Infectious Skin Diseases of Cattle

Symposium on Large Animal Dermatology

Infectious Skin Diseases of Cattle

Elaine Hunt, D.V.M.*

DERMATOPHYTOSIS (RINGWORM) The pathogenic cutaneous fungi are capable of enzymatic degradation of nonliving fully keratinized tissues; in cattle, the structures affected are limited to the hair and stratum corneum of the skin. 25,43 The most prevalent etiologic agents in cattle are Trichophyton mentagrophytes and the most common isolate, T , verrucosum, Although rarely identified as a major cause of economic losses in this country, considerable damage to the hide can be caused by the infection, This only becomes apparent after tanning is completed; the value of the hide can be considerably compromised ,26 The unsightly plaques can be a severe problem in intensively reared or in housed cattle during the winter months. Ringworm may be of utmost importance in purebred cattle when its presence precludes the show, sale, or exportation of animals. Humans can contract Trichophyton spp. , so the infection is of public health significance as well.

Clinical Signs Ringworm infections are common in confined cattle; calve s between 2 and 7 months of age are most susceptible to new infection. 53 They are generally hairless, noninflammatory, circular, nonpruritic, gray ("asbestos-like") lesions that occur diffusely on the head, neck, trunk, and occasionally the limbs. 5 ,57 If the crust-like le sions are pulled away, bleeding often occurs. These lesions may persist for 5 to 9 months. Curiously, an age and sexual variation is noted in the location of the lesions . In animals under 12 months of age, there is no difference between sexes in distribution of the lesions; rather, generalized distribution is most common, especially around the eyes, ears, and back. Lesions around the eyes are seen most commonly in calves (Fig. lA); limbs and thorax are more commonly affected in cows and heifers. Bulls over 12 months of age develop characteristic lesions most frequently *Diplomate, American College of Veterinary Internal Medicine; Assistant Professor, Department of Medicine, North Carolina State University School of Veterinary Medicine , Raleigh, North Carolina

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Figure 1. A, Calves between 2 and 7 months of age are most susceptible to ringworm infections, which may persist for 5 to 9 months. The hairless, noninflammatory, non pruritic, and circular lesions appear most often around the eyes and ears. 8, In adult cattle, ringworm lesions tend to cause a folliculitis that may not manifest as typical, circular, asbestos-like lesions. These lesions (on the brisket of a mature cow) could also have been caused by mites or a bacterial pathogen.

on the dewlap, intermaxillary area, and buttocks (Fig. IB) . These variations are probably due to differences in ethology, especially in fighting and licking habits. Lesions are spread randomly and do not develop in a centrifugal manner from one primary lesion. 57 No reinfection occurs in cured animals. 53 Diagnosis Although most diagnoses are determined on the basis of clinical signs, direct examination of specimens and dermatophyte cultures are also used. Neither T. verrucosum nor T. mentagrophytes fluoresces under ultraviolet light. Lesions can be scraped with a scalpel, and the material collected on a microscope slide. One drop of a 10 to 40 per cent solution of potassium hydroxide is added, and the slide is lightly waved before a flame to dissolve the lipids in the sample. Large numbers of spherical spores should be seen around the base of hairs pulled or scraped from the margin of the lesions. These arthrospores should always appear outside the hair shaft, rather than within. Scrapings or hair remnants from the periphery of the lesion can be cultured on a medium that will inhibit bacterial growth. Among such media are Sabouraud's dextrose agar (the acid pH inhibits bacteria), CC medium (a similar agar that also contains cycloheximide and chloramphenicol to in-

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hibit bacteria and nonpathogenic fungi), and dermatophyte test medium which provides a useful means of separating saprophytes from pathogenic dermatophytes. Dermatophyte test medium couples colony color, pH changes in the medium (when the phenol red indicator in the medium changes color to red, usually a dermatophyte is present), and a relative time of color change. Other commercial agar preparations are also available for the practitioner who prefers to culture and identify microbes in his own laboratory. Microscopic examination of the colonies cultured should show rare macroconidia, numerous microconidia, and arthrospores external to the hair shaft. None of the standard hematologic or blood chemistry tests have been reported to alter in cattle with ringworm infection. However, specific inhibition of blood leukocyte migration has been detected 4 to 5 weeks after infection, and this persists for approximately 5 months. 68 As the infection resolves, humoral and cell-mediated immunity develops, presumably protecting the animal for life.?-s Epizootiology As mentioned previously, intensive rearing, lack of sunlight, and age are primary factors contributing to the spread of ringworm in cattle. The fungus is capable of surviving for months, even though cattle have been removed from the premises. Soil, straw, wood, and dung are all potential reservoirs of the fungi. 14 Asymptomatic carriers may also playa role in the spread of the disease. 5 Latent carriers may be the most important means of spreading the infection among cattle. Insects have also been incriminated in the spread of the disease. 11 An exposed animal will incubate the infection for 1 to 4 weeks, after which the hair begins to fall out or break off and a round, scabby lesion develops. 25 Management Therapeutic modes are often limited in cattle because large numbers of animals are frequently involved. Topical solutions or ointments applied to individual lesions require time to administer, involve application almost on a daily basis, necessitate thorough debriding of the lesion sites, and are rapidly licked off by cattle. In fact, topical application of an ammoniated mercurial compound formulated for human ringworm therapy resulted in mercury toxicity and death of several valuable animals that ingested the medication over a period of several weeks. 31 Nevertheless, topical therapy still remains popular and is the most cost-effective mode of therapy if fewer than five animals are involved. Thiabendazole (3.75 per cent in glycerine) has been reported to be efficacious when applied topically at 3-day intervals for a total of four applications. Recrudescence was not a problem. 56 A single application of a 5 per cent solution of thiabendazole has also been reported to be successful in 80 per cent of cattle treated. 25 A tolnaftate topical preparation has also been reported to be successful in resolving infections within 7 to 10 days. 27 Application of a 5 per cent tincture of iodine reportedly cures only 50 per cent of affected animals when used at 3-day intervals over a 12day period. 56 Chlorine bleach, tamed iodine, lime sulfur, and copper naphthenate are all reported to have little efficacy against dermatophytosis. s

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Application of sprays appears to be the most practical means of resolving fungal infection in large numbers of animals. Imidazole derivatives (2000 ppm) sprayed on a weekly basis for 4 weeks (or twice weekly for 2 weeks) resulted in a very high cure rate: 92% recovery was claimed within the first 2 weeks. 35 Initial spraying involved the entire body of each animal; subsequent sprays were directed at the individual lesions. This compound is an active antifungal in the vapor phase and may provide a means of eliminating infection from environments where the organism persists from year to year. The one disadvantage to this therapy is the recommendation that scabs be removed with a sponge or brush prior to the first treatment. The solution can also be applied topically if spray equipment is not available. 17 Regrettably, this product is not yet available for use on American livestock. A 0.1 per cent natamycin spray has also been effective in ringworm therapy and prophylaxis. This agent is inactivated in sunlight, so spraying must be done inside or in the evening. Heavy metals also inactivate the fungicide , so galvanized or plastic containers must be used to contain the material. 52 The spray is not irritating to the bovine eyes, leaves no tissue residues, and is reported to have no toxic effects. 26 About 1 L should be sprayed on each animal; two treatments at 3-day intervals is effective. 52 Twoto five-month-old calves will be cured of infection in 7 to 8 weeks; sevento twelve-month-old calves will often be free of infection in 4 weeks. 53 This drug is not yet available in the United States as a spray for use on livestock. Systemic therapy is also possible in the individual animal. Intravenous administration of 10 to 15 ml of sodium iodide in 100 to 200 ml of saline solution has been reported to be effective. S Oral administration of ultrafine (particle size) griseofulvin has been successful in shortening the length of infection. 6 Griseofulvin feed supplements are available in Great Britain. A 91 per cent cure was reported when a 2 per cent griseofulVin feed supplement was administered orally at 10 mg per kg for 7 days.25 A 100 per cent cure rate was reported when this therapy was extended from 18 to 30 days at 15 to 35 mg per kg. However, unless the premix becomes available in this country, daily oral administration of this drug will remain too time-consuming to be practical when many animals are involved. Currently, the drug is also too expensive to be utilized on a large scale, and it cannot be used in pregnant cattle because it causes fetal anomalies. 52 In addition, griseofulvin is fungistatic and does not kill spores in the environment or on the affected animal. Although lesions may regress on treated animals, T. verrucosum can still be cultured from 80 per cent of these cattle for up to 2 months following therapy. Only 10 per cent of cattle treated with natamycin spray will continue to harbor infective organisms for this period of time. 25 Immunization Although not currently marketed in this country, an efficacious vaccine has been developed in Russia and tested extensively in Europe. This vaccine is reported to be so successful that I am hopeful that the vaccine will ultimately be utilized in this country. In anticipation of this, the following information about the vaccine is provided. Over a 3-year period, more than 250,000 Norwegian cattle were inoculated with LTF 130, a live vaccine from an apathogenic strain of T. ver-

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rucosum. The suggested use of this product includes vaccination of all breeding stock in newly affected herds, all calves (including neonates) in infected herds, and all breeding animals sold or purchased. Two injections are administered 10 to 14 days apart; pregnant cattle are not vaccinated past the seventh month of gestation. I The prophylactic success of the vaccine was reported to approximate 100 per cent. Subclinical cases that were vaccinated while incubating T. verrucosum experienced clinical ringworm rapidly following vaccination but recovered more quickly than field cases. 2 Where neonatal infection is a problem, vaccination has been utilized at 4 to 6 days of age and for 12 days thereafter. Calves are kept isolated from older animals during this time; protection is confirmed at 4 weeks after the initial injection. 49 The Norwegian studies found that use of the vaccine was contraindicated in animals already displaying lesions. About 50 per cent of animals with obvious ringworm lesions reacted to vaccination with acute outbreaks of ringworm that involved large segments of skin and did not heal for an extended period of time. Other side effects of the vaccination program were minimal. Restlessness, dyspnea, and possibly diarrhea were detected in a few calves after vaccination . Pharyngeal edema, or anaphylaxis, or both, caused death in four calves. A few animals occasionally experienced a mild febrile response. Muscle tenderness and lameness was also recorded in a few animals; one abortion was also noted. I All in all, side effects were minimal and well-documented studies are very supportive of the vaccination program. DERMATOPHILOSIS Dermatophilosis (also called cutaneous streptothricosis) is an unsightly seasonal dermatitis occurring in North American cattle exposed to prolonged periods of moist weather. The causative agent is the aerobic actinomycete Dermatophilus congolensis, a gram-positive, filamentous bacterium of the epidermis. The time of the year during which infections are most prevalent varies with the regional rainfall. For example, cattle in northern California might experience most severe cases in the wet winter months, whereas cattle in Mississippi might develop infections during the spring and summer months. Stress may also be an important factor, since Midwestern cattle have been found to develop clinical disease in the winter months, presumably following asymptomatic infection that occurred in the warm, wet months of summer. 29 Affected cattle usually experience a chronic proliferative and exudative dermatitis that is followed by the formation of a crust or scab. If seen very early in the course of the disease, small vesicles, papules, or pustules may be noted. The more typical lesions are confluent areas of scabs or crust that surround the hair, adhering to it and giving a matted appearance. The scabs may thicken and even appear horn-like; the hair beneath these scabs tends to break when the scab or hair is pulled. When moist scabs are detached, a raw, denuded, shallow, weeping lesion is exposed beneath the crust. If healing has begun, removal of the scab may simply reveal a soft, pink scar. Classically, the hairs appear to have grown right through the scabs . The

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lesions may be very small or may coalesce to cover large areas of the animal's body. These lesions may be distributed along the dorsal midline from neck to tailhead, extending down the sides of the abdomen, flanks, and perineum, especially when precipitation is the major cause of environmental moisture. The disease may be localized to the extremities and scrotum, where standing water is a chronic source of moisture. When cattle are grazing tall, moist forage, the muzzle is frequently involved. Concurrent ringworm infection may contribute to the severity of or may actually mask the presence of dermatophilus infection. 29.39 Mild cases may not affect the animal's health, but severe hide damage, emaciation, debilitation, and death is possible in animals if generalized cutaneous infection leads to extensive secondary bacterial complications. Various sex, age, and breed predilections for the disease have been reported in countries in the southern hemisphere. Not all of these claims have been substantiated in North American cattle, but it may be useful to mention them at this time. Greatest susceptibility is reported in animals of 6 to 18 months of age. 5 Native West African Zebu cattle are reported to be more resistant than long-haired European breeds. 29 Males are reported to be more susceptible to infection than females. 40 Reproductive performance has been noted to decline in cows with severe generalized infection. It is unknown whether this is due to the debilitating effects of the disease or if the generalized D. congolensis develops only in the already debilitated animal. A second effect of the infection upon reproductive performance of the animal may be manifest when severe, localized, perineal infection interferes with mating, a problem noted in African cattle but unmentioned in the American literature. 51 Although many bulls are affected with unsightly scrotal streptothricosis, there appears to be no correlation between the severity of infection and abnormal spermatogenesis, testicular degeneration, or inflammation. The slight increase in scrotal thickening caused by localization of the bacterium apparently does not affect scrotal thermoregulatory function. 37 In addition to its association with chronic debilitation, emaciation, hide damage, and possible reproductive impairment in the severely affected cow, dermatophilosis has been shown in warm , moist climates to contribute to fly strike involving at least one species of fly. The presence of secondary bacterial infection increased the attractiveness of the lesion to the fly, but the moistened dermatophilus lesion alone was capable of providing the protein necessary for larval development. 24 Pathogenesis Normal healthy skin is thought to be refractory to infection by D. congolensis. 29 Breaks in the rain-softened skin may allow entry of the infective stage of the bacterium, but infection can occur regardless of the absolute thickness of the cornified layer and without the presence of detectable subcellular skin fissures. 4 1 Following penetration , proliferation of the mycelium occurs deep within the living epidermis. Epidermal hyperkeratosis results, inadvertently providing protection for the maturing mycelium. The epidermis separates from the dermis owing to the formation of a purulent exudate. 29 Regeneration of

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the epidermis continues, but reinfection occurs from hyphae that spread outward from the infected hair follicles. The scabs are formed by a collection of alternate layers of exudate and sheets of cornified epidermis. In the cornifying epidermis, the developing mycelium fills with packets of zoospores that are ultimately released upon wetting of the contaminated scabs. 40 Thus, clinging scabs may serve as a source of infection, even when arid conditions result in spontaneous recovery. Another site for harboring infection may be the small, chronic lesions that persist in the ears of cattle during periods of arid weather. 29 Transmission may be through biting arthropods or by direct contact from animal to animal. Following heavy rainfall, abrasion, maceration, or blunt trauma to the skin, infection can easily be established during the next 24 hours . After this time , resistance to infection is noted, regardless of the degree of skin damage sustained. This may be due to the hardening of freshly secreted sebum in the infundibula of the hair follicl es and also in the interfollicular region. 29.41 Malnutrition and concurrent disease may also contribute to infection, yet humidity and environmental temperature alone appear to have no effect on the natural resistance of the animal. 41 Serum magnesium , zinc, calcium, potassium, and copper levels are not lowered in infected calves, so nutritional deficits of these minerals are not likely primary causes of this condition. 22 Attempts to reproduce the disease experim entally have failed to produce generalized lesions similar to those in natural field cases; only localized lesions have been created.·3 Recent studies have demonstrated that concurrent infection with ort virus and D. congolensis was successful in experimentally creating the ovine disease "strawberry foot rot," an infective process similar to generalized bovine dermatophilosis. 3 It has been suggested from this information that D . congolensis acts synergistically with a second agent (bacterium, virus, parasite, or fungus ) to produce the severe generalized skin lesions of naturally occurring dermatophilosis. Both immediate and delayed cell-mediated hypersensitivity appear to playa role in the pathogenesis of dermatophilosis. Previous infection with D. congolensis does not protect against reinfection. 3 However, healing appears to occur more rapidly after reinfection , so some transitory resistance may be conferred by infection. Great individual variability in susceptibility exists in previously unexposed cattle challenged similarly with D . congolensis, and genetic selection for more resistant animals may be important in future control of the infection. 41 Diagnosis Although the appearance of the lesion is generally specific enough for definitive diagnosis, direct microscopic examination of smears made from the ventral portion of scabs and crusts can be completed using Giemsa, Wright's or methylene blue stains. Gram-positive branching filaments containing ovoid bodies (which then appear "beaded") should be noted. When exposed to water, the septa will form motile zoospores. Indeed, allowing the specimen to sporulate in sterile distilled water for 31.;,; hours and culturing loopfuls of the water may enhance the retrieval of the organism from contaminated scabs, while preventing the overgrowth of more rapidly growing secondary bacteria. Ifbacterial culture is necessary, cultivation with enriched

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media (blood agar) will result in the formation of pigmented, often hemolytic colonies adherent to the agar. Brain-heart infusion agar may also be utilized. 29 If culture techniques are unsuccessful, often it is because either an old lesion was sampled, or the scabs dried, or only a superficial area was cultured. There are various serologic tests for Dermatophilus. The single radial immunodiffusion technique is a sensitive method of identifying existing antibodies in animals previously affected with D. congolensis. Its value as a rapid diagnostic test is uncertain , since it requires 12 to 18 hours to complete and its success in identifYing early clinical cases has not been reported .44 An enzyme-linked immunosorbent assay (ELISA) test has also been developed recently. Many subclinical infections were detected with the ELISA technique, even in cattle maintained in filVorable conditions, and the existence of subclinical reservoirs was suggested upon the basis of this study. 39 Whether this diagnostic tool will develop into a field test remains to be seen. Other laboratory techniques (such as fluorescent antibody and agar gel precipitation) are of academic rather than diagnostic interest. 29 Histopathologic examination may demonstrate edema, congestion, massive leukocyte infiltration of the dermis and epidermis, and filamentous forms of D. congolensis throughout. Proliferative changes such as parakeratosis and hyperkeratosis may also be noted. 29 Three times as many capillaries and venules may be evident in the upper dermis as would be expected in normal dermis; these appear dilated and engorged with red cells and leukocytes. 4 The differential diagnosis may include fungal infections (especially Trichophyton spp.) and ectoparasite infestation (including mites). Some of the viral skin diseases may occasionally resemble D. congolensis infection. 29 It has been my experience that "atypical warts" (papillomas) on the limbs may resemble streptothricosis and that D . congolensis may even be a secondary opportunistic infection in these lesions . Management Topical preparations are not very useful in field conditions involving multiple animals, particularly considering the tendency of the bovine to lick itself or other animals, so systemic therapy is presently the most popular mode of treatment. In vitro studies with one strain of D. congolensis found that broad-spectrum antimicrobials (penicillin, tetracycline, oxytetracycline, bacitracin) were most efficacious against the organism , while methicillin, novobiocin, nalidixic acid, furazolidone , and many of the sulfonamides had no inhibitory action. 50 A single, large systemic dose of penicillin (70,000 IU per kg body weight) has been endorsed by writers in the northern hemisphere, but this therapy was unsuccessful in alleviating infection or preventing relapse in severely affected animals in African studies. 23 , 29.30,4[) In one author's experience, five injections (one every 24 hours for 5 days) of penicillin (5000 IU per kg) and dihydrostreptomycin (5 mg per kg) are effective. 4o This therapy is not practical if large numbers of animals or intractable cattle are involved. 40 A single injection of long-acting oxytetracycline (20 mg per kg) is not very successful in controlling dermatophilosis. 23 In isolated cases, protecting the affected animals from the source of moisture is advisable. Concurrent use of steroids is said to increase the

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severity of the lesions . 3 Since lowered serum sodium values have been noted in some affected cattle, access to salt may be advisable. The addition of zinc to the diet neither increases recovery rates nor improves the degree of recovery. 23 There is still no successful means of preventing streptothricosis in this country. When small numbers of animals are at risk, housing during wet weather conditions may be advisable, but this is impractical for most commercial operations. If the moist weather conditions coincide with peak fly seasons, it is advisable to control biting vectors, including ticks. 29 . 37 If dips are used for vector control, they must be frequently discarded and the dipping vats kept scrupulously cleaned to prevent contamination of other animals. The quaternary ammonium compounds (when added to the dip at a maximim of 0.5 mg per L) can help prevent contamination of the dip with D. congolensis. If the gamma-isomer of benzene hexachloride is used as a parasiticide dip, it has an inhibitory effect upon D. congolensis, so the addition of quaternary ammonium to the dip is unnecessary. 29 Where streptothricosis is a problem in neonates (in which it can be devastating) , proper colostrum intake must be assured, since D. congolensis antibodies have been detected in milk. 45 Experimental vaccines have been developed, but none has yet proved to be satisfactory. An intradermal vaccine presently shows greatest promise. 4o •4 1 Some of the vaccines under development have caused severe lesions at the site of inoculation; others have resulted in scab formation or persistent pea-size swellings. 29.41 Prolonged contact with sheep or horses affected with dermatophilus has resulted in infection in humans. These infections are generally self-limiting and are considered only mildly significant. 29

FIBROPAPILLOMATOSIS AND PAPILLOMATOSIS Bovine papilloma virus (BPV) is the etiologic agent that induces formation of fibropapillomas or "warts," the benign, hairless tumors of the skin that occasionally affect the cornea, mucosa of the genitalia, udder, teats , alimentary tract, or urinary bladder. Additionally, a strain of this virus is also thought to cause the less common bovine papillomas, or so-called "atypical warts," that may affect the neck, body, limbs, and feet of adult cattle. At least four of the five identified strains of BPV are antigenically similar but lack immunologic cross-reactivity and are distinctly different from papilloma viruses of other species. 13 •6o Each of the five strains of BPV usually causes lesions with a specific histologic and/or morphologic gross appearance and a fairly specific site of predilection. 13 Early in vitro virus cultivation systems were not highly successful, so study of the virus and subsequent development of a highly efficacious vaccine was inhibited. The existence of multiple strains of virus that demonstrated no immunologic cross-reactivity surely contributed to some commercial vaccine failures. 60 Recently, studies linked BPV with carcinoma of the eye, bladder, and alimentary tract in cattle, a factor that has stirred greater interest in the medical profession than in the veterinary profession. 12•21 ,32,38 This renewed interest, coupled with improved techniques in the field of molecular biology, has resulted in a

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dramatic increase in studies of BPV It is hoped that information derived from these studies will result in the production of a more successful multivalent papilloma and fibropapilloma vaccine.

Clinical Signs Bovine fibropapillomas and papillomas are often self-limiting infections of young cattle under 18 months of age that generally regress within 1 to 12 months. 7 These growths are commonly slate-colored, firm, hairless, protruding masses with a dry, often horny surface. Varying from 1 mm to several centimeters in diameter, they may be coarse, cauliflower-like, broad-based lesions or may exhibit a narrowed or pedunculated area of attachment to the underlying epidermis. They may be single growths, or hundreds may be present. Cutaneous sites of predilection include the face, head, neck, dewlap, and occasionally the eyelids or teats. 34 Various strains of the virus result in lesion localization in different anatomic sites. The tumor types seen most commonly in the United States are caused by BPV-5, BPV-2, BPV-l, and the as yet unidentified ocular fibropapilloma virus. Teat or udder lesions that are white, smooth, elongated nodules-so-called rice grain papillomas-are caused by BPV-5, a virus predisposed to affecting cutaneous stratified epithelium. 38 These lesions will not cause problems unless complicated by bacterial or other viral infections. If the lesions appear filamentous or frond-like and are present on the nose or teats of either sex or upon the glans penis of the male, BPV-l has been incriminated as the causative agent. 13 Fibropapillomas present on the glans penis may interfere with breeding, are transmitted through coitus, and are often difficult to remove surgically owing to their extreme vascularity and the presence of very fibrous connective tissue elements within the growths. 34 The common fibropapilloma present upon the head and neck is caused by the virus identified as BPV-2.13 These raised, pedunculated masses generally do not recur after regressing. 7 Occasionally, an animal naturally infected with fibropapillomas will suffer extensive generalized tumor development, especially in the regions of the head, neck, shoulders, dewlap, and brisket. These lesions persist for months and show no evidence of tumor regression . 38 In one such instance, interference with normal cell-mediated immunity was detected . IR BPV-4 has been recovered from the warts present in the alimentary tract and the urinary bladder. 21 .32.66 Since an estimated 20 per cent incidence of the alimentary papillomas has been recorded in the United Kingdom , the tendency of these tumors to undergo metastatic transformation is very significant in that country.32 Papillomas of the urinary bladder have been associated with enzootic hematuria and also with concurrent transitional cell carcinoma. 38 Ocular papillomas are variable in appearance: Some are long, frondlike, branching growths attached to the eyelid or corneoscleral junction by a small base, while others may appear as rounded protuberances with a large area of attachment to the ophthalmic structures. 66 Spontaneous regression may occur in 25 to 50 per cent of these ocular papillomas, but many give rise to squamous cell carcinomas. Although BPV has not yet been recovered from these proliferative ocular lesions, virions resembling those of papilloma

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viruses have been detected in some of these papillomas. This incidence has been construed to indicate that BPV was present in the original fibropapillomas and therefore contributes to formation of the lesions which may, in the presence of sunlight or other carcinogens, develop into ocular squamous cell carcinomas. 21 Considering the importance of this tumor to the cattle industry, a vaccine capable of preventing formation of ocular fibropapillomas, which might otherwise undergo malignant transformation to squamous cell carcinoma, would be an obvious asset to livestock production, particularly in the southern and western states. BPV-3 is the virus type identified with "atypical warts," nonpedunculated, flat, circular, growths that do not protrude from the skin surface as prominently as regular warts. These neoplasms, induced from cutaneous stratified epithelium, are not horny in appearance but are delicate and frondlike, often with hair growing between the fronds. 7.3H These warts may coalesce to cover such large areas of skin that excision is impossible. Herd outbreaks of atypical warts can occur and affect large numbers of animals concurrently. Cases have been reported in animals of all ages, down to ll-month-old calves. These papillomas often do not regress; some have been observed for over 4 years. In other instances, they may regress only to have new lesions recur. Animals suffering concurrent infections with typical fibropapillomas experience the normal regression expected with these tumors. Although natural transmission appears to occur, experimental attempts to inoculate unaffected cattle with these tumors have been unsuccessful. 7 Interdigital papillomatosis has been described recently in two herds of housed dairy cattle. 61 This chronic problem affected one third to three fourths of the cows confined to free stalls. The hindlimbs were most commonly involved in these animals, and such discomfort resulted that the cows experienced weight loss and decreased milk production; estrus often went undetected in affected cows. These verrucous growths occurred on the dorsal and palmar aspects of the interdigital space, primarily between the bulbs of the hooves. Serum frequently oozed from the lesions, and even the early lesions were extremely painful. No warts were detected elsewhere on these animals. The frond-like appearance of these warts and the failure of these lesions to regress suggest that they may also be a type of "atypical" warts, although B PV -3 has not yet been recovered from these growths. 61 Diagnosis Fibropapillomatosis caused by BPV-1 and BPV-2 differs £Tom papillomatosis of other species in that a significant connective tissue component with dermal fibroplaSia is present. 15.38 Dermal fibroplaSia is minimal or lacking in papillomas induced by BPV-5 (nodular teat form) or BPV-4 (alimentary form), or in the atypical warts (BPV-3). Hyperkeratosis of the epidermis does not extend into the dermis in the atypical warts. Gross diagnosis occurs so commonly that histopathologic examination is usually not necessary for diagnosis, except in persistent or atypical lesions. If histopathologic examination is necessary, tissues should be fixed in 10 per cent formalin or Bouin's fixative. Serologic methods (complement fixation, serum neutralization, and agar gel precipitin tests) are not predictable diagnostic aids, generally are used as research tools, and are rarely utilized for routine diagnosis. 34 With

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suspected "atypical warts ," a cross section cut through one of the excised warts provides a rapid means of identifying them, since the fine, delicate fronds are very obvious, even when the wart is covered with an adherent surface of mud. Epidemiology The lesions generally appear from 1 to 4 months after exposure, depending on dose and method. Minor surgical procedures such as dehorning have been incriminated in dissemination of the infection. Affected cattle spread the disease to other animals, while contact with sharp or abrading objects in the environment (barbed-wire fences , feeding bunks, halters) may also contribute to the spread of the infection. Direct contact of the virus upon an abraded skin surface can result in growth of a fibropapilloma at the site of skin injury. Transplacental transmission is also thought to be possible. lO Insect bites have been incriminated on occasion in outbreaks of fibropapillomas but have never been documented. 34 The atypical papillomas have the most obscure epidemiology, since point herd-outbreaks occur which involve large numbers of animals. Experimental transmission of these tumors to uninfected animals or transmission of autogenous tumors to other anatomic sites in an animal with an ongoing papilloma infection has been unsuccessful thus far. 7 Management Uncomplicated warts usually cause no problems except in valuable animals used for competitive shows or overseas sales. Since lesions of uncomplicated fibropapillomatosis (the "neck" form) generally regress spontaneously, treatment is rarely required. 34 Uncomplicated fibropapilloma infection will result in an immunologic response, and repeated exposure to BPV will result in resistance to the virus, but on occasion cattle can be reinfected. 34 Vaccination is said to have no effect on regression of ongoing cases of warts. 38 Indeed, vaccination in the early stages of the disease has been suggested to increase the size of the warts and prolong the course of the disease. In spite of this, for many years clinicians and farmers alike have believed that wart maceration or surgical removal of one fibropapilloma may result in self-immunization and rapid rejection of other warts. Cryosurgery has also been utilized in hopes of causing antigen release and stimulation of sufficient immunologic reaction to cause rejection of other fibropapillomas. In the case of severe, generalized fibropapillomatosis, autogenous vaccines from excised warts have also been used to stimulate an immune response. When more than 20 per cent of the body is affected, prognosis for a recovery is poor. 65 Failure of cell-mediated imunity has been demonstrated in these persistent cases: Affected cattle fail to respond to the TB test and have diminished gamma globulin levels. 18 Vaccination with autogenous or commercial vaccines has not been successful in causing regression of atypical papillomas . 7 Similarly, the lesions of interdigital papillomatosis do not regress following vaccination with autogenous vaccine, and surgical extirpation is currently the only known means of treatment. Use of a tourniquet, local anesthetic, and systemic tranquilizer is recommended. To be successful, all abnormal tissue of the papilloma must

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be removed, otherwise regrowth can occur. Application of an antimicrobial dressing underneath a cotton wrap is advisable. If the surgery has been successful in completely removing the papilloma, the cow can be expected to appear sound within 48 hours. If this has been a chronic problem, routine hoof care for contracted bulbs is necessary. 61 Surgical removal of generalized atypical warts has not been attempted, since such large quantities of nonconfluent skin would be affected and new tumors tend to grow at alternate sites. 7 Farms experiencing a herd problem of the common form of warts should eliminate sharp or abrasive elements in the environment and prevent the interchange of halters, ropes, and brushes. Segregation of affected cattle may also be helpful in limiting the spread of the virus. Repeated use of commercial wart vaccines probably has some protective value for uninfected cattle (20 to 25 ml subcutaneously or intramuscularly). Autogenous fibropapilloma-derived vaccines are reported to be an effective means of prophylaxis of cutaneous and penile warts. 54 Autogenous vaccines for prophylaxis can be prepared by a properly equipped laboratory, using formalin-treated ground warts taken from animals on affected premises (1. 5 to 2 ml intradermally once a week for 3 weeks).65

PSEUDORABIES Pseudorabies (Aujeszky's disease, mad itch or infectious bulbar paralysis) is a herpesvirus that primarily affects swine. In cattle, it causes a rapidly progressive, lethal, nonsuppurative encephalomyelitis. Although not a major cause of mortality in American cattle, the disease can be very significant to the individual farm that experiences multiple fatal infections in its cattle population. Dyspnea and neurologic signs are the most prevalent clinical signs, but other common manifestations include profuse salivation, bruxism, anorexia, bloat, and frenzied self-mutilation from unilateral pruritus. Neurologic signs include ataxia, pyrexia, aggressive behavior, and twitching of facial muscles. Terminally, convulsions may occur; most cattle die within 24 to 72 hours of onset of signs. 34.69 The self-mutilation begins with the onset of the pyrexia. The site of itching is determined by the site of viral infection in the spinal ganglia, sensory neurons of the dorsal horns, and brain stem. As the neurons of the sensory ganglia degenerate, a sensation of itch is provoked in the skin innervated by these fibers. The tormented cattle continuously rub, kick, bite, and lick the cutaneous sites and may cause such extreme excoriation that wounds may extend into the subcutaneous and muscular tissues. Common sites of pruritus include the ears, eyes, mandible, neck, thorax, perineum, and thighs;33 flanks and vulva may also be affected. 34 Although abortions are a major clinical sign in swine affected with pseudorabies, cattle succumb so rapidly that abortions have not been reported. Cattle that do not manifest the self-mutilation syndrome may simply display fever, depression, tremors, circling, and death. 33 Signs of bloat, dorsolateral strabismus, nystagmus, blindness, spastic jerking of the head, tongue-chewing, hypcrpnca, circling, salivation, incoordination, and sudden

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death were reported in a feedlot outbreak in which 25 cattle died and only one animal was found with evidence of pruritus. H Necropsy Findings The primary gross necropsy findings are compatible with agonal death (including pulmonary edema) and mutilation of skin surfaces. Congestion of the meningeal vessels may be detected and serosal surfaces may be diffusely covered with petechial hemorrhages. Histologic examination of the selfinflicted wounds shows only laceration, acute inflammation, hemorrhage, necrosis, and edema. Peripheral nerves supplying the affected area may demonstrate foci of lymphocytic infiltration .' 3 Nonsuppurative meningoencephalitis and ganglioneuritis is evident in the central nervous system. Affected spinal ganglia may show neuronal swelling, intranuclear inclusions and necrosis. Spinal cord segments from the level of the affected ganglia to the brain stem also display necrosis and neuronal degeneration. Other Diagnostic Methods Acutely affected animals may demonstrate a leukopenia, but other alterations in clinical laboratory findings have not been reported. Serology is not readily utilized, since cattle die so rapidly. If serology is necessary, the agar gel immunodiffusion test is superior to the microtitration serum neutralization test (the test generally done on swine serum), which can record false positives if the bovine s'erum has an IBR titer. 2H ..5H The brain, brain stem and cervical spinal cord are the specimens of choice to submit for laboratory diagnosis. Fluorescent antibody preparations of cervical spinal cord, brain stem, and particularly the medulla oblongata can provide results in 24 to 48 hours, although cross reactions with other herpesvirus strains can occur. 28 Isolation of pseudorabies virus from brain tissue by cell culture inoculation is the most productive, specific, and useful diagnostic technique for diagnosis in cattle, although it is time consuming. 34 If the brain is not available for submission to the laboratory, nasal swabs, conjunctival swabs, or swabs of tissues from areas where wounds are present can be submitted for virus isolation. Isolation of the virus from nasal swabs of mature cattle appears to be much more successful than isolation from nasal swabs of calves. 69 If respiratory signs are noted, pulmonary tissues can be submitted for fluorescent antibody studies. 2R Epidemiology Swine are the natural hosts and only known source of pseudorabies infection. Affected cattle almost always have a history of direct contact with swine. The incubation period in cattle appears to be about 7 days. Swine may be asymptomatic; nasal discharges from affected swine may be the immediate source of infection. Cattle, sheep, dogs, and cats can all contract the disease but are terminal hosts, rarely transmitting it unless carcass consumption occurs. Rats are probably not an important means of disease transmission. 34 Because the virus is shed in adult bovine nasal secretions, cowto-cow transmission may be possible, but has been discounted in in vivo studies. 16.07 Iatrogenic outbreaks have been reported in sheep receiving an inoculation from syringes rinsed with saline that had been contaminated with

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pseudorabies live vaccine for swine. Over 50 per cent of the sheep inoculated died, and only one of the sheep that seroconverted survived .36 Thus , use of the swine vaccine must be judicious where species cross-contamination is possible. Management There is no known means of reversing the disease process once clinical signs are evident, although tranquilizers or sedatives may relieve the discomfort of affected animals. Once pseudorabies is suspected, separation of cattle and swine is imperative. New cases may occur for the 7 days following separation, and then losses generally cease. Separation of swine and cattle by only a double fence-lin e has been successful in stopping an outbreakY Immunization The use of IBR vaccine, intranasal attenuated pseudorabies vaccine , or inactivated virus vaccine was unsuccessful in protecting cattle against intranasal challenge with pseudorabies virus. 9 This is in opposition to several field trials that reported a positive response when an inactivated vaccine was administered twice (4 weeks apart) to halt an ongoing outbreak and to prevent another outbreak when active swine seroconversion was occurring. 62. 70

MALIGNANT CATARRHAL FEVER Malignant catarrhal fever (MCF; also called "snotsiekte" or malignant head catarrh) is an acute , highly fatal systemic disease of cattle and wild ruminants. The disease exists in at least two forms. The "wildebeest-associated" form is described in Africa and is caused by a herpesvirus . The "sheep-associated" form is seen throughout the world, especially in cattle having contact with sheep. The sheep-associated form is also assumed to be caused by a virus, presumably harbored by-but not affecting-the ovine. Several different forms of the disease can be encountered. The less common disease forms include peracute fever (up to 108°F) followed rapidly by death , neurologic signs only, or intestinal signs only followed by death in 1 to 2 days. The most common clinical manifestation is the "head and eye" form , which is characterized by remarkable mucopurulent nasal discharges, lacrimination, photophobia, conjunctivitis, scleral injection, oral erosions, and diffuse corneal edema (from panophthalmitis) which causes the eyes to appear blue. Systemic signs include pyrexia, depression, lymphadenopathy, coughing, and watery and bloody diarrhea. 34 Skin lesions can occasionally be seen in the head and eye form of the disease. Small areas of papular exanthema-purple blotches from which the overlying skin may slough-may be noted first and misdiagnosed as papules or small vesicles. Scabs may form and be particularly noticeable upon the teats or lightly haired areas. On heavily haired surfaces, these areas become thickened and elevated with the exudation of a plasma-like fluid. The teats, back, medial thigh, and escutcheon are most commonly affected. The skin of the udder and the coronary bands may also appear reddened, and separation of the hoof-walls may occur. 34,55

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Etiology and Epidemiology Despite repeated attempts, herpesvirus has not been demonstrate d to be the definitive etiologic agent in the sheep-associated (American) form of MCF, although blood or tissue inocula have been used to transmit the disease to uninfected cattle . A bovine syncytium-forming virus , a ce ll-associated herpesvirus , an agent thought to be a togavirus , and several enteroviruses have all been incriminated as possible e tiologic agents. 34 One interesting theory concerning etiology is that two distinct viral agents may be acting synergistically to cause the disease. The first virus might be bovine virus diarrhea (BVD) virus or Border disease (BD) virus of sheep. The BD virus is so closely related to BVD virus that som e inve stigators cannot or do not distinguish the two. Since BD/BVD organism has been recovered from ewes at lambing time, and because many outbreaks of sheep-associated MCF are associated with lambing ewes, some investigators believe this may warrant further transmission studies. The second virus has been sugge sted to be a non-IBR (infectious bovine rhinotrache itis) herpe svirus. These viruses have properties that classify them as he rpesviruses , but they are antigenically different from IBR virus. Although not yet validated, this theory of infection by two viruses may explain some of the confusing aspects of the disease process . 20 The wildebeest-associated form of MCF appears to occur in the nasal and ocular secretions of the young wildebeest. The herpe svirus at this time is stable and exists in a cell-free state. The cell-free virus is abse nt in the secretions of cattle showing signs of MCF. Thus , the cell-free virus is contagious from wildebeest to cow but is not transmitted from cow to cow. 47 Pathogenesis The viral infection appears to cause a necrotizing vasculitis, and many veterinarians have accepted the hypothesis that a cell-mediated immunopathologic (hypersensitivity-like) reaction may be occurring. A recent study of alterations in immunoglobulins, he molytic complement , and serum complement-3 indicated that the wildebeest-associated form of MCF is probably not a typical immune complex-mediated disease , as was previously thought. 46 This does not agree with studies showing deposition of immune-complexes (comprised of immunoglobulin, complement, and conglutin) in kidneys of terminally infected cattle. 58 Thus , this issue remains unresolved. Diagnosis The diagnosis is ofte n made upon physical findings when a veterinarian examines the affected cow. Few other disease processes are as damaging to the varied organ systems as is MCF . Historical evide nce of exposure to sheep is also helpful in determining a diagnosis. Other diseases that may be considered in the differential diagnosis of MCF include IBR, BVD-mucosal disease, bluetongue, salmonellosis , polioencephalomalacia, Buss disease, rabies, infectious thromboembolic meningoencephalitis, listeriosis, heavy metal or pesticide toxicosis , and infectious bovine keratoconjunctivitis (pinkeye). Serologic tests for the wildebeest-associated MCF virus have been de-

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veloped. The immunoperoxidase technique appears to be superior to the immunofluorescent antibody technique, and a complement fixation test also has been reported to be useful. 63.64 If the wildebeest-associated (or African) form of MCF is suspected, serologic and tissue samples are best referred to the Plum Island Animal Disease Center* for diagnosis. Necropsy findings include severe inflammation, congestion, and necrosis of the nasal turbinates; esophageal ulceration and erosions of the oral mucosa; abomasal ulcers and petechial hemorrhages; and petechial hemorrhages in the alimentary tract. The lymph nodes of the head and neck may be swollen and edematous, and white foci are present in the kidney cortex. 34 The characteristic histopathologic lesion is a necrotizing vasculitis in skin and internal organs. Epidemiology Wildebeest, hartebeest, and other wild ruminants (commonly found in American zoological parks) are reservoirs of the African form of MCF. Sheep are presumed to be the reservoir of the form of MCF found in this country. Nasal secretions are presumed to be a source of infective organisms, although placental tissues or fluids are also incriminated. Insect transmission has not been eliminated; cow-to-cow transmission seems unlikely, although new cases of MCF have occurred several months after cattle and sheep have been separated. Management and Prevention No consistently successful therapy for this disease has been reported, although the use of aspirin, corticosteroids, and intravenous fluids is advocated. In one field case, levamisole has been reported to be useful in stimulating T-cell function, but laboratory trials have not been successful. 48 Separation of cattle and sheep (or other suspected ruminant reservoirs) has been the only successful means of preventing the disease.

PARAVACCINIA SCROTAL INFECTIONS Paravaccinia viruses cause pseudocowpox and papular stomatitis. Lesions from pseudocowpox are found on the udder and teats; those from papular stomatitis occur on the muzzle and in the mouth of calves. This virus has also been isolated from scrotal lesions from adult bulls. The skin of the lower third of the scrotum appears "scabbed over with a pale crust. "19 The skin beneath the crust is raw, denuded, and congested; grossly, dermatophilosis appears to be the most likely etiologic agent. Histopathologic examination shows ulceration with early granulation tissue and infiltration of neutrophils (in response to secondary bacterial infection) within the ulcers. Multiple tiny pustules and vesicles are evident in adjacent epidermis. Intracytoplasmic inclusion bodies, typical of poxviruses, may be detected in the unaffected epidermis surrounding the ulcers . Removal of the scabs and topical treatment with 2 per cent iodine have not 'P.O. Box 848, Greenport, Long Island, New York 11944.

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caused adverse reactions . Because the virus is transmissible to humans , gloves should be worn while examining and treating the lesions. 19

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Zentralbl. Veterinarmed. [B], 29:451-456, 1982. 2. Aamodt, 0., Naess, B. , and Sandvik, 0.: Vaccination of NOIwegian cattle against ringworm. In Proceedings of the Twelfth World Congress on Diseases of Cattle, 1982. 3. Abu-Samra, M.T., and Walton , G.S.: The inoculation of'rahhits with Dermatophilus congolensis and the simultaneous infection of sheep with D. congolensis and orf virus. J. Compo Pathol., 91:317-329,1981. 4. Amakiri, S. F., and Nwufoh, K.J.: Changes in cutaneous blood vessels in bovine dermatophilosis. J. Compo Pathol. , 91:439-442, 1981. 5. Amstutz, H .E.: Bovine skin diseases: A brief review. Mod. Vet. Pract., 60:821-824,1979. 6. Andrews, A. H., and Edwardson, J.: Treatment of ringworm in calves using griseofulvin. Vet. Rec. , 108:498-500, 1981. 7. Barthold, S.W., Keller, L.D ., and Olson, C., et al.: Atypical warts in cattle. J. Am. Vet. Med. Assoc., 165:276-280, 1974. 8. Beasley, VR, Crandell, R.A. , and Buck, W.B ., et al.: A clinical episode demonstrating variable characteristics of pseudorabies infection in cattle. Vet. Res. Commun. , 4:125-129, 1980. 9. Biront, P., Vandeputte, J., and Pensaert, M.B., et al.: Vaccination of cattle against pseudorabies (Aujeszky's disease) with homologous virus (herpes suis) and heterologous virus (herpes bovis 1). Am. J. Vet. Res., 43:760-763, 1982. 10. Blood, D.C. , Henderson, J.A., and Radostits, O.M., et al.: Veterinary Medicine. Edition 5. Philadelphia, Lea & Febiger, 1979. 11. B6hm, K.H .: General aspects offungi and mycotic infections. In Proceedings of the First European Congress on Trends in Veterinary Pharmacology and Toxicology, 1980. 12. Campo, M.S ., Moar, M.H., and Jarrett, W.F.H., et al.: A new papilloma-virus associated with alimentary cancer in cattle. Nature, 286:180-182, 1980. 13. Campo, M.S., Moar, M.H., and Laird, H.M ., et al.: Molecular heterogeneity and lesion site specificity of cutaneous bovine papillomavirus. Virology, 113:323-325, 1981. 14. Chatterjee, A., Chakrabarti, A., and Chaddopadhyay, D., et al.: Isolation of dermatophytes from dung. Vet. Rec., 107:399, 1980. 15. Cheville, N. F., and Olson, C.: Epithelial and fibroblastic proliferation in bovine cutaneous papillomatosis. Pathol. Vet. , 1 :248- 257, 1964. 16. Crandell, RA., Mesfin, G. M., and Mock, R E.: Horizontal transmission of pseudorabies virus in cattle. J. Am. Vet. Res. , 43:326-328, 1982. 17. Desplenter, L.: New possibilities in the treatment of dermatomycoses. In Proceedings of the First European Congress on Trends in Veterinary Pharmacology and Toxicology, 1980. 18. Duncan, J.R, Corbeil, L.B., and Davies, D.H ., et al.: Persistent papillomatosis associated with immunodeficiency. Cornell Vet., 65:205-211, 1975. 19. Eugster, A. K., Fiske, R.A. , and Sneed, L., et al.: Paravaccinia infections of the scrotum of bulls. Southwest. Vet., 33:227, 1980. 20. Evermann, J.F.: Etiology of malignant catarrhal feve r. J. Am. Vet. Med. Assoc., 178:100- 102, 1981. 21. Ford, J. N., Jennings, P.A., and Spradbrow, P. B.: Evidence for papilloma-Viruses in ocular lesions in cattle. Res. Vet. Sci., 32:257-259, 1982. 22. Gbodi, T. A.: Serum mineral status of normal and Dermatophilus con golensis-infected Friesian calves. Bull. Anim. Health Prod. Afr., 28:348-350, 1980. 23. Gbodi, T.A., and Ndife, L.: Some observations on chemotherapy of bovine dermatophilosis . Br. Vet. J., 138:288-294, 1982. 24. Gherardi, S.G., Monzu, N., and Sutherland, S.S., et al.: The association between body strike and dermatophilosis of sheep under controlled conditions. Aust. Vet. J ., 57:268-271, 1981.

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