PEER REVIEWED

Case Reports - Blister Poisoning (Cantharidiasis) of Dairy and Beef Cattle

Gene A. Niles, DVM; W. C. Edwards, DVM, MS, DABVT; Sandra Morgan, DVM, MS, DABVT Oklahoma Disease Diagnostic Laboratory, College of Veterinary Medicine, Oklahoma State University, Stillwater, Oklahoma 74076

Abstract troupeaux laitiers ont ingere des meloes dans une ra­ tion totale melangee contenant de la luzerne hachee . poisoning (cantharidiasis) of horses fraiche. Les signes cliniques les plus significatifs has been well documented. Primary exposure to blis­ etaient le refus en masse de manger la luzerne hachee, ter is through consumption of contaminated meme si les vaches semblaient avoir faim, et en alfalfa hay. Confirmed cases of bovine cantharidiasis parallele la baisse dramatique de la production de lait. due to natural exposure have not previously been docu­ Des vaches dans un petit troupeau laitier et un mented in veterinary literature. This report describes troupeau de boucherie consommerent des bottes de foin blister beetle poisoning in three dairy herds and one rondes de luzerne qui contenaient des meloes. Au beef herd. Cows in two large dairy herds consumed contraire des vaches qui avaient mange de la luzerne blister beetles in a total mixed ration containing green hachee, le refus de s'alimenter n'a ete observe que chez chop alfalfa. The most significant clinical signs were certains individus. Les autres signes cliniques inclurent mass refusal to eat the freshly cut green chop alfalfa, la salivation, le bruxisme, !'urination frequente, la although the cows appeared hungry, and the corre­ diarrhee, la resistance a se deplacer, la douleur sponding dramatic decrease in milk production. Cows abdominale, l'ataxie et le decubitus. L'examen post­ in a smaller dairy herd and a beef herd consumed large mortem n'a pas revele de lesions macro- OU round bales of alfalfa hay containing blister beetles. microscopiques. La cantharidine a ete detectee a la fois In contrast to cows exposed to the beetles in green chop, dans les echantillons d'urine et d'aliments avec l'aide feed refusal in these cases was limited to individual d'un spectrophotometre de masse avec cows. Other clinical signs included salivation, brux­ chromatographie au gaz. De plus, des meloes ont ete ism, frequent urination, diarrhea, reluctance to move, trouves dans le foin et la luzerne hachee. abdominal pain, ataxia and recumbency. Postmortem examination did not reveal significant gross or micro­ Introduction scopic lesions. Cantharidin was detected by gas chro­ matography-mass spectrometry analysis of either urine Consumption of blister beetles ( sp; Fig­ or feed samples. In addition, blister beetles were found ure 1) in alfalfa is a common cause of severe and often 1 8 9 14 15 in the alfalfa green chop or hay. fatal disease of horses. • • • • Documentation of cantharidiasis in cattle naturally exposed to blister Resume beetles is lacking. The following cases illustrate that blister beetles can cause severe economic loss in cattle. L'empoisonnement par des meloes (coleopteres qui causent des claques) chez les chevaux est bien Case Reports documente. L'exposition primaire aux meloes se fait par la consommation de foin de luzerne contamine. Des Case 1. In June 1995, 2000 Holstein cows on a cas confirmes de cantharidiase chez les bovins suite a dairy in southeastern New Mexico were fed freshly cut une exposition naturelle n'ont pas ete rapportes dans green chop alfalfa during the morning feeding, and no la litterature veterinaire. Ce rapport decrit des cas abnormalities were noted. When fed that evening, the d'empoisonnement dans trois troupeaux laitiers et un cows were reluctant to eat the green chop alfalfa, al­ troupeau de boucherie. Les vaches dans deux gros though they appeared hungry. Milk production was

166 THE BOVINE PRACTITIONER-VOL. 35, NO. 2 Clinical signs included increased urination, reluc­ tance to move and significantly decreased milk produc­ tion. No deaths were reported. Seven Epicauta apache blister beetles per kilogram were found in the sample of the TMR submitted to the OADDL. This TMR contain­ ing the green chop alfalfa was delivered to five dairies that day, but fortunately it was only fed at this particu­ lar dairy that morning. Early recognition of feed re­ fusal in this herd prompted notification of a suspected problem, therefore the other dairies did not feed it. Case 3. During December 1997, a northwestern Oklahoma dairyman observed five acutely ill cows in his 70-cow Jersey herd. Two of the five cows died. Cows were allowed free-choice access to round bales of al­ Figure 1. A. Epicauta immaculata falfa hay, and were fed a pelleted dairy concentrate B. Epicauta apache while in the milking parlor. While in the milking par­ C. Epicauta occidentalis lor, cows would attempt to eat but would start cough­ D. Pyrota sp. ing after ingesting one or two bites of pellets. After expelling the ration, cows would salivate profusely, and decreased, cows were reluctant to move, exhibited fre­ were reluctant to attempt any further eating. quent urination and many had diarrhea. Subsequently, One of the two dead cows was submitted to the four cows became ataxic, had increased salivation and OADDL for a necropsy examination; no significant profuse diarrhea. gross or microscopic lesions were observed. The urine The following morning the green chop alfalfa was from this cow was negative for cantharidin, but urine removed and replaced with dry hay; the cows immedi­ submitted from a herdmate collected at the time of ately resumed eating. Total herd milk production was acute illness contained 5 ppb cantharidin. Striped blis­ significantly depressed for four days. Two of the four ter beetle fragments were found in the hay but were acutely ill cows died in less than 24 hours after the not submitted for identification. onset of clinical signs, and the two remaining cows were Case 4. Three cows in a 45-head Hereford herd salvaged at a local packing plant the next day. Oral in northwestern Oklahoma died in January 1999. ulcers were observed in the slaughtered . Clinical signs observed by the owner included mild A urine sample from one of the salvaged cows was ataxia, bruxism, abdominal pain, recumbency and submitted to the Oklahoma Animal Disease Diagnos­ death within 24 hours. The cows had been grazing tic Laboratory (OADDL) and contained 36 ppb dormant native grass pastures, and were supplemented cantharidin when analyzed by gas chromatography­ with natural protein cubes and large round bales of mass spectrometry (GC/MS). Two samples of the green alfalfa hay. chop alfalfa and one sample of the total mixed ration Postmortem lesions observed by the local veteri­ (corn, cottonseed meal, and green chop alfalfa) were narian included scattered areas 9fmucosal hemorrhage analyzed by GC/MS and contained 680, 4450 and 550 throughout the small intestine, and multiple focal pale ppb cantharidin, respectively. Blister beetles were areas on the surface of the kidneys. Urine and forma­ found in the green chop alfalfa, and were identified lin-fixed kidney from one cow were submitted to the as Epicauta apache by the Oklahoma State University OADDL. Four hundred-twenty ppb cantharidin was Department of Entomology. detected in the urine by GC/MS analysis. Microscopic Case 2. This case occurred in August 1996 and examination of the kidney tissue did not reveal any involved another southeastern New Mexico dairy lesions. milking 2000 Holsteins. These cows were fed a total The cattleman found black blister beetles in the mixed ration (TMR) which included fresh green chop alfalfa hay. They were not submitted for identification. alfalfa, which was supplied to the dairy by a custom harvester. The alfalfa was harvested between 9 and Discussion 10 AM, and fed by 2 PM the same day. All of the cows offered the feed containing the recently cut alfalfa Cantharidin, the toxic component found in blis­ green chop appeared hungry, but refused to eat. When ter beetles, has been classified as a drug for over 25 the green chop alfalfa was replaced with alfalfa centuries. Hippocrates prescribed the drug for dropsy, haylage from a different source the cows immediately and as late as the early 1900s it was still used to treat began to eat. pleurisy and pericarditis.4 Its centuries-old reputation

JUNE, 2001 167 as an aphroidisiac and abortifacient, know as "Span­ Although appropriate therapy for cantharidin tox­ ish Fly," is well known even though unfounded, and its icity of cattle has not been established, symptomatic use as an abortifacient has caused the death of women treatment, including the administration of activated that have used it. 4 charcoal and saline cathartics, should be considered. Cantharidin's effect on the horse, and association The administration of calcium, intravenous fluids and with blister beetles in alfalfa, was first documented in analgesics may be warranted. the 1970s.14 Although three calves experimentally poi­ Adult blister beetles travel in swarms, and gen­ soned with blister beetles died within 56 hours, clini­ erally travel less than 50 yards from where they were cal signs of cantharidiasis in cattle naturally exposed hatched.16 Adults prefer the blossom of flowering plants to blister beetles have not been previously documented.2 but do eat leaves when blossoms are unavailable. The Hypocalcemia and hypomagnesemia are constant beetles feed on goldenrod, pigweed, peanuts, soybeans, 2 10 15 16 findings in horses with cantharidiasis. • • Clinical ob­ and many other flowering plants, as well as alfalfa. servation of synchronous diaphragmatic flutter is Blister beetle pupa feed on grasshopper eggs before thought to result from the hypocalcemia.15 Further in­ over-wintering in the soil; therefore habitat surround­ vestigation of bovine cantharidiasis is needed to de­ ing alfalfa fields that is favorable for grasshoppers in­ termine if hypocalcemia also occurs in cattle, and if creases the probability that blister beetles may be decreased serum calcium levels cause the ataxia and present. 16 The referring New Mexico veterinarian was recumbency seen with bovine cantharidiasis. told by the area "old timers" that "beetles are found in Many cases of bovine cantharidiasis probably go greater numbers in alfalfa fields bordered by range undiagnosed or are attributed to non-specific gas­ land". The green chop alfalfa was harvested from a trointestinal or urinary tract disease. The increased field bordered on three sides by range land. When awareness of the potential for blister beetle poison­ spraying alfalfa fields to control blister beetles, it is ing of cattle will hopefully lead to increased submis­ important to examine the forage surrounding the field sion of urine, stomach, and feed samples for for blister beetles, and include the outer boundary of 11 12 cantharidin analysis. • Blood samples from sus­ the field and adjacent fence rows and ditches in the pected cases allow evaluation of the clinical pathol­ area to be sprayed. ogy changes that occur in cattle. The length of time Haying equipment that crimps the plant at the cantharidin is detectable in urine is dose-dependent.13 time of mowing improves the quality of the hay but Urine samples taken from cows more than 72 hours kills entrapped beetles and potentiates the possibility after ingesting blister beetles may not contain detect­ of poisoning. When using harvesting equipment that able levels of canthaddin. 5 There are no consistent does not crimp the forage, live beetles can migrate out gross or microscopic changes that are diagnostic for of the mowed alfalfa, decreasing the likelihood of their cantharidiasis in equine. 3 Whether this is true for presence in the baled hay. cattle is still unknown. There are over 200 species of blister beetles in Conclusions the United States, and the amount of cantharidin in the beetles ranges from less than 1 % to almost 6%. 15 Cantharidiasis is routinely included in the differ­ Cantharidin is found in the hemolymph and gonads, ential diagnosis when horses are experiencing abdomi­ and is exuded by blister beetles as a defense mecha­ nal or urinary tract discomfort and have been fed alfalfa. nism. Adult male blister beetles contain significantly These cases suggest that blister beetle poisoning more cantharidin than the female, whose cantharidin can also cause significant economic losses in cattle be­ 3 6 level decreases from the pupa to the adult stage. • cause oflost milk production, animal illness and death. During mating, the female obtains cantharidin from When there is a history of exposure to alfalfa hay or the male.5 green chop alfalfa and hungry cattle refuse to eat, and Although the striped blister beetles (Epicauta experience salivation, abdominal discomfort, polyuria, occidentalis and E. temexia) are most commonly asso­ ataxia, acute downers, and unexplained death, ciated with equine poisoning in the southwestern cantharidiasis should be included in the differential di­ United States, spotted and black blister beetles agnosis. When bovine cantharidiasis is suspected, urine, (Epicauta apache and E. pennsylvanica, respectively), rumen content, and feed samples should be analyzed 2 6 along with beetles in the Pyrota sp also cause illness. • for cantharidin, and the suspected feed should be thor­ The species of blister beetles that produced illness in oughly examined for the presence of blister beetles. both dairy and beef cattle in northwestern Oklahoma was not determined. Epicauta apache, found in the References alfalfa in the large dairy outbreaks, is found in the higher elevations of New Mexico and Arizona. 1. Beasley VR: Cantharidin toxicosis in horses. J Am Vet Med Assoc 182:283-284, 1983.

168 THE BOVINE PRACTITIONER-VOL. 35, NO. 2 2. Beasley VR, Dorman DC, Fikes JD, et al: Blister beetle - canthari­ EXCENEL® RTU din toxicosis, in A Systems Approach to Veterinary Toxicology, Ref­ brand of ceftiofur hydrochloride sterile suspension erence notes for Toxicology VB320. Urbana, IL 1998, pp 424-426. For intramuscular and subcutaneous use in cattle. 3. Capinera JL, Gardner DR, Stermitz FR: Cantharidin levels in CAUTION: Federal (USA) law restricts this drug to use by or on the order of a blister beetles (Coleptera: Meloidae) associated with alfalfa in Colo­ licensed veterinarian. rado. J Econ Entomol 78:1052-1055, 1985. INDICATIONS 4. Cheng KC, Lee HM, Shum SFB: A fatality due to the use of EXCENEl RTU Sterile Suspension is indicated for treatment of bovine respiratory disease (BRO, shipping fever, pneumonia) associated with cantharides from phalerata as an abortifacient. Med Sci Pasteurella haemolytica, Pasteurel/a multocida and Haemophilus somnus. Law 30:336-340, 1990. EXCENEl RTU Sterile Suspension is also indicated for treatment of acute 5. Edwards WC: Personal communication, 2000. bovine interdigital necrobacillosis (foot rot, pododermatitis) associated with 6. Edwards WC, Edwards RM, Ogden L: Cantharidin content of two Fusobacterium necrophorum and Bacteroides melaninogenicus. species of Oklahoma blister beetles associated with toxicosis in CONTRAINDICATIONS horses. Vet Hum Toxicol 31:442-444, 1989. As with all drugs, the use of EXCENEl RTU Sterile Suspension is contraindicated in animals previously found to be hypersensitive to the drug. 7. Gayle LG, Reagor JC, Ray A, et al: Cantharidin poisoning in cattle. J Am Vet Med Assoc 179:236, 1981. DOSAGE AND ADMINISTRATION Administer by intramuscular or subcutaneous administration at the dosage of 8. Guglick MA, MacAllister CG,Panceria R: Equine cantharidiasis. 0.5 to 1.0 mg ceftiofur equivalents/lb (1 .1 to 2.2 mg/kg) BW (1 to 2 ml sterile Compend Contin Educ Pract Vet 18:77-83, 1996. suspension per 100 lb BW). Administer daily at 24 h intervals for a total of three 9. Helman HG, Edwards WC: Clinical features of blister beetle poi­ consecutive days. Additional treatments may be administered on Days 4 and 5 for animals which do not show a satisfactory response (not recovered) after the soning in equids: 70 cases (1983-1996). J Am Vet Med Assoc 211:1018- initial three treatments. In addition, for BRO only, administer 1021, 1997. intramuscularly or subcutaneously 1.0 mg ceftiofur equivalents/lb (2.2 mg/kg) 10. Osweiler GW: Zootoxins , in Toxicology, Philadelphia, Wil­ BW every other day on Days 1 and 3 (48 h interval). Do not inject more than liams & Wilkins 1996, pp 437-438. 15 ml per intramuscular injection site. 11. Ray AC, Post LO, Reagor JC: GC/MS confirmation of canthari­ Selection of dosage level (0.5 to 1.0 mg/lb) and regimen/duration (daily or din toxicosis due to ingestion of blister beetles. P&TCN 8:398-399, every other day for BRO only) should be based on an assessment of the sever­ ity of disease, pathogen susceptibility and clinical response. 1980. 12. Ray AC, Kyle LG, Murphy MJ, et al: Etiologic agents, incidence, Shake well before using. and improved diagnostic methods of cantharidin toxicosis in horses. WARNINGS NOT FOR HUMAN USE. KEEP OUT OF REACH OF CHILDREN. Am J Vet Res 50:187-191, 1989. Penicillins and cephalosporins can cause allergic reactions in sensitized 13. Ray RC, Post LO, Hurst MJ, et al: Evaluation of an analytical individuals. Topical exposures to such antimicrobials, including ceftiofur, may method for the diagnosis of cantharidin toxicosis due to ingestion of elicit mild to severe allergic reactions in some individuals. Repeated or blister beetles (Epicauta lemniscata) by horses and sheep. Am J Vet prolonged exposure may lead to sensitization. Avoid direct contact of the prod­ uct with the skin, eyes, mouth, and clothing. Res 41:932-933, 1980. 14. Schobe TR, Panceria RJ: Pathology of blister beetle (Epicauta) Persons with 'a known hypersensitivity to penicillin or cephalosporins should avoid exposure to this product. in horses. Vet Pathol 16:18-31, 1979. In case of accidental eye exposure, flush with water for 15 minutes. In case of 15. Shawley RV, Rolf LL: Experimental cantharidiasis in the horse. accidental skin exposure, wash with soap and water. Remove contaminated Am J Vet Res 45:2261-2266, 1984. clothing. If allergic reaction occurs (e.g., skin rash , hives, difficult breathing), 16. Shawley R, Coppock S, Rommann LM: Blister beetles. OSU Ex­ seek medical attention. tension Facts No. 2072 pp 2072.1-2072.2. The material safety data sheet contains more detailed occupational safety 17. Sipple WL: Blister beetle poisoning. The Cattleman 63:208-210, information. To report adverse effects in users, to obtain more information or 1976. obtain a material safety data sheet, call 1-800-253-8600. RESIDUE WARNINGS: No pre-slaughter drug withdrawal interval is required when this product is used in swine. Treated cattle must not be slaughtered for 48 hours (2 days) following last treatment because unsafe levels of drug remain at the injection sites. No milk discard time is required when this product is used according to label ... directions. Use of dosages in excess of those indicated or by .. • unapproved routes of administration, such as intramammary, may result in illegal residues in edible tissues and/or in milk. A withdrawal period has not been established in pre-ruminating calves. Do not use in calves to be processed for veal. PRECAUTIONS Following intramuscular or subcutaneous administration in the neck, areas of discoloration at the site may persist beyond 11 days resulting in trim loss of edible tissues at slaughter. Following intramuscular administration in the rear leg, areas of discoloration at the injection site may persist beyond 28 days resulting in trim loss of edible tissues at slaughter. STORAGE CONDITIONS Store at controlled room temperature 20° to 25° C (68° to 77° F) [see USP]. Shake well before using. Protect from freezing. U.S. Pat. Nos. 4,902,683; 5,736,151 NADA# 140-890, Approved by FDA Pharmacia & Upjohn Company Kalamazoo, Michigan 49001, USA Revised May 2000 816 323 306A 692431

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