Cattle Practice 5.4

Cattle Practice NOVEMBER 1997 Volume 5 Part 4

CONTENTS A Clinical Approach to the Diagnosis of Skin Disease 273 P G G Jackson Treatment and Control of Ectoparasites of Cattle 279 M A Taylor Epidemiology and Treatment of Bovine Respiratory Disease in Beef Cattle 283 P R Scott Marbofloxacin: An Advanced Fluoroquinolone for use in Beef and Dairy Cattle 289 C Eyett-Burton An Epidemiology Study of Husk in Adult Cows in 32 UK Herds (Preliminary Findings) 295 G P David “The Milk Development Council – What’s in it for Dairy Farmers and Vets?” 299 P Merson Staff Training and Appraisals – Team Development in Veterinary Practice 303 J M Bower Arsenic Poisoning in a Dairy Heifer Following Contamination of a Redundant 307 Industrial Site with a Wood Tannalising Compound R J Monies The Economic Impact of “Husk” in Dairy Cattle 315 H Woolley Persistance of Immunity after Vaccination with Huskvac in Ivermectin Bolus Treated Calves 319 I Mawhinney A Survey of Lungworm Serology and Vaccination in First and Second Season Grazing Cattle 323 I Mawhinney Experiences with Venereal Campylobacter Infection in Suckler Herds 327 G L Caldow Neospora Caninum Antibody Levels in an Endemically-Infected Dairy Herd 335 L Dannatt A Comparison of Three Treatments for Endometritis 339 I M Sheldon Septic Physitis, Arthritis and Osteomyelitis Probably Caused by 345 Salmonella typhimurium DT104 in Beef Suckler Calves N Blake Sporadic Milk Drop in Dairy Cows 347 R F Gunning Additional Papers Nottingham Fertility Meeting Early Pregnancy in the Cow 349 G E Mann Strategic Milk Progesterone Monitoring 353 A O Darwash Subfertility in Dairy Cattle: Potential Genetic and Environmental Influences 357 G E Lamming Nutritional Influence on Subfertility in Cattle 361 R Webb The Advantages of Milk Progesterone Monitoring 369 J Lamming The Advantages of Milk Progesterone Monitoring 371 A E H Dally “Play the Odds to get Results” 373 Milk Progesterone Sampling and Fertility Control in the Dairy Cow C Watson Ultrasound Studies of Persistent Large Follicles (Follicular Cysts) in Cattle 379 K Noble Do-It-Yourself Artificial Insemination: The Influence of the Number of 381 Training Days Spent in an Abattoir with Access to Live Cows H M J Howells

CATTLE PRACTICE VOL 5 PART 4 A Clinical Approach to the Diagnosis of Skin Disease Jackson P.G.G., Department of Clinical Veterinary Medicine, Madingley Rd, Cambridge. CB3 0ES ABSTRACT Effective treatment of skin disease requires accurate diagnosis of its cause. Skin abnormalities may result from specific causes but can also reflect the general health of the patient. A careful examination of the whole patient and a methodical examination of it’s skin are essential parts of the clinical examination. In some cases further investigation is required to confirm the diagnosis. The zoonotic nature of some bovine skin diseases and the restrictions on drug therapy in milk and meat producing animals are important considerations when planning treatment. KEYWORDS Cattle, Clinical diagnosis of skin disease. INTRODUCTION Although the clinician is rarely called to attend specific cases of skin disease in cattle, skin abnormalities are frequently encountered during a routine clinical examination. Many skin lesions are caused by the physically challenging environment in which cattle – especially dairy cattle – live and where repetitive damage to the skin can easily occur. The skin is the largest organ in the body with protective and regulatory functions. Its condition is a reflection of the general health of the animal and the environment in which it lives. Some skin diseases cause patient distress, some interfere with showing and some are zoonotic endangering the health of farm staff. Specific diseases of the skin can be caused by many factors of which parasitic and fungal infestations are the most common. Some conditions such as ringworm are so common that they are readily recognised. Others – including chronic cases complicated by self-inflicted secondary damage – require greater diagnostic effort using techniques such as skin scrapings or biopsies. Early and accurate diagnosis is very important and is essential if treatment is to be effective and the economic consequences of disease minimised. In every case the starting point in the diagnostic process is a careful and methodical clinical examination. Treatment must be carefully planned and may be time consuming. Great care must be taken to ensure that any drugs used do not compromise the sale of milk and meat. THE DIAGNOSTIC PROCESS Although some cases of the more common skin diseases in cattle are easily recognised others are not and require a more methodical diagnostic approach. The following sequence of clinical diagnosis is suggested: - Stages In The Clinical Diagnosis Of Bovine Skin Disease • History Of The Patient • Visual Appraisal of the Skin & Environment • Clinical Examination of the Whole Patient • Manual Appraisal of the Skin & Lymph Nodes • Distribution of Skin Lesions • Tissues Involved in the Lesions • Description of Lesions • Knowledge of Possible Causes • Differential Diagnosis • Special Diagnostic Tests • Confirmation of Diagnosis • Treatment – Specific or Symptomatic • Response to Treatment • Future Prophylaxis The history of the herd, the patient and the knowledge of the area– including local mineral deficiencies may provide useful information for the clinician. Previous skin disease problems on the farm may provide information which will help in the present case. Recent attendance at shows, sales or contact with other groups of cattle and changes in diet and management provides further information. Poor nutrition can give rise to a dull, dry, thin and brittle coat. Loss of condition or other recent skin disease problems may have contributed to or been the consequence of skin abnormality. The stock person may have noticed cattle showing signs of skin irritation or detected painful areas of skin during handling procedures. The breed, age and sex of the patient provides further useful background information as does the response to any treatment given by the farmer. Visual appraisal of the environment – many farms have hazards like badly designed cubicles where the animals skin can be damaged. In such cases numbers of animals may have similar skin lesions. Old wooden buildings may provide an ideal environment for survival of ringworm spores or parapox virus particles. Clinical Examination – should start with a visual appraisal of the whole body. The body surface is methodically inspected from a distance and then more closely to locate areas of abnormal hair or skin BCVA 1997 273

CATTLE PRACTICE VOL 5 PART 4 which will later be subjected to detailed scrutiny. The clinical examination should include a complete examination of the patient including the entire body surface. Observation of the patient before it is caught may reveal signs of restlessness, pruritis or excessive grooming all of which may indicate skin irritation. The clinical examination should show whether the skin alone is affected or if the skin lesions are part of a general disease process. A louse infestation will cause signs of pruritis and alopoecia but usually little systemic illness. In contrast in Mucosal Disease skin lesions are seen as part of the disease process but the most significant lesions are those in the gastrointestinal tract. Manual appraisal of the skin and lymph nodes – this should cover as much of the body as possible. Lack of handling facilities on some farms and the patient’s temperament may occasionally make this difficult to achieve in safety. The clinician may palpate lesions which are not visible – for example beneath matted hair. Any enlarged lymph nodes should be noted and the cause of their enlargement determined. The thickness of the skin and the presence of any subcutaneous oedema or infection should also be noted. The skin thickness in the adult cow averages 6mm with a decreasing measurement from the dorsal to the ventral body surfaces. One rather deceptive area is the brisket where the skin is quite thick and mobile and may give a false impression of subcutaneous oedema (although it does not pit on pressure) in this location where genuine oedema may present e.g. in cases of heart failure. Distribution of the skin lesions – an important diagnostic observation. Photo-sensitisation lesions for example are commonly seen in lightly pigmented areas on the dorsal parts of the body which are exposed to sunlight. Description of the skin lesions – when possible the clinician should determine exactly what abnormalities are present in the skin, what tissues are involved and how deeply the disease process extends into the skin. Close examination of all affected areas of skin is essential aided by good light and a hand lens. Skin temperature, thickness, consistency and colour are observed and compared with adjacent areas. Subcutaneous oedema or increased skin turgor may be caused by hypoproteinaemia and dehydration respectively but can also be the result of a local insult. The clinician should ensure that all the lesions present are the same (possibly at different stages of the disease process) – since it is also possible to have more than one condition present at the same time. Self inflicted trauma can modify and mask the clinical picture. Skin abnormalities may involve some or all of the component structures of the skin, the hair, hair follicles, the epidermal, dermal and subcutaneous tissues. There may be abnormalities of the sebaceous and sweat glands or proliferation of the superficial epidermal layers. Skin lesions may be primary or secondary and the categories are defined as follows: - Primary lesions are the direct result of the skin disease. They are usually most obvious in the early stages of a skin disease and are those upon which the definitive diagnosis should be based. An example is the papule – a raised area < 1cm diameter e.g. the lesions of bovine papular stomatitis. Secondary lesions are mostly non-specific and are caused by pathological changes which result from the primary disease and it’s legions or by selfinflicted damage by the patient. An example is a fissure as seen in the later stages of photosensitisation. Knowledge of the Causes of Bovine Skin Disease There are nine main causes of skin disease in cattle. They are listed below: - • Parasitic • Bacterial • Fungal • Viral • Neoplastic • Nutritional • Toxic • Phyisical • Congenital An example of a skin disease from each of these categories is given below together with brief details of their diagnosis. Parasitic Skin Disease Causes from this category are the most frequently encountered in practice. Despite or perhaps because of their incidence they are often overlooked. Lice are one of the most common, and perhaps most underestimated causes of bovine skin disease. Three species of blue-grey sucking lice and one biting louse are commonly found in Britain. Lice are capable of rapid multiplication and spread especially in housed cattle in winter. Signs of infestation – pruritis causing rubbing, excessive grooming and alopoecia. Adult lice are visible to the naked eye at their predilection site along the dorsum of the neck and back. Solenopotes capillatus is the least common species and is found especially around the eyes of cattle where it may produce a ‘spectacled’ appearance similar to that in Copper deficiency. Sucking species may cause quite severe anaemia. In calves severe infestation may occur, with very large numbers of lice being found all over the body surface. Surprisingly in such cases there may be very little pruritis. Diagnosis is based on clinical signs, gross presence of lice and microscopic identification of the lice or their egg cases. Application of ‘louse BCVA 1997 274

CATTLE PRACTICE VOL 5 PART 4 powder’ –gamma benzene hexachloride- was a popular and effective treatment. Its withdrawal has left a gap which has been associated with a marked increase in the incidence of these unpleasant and underestimated parasites. Some newer treatments have limited application especially in milking cows. We will hear more about these in later papers this afternoon. Bacterial Skin Disease There is a heavy presence on normal bovine skin but skin disease caused by bacteria is less common than in some other animal species. Chronic superficial trauma, very heavy contamination, continued damp or reduced dermal immunity may predispose to infection. The presence of bacteria on skin swabs does not however necessarily signify their involvement in disease. One of the most common examples of such bacterial infection predisposed to by trauma is subcutaneous Actinomyces pyogenes infection occurring over pressure points or anywhere along the dorsum of the back. The condition can be difficult to treat especially in chronic cases which usually require surgical drainage and aggressive care to prevent abscesses forming again. Diagnosis is based on the clinical signs and the presence of pus can be confirmed by the insertion of a wide bore needle. The presence of the opportunist bacteria can be confirmed by culture. Daily hosing with water after surgical drainage has been found to be very effective. Fungal Skin Disease Ringworm is an extremely common and very well known cause of skin disease in cattle, especially in those under one year of age. Grey, raised crusty lesions, often circular and usually associated with area of alcopoecia are seen. Lesions are particularly common on the head and neck. Lesions in early cases of bovine papillomatosis and in sporadic lymphosarcoma can resemble ringworm and in cases of doubt histological confirmation may be necessary. Ringworm is often self-limiting and the lesions disappear spontaneously within four months. The risk of human infection is high even in people who have been chronically exposed to infected cattle. Affected calves may have a reduced sale value. Diagnosis is by demonstration of fungal spores and mycelia in skin scrapings or broken hairs carefully prepared in 20% KOH before microscopic examination. The majority of British cases of ringworm are caused by Trichophyton verrucosum which does not fluoresce with Wood’s lamp. Treatment is time consuming and not always effective as are attempts to rid the environment of spores. Vaccination is now available. Viral Skin Disease BCVA 1997 Bovine viral papillomatosis - the wart or angleberry - is one of the most common causes of bovine skin disease. At least five strains of the causal papovavirus have been identified, each being responsible for a particular type or location of lesion. There is great variation in distribution and size of the papillomata from the small individual wart on the teat to the large pedunculated angleberry hanging from the neck or abdomen. Penile warts may cause pain or bleeding at the time of service and if untreated may lead to penile deviation. Young cattle are particularly common victims and spontaneous resolution of the problem may occur within a few months. Multiple warts on the teats of down calving heifers present a particularly difficult problem to deal with. Warts – fibropapillomas are hard outgrowths from the epidermis and in the early stages of their development they may be confused with the lesions of ringworm or the cutaneous form of lymphosarcoma. Histology will confirm their presence and may enable the viral cause to be classified. Although most fibropapillomas will disappear within a few months’ large angleberries can be caught in fences causing profuse haemorrhage. Surgical removal may be required in such cases as it is with penile warts. Treatment by autogenous vaccine may be useful especially where numerous warts are present but its efficacy is unreliable. Neoplastic Skin Disease An example is Squamous cell carcinoma – these tumours are seen in poorly pigmented areas at the muco-cutaneous junctions of the body. The eye and adjacent structures are the most common sites. The incidence in the UK may be increasing possibly as the result of recent hot sunny summers. Diagnosis can be confirmed histologically and early surgical removal with a wide margin of normal is often effective. Nutritional Causes of Skin Disease Gross deficiency of major dietary components or insufficient quantities of food will have an adverse effect on skin health. A dull, dry non-elastic skin is seen with poor growth of scant and brittle hairs and a predisposition to infection. Deficiencies of some vitamins and trace elements may cause skin lesions. Copper deficiency in cattle may produce subtle coat colour changes around the eye. Other symptoms of deficiency can include infertility, diarrhoea, poor growth – all of which can be seen in other diseases. A diagnosis of copper deficiency is confirmed by estimation of blood and liver copper status in the herd. Toxic Causes of Skin Disease Excess intake of a number of elements such as arsenic, selenium and molybdenum may produce signs of skin disease along with other symptoms. Potassium iodide is seldom used nowadays to treat 275

CATTLE PRACTICE VOL 5 PART 4 diseases such as wooden tongue. Prolonged administration may lead to signs of iodism which includes a generalised dry seborrhoeic dermatitis. Treatment of toxic conditions may be specific or supportive. Iodism is rarely fatal if the source is removed. Physical Causes of Skin Disease A poorly designed uncomfortable environment may produce a number of skin lesions in cattle mostly the result of chronic injury to the integument. Subcutaneous haematomata are readily produced by injury and are occasionally exacerbated by underlying clotting defects although these are rare in cattle. Congenital Causes of Skin Disease An example is the Baldy Calf Syndrome, which in Holstein cattle is believed to be hereditary. Normal at birth, affected calves show hair loss and thickening of the skin of the head, neck, shoulders and other parts of the body. Severe cases may be incompatible with life and euthanasia may be required in some cases. Special Diagnostic Procedures In many cases of skin disease diagnosis can be based on clinical signs. In cases where the diagnosis is not clear or confirmation is needed one or more of the following special diagnostic techniques may be required:- • Bacterial Culture • Skin Scraping • Skin Biopsy • Other Diagnostic Tests Bacterial Culture Normal bovine skin has a large population of bacteria and fungi. The bacterial population rises dramatically in wet conditions. The bacterial flora live symbiotically with their host but they can be opportunist pathogens if host defences are lowered in any way. Staphlococci, streptococci, corynebacteria and coliforms are commonly found but heavy growths of any of these in pure culture may be significant. Swabs should be taken with care and processed as quickly as possible. Pustular content may be aspirated by sterile needle for culture. Skin biopsies may also be cultured. Skin Scraping The skin scraping is particulary useful in the diagnosis of mange but must be employed at an early stage if mites are to be found. Mite numbers fall rapidly as they encounter the skin’s defence mechanisms. The scraping is best taken with a scalpel blade to a depth at which capillary bleeding just appears. The scraping may be examined directly or after treatment with potassium hydroxide. Skin Biopsy Skin biopsy is often the most useful of the special diagnostic tests. Biopsies must be taken early in the disease process before secondary changes predominate. Fully developed primary lesions are particularly useful and, where practical, multiple biopsies may also be helpful. Interpretation of slides by a skilled pathologist is necessary. The biopsy must be taken with care. A small piece of skin is removed by surgical excision or by punch biopsy. Before removal, hairs should be gently clipped short and the skin gently cleaned with 70% alcohol before local anaesthesia is instilled around and under the proposed biopsy site. The biopsy should be at least 5mm in size and should be fixed in 10% buffered formalin as soon as it has been taken. The volume of fixative should be 10 times that of the biopsy. Attention to detail when taking this valuable diagnostic aid is important to ensure maximum value for the expense incurred. Other Diagnostic Tests Other tests available include direct microscopy of larger parasites such as lice and the identification of the spores of ringworm in superficial skin debris. Electron microscopy will provide definitive diagnosis of viral infections such as papular stomatitis. In other virus diseases with skin lesions, serial serological samples may provide evidence of recent infection. Immune deficiency disease has not been recognised as a major problem in cattle but immunological diagnostic methods including fluorescent antibody tests are available in some laboratories. Confirmation of Diagnosis In the most cases of skin diseases seen in practice, diagnosis is relatively straightforward. Special tests are not required and confirmation of diagnosis is provided by satisfactory response to appropriate treatment. Difficulty will be encountered in longstanding cases whose primary clinical signs have been obscured by time, secondary changes and inappropriate home treatment. Even in these difficult cases a methodical approach to differential diagnosis should prove successful. REFERENCES Bovine Medicine (Disease & Husbandry of Cattle) (1992) Ed. A.H Andrews. Oxford. Blackwell Scientific Publications Diseases of Dairy Cattle (1995) Rebhun, W.C Baltimore. Williams & Wilkins. Jackson, P.G.G. (1993) Differential Diagnosis of Common Bovine Skin Disorders In Practice 15. 119-127 & 193 – 196 Jackson, P.G.G. (1996) Skin Diseases of the Bovine Udder & Teat In Practice. 18. 76 –80 Jackson, P.G.G. (1996) Bovine Skin Disease – the Situation in the 90’s. Vet Annual. 36. 332-345 BCVA 1997 276

CATTLE PRACTICE VOL 5 PART 4 Large Animal Dermatology. Danny W.Scott. 1988 Philadelphia. WB Saunders. Veterinary Medicine 8thEdit. (1994) Radostits, O.M., Blood, D.C. & Gay, C.C London. Bailliere Tindall. Large Animal Internal Medicine 2nd Edit. (1996) Ed. B.P. Smith. St Louis Mosby – Year Book. BCVA 1997 277

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CATTLE PRACTICE VOL 5 PART 4 Treatment and Control of Ectoparasites of Cattle Taylor M A., Central Veterinary Laboratory, Veterinary Laboratories Agency, New Haw, Addlestone, Surrey KT15 3NB ABSTRACT Cattle can become infested with a number of insect and arachnid ectoparasites requiring detailed knowledge on the range and efficacy of chemical compounds used in their control. The introduction of the endectocide antiparasitics, coupled with a reduction in use of more traditional pesticides, has lead to new approaches in the treatment and control of ectoparasites. This paper provides a review of the ectoparasiticide treatments currently available for cattle in the UK. KEYWORDS: Ectoparasiticides, cattle, avermectins, milbemycins, organophophates, synthetic pyrethroids INTRODUCTION Ectoparasites can cause intense irritation leading to loss of condition and effects on performance such as weight loss, reduced milk yield or hide damage. In addition they may be responsible for transmission of disease. The choice and use of chemicals and the method for their control depends to a large extent on husbandry and management practices as well as the type of ectoparasite causing the infestation. Parasites that live permanently on the host, such as lice and mites, are relatively easily controlled and once eradicated, re-infestation only occurs from contact with infested stock. Non-permanent parasites (ticks and flies) are less easily controlled because only a small proportion of the population can be treated at any one time, and they may be maintained by other hosts. Most infestations in cattle are seasonal and predictable and can be countered by prophylactic use of ectoparasiticides. Thus biting and nuisance flies occur predominantly from late spring to early autumn, tick populations increase in the spring and autumn and lice and mites may increase in winterhoused stock. ECTOPARASITES ON CATTLE Obligate parasites found on cattle include the mites Psoroptes bovis, Sarcoptes scabiei, Chorioptes bovis and Demodex bovis, the sucking lice Haematopinus eurysternus, Linognathus vituli and Selenopotes capillatus and the biting louse Bovicola (Damalinia) bovis. Flies may parasitise cattle hosts as larvae or as adults. Larval stages of the warble flies Hypoderma bovis and H. lineatum are parasitic, adult flies do not feed but can cause panic in cattle when egg-laying. Larvae of blowflies (Lucilia sericata) may occasionally infest wounds. Adult biting flies include the Horn fly Haematobia (Lyperosia) irritans, and the stable fly (Stomoxys calcitrans. Other biting flies that may be found on or around cattle include the tabanids (Tabanus - horseflies, Haematopota - clegs, Chrysops - deerflies), blackflies (Simulium spp.), mosquitoes (Culex spp., Anopheles spp.), midges (Culicoides spp.) and louse flies (Hippobosca spp). Nuisance flies include the common house fly (Musca domestica), the face fly (Musca autumnalis), the head fly (Hydrotaea irritans) and the sweat fly (Morellia simplex). Ticks only feed for a short period and are seasonal in occurrence. Species found on cattle in the UK include Ixodes ricinus, Dermacentor reticulatus and Haemaphysalis punctata. The latter two species are localised in distribution within the UK. The main parasites affecting cattle and the compounds effective against them are shown in Table 1. ECTOPARASITICIDE GROUPS Available ectoparasiticides act either systemically or by direct contact with the target organisms. Systemic ectoparasiticides may be given parenterally or applied topically to the skin as ‘pour-on’ formulations from where the active ingredient is absorbed percutaneously and taken up into the blood circulation. Topical ectoparasiticides have a direct effect on the target parasite on the surface of the skin. Most existing ectoparasiticides act primarily on targets in the ectoparasites’ nervous system. A. Systemic Ectoparasiticides In cattle, available systemics in the UK include the avermectins and milbemycin endectocide compounds and the organophosphate, phosmet. Avermectins, and the structurally related milbemycins, are macrocyclic fermentation products of Streptomyces avermilitis and Streptomyces cyanogriseus respectively. The spectrum of activity and duration of action of individual compounds is affected by the lipophilicity of the molecule. All are highly lipophilic and are stored in fat tissue and released slowly. The avermectins include abamectin, doramectin, eprinomectin and ivermectin which are active against a wide range of nematodes and arthropods. BCVA 1997 279

CATTLE PRACTICE VOL 5 PART 4 Moxidectin belongs to the milbemycins and has similar wide ranging activity. The mode of action of the avermectins has been studied but has not been completely elucidated. Ivermectin has been shown to cause paralysis in nematodes and arthropods and was originally thought to act as a gamma-aminobutyric acid (GABA) neurotransmitter agonist. More recent studies suggest that it may act on glutamate-gated chloride ion conductance at the post-synaptic membrane or neuromuscular end plate. It is likely that all members of this class of compounds have similar modes of action. With the exception of abamectin, which is given parenterally, and eprinomectin which is given by pour-on, all are available as injectable and pour-on preparations for cattle. As well as being effective against gastrointestinal roundworms and lungworms, all have activity against warbles, sucking lice and mange mites. Control against the biting louse, Bovicola bovis, the mite, Chorioptes bovis, and the hornfly, Haematobia (Lyperosia) irritans varies between products and the method of administration. With the excception of eprinomectin which has a zero milk withdrawel period, treatment with this class of compounds cannot be given to cows in milk or in the last 2months of pregnancy. Phosmet is now the only member of the organophosphate (OP) group of chemicals licensed for use in cattle in the UK. Organophosphates are neutral esters of phosphoric acid or its thio analogue and act by inhibiting the action of acetylcholinesterase at cholinergic synapses and at muscle end plates leading to an accumulation of acetylcholine at the post-synaptic membrane and neuromuscular paralysis. Phosmet is available as a pour-on formulation and is active against warble fly larvae, lice and mites on cattle. Treatments for these infestations are best administered during the autumn. Specific contraindications for use against warble fly larvae during the period 1st December to 14th March used to be applied because of the risk of death from anaphylaxis to dying larvae in the spinal column. Current datasheets caution as to possible adverse reactions during this period. Studies have also shown that spring treatment for warble fly is less effective than autumn treatment. Efficacy may be increased by direct application to visible ‘warbles’. B. Topical Ectoparasiticides Topical compounds for use in cattle in the UK include the synthetic pyrethroids, the amidine, amitraz, an insecticidal wound dressing powder and several fly repellents. Natural pyrethrins are derived from pyrethrum which is a mixture of alkaloids from the chrysanthemum plant. Synthetic pyrethroids (SP) used on cattle include cypermethrin, deltamethrin, fenvalerate (type II with α-cyano moiety) and permethrin (type I without α-cyano moiety). The content of some synthetic pyrethroids is also expressed in terms of the drug isomers, for example cypermethrin preparations may contain varying proportions of their cis and trans isomers. In general terms cis isomers are more active than the corresponding trans isomers. The mode of action appears to be an interference with sodium channels of the parasite nerve axons resulting in delayed repolarisation leading to paralysis. The lethal activity of pyrethroids seems to involve action on both peripheral and central neurones, while the knockdown effect is probably produced by peripheral neuronal effects only. Formulations include pour-on, spot-on and sprays. All are active against biting and nuisance flies and lice. Some permethrin products are active against sarcoptic and chorioptic mange. Treatments for lice are best administered in the autumn. Periods of protection against flies vary between products and method of application but generally last for up to 1 month for most species of flies. Mange treatments should be repeated after 1 month. Cypermethrin and permethrin are also available as ear tags for use on dairy cattle, beef cattle and calves and provide protection against biting and nuisance flies for up to 5 months. In severe cases of head or face fly attack then both ears can be tagged. Amitraz acts at octopamine receptor sites in ectoparasites giving rise to increased nervous activity. When applied as a spray it is active against mites, lice and ticks in cattle. In severe cases of mange and lice, treatments should be repeated in 7- 10 days; for tick control treatments should be repeated every 9-10 days during the risk period. Fly repellents containing diethyltoluamide and dimethyl phthalate are applied on the basis of need rather than anticipated challenge. They may be applied either as a spray or as a topical lotion around wounds to prevent wound contamination or strike by flies. A larvicidal and bacteriostatic wound dressing powder containing the carbamate, propoxur, the organophosphate coumaphos and the antibacterial, sulphanilamide can be used at regular intervals on wounds. REFERENCES 1. NOAH Compendium of Data Sheets for Veterinary Products 1997-98, National Office of Animal Health, Enfield, UK 2. Ectoparasiticides. The Veterinary Formulary 3rd Edition (Ed Yolande Bishop), p153-179, Royal Pharmaceutical Society of Great Britain and British Veterinary Association, London UK (1996) 3. Taylor M.A. (1997). Antiparasitics. Farmers Weekly Supplement (April 1997) S3-S14 BCVA 1997 280

CATTLE PRACTICE VOL 5 PART 4 Table 1. Activity of ectoparasiticides against common ectoparasite infestations in cattle Ectoparasite Group Parasite Species Ectoparasiticides Biting Flies Haematobia (Lyperosia) irritans Horn fly Stomoxys calcitrans Stable fly Simulium spp Blackfly Ivermectin‹ doramectin‹ eprinomectin‹ moxidectin‹ cypermethrin, deltamethrin fenvalerate permethrin Nuisance Flies Hydrotaea irritans Head fly Musca autumnalis Face fly Musca domestica House fly Morellia simplex Sweat fly Cypermethrin deltamethrin fenvalerate permethrin Warble Flies Hypoderma bovis Hypoderma lineatum Abamectin doramectin Eprinomectin ivermectin moxidectin phosmet Sucking Lice Haematopinus eurysternus Linognathus vituli Selenopotes capillatus Abamectin doramectin eprinomectin ivermectin moxidectin phosmet cypermethrin deltamethrin fenvalerate permethrin amitraz Biting Lice Bovicola (Damalinia) bovisD DoramectinD eprinomectin ivermectinD moxidectinD phosmet cypermethrin deltamethrin fenvalerate permethrin amitraz Mites Psoroptes bovis Sarcoptes scabiei Chorioptes bovis AbamectinD doramectinD eprinomectin ivermectinD moxidectinD phosmet amitraz Ticks Ixodes ricinus Dermacentor reticulatus Haemaphysalis punctata Amitraz ‹ Pour-on preparations with activity and protection against horn flies [Haematobia (Lyperosia) irritans] D Efficacy varies depending on method of application. Injectable preparations aid in the control of biting lice and chorioptic mange. BCVA 1997 281

CATTLE PRACTICE VOL 5 PART 4 Table 2: Licensed Cattle Ectoparasiticide Products in the UK Name Company Chemical Use Withdrawal Active against Periods Ticks Mites Flies Warbles Lice Avermectins Dectomax Injectable Pfizer Limited Doramectin Injection Meat 42 days Milk ** 9 9 9 Dectomax Pour-on Pfizer Limited Doramectin Pour-on Meat 35 days Milk ** 9 9z 9 9 Enzec Eprinex Janssen Meriel Animal Health Abamectin Eprinomectin Injection Pour-on Meat 42 days Milk ** Meat 21 days Milk 0 days 9 9 9z 9 9 9 9 Ivomec Injection for Cattle Merial Animal Health Ivermectin Injection Meat 35 days Milk ** 9 9 9 Ivomec Pour-on Merial Animal Health Ivermectin Pour-on Meat 28 days Milk ** 9 9z 9 9 Ivomec SR Bolus Merial Animal Health Ivermectin Bolus Meat 180 days Milk ** 9 9 9 Ivomec Super Injection Merial Animal Health Ivermectin Clorsulon Injection Meat 28 days Milk ** 9 9 9 Panomec Merial Animal Health Ivermectin Injection Meat 35 days Milk ** 9 9 9 Milbemycins Cydectin 1% Injectable Fort Dodge Moxidectin Injection Meat 45 days Milk ** 9 9 9 Cydectin 0.5% Pour-on Fort Dodge Moxidectin Pour-on Meat 14 days Milk ** 9 9z 9 9 Organophosphates Nupor C-Vet VP Phosmet Pour-on Meat 14 days Milk 2 days 9 9 9 Dermol Plus Crown Veterinary Phosmet Pour-on Meat 14 days Milk 6 hours 9 9 9 Poron 20 Young’s Animal Health Phosmet Pour-on Meat 14 days Milk 6 hours 9 9 9 Synthetic Pyrethroids Auriplak Virbac Permethrin Ear Tag Meat Nil Milk Nil 9 9 Deosan Dysect Pour-on Diversey Lever Cypermethrin Pour-on Meat 28 days Milk Nil 9 9 Deosan Flectron Fly Tags Diversey Lever Cypermethrin Ear Tag Meat Nil Milk Nil 9 9 Deosan Flyaway Diversey Lever Fenvalerate Spray Meat 1 day Milk Nil 9 9 Flypor Crown Veterinary Permethrin Pour-on Meat 3 days Milk Nil 9 9 9 Ridect Pfizer Permethrin Pour-on Meat 3 days Milk Nil 9 9 Ryposect C-Vet VP Permethrin Pour-on Meat 3 days Milk Nil 9 9 9 Renegade Sorex Cypermethrin Pour-on Meat 28 days Milk Nil 9 9 Swift Young’s Animal Health Permethrin Pour-on Meat 3 days Milk Nil 9 9 Spot on Insecticide ScheringPlough Deltamethrin Spot-on Meat 3 days Milk Nil 9 9 Amidines Taktic Hoechst Roussel Amitraz Spray Meat 1 day Milk 2 days 9 9 9 Miscellaneous 9 Negasunt Bayer Propoxur Coumaphos Sulphanilamide Dusting Powder Meat 28 days Milk 7 days 9— Fly Repellant Battle Hayward and Bower Diethyltoluamide Dimethyl Phalate Spray Meat Nil Milk Nil 9 Fly Repellant Liquid Battle Hayward and Bower Diethyltoluamide Dimethyl Phalate Topical Lotion Meat Nil Milk Nil 9 9 Indicates activity against parasite group. Activity against individual species may vary. Refer to individual datasheets. ** Do not use in cattle producing milk for human consumption. Do not use in non-lactating dairy cattle including pregnant heifers within 60 days of calving z Controls horn flies (Haematobia irritans) for up to 35 days — Larvicidal wound dressing BCVA 1997 282

CATTLE PRACTICE VOL 5 PART 4 Epidemiology and Treatment of Bovine Respiratory Disease in Beef Cattle Scott P.R., Department of Veterinary Clinical Studies Royal (Dick) School of Veterinary Studies Easter Bush, Roslin, Midlothian, EH25 9RG, ABSTRACT Respiratory disease affected 33/47 (70.2%) and 41/48 (85.4%) autumn-born beef calves, and 23/31 (74.2%) spring-born cattle two to three weeks after housing. Significant seroconversion to BRSV was demonstrated in the spring-born group, but high acute phase BRSV and PI3 titres prevented further interpretation in the two younger groups. Marbofloxacin effected rapid reductions in calves’rectal temperatures within 24 hours which were generally greater than those improvements achieved with ceftiofur. The antibiotic re-treatment rates were low and no deaths occurred during the six month follow-up study. Liveweight gains were similar for those cattle which developed respiratory disease and were treated with either marbofloxacin or ceftiofur. Veterinary monitoring during outbreaks of respiratory disease ensured prompt detection and appropriate treatment of respiratory disease, and maintenance of target growth rates. Good handling facilities allowed 60 or more cattle to be treated per hour. The role of the veterinary surgeon in the treatment and control of bovine respiratory disease is discussed with particular reference to fears of the general public over indiscrimate antibiotic use in farm animal species. KEYWORDS: Respiratory Disease, Cattle, Antibiotic Treatment, Epidemiology, Food Safety INTRODUCTION Respiratory disease is one of the major causes of financial loss from infectious disease in calves and growing cattle. Economic losses result not only from deaths but also veterinary attendance and antibiotic treatment of affected cattle, reduced short-term (Schumann and others 1990, 1991; Schakel 1994), and lifetime growth rates (Pignatelli 1978). The cost of preventive programmes such as the use of respiratory virus vaccines should also be added to the total disease costs. Jones (1992) estimated that viral respiratory disease cost the UK cattle industry £60 million per annum arising from mortality, treatment costs and reduced performance. The aetiology of an outbreak of respiratory disease has been described as multifactorial and includes physiological, managemental and environmental factors in conjunction with viral, mycoplasmal, and bacterial infectious agents (Martin and others 1990; Wikse 1990, Laven and Andrews 1991; Bee 1992; Hogg 1992; Caldow 1994). Transportation over long distances, delays in markets, poor appetite after arrival on farm (Hutcheson and Cole 1986), and changes in ration may each compromise immune system function. Weaning, creep feeding, and performance of routine surgeries at least three weeks before transport reduced respiratory disease by up to 30 per cent (Cole 1985). While routine procedures such as anthelmintic treatment, castration, and dehorning can be delayed for some weeks after arrival or housing, experimental studies failed to demonstrate increased susceptibility of calves to respiratory diseases associated with physical stressors (Fillion and others 1984) although further studies are overdue. Confinement in cattle sheds increases contact between cattle with aerosol challenge from infectious agents, adverse physical conditions including poorer air quality, large fluctuations in temperature and humidity, and the presence of dust particles. Outbreaks of respiratory disease have been associated with climatic changes and a fall in daily ambient temperature (Pirie and others 1981). Outbreaks of respiratory disease in a UK study involving almost 1800 home-bred cattle occurred within 30 days after housing (Scott 1995a) indicating that environmental factors play an important role in respiratory disease. A mean interval of 19.3 days between arrival and onset of respiratory disease was reported in a large Irish feedlot (Healy and others 1993). The epidemic curve for respiratory disease morbidity and mortality under feedlot conditions in North America reached peak values within two weeks after arrival (Kelly and Janzen 1986; Schumann and others 1990; Allen and others 1991), and such data suggest that cattle are incubating disease when they arrive at the feedlot (Frank and Smith 1983). Under UK and Irish management systems the respiratory disease epidemic curve reachs a peak between two to four weeks after housing (Cole 1985; Healy and others 1993; Scott 1994a,b; Scott 1995a,b,c). The different epidemic curves may reflect the initiating role of respiratory virus infections in northern Europe compared to classical pasteurellosis (shipping fever) in North America. These BCVA 1997 283

CATTLE PRACTICE VOL 5 PART 4 differences become important when one considers prophylactic and therapeutic strategies. It is generally accepted that prior viral infections increase the ability of bacteria, particularly Pasteurella haemolytica which is a normal inhabitant of the nasopharynx (Allen and others 1991), to invade and colonise the lung (Martin 1984; Hjerpe 1986; Gorham and others 1990; Espinasse and others 1991; Giles and others 1991). P. haemolytica A1 was the most common pathogen isolated from lungs of feedlot cattle that died of respiratory disease (Confer and others 1988). Establishing a causal link between involvement of certain respiratory disease viruses, determined by significant seroconversion, and respiratory disease remains problematic because seroconversion can occur in groups of cattle without occurrence of respiratory disease. Vaccination studies in North America have concentrated on P. haemolytica vaccines whereas respiratory virus vaccines have been more widely used in Europe. Despite encouraging respiratory virus vaccine trial results (Stott and others 1987), field studies have questioned the potential cost benefits of combined BRSV and PI3 vaccination in Europe (Thomson and others 1986; Mee and others 1994). In addition, it is believed that passivelyderived BRSV antibody can interfere with parenteral vaccination in young calves (Kinman and others 1989; Jones 1992). These published data often conflict with the practical results obtained in field situations. If BRSV has been implicate in previous outbreaks of respiratory disease in cattle then a pilot vaccination programme should be considered for the next group of cattle. In this author’s practice vaccination of suckled beef calves as young as two weeks old, repeated two to three weeks later at housing, has proved very encouraging despite high circulating levels of passively-derived BRSV antibody. Problems exist when comparing data from different years, nevertheless with sufficient data for pre- and post-vaccination years it should be possible to evaluate overall trends. It is essential that the facilities on the farm and stockmen encourage stress-free handling such that monitoring of all cattle in the group can be undertaken on a regular, sometimes daily, basis when respiratory disease or other conditions require investigation and/or treatment. Selection of cattle with suspected respiratory disease must not be limited to visual appraisal by the stockman otherwise cattle will not be detected during the early stages of disease (Scott 1995a). A large amount of the veterinary surgeon’s time can be wasted on the farm trying to select individual cattle with respiratory disease from groups of 30 or more cattle. Veterinarians have employed a range of selection criteria to establish a diagnosis of bovine respiratory disease (Wikse 1990; Laven and Andrews 1991; Schumann and others 1991; Radostits and others 1994). Clinical parameters such as nasal discharge and cough were poorly correlated with respiratory disease (Allen and others 1991). It has been stated that the selection of sick feedlot cattle based upon visual appraisal from a distance may be a random event (Radostits and others 1994). Studies on beef suckler farms in Scotland, including the present marbofloxacin investigations, have focused on detection of pyrexia >39.5°C as the major selection criteria for respiratory disease. The regular monitoring and early respiratory disease recognition has achieved good success with very low mortality and maintenance of daily growth rates (Scott 1995b; Scott and others 1996b). Determination of rectal temperature was considered to be the most cost effective means of evaluating the presence of bovine respiratory disease (Mechor et al 1988; Radostits and others 1994), and greater cost effectiveness was achieved when antibiotic treatment was initiated at >39.5°C compared to 40.0°C (Bateman and others 1990). In most cattle handling systems it should be possible for the veterinary surgeon and two stockmen to check rectal temperatures and treat up to 60 cattle per hour. The large range of threshold rectal temperatures considered indicative of bovine respiratory disease by various authors (Table 1) illustrates the difficulties in establishing uniformity for the diagnosis of bovine respiratory disease reported in the literature, and then offering practical advice based upon such studies. Table 1 Threshold rectal temperatures considered indicative of bovine respiratory disease Threshold rectal temperature Reference 39.0°C Lauridsen and others 1994 39.3°C Bols and de Kruif 1994 39.5°C Scott 1994a 39.7°C Laven and Andrews 1991; Young 1995 40.0°C Allen and others 1991;Schumann and others 1991; Giles and others 1991; Espinasse and others 1994; Herout 1994; Highland and others 1994;Lockwood and others 1994 >40.5°C Mechor and others 1988; Gorham and others 1990; Picavet and others 1991;Morck and others 1993; There has also been considerable debate in the veterinary literature regarding the generation and description of adventitious lung sounds (Kotlikoff and Gillespie 1983), and their clinical significance (Roudebush 1982; Kotlikoff and Gillespie 1984; Verhoeff and others 1986; Wikse 1990; Giles and others 1991). It is highly unlikely that auscultation of the chest alone would establish a diagnosis of respiratory disease except in either extreme (peracute BRSV with emphysematous bullae) or chronic situations (widespread wheezes and crackles in chronic suppurative pulmonary disease).Antibiotic treatment of cattle with suspected respiratory disease BCVA 1997 284

CATTLE PRACTICE VOL 5 PART 4 based primarily on demonstration of pyrexia, as opposed to all cattle receiving metaphylactic antibiotic injections, has been undertaken by this author in the UK for the past five years (Scott 1995a). In the majority of respiratory disease outbreaks 30 per cent, or more, of the cattle at risk did not require antibiotic treatment. Furthermore, many cattle which received antibiotic treatment were not treated during the first few days of the respiratory disease outbreak, and therefore would not have been protected by the metaphylactic antibiotic injection injected on day 1 (Scott 1995a). In a further small study (Scott 1995b) metaphylactic antibiotic injection did not influence the subsequent appearance of respiratory disease cases. This field study investigated the epidemiology of respiratory disease in beef cattle by regular monitoring of calves’ rectal temperatures, and evaluated the efficacy of either marbofloxacin or ceftiofur in the treatment of respiratory disease. In addition the calves’ future liveweight gains was monitored for two to four months after antibiotic therapy on two farms. BCVA 1997 MATERIALS AND METHODS The study was undertaken on three beef farms in south east Scotland. Groups of 47 and 48 home-bred autumn born beef suckler calves (2 to 4 months-old), and 31 weaned spring-born calves (5 to 7 monthsold), were included in the study. All calves in the group were examined daily after the first case of respiratory disease was diagnosed and antibiotic therapy administered if the rectal temperature exceeded 39.5°C. The calves were examined every day for the first five days of antibiotic therapy, and one week later. Pyrexic cattle were randomly allocated to one of two treatment groups; either Group M 2.0 mg/kg marbofloxacin administered subcutaneously for five consecutive days, or Group C 1.0 mg/kg ceftiofur administered intramuscularly for five consecutive days. No other treatments such as non-steroidal anti-inflammatory drugs (NSAID’s) were administered to pyrexic cattle. Cattle which did not record a rectal temperature greater than 39.5°C during the monitoring period did not receive antibiotic therapy and formed the ‘control group’. It was possible for two stockmen and the supervising veterinary surgeon to check the rectal temperatures and treat up to 60 cattle per hour. The cattle were weighed using electronic load bars accurate to 0.5 kg at the start of the respiratory disease outbreak, and 60 days (Halls Farm) and 120 days (Blackcastle) later. The difference in group mean rectal temperature reductions were compared using student’s t test. RESULTS The first cases of respiratory disease were detected two to three weeks after housing. The farmers commented that a number of cattle ‘had not looked well for at least a couple of days’, and individual animals had been treated over the previous two days on two farms. The majority of cattle were treated at the first veterinary visit on two of the three farms (Table 2). The percentage of cattle treated were 70.2 per cent and 85.4 per cent for the young calves and 74.2 per cent for the weaned cattle, respectively. The number of antibiotic re-treatments during the five days’ antibiotic treatment period (Table 2) were 6/41 (14.6%), 0/33 (0%), and 3/23 (13.0%), respectively. Table 2 Occurrence of respiratory disease relative to the first veterinary visit on three beef farms, and interval to antibiotic re-treatment Total No. of calves 48 47 31 No affected (%) 85.4 70.2 74.2 31 Day 1 5 29 23 Day 2 36 2 0 Day 3 0 2 0 Interval to re-treatment days 3,3,3,3,4,4 - 2,4,6 No re-treated (%) 6(14.6%) 0(0%) 3(13.0%) There was a marked reduction in the mean rectal temperature of marbofloxacin- and ceftiofur-treated calves after 24 hours on the three farms (Table 3). Table 3 Mean rectal temperature of beef cattle and reductions (°C) relative to the first day of either marbofloxacin or ceftiofur five consecutive days’ treatment for respiratory disease Stoddart, Halls 38.5 39 39.5 40 40.5 41 Day 1 Day 2 Day 3 Day 4 Day 5 MARBO CEFT Grant, Blackcastle 38.5 39 39.5 40 40.5 Day 1 Day 2 Day 3 Day 4 Day 5 MARBO CEFT 285

CATTLE PRACTICE VOL 5 PART 4 Graham, Ravensneuk 38.5 39 39.5 40 40.5 Day 1 Day 2 Day 3 Day 4 Day 5 MARBO CEFT The average liveweight gain was similar for marbofloxacin and ceftiofur groups over 120 days at Blackcastle (Table 4; 153 kg versus 154.5, respectively) but significantly greater (P<0.05) for the marbofloxacin-treated group at Halls after 60 days (40.3 kg versus 20.4 kg, respectively). Table 4 Mean liveweight gain 60 days (Halls) to 120 days (Blackcastle) after marbofloxacin or ceftiofur five consecutive days’ treatment for respiratory disease Farm Marbofloxacin Ceftiofur Halls (kg gain over 60 days) 40.3 20.4 Blackcastle (kg gain over 120 days) 153.0 154.5 BCVA 1997 DISCUSSION The high respiratory disease morbidity rate on all three farms could not be readily explained. The cattle in the present study were home-bred, and only one group had been recently weaned. Significant seroconversion to BRSV was only recorded in the group of older cattle. The high acute phase titres in the young calves, presumably arising from maternally-derived antibody, often resulted in a fall in individual titres associated with respiratory disease. All three groups had been housed two to three weeks previously, and the older spring-born cattle had encountered a sudden dietary change from grazing to a straw and concentrate ration. It could be reasoned that some pyrexic cattle (>39.5C) did not require antibiotic treatment, and that that the threshold rectal temperature was too low. However, the absence of mortality and maintenance of subsequent target daily liveweight gains would support the disease monitoring exercise undertaken in the present studies. There have been no large scale UK studies which have monitored febrile cattle suffering from respiratory disease which have not received antibiotic treatment. Studies carried out for FDA licensing purposes in the USA have invariably reported unacceptably high mortality rates in untreated pyrexic cattle with respiratory disease (Hamm and others 1996). The present studies demonstrated a substantial reduction in mean rectal temperature of the marbofloxacin-treated calves within 24 hours. Other field studies have also demonstrated a marked reduction in calf rectal temperature 24 hours after the start of various antibiotic treatments (Gorham and others 1990; Giles and others 1991; Lockwood and others 1994; Richard and others 1994; Scott 1994a; Scott 1995a,b; Scott 1996) indicating efficacy of that antibiotic in the treatment of respiratory disease (Radostits and others 1994). Other field studies, which have included oxytetracycline as one of the antibiotic treatments (Mee and O'Farrell 1991; Laven and Andrews 1991) have assessed rectal temperature reduction after two or three days later, respectively. Reasons against regular rectal temperature monitoring of all cattle after clinical symptoms suggestive of respiratory disease appear in the group have included fears regarding further stress-induced disease, exacerbation of existing problems, and additional cost of farm labour. A disturbing trend has developed in the UK towards whole group antibiotic injection in the face of an outbreak of respiratory disease despite the lack of supportive UK field trial data. Much of the data quoted to support whole group antibiotic injection (antibiotic metaphylaxis) have been generated in feedlot situations in North America where the epidemiology of respiratory disease often markedly differs from many northern European situations. More recent studies in North America have demonstrated the efficacy and financial benefits of regular rectal temperature monitoring for respiratory disease with antibiotic treatments administered at >39.6 C compared to whole group antibiotic metaphylaxis (Galyean and others 1995; Musser and others 1996). Veterinary involvement in respiratory disease outbreaks should not be limited to the initial visit with whole group antibiotic injection. This situation prevails on many farms despite the fact that determination of treatment efficacy based on general demeanour, without reference to rectal temperature, has been associated with high respiratory disease relapse rates (Mechor and others 1988). In studies of respiratory disease (Scott 1995a), including the present study with marbofloxacin, the calves' rectal temperatures were reduced from >40.0°C to a range of 39.0 to 39.3°C after one day's antibiotic therapy but often did not return to 38.5°C for five or more days. The rapid fall in rectal temperature that occurred within 24 hours of initial antibiotic injection, but little or no further reduction despite additional treatments questions whether daily injections of bacteriocidal antibiotics should be continued for more than three days. Indeed, recent studies of antibiotic treatment of shipping fever in the USA have demonstrated the efficacy of a single subcutaneous injection of enrofloxacin, within a range from 7.5 to 12.5 mg/kg, for the treatment of bovine respiratory disease (Hamm and others 1996). 286

CATTLE PRACTICE VOL 5 PART 4 Work in laboratory animals has demostrated that peak serum concentration (Cmax) and the area under the curve, but not the time above minimum inhibitory concentrations, were the most important pharmacokinetic parameters determining clinical efficacy of fluroquinolones (Drusano and others 1993; Meinen and others 1995). The slight pyrexia that persisted despite antibiotic therapy may have resulted from either resolving lung pathology, consequent to the release of inflammatory mediators, or associated viral infection(s) as BRSV infection can cause fever (Pirie and others 1981; Bryson and others 1983; Verhoeff and others 1984, 1988). While the selection criteria for antibiotic treatment of suspected bovine respiratory disease cases have remained poorly-defined, accepted guidelines detailing when antibiotic re-treatments may be indicated (Clarke and others 1991) do not exist. The mean interval to antibiotic re-treatments in the present series was 4 days, and probably resulted from continuing compromise of the lung’s physical defence mechanisms after viral-induced damage with secondary bacterial colonisation rather than the rapid development of bacterial resistance. Previous studies have indicated that treatment of recurrent pyrexia, after four or more days interval, with the same antibiotic gave comparable responses to the first antibiotic treatment course. In those cattle where pyrexia was detected within four days of the previous antibiotic treatment course it would be prudent to select a different antibiotic and monitor progress. Antibiotic re-treatment rates were considerably higher in calves aged between two to five months than those more than 8 months-old (Scott 1994a; Scott 1995a; Scott 1996c). Criteria used to determine antimicrobial efficacy have included initial treatment response, relapse (antibiotic re-treatment) rates, chronically affected calves, and case fatality rate (Gibbs and Bottner 1994; Young 1995). No deaths were recorded in the present series. Mortality rates between 0.18 to 0.6 per cent have been reported in European studies of respiratory disease (Caldow and others 1993; Gibbs and Bottner 1994; Richard and others 1994) although mortality rates between 3 to 5 per cent have been reported in severe outbreaks of respiratory disease (Stott and others 1987; Bee 1992). Cattle with respiratory disease had reduced liveweight gain for a period despite antibiotic treatment (Bateman and others 1990; Young 1995). Subsequent growth rates of 0.7 kg/day and 1.2 kg/day on the two monitored farms in the present studies were in line with the feeding regimens. Unlike earlier reports (Thomas and others 1978; Pignatelli 1978), no long term reductions (up to 300 days study period) in subsequent growth rate were recorded in previous studies (Scott 1995a), however problems may exist with an accurate definition of control cattle. In previous studies involving over 500 cattle (Scott 1995a), the growth rate of pyrexic cattle treated for suspected respiratory disease was not significantly different to non-pyrexic (less than 39.7°C throughout the study period; minimum 28 days’ surveillance). There are obvious animal welfare benefits from the early detection and effective treatment of respiratory disease by the veterinarian. The avoidance of chronic suppurative pulmonary disease, and associated suffering (Bee 1992), has been a feature of intensive respiratory disease monitoring programmes (Scott 1994a; Scott 1995a). Recent food scares have further heightened the fears of the general public with respect to bacterial contamination of meat, presence of antibiotic residues, and widespread indiscriminate use of antibiotics in farm animal species. Direct veterinary supervision of respiratory disease outbreaks guarantees responsible use of broad spectrum antibiotics and observation of withdrawal periods thus ensuring food safety and consumer confidence in the cattle industry and veterinary profession. There can be few justifiable reasons to dispense large volumes of broad spectrum antibiotics to farmers for the treatment of considerable numbers of cattle with suspected respiratory disease. CONCLUSION The system outlined in this article describes a practical cost-effective method for monitoring outbreaks of bovine respiratory disease in general practice where the veterinary surgeon plays the key role. 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(1994) Proceedings of the French Buiatrics Congress, Paris, France. p151-167. LECHTENBERG, K., JOHNSON, E., MILES, D., APLEY, M. & WRAY, M. (1994) Proceedings of the XVIII World Buiatrics Congress, Bologna, Italy. p627-630. SCHUMANN, F.J., JANZEN, E.D. & McKINNON, J.J. (1990) Canadian Veterinary Journal 31, 285-288. HJERPE, C.A. (1986) In Howard J.L. (ed): Current Veterinary Therapy in Food Animal Practice 2. Philadelphia, WB Saunders. p.670 SCHUMANN, F.J., JANZEN, E.D. & McKINNON, J.J. (1991) Veterinary Record 128, 278-280. SCOTT, P.R. (1994a) Veterinary Record 134, 325-327. HOGG, A. (1992) Proceedings, British Cattle Veterinary Association. p347-352. SCOTT, P.R. (1994b) Cattle Practice 2, 349-354. SCOTT, P.R. (1995a) Cattle Practice 3, 393-402. HUTCHESON, D.P. & COLE, N.A. (1986) Journal of Animal SCOTT, P.R. (1995b) British Veterinary Journal 151, 587-589. Science 65, 543-554. SCOTT, P.R. (1995c) Dien en Arts 7, 349-352 SCOTT, P.R., McGOWAN, M., SARGISON, N.D., PENNY, C.D. & LOWMAN, B.G. (1996a) Australian Veterinary Journal 73, 62-64 JONES, P. (1992) Proceedings, British Cattle Veterinary Association p393-396. KELLY, A.P. & JANZEN, E.D. (1986) Canadian Veterinary Journal 27, 496-500. SCOTT, P.R., SARGISON, N.D., STRACHAN, W.D. & PENNY, C.D. (1996b) XIX Woirld Buiatrics Conference Edinburgh p 35- KIMMAN, T.G., ZIMMER, G.M.. STRAVER, P.J. & 38 . DELEEUW, P.W. (1986) American Journal of Veterinary Research 47, 143-147. SCOTT, P.R., SARGISON, N.D., STRACHAN, W.D. & PENNY, C.D. (1996c) XIX Woirld Buiatrics Conference Edinburgh p 38- KIMMAN, T.G., WESTENBRINK, F., SCHRENDER, B.E.C. & 39 . STRAVER, P.J. (1987) Journal of Clinical Microbiology 25, 1097-1106. STOTT, E.J., THOMAS, L.H., HOWARD, C.J. & GOURLAY, R.N. (1987) Veterinary Record 121, THOMAS, L.H., WOOD, P.D.S., & LANGLAND, J.M. (1978) KOTLIKOFF, M.I. & GILLESPIE, J.R. (1983) Compendium of British Veterinary Journal 134, 152-161. Continuing Education for the Practising Veterinarian 5, 634-639. THOMSON, J.R., NETTLETON, P.F., GREIG, A. & BARR, J. KOTLIKOFF, M.I. & GILLESPIE, J.R. (1984) Compendium of (1986) Veterinary Record 119, 450-453. Continuing Education for the Practising Veterinarian 6, 462-467. VERHOEFF, J. & van NIEUWSTADT, A.P.K.M.I. (1984) Veterinary Record 114, 288-293. LAURIDSEN, B.H., JORGENSEN, J., OLSEN, L. & NELL, T. (1994) Proceedings of the XVIII World Buiatrics Congress, Bologna, Italy. p713-715. VERHOEFF, J., WIERDA, A., VULPEN, C. van, & DORRESTEIJN, J. (1986) Veterinary Record 118, 14-16. VERHOEFF, J., WIERDA, A. & BOON, J.H. (1988) Veterinary Record 123, 346-350 LOCKWOOD, P.W., HAAS, V. de, KATZ, T. & VARMA, K.J. (1994) Proceedings of the XVIII Buiatrics Congress, Bologna, Italy. P551-554. WIKSE, S.E. (1990) The bronchopneumonias. In Smith B.P. (ed), Large Animal Internal Medicine. St Louis, The CV Mosby MARTIN, S.W. (1984) Canadian Veterinary Journal 25, 44-48. Company. p 582-594 MARTIN, S.W., BATEMAN, K.G., SHEWEN, P.E., ROSENDAL, S., BOHAC, J.G. & THORBURN, M. (1990) Canadian Journal of Veterinary Research 54, 337-342. YOUNG, C.R.(1995) Compendium on Continuing Education for the Practising Veterinarian17, 133-142 MECHOR, G.D., JIM, G.K. & JANZEN, E.D. (1988) Canadian Veterinary Journal 29, 438-443. BCVA 1997 288

CATTLE PRACTICE VOL 5 PART 4 Marbofloxacin : An Advanced Fluoroquinolone for use in Beef and Dairy Cattle Eyett-Burton C., Vétoquinol (UK) Ltd, Wedgwood Road, Bicester, Oxfordshire OX6 7UL ABSTRACT Marbofloxacin is a novel fluoroquinolone antimicrobial developed specifically for veterinary use. It has been widely used in the small animal sector since its launch at the British Small Animal Veterinary Association Congress in the Spring of 1995 (Marbocyl Tablets, Vétoquinol). The widespread acceptance of this antimicrobial by the veterinary profession has confirmed its efficacy and safety in use for a range of indications in the companion animal sector. Investigation of the pharmacokinetics of marbofloxacin in cattle, coupled with a knowledge of its broad spectrum of activity led to its development for the treatment of bovine respiratory disease (BRD). This paper seeks to summarise the salient features of this development and demonstrate some results obtained in a UK field study in which marbofloxacin was used in the treatment of BRD. KEYWORDS: Marbofloxacin, Fluoroquinolone, Bovine respiratory disease. PHARMACOLOGY to this activity, resulting in a favourable margin of safety. Marbofloxacin is a novel fluoroquinolone, the structure of which is shown in Fig. 1 below:- The unique mode of action of the fluoroquinolones allows them to be effective against bacteria that have developed resistance to other classes of antibiotic. Fig. 1 Marbofloxacin SPECTRUM OF ACTIVITY The broad spectrum bactericidal activity of marbofloxacin covers a wide range of Gram positive and Gram negative bacteria and Mycoplasmas. The spectrum of activity includes all the major pathogens involved in BRD, including Pasteurella spp., Haemophilus spp. and Mycoplasma spp. Other bacteria that are extremely sensitive to marbofloxacin include Escherichia coli, Klebsiella spp. and Salmonella spp. Table 1 demonstrates the susceptibility of major bovine respiratory pathogens to marbofloxacin (MIC Widely available for oral administration to dogs and cats in tablet form, marbofloxacin has now been developed as a 10% solution for injection for cattle and pigs under the trade name Marbocyl 90 = the concentration of antibacterial that inhibits the growth of 90% of a bacterial population). The kill kinetics of marbofloxacin has also been investigated. In an ex vivo study, sera was obtained from cattle at regular time intervals following injection and mixed with cultures of Pasteurella haemolytica and Pasteurella multocida. The duration of bactericidal activity was calculated and the results showed that the killing rate of serum samples appeared very similar at different time intervals, indicating that marbofloxacin had a fast and long lasting bactericidal effect for both bacterial species (up to 33 hours). The duration of bactericidal activity of the serum is shown in Table 2. ®. MODE OF ACTION Marbofloxacin is a bactericidal antibacterial. Its mechanism of action is as an inhibitor of DNA gyrase. DNA gyrase is an essential cell enzyme, necessary for the supercoiling of DNA, which allows bacterial DNA to fit within the bacterial cell. Inhibition of DNA gyrase leads to rapid bacterial cell death. Mammalian gyrase has an inherent resistance Table 1 Pasteurella multocida Patheurella haemolytica Haemophilus sommus Mycoplasma bovis No. of strains 194 120 31 56 MIC (μg/ml) 0.057 0.17 0.03 0.48 90 BCVA 1997 289

CATTLE PRACTICE VOL 5 PART 4 Table 2 Duration of bactericidal activity of serum. Dose & route Pasteurella haemolytica Pasteurella multocida Duration of bactericidal activity Mean serum concentrations Duration of bactericidal activity Mean serum concentrations 2mg/kg IV 17h 0.03 :g/ml 11h 0.08 :g/ml 2mg/kg IM 20h 0.03 :g/ml 15h 0.07 :g/ml 2 mg/kg SC 21h 0.03 :g/ml 14.5h 0.1 :g/ml 4 mg/kg IM 33h 0.02 :g/ml 24h 0.05 :g/ml PHARMACOKINETICS Table 3 Pharmacokinetic parameters calculated Marbofloxacin (Marbocyl 10% Injection) may be in sick and healthy calves. injected by the intravenous, intramuscular and subcutaneous routes. BCVA 1997 Pharmacokinetic studies have investigated the absorption, distribution, metabolism and excretion of marbofloxacin in pre-ruminant and ruminant calves and lactating cattle. Comparable results were obtained following intramuscular and subcutaneous injections of 2mg/kg marbofloxacin. Absorption is rapid and complete, with a high, rapid peak concentration appearing in plasma within an hour of administration. Maximal plasma concentrations of around 1.5µg/ml exceed by far the MIC90s of typical respiratory pathogens. The volume of distribution is large, indicating wide tissue distribution, which is a consistent feature of the fluoroquinolone group of antibacterials (Bahri & Blouin 1991). The elimination half life of marbofloxacin in cattle is approximately 7.7 hours (9.1 hours in preruminants). This extended elimination half life means that the plasma concentration remains above the MIC (minimum inhibitory concentration) for the major pathogens involved in BRD for a prolonged period, thus fully justifying the once daily dosage regime of Marbocyl. Marbofloxacin appears to be weakly bound to plasma proteins, being mainly present in plasma as free active drug. Metabolism of marbofloxacin is limited with unchanged marbofloxacin forming the major component in all samples of urine, faeces and milk. Excretion via urine and faeces occurs in approximately equal amounts in ruminating animals. The major route of elimination in pre-ruminating animals is via the urine. Comparison of the pharmacokinetic profile between healthy and sick (infected with Pasteurella haemolytica) pre-ruminating calves showed no significant differences, although a slower elimination rate was recorded in the sick calves. (Table 3). PARAMETERS HEALTHY SICK p t2$ (h) 9.12 " 1.78 12.32 " 3.86 0.10 AUC064 (:g.h/ml) 15.32 " 5.08 16.44 " 4.18 0.70 Cmax (:g/ml) 1.56 " 0.29 1.50 " 0.31 0.74 Tmax (h) 0.71 " 0.19 0.60 " 0.11 0.28 POST ANTIBIOTIC EFFECT An interesting feature of some antimicrobials is that if bacteria are exposed to an antibacterial and then that antibacterial is removed, the bacteria continue to die for a period afterwards. This does not occur with all antibacterials but it has been demonstrated with marbofloxacin against a range of bacteria (Table 4). Whilst the importance of this post antibiotic effect is still being investigated, it is likely to mean that antibacterial activity in vivo is, in effect, being provided for even longer than the pharmacokinetic data would indicate. RESIDUES Extensive residue studies have been conducted in beef and dairy cattle. The UK milk and meat withdrawal times for cattle set as a result are 36 hours and 6 days respectively. TOLERANCE Specific tolerance studies and field trials have shown marbofloxacin to be very well tolerated in cattle following intravenous, intramuscular and subcutaneous injection. Local reactions were not a feature after intramuscular injection, while subcutaneous injections led to occasional mild inflammatory reactions at the injection site, not leading to muscular damage (data on file, Vétoquinol). Table 4 Post antibiotic effect duration (hours) according to antibiotic concentrations and to strains. Strains Marbofloxacin Enrofloxacin MIC (:g/ml) PAE duration (h) MIC (:g/ml) PAE duration (h) 2 x MIC 4 x MIC 2 x MIC 4 x MIC Escherichia coli 0.24 0.53h 1.90h 0.012 0.17h 0.63h Salmonella typhimurium 0.024 0.50h 1.33h 0.024 0.60h 0.85h Pasteurella multocida 0.012 1.57h 0.77h 0.006 1.73h 0.43h 290

CATTLE PRACTICE VOL 5 PART 4 Efficacy of Marbofloxacin in the Treatment of Bovine Respiratory Disease INTRODUCTION or more of the following symptoms, dyspnoea, abnormal nasal discharge, abnormal lung sounds, tachypnoea. Bovine Respiratory Disease (BRD) remains one of the most important disease complexes seen on the farm, not least from health, welfare and economic standpoints. Despite the advances in understanding of the aetiology, pathogenesis and prophylaxis of BRD, it remains highly prevalent and its importance to the farmer and veterinary surgeon shows no sign of abating. Antibiotic treatment remains the cornerstone of therapy and any antibacterial used should be effective against the susceptible pathogens involved, with a good margin of safety. The antibacterial used should be easy to inject and well tolerated. It should reach effective concentrations in target tissues and be rapidly clinically effective. Meat and milk withhold periods should be taken into account and their importance evaluated depending on the type of animal concerned. Cattle were excluded from the trial if they had suffered respiratory disease or received antibiotic therapy within the previous 5 days. The veterinary surgeon clinically assessed each individual animal and a clinical score was calculated for each calf to provide a numerical means of assessing clinical progression. By quantifying the severity of disease, a statistically valid assessment of the treatments’ relative efficacies could be made. Table 5 shows the indicators and multipliers for calculation of clinical score. (Table 5). Table 5 Indicator Score Weighting Respiratory rate >30/minute 1 x1 BCVA 1997 When selecting an antibiotic, the important pathogens to consider are Pasteurella multocida, Pasteurella haemolytica, Haemophilus somnus and Mycoplasma bovis. The debate over the relative importance of these as primary or secondary pathogens continues, but time and again they are implicated in lung pathology and clinical disease and their control can be considered essential in practical, effective management of BRD. ≤30/minute 0 Dyspnoea Severe difficulty 2 Some difficulty 1 x5 absent 0 Depression very depressed (difficult to move/moribund) 2 depressed (difficult to move) 1 x5 normal (moves willingly) 0 Whilst bacterial culture and sensitivity testing remains only rarely performed in the field, it is undoubtedly the case that a number of antibiotics commonly used in BRD may be ineffective against the pathogens involved. With its bactericidal, broad spectrum of activity against a range of pathogens, including Pasteurella multocida, P. haemolytica, Haemophilus somnus and Mycoplasma spp., marbofloxacin has been tested in a series of clinical and field studies for the treatment of BRD in preruminating, ruminating and lactating cattle. An additional clinical study was conducted under typical UK field conditions in the Autumn and Winter of 1996-1997, and is described below. Rectal temperature ≥39.5º C 1 x10 <39.5º C 0 Abnormal nasal discharge present 1 x1 absent 0 Abnormal ocular discharge present 1 x1 absent 0 Bilateral conjunctivitis x1 present 1 absent 0 Abnormal lung sounds present 1 x1 absent 0 Mandibular lymph node MATERIALS AND METHODS enlargement present 1 x1 A controlled, randomised, multicentric field study investigating the efficacy of marbofloxacin in the treatment of BRD was initiated in November 1997 in 11 veterinary practices around the UK. absent 0 Cough on tracheal pinch present 1 x1 absent 0 The reference drug used was ceftiofur sodium (Excenel Sterile Powder, Pharmacia & Upjohn Limited). Following random allocation, treatment was initiated with either marbofloxacin 10% at a dose of 2mg/kg by intramuscular or subcutaneous injection, or Excenel Sterile Powder reconstituted with Water for Injection at a dose of 1mg/kg by intramuscular injection. The intravenous route of administration, Calves were included in the study on the basis of veterinary clinical examination. Inclusion criteria consisted of acute respiratory disease, as evidenced by a rectal temperature greater than 39.5°C and one 291

CATTLE PRACTICE VOL 5 PART 4 Breeds represented included pure and partbred Friesian Holstein, Charolais, Limousin, Hereford, Simmental, Belgian Blue and Longhorn. for which marbofloxacin 10% is also licensed in cattle, was not utilised in this study, in order to limit the number of variables between the two comparative products. Treatment was continued on farm by daily injection for 5 days. Veterinary clinical assessment was performed on days 3 and 5, with clinical parameters being scored as before. Cattle from 28 farms were involved in the trial, with the number of cattle on each farm involved in the trial ranging from 2 to 43. The two treatment groups were comparable on day 1, at the start of the study (Table 6). RESULTS The trial involved 399 cattle, ranging in age from 1 week to 16 months (average 4.4 months). Table 6 : Comparison of treatment groups at baseline Ceftiofur Marbofloxacin Comparison (p value) Sex Male 100 (68.0%) 103 (69.1%) p=0.90 Female 47 (32.0%) 46 (30.9%) n.s. (75 missing values) (1) Age (months) Mean 4.4 4.5 p=0.83 Std 2.54 2.70 n.s. (7 missing values) (2) Breed Belgian White and 3 (1.7%) 4 (2.2%) Blue 3 (1.7%) 3 (1.6%) Charolais 64 (35.8%) 65 (35.0%) p=0.69 Friesian Holstein 1 (0.6%) 0 n.s. Hereford 31 (17.3%) 33 (17.7%) (3) Limousine 3 (1.7%) 2 (1.1%) Longhorn 2 (1.1%) 0 Simmental 72 (40.2%) 79 (42.5%) Cross breed (6 missing values) Respiratory rate >30/min 150 (81.5%) 157 (84.0%) p=0.58 n.s. (no missing value) (1) Dyspnoea 0 101 (54.9%) 98 (52.4%) p=0.50 1 79 (42.9%) 81 (43.3%) n.s. 2 4 (2.2%) 8 (4.3%) (3) (no missing value) Depression 0 129 (70.9%) 127 (67.9%) p=0.79 1 51 (28.0%) 57 (30.5%) n.s. 2 2 (1.1%) 3 (1.6%) (3) (2 missing values) Temperature >39.4º C 184 (100%) 187 (100%) - (no missing value) Nasal discharge Present 99 (53.8%) 94 (50.3%) p=0.53 n.s. (no missing value) (1) Conjunctivitis Present 29 (15.8%) 32 (17.1%) p=0.78 n.s. (no missing value) (1) Lung sounds Abnormal 156 (84.8%) 159 (85.5%) p=0.89 n.s. (1 missing value) (1) Mand. lymph nodes Present 59 (32.2%) 59 (31.7%) p=0.99 n.s. (2 missing values) (1) Cough Present 62 (34.1%) 59 (31.7%) p=0.66 n.s. (3 missing values) (1) Overall clinical Mean 16.9 17.2 p=0.56 score Median 17 17 n.s. Std 4.40 4.72 (4) (7 missing values) (1) Fishers exact test ; (2) Students t test ; (3) Likelihood ratio Chi-Square test ; (4) Wilcoxon Rank-Sum test BCVA 1997 292

CATTLE PRACTICE VOL 5 PART 4 Following treatment, the total clinical score rapidly DISCUSSION declined in both groups, with the decrease in clinical score being significantly faster (p< 0.01) in the marbofloxacin group (Table7, Fig 2). It is unusual to find statistically significant differences in efficacy parameters in field studies with an active control. In the study, marbofloxacin resulted in a significantly faster decrease in rectal temperature than ceftiofur (p< 0.05) and a significantly faster decrease in clinical score (p< 0.01). This is likely to be in part due to the large numbers of calves involved in the study, as well as the enhanced efficacy shown by marbofloxacin. Whilst detailed laboratory back-up was not performed, it is interesting to speculate whether the differences may also relate to the lack of activity of cephalosporins against Mycoplasma spp. Mycoplasmal involvement in BRD, particularly that of M. bovis is becoming an increasingly recognised problem (Bryson, 1996). The MIC Table 7 Overall clinical score Ceftiofur Marbofloxacin D1 Mean 16.8 17.3 D3 Mean 7.8 5.5 D5 Mean 4.4 3.8 Fig. 2 Overall clinical score 0 2 4 6 8 10 12 14 16 18 20 D1 D3 D5 DAY SCORE Ceftiofur BCVA 1997 Marbofloxacin 90 of marbofloxacin for M. bovis is 0.48μg/ml, compared to the inherent resistance of mycoplasmas against cephalosporins. The Investigators considered marbofloxacin to be easy to inject with a low dose volume and good syringeability. Tolerance of both products was good, with no adverse reactions requiring cessation of treatment. CONCLUSION Marbofloxacin is a bactericidal, broad spectrum antimicrobial of the fluoroquinolone family, developed specifically for veterinary medicine and recently licensed for use in the treatment of bovine respiratory disease (BRD). This rapid clinical efficacy with marbofloxacin was further evidenced by the rapid reduction in rectal temperature. The decrease in rectal temperature was significantly faster (p< 0.05) in the marbofloxacin group. (Table 8, Fig 3). In a controlled, randomised, multicentric UK field study involving 399 calves, the superior efficacy of marbofloxacin in BRD was demonstrated, with significantly faster reductions in rectal temperatures and total clinical score compared with the comparative product (ceftiofur sodium). This rapid clinical efficacy, leads to fast return to appetite and hence, maintained weight gain with associated heath, economic and welfare benefits. Table 8 Rectal temperature Ceftiofur Marbofloxacin D1 0 0 0 1 158 (100%) 171 (100%) D3 0 117 (74.05%) 151 (88.30%) 1 41 (25.95%) 20 (11.70%) D5 0 140 (88.61%) 157 (91.81%) 1 18 (11.39%) 14 (8.19%) Fig.3 ACKNOWLEDGEMENTS Many thanks go to all the practitioners involved in the study, many of whom were taking rectal temperatures and calculating clinical scores over Christmas and New Year. Rectal temperature Percent >39.5o C 0 20 40 60 80 100 120 D1 D3 D5 DAY Percent J L Davot is also acknowledged for adeptly Ceftiofur managing the statistical analysis. Marbofloxacin REFERENCES Bahri L E & Blouin A (1991). Fluoroquinolones : A New Family of Antimicrobials. The Compendium, European Edition. Vol 13, No 12, pp 825-828. Bryson D (1996). Infectious Bovine Respiratory Disease - Emerging Issues and Progress Towards Control. XIX World Buiatrics Congress, Edinburgh, pp 1 - 8. 293

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CATTLE PRACTICE VOL 5 PART 4 “The Milk Development Council – What’s in it for Dairy Farmers and Vets?” Merson P. Chief Executive, Milk Development Council, 5-7 John Princes St. London WIM 0AP ABSTRACT The Milk Development Council (MDC) is a Public Body, formed in 1995 and funded by a levy on all milk produced in Great Britain. Its activities include the funding of near-market Research and Development and other priority areas such as enhancing the public image of milk. This paper reviews the MDC’s work over its first two and a half years, with particular reference to the veterinary surgeon. KEYWORDS: Research and development, Project management, Communication, Farm assurance INTRODUCTION: I would like to thank the the British Cattle Veterinary Assocation for the opportunity to address this meeting. The purpose of this paper is to provide an update on the progress of the Milk Development Council (MDC) as it nears the end of its initial period of office, with a particular focus on the interests of Veterinary Surgeons. The MDC was established by Order of Parliament in February 1995 with a remit to collect a statutory levy on all milk sold ex-farm in Great Britain, and to use it to fund certain work which had previously been undertaken by the Milk Marketing Boards. Within this remit, the MDC has established its mission as:- “To enhance the technical strength and to advance the competitive position of Great Britain’s Dairy Farmers”. The MDC has also set itself the following six strategic objectives for its first three year term:- To Fund Research and Development Appropriate to the Ongoing Needs of Dairy Farmers. To Pursue Synergy with Government and other Research Funding Agencies. To Communicate Results Effectively. To Enhance The Public Image of Dairy Products. To Improve The Genetic Merit of British Dairy Cattle. To Publish Strategic Information about the Dairy Industry. In this paper I aim to provide a brief update on the progress of the MDC towards realisation of these objectives under the headings of Funding Activities, Research and Development and Effective Communication of Results. Finally I would like to explore some areas where I believe that the interface with veterinary surgeons could be of greatest benefit to the industry. FUNDING ACTIVITIES: MDC funds have provided support in three broad areas; to defend and enhance the public image of milk, to carry out the genetic evaluation of dairy cattle, and to develop a programme of research and development on behalf of producers. The National Dairy Council (NDC) carries out the first of these functions, and MDC has provided in the region of £1 million per annum to the NDC. The greater part of this funding supports the NDC’s work in education through schools and health professionals. MDC funding also supports the Nutrition Monitor Database, which provides a comprehensive reference source in the field of diet and health. Under MDC sponsorship, the National Dairy Council has taken over the production of Dairy Facts and Figures. An edition covering the years 1994/95 and 1995/96 was published in January 1997 and is available from NDC at a cost of £40. The 1996/97 edition will be published by the end of the year. The NDC’s Information Services division also provides an expert resource for crisis management within the dairy industry, and has been very active in the last year or two, covering issues such as lindane and phthalates in milk, besides keeping a close watching brief on BSE. Historically NDC was funded on a 50/50 basis by the MMBs and the Dairy Trade Federation. The successor to the latter, the Dairy Industry Federation (DIF) has been unable to persuade all its members to continue to support NDC at this level, and therefore reduced its contribution to NDC to £275k this year. This necessitated a restructuring and rebudgeting of BCVA 1997 299

CATTLE PRACTICE VOL 5 PART 4 the NDC, in which the Milk Development Council took an active part. We have thus been able to ensure that the key core tasks of the NDC have been maintained within a more streamlined operation. The genetic evaluation of cattle within the UK is carried out by the Bull and Cow Evaluation Unit (BCEU). Responsibility for this unit has now passed from the MMB to the Animal Data Centre Ltd, which has been funded by the MDC since November 1995, with a contribution from United Dairy Farmers (Northern Ireland). During the last 18 months, the ADC has moved to new offices in Chippenham, has published three sets of genetic evaluations on schedule and within budget, and has been instrumental in developing a new code of practice for advertising genetic material. The ADC has also been responsible for maintaining the official international conversions of genetic proofs relating to the UK, and for liaison with Interbull. Work in progress includes improvements to the ITEM index, and the inclusion of somatic cell counts into genetic evaluations. It is now over seven years since the Wilson Committee report was published; a period which has seen considerable change in the UK and international dairy industry, alongside a revolution in information technology. The MDC therefore commissioned an independent review into genetic evaluation in the UK, carried out by Dr Maurice Bichard. The Review made 24 specific recommendations and was published in July 1997. Feedback has been sought from interested organisations, and an industry meeting is to be held in November to discuss their implementation. RESEARCH AND DEVELOPMENT: An early priority for the MDC was the establishment of a strategy for research and development. Following wide consultation, this was published by the time of the 1995 European Dairy Farming Event, and remains broadly unchanged today. The MDC’s R&D Strategy is designed to:- • Identify the needs of the industry in the medium to long term • Make appropriate use of producer funding • Enable effective selection and monitoring of projects • Build on links with other funding bodies • Establish a framework for communication and feedback • Establish and develop a “brand image” • Involve farmers in determination of policy and strategy. Making appropriate use of producer funding The levy paid by farmers to the MDC (0.03 pence/litre) generates about £4million, some two thirds of which will be spent on supporting Research and Development projects. In deciding where milk producers’ money should be spent, the first consideration must be to improve the profitability and competitiveness of Britain’s dairy farmers. Proposals that are unable to show this benefit will not receive MDC support. The determination of cost/benefit ratios for research projects is notoriously difficult, but projects will nevertheless be subjected to financial scrutiny in all cases. Projects that are able to show benefits at the level of individual farms are more credible than those that can only show “global” figures, which can be more easily massaged. Beside the principal objective of improving farm profitability, other benefits will also be sought. These include improvements in cattle welfare, increases in consumer choice and safety, and environmental benefits. Projects that are neutral in respect of some of these benefits may be appropriate for MDC funding, but any with likely negative impact will be rejected. Effective selection and monitoring of projects All proposals are systematically assessed against a standard set of criteria. Most important are the economic benefits indicated above. The expertise of the research team is carefully assessed. The MDC uses independent experts to evaluate the competence of teams, and the scientific and innovative merit of projects. I am grateful to several BCVA members who have acted for the MDC in this capacity. To qualify for MDC support, projects have to have clearly stated objectives. Wherever possible, these should be quantifiable. Defined, measurable milestones must be built into the proposal, against which the progress of the project can be objectively assessed. There is little point in discovering that a project is not going anywhere six months before the end of MDC funding! A Project Manager is assigned to each project, and projects are subject to regular scientific and financial scrutiny. Trials and experiments must be set up in a way that enables the results to be statistically meaningful. The MDC seeks to fund work that is innovative, and does not merely repeat what has already been done elsewhere. An exception to this might be made in the case of a project aiming to test the applicability of work done in a research institute to practical farm BCVA 1997 300

CATTLE PRACTICE VOL 5 PART 4 conditions. It may also be appropriate to repeat overseas work under UK farming conditions. Priority Areas For Research • Economic feeding of cattle. Feed represents the major cost on most dairy farms. New systems of feeding dairy cows to produce the quality of milk demanded by the market are of vital interest to the industry. • Hygienic and safe food production. MDC will do everything in its power to foster positive images of dairy farming and dairy foods, both through R&D projects, and by financial support to the National Dairy Council (jointly funded with the DIF). • Reduction of productivity loss. The three most important areas of productivity loss in dairy cattle are reproductive inefficiency, lameness, and mastitis. Projects with realistic chances of reducing these losses will be supported by MDC. • Cattle housing, equipment and environment. The changing structure of the industry and changes to cows themselves means that research is needed into these aspects of dairy cow management. • Genetic tools. Great strides are being made in molecular biology. The MDC is keen that these should be applied at a practical farm level. Genetic tools are becoming available to reduce disease, as well increase productivity. An informal survey of dairy farmers priorities for MDC funded R&D drew over 1000 responses. Of 10 prompted topics the most highly rated were infertility, mastitis, lameness and economic feeding. To date the MDC has considered around 250 research proposals, and has approved nearly 100 projects. The funding awarded to date broadly follows farmers priorities. In its first two years, the MDC awarded research grants primarily in response to submitted proposals. As the portfolio of projects developed, it became apparent that there were a number of gaps in funding in important areas. The MDC has therefore undertaken to commission work in some of these fields. A first step in this direction was the integrated project on improved characterisation of ruminant feeds, jointly funded by MAFF and a feed industry consortium under the Link programme in Sustainable Livestock Production. MDC was instrumental in persuading the various research teams to coordinate their proposals for the greater good of the industry. Over the past six months, the MDC has held review meetings on nutrition, gene mapping, and fertility, and has commissioned reviews in (among others) the areas of forage production, protein crops and the application of sensors to health and fertility. EFFECTIVE COMMUNICATION OF RESULTS: Of the three key tasks of the Milk Development Council, effective communication is by far the most difficult. This is largely due to the need to reach 35,000 milk producers, widely scattered throughout the land, and encompassing a wide range of different farming systems and business requirements. The MDC has established a communications strategy which aims to understand the needs of the industry and the most effective methods and routes of communication. To date we have published seven issues of our newsletter “Milk Developments”, which is direct mailed to all milk producers. Included with some of these mailings have been the first fourteen titles in the “Research into Practice” series, which aims to provide a brief digest of recent research results in farmer friendly format. With each mailing we have included a form to enable feedback from producers. We regularly receive over 1,000 responses, and we record and act on these, as well as reporting the results back to farmers. MDC is grateful to all those who respond and are anxious to develop more interactive communications. We have undertaken some “benchmark” market research to establish the most appropriate means of contact with producers, and will repeat this periodically as a means of monitoring the effectiveness of our communications. MDC has established a “marketing database” of key opinion formers in and associated with the dairy industry, and we are using this for targeted mailings. MDC has achieved wide press coverage, particularly over the last year. As our projects start to show results, we will build on our good relations with the farming press, to help ensure that producers are aware of the work which their money is supporting and able to exploit the results. MDC also takes stand space at key agricultural events. MDC is keen to provide speakers to relevant groups, and we have sponsored events such as the “Grassland Utilisation Roadshows”, the British Mastitis Conference and the visits of New Zealand grassland consultants to the UK. The Council also recognises that there is a gap in the provision of practical hands-on training for dairy farmers and herdspersons, following the reorganisation of the ATB. We are therefore, in conjunction with the RABDF, launching a new national training programme. The modular courses will be based at agricultural colleges and universities, and will include such aspects as business performance analysis, breeding and fertility, dairy cattle nutrition, milk hygiene and product assurance, health and BCVA 1997 301

CATTLE PRACTICE VOL 5 PART 4 welfare. Tutors will include veterinary surgeons, consultants, college staff and leading dairy farmers. The courses themselves will be self-financing, but the sponsors will provide overall co-ordination and quality control. SO, WHAT’S IN IT FOR VETERINARY SURGEONS? I started by thanking the BCVA for the opportunity to speak to you. In the final part of my paper I would like to explore some of the ways in which the Council can work more closely with veterinary surgeons to improve the lot of the British dairy cow and those whose livelihood depends on her:- • Projects. I have already mentioned the valuable work that certain BCVA members have undertaken in relation to the evaluation and management of MDC R&D projects. We are always on the lookout for people with the ability to understand the needs of dairy farmers and the research community, who can provide us with logical, practical advice. Veterinary surgeons are well placed to help in many of our priority areas. Should we have more regular or formal links with BCVA? • Communication. Veterinary surgeons are a key source of trusted, impartial advice to dairy farmers. MDC recognises that only a small minority of producers will take the trouble to seek out research findings for themselves or read all the material we produce. The veterinarian could play a key role in getting our message across, but how good are we at reaching veterinary surgeons? How can we do the job better? • Education and Training. As mentioned in the previous section, MDC sees the veterinary practitioner playing a crucial role in the new courses for farmers and herdspersons. Are there further opportunities in this field? At risk of sounding patronising, should the MDC too become involved in the education of vets? • Farm Assurance. Together with the NFUs, last year MDC helped to draw up and publish the Framework Code of Practice for Dairy Farms and its Scottish equivalent. We are now involved in the harder work of translating this into a practical farm assurance scheme. Again, the involvement of veterinary surgeons is critical in providing guidelines and advice in the establishment of health and welfare standards and in the subsequent monitoring and auditing of schemes. I would like to see a central role for the veterinary surgeon in drawing up action plans to improve the standards on individual farms and to provide credibility with customers and consumers. CONCLUSION: In summary, it is my belief that the Milk Development Council and the British Cattle Veterinary Association have much to gain by closer co-operation. Thank you for your patience in listening to me. I welcome the opportunity to discuss some of the issues arising from my paper. BCVA 1997 302

CATTLE PRACTICE VOL 5 PART 4 Staff Training and Appraisals - Team Development in Veterinary Practice Bower J.M. The Veterinary Hospital, Colwill Road, Plymouth, Devon. ABSTRACT Initial training, periodic assessments and performance appraisals are as important to the team development as obtaining the right staff initially by in-depth and consistent interviewing. It is a great mistake, and one I am sure we have all made, to employ the right person, explain a little about the task, then leave them to it, and grumble or sack them when they don't come up to expectation. Training and periodic assessment are missing from the formula - both of which benefit the practice and the employee. TRAINING Specific training, such as veterinary nurse training, is such an obvious, structured matter that it is not necessary to examine it in depth here. What is missing from many of our practices is the less obvious, but very necessary training of new staff members to the ways of our own practice. It is important that new members of staff learn the practices and procedures as quickly as possible, so that they become part of the team in the shortest possible time. A structured induction programme achieves this and also reduces the level of anxiety naturally felt by anyone joining a new employer. The induction is carried out as a matter of routine and starts on the employee's first day in the practice by the practice manager, or other responsible practice member. A comprehensive Practice Manual is an excellent way of communicating the basics, and eliminates the need for these procedures to be outlined laboriously whenever a new member joins. It is obvious, however, that the induction programme for new staff will vary - for a secretary, the programme will be different from that for a veterinarian, or a new receptionist or student nurse. An example of a Practice Manual (i) will be available at the meeting. APPRAISALS Staff appraisals should not be linked to, or combined with salary reviews - these should be separate items. The most successful appraisal includes an element of self assessment in advance of the meeting, and then a comparison of the employee's and employer's comments and opinions. This leads naturally into a discussion as to how things can be improved, and indeed rarely do the opinions differ. The assessment should have no vindictive aim at all, but rather work on the concept of emphasising the good points and identifying a few areas where more work or effort is needed. Clarify at the outset what the appraisal is all about, work hard at avoiding the staff getting the wrong impression and take care to present the process as a means of:- • Learning from the past to aid the future • Recognising abilities and potential • Developing knowledge, skills and attitudes • Building on successes and overcoming difficulties • Increasing motivation and job satisfaction • Enhancing relationships and furthering team work Plan the appraisal thoroughly and address the basic questions of Why, Who, Where, When, What, and How in readiness for a 'meeting of minds'. In fact everyone involved should give it advance thought. It should be a collaborative venture between management and staff as one-sided planning will tend to give a one-sided discussion and one-sided outcome. Appraisals should never be treated as an interview but as a discussion. They should be carried out at regular intervals but one should avoid the annual ritual concept - i.e. consider a 10 monthly frequency. Instigate frequent mini appraisals that look at:- • How the job is going • How the staff member is doing • How can they develop • What can you do to make it happen. It is useful to use an assessment form and an example is included as an annexe. This assessment form should be issued a week or so before the meeting is arranged to give time for both the employee and employer to fill in the sections in advance. Both parties then get together and talk through the various topics. It seems sensible to discuss the employee's opinion of their performance first, and then any differences. To obtain the maximum amount of benefit to both the practice and the individual, emphasis should be placed firstly on the good points, with a discussion then on the areas to be worked on. It is prudent to get agreement on these areas, and a timescale for the next appraisal, and to have a copy of the meeting notes with actions signed by both parties. BCVA 1997 303

CATTLE PRACTICE VOL 5 PART 4 WHO ASSESSES WHOM? In a small practice, obviously the principal will carry out all the assessments, and if he or she is brave enough, ask if there are any comments on their (the principal's) general attitudes to clients and staff. In a larger practice, assessment can be delegated. For example the Head Nurse should assess the nursing staff, and will in turn be assessed by the practice manager or partners. The Practice Manager will be assessed by a partner. What about the partners? Appraisal should not stop here – each partner should be appraised by another partner. This I feel is a valuable move in the practice. CONCLUSION Regular, perhaps annual assessments will help the practice team enormously. They help in the development of staff skills and roles, they prevent the continuance of bad habits, and can sort out differences in aims and opinions. In the absence of regular appraisals, an invitation to "see the boss" invariably means a confrontation, a difficult interview. If an appraisal is imminent, then the same needed interview becomes a discussion with a different, indeed positive attitude, and the whole practice benefits. ACKNOWLEDGEMENT This paper is based on a chapter by the author in Veterinary Practice Management, Blackwell Science, 1997 REFERENCE (i) Bower, JSM, J & P Gripper & S Dixon Gunn – Veterinary Practice Management, Blackwell Science, 1997 BCVA 1997 304

CATTLE PRACTICE VOL 5 PART 4 ANNEXE: EXAMPLE OF AN ASSESSMENT FORM Preparation for Appraisal (Employee self-assessment) A. The Job 1. What are the main tasks or responsibilities in your job? 2. Which areas of your work do you think have gone particularly well in the last six months or so? Also why did those go particularly well? 3. Which areas of your work have proved particularly difficult? Again why do you think this? 4. How would you anticipate your job could develop or otherwise change over the next year? Prioritise if necessary. B. Work Partnerships 1. At work, which member(s) of the team most directly affects the way you perform your job? 2. Which people at work are most directly affected by the way you perform your job? 3. At work, what support and assistance do you receive from others? 4. At work, what support and assistance do you give them? 5. How would you like to see your working relationships change or develop over the next year? C. This veterinary practice and You. 1. How do you feel in general terms about working with this veterinary practice? Please detail things about this practice and its work about which you feel particularly happy or unhappy. 2. How do you see your future wioth this practice? Please detail any particular aspirations and ambitions you have. D. Other Aspects 1. Are there any other points you would like to raise that haven’t been covered so far? E. Ideas for Action 1. What would you like to see done to help with the items in Section A, B, C and D? 2. What could you do to help things along? BCVA 1997 305

CATTLE PRACTICE VOL 5 PART 4 BCVA 1997 306

CATTLE PRACTICE VOL 5 PART 4 Arsenic Poisoning in a Dairy Heifer Following Contamination of a Redundant Industrial Site with a Wood Tannalising Compound. Monies, R.J., Veterinary Investigation Officer, Polwhele VI Centre, Truro, Cornwall ABSTRACT In this paper the clinical and post mortem findings of a case of arsenic poisoning in a Holstein heifer are described. Compounds most commonly involved with arsenic toxicity in cattle are reviewed. In the case described, once the source of arsenic was identified, regional radio, TV and press focused on the implications of environmental pollution. INTRODUCTION Lead is the most important single cause of poisoning in cattle and 30-40 years ago arsenic was the second most important (Humphreys, 1980). Cases of arsenic poisoning from naturally occurring forms of the metal are relatively rare and most poisoning incidents are the result of incorporation of arsenic into other chemical forms for agricultural and industrial use. Most of these uses relate to herbicide and insecticide compounds. Increased knowledge of the toxic properties of arsenic as well as replacement of arsenical compounds by organic compounds has resulted in a sharp decline in the use of arsenic in recent years. This has been accompanied by a decline in the number of incidents of arsenic poisoning in recent years and other organic and inorganic compounds have replaced arsenic in the order of importance as causes of toxicity in cattle. CASE REPORT History BCVA 1997 At the beginning of May 1995 a group of 12 Holstein and Holstein cross Limousin yearling heifers were turned out from winter housing into a seven acre grass field. The field was temporary rented grazing, separate from the main farm and used for the first time by this particular farmer. Prior to then the land had been used for grazing stock. The heifers were fed a mixture of 50% home produced barley and 50% proprietary concentrate pellets at a rate of 3 kg per head per day. A general-purpose mineral was provided ad-lib and water was from the main supply. In the middle of May 1995 one heifer was noticed to have severe abdominal pain accompanied by bellowing, grunting, teeth grinding and profuse salivation. Further veterinary examination showed that her temperature was normal, pulse was weak and rapid and that she was showing a profuse and watery diarrhoea. Although the animal was weak and staggering no specific nervous signs were seen; she was not blind. The heifer was treated intravenously with 25 ml of Trimethoprim and Sulfadoxine (Trivetrin; Mallinckrodt,20 ml of Vitamin complex (Combivit; Norbrook Laboratories) and 20 ml of a mixture of hyoscine N-butyl bromide and dipyrone (Boscopan: Boehringer Ingelheim). She collapsed into sternal recumbency three hours later and died a further six hours later. Blood films stained with Macfadyean’s methylene blue were examined for anthrax bacilli with negative results. Post Mortem Post mortem examination was carried out at Polwhele VIC, Truro. The mouth, oesophagus, rumen and reticulum were normal in appearance. The rumen contained a good quantity of leafy and fibrous material and the reticulum contained quite a large amount of earth and other gritty material. A number of small petechial haemorrhages were visible on omasal folds and closer examination also revealed some small haemorrhagic ulcerations. The entire surface of the abomasal mucosa was coloured a distinctive orange/pink colour, similar to the colour of smoked salmon. Extensive oedema of the mucosa was evident and again one or two hyperaemic erosions were seen. Although the carcase was fresh at post mortem the abomasal wall was very friable. The mucosa of the first 20 cm of the duodenum was inflamed and showed a number of small haemorrhages. Contents were liquid and showed an unusual greenish yellow colour. Lower parts of the small intestine and the large intestine showed patches of mucosal congestion, again the contents were very liquid but they also showed a distinctive and abnormal green colour. The liver was very friable and the surface had assumed a grey discoloration. The gall bladder contained bile of normal appearance and consistency. Cortices of both kidneys showed linear haemorrhages, the bladder was normal and empty. The lungs showed diffuse congestion and interlobular oedema throughout all lobes. A quantity of serosanguinous fluid was present in both the abdominal and the thoracic cavity and a number of ecchymotic were seen on the parietal pleura of the thoracic wall and diaphragm. Similar haemorrhages were seen over the serosal surface of the trachea and over the thymus. Sub-epicardial haemorrhages were seen over both ventricles of the heart and over the major vessels. The pericardium contained an excessive quantity of serosanguinous fluid. Bacteriology Samples of heart blood, liver, lung and brain were collected aseptically and cultured for up to 48 hours 307

CATTLE PRACTICE VOL 5 PART 4 at 37°C on 5% sheep blood agar and MacConkey agar. Intestinal contents were inoculated into Selenite F liquid medium, incubated at 37°C for 48 hours and then subcultured onto brilliant green agar for a further 48 hours at 37°C. No organisms were isolated from the heart blood, liver or brain. Escherichia coli was isolated from the lungs. Culture of intestinal contents for Salmonella sps. was negative. Virology Samples of abomasal lesions and lymphoid tissue were collected and examined for BVD virus at Langford Veterinary Investigation Centre with negative results. Parasitology Intestinal and abomasal contents were examined for evidence of parasites. None were found. Biochemistry pH of ruminal fluid was 5.7 and examination of aqueous humour for nitrate was negative. Samples of liver, kidney, pancreas and brain were collected and analysed for lead and arsenic levels. Kidney tissue was examined for lead by graphite furnace absorption spectroscopy and arsenic levels of kidney, pancreas and brain were determined spectrophotometrically as arsenic diethyldithiocarbamate at 530 nm using a Jasco v550 uv-vis Streptophotometer following wet digestion with sulphuric, nitric and perchloric acid and hydride generation. The results are recorded below. Table 1 Kidney Liver Pancreas Brain Lead 1.2 μmol/kg NE NE NE Arsenic 13.8 ppm 16.6 ppm 2.7 ppm 1.7 ppm BCVA 1997 These results are for wet tissue. NE = Not examined. The lead levels were considered to be normal but the arsenic levels were high with a concentration of 16.6 ppm in the liver. Differential Diagnosis The following conditions were considered to be relevant to the differential diagnosis: Acute BVD This condition is usually febrile. No oral or mouth lesions were found. Such rapid death is not usually a feature of BVD although a failure to observe earlier clinical signs was considered. Acute Salmonellosis: Again an earlier febrile response would have been expected. Negative cultures of intestinal contents ruled Salmonellosis out. Poisonous plant toxicity: Water dropwort was considered but ruled out on lack of availability and on post mortem examination of rumen contents. Nitrate toxicity: Nitrate is readily found in body fluids such as aqueous humour, in cases of nitrate poisoning. Negative findings together with a lack of a likely source of nitrate enabled this to be ruled out. Barley acidosis: This was ruled out by the rumen pH and the feeding history of the group of heifers. Lead poisoning: This was ruled out on clinical signs and on biochemical examination of kidney tissue. Arsenic poisoning: Clinical signs and post mortem findings supported a diagnosis of arsenic poisoning which was confirmed by biochemical analysis. INVESTIGATION AT THE FARM The group of 12 yearling heifers were grazing a seven acre field which had a boundary fence of some 100 metres, against a new housing development. Half of the site had been completed two years previously and was inhabited, the other half had only just been started. During preliminary excavations earth from the site had been pushed under a stretch of perimeter fence approximately 30 metres long. The earth varied from discoloured green to pure jade green powder. Visual inspection of the excavations on the site revealed large areas of the earth discoloured green. The site foreman said he hadn’t noticed this as he was unfortunately colour blind ! Samples of the soil pushed under the fence showed Arsenic levels of 36125 ppm (27966 ppm of copper and 9312 ppm of chromium were also present). It became apparent that the site was occupied some 15 years previously by a timber company tannalising wood for fence posts, gates and agricultural sheds. The compound used for the wood tannalising process consists of copper sulphate, potassium dichromate and arsenic pentoxide - otherwise known as CCA. The tannalising process involves the treatment of timber in pressure vessels containing a solution of CCA. Treated wood is stacked in yards to drain and dry. Unfortunately a number of the older sites did not have satisfactory arrangements for the disposal or recycling of the compound draining from the stacked timber or discarded from the pressure vessels and 308

CATTLE PRACTICE VOL 5 PART 4 long term run off had contaminated the soil beneath and around the site. On vacating the site the timber company had concreted over much of the yard drains and debris. Removal of this concrete seal had exposed the contaminated earth. The remaining animals were moved from the field. Because of the necessity to protect the food chain it was agreed that these would not be moved off the farm for a further 6 weeks. Excavation of the earth in the field revealed, over the years, that run-off had also caused contamination of the sub-soil on the field side of the perimeter fence. The owner decided to give up his short term rental agreement of the field. Unfortunately some of the concrete and rubble from the site had been moved onto two nearby farms. At one it was awaiting to be used to form a solid base for a silage pit and at the second it had been used to form a hard-standing parking area only some 15 metres away from the spring supplying drinking water for livestock. The Environmental Health Office and the Health and Safety Executive were quickly on the site and public interest in the local community was aroused, the local and regional media soon became involved. All the excavation work for the development of the site was stopped pending analysis of soil samples across the site by the Environment Agency and the County Council.. Their findings are shown on the plan of the site. The results given are for samples BOB.PPT (powerpoint document) also on disk goes on this page - see copy of report. taken at a depth of 10 cm, the values obtained decreased at 20, 30 and 60 cm. The areas high in arsenic were also high in copper and chromium and it was decided to strip the earth from the site to a depth of half a metre on the western half, where the high readings were obtained, and a depth of 20 cm on the eastern half, where the analysis showed considerably lower levels of contamination. The threshold level for gardens and public places is given as 40 ppm and the threshold level for allotments and gardens is 10 ppm, the “action” level is considered to be somewhat higher. It was also recommended that uncontaminated top soil was imported back onto the site. A spring was present and this drained into a small stream leading into the River Fal. The Environment Agency found no evidence of arsenic pollution in the stream but the whole of the exposed site was sheeted down prior to the removal of the contaminated layer as heavy rain was expected. The contaminated earth was removed to a licensed tip and stringent precautions taken for the protection of lorry drivers and staff operating the mechanical diggers. The material which had been moved onto the two farms was also taken onto the same site where it’s arrival provoked protests from a local action group. The whole procedure, involving the movement of thousands of tons of earth and debris, was carried out under close attention from the media. A large part of the former timber yard had already been developed two years previously. DISCUSSION Biochemistry findings in arsenic poisoning Arsenic compounds appear to be quite palatable to cattle. Compounds consist of trivalent arsenites and pentavalent (arsenates) forms as well as organic compounds. Trivalent forms are the most toxic. Toxicity varies with solubility, organic compounds are far less toxic. The lethal dose of inorganic compounds varies between 1 and 25 mg/kg. Whereas organic compounds tend to accumulate, most poisoning incidents are from ingestion of inorganic compounds and are acute in nature. Arsenic reacts intracellularly with sulphydryl groups and inhibits sulphydryl enzyme systems necessary for oxidative phosphorylation. The resulting disruption in cellular metabolism has effects on brain, lung, liver, kidney and alimentary mucosa, but arsenic also has a direct action on capillaries producing an increase in permeability of vessels. The changes seen in the abomasum are the result of this, however they are not local effects as systemic administration of arsenic also produces the same changes. The normal background level of arsenic in cattle tissues is <0.5 ppm. (Casteel et al, 1986) Documented cases of arsenic toxicity mostly record liver levels ranging between 10 and 15 ppm, occasionally levels as high as 60 ppm have been seen. Where the animal has survived and several days have passed since exposure tissue levels may be less than 10 ppm. Similar levels of arsenic are seen in kidney. Rumen or abomasal contents of poisoned cattle show elevated arsenic levels but levels recorded vary between 5 and 800 ppm. Uneven distribution of the compound in rumen contents would be expected and higher than normal levels only give evidence that exposure has occurred. Arsenic is rapidly excreted and arsenic urine levels are quickly elevated following ingestion of the toxic compound. Hair samples may be useful as a method of assessing herd exposure where cases may already have occurred. Values of 1-40 ppm of arsenic in soil are considered to represent normal “safe” levels. (Osweiler, 1979). Clinical, pathological and histological findings in arsenic poisoning A number of cases of arsenic toxicity have been recorded in the literature and a range of clinical signs and post mortem findings have been described. A rapid onset of almost entirely gastro-intestinal signs occurs within 3-4 hours of ingestion of the toxic compound is almost consistently described. Colic, staggering, weakness, mucoid to watery haemorrhagic diarrhoea, salivation and nasal and BCVA 1997 309

CATTLE PRACTICE VOL 5 PART 4 conjunctival discharge are commonly described. Cyanosis and dyspnoea are sometimes seen. Animals are usually afebrile and most show tachycardia. Quite often cattle are first noticed in recumbency and collapse, but death without clinical signs is reported. More usually death occurs within 24 hours of first clinicial signs. The small percentage of recovering animals show diarrhoea for 2-7 days and damage to intestinal mucosa often leaves them “as poor performers”. Where chronic poisoning is described unthriftiness sometimes with the presence of multiple abscess formation has been seen, the affected animals are often rough coated. One author describes nervous signs with the head held out straight and rigid, the affected animal also showing ataxia and eventual convulsions. In this case the arsenic dose was thought to be lower and the symptoms less acute (Boosinger et al, 1980). Severe changes in the gastrointestinal tract of poisoned animals are consistently described. Submucosal oedema of abomasum and intestinal tract are seen as well as marked hyperaemia and ulceration of abomasal and intestinal mucosa. The mucosal surface of the abomasum is often described as being “cherry red” in colour. Ulceration of omasal leaves has been recorded (Casteel et al, 1986). Occasionally ulceration of mouth and tongue are seen. Haemorrhages over the surface of the kidneys and a change in the colour of the liver to a copper or to gun-metal grey colour are described, usually liver parenchyma is congested. Where cases of arsenic poisoning occur after topical application of chemical the same alimentary tract lesions are seen as well as severe oedema and swelling at the site of application (Robertson et al, 1984). Congestion of lungs is noted in many cases, epicardial and subendocardial haemorrhages as well as haemorrhages over other viscera, notably parietal pleura and thymus, are described. Histological changes associated with arsenic poisoning are not well documented. Congestion of the capillaries in mucosal surfaces and desquamation of epithelial cells throughout the alimentary tract are described as well as glomerular and tubular degeneration and necrosis in kidneys (Thatcher et al, 1988). Multifocal necrosis of the liver accompanied by hepatocellular lipidosis particularly of periportal areas is noted in one case. The same author describes cerebral oedema and anoxic type degeneration of nervous tissue throughout the cerebral cortex (Boosinger et al, 1980). It would seem likely that CNS changes occur where lower levels of arsenic produce a less acute syndrome - perhaps where low doses of naturally occurring arsenic or organic arsenical compounds are involved. Peracute cases show no histological CNS lesions. Food Safety considerations The clinical symptoms of arsenic poisoning itself are the most important factor in preventing arsenic entering the food chain, ie death usually follows quickly. No significant excretion in milk has been found, principle excretion is in urine and this is rapid - urine levels almost equalling the daily intake. Permitted levels are <2 ppm in liver and edible byproducts and <0.5 ppm in muscle (Selby et al, 1974). Animals which are exposed to low doses of arsenic over a longer period may accumulate arsenic in the liver, spleen and kidneys. Risk assessment suggests that it will take approximately 6 weeks to deplete arsenic to below the permitted levels in the body tissues of these animals. For this reason a period of 6 weeks movement restrictions is sought for cattle which have been exposed to arsenic. Sources of arsenic in recorded cases of arsenic poisoning The majority of cases of arsenic poisoning involve compounds which incorporate inorganic salts of arsenic as weedkillers, fungicides, insecticides and wood preservatives. Although these compounds are now mostly not used a number of incidents involve access to carelessly discarded chemicals. A disastrous case in Australia involved the death of 101 mixed beef cattle treated with what was thought to be a pour on compound for the treatment of lice. Unfortunately the container had been reused and contained a sheep dip concentrate thought to be arsenic trioxide. Levels of up to 15 ppm of arsenic in liver and 23 ppm of arsenic in kidney were seen in the poisoned cattle none of which survived (Robertson et al, 1984). The same compound was responsible for 67 out of 260 cattle deaths in Kenya following a build up of arsenic in the soil in an area up to 30 metres around abandoned cattle dip (Matai et al, 1975). Lead arsenate formed the basis of an insecticide used in tobacco, cotton and fruit production and a high incidence of arsenic poisoning has been seen in the southern states of the USA in association with this compound (Reagor, 1973). In Texas arsenic is the most important heavy metal causing toxicity in cattle (Casteel et al, 1986). Although lead arsenate has been long since withdrawn cattle sometimes gain access to discarded bags or drums of the compound. Symptoms are usually peracute and in two recorded cases a morbidity of approximately 10% and a mortality of 100% was seen in large groups of cattle (Braun et al, 1980, Stair et al, 1995). Until the mid 1980’s monosodium methane-arsenate (MSMA) was used as a weedkiller, this compound appears to be attractive to cattle. 29 out of 42 yearling heifers died after grazing grass which had been recently sprayed around oil tanks in pasture in Oklahoma. The salty taste of the weedkiller was thought to have appealed to the cattle during a hot dry spell (Morgan et al, 1984). Sodium arsenite is also used as a weed killer and is a very soluble and therefore very toxic. Use of this chemical on a rubber plantation in Nigeria killed 5 cattle which grazed BCVA 1997 310

CATTLE PRACTICE VOL 5 PART 4 there one night whilst in transit (Adeyemo, 1974). Sodium arsenite was suspcted as being responsible for deaths of suckled calves in the eastern counties of England 3 or 4 years ago. Although the compound was withdrawn from agricultural use in 1960 the cattle had gained access to a heap of old drums which were thought to have contained the compound once used as a defoliant during the production of potatoes. (Personal communication Andrew Gresham). Although its efficacy was very much in doubt arsenic trioxide has been used in compounds for foot bathing sheep in the control of foot rot. Two cases recorded in the early 1970’s described poisoning in both cattle and sheep gaining access to foot baths not cleaned out after use. Again losses were heavy - 8 out of 58 heifers and 11 out of 52 store lambs died (Stubbings et al, 1973). There are a number of recorded incidents where CCA tannalising compound has been incriminated as the source of arsenic but these tend to be in the more recent years than the sources hitherto noted. Wood tannalising is the vacuum and pressure impregnation of wood with the compound CCA. Arsenic pentoxide is included in CCA for it’s insecticide and fungicide properties. Modern tannalising plants consist of a large pressure vessel which is supplied by a tank of CCA. After treatment wood is stacked to dry in the yard and the drains and yard are constructed to recycle the compound. The older plants were not subject to regulations, yards were inadequately concreted and “run off” went freely into the earth of the areas surrounding the yards. Shortly after the Cornish case Shrewsbury VI Centre investigated the death of a single suckled calf which was subsequently found to have high liver levels of arsenic. A visit to the premises revealed that the suckler herd had broken through the fence into a neighbouring timber treatment yard. At the follow up investigation it was evident that the yards contained large pools of green liquid. Run-off from the yard had also contaminated a nearby stream. (Personal communication Graham David). Treated timber is widely used in agriculture and is accepted to be safe. There are incidents recorded which highlight possible dangers. Sheep and cattle on neighbouring farms in New Zealand were affected by acute arsenic poisoning. The common factor was that a local electricity company had stock piled some newly tannalised poles on both farms. The tannalising process leaves the treated wood safe, however in this case it was noted that many of the posts were coated in a green sludge and it was assumed that the process had not been completed leaving the arsenic still in a soluble form (Lincoln Animal Health Laboratory, New Zealand, 1980). For this reason it may be advisable to leave newly tannalised timber out of access to stock for a period of 4 weeks. Concentrated ashes from burnt tannalised timber (eg fence posts or stock buildings) contain high levels of arsenic, copper and chromium. Bonfire ash was recorded as the cause of arsenic toxicity killing five cattle in Kentucky (Knapp et al, 1977). The ash contained over 30,000 ppm of arsenic. Another case recording the same source of arsenic noted a pile of ashes which a herd of suckler cows had licked, the authors suggested the ash may well be attractive to cattle. They also recorded high levels of chromium in liver and kidney and suggest that the inflammatory action of chromium on the alimentary tract may well exacerbate the effects of arsenic (Thatcher et al, 1985). The same authors noted that liver copper levels remained normal despite the presence of high levels of copper in the ash, for some unknown reason the copper was apparently not well absorbed. The use of tannalised timber, particularly for livestock buildings has increased considerably over the last 30 years. As some of these sheds are replaced and the old timber burnt we may see an increase in cases arising from timber ash - it has been suggested that burning converts the pentavalent compound to the more toxic trivalent compound. Cases of poisoning by naturally occurring forms of arsenic, so called arsenic pyrites, are less common but are recorded. Volcanic soil in an area of New Zealand near Rotorua is known to be high in arsenic. Precipitous milk drop in a herd of 200 dairy cows was followed by the deaths of six cows and arsenic toxicity was confirmed biochemically showing arsenic liver levels greater than 10 ppm. An area of pasture had recently been flooded and large amounts of volcanic material were left behind. Levels of 6618 ppm of arsenic were seen in samples of the soil. Uptake in grass and plants is low and it is probable that cattle licked areas of exposed earth (Hopkirk, 1987). A similar case was reported from South Dakota in the USA. The rivers in the area had been contaminated by mine tailings after many years of gold mining. A herd on the flood plain of one of the rivers tipped silage on the ground before it was scooped up with a front end loader into the silo but unfortunately earth was carried in with it. The problem presented a more chronic form with cattle showing progressive weakness and emaciation before death. Some cattle showed hind limb ataxia and recurrent convulsions. Tissue levels of arsenic recorded in this case were lower as was the arsenic content of the soil - 2200 ppm (Bergeland et al, 1977). VI centres in England and Wales have reported suspected cases of arsenic toxicity associated with mine waste over the years. Organic arsenical compounds are less soluble and therefore less toxic. They are used as additives in pig and poultry rations and have been implicated in the contamination of dairy concentrates. Mortality was lower and symptoms seen were less severe. Although two cows died a number showing haemorrhagic BCVA 1997 311

CATTLE PRACTICE VOL 5 PART 4 gastro-enteritis recovered following symptomatic therapy (Boosinger et al, 1980). TREATMENT OF ARSENIC TOXICITY Treatment of arsenic poisoning has relied on two compounds but with very little recorded success. Dimercaprol (BAL - British Anti-Lewisite) and sodium thiosulphate have been used in the specific treatment of arsenic poisoning. Dimercoprol is given at a rate of 2 mg/lb intravenously every 4 hours. This treatment is continued for two days but is expensive and uneconomical for commercial animals. It has been suggested that it’s failure has resulted from failure to administer the compound every four hours. However because absorption of arsenic, with resulting toxicity and excretion is so rapid, it is of doubtful value in acute cases. A 20% sodium thiosulphate solution given intravenously at 30-40 mg/kg has also been used, but, for the same reasons it’s value is again doubtful. Work carried out under experimental conditions in the USA some twenty years ago concluded that thiosulphate alone or combined thiosulphate and BAL therapy was beneficial in the treatment of experimentally induced arsenic toxicity (Hatch et al, 1978). In this work treatment began 12 hours after oral administration of a lethal dose of sodium arsenite. This situation is unlikely to happen in field conditions. Saline purgatives with supportive fluid and electrolyte therapy have been used in the treatment of arsenic poisoning, but most incidents are very acute and prognosis is grave. ACKNOWLEDGEMENTS I would like to thank Brian Preece and Vic Simpson for helpful advice, staff at Polwhele and Starcross VI Centres for Laboratory support and Alan Hunt at Sutton Bonington VI Centre for carrying out arsenic analyses. I am grateful to Patrick Hunt of Kenwyn Veterinary Centre, Truro for submitting the case and to Colin Brewer of the Environment Agency for helpful discussion. Thanks are also due to staff at the Central Veterinary Laboratory Library for support and to Lyn Penrose for typing the manuscript. REFERENCES 1.Adeyemo, O. (1974) An outbreak of arsenic poisoning in trade cattle around Calabar: a field report. Journal of the Nigerian Veterinary Medical Association. 3, 1, 31-33. 2.Bergeland, M.E., Ruth, G.R., Stack, R.L. and Emerick, R.J. (1977) Arsenic toxicosis in cattle associated with soil and water contamination from mining operations. Proceedings of the 19th annual meeting of the American Association of Veterinary Laboratory Diagnosticians, 1976. 311-316. 3.Boosinger, T.R., Riviere, J.E. and Everson, R.J. (1980) Arsenic induced haemorrhagic enterocolitis in cattle. American Association of Veterinary Laboratory Diagnosticians. 23rd Annual Proceedings 397-404. 4.Braun, R.K., Kahrs, R.F., Stoddard, H.L., Stoddard, L.G. and Edds, G.T. (1980) Lead arsenate poisoning in Florida dairy cattle. Florida Veterinary Journal. 9, 3, 32-35, 43. 5.Casteel, S.W., Bailey, E.M. Jr., Murphy, M.J., Ray, A.C. and Reagor J.C. (1986) Arsenic poisoning in Texas cattle: the implications for your practice. Veterinary Medicine. 81,11, 1045- 1049. 6.Hatch, R.C., Lark, J.D. and Jain, A.V. (1978). Use of thiosulphate for treatment of experimentally induced acute arsenite toxicosis in cattle. American Journal of Veterinary Research. 39, 9, 1411-1414. 7.Hopkirk, R.G. (1987). Arsenic poisoning in dairy cattle from naturally occurring arsenic pyrites. New Zealand Veterinary Journal. 35, 170-172. 8.Humphreys, D.J. (1980). Recent trends in animal poisoning [in UK]. Trends in veterinary pharmacology and toxicology. Proceedings of the first European congress, Zeist, September 1979. 307-313. Series: Developments in Animal and Veterinary Servicers, volume 6. 9.Knapp, F.W., Labore, D.E. and MacLean, G.J. (1977). Cattle poisoned after ingestion of ashes from wood treated with heavy metals preservative. Veterinary Medicine and Small Animal Clinician. 72, 12, 1883-1884. 10.Maitai, C.K., Kamau,J.A., Gacuhi, D.M.and Njoroge, S. (1975). An outbreak of arsenic and toxaphene poisoning in Kenyan cattle. Veterinary Record, 96, 7, 151-152. 11.Morgan, S.E., Morgan, G.L. and Edwards, W.C. (1984) Pinpointing the source of arsenic poisoning in a herd of cattle.Veterinary Medicine and Small Animal Clinician.79,12,1525-1528. 12.New Zealand, Lincoln Animal Health Laboratory. (1980) Tanalized timber poisoning [arsenic poisoning in cattle and sheep]. Surveillance, New Zealand. 7, 5, 19. 13.Osweiler, G.D. (1979).Diagnosis and management of bovine chemical toxicoses. Bovine Practitioner. 14, 155-165. 14.Reagor, J.C. (1973). Arsenic poisoning in cattle. Southwestern Veterinarian.26,4,295-296. 15.Robertson, I.D., Harms, W.E. and Ketterer, P.J. (1984) Accidental arsenical toxicity of cattle. Australian Veterinary Journal. 61, 11, 366-367. 16.Samad, M.A. and Chowdbury, A.(1984) Clinical cases of arsenic poisoning in cattle. Indian Journal of Veterinary Medicine. 4, 2, 107-108. 17.Selby, L.A., Case, A.A., Dorn, C.R. and Wagstaff, D.J. (1974). Public health hazards associated with arsenic poisoning in cattle. Journal of the American Veterinary Medical Association. 165, 11, 1010-1014. 18.Stair, E.L., Kirkpatrick, J.G. and Whitenack, D.L. (1995). Lead arsenate poisoning in a herd of beef cattle. Journal of the American VeterinaryMedical Association. 207, 3, 341-343. 19.Stubbings,D.P.,Littlejohn,A.I.and Hunt,G.E.(1973).The Danger to Livestock of Arsenical Preparations intended for the Treatment of Foot Rot. The Veterinary Record.93, 118-119. 20.Thatcher, C.D., Meldrum, J.B., Wikse, S.E. and Whittier, W.D. (1985) Arsenic toxicosis and suspected chromium toxicosis in a herd of cattle. Journal of the American Veterinary Medical Association. 187, 2, 179-182. BCVA 1997 312

CATTLE PRACTICE VOL 5 PART 4 BCVA 1997 313

CATTLE PRACTICE VOL 5 PART 4 BCVA 1997 314

CATTLE PRACTICE VOL 5 PART 4 The Economic Impact of “Husk” in Dairy Cattle Woolley H., ADAS, Woodthorne, Wergs Road, Wolverhampton, Staffs WV6 8TQ ABSTRACT The incidence of lungworm cases in the UK has increased significantly since 1990. This trend has coincided with a decline in the use of lungworm vaccine. Many of these outbreaks are in adult milking cows. The potential economical loss to dairy farmers whose herds become infected can be considerable. This paper reports the preliminary findings of a study to quantify the losses and calculate the potential economic cost of an outbreak. Two example cases representing outbreaks of mild and moderate severity have been developed. The economic losses are associated with; lost milk revenue, reduced fertility performance, treatment, veterinary costs and livestock losses. The total losses associated with the outbreaks were £4,806 or £5,679, depending on treatment programme for the example case representing mild severity and £20,354 for example case representing moderate severity. KEYWORDS: lungworm, husk, economic appraisal, dairy cows INTRODUCTION The incidence of lungworm cases in the UK has increased significantly since 1990. This increase has coincided with a decline in the use of lungworn vaccine. BCVA 1997 In 1993 there was a dramatic increase in the reported number of lungworm outbreaks compared to the previous year. Many of these outbreaks were in adult cattle something which had not been seen before. This trend of outbreaks in adult cattle has continued. A survey by Graham David, Veterinary Investigation Centre, Shrewsbury and reported to BCVA in Autumn 1996 concluded that the appearance of husk in adult cattle was due to changes in vaccination policy, climatic factors and changes in use of preventative anthelmintics. His survey showed that an outbreak of clinical husk in a dairy herd could be dramatic. The potential economic loss to dairy farmers whose herds become infected can be considerable. In addition to the direct costs of treatment and consequential discarding of milk there are indirect costs associated with reduced animal performance these include lower milk yield, poorer growth rates and reduced fertility performance. This paper reports the preliminary findings of a study which attempts to identify and quantify these losses and calculate the potential economic cost of an outbreak of lungworm in a herd of dairy cattle. METHOD The study was split in two parts. At the time of going to press only the results of the initial phase were available. In this part of the study the nature and scale of the losses which could be expected were established. This was done by discussing the results of the survey with Graham David, and following up a number of the dairy farmers and their veterinary surgeons who had experienced an outbreak of lungworm in their dairy herd. From these discussions it was possible establish the type and scale of loss associated with an outbreak. From these, two example cases were developed and the losses associated with each calculated:- 1. Outbreak confined to milking heifers – mild/moderate severity. 2. Whole herd – moderate severity. RESULTS Losses associated with an outbreak of lungworm Many of the losses associated with and outbreak are immediate, very visible and easily quantified. Others are more difficult to quantify but are never the less significant and will often continue to have an effect on profitability after the clinical symptoms of the disease have been treated. The economic losses associated with an outbreak of Husk can be split into 4 broad areas:- • loss of milk sales This occurs as a consequence of:- 1. Milk discarded following drug treatment. 315

CATTLE PRACTICE VOL 5 PART 4 2. Reduced milk output of animals affected by the disease. • reduced fertility performance This will depend on the pregnancy status of the cow when affected. For those not in calf reduced fertility performance will be seen as:- 1) An extended calving interval as a result of:- • delays in calving to first service • delays from first service to conception. 2) Increase in semen costs associated with lower pregnancy rates. For those incalf at the time of infection there is a significant risk of abortion. The losses associated with abortions are well documented and include; loss of the calf, loss of milk production, higher insemination costs, potential culling of the animal. • treatment costs These will vary depending on the severity of the case. They can be easily identified and would normally include wormers and antibiotic treatment together with veterinary time. BCVA 1997 • livestock losses Death and culling as a direct result of lungworm infections are common in herds which have been affected. An Economic Appraisal Of The Cost Of Lungworm In Milking Cattle The following example cases give an indication of the losses relative to disease severity. Disease severity parameters are based on actual outbreaks. Example Case 1 100 cow herd with an average annual yield of 7,000 litres. 20% replacement rate with annual heifer yields of 6,300 litres. 10 heifers diagnosed as having lungworm one of which subsequently dies. Heifers had not been vaccinated. Other cows in herd not clinically affected. Assumptions Treatment with single dose of a wormer which has 3 days milk withhold time. All animals were affected in early lactation at peak milk yield (Average peak yield 32 litres/day). Peak milk yield of animals affected, reduced by 40% and total lactation yield by 25%. Fertility Parameters • Prior to outbreak of husk herd average calving interval 365 days with semen use of 1.6 straws/conception. • Half of the heifers affected prior to first service resulting in a delay from calving to first service and a slight increase in semen use. • Half of the heifers affected soon after first service - all fail to conceive to this service and as a result of the outbreak. There is an increase in the number of days from first service to conception and increased semen use. Economic Parameters • Milk price 25p/litre • Quota leasing 12p/litre • Replacement cost (heifer for heifer) £900 • Cost per cow/day for extended calving interval £1.90/cow/day, excluding replacement costs and additional semen costs. • Cost of treatment £3.50/dose of wormer. Table 1 Summary Of Estimated Costs Area of Loss Heifer Treatment £ Whole Herd £ Loss of Milk 2,015 2,608 Fertility 1,133 1,133 Treatment excl. vet visits 118.00 398.00 Replacement cost 1,540 1,540 Total Loss £5,113 5,986 *If the outbreak occurs in a herd which has not vaccinated for many years then the recommendations may be to treat the whole herd with wormer as a precaution even though only the heifers showing symptoms. Table 2 Estimated Loss in Milk Revenue Loss of Milk Heifers Only Whole Herd Treatment 20 Heifers treated – withhold 1200 litres £300/treatment If whole herd treated – 1520 litres/day £1,140 2 animals clinical treated antibiotics further 4 day withhold £30.00 Lost lactation production 1575 litres x 9 lactations £3,544 Sub total £3,874 £5,014 Less quota released (-£1,859) (-£2,406) Total £2,015 £2,608 The effect of two treatment programmes have been given. One showing the effect of treating the heifers only and the other the implications if the whole herd is treated. Whilst the current quota regime exists 316

CATTLE PRACTICE VOL 5 PART 4 there is an opportunity cost to the quota released as a result of the outbreak. In this case 15,495 litres or 20,050 litres of quota (depending on treatment programme) have been ‘saved’ as a consequence of the outbreak. At the time of the study the forward leasing price was approx. 12p/litre. Table 3 Estimated Loss Due To Reduced Fertility Performance Fertility £ Increase in services/conception 2.9 for 9 heifers Semen cost £30/straw x 0.9x9 243 Extended CI by 52 days per heifer @ £1.90/day 890 Total 1,133 BCVA 1997 Table 4 Estimated Cost Of Treatment Treatment Costs Heifers Only Whole Herd Treatment* Heifer anthelmintics treatment 20 @ £3.50/cow £70.00 £70.00 2 animals treated with antibiotics £48.00 £48.00 If whole herd treated – anthelmintic £280.00 Total (excl vet visit £118.00 £398.00 Livestock Losses Heifers Only Whole Herd Treatment* 1 dead £900.00 2 culled due to Lungworm (replacement cost) £640.00 Total £1,540 Table 5 Lungworm Prevention Disease cost for Example Case 1 (Heifers only treated) Vaccination Costs £/Animal £/Total Cost of vaccination – 20 animals/year 5.50 110.00 Disease cost 48.06 4,806.00 The cost of vaccination is small compared to the potential losses which would be incurred if there was an outbreak of husk. Example Case 2 100 cow herd average 7,000 litres 20 animals bought in which introduced lungworm to the farm. The whole herd showing some level of infection. All year round calving 2 deaths, and 6 culled of which 3 were as a result of abortions. There has been no vaccination policy in the herd for many years. Assumptions Whole herd treated with wormer requiring 3 day withhold time, two doses required as animals not transferred to clean pasture. Average daily yield 19 litres per day Average estimated loss of yield at time of infection 30% and 10% loss of lactation yield across herd. Fertility Parameters • Prior to outbreak of husk herd average calving interval 365 days with semen use of 1.6 straws/conception. Economic Parameters • Milk price 25p/litre • Quota leasing price 12p/litre • Replacement animal £900/animal • Cull value £480 • Cost per cow per day per extended calving interval £1.90/cow/day. Table 6 Summary Of Estimated Loss Area of Loss Heifer Treatment Loss of Milk £12,166 Fertility £3,180 Treatment excl. vet visits £888.00 Replacement cost £4120 Total £20,354 Table 7 Estimated Loss In Milk Revenue Loss of Milk £ Rejected Milk - 1st treatment - 120 cows £1,170 Rejected milk - 2nd treatment £1,170 2 animals antibiotics £30.00 Lost lactation production 700 litres x 120 lactations £21,000 Sub total £23,370 (Less quota released 93360 litres @ 12p) (-£11203.20) Total £12,166 Table 8 Estimated Loss Due To Reduction In Fertility Performance Fertility £ Increase in services/conception 1.6 to 1.9 900.00 Extended CI by 10 days @ £1.90/cow/day 2,280 Total 3,180 Table 9 Estimated Cost Of Treatment Treatment Costs £ Herd treatment 120@ £3.50/cow x 2 treatments £840.00 2 animals antibiotics £48.00 Total (excl vet visits) £888.00 Table 10 Estimated Livestock Losses Livestock Losses 2 dead £1,600 6 culled due to Lungworm (replacement cost £420/animal) 3 Abortions - loss of calf value @ £120/calf £2520 £360.00 Total £4120 317

CATTLE PRACTICE VOL 5 PART 4 Table 11 Lungworm Vaccination Costs For Example Case 2 BCVA 1997 Vaccination Costs £/Animal £/Total Initial Cost - 120 cows 5.50 660.00 Annual Cost - 24 replacement animals/year 5.50 132.00 Disease outbreak - moderate 169.80 20,354 CONCLUSION These case studies show that the losses associated with an outbreak of lungworm in a milking herd can be considerable. In addition to the actual cost an outbreak of lungworm is depressing for those working with the stock, disrupts the routine and causes unnecessary suffering to the animals. Since the economic appraisal was completed milk prices, quota and feed costs have fallen. The profitability of dairy farms has fallen as a result and whilst the actual cost of an outbreak may be lower due to the fall in prices the impact on bottom line profits will be greater. ACKNOWLEDGEMENTS The author would like to thank all the dairy farmers and veterinary surgeons who have participated in this project. REFERENCES: ADAS Milk Cheque UK Annual Report 1996. Andrew T., (1994) Where cattle safely graze. Farmers Weekly 28 January, Reeds Publishing Press Ansell, D.J., (1998). Research into Bovine Parasitic Bronchitis an Economic Appraisal. CAS, University of Reading Publication. Blowey, R.W., (1990). A veterinary book for dairy farmers.. Farming Press Books. David, G., (1997) Personal Communication. Nix, J., (1996). Farm Management Pocketbook 27. London Wye College Press. Poynter, D., Peacock, R., Menear, H.C., (1970) The Prevention and Treatment of Husk. The Veterinary Record 86: 148-160. Williams, J.C., (1995) Endoparasites of cattle: diagnosis and assessment of infection and prevention nd control from now to the foreseeable future. The Bovine Proceedings 27: 21-30. 318

CATTLE PRACTICE VOL 5 PART 4 Persistance of Immunity after Vaccination with Huskvac in Ivermectin Bolus Treated Calves Mawhinney I.C.. Intervet UK Ltd, Science Park, Cambridge CB4 4FP. ABSTRACT Immunity to lungworm recedes from 6-12 months after challenge or vaccination. The use of long-acting wormers have been suggested as making first season vaccinaton redundant because the anthelmintic can outlast the immunity. This study indicates that there is a suppression of natural boosting effect during the period of anthelmintic activity of over 130 days, but at this time immunity is still measurable in vaccinated calves. A low level of exposure at the end of the grazing season, after expiry of the anthelmintic bolus, boosted this immunity compared to unvaccinated calves. The conclusion is that whilst use of a long acting wormer probably has a detrimental effect on immunity boosting in the first season and therefore may reduce the benefit of vaccination, vaccinated animals have a stronger immune status to respond to challenge at the end of the first season, and therefore better placed for the beginning of the second season, than unvaccinated animals using the same worming regime. This confirms the advisability of continuing first season vaccination regardless of the worming system used. INTRODUCTION The duration of immunity to lungworm in the absence of field boosting is believed to be solid for at least 3 months but protection has declined at 6 months and only the immune memory probably remains at 12 months, ( Michel and others 1965, and Taylor and others 1990). The use of vaccination to induce immunity has declined in recent years as recommendations for use of anthelmintics have changed. There has been doubt expressed in some circles over the viability or benefit of the traditional policy of vaccinating prior to first year turnout, if a long acting bolus is used, since the immunity from vaccination may have largely expired before the anthelmintic has, thus leaving the calf to rely on natural exposure for immunity, and negating the benefit of vaccination. The manufacturers of avermectin and long-acting benzimidazole compounds recommend the use of vaccination for animals requiring immunity, especially those expected to experience more than 1 season on pasture eg all replacement heifers, or traditionally grass reared beef. The purpose of this study was to examine how immunity to lungworm evolves in the first season at pasture, as measured by serological profile, in 2 groups of calves exposed to normal pasture contamination, and any advantage that exists from practising traditional 1st season vaccination when long acting wormers are used. MATERIALS AND METHODS Two farms on the Devon/ Cornwall border had been previously involved in assessing the effect of vaccination after the first season at grass. In the next year they made available naive calves for the purpose of this survey. Calves on each farm were randomly allocated to 2 groups, one group was vaccinated and the other left unvaccinated prior to first season turnout. Both groups were run together and managed identically per farm. All calves were wormed with a commercially available ivermectin bolus according to the farm’s normal policy. On farm 1 this was 1 month after turnout, on farm 2 this was on the day of turnout. It was expected that on farm 1 some worm exposure would occur prior to worming possibly stimulating immunity and the period after expiration of the wormer and before housing would be reduced. Exposure to pasture Dictyocaulus was entirely natural; there was no seeding of pastures. Blood samples were taken at strategic times, namely post vaccination (at turnout), at bolusing, at the expected time of bolus expiration (approximately 130 days later) and at subsequent housing. Housing occurred one month after the 130 days on Farm 1 and very late (5 mths) after the 130 days on farm 2. 10 calves from each group were monitored serologically throughout. Unvaccinated calves were assigned negative titres prior to turnout. Serology results for adult and L4 antigen were measured by ELISA as previously described. Statistics were calculated using a t-test. RESULTS Serology ranges for L4 are shown in table 1, and graphically for each farm in figures 1 and 2 BCVA 1997 319

CATTLE PRACTICE VOL 5 PART 4 Table 1 Averages and Ranges of L4 titres in calves Turnout Bolusing ~130d Housing Farm1 vacc 6.2 (2-9) 4.9 (2-8) 2.5(1-6) 5.4 (1-9) Farm1 unvacc 1 1 (1) 1.1(1-2) 3.9 (1-7) Farm2 vacc 7.4 (7-8) at turnout 2.9 (1-7) 4.3 (2-6) Farm2 unvacc 1 “ 1.2 (1-2) 3.2 (2-6) total vacc 6.8 2.7 4.9 total unvacc 1 1.2 * 3.6 *p < 0.05 vaccinated vs unvaccinated. Table 2 Averages and Ranges of Adult titres in calves Turnout Bolusing ~130d Housing Farm1 vacc 5 (2-9) 3.5 (1-7)* 1.9 (1-4) 3.1 (1-6) Farm1 unvacc 1 1 (1) 1.3 (1-2) 2.1 (1-5) Farm2 vacc 6.5 (5-8) at turnout 2.8 (1-6) 2.4 (2-4) Farm2 unvacc 1 “ 1.2 (1-2)* 1.7 (1-2)* total vacc 5.8 2.4 2.8 total unvacc 1 1.3 1.9 # * p< 0.05 vaccinated vs unvaccinated. #p =0.06 On both farms normal responses to vaccination were recorded at the time of turnout. On farm 1 , there is no rise in titre by the time of bolusing 1 month post turnout, despite some of the unvaccinated calves developing a cough which was not specifically diagnosed. No apparent immunity stimulation took place during this first month of turnout. Titres in both groups decline during the bolus period suggesting no L4 or adult Dictyocaulus immunity boosting occurred. At the time of 130 days there are still detectable titres in most of the vaccinated calves. No titres have developed in unvaccinated calves. At the time of housing 1 month later, low titres are present in unvaccinated calves and higher titres are present in vaccinated calves. There was highly significant difference between titres at time of bolusing between vaccinates and non vaccinates. Titres at 130 days approached significance for L4 but not adults. On farm 2 the same trends were seen but with significant differences at 130 days for both L4 and adult. The overall results of both farms gives greater numbers for comparison and show a very significant difference in titres for L4 and adult at 130 days post bolusing, and still approaches significance at housing. The period from 130 days to housing on farm 2 was a very long 5 months, housing not occurring until February. Despite this long period on pasture at the end of the season, titres at housing were relatively low and for adult antigen significantly different between vaccinates and nonvaccinates, with none of the unvaccinated animals having more than borderline adult titres. L4 titres followed a similar pattern. This suggests that little lungworm challenge had occurred during this long end-of-season period on pasture. Fig 1 Bolusing was 1 month after turnout. Farm 1 Average L4 Titres Average L4 Titres 0 1 2 3 4 5 6 7 Jan-96 Feb-96 Mar-96 Apr-96 May-96 23/06/96 27/06/96 Jul-96 Aug-96 01/09/96 24/10/96 28/11/96 Dec-96 Date Titre Vaccinates Non-Vaccinates Fig 2 Bolusing was at time of turnout Farm 2 Average L4 Titres Average L4 Titres 0 1 2 3 4 5 6 7 8 Jan-96 Feb-96 Mar-96 25/04/96 May-96 Jun-96 Jul-96 Aug-96 05/09/96 Oct-96 Nov-96 Dec-96 Jan-97 13/02/97 Date Titre Vaccinates Non-Vaccinates BCVA 1997 320

CATTLE PRACTICE VOL 5 PART 4 DISCUSSION The presence of residual immunity from vaccination at 130 days post bolusing is not unexpected in the light of previous work, particularly that of Fisher and Jacobs 1995, which showed that vaccination prior to use of a 3,8,13 or pulse-release bolus gave protection against end of season lungworm challenge where unvaccinated animals on the same anthelmintic treatments were not immune and not protected at the end of the season. The serology indicates exposure occured on these farms after the bolus expired, producing a degree of immunity at housing I month later, although serology suggests that this exposure was not great. The titres are higher in the vaccinated group. There is evidence that these animals are more consistently immune at housing and therefore, since immunity declines over housing at nearly 1 level per month, the vaccinated calves will have more residual immunity at turnout for season 2. No unbolused group existed to act as a control so it is not possible to say if or what degree of impairment by the anthelmintic to any boosting of immunity by natural exposure had occured. However it strongly suggests that calves vaccinated prior to bolusing are in a better position to respond to natural exposure boosting than unvaccinated calves at the end of season and are housed with more immunity than unvaccinated calves, presumably meaning there is a greater chance of them having immunity at the time of second season turnout. It also indicates that delaying use of a bolus after turnout is no guarantee of creating an immunising natural exposure. The possibility of natural challenge at the beginning and end of the season is dependant on grazing rotation policy and the weather. The survey results support the policy of continued use of vaccination prior to 1st season turnout regardless of worming policy used. The degree of exposure at the end of the season and the likelihood of use of anthelmintic on second season turnout are factors which determine the possible benefit of a booster prior to second season turnout. ACKNOWLEDGEMENTS. Special thanks to Tim Bebbington MRCVS at Castle Vet Group, Launceston, for identifying farms for the survey and carrying out all the blood sampling. Thanks to Jayne Bennett and Nicky Reynolds of Intervet UK Ltd for performing ELISA tests and compiling the results respectively. REFERENCES G David Cattle Practice, Oct 1996 CVL VIDA III,1995 J F Michel and A Mackenzie Res vet Sci, 1965, 6, 344. S M Taylor, T R Mallon, W P Green, Vet Rec, 1990, 126,185 MA Fisher and D E Jacobs Vet Rec 1995, 137, 581-585. BCVA 1997 321