Journal of Wildlife Diseases, 47(4), 2011, pp. 917–924 # Wildlife Disease Association 2011

TREATMENT OF EQUINE SARCOID IN SEVEN CAPE MOUNTAIN (EQUUS ZEBRA ZEBRA)

Hendrik J. Marais1,2 and Patrick C. Page1 1 Department of Companion Clinical Studies, Private Bag X04, Faculty of Veterinary Science, Onderstepoort, University of Pretoria, South Africa 2 Corresponding author (email: [email protected])

ABSTRACT: Equine sarcoid has been diagnosed in endangered Cape (Equus zebra zebra) in at least two game reserves in South Africa, with prevalence as high as 53% in

Bontebok National Park. Seven Cape mountain with sarcoids were treated with either Downloaded from http://meridian.allenpress.com/jwd/article-pdf/47/4/917/2239705/0090-3558-47_4_917.pdf by guest on 01 October 2021 surgical excision, 5-fluorouracil, allogenous vaccine, or a combination of 5-fluorouracil and allogenous vaccine. One of the two sarcoids on one of the 5-fluorouracil–treated zebras was left untreated. The microscopic features of the tumors evaluated showed either all or most of the typical epidermal and dermal histologic features of equine sarcoid. The zebras were examined 2 yr posttreatment to determine outcome. All sarcoids had resolved except on the zebra on which one of the sarcoids was left untreated. The efficacy of the three treatment methods in Cape mountain zebra is encouraging. Key words: Allogenous vaccine, Cape mountain zebra, 5-fluorouracil, sarcoid, surgical excision.

INTRODUCTION Equine sarcoid affects of all ages, The term equine sarcoid was introduced types, and colors worldwide without obvi- in 1936 in South Africa to describe a ous sex predilection. The prevalence of unique tumor occurring in the skin of sarcoid in horses ranges from 0.5% to horses (Equus ferus caballus)andto 2.0% (Marti et al., 1993; Goodrich et al., distinguish them from other fibroblastic 1998). Sarcoid prevalence in two separate skin tumors such as fibromas, fibrosarco- populations of Cape mountain zebra has mas, and papillomas (Jackson, 1936). Sar- been reported to be 53 and 25%, respec- coid means fibrosarcoma-like and refers to tively in South Africa (Marais et al., 2007). the characteristic behavior of these tumors The treatment of sarcoids may represent in that they are locally invasive, recur after a considerable expense to owners surgical excision, and do not metastasize (Nasir and Reid, 1999). In zebras, the (Goodrich et al., 1998). It is widely ac- expense is increased due to the cost of cepted that bovine papillomavirus (BPV) capture and follow-up treatment or exami- types 1 and 2 are associated with the nations. Should an animal require repeat pathogenesis of equine sarcoid. Although treatments or be monitored after surgery, it sarcoids do not produce infectious virions, must be kept in a sheltered enclosure, with they contain detectable viral DNA and additional cost and risk of injury or mortality RNA and express BPV type 1 and 2 major due to stress and anxiety. In addition, equine transforming protein E5 (Marchetti et al., sarcoid poses a threat to the genetic diversity 2009). Although sarcoids in horses occur of these rare . All currently primarily on the legs, head, and ventral available treatment options have limitations abdomen (Brostrom, 1995; McConaghy concerning their effectiveness in horses or et al., 1996), the most common site for arising from the practical difficulties in sarcoids in Cape mountain zebra (Equus treating wild . zebra zebra) is the ventral abdomen and Reports of neoplastic growths in wild legs (Marais et al., 2007). Despite their zebras are sparse and few discuss treat- characteristic anatomical distribution and ment (Lohr et al., 2005; Nel et al., 2006; gross appearance, a biopsy specimen is Marais et al., 2007). Sarcoids are complex required for definitive diagnosis. and many treatments have been described

917 918 JOURNAL OF WILDLIFE DISEASES, VOL. 47, NO. 4, OCTOBER 2011 in horses, including surgical excision sarcoid. Animals were immobilized from a (Martens et al., 2001), Bacillus-Calmette- helicopter using a combination of etorphine hydrochloride (M99, Novartis Animal Health, Guerin immunotherapy (Lavach et al., Johannesburg, South Africa), azaperone 1984, 1985), cryotherapy (Lane, 1977; (Stresnil, Bayer Animal Health, Johannesburg, Martens and De Moore, 1996b), intersti- South Africa), and hyaluronidase (Hyalase, tial brachytherapy (Turrel et al., 1985; Kyron Laboratories, Johannesburg, South Theon and Pascoe, 1995), hyperthermia Africa). Once animals were recumbent, a ground team covered their eyes and blocked (Hoffman et al., 1983), intralesional cis- their ears to reduce stimulation. All animals platin (Theon et al., 1993), topical chemo- were identified by microchip, and the coat

therapy (Theon et al., 1993; Martens and patterns were recorded by means of digital Downloaded from http://meridian.allenpress.com/jwd/article-pdf/47/4/917/2239705/0090-3558-47_4_917.pdf by guest on 01 October 2021 De Moore, 1996a), excision by carbon photography. Reversal was done with dipre- dioxide laser (Carstanjen et al., 1997), norphine HCl (M50-50, Novartis Animal Health). mistletoe extract (Christen-Clottu et al., Eight of the 15 animals were diagnosed 2010), and photodynamic therapy (Martens presumptively with sarcoid and seven were and De Moore, 1996a; Giuliano, 2010). treated. Diagnoses were confirmed by histo- These treatments may be costly, technically pathologic examination. Two animals each difficult to administer, or have variable were treated with surgical excision, chemo- therapy, and allogenous vaccine; one was efficacy (Owen and Jagger, 1987; Theon treated with both chemotherapy and alloge- et al., 1993; Theon and Pascoe, 1995; nous vaccine (Table 1). No antimicrobials or Carstanjen et al., 1997). Regardless of the anti-inflammatory drugs were administered. approach decided on, multiple treatments The ethics committee of South African Na- are often necessary for complete regression tional Parks approved this study. of sarcoids (McConaghy et al., 1994, 1996; Biopsy and histopathology Knottenbelt et al., 1995). The Cape mountain zebra has been Biopsies were taken from all sarcoid-like tumors. The sarcoids were either surgically described as one of the rarest mammals in excised or a representative biopsy was taken the world (Penzhorn and Novelli, 1991). using a biopsy punch. Where two or more There are approximately 1,500 animals tumors were present on a zebra, a maximum of remaining worldwide, distributed among two samples was taken from each tumor. The national parks, game reserves, zoos, and tissues were fixed in 10% buffered formalin, trimmed into blocks and routinely processed, private reserves. The Bontebok National stained with hematoxylin and eosin, and Park is in the foothills of the Langeberg examined with a light microscope. Suspected Mountains, in the region of Swellendam. sarcoids were examined for typical epidermal The region has a temperate climate with and dermal histologic features of equine an average annual rainfall of about sarcoid such as epidermal hyperplasia, epider- mal hyperkeratosis, rete peg formation, and 500 mm, occurring mainly during early proliferation of fibroblast-like cells (Martens summer and winter and is also one of the et al., 2000). largest remaining ‘‘renosterveld islands’’ containing several plant species found Treatment nowhere else. Our objective was to Surgical excision: Surgical excision of sarcoids investigate clinical and pathologic find- was performed on two animals. After immo- ings, treatment, and outcome of sarcoids bilization, a tarpaulin was placed under the animal to attain optimal cleanliness under field in a population of free-ranging Cape conditions. The area around the tumor was mountain zebra. washed with water and dried with a clean towel, but not shaved due to time constraints. MATERIALS AND METHODS An elliptical incision was made through the skin and subcutis with a number 20 scalpel The entire population of Cape mountain blade around the tumor. The tumor and zebra (n515) in Bontebok National Park adjacent skin were removed by blunt dissec- (34u04933.70S, 20u27919.30E) was examined tion with Metzebaum scissors. The sarcoids in 2002 and 23 mo later (2004) for equine were excised in totality using a 10 mm margin. MARAIS AND PAGE—TREATMENT OF EQUINE SARCOID IN CAPE MOUNTAIN ZEBRA 919

TABLE 1. Identification, description of sarcoids, and treatment applied for seven Cape mountain zebra (Equus zebra zebra) in Bontebok National Park, South Africa, with equine sarcoid.

Zebra Description of sarcoid (location, size, type) Treatment

1 Ventral abdomen, 90360315 mm, verrucous/fibroblastic Surgical excision and ulcerated 2 Ventral abdomen, 85365315 mm, verrucous/fibroblastic Surgical excision and ulcerated 3 Udder, 20320310 mm, verrucous 5-Fluorouracil Left inner medial thigh, 20315315 mm, verrucous 5-Fluorouracil 4 Medial left axilla, 20315315 mm, verrucous 5-Fluorouracil Downloaded from http://meridian.allenpress.com/jwd/article-pdf/47/4/917/2239705/0090-3558-47_4_917.pdf by guest on 01 October 2021 Medial right elbow, 15315310 mm, verrucous No treatment 5 Ventral abdomen, 20320315 mm, verrucous and ulcerated Allogenous vaccine Medial left elbow, 20320310 mm, verrucous 6 Ventral abdomen, 15315310 mm, verrucous Allogenous vaccine 7 Medial right elbow, 30330315 mm, verrucous 5-Fluorouracil and allogenous vaccine

Minor bleeding was controlled by application using 15 g minced and filtered sarcoid, 84 ml of mosquito forceps, while major blood vessels glycerol–saline (50% glycerol and 50% 0.9% were tied off with 1/0 chromic catgut (Johnson NaCl), 1 ml 10% formalin, 150,000 IU sodium and Johnson, Johannesburg, South Africa). penicillin, and 100 mg dihydrostreptomycin. Closure was routine using 2/0 nylon (Johnson Real-time polymerase chain reaction targeting and Johnson) in a simple continuous pattern. E5 open reading frame genes of BPV (Van This suture pattern was chosen for speed, over Dyk et al., 2009) was used to detect and the simple interrupted pattern. A wound spray confirm the presence of both BPV-1 and -2 (Necrospray, Bayer Animal Health) was ap- DNA in the vaccine. Each zebra was treated plied over the surgical site. once with 1 ml of allogenous vaccine injected subcutaneously in the left neck area, halfway 5-Fluorouracil treatment: Two animals were between the shoulders and head. treated with 5-fluorouracil (5-FU) (Abic Fluo- rouracil, 500 mg/10 ml, Johannesburg, South Combined 5-FU treatment with autogenous vaccine: Africa). Both sarcoids on Zebra 3 were The zebra receiving intralesional 5-FU and injected with intralesional 5-FU. The axillary was treated concurrently with the allogenous lesion on Zebra 4 was treated, but the elbow vaccine, as previously described. lesion was left untreated in order to evaluate Follow-up examination was conducted by any spontaneous regression thereafter. Latex visual assessment on immobilized animals 2 yr gloves were worn for 5-FU application. The after treatment to establish response to authors used a dose of 50 mg/cm3 (Stewart treatment and to detect any new tumors. et al., 2006). Thus, 4–5 ml of 5-FU was infiltrated at the base of a 5 cm3 tumor using a grid pattern. A 16-gauge needle, connected to RESULTS a 20 ml luer-lock syringe, was advanced its full length and the 5-FU was slowly injected on Sarcoids were classified as resolved in needle withdrawal. This procedure was re- six of the seven zebras treated (Table 2). peated several times depending on the size of Figures 1 and 2 illustrate the response to thetumortoensureitsentirebasewas treatment in Zebra 2. Zebra 4, which had infiltrated. Digital pressure was applied to the needle insertion sites for 2 min after been treated with 5-FU in the axillary injection to minimize 5-FU leakage. area, while the elbow lesion was left untreated, was classified as persistent Allogenous vaccine: Two animals were treated and with new growth. This zebra was with allogenous vaccine. A crude allogenous euthanized at the follow-up examination vaccine was manufactured by using sarcoids collected from two previously sampled animals because he suffered from several sarcoids in the park that were not part of the current consisting of verrucous and fibroblastic study. Briefly, the vaccine was manufactured forms on the ventral abdomen, both 920 JOURNAL OF WILDLIFE DISEASES, VOL. 47, NO. 4, OCTOBER 2011

TABLE 2. Classification system for response to treatment (2 yr post-treatment) for Cape mountain zebra (Equus zebra zebra) in Bontebok National Park, South Africa, with equine sarcoid.

Classification Criteria

Resolved Tumor not visible Persistent Tumor still grossly visible New growth New tumors identified Downloaded from http://meridian.allenpress.com/jwd/article-pdf/47/4/917/2239705/0090-3558-47_4_917.pdf by guest on 01 October 2021 stifles, the right hock, and left axilla. There was severe subcutaneous edema with enlargement of the axillary lymph nodes. Microscopic features of the tumors eval- FIGURE 2. Appearance of ventral abdomen of uated showed all or most of the typical Zebra 2, 2 yr after surgical resection of equine sarcoid. epidermal and dermal histological features prominent proliferation of the surface of equine sarcoid. The epidermal changes epidermis associated with hyperkeratosis included hyperplasia, atrophy, hyperkerato- and crust formation. Several tumors were sis, and partial surface ulceration. Dermal histologically classified as aggressive, refer- changes consisted of increased density of ring to tumor cell infiltration that was fibroblasts, replacing the dermal collagen, extensive with multifocal groups of cells and a whorling fibroblast pattern. The infiltrating the deeper stroma. formation of long rete pegs was frequent and often associated with epidermal hyper- DISCUSSION plasia (Fig. 3). The cells had spindle-shaped nuclei with occasional double nuclei and Surgical resection, 5-FU alone, alloge- elongated eosinophilic cytoplasm. Differen- nous vaccine, or a combination of 5-FU and tiation of the tumor cells varied from allogenous vaccine were effective in treat- anaplastic to well differentiated, with the ing sarcoids in six of seven Cape mountain latter present in tumors of a more chronic zebra after a follow-up of 2 yr. One zebra nature. Some tumors had partial epidermal showed a poor response to treatment and ulceration, with infiltration of polymorpho- nuclear inflammatory cells; others showed

FIGURE 3. Histologic section of equine sarcoid from zebra showing typical long rete pegs (black FIGURE 1. Appearance of equine sarcoid on arrows) extending from hyperkeratotic epidermis ventral abdomen of Zebra 2 before sarcoid removal. into dermal sarcoid fibrous tissue (white arrow), Increments on scale are centimeters. hematoxylin and eosin stain, 4003. Bar 5 100 mm. MARAIS AND PAGE—TREATMENT OF EQUINE SARCOID IN CAPE MOUNTAIN ZEBRA 921 developed new tumors, and was eutha- and Knottenbelt (1999) and included nized. Treatment of sarcoid is notoriously occult, verrucous, nodular, fibroblastic, difficult and is reflected in the variety of mixed (verrucous, nodular, and fibroblas- treatments available. No single approach to tic), and malevolent. Two zebras that therapy has proved universally successful. underwent surgery suffered from a mix- Small, well-defined tumors carry the best ture of the verrucous and fibroblastic prognosis for surgical removal in horses, forms, while all the other zebras that were while extensive areas of poorly defined treated had verrucous sarcoids based on verrucous sarcoid may result in rapid macroscopic classification.

regrowth (Knottenbelt et al., 1995). Most The two zebras that underwent surgical Downloaded from http://meridian.allenpress.com/jwd/article-pdf/47/4/917/2239705/0090-3558-47_4_917.pdf by guest on 01 October 2021 reports of treatment efficacy originate from resection showed no evidence of regrowth large veterinary hospitals where horses after 2 yr, and the ventral abdomen of both treated for sarcoids are likely to have animals appeared normal. Wide surgical multiple, recurrent, and large tumors. The excision, including a 0.5 to 1.0 cm margin of success rate for therapy in this population is normal tissue is recommended if surgery is therefore expected to be less than the to be performed as a treatment of choice. success rate in private practice, where Although the guideline of a wide margin was horses tend to have solitary and less followed, the surgical approach was selected aggressive lesions. The choice and success for speed rather than for best surgical of therapy depends on many factors practice. A previous study reported success- including site and size of the tumor, type ful surgical resection of two sarcoids in of sarcoid, number of lesions, and previous captive zebra (Equus burchellii;Lohretal., treatment (Knottenbelt and Walker, 1994; 2005). These sarcoids were in the inguinal Knottenbelt et al., 1995). With regards to a and nose areas and neither recurred after wild population of animals, factors such as 7 mo. Surgical resection alone however is availability of equipment and facilities play rarely successful in horses with recurrence an even bigger role. In this study the exact rates as high as 50% within several months time for tumor resolution could not be (Ragland et al., 1970; Cotchin, 1977; established because all of the animals were Genetzky et al., 1983; Fadok, 1995). A free-ranging. Although it has been reported recurrence rate of 64%, with most regrowth that sarcoid lesions may reoccur at the occurring within 6 mo, was reported in same site following apparent complete horses (Foy et al., 2002). Small, well-defined surgical removal up to 5 yr or longer, tumors carry the best prognosis for surgical others have considered 1 yr of no recur- removal if the surgeon is able to define the rence as a complete cure (Pascoe and limits (Knottenbelt et al., 1995). Surgical Knottenbelt, 1999; Martens et al., 2001). resection is primarily used to debulk the Sarcoids present a variable clinical massaloneortoremovemostofthetumor appearance and confusion exists in the in order to increase the efficacy of other literature on the classification of gross modes of therapy. The tumors that were lesions. A previous study classified the resected on the ventral abdomen of the gross appearance into four broad catego- zebras reported were fairly large but well ries; namely, verrucous, fibroblastic, defined. These tumors were in an area that mixed verrucous and fibroblastic, and flat may be exposed to trauma from the prickly (Ragland et al., 1970). A second classifi- bush (Cliffortia ruscifolia), a sturdy fynbos cation included verrucous, fibroblastic, shrub with needle-like, spiny leaves that and mixed (McConaghy et al., 1996). A traumatize exposed skin. The exact role of third classification reported occult, verru- this plant in the epidemiology of sarcoids in cous, nodular, and fibroblastic (Foy et al., Cape mountain zebra is unknown. 2002). The classification used in the Both topical and intralesional chemo- present study was described by Pascoe therapeutic agents have been used widely 922 JOURNAL OF WILDLIFE DISEASES, VOL. 47, NO. 4, OCTOBER 2011 for treatment of equine sarcoid (Murphy suffered from primary sarcoid tumor et al., 1979; Theon et al., 1993; Goodrich showed complete regression, while five et al., 1998; Rush and Flaminio, 2000; of nine horses that suffered from recur- Mattil-Fritz et al., 2008). Serial injections rent tumor showed complete regression. of cisplatin, have been used with a high Four sarcoids recurred in the recurrent success rate (87–94%) in horses, either as tumor group, while one recurred in the a primary treatment or following surgical primary group. These results indicate that debulking (Theon et al., 1993, 1994). horses with primary tumors may react 5-Fluorouracil is a fluorinated pyrimidine more positively to treatment with autoge-

antimetabolite that interferes with nuclear nous vaccine than horses with recurrent Downloaded from http://meridian.allenpress.com/jwd/article-pdf/47/4/917/2239705/0090-3558-47_4_917.pdf by guest on 01 October 2021 DNA biosynthesis, leading to cell death or tumors. The aim of autogenous vaccina- increased susceptibility to the immune tion is to stimulate multifactorial physio- system. The dose of 50 mg/cm3 we used logical components responsible for the has been reported earlier (Stewart et al., normal transcription of differentiated 2006). Serial injections of 5-FU have cells. Tumor regression seems to be linked showed a success rate of 71.4% at 6 mo to the emergence of transformed mito- and 61.5% at 3 yr (Stewart et al., 2006). In chondria or ‘‘black bodies,’’ in the stroma the same study smaller sarcoids and of the tumor cells (Kinnunen et al., 1999). sarcoids that were not treated beforehand Allogenous vaccination is relatively easy were significantly more likely to resolve and cheap to perform and the subcutane- with treatment and all cases that respond- ous injections are painless and carry a low ed to 5-FU did so within five treatments, risk of side effects. In our study both while recurrent or persistent tumors zebras treated with the allogenous vaccine received seven treatments. This study showed complete regression and no side concluded that sarcoids susceptible to effects were recorded, consistent with 5-FU resolve within five treatments and previous reports using immunotherapy. that further 5-FU therapy is unlikely to be The vaccine used in this study, which of value (Stewart et al., 2006). In our study contained both BPV-1 and -2 DNA, Zebra 3, which had sarcoids that were induced a better response than the small and had not undergone any treat- vaccine reported in the Gariep Dam ment previously, responded well to the Nature Reserve, which contained only single dose of 5-FU. However, 5-FU had BPV-1 DNA (Van Dyk et al., 2009). no effect on the treated sarcoid in Zebra 4 The degree of inbreeding of zebras in and the lesion that was not treated on the Bontebok National Park and Gariep Dam right elbow enlarged markedly such that Nature Reserve has been investigated using the animal had difficulty in feeding. This domestic horse microsatellites to obtain discrepancy in response to 5-FU may be allellic information (Sasidharan, 2005). The due to genetic susceptibility to sarcoid two populations of zebras were compared rather than the treatment being ineffec- with populations without any history of tive. Additional cases need be evaluated sarcoids. The sarcoid-affected populations before 5-FU can be advocated as a safe had the lowest level of heterozygosity and and effective method for treatment of polymorphism, confirming their limited sarcoid in Cape mountain zebra. genetic diversity. There is strong association Few reports exist in the literature on between risk of sarcoid development and treatment of sarcoid by autogenous or certain alleles of the Class II region of the allogenous vaccine. In one study 21 horses equine major histocompatibility complex were treated with autogenous vaccine over (MHC; Chambers et al., 2003). Genetic 6 yr with a vaccine made from extirpated predisposition has been shown between tumor tissue by polymerization (Kinnunen certain MHC class II genes and the et al., 1999). Eleven of 12 horses that development of tumors induced in rabbits MARAIS AND PAGE—TREATMENT OF EQUINE SARCOID IN CAPE MOUNTAIN ZEBRA 923

(Han et al., 1992) and in human cervical extract (Viscum album austriacus). Journal of carcinoma associated with human papillo- Veterinary Internal Medicine 24: 1483–1489. COTCHIN, E. 1977. A general survey of tumours in the mavirus types 16, 18, 31, and 45 (Munoz horse. Equine Veterinary Journal 9: 16–21. et al., 2003). Therefore, a possible reduction FADOK, V. A 1995. Overview of equine papular and in MHC diversity due to genetic bottlenecks nodular dermatoses. Veterinary Clinics of North and subsequent inbreeding may contribute America, Equine Practice 11: 61–74. to uniform population sensitivity and the FOY, J. M., A. M. RASHMIR-RAVEN, AND M. K. BRASHIER. 2002. Common equine skin tumours. subsequent development of sarcoid tumors Compendium on Continuing Education for the in Cape mountain zebra populations. Suc- Practicing Veterinarian 24: 242–253. GENETZKY,R.M.,R.D.BIWER, AND R. K. MYERS. 1983. cessful treatment of breeding animals that Downloaded from http://meridian.allenpress.com/jwd/article-pdf/47/4/917/2239705/0090-3558-47_4_917.pdf by guest on 01 October 2021 may potentially harbor genes that make Equine sarcoids: Causes, diagnosis, and treatment. them susceptible to sarcoid may be detri- Compendium on Continuing Education for the Practicing Veterinarian 5: S416–S420. mental to the zebra population as a whole GIULIANO, E. A. 2010. Equine periocular neoplasia: because these genes may be passed on to Current concepts in aetiopathogenesis and their progeny. emerging treatment modalities. Equine Veteri- Inbreeding could compromise the im- nary Journal Supplement 37: 9–18. mune system, causing the sarcoids to become GOODRICH,L.,H.GERBER,E.MARTI, AND D. F. ANTCZAK. 1998. Equine sarcoids. Veterinary Clinics more aggressive. However, complete resolu- of North America, Equine Practice 14: 607–623. tion of the sarcoids suggests that there may HAN, R., F. BREITBURD,P.N.MARCHE, AND G. ORTH. be an advantageous immunologic response in 1992. Linkage of regression and malignant these animals. Despite the low number of conversion of rabbit viral papillomas to MHC treated zebras, the efficacy of the treatment class II genes. Nature 356: 66–68. HOFFMAN, K. D., R. A. KAINER, AND R. K. SHIDELER. protocols is encouraging. Poorly understood 1983. Radio-frequency current-induced hyper- aspects of sarcoids in Cape mountain zebra thermia for the treatment of equine sarcoid. relating to environmental factors, histocom- Equine Practice 5: 24–29. patibility antigens, and genetic diversity JACKSON, C. 1936. The incidence and pathology of require further investigation. tumours of domestic animals in South Africa. A study of the Onderstepoort collection of neo- plasms with special reference to their histopa- ACKNOWLEDGMENTS thology. Onderstepoort Journal of Veterinary We thank L. Lange for processing and Research 6: 1–460. evaluation of biopsy specimens. We gratefully KINNUNEN, R. E., T. TALLBERG,H.STENBACK, AND S. acknowledge the staff at Bontebok National SARNA. 1999. Equine sarcoid tumour treated by Park for cooperation. Financial support was autogenous tumour vaccine. Anticancer Re- received from the Equine Research Centre, search 11: 3367–3374. Onderstepoort. KNOTTENBELT, D. C., AND J. A. WALKER. 1994. Topical treatment of the equine sarcoid. Equine Veter- LITERATURE CITED inary Education 6: 72–75. ———, S. EDWARDS, AND E. DANIEL. 1995. Diagno- BROSTROM, H. 1995. Equine sarcoids. A clinical and ses and treatment of the equine sarcoid. In epidemiological study in relation to equine Practice 17: 123–129. leucocyte antigens (ELA). Acta Veterinaria LANE, J. G. 1977. The treatment of equine sarcoids Scandinavica 36: 223–236. by cryosurgery. Equine Veterinary Journal 9: CARSTANJEN, B., P. JORDAN, AND O. M. LEPAGE. 1997. 127–133. Carbon-dioxide laser as a surgical instrument for LAVACH, J. D., G. A. SEVERIN, AND D. LUEKER. 1984. sarcoid therapy—A retrospective study on 60 Immunotherapy of periocular sarcoids in horses. cases. Canadian Veterinary Journal 38: 773–776. Veterinary Clinics of North America, Large CHAMBERS, G., V. A. ELLSMORE, P. M. O’BRIEN,S.W. Animal Practice 6: 513–518. REID,S.LOVE,M.S.CAMPO, AND L. NASIR. 2003. ———, K. E. SULLINS,S.M.ROBERTS,G.A.SEVERIN, Association of bovine papillomavirus with the C. WHEELER, AND D. C. LUEKER. 1985. BCG equine sarcoid. Journal of General Virology 84: treatment of periocular sarcoid. Equine Veteri- 1055–1062. nary Journal 17: 445–448. CHRISTEN-CLOTTU, O., P. KLOCKE,D.BURGER,R. LOHR,C.V.,C.JUAN-SALLES,A.ROSAS-ROSAS,G.A. STRAUB, AND V. GERBER. 2010. Treatment of PARAS,M.GARNER, AND J. P. TEIFKE. 2005. Sarcoids clinically diagnosed equine sarcoid with a mistletoe in captive zebras (Equus burchellii): Association 924 JOURNAL OF WILDLIFE DISEASES, VOL. 47, NO. 4, OCTOBER 2011

with bovine papillomavirus type 1 infection. NASIR, L., AND S. W. REID. 1999. Bovine papilloma- Journal of Zoo and Wildlife Medicine 36: 74– viral gene expression in equine sarcoid tumours. 81. Virus Research 61: 171–175. MARAIS, H. J., P. NEL,H.J.BERTSCHINGER,J.P. NEL, P. J., H. BERTSCHINGER,J.WILLIAMS, AND P. N. SCHOEMAN, AND D. ZIMMERMAN. 2007. Prevalence THOMPSON. 2006. Descriptive study of an out- and body distribution of sarcoids in South break of equine sarcoid in a population of Cape African Cape mountain zebra (Equus zebra mountain zebra (Equus zebra zebra) in the zebra). Journal of the South African Veterinary Gariep Nature Reserve. Journal of the South Association 78: 145–148. African Veterinary Association 77: 184–190. MARCHETTI, B., E. A. GAULT,M.S.CORTESE,Z.YUAN, OWEN, R. A., AND D. W. JAGGER. 1987. Clinical S. A. ELLIS,L.NASIR, AND M. S. CAMPO. 2009. observations on the use of BCG cell wall fraction for treatment of periocular and other equine Bovine papillomavirus type 1 oncoprotein E5 Downloaded from http://meridian.allenpress.com/jwd/article-pdf/47/4/917/2239705/0090-3558-47_4_917.pdf by guest on 01 October 2021 inhibits equine MHC class I and interacts with sarcoids. Veterinary Record 23: 548–552. equine MHC I heavy chain. Journal of General PASCOE, R. R., AND D. C. KNOTTENBELT. 1999. Manual Virology 90: 2865–2870. of equine dermatology. W. B. Saunders, Lon- MARTENS, A., AND A. DE MOORE. 1996a. Sarcoid in don, 290 pp. horses. Chemotherapy, homeopathy and biolog- PENZHORN, B. L., AND P. A. NOVELLI. 1991. Some ical therapy. Vlaams Diergeneeskundig Tijds- behavioural traits of Cape mountain zebras chrift 65: 25–30. (Equus zebra zebra) and their implications for the management of a small conservation area. ———, AND ———. 1996b. Sarcoid in horses. II. Surgical excision and treatment with lasers, Applied Animal Behaviour Science 29: 293–299. hyperthermia, cryotherapy and radiotherapy. RAGLAND, W. L., G. H. KEOWN, AND G. R. SPENCER. Vlaams Diergeneeskundig Tijdschrift 65: 18–24. 1970. Equine sarcoid. Equine Veterinary Journal 2: 2–11. ———, ———, J. DEMEULEMEESTER, AND R. DUCA- RUSH, B. R., AND M. J. FLAMINIO. 2000. Immuno- TELLE. 2000. Histopathological characteristics of modulation in horses. Veterinary Clinics of five clinical types of equine sarcoid. Research in North America, Equine Practice 16: 183–197. Veterinary Science 69: 295–300. SASIDHARAN, S. P. 2005. Comparative genetics of ———, ———, L. VLAMINCK,F.PILLE, AND M. selected southern African mountain zebra pop- STEENHAUT. 2001. Evaluation of excision, cryosur- ulations. MSc Dissertation, University of Pre- gery and local BCG vaccination for the treatment of toria, Onderstepoort, South Africa. 105 pp. equine sarcoids. Veterinary Record 149: 665–669. STEWART, A. A., B. RUSH, AND E. DAVIS. 2006. The MARTI, E., S. LAZARY,D.F.ANTCZAK, AND H. GERBER. efficacy of intratumoural 5-fluorouracil for the 1993. Report of the first international workshop treatment of equine sarcoids. Australian Veter- on equine sarcoid. Equine Veterinary Journal inary Journal 84: 101–106. 25: 397–407. THEON,A.P.,AND J. R. PASCOE. 1995. Iridium-192 MATTIL-FRITZ,S.,D.SCHARNER,K.PIUKO,N.THONES,L. interstitial brachytherapy for equine periocular tu- GISSMAN,H.MULLER, AND M. MULLER. 2008. mours; Treatment results and prognostic factors in Immunotherapy of equine sarcoid: Dose-escalation 115 horses. Equine Veterinary Journal 27: 117–121. trial for the use of chimeric papillomavirus-like ———, J. R. PASCOE,G.P.CARLSON, AND D. N. KRAG. particles. Journal of General Virology 89: 138– 1993. Intratumoral chemotherapy with cisplatin in 47. oily emulsion in horses. Journal of the American MCCONAGHY, F. F., R. E. DAVIS,G.P.REPPAS,R.J. Veterinary Medical Association 202: 261–267. RAWLINSON,S.A.MCCLINTOCK,D.R.HUTSCHINS, ———, ———, AND D. M. MEAGHER. 1994. AND D. R. HODGSON. 1994. Management of Perioperative intratumoral administration of equine sarcoids: 1975–93. New Zealand Veter- cisplatin for treatment of cutaneous tumors in inary Journal 42: 180–184. . Journal of the American Veterinary ———, ———, AND D. R. HODGSON. 1996. Equine Medical Association 205: 1170–1174. sarcoid: A persistent therapeutic challenge. TURREL, J. M., S. M. STOVER, AND J. GYORGYFALVY. Ippologia 7: 41–44. 1985. Iridium-192 interstitial brachytherapy of MUNOZ, N., F. X. BOSCH,S.DE SANJOSE,R.HERRERO, equine sarcoid. Veterinary Radiology 26: 20–24. X. CASTELLSAGUE,K.V.SHAH,P.J.SNIJDERS, AND VAN DYK, D. E., M. C. OOSTHUIZEN,A.M.BOSMAN,P. C. J. MEIJER. 2003. Epidemiologic classification J. NEL,D.ZIMMERMAN, AND E. H. VENTER. 2009. of human papillomavirus types associated with Detection of bovine papillomavirus DNA in cervical cancer. New England Journal of Med- sarcoid-affected and healthy free-roaming zebra icine 348: 518–527. (Equus zebra) populations in South Africa. MURPHY, J. M., G. A. SEVERIN,J.D.LAVACH,D.I. Journal of Virological Methods 158: 141–151. HEPLER, AND D. C. LUEKER. 1979. Immunotherapy in ocular equine sarcoid. Journal of the American Submitted for publication 17 January 2011. Veterinary Medical Association 174: 269–272. Accepted 13 April 2011.