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.     

Endodontic decisions based on clinical appearance.

Too often, endodontically compromised teeth are ignored because they are not accurately identified, nor their significance realized. By systematically evaluating each potentially affected tooth, a practitioner can correctly diagnose endodontic cases and plan therapy accordingly. Endodontic pathology, with non-vital pulps and subsequent abscessation, can affect not only the tooth but also the rest of the patient. Physical examination, both external and oral, can be combined with tactile and transillumination assessment. Radiographic appraisal is essential in determining periapical health, both to determine the vitality of the tooth and to ascertain if endodontic therapy is appropriate, of if extraction is the best choice. This report aims to provide the reader with a clearer understanding of diagnosing endodontic cases to facilitate selection of the appropriate treatment.     

Endodontic decisions based on radiographic appearance

Endodontic disease or disease that affects the internal portion of the tooth is a frequently encountered oral problem of the cat and dog. There are many etiologies that can cause the tooth's health and longevity to be adversely affected. Trauma, tooth malformations of either congenital or acquired origin, and bacterial periodontal ascending infections all can lead to pulpal inflammation, necrosis, and tooth death. One must correlate history, physical exam and radiographic impressions of the tooth, and its supporting structures and adjacent teeth in determining proper treatment options and aftercare. Based on extent, timing, and involvement of adjacent structures, resulting pathology of the tooth may be endodontically treated with either a vital pulpectomy, standard root-canal therapy, surgical root-canal therapy, or when the disease is too extensive by extraction. Through a case presentation, we will discuss some of the decisions that enter into the therapy used to treat presenting pathology. It is the authors' intent to present a thought process for deriving a treatment plan to promote healing. There are many ways to achieve this healing, and therefore, there is no right or wrong plan, but rather one that is based on all the presenting factors.     

Bovine mycoplasma mastitis from intramammary inoculation of small numbers of Mycoplasma bovis. I. Microbiology and pathology

Intrammary inoculation of 70 colony forming units (cfu) of Mycoplasma bovis into one quarter of four previously non-infected cows resulted in severe mastitis in inoculated and uninoculated quarters. Hematogenous spread of the infection was most likely, as mycoplasma was isolated from the peripheral blood of three of four cows and the milking machine was designed to prevent quarter to quarter communication of milk and air. The presence of large numbers of mycoplasma exceeding 10⁶ cfu/ml of milk preceded the onset of overt sero-purulent mastitis by 1–3 days. In general, the severity, duration of the infection and within cow spread of mastitis to adjacent quarters after the inoculation of 70 cfu was indistinguishable from naturally occurring mycoplasma mastitis.The pathology of the chronically infected quarters consisted of alveolar involution and moderate to severe mononuclear infiltration and an increase in interalveolar and loose connective tissue. The quarters of one cow resolving the infections at the time of slaughter were not as severely affected and contained numerous milk-producing alveoli and many alveoli with hyperplasia of the alveolar cells.     

以预警观点反思英国BSE控制决策

BSE对人类健康的风险,一开始就明显存在大量的不确定,有些不确定至今依然存在。当面对BSE对人类健康的潜在风险,也即当现有科学证据无法排除BSE传染人的可能性,也无确凿证据证明BSE对人类健康影响时,需要决策者突破肯定科学证据决策框架尽早采取预警行动。本文将从预警触发、决策和应用三个阶段反思英国和欧盟BSE控制决策和措施,并分析其失误原因。1预警简介预警“思想”已有很长的历史,广义的预警可追溯到公元前400年的希波克拉底医学誓言“首先不要造成伤害”。1854年英国医生JohnSnow在面对霍乱传播与汲井之间科学因果关系不确定…     

The anterior pituitary gland: lessons from livestock

There has been extensive research of the anterior pituitary gland of livestock and poultry due to the economic (agricultural) importance of physiological processes controlled by it including reproduction, growth, lactation and stress. Moreover, farm animals can be biomedical models or useful in evolutionary/ecological research. There are for multiple sites of control of the secretion of anterior pituitary hormones. These include the potential for independent control of proliferation, differentiation, de-differentiation and/or inter-conversion cell death, expression and translation, post-translational modification (potentially generating multiple isoforms with potentially different biological activities), release with or without a specific binding protein and intra-cellular catabolism (proteolysis) of pituitary hormones. Multiple hypothalamic hypophysiotropic peptides (which may also be produced peripherally, e.g. ghrelin) influence the secretion of the anterior pituitary hormones. There is also feedback for hormones from the target endocrine glands. These control mechanisms show broadly a consistency across species and life stages; however, there are some marked differences. Examples from growth hormone, prolactin, follicle stimulating hormone and luteinizing hormone will be considered. In addition, attention will be focused on areas that have been neglected including the role of stellate cells, multiple sub-types of the major adenohypophyseal cells, functional zonation within the anterior pituitary and the role of multiple secretagogues for single hormones.     

Estimating the impact on the food chain of changing bovine spongiform encephalopathy (BSE) control measures: The BSE Control Model

The decline in the bovine spongiform encephalopathy (BSE) epidemic in Great Britain (GB) demands a review of control strategies to ensure that they remain proportionate. Amongst controls that are subject to review are those intended to minimise the risk of BSE exposure of consumers through food. Such risk mitigation steps are costly, and the relative impact of each in terms of human exposure to BSE infectivity is not known. This risk assessment, termed the BSE Control Model, aims to estimate by use of stochastic simulation the impact of testing of cattle at slaughter and the removal of Specified Risk Materials (SRM) on potential BSE infectivity consumed. This paper describes the use of the model to investigate the effect of different risk management methods that have been or could be implemented between 2005 and 2010.Our results suggest that the amount of infectivity consumed in 2005 with the Over Thirty Month (OTM) rule in place was a mean of 0.03 bovine oral ID₅₀ (BO ID₅₀). This is an extremely low amount, particularly considering that it would be spread over, on average, 236 infected carcases that would be further sub-divided into portions for human consumption. The highest contributor to the total amount of infectivity consumed per year is spinal contamination at carcase splitting (35%). In 2006 the OTM scheme was discontinued and head meat was again permitted into the food chain. These changes resulted in an increase in the amount of infectivity consumed, rising to an estimated 28 BO ID₅₀ in 2006, and 19 BO ID₅₀ in 2007.In 2008 the age at removal of vertebral column was raised from 24 to 30 months, and an estimated 24 BO ID₅₀ of infectivity was consumed. At the beginning of 2009 the age at testing of cattle was raised to 48 months for healthy slaughter, emergency slaughter and fallen stock. Under these conditions, an estimated mean of 24 BO ID₅₀ will be consumed in 2009, decreasing to 20 BO ID₅₀ in 2010. Even though presented in terms of bovine rather than human oral ID₅₀, such estimates represent an extremely low exposure of the British population. Considerable uncertainty would surround any attempt to try to convert such exposure into estimates of new cases of vCJD, but the most recent estimates of the size of the species barrier between cattle and humans (4000, EFSA, 2006) suggest that there would be few, if any, new cases of vCJD arising from such exposure levels.     

Myasthenia gravis: lessons from the past 10 years

Over the past 10 years, significant advances have been made in our understanding of acquired myasthenia gravis (MG) in companion animals. The broad spectrum of presenting clinical signs has been defined and an accurate and sensitive diagnostic test is available. Even with these advances, the mortality rate in dogs with acquired MG remains unacceptably high. While an understanding of the genetic basis for susceptibility to autoimmune disease has started to be developed, the trigger for the initiation of this disease is not known and a mechanism for specific suppression of the aberrant immune response against the acetylcholine receptor remains a mystery.     

Avian B cell development: lessons from transgenic models

The bursa of Fabricius is critical for the development of B lymphocytes in avian species. Despite considerable advances in our understanding of the molecular mechanisms by which avian antibody diversity is generated, many stages of B-cell development in the bursa and the means by which they are regulated remain unclear. Here we discuss the use of productive chicken retroviral vectors which allow gene transfer in vitro or in vivo as tools to probe the requirements for bursal B-cell development. Expression of a truncated form of bursal cell surface IgM, lacking variable region encoded determinants, is sufficient to promote the initial colonization and clonal expansion of B-cells within the bursa. Expression of this truncated IgM does not, however, protect developing bursal cells against the apoptosis that occurs within the bursa after hatch. Conversely, over-expression of the proto-oncogene bcl-2, following retroviral gene transfer, protects cells against apoptotic cell death but is not sufficient to allow B lineage progression in the absence of sIgM expression. Finally we discuss the use of regulated promoters within the retroviral gene transfer system to show that while bursal cells are susceptible to transformation by the v-rel oncogene in vitro, this oncogene preferentially targets mature peripheral cells in vivo.     

Market value and managerial decisions: implications from a decade of feeder cattle teleauctions.

Data from feeder cattle teleauction sales in Georgia from 1977 to 1988 were analyzed using least squares analysis of variance to detect significant (P less than .05) influential factors on price. The sample was divided into two periods, 1977 to 1982 and 1983 to 1988, to test whether the influence of factors had changed over the time periods. The test of equality was rejected (P less than .01) using a Chow test, thus suggesting a change had occurred. Hereford breeds were discounted in the latter period whereas Angus breeds generated a premium in the earlier period. Treatment for specific diseases resulted in premium prices, as did preconditioning, during the 1983 to 1988 period. The effect of seasonality on prices decreased over the two time periods. The optimal lot size increased from 228 to 280 cattle during the time periods.     

West Nile virus: lessons from the 21st century

Introduction: West Nile virus (WNV) first appeared in the United States in 1999, causing illness and death in birds, horses, and humans. While the initial outbreak of this sometimes deadly viral disease was limited to the northeastern United States, the virus had an inexorable migration across the continental United States over the next 3 years, causing huge losses among the affected species. The purpose of this review is to present currently available information regarding the epi‐demiology, diagnosis, treatment, and prevention of WNV infection. Veterinarians, particularly those in an emergency practice, serve as an important source of reliable information regarding this disease for animal owners and the public in general. Data sources: Data sources used for the preparation of this review include computer‐based searches of PubMed and Commonwealth Agricultural Bureaux (CAB) abstracts. A search in PubMed using ‘West Nile’ retrieved 1468 ‘hits’ or references, while a similar search in CAB abstracts produced 815 references. Additional information was obtained from various meeting proceedings, particularly data presented in abstract form, and from the Centers for Disease Control (CDC) website dedicated to WNV. Human data synthesis: Prior to the mid‐1990s, reported large‐scale epidemics of WNV infection in humans predominantly presented as acute, mild, febrile disease, sometimes associated with lymphadenopathy and skin rash. The recent large epidemic in the United States, in contrast, has prominently featured encephalitis, particularly among the elderly. Additionally, polio‐encephalomyelitis‐like complications resulting in long‐term neurologic sequelae have been reported. There are many WNV‐permissive native avian and mosquito hosts in the Unites States and there appear to be few limitations to the spread of the disease in the United States. It is expected that the virus will be identified in all 48 continental states, Mexico, and Canada by the end of 2003. Veterinary data synthesis: The horse is the animal species most affected by the recent WNV epidemic in the United States, and losses to the equine industry have been large and unprecedented. A United States Department of Agriculture (USDA)‐approved vaccine against WNV has been in use in horses since 2001 and appears to be effective in limiting the incidence of disease in well‐vaccinated populations. WNV infection has been documented in other species of mammals, including camelids (alpaca/llamas) and dogs, and veterinarians should include WNV as a differential diagnosis for animals presenting with clinical signs consistent with central nervous system infection. A large concern exists for endangered bird populations, particularly birds of prey, whether in zoos or in the wild.