and 1996, and BSE case data collected up to June 30, 1997. The unit of interest was individual adult cattle recorded on annual agricultural censuses between June 1986 and June 1996. Univariate and multivariate survival analysis techniques were used to characterise the age of onset of clinical signs. In total 167,366 cases of BSE were diagnosed in Great Britain up to June 30, 1997. The cumulative incidence of BSE between July 1986 and June 1997 was 1.10 (95 per cent confidence interval [CI] 1.09 to 1.10) cases per 100 adult cattle at risk. Cattle from the South east, South west and Eastern regions of England had 4.26 to 5.96 (95 per cent CI 4.15 to 6.14) times as great a monthly hazard of being confirmed with BSE as cattle from Scotland. Compared with cattle born before June 1985, those born between July 1987 and June 1988 had 22.5 (95 per cent CI 22.1 to 22.8) times the monthly hazard of being confirmed with BSE, whereas those born in the 12 months after July 1988 had only 7.39 (95 per cent CI 7.24 to 7.54) times the monthly hazard of being confirmed with BSE. This reduction in hazard was directly attributable to the ban on the use of ruminant protein as a feed instituted in July 1988. Successive cohorts from 1989 to 1991 experienced further reductions in the hazard of experiencing BSE. The additional decrease in hazard observed for the 1990 cohort may be attributed to the effect of the Specified Bovine Offal ban instituted in September 1990.

Animals↗

Temporal aspects of the epidemic of bovine spongiform encephalopathy in Great Britain: holding-associated risk factors for the disease.

The objectives of this study were first to describe the pattern of the epidemic of bovine spongiform encephalopathy (BSE) in Great Britain in terms of the temporal change in the proportion of all cattle holdings that had experienced at least one confirmed case of BSE to June 30, 1997, and secondly to identify risk factors that influenced the date of onset of a holding's first confirmed BSE case. The analyses were based on the population of British cattle at risk, derived from agricultural census data collected between 1986 and 1996, and the BSE case data collected up to June 30, 1997. The unit of interest was the cattle holding and included all those recorded at least once on annual agricultural censuses conducted between June 30, 1986, and June 30, 1996. The outcome of interest was the date on which clinical signs were recorded in a holding's first confirmed case of BSE, termed the BSE onset date. Univariate and multivariate survival analysis techniques were used to describe the temporal pattern of the epidemic. The BSE epidemic in Great Britain started in November 1986, with the majority of affected holdings having their BSE onset date after February 1992. After adjusting for the effect of the size and type of holding, holdings in the south of England (specifically those in the Eastern, South east and South west regions) had 2.22 to 2.43 (95 per cent confidence interval [CI] 2.07 to 2.58) times as great a monthly hazard of having a BSE index case as holdings in Scotland. After adjusting for the effect of region and type of holding, holdings with more than 53 adult cattle had 5.91 (95 per cent CI 5.62 to 6.21) times as great a monthly hazard of having a BSE index case as holdings with seven to 21 adult cattle. Dairy holdings had 3.06 (95 per cent CI 2.96 to 3.16) times as great a monthly hazard of having a BSE index case as beef suckler holdings. These analyses show that there were different rates of onset in different regions and in holdings of different sizes and types, that the epidemic was propagated most strongly in the south of the country, and that the growth of the epidemic followed essentially the same pattern in each region of the country, with modest temporal lags between them. The control measures imposed in 1988 and 1990 brought the expansion of the epidemic under control, although the rate of progress was slowed by those regions where the effectiveness of the control methods took some time to take full effect.

Animals↗

Scrapie surveillance in Great Britain: results of an abattoir survey, 1997/98.

A randomised sample of 2,809 apparently healthy sheep, 55 per cent of them less than 15 months of age, which were slaughtered for human consumption at abattoirs in Great Britain in 1997/98, was taken to establish the prevalence of scrapie infection. The medulla oblongata of each sheep was examined histopathologically at the level of the obex, and fresh brain tissue was examined for scrapie-associated fibrils (SAF) to establish whether there was evidence of scrapie. In addition, histological sections of the medulla from 500 of the sheep were immunostained with an antiserum to PrP, and the same technique was also applied to any animal found positive or inconclusive by the histological or SAF examinations. Any sheep which was positive by any of these diagnostic methods was also examined by Western immunoblotting, for the detection of the disease-specific protein PrP(Sc). A total of 2,798 sheep (99.6 per cent) were negative by all the methods applied. Ten animals were SAF-positive but negative by all the other methods, and in one animal there was immunohistochemical staining which could not be interpreted unequivocally as disease-specific. A mathematical model was used to estimate the prevalence of scrapie infection in the national slaughtered sheep population which would be consistent with these results. By this model, the absence of unequivocally substantiated cases of scrapie in the sample was consistent with a prevalence of infection in the slaughter population of up to 11 per cent.

Abattoirs↗

Surveillance of BSE.

The current method used to identify suspect BSE cases is based on reporting cattle displaying clinical signs compatible with BSE. The reporting of such cases is dependent on the ability of farmers and veterinarians to recognise the disease symptoms and on the willingness to report such cases. Furthermore, it depends on the stage of the disease, because early clinical signs of BSE are not always typical. Histology and immunohistochemistry are established and reliable to confirm BSE in cattle, but the procedure is cumbersome, time consuming and therefore not suited for mass testing of animals. A targeted surveillance system using the Prionics-Western-Blot Test was initiated in Switzerland in 1999. Prionics-positive results are confirmed by histology or immunohistochemistry by the BSE-reference laboratory. This surveillance scheme has confirmed fallen stock and cows subjected to emergency slaughter as the major risk groups. Currently all cattle from these two categories are tested. As a further measure a random sample of cows from regular slaughtering is tested. This enables to determine the BSE status independent of the inaccuracies of a clinical case reporting system. This approach may be helpful to reliably assess the BSE situation in countries with low incidence in order to verify their BSE status and in countries which want to prove their BSE-free status.

Animals↗

Bovine tuberculosis in Northern Ireland: a case-control study of herd risk factors.

This paper presents the results of the first formal epidemiological study in Northern Ireland of risk factors for bovine tuberculosis (TB) associated with farm boundaries, neighbours and wildlife. The study was designed as a case-control study and 427 dairy herds were investigated between December 1993 and January 1995. The case herds had more than 30 cattle, and herds in which the source of infection had been ascribed to purchased cattle were avoided. Data on the Department of Agriculture Animal Health Computer were used in conjunction with data collected through a questionnaire to examine a range of possible risk factors, including the number and nature of the farm boundaries, the number of neighbours and their TB history, the number of hedgerows, the presence of badger setts, whether badger carcases had been found on the land, and the possible presence of deer. A follow-up telephone survey was conducted to minimise bias. The results highlighted two main associations with TB breakdowns, the presence of badgers, and contiguous neighbours who had had confirmed TB breakdowns. The estimated aetiological fraction for both associations was approximately 40 per cent, suggesting that although infected cattle may have a significant role in the transmission of TB their importance relative to the badger may have been over-estimated in the Northern Ireland TB scheme. The contribution of the badger is possibly one of several main reasons for the lack of significant progress in TB eradication despite strenuous efforts associated with all aspects of the scheme.

Analysis of Variance↗

Geographical distribution of variant CJD in the UK (excluding Northern Ireland).

BACKGROUND: The agent that causes variant Creutzfeldt-Jakob disease (variant CJD) is indistinguishable from the causative agent of bovine spongiform encephalopathy (BSE). The transmission route by which human beings are infected has not been established. One hypothesis is that cases of variant CJD have resulted from exposure to the BSE agent via rendering plants involved in the production of meat and bone meal, the main vehicle of the BSE epidemic. METHODS: We identified cases of variant CJD through the National CJD Surveillance Unit, and obtained lifetime residential histories of cases by interviewing a relative. The addresses of all rendering plants in the UK (excluding Northern Ireland) in production in 1988 were available from a survey done in that year. We calculated the distance between each case's place of residence on Jan 1, 1988, and the nearest rendering plant from postcode data, and used data from the 1991 UK census to estimate the population living within various distances of rendering plants. We compared the observed number of cases of variant CJD within a particular distance of a rendering plant with the number expected if there is no association between residential proximity to a rendering plant and the risk of developing variant CJD. FINDINGS: Up to Aug 31, 1998, 26 cases of variant CJD with onset in the UK (Northern Ireland not included) had been identified. The observed and expected numbers of variant CJD cases living within a specified distance of any rendering plant up to 50 km were almost the same. Two plants in the county of Kent each had four cases within 50 km in 1988, significantly more cases than expected (plant A, 1.04 expected; plant B, 0.74 expected). Multiple significance tests were done, so some tests would be expected to appear significant by chance alone. Computer simulations suggested that the observation of four cases of variant CJD living in an area with a population of 1.5 million (the size of Kent) is not unexpected. INTERPRETATION: There is no evidence that people with variant CJD tended to live closer than the population as a whole to rendering plants in the 1980s. The reported cluster of variant CJD cases in Kent is most probably a chance finding.

Abattoirs↗

Analysis of dam-calf pairs of BSE cases: confirmation of a maternal risk enhancement.

We investigate whether a calf born to a dam that develops bovine spongiform encephalopathy (BSE) (prior or subsequent to the birth) is itself at an enhanced risk of developing BSE. Analyses utilize the main database on reported BSE cases in the British cattle herd maintained by the Central Veterinary Laboratory in Weybridge to trace the dams of BSE-affected animals born following the ruminant feed ban in July 1988. The data reveal a significantly enhanced risk of disease in calves born to BSE-affected dams, with the risk being greatest when birth occurs after the onset of clinical signs of disease in the dam. The dependence of the maternally enhanced risk on the maternal incubation stage at birth argues for a significant component of direct maternal transmission of the aetiological agent of BSE, and offers little support for the hypothesis of genetic predisposition. Using a statistical likelihood model, we obtain estimates of the rate of direct maternal transmission by maternal incubation stage; however, biases in the available data make these values minimum estimates.

Animals↗

Comparison of histology with maternal and fetal serology for the diagnosis of abortion due to bovine neosporosis.

An indirect fluorescent antibody test was applied to sera from normally calving and aborting cows and to samples of pleural fluid from their aborted calves, and the antibody titres were compared with histology and immunocytochemistry for the diagnosis of Neospora-associated abortion. Two groups of aborting cows and a third group of cows which had calved normally were used; group A consisted of 36 cows which aborted calves showing characteristic non-suppurative inflammatory lesions in which Neospora was demonstrated by immunocytochemistry, group B consisted of 100 cows which aborted calves without histological evidence of neosporosis, and group C consisted of 128 normally calved cows which were sampled within one month of calving. Serology on the maternal sera and fetal fluids was highly specific and sensitive for Neospora infection although 5 per cent of the cows which aborted Neospora-negative calves and 4.7 per cent of the normally calved cows were also seropositive. Anti-Neospora antibodies were also detected in 7 per cent of the samples of fetal fluid from Neospora-negative abortions.

Abortion, Veterinary↗

A cohort study to examine maternally-associated risk factors for bovine spongiform encephalopathy.

This long-term cohort study, initiated in July 1989, was designed to examine maternally-associated risk factors for bovine spongiform encephalopathy (BSE), forming part of the epidemiological research programme to assess the risks of non-feedborne transmission of BSE. In this study, the incidence of BSE in offspring of cows which developed clinical signs of BSE is compared with that in offspring, born in the same calving season and herd, of cows which had reached at least six years of age and had not developed BSE. All offspring were allowed to live to seven years of age. The results indicate a statistically significant risk difference between the two cohorts of 9.7 per cent and a relative risk of 3.2 for offspring of cows which developed clinical BSE. However, there is some evidence that this enhanced risk for offspring of BSE cases declined the later the offspring was born, but was increased the later the offspring was born in relation to the stage of the incubation period of the dam. The results presented cannot distinguish between a genetic component and true maternal transmission or a combination of both risks, but they do not indicate either that the BSE epidemic will be unduly prolonged or that the future incidence of BSE in Great Britain will increase significantly.

Animals↗

Risk of BSE from the import of cattle from the United Kingdom into countries of the European Union.

This study assesses quantitatively the risk that other countries, in particular those within the European Union, have incurred by importing cattle from the United Kingdom during the period before or shortly after the ban on the import of live breeding stock was introduced in 1989. It does this by assessing the probability that animals imported from the UK in a certain year would have become a detected BSE case, had they not been exported. Using the annual incidence rates available for separate birth cohorts and a given culling rate, a cumulative incidence for each birth cohort was calculated. These figures were then combined with the numbers of live breeding cattle imported from the UK into the other countries of the EU, to give an import-related risk index for each country, assuming that their culling rates were similar to that in Great Britain. The countries could thus be categorised in terms of the number of cases of BSE they might have expected.

Animals↗

Sporadic Creutzfeldt-Jakob disease in the United Kingdom: analysis of epidemiological surveillance data for 1970-96.

OBJECTIVE: To identify changes in the occurrence of Creutzfeldt-Jakob disease that might be related to the epidemic of bovine spongiform encephalopathy. DESIGN: Epidemiological surveillance of the United Kingdom population for Creutzfeldt-Jakob disease based on (a) referral of suspected cases by neurologists, neuropathologists, and neurophysiologists and (b) death certificates. SETTING: England and Wales during 1970-84, and whole of the United Kingdom during 1985-96. SUBJECTS: All 662 patients identified as sporadic cases of Creutzfeldt-Jakob disease. MAIN OUTCOME MEASURES: Age distribution of patients, age specific time trends of disease, occupational exposure to cattle, potential exposure to causative agent of bovine spongiform encephalopathy. RESULTS: During 1970-96 there was an increase in the number of sporadic cases of Creutzfeldt-Jakob disease recorded yearly in England and Wales. The greatest increase was among people aged over 70. There was a statistically significant excess of cases among dairy farm workers and their spouses and among people at increased risk of contact with live cattle infected with bovine spongiform encephalopathy. During 1994-6 there were six deaths from sporadic Creutzfeldt-Jakob disease in the United Kingdom in patients aged under 30. CONCLUSIONS: The increase in the incidence of sporadic Creutzfeldt-Jakob disease and the high incidence in dairy farmers in the United Kingdom may be unrelated to bovine spongiform encephalopathy. The most striking change in the pattern of Creutzfeldt-Jakob disease in the United Kingdom after the epidemic of bovine spongiform encephalopathy is provided by the incidence in a group of exceptionally young patients with a consistent and unusual neuropathological profile. The outcome of mouse transmission studies and the future incidence of the disease in the United Kingdom and elsewhere, will be important in judging whether the agent causing bovine spongiform encephalopathy has infected humans.

Adolescent↗

Transmission dynamics and epidemiology of BSE in British cattle.

A comprehensive analysis of the bovine spongiform encephalopathy (BSE) epidemic in cattle in Great Britain assesses past, present and future patterns in the incidence of infection and disease, and allows a critical appraisal of different culling policies for eradication of the disease.

Age Factors↗