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22 January 2003The Moredun Foundation - Press BriefingMedicines, Scrapie, BSE, Orf, Worm Control, CryptosporidiosisDecember 2002The Moredun Foundation, Roslin, Edinburgh,
gave a press briefing in The future of veterinary medicines
A Note from Land-CareUnfortunately we find the recommended
website - www.moredun.org.uk
- and its associated websites such as Moredun Research - singularly
difficult to use as a source of useful information.
THE FUTURE OF VETERINARY MEDICINESProfessor Quintin McKellerConcern has been raised within the Veterinary profession about the initial proposals made by the competition commission regarding the prescription, sale and dispensing of veterinary drugs. These proposals are still in draft form and may be modified prior to enactment. The purpose of the enquiry is to ensure that consumers are receiving a fair deal from vets for the provision of drugs for their animals and to ensure that vets are not able to monopolise the market in animal medicines. Moredun is concerned with the health and welfare of livestock and supports the role of veterinarians and stockmen in the provision of care for animals. In this regard we have particular concern that the competition commission may recommend changes to the legal status of some drugs which will allow their more general use without the control of the veterinary surgeon and may thus permit their inappropriate use. Thus changes in status from prescription only to pharmacy or general sales status could result in an increase in adverse reactions or resistance development in the animals and pathogens being targeted. Great concern has already been expressed over the use of organophosphate dips and some anti-inflammatory drugs in man and target animals respectively where these drugs have not been under veterinary control. Similarly the debate around the use of antibiotics in animals and the potential for transfer of resistant organisms to man has focused on antibiotic growth promoters which were not under veterinary control. The appropriate use of drugs requires extensive training in diagnosis epidemiology and pharmacology and is best provided by the veterinarian. Indeed the general drift throughout Europe has been to tighten controls on the use of drugs, particularly antibiotics, rather than slacken it. The task of the competition commission is going to be to ensure sufficient competition between vets and thus a fair deal for farmers but to maintain sufficient control of drugs to ensure their safe use. For further information
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THE CONTROL OF SCRAPIEDr Hugh ReidThe Transmissible Spongiform Encephalopathies (TSE) are a group of diseases affecting man and animals characterised by a long incubation period and slowly progressive neurological degeneration which is invariably fatal. Despite the enormous effort to research these diseases there is still a surprising level of uncertainty regarding their mode of transmission, pathogenesis and even the nature of the infecting agents. The devastating effect that BSE has had and continues to threaten our animal industry does not require to be restated. There still remains profound uncertainty with regard to the future scale of the variant CJD epidemic in humans. The good news is that BSE in cattle is declining rapidly as predicted through the control measures that have been put in place. There is also the prospect of the control and even eradication of scrapie from our sheep flock through the implementation of the National Scrapie Plan for Great Britain (NSP-GB). The NSP-GB sees the application of basic research to practical animal breeding. The link between sheep genotype and resistance/susceptibility to scrapie had been defined over 40 years ago but by applying the extraordinary power of molecular biology this was identified to being largely controlled by one amino acid in the Prion Protein (PrP) gene. This gene is composed of 256 codons each responsible for one amino acid which comprise the whole protein. By sequencing the DNA of this gene scrapie resistant animals are selected for breeding and the most susceptible eliminated. Thus it is anticipated that the eradication of scrapie from the National Flock will be achieved. Similar schemes will be adopted across Europe ensuring that scrapie is eliminated from the whole sheep population of Europe. In adopting the NSP-GB there will be the additional advantage that it will give further assurance to the public that the theoretical possibility of BSE having established in the sheep flock does not present a risk. The Food Standards Agency (FSA) with its laudable openness makes public everything that emanates from their horizon scanning and thus while we can not deny that their deliberations with regard to the possible transmission of BSE to sheep are theoretically possible, the evidence all tends to support the view that this is extremely unlikely. There is no doubt that when high doses of BSE infectivity are experimentally fed orally to sheep of scrapie susceptible genotype they develop clinical disease similar to scrapie. It is also indisputable that some sheep would have been fed rations containing meat and bone meal (MBM) which potentially could have contained infectivity prior to the ban on MBM. Thus there is a theoretical possibility that sheep were exposed to BSE and did become infected. However in appraising this risk the evidence (see notes) make it extremely unlikely that sheep represent a possible source of infection to man at the present time. The latest announcement that clinical disease has occurred in the most resistant genotype of sheep following inoculation of BSE directly into the brains of sheep while of scientific interest does not have any bearing on the possible transmission of BSE to sheep in MBM. For further information
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NOTES ON WHY WE DO NOT BELIEVE BSE IS IN THE BRITISH SHEEP FLOCKDr Hugh Reid
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RESEARCH ADVANCES IN ORF VIRUSDr David HaigOrf is a severe skin disease of sheep and goats worldwide that also affects people who handle these animals. It is caused by a poxvirus known as Orf virus that may persist in sheep populations, but certainly can persist in dry conditions in the environment, for example in sheep housing. Orf is mainly a disease of young lambs and kid goats that have not developed any immune resistance to the disease. It is rarely fatal, but is a serious welfare problem and is responsible for lack of thrift in affected animals. Our interest in Orf virus is that it is common in the UK, is a zoonosis (a disease of humans picked up from infected animals), and current control measures are poor. A vaccine for Orf exists, and is useful in preventing the severity of the disease, but can itself give rise to outbreaks of disease. Around 2.5 million doses of this vaccine are sold every year in the UK. At the Moredun Research Institute, we have discovered that the immune response to Orf virus infection in sheep is apparently normal, with key components of the response in place to potentially eliminate the virus. In spite of this immune response, the virus can repeatedly infect animals. We have discovered that this is due to an extraordinary phenomenon in which the virus has hijacked key host (sheep) immune response components during its evolution as an infectious agent of sheep and goats. It is then able to use these acquired components to block or subvert important elements of the host anti-virus immune response. The challenge is to identify these hijacked genes and their functions during infection, and devise ways to block their action as part of a new disease control strategy. Progress is such that we envisage improved disease control strategies to be tested experimentally within the next four years. For further information
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NEW STRATEGIES FOR WORM CONTROL IN SHEEPDr Bob CoopSince the advent of effective broad spectrum anthelmintics some 40 years ago farmers have come to rely upon these chemicals, coupled wherever possible with grazing management, to control parasite problems on their farms. Whilst these drugs remain effective arguably the crucial question for any farmer was “When, and how often, should I treat my animals?” Although this seems a simple question in fact it poses a number of problems since the adopted control strategy not only has to try to cope with some of the unpredictable aspects of parasite development and availability, but also needs to take into account the system of management on the farm. Until recently the focus of advice to farmers has been how to reduce the risk of developing anthelmintic resistance. However at Moredun we feel that the time has now come for us to focus on practical ways of managing drug resistance under modern farming conditions. The increasing prevalence of anthelmintic resistance (80% of lowland farms in Scotland may have ‘white drench’ resistance), the emergence of multiple resistance to all three drug families and changes in our seasonal weather patterns mean that today the sheep farmer needs to consider several key questions and this will invariably mean a reassessment of current worming strategies:
In order to answer the first two questions farmers will need to carefully monitor the performance of their animals and their anthelmintics by taking mob faecal samples to examine the parasite challenge faced by animals and the post-treatment efficacy of anthelmintics. The third question relates to the importance of avoiding importing drug resistant worms onto the farm. New stock should be treated on arrival and ideally held on hard standing for 24 hours before being turned out. Stock coming onto the farm following quarantine drenching should also not be placed on ‘clean’ pasture since this practice confers a huge advantage to any surviving resistant worms. Although multiple resistance has now been recorded in sheep in the UK the commonest form of resistance is against the benzimidazoles (white drenches) and thus it is important not to use this family on its own for quarantine treatments. In studies at Moredun we have shown that combinations using a macrocyclic lactone (group III) and levamisole (group II) are very effective in removing worms that are resistant to a single drenches of group I, Group II and group III anthelmintics. It is imperative that we conserve the efficacy our endectocidal drugs, which at present are crucial both for roundworm and sheep scab control. Interesting areas for debate with regard to management of resistance include the use of combination products and the value of annual drug rotations on farms where there is evidence of resistance. In the UK at present no combination products containing anthelmintics from groups 1 and II and/or groups I, II and III are licensed for use despite a body of evidence from abroad that these combinations may play a valuable role in maintaining production and in the management of resistance. For further information
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CRYPTOSPORIDIOSIS – DETECTION OF ENVIRONMENTAL CONTAMINATIONDr Bob CoopCryptosporidium parvum is a zoonotic protozoan intestinal parasite which causes diarrhoea in lambs and calves and is responsible for severe diarrhoeic episodes in humans. Human infection is not age limited and occurs in otherwise healthy immunocompetent but susceptible adults as well as in the immunocompromised. The infective stage, the oocyst, is small, very robust and can survive exposure to most common disinfectants, including chlorine. Transmission is either direct, via the faecal-oral route or indirect, via environmental contamination with human or livestock waste. As there is not effective drug therapy for this parasite, cryptosporidiosis can be life threatening for the immunocompromised and can severely debilitate the immunocompetent. However the dehydration caused by acute diarrhoea can be alleviated by oral or intravenous fluids and electrolyte replacement. Oocysts can survive for protracted periods in both fresh- and seawater, therefore having the potential to contaminate watercourses, potable waters and estuarine environments – the latter posing a threat of contamination to marine organisms destined for human consumption. The research at Moredun is investigating three main areas:
Water safetyCryptosporidium is drawn to the public’s attention when water filtration systems fail or are overwhelmed, for example after periods of heavy rainfall. The outbreak of Cryptosporidium which affected approximately 80 people in Glasgow (2000) and about 140 people in Aberdeen (2002) caused public concern. The infective oocysts of Cryptosporidium are highly resistant to disinfectants and are not killed by the levels of chlorination used for potable water supplies. The water authorities use physical means to remove oocysts, namely gravity filtration and 1 micron absolute filters. It is known that ultra violet light has a detrimental effect on oocyst viability but a greater intensity is required than that commonly used to sterilize water for bacteria and viruses. Moredun is currently evaluating high power UV systems which will penetrate the oocyst wall. One of the problems is that to be effective the water needs to be of low turbidity as peaty water and particulates will absorb some of the UV and reduce the effectiveness of the treatment. It is hoped that an effective UV treatment system would be a catch-all for use in moderately turbid water. Any new system would require full validation for use in the UK by the water authorities.
Food safetyBivalve molluscs are known to harbour environmentally derived enteropathogens of humans as a result of filtering large volumes of water and concentrating the recovered particles. Eating raw or lightly cooked shellfish (especially oysters and mussels) is common practice in many countries and has increased significantly the public health risk of enteric pathogen infections. Recently C. parvum has been shown to concentrate in filter-feeding molluscs both naturally and experimentally, although there have been no outbreaks of gastroenteritis associated with Cryptosporidium in shellfish. This project, funded by the Food Standards Agency, focuses on the detection of C. parvum in shellfish and the process involved in purging these animals of their contaminants. We have evaluated the various methodologies available for extraction and identification of C. parvum oocysts from environmental samples and determined that immunomagnetic separation is the most suitable method for shellfish tissues. We are also investigating the time taken for shellfish to purge themselves of contaminants (depuration). For depuration to be effective, the molluscs must be immersed in tanks of clean seawater so that they rid themselves of contaminants naturally. A UV light source sterilises bacterial contaminants but may be insufficiently powerful to kill Cryptosporidium oocysts. At present a minimum of 42 hours is deemed sufficient to complete the process of depuration in industry but previous studies have shown that for mussels to purge themselves completely of C. parvum a longer depuration time may be required. We aim to investigate this and, if needed, manipulate the current protocol to suit the depuration of C. parvum.
Detection methodsThe problem is one of detecting low numbers of oocysts and assessing whether or not they are viable (infective). The infectivity dose for humans is very low (approximately 30 oocysts). Currently if water authorities detect Cryptosporidium oocysts in water samples they have to assume that they are viable and this evokes a ‘boil’ notice for potable supplies. Moredun is currently investigating in vitro tissue culture systems combined with molecular analysis which will detect low numbers of viable oocysts. Evaluation of this detection system will be of considerable benefit to the UK water authorities. For further information
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BACKGROUND INFORMATION ON SCIENTISTS TAKING PART IN MAIN MEETINGProfessor Quintin McKellarQuintin McKellar graduated from Glasgow Vet School in 1981. He went on to gain his PhD in 1984 and was appointed a lectureship at the Veterinary School in the same year. He then became head of the Veterinary Pharmacology department in 1990, when still only 32 and was also appointed to the prestigious Veterinary Products Committee. He was awarded a personal professorship by Glasgow Vet School in 1996 and in August 1997 Professor McKellar took up the post of Scientific Director of Moredun Research Institute and Chief Executive of the Moredun Foundation.
Professor Willie DonachieWillie Donachie graduated from the University of Glasgow in 1978 with a BSc in Microbiology and immediately joined the staff at the Moredun Research Institute in Edinburgh. He completed his PhD in studies on Pasteurella haemolytica at the University of Edinburgh in 1984 and is currently Deputy Director and Head of Bacteriology at Moredun but with specific research interest in Pasteurella. Professor Donachie is an Honorary Senior Lecturer, Faculty of Medicine, University of Edinburgh and an Honorary Fellow, Department of Veterinary Pathology, University of Edinburgh. He is currently on the Scientific Advisory Committee of the Animal Health Trust and the Editorial Board of 2 scientific journals.
Dr Bob CoopBob Coop is currently Head of the Parasitology Division at the Moredun Research Institute, Edinburgh. He started his career by studying Biochemistry at the University of Liverpool in 1961 and then undertook a PhD on lungworm infection in pigs at the University of Wales, Bangor. He joined Moredun in 1968 working on the epidemiology of nematode infections in small ruminants and the impact of gastrointestinal parasitism on the efficiency of food utilisation and carcass quality. More recently his interests have covered the influence of host nutrition, particularly protein, on the acquisition and expression of resistance and resilience to gastrointestinal parasitism in ruminants.
Dr David HaigDavid Haig graduated from the University of Glasgow in 1973 with a B.Sc. in Biochemistry. He gained his Ph.D. in 1982 at Glasgow University for studies on the development and function of mast cells. In 1985 he joined the Moredun Research Institute as an immunologist studying cell-mediated immunity to infectious pathogens. Since 1991, Dr. Haig has been studying immunity to the parapoxvirus orf virus and, more recently, the gammaherpesviruses of malignant catarrhal fever. In June 2002, he became Head of the Division of Virology. He is currently on the Scientific Advisory Committee of the Animal Health Trust and is Chair of the Editorial Board of Research in Veterinary Science.
Dr Hugh ReidHugh Reid graduated from the Royal (Dick) School of Veterinary Studies in Edinburgh in 1966 and has devoted much of his career to the research of virus diseases of animals both in the UK and the tropics. His particular interests have been in louping ill and malignant catarrhal fever and the way in which these impact on domestic animals and wildlife and gained a PhD for studies in the former disease. He was appointed to Moredun in 1968 and has remained with the Institute ever since. During this time he has been seconded to Kenya and Indonesia to further his studies and became Head of the Virology Division in 1990. Retiring in June 2002 he became a Moredun Foundation Fellow with responsibility for co-ordinating the TSE research programme. For further information
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