A stochastic model to estimate the prevalence of scrapie in Great Britain using the results of an abattoir-based survey

In 1997/1998, an abattoir survey was conducted to determine the likely exposure of the human population to transmissible spongiform encephalopathy (TSE) infection in sheep submitted for slaughter in Great Britain. The survey examined brain material from 2809 sheep processed through British abattoirs. Sampling was targeted by age: 45% of animals tested were ≥15 months old. All samples of adequate quality (98%) were tested for signs of scrapie infection using histopathology and scrapie-associated fibril (SAF) detection and 500 were tested using immunohistochemistry (IHC). No conclusive positive animals were found using either histology or IHC. Ten animals were positive by SAF. Standard statistical analyses suggest (with 95% confidence) that the prevalence of detectable (by histopathology) infection in the slaughter population was ≤0.11%. However, the incubation period of scrapie is long (usually around 2–3 years) and none of the tests used in the survey is capable of detecting scrapie infection in the early stages of infection. We present an age-structured stochastic model incorporating parameters for the incubation period of scrapie, prevalence of infection by age and test sensitivity. Using the model, we demonstrate that the negative results obtained for all samples using IHC and histopathology are consistent with a true prevalence of infection in the slaughter population of up to 11%. This suggests that up to 300 of the animals tested might have been infected but the infection was not sufficiently advanced in these animals to be detectable by IHC or histopathology. The survey was designed to detect a prevalence of 1% with a precision of ±0.5% and a confidence level of 95% in each age group assuming that diagnostic tests were 100% specific and sensitive from a known stage in the incubation period. The results of the model demonstrate that to estimate a true prevalence of scrapie infection of 1% with an accuracy of ±0.5% would have required a far larger sample size. An accurate estimate of the required sample size is complicated by uncertainty about test sensitivity and the underlying infection dynamics of scrapie. A pre-requisite for any future abattoir survey is validation of the diagnostic tests used in relation to both stage of incubation and genotype. Sampling in the <15-month age group was of no value in this survey because the diagnostic tests used were thought to be ineffective in most of the animals in this age group.     

Estimation of the age-dependent risk of infection to BSE of dairy cattle in Great Britain

An important aspect of the bovine spongiform encephalopathy (BSE) epidemic has been an apparent age-dependent risk of infection, with younger cattle being more likely to become infected than older cattle. Our objective was to determine the age-dependent risk of infection of dairy cattle. We first reviewed unpublished data on the feeding patterns of proprietary concentrates for dairy-replacement cattle. These data showed that autumn- and spring-born cattle would receive different feeding patterns of proprietary concentrates, and so age-dependent risk of infection profiles were obtained separately for autumn- and spring-born cattle. We used back-calculation methods to analyse BSE-epidemic data collected in Great Britain between 1984 and 1996.

Dairy cattle were most at risk in the first 6 months of life; adult cattle were at relatively low risk of infection. Between 6 and 24 months of age, risk profiles reflected feeding patterns of proprietary concentrates in each of the autumn- and spring-born cohorts.     

Co-existence of classical scrapie and Nor98 in a sheep from an Italian outbreak

Nor98 is an atypical scrapie strain characterized by a molecular pattern and brain distribution of the pathological prion protein (PrP^Sc) different from classical scrapie. In Italy, 69 atypical cases have been identified so far and all were characterized as Nor98 strain. In this paper we report an unusual case in a sheep which showed immunohistochemical and molecular features of PrP^Sc different from the other atypical cases. The sheep was from an outbreak where the index and the other four cases were affected by classical scrapie. Histopathological, immunohistochemical and Western blot analyses on the brain of the unusual case revealed the simultaneous presence of pathological features characteristic of Nor98 and classical scrapie. Interestingly, the prevalent disease phenotype in the brainstem was classical scrapie-like, while in the cerebral cortex and cerebellum the Nor98 phenotype was dominant. The sub-mandibular lymph node was positive and showed a PrP^Sc molecular pattern referable to classical scrapie. The PrP genotype was AL₁₄₁RQ/AF₁₄₁RQ. Taken together, the occurrence of classical scrapie in the outbreak, the PrP genotype, the involvement of different cellular targets in the brain and the pathological and molecular PrP^Sc features observed suggest that this unusual case may result from the co-existence of Nor98 and classical scrapie.     

Effect of the dimethoate administration on a Scrapie murine model

Some authors have associated organophosphate compounds with susceptibility to transmissible spongiform encephalopathy (TSE) and even with the origin of this group of diseases. Nevertheless, the actual role played by these compounds still remains unclear. The aim of this study was to assess the effect of oral exposure to dimethoate (DMT) on the development of Scrapie using a genetically modified murine model. A total of 70 C57BL/6 mice over-expressing the PrP gene (Tg20) were included in the present study. A portion of the mice were intraperitoneally inoculated, while the rest were maintained as non-infected controls. Animals from the treated group were exposed to dimethoate dissolved in drinking water from the beginning of the experiment. Variables of incubation period, spongiosis, PrPsc deposits, glial over-expression, neuronal loss, and amyloid plaques were assessed in all animals. According to the results, a treatment consisting of a daily 15 mg/kg dose of DMT for 5 weeks did not show any effect on any of the variables assessed. Although more exhaustive studies for assessing different doses and organic compounds are required, this finding constitutes an empirical study that rules out the possibility that this compound may have a predisposing effect on TSEs.     

Application of one-list capture-recapture models to scrapie surveillance data in Great Britain

In this paper, we apply one-list capture-recapture models to estimate the number of scrapie-affected holdings in Great Britain. We applied this technique to the Compulsory Scrapie Flocks Scheme dataset where cases from all the surveillance sources monitoring the presence of scrapie in Great Britain, the abattoir survey, the fallen stock survey and the statutory reporting of clinical cases, are gathered. Consequently, the estimates of prevalence obtained from this scheme should be comprehensive and cover all the different presentations of the disease captured individually by the surveillance sources. Two estimators were applied under the one-list approach: the Zelterman estimator and Chao's lower bound estimator. Our results could only inform with confidence the scrapie-affected holding population with clinical disease; this moved around the figure of 350 holdings in Great Britain for the period under study, April 2005-April 2006. Our models allowed the stratification by surveillance source and the input of covariate information, holding size and country of origin. None of the covariates appear to inform the model significantly.     

The Shetland Islands scrapie monitoring and control programme: analysis of the clinical data collected from 772 scrapie suspects 1985-1997

There were 574 scrapie positive suspects (histopathological scrapie lesions present) and 198 scrapie negative suspects (histopathological scrapie lesions absent). The greatest number of scrapie cases were recorded in sheep of 2, 3 and 4 years of age which represented 17%, 36% and 23% of the scrapie positive suspects, respectively. The sign sensitivities and specificities for the ten recorded signs were, respectively: pruritus (62%, 42%), ataxia (23%, 74%), hyperaesthesia (32%, 74%), wool loss (25%, 73%), fleece discolouration (29%, 85%), bruxism (23%, 69%), nibbling reflex (17%, 58%), head rubbing (47%, 78%), poll rubbing (25%, 83%). These single signs had poor discriminatory values with likelihood ratios close to one (range 0.89-1.21); combinations of the four signs, pruritus, wool loss, ataxia, hyperaesthesia and emaciation were more discriminatory (range 0.30-4.3). This study covered a time period when bovine spongiform encephalopathy (BSE) might have been introduced into the sheep population on the Shetland Islands via contaminated feed. No temporal changes could be detected in the age structure of the affected animals.     

Trends in genotype frequency resulting from breeding for resistance to classical scrapie in Belgium (2006~2011)

In sheep, susceptibility to scrapie is mainly determined by codons 136, 154, and 171 of the PRNP gene. Five haplotypes are usually present (ARR, ARQ, ARH, AHQ, and VRQ). The ARR haplotype confers the greatest resistance to classical scrapie while VRQ renders animals most susceptible. In 2004, the European Union implemented a breeding program that promotes selection of the ARR haplotype while reducing the incidence of VRQ. From 2006 to 2011 in Belgium, frequency for the ARR/ARR genotypes increased from 38.3% to 63.8% (n = 6,437), the ARQ haplotype diminished from 21.1% to 12.9%, and the VRQ haplotype decreased from 2.0% to 1.7%. The status of codon 141, a determinant for atypical scrapie, was also evaluated. Out of 27 different breeds (n = 5,163), nine were abundant. The ARR/ARR frequency increased in eight of these nine major breeds. The selection program has had a major impact on the ARR haplotype frequency in Belgium. However, the occurrence of atypical scrapie represents a critical point for this program that warrants the continuous monitoring of scrapie. Additionally, genotype frequencies among the breeds varied greatly. Texel, a breed that is common in Belgium, can still be selected for due to its average ARR frequency.     

A model (BSurvE) for estimating the prevalence of bovine spongiform encephalopathy in a national herd

We developed the BSurvE spreadsheet model to estimate the true prevalence of bovine spongiform encephalopathy (BSE) in a national cattle population, and evaluate national BSE surveillance programs. BSurvE uses BSE surveillance data and demographic information about the national cattle population. The proportion of each cohort infected with BSE is found by equating the observed number of infected animals with the number expected, following a series of probability calculations and assuming a binomial distribution for the number of infected animals detected in each surveillance stream. BSurvE has been used in a series of international workshops, where analysis of national datasets demonstrated patterns of cohort infection that were consistent with infection-control activities within the country. The results also reflected the timing of known events that were high-risk for introduction of the infectious agent.     

The evolution of the prevalence of classical scrapie in sheep in Great Britain using surveillance data between 2005 and 2012

After the decline of the Bovine Spongiform Encephalopathy (BSE) epidemic in Great Britain (GB), scrapie remains the most prevalent animal Transmissible Spongiform Encephalopathy (TSE) present in GB. A number of control measures have been implemented for classical scrapie, and since 2005 there has been a large reduction in the number of observed cases. The objective of this study is to estimate two measures of disease frequency using up to date surveillance data collected during and after the implementation of different control measures established since 2004, and breeding for resistance schemes that ran from 2001 until 2009. This would enable an assessment of the effectiveness of both the breeding for resistance programme and the compulsory eradication measures in reducing the prevalence of scrapie in GB. Evaluation of the sensitivity of the rapid post-mortem test for scrapie indicated that it detected scrapie in the last 25% of the incubation period. A back-calculation model was developed to estimate the prevalence of infection at animal and flock-level. The results of the model indicated a mean drop of infection prevalence of 31% each year, leading to a 90% drop in infection prevalence between 2005, with an estimate of 5737 infected sheep in GB in 2012.     

Determining the relationship between restorative potential and size of a gene bank to alleviate the risks inherent in a scrapie eradication breeding programme

Breeding plans are being adopted in many countries to eradicate scrapie from the sheep populations. The European plans are based on selection for increased frequency of the resistant ARR haplotype and removal of the most scrapie susceptible haplotype (VRQ). This approach of a genotype eradication breeding programme incurs a number of risks including those associated with novel spongiform encephalopathy causing agents that are as yet unknown, but may emerge in the future and the possible loss of favourable attributes of a breed either through linkage or pleiotropic effects when selecting on a specific haplotype. Semen gene banks have been proposed to provide the potential for future reintroduction of removed haplotypes. Computer simulations were run for hill, crossing and terminal breed types to investigate the restorative potential of a gene bank required for the reintroduction of an alternative haplotype in the future. Differences existed in the restorative potential between the different breed types considered. This was largely dictated by variable levels of fertility, litter size, survival and mating ratio. It was shown that terminal breeds would require two and a half times as many semen straws as hill breeds to produce the same frequency of ewes homozygous for the desired haplotype in the population after a ten year reintroduction period.     

The role of mathematical modelling in understanding the epidemiology and control of sheep transmissible spongiform encephalopathies: a review

To deal with the incompleteness of observations and disentangle the complexities of transmission much use has been made of mathematical modelling when investigating the epidemiology of sheep transmissible spongiform encephalopathies (TSE) and, in particular, scrapie. Importantly, these modelling approaches allow the incidence of clinical disease to be related to the underlying prevalence of infection, thereby overcoming one of the major difficulties when studying these diseases. Models have been used to investigate the epidemiology of scrapie within individual flocks and at a regional level; to assess the efficacy of different control strategies, especially selective breeding programmes based on prion protein (PrP) genotype; to interpret the results of scrapie surveillance; and to inform the design of surveillance programmes. Furthermore, mathematical modelling has played an important role when assessing the risk to human health posed by the possible presence of bovine spongiform encephalopathy in sheep. Here, we review the various approaches that have been taken when developing and analysing mathematical models for the epidemiology and control of sheep TSE and assess their impact on our understanding of these diseases. We also identify areas that require further work, discuss future challenges and identify data gaps.     

Design of a village breeding programme for a llama population in the High Andes of Bolivia

No national breeding programme for llamas is in place in Bolivia. Initiatives for genetic improvement are rarely found and are usually carried out by NGOs working in rural development or improvement of livestock production or research stations. Farmers in the Province of Ayopaya in the District of Cochabamba have formed a breeders’ organization with the aim of improving fibre production. In this study, a detailed outline of a breeding programme with a focus on organizational and technical details is described. Facing constraints like illiteracy of farmers, bad infrastructure and lack of finances, a simple breeding programme is set up. The breeding goal is a higher fleece weight while keeping the fleece quality at the current high level. Greasy fleece weight and fibre diameter are identified as main selection criteria. Mass selection of males is carried out. Selected males are either exchanged between farmers and used in the herds or are kept during the mating season in a central mating station owned by the breeders’ organization. Model calculations were carried out with the program zplan , which is based on a deterministic approach. zplan evaluates the genetic and economic efficiency of breeding strategies considering one cycle of selection. Scenarios with only intra-herd use, using only the central mating station or combinations of those were compared in terms of expected genetic gain and expected increase of inbreeding. Fastest genetic progress is achieved when the males are kept in a central mating station as the selection intensity is on a high level. Rates of inbreeding vary between 0.08 and 0.32% per generation.     

Applicability of a rapid chromatographic immunoassay for analysis of the distribution of PrPBSE in confirmed BSE cases

The Prionics-Check PrioSTRIP is a rapid chromatographic immunoassay for bovine spongiform encephalopathy (BSE) approved by the European Union in 2004. In this study, the PrioSTRIP was used to analyse PrP(BSE) in 16 different brain areas of nine confirmed BSE cases. The levels of PrP(BSE) in the different brain areas were plotted to give the brain PrP(BSE) distribution curve (BPDC) and compared with the BPDC obtained previously by Western blotting and enzyme-linked immunosorbent assay (ELISA) methods on the same samples. The distribution of PrP(BSE) in different areas of the brain was similar, irrespective of the test applied, indicating that each test could be used for the characterisation of BSE cases.     

A field experiment to evaluate a practical hygiene programme for the control of bovine mastitis

Abstract

Extract

The control of the spread of mastitis infection by good hygiene in the milking shed has long been advocated but the methods used have varied in their efficiency and practicability. Moller (1957 Moller, K. 1957. N.Z. vet. J., 5: 79–79. [Taylor &; Francis Online] , [Google Scholar]) reported good results in the control of Streptococcus agalactiae infection when running water was used to wash the udder, and teat cups were dipped in Chlorhexidine solution between cows. However, many farmers find that dipping cups is irksome and, unless it is carefully done, it becomes ineffective.     

Evidence for the transmission of scrapie to sheep and goats from a vaccine against Mycoplasma agalactiae

An accidental infection from a vaccine was suggested as the explanation for the sudden increase in outbreaks of scrapie in Italy in 1997 and 1998. This paper describes a recent outbreak of scrapie in sheep and goats which were exposed to the same vaccine. No ewes or goats had been imported into the herd since 1992, but a vaccine against Mycoplasma agalactiae had been administered twice, in 1995 and 1997. High rates of crude mortality and scrapie incidence were experienced by both species, all birth cohorts were involved and a large proportion of aged animals was affected. A pattern of brain lesions was observed, with slight differences between the sheep and goats, which was very similar to the pattern observed in animals previously exposed to the same vaccine but clearly different from that observed in the brains of sheep with scrapie in a flock not exposed to the vaccine. Regardless of their exposure status, genotype analysis of the sheep showed the presence of polymorphism only at codon 171. The patterns of both incidence and brain lesions provide evidence that the epidemic of scrapie was due to the use of the vaccine.     

A method for the prediction of multitrait breeding values for use in stochastic simulation to compare progeny-testing schemes, with large progeny groups for proven sires

A method of approximating estimated breeding values (EBV) from a multivariate distribution of true breeding values (TBV) and EBV is proposed for use in large-scale stochastic simulation of alternative breeding schemes with a complex breeding goal. The covariance matrix of the multivariate distributions includes the additive genetic (co)variances and approximated prediction error (co)variances at different selection stages in the life of the animal. The prediction error (co)variance matrix is set up for one animal at a time, utilizing information on the selection candidate and its offspring, the parents, as well as paternal and maternal half- sibs. The EBV are a regression on TBV taking individual uncertainty into account, but with additional 'free' variation drawn at random. With the current information included in the calculation of the prediction error variance of a selection candidate, it is concluded that the method can be used to optimize progeny-testing schemes, where the progeny-tested sires are utilized with large progeny groups, e.g. through artificial insemination.     

Making use of equine population demography for disease control purposes: preliminary observations on the difficulties of counting and locating horses in Great Britain

Detailed knowledge of horse populations can better facilitate effective control of equine diseases. Preliminary studies were undertaken to ascertain the type of information held on the UK's National Equine Database (NED) and to determine the geographical resolution at which mandatorily recorded owner addresses might be a suitable proxy for predicting horse locations. Results indicated that relatively few UK passport-issuing organisations requested details of where horses were kept in addition to owner address details. Examination of data on 1440 horses held on an Animal Health Trust syndromic surveillance database showed that 90% of them were kept within 10 km of their owners. While owner location may provide an indication of where most horses are kept, further work is also needed to evaluate the usefulness of NED as an epidemiological resource in future equine disease control measures.     

1～21 日龄黄羽肉鸡豆粕净能预测模型

本试验旨在建立合理的1～21日龄黄羽肉鸡豆粕净能(NE)预测模型.对豆粕净能进行测定,为维持净能(NEm)与沉积净能(NEp)之和,NEm测定采用回归法,NEp测定采用套算法;测定21个豆粕样品的概略养分含量,并进行NE与表观代谢能(AME)、化学成分的一元或多元线性回归分析,建立模型;将21个豆粕样品水分分别调整为1...     

水土保持优良植物--牧场草在黄土高原地区的引种适宜性评价

由美国引进的水土保持优良植物——牧场草,在黄土高原大部分地区种植后,适应性较强。结合气候相似法、模糊综合评判法以及引种栽培试验,得出牧场草的适生中心区位于黄土高原的北温带部分,呈一条东北-西南走向的非常宽阔的带,包括黄土高原沟壑区、丘陵沟壑区所有副区、风沙区等类型。