Volume 59 | Issue 1 Article 11

1997 Infectious Bovine Keratoconjunctivitis Dane DeBower Iowa State University

James R. Thompson Iowa State University

Follow this and additional works at: https://lib.dr.iastate.edu/iowastate_veterinarian Part of the Diseases Commons, Eye Diseases Commons, Large or Food Animal and Equine Medicine Commons, and the Veterinary Infectious Diseases Commons

Recommended Citation DeBower, Dane and Thompson, James R. (1997) "Infectious Bovine Keratoconjunctivitis," Iowa State University Veterinarian: Vol. 59 : Iss. 1 , Article 11. Available at: https://lib.dr.iastate.edu/iowastate_veterinarian/vol59/iss1/11

This Article is brought to you for free and open access by the Journals at Iowa State University Digital Repository. It has been accepted for inclusion in Iowa State University Veterinarian by an authorized editor of Iowa State University Digital Repository. For more information, please contact [email protected]. Infectious Bovine Keratoconjunctivitis

Dane DeBowel; DVMt James R. Thompson, DVM, Mstt

Infectious Bovine Keratoconjunctivitis (IDK) is an internationally recognized ocular dis~ ease of . Also known as pinkeye, IRK p.as a significant economic impact on the cattle industry. The costs corne as a result of decreased weight gain, milk discard, de~ creased show value and costs of therapy. The etiologic agent of IBK is a bacterial organism, Moraxella bovis.1 MOl'axella bovis is a Gram. negative rod that is spread rap~ idly by direct contact and by vectors such as domestica, Musca autumnalis, and Stomoxys calcitrans. Typi~ Scanning EM of'Moraxella bovis in. a "pit" on the cal lesions include corneal ulceration with surface of corneal epithelium. (Magnification possible perforation, corneal opacity, con~ 20,OOOX) junctival hyperemia and edema.2 Clinical signs can disappear at any 'stage but may conjunctival tissues permitting secondary M. persist in untreated individuals for 30 days bovis infection. Clinical diagnoses afe often or more. These factors and many more have misinterpreted 'in that conjunctivitis, 'made epidemiological, clinical, and patho~ blepharospasm, and corneal ulceration are logical research of utmost veterinary impor­ common to both IBR and IBK tance. This article will highlight what is Primary irritation of conjunctival or cor­ cUn'ently known about the etiology, treat­ neal tissues is required for initiation and ment, and prevention of IBK. progression of disease. Irritation can result from windblown dust, desiccation, ammonia­ Etiology laden air, plant material, feedstuffs, ultra~ violet (UV) light, and .l,G Most sig­ Moraxella bouis is primarily implicated in nificant are plant materials, UV radiation, the progression of IBK to clinical manifes­ and insects. tations.s In 60% of caBes M. bovis isolates Plant materials pose a greater risk to are found, whereas in 30% of cases range cattle where tall grasses such as wild Brannamella ovis is isolated. rye and shrubs provide air~borne and me­ Important to the pathogenesis ofIBK are chanical irritation. Feedstuffs, especially several predisposing factors. Evidence sug­ h~y, pose a similar problem to cattle on feed. gests that concurrent Mycoplasma bovoculi Bale feeders an~ problematic by virtl1e of and/or Infectious Bovine Rhinotracheitis design.6 Cattle given round bales feed pri­ (IBR) virus infections predispose an animal marily from the center, creating a plateau to IBK. 4 IBR virus may damage corneal and from which hay, dust, and other irritants rllin down into the eyes. Additionally, direct con­ tact between is high given current tDr. DeB ower is a 1996 graduate of the Iowa State Uni­ feeder design, thereby maximizing the versity College of Veterinary Medicine. spread of infectious agents. UV radiation is an environmental prob­ ttDr. Thompson is an associate professor in Veterinary lem for range cattle, especially white-faced Clinical Sciences at the Iowa State University College of Veterinary Medicine. cattle.1,6 Non-pigmented conjunctival epi-

20 Iowa State University Veterinarian thelium associated with white-faced ,cattle been associated with the ability to maintain allows high amounts of UV radiation to fall persistent infection by invading deeper tis­ upon ceils of the cornea and~onjunctiva, sen­ sues. Type Q pili have been shown to en­ sitizing them to inflammation and infection. hance the ability of M. bovis to adhere to Finally, insects can be especially irritat­ corneal epithelium. Interestingly, M. bouis ing as they feed on lacrimal s'ecretions. The has the ability to switch phase from type I face Musca autumnalis, the . to type Q thereby enhancing infectivity. Musca domestica, and the biting fly Concurrently, heterogeneity and resistance Stomoxys calcitrans are all important irri­ to host defenses associated with type I pili tating agents as well as vectors for M. are conferred. bovis,l,3 These vectors, most prevalent in Lipopolysaccharide also appears to play late summer, feed on lacrimal and mucosal a role in virulence associated with 0 anti­ secretions on the face of all cattle. Moraxella gens.S:ll A full compleijlent of 0 antigen in bovis can survive on the body surface and in LPS confers smooth colonies of M. bouis the salivary organs ofthese vectors for up to whereas areas absen't "in antigen denote 72 hours. The relatively limited circulating rough colonies. The effects of the M. bouis radius of these , however, does help limit LPS are dramatic. LPS introduced into rab­ spread from herd to herd.7 bits elicits pyrogenicity, dermal Shwartzman reaction, tumor necrosis factor (TNF) and .Virulence Factors' Interleukin-l (lL-l). Significantly, TNF has been implicated as the primary mediator of Once host defense mechanisms are compro­ LPS biological activity, namely the release mised, M. bouis has many virulence factors ofIL-l. The release ofIL-l has a great im­ that enable it to establish infection. Even pact on the response to M. bovis in bovine though there is no bacterial collagenase pro­ ocular tissues, especially regarding chemot­ duction, collagen is broken down in the dis­ axis of phagocytes to the area. ease process through host neutrophil action. Host neutrophils release hydrolytic enzymes Host Response on the surface of the cornea and cause break­ down of the corneal collagen matrix. The Once M. bovis has adhered to epithelial cells importance of recognizing this is that cor­ of the cornea, the sequence of events associ­ neal damage can be decreased by lowering ated with an immune response are initiated.7 the immune response with corticosteroid Neutrophils attracted to the area can be therapy. found in the intercellular spaces of edema­ The lack of collagenase is by no means tous tissue occasionally containing phagocy­ indicative of a total lack ofM. bovis enzym~s. tized bacteria. In unresolved inflammation, A large number of enzymes are present, in­ the cells of the stratum spinosum necrotize cluding fibrinolysin, phosphatase, hyalu­ and detach from the underlying stratum ronidase, and aminopeptidase. These en­ basale, leaving erosions. On the site of the zymes are all important in breaking down erosion, continued invasion of bacteria pro­ corneal epithelial cell matrices and allowing gressing through the basement membrane colonization. Equally important are hemol­ into'the propria leads to corneal ulceration. ysins, leukotoxins, proteases, pili, and a dis­ This process will allow 3 mm diameter le­ tinctive lipopolysaccharide (LPS),8 sions to form within 72 hours. Lesion reso­ The presenc~ and type of pili seem to lution includes fibroblast proliferation, fi­ play a highly important role in virulence. brinous exudate, and serofibrinous Colonies ofM. bovis that appear rough have infiltration of surrounding tissues. been characterized as virulent, piliate organ­ Histopathological examination of diseased isms, whereas smooth colonies are consid­ periorbital tissues shows accumulation of ered to be avirulent, non-piliate organisms.9 lymphoid tissue with marked hyperplasia in The pili of M. bovis are filamentous ho­ . the sub-epithelial conjunctival tissue.1,7,12 mopolymers of protein subunits. Two types In chronic ulcerated regions of the cornea, of pili have been identified from M. bovis, intensive neovascularization and namely type I and type Q,lo Type I pili have iridocyclitis develop. These areas of

Spring, 1997 21 j ~ ~ Scanning electron micrograph of Moraxella bovis colonizing a corneal ulcer. (Magnification 3,240X) neovascularizatioll with young capillaries Subconjunctival administration provides proceed from the limbus toward the ulcer. pharmacological advantages over deep Clinically the affected animal exhibits muscle administration. Most importantly, excessive lacrimation, redness of periorbital lower dosages may be used which yield tissues and corneal opacity.13 Additionally higher ocular concentrations. Difficulty of the animal will be photophobic, subconjunctival administration is a draw­ blepharospastic, and anorexic. These signs back which must be considered. Penicillin are often good initial clues in diagnosing and aminoglycosides are the most commonly IBK. used subconjunctival preparations.14 Al­ though these drugs result in high ocular con­ Treatment centration, healing rates are not markedly different from deep muscle parenteral Antimicrobial susceptibility studies have oxytetracycline.2 Despite desirable healing shown M. bovis to be susceptible to penicil­ rates, subconjunctival penicillin results in lin, streptomycin, gentamicin, tetracycline, more corneal ulcer recurrence and increased cephalosporin, nitrofurans and shedding of M. bovis when ineffective. sulfanilomides. 2, 7 Unfortunately, suscepti­ Topical adIninistration of antimicrobials bility and efficacy are not synonymous. The has been insufficiently studied. What is lack of effective treatment is due to short tear known is that topical preparations do not half-life of topical antimicrobials and the lim­ remain in the eye due to excessive lacrima­ ited ocular presence of parenterally admin­ tion, thereby minimizing their effect. Topi­ istered drugs.2 Long-acting oxytetracycline cal preparations such as Furazolidone spray is effective for treatment of infected calves. reduce the numbers ofM. bovis that are shed Following deep muscle parenteral adminis­ as well as reduce ulcer sizes. Neomycin­ tration of long-acting oxytetracycline, con­ tylosin spray results in activity mimicking junctivallevels remain at 2 mglmL or greater that of Furazolidone. for 72 hours.2 This amount has proven effi­ Showing much promise for topical ad­ cacious for treatment of infected animals. ministration is benzathine cloxacillin. Oil-

22 Iowa State University Veterinarian based formulations ofbenzathine cloxacillin reduce the shedding of.M; bovis and hasten the resolution of cqrneal ulcers.14,16 Two doses of benzathine cloxacillin 72 hours apart yield up to 10 mg/mL ocular concen­ tration for seven days. Should FDA approval be forthcoming, a 375 mg topical dose has been suggested as very effective. High effi­ cacy, low cost, I;l.D.d short withdrawal times would make benzathine cloxacillin an ap­ pealing alternative. What is evident in looking at antimicro­ bial therapy is that it is costly and not al­ ways effective. Treatment is costly due to drug expense, labor costs, and weight gain Photograph of a bovin.e eye infected with MOl'axella bovis. Clinically affected animals typi­ losses. As is true with so many diseases, cally exhibit signs of excessive lacrimation, red­ prevention is the ultimate goal which on ness of periorbital tissues, and corneal opacity. many levels surpasses the best xenobiotic therapy.

Prevention Preventative approaches of this kind have With annual losses of$150 million estimated often proved nl0re economically feasible than in the U.S., IBK has a profound economic contemporary treatment practices. impact.6 Efforts are being concentrated on With respect to IBK specifically, several prevention of this disease in an effort to mini­ management-related means of control mize these costs. Primary prevention efforts should be considered. Attempts to reduce have centered on immunologic research. It mechanical irritation should be imple­ is known that an active IgA response is nec­ mented. Tall grasses, noxious weeds, and essary to prevent IBK. Studies have shown shrubs should be cleared from pastures. that upon recovery from infection with M. Modifying bale feeders by increasing head bovis, cattle show high levels ofIgA on mu­ space from 9 to 15 inches decreases expo­ cosal surfaces thereby lending resistance to sure of the animal to hay stems and also to reinfection. Most vaccines that have been nearby individuals who may be carriers.6 recently tested elicited an IgG response Irritation due to face flies should be limited which has not proven effective in prevent­ as much as possible. Insecticide ear tags, ing infection. Recent efforts have included dust bags and Insect Growth Regulator-con­ both heat and formalin killed bacterins, such taining rations can be of some help in this as Addison Biologics' product, adjuvant and area. The amount of stress on the animal pilus vaccines by Schering-Plough, Smith should be limited to reduce the incidence of Kline Beacham, and others. None of these disease. By recognizing and dealing with vaccines have proven successful,13 Pilus stresses such as shipping, high fly popula­ vaccines currently on the market have some tions, or excessive sunlight, intervention producers convinced of their efficacy; how­ may be preventative. For instance, prior to ever, when quantitatively compared to non­ shipping to pasture, a prophylactic dose of vaccinates, no appreciable difference can be long-acting oxytetracycline may override the noted. critical post-shipping stress period, allow­ Perhaps the producer is left with what ing native defenses to recover. As with any may prove to be the best medicine for the infectious disease and especially with IBK, future: management. A revolution is in infected animals should be isolated, prefer­ progress which exemplifies the benefits of ably in a dark area, to minhnize contact with total herd management. By maintaining an other animals and T.N radiation. By thus optimal environment, disease frequency managing early breaks, spread can be lim­ among all production animals decreases.16 ited.

Spring, 1997 23 Discussion pilin expression in calves inoculated with Mora:rell bovls pilin-specific isogenic variants. Am J Vet R a 1993;54:249-253. es In a severely competitive economic climate, the beef producer and veterinarian alike 11. Kagonyera GM, Munn R, George LW. Cytopathi must work to prevent costly diseases such effects of Moraxella bovis on cultured bovine neutr: as IDK.· Current therapies provide an ad­ phils and corneal epithelial cells. Am J Vet Res 1989;50: 10-17. equate means for treating IDK if it is de- . tected prior to corneal ulceration, yet the 12. Batenlan KG, Leslie RE, Scholl TP. A field trial of costs inherent are substantial. An effective a piliated Moraxella bovis bacterin for the prevention vaccine is needed to nullify the expense of of infectious bovine keratoconjunctivitis. Can VE!t J 1986;27:23-27. treatment of disease. Lack of such a vaccine has ensured that carriers and relapses will 13. Smith PC, Blankenship T, Hoover TR, et al. Effec­ potentiate IBK over time. Lack of death tiveness of two commercial infectious bovine losses disguises IBK as an unimportant dis­ keratoconjunctivitis vaccines. Am J Vet Res 1990;51:1147-1150. ease, and this does not help the cause for research dollars. Regardless, the cattle pro­ .. 14. Abeynayake P, Cooper BS.· The concentration of ducer and veterinarian need adequate tools penicillin in bovine conjunctival Bac fluid as it pertains to deal with this menace of the bovine eye .• to the treatment of Moraxella bovis infection. J VE!t Pharm 1989;12:25-30. .

References 15. Diagneault, George LW. Topical benzathine cloxacillin for the treatment of experimentally induced 1. Brown JF, Adkins TR. Relationship offeeding activ­ infectious bovine keratoconjunctivitis. Am J vet Res ity offace fly (Musca autumnalis De Greer) to produc­ 1990;51:1153-1156. tion of keratoconjunctivitis in calves. Am J Vet Res 1972;33:2551-2555. 16. Caley HK. Pinkeye. Cooperative Extension Ser­ vice, Kansas State University 1991:983:1-2. 2. George LW. Antibiotic treatment of infectious bo­ vine keratoconjunctivitis. Cornell vet 1990;80:229-235.

3. Powe TA, Nusbaum KE, Hoover TR, et aI. Preva­ lence of nonclinical Moraxella bovis infections in bulls as determined by ocular culture and serum antibody titer. Jvet Diagn Invcst 1992;4:78-70. .

4. RosenbuHch RF. Influence of mycoplasma preinfection on the expression of Moraxella bovis patho­ genicity. Am Jvet Res 1983;44:1621-1624. Guaranteed Lowest Pricel

5. Hughes DE, Pugh GW, McDonald TJ. Ultraviolet Surgical Instruments Direct radiation and Moraxella bovis in the etiology of bovine infectious keratoconjunctivitis. Am J vet Res 1965;· from Manufacturer at 26:1331-1338.

6. Maxwell K. Prevention and cure of pinkeye. Pink­ 30-S0%OFF eye Practicum 1993;1:1-2. LIST PRICE! 7. Nagy A, Vandermissen E, Kapp P. Further data to the aetiology, pathogenesis and therapy of infectious bovine keratoconjunctivitis. Comparative Immunology, Microbiology and Infectious DiSease 1989; 12:115-127.

8. Johansen KA, Wannemuehler MJ, Rosenbusch RF. Biological reactivity ofMoraxella bovis lipopolysaccha­ ride. Am J vet Res 1990;51:46-51.

9. Wilt GR, Wu G, Bird RC, et al. Plasmid content of piliated and nonpiliated forms of Moraxella bovis. Am J vet Res 1990;51:171-173. SPECTR 10. ReuhI WW, Marrs CF, George LW, et al. Infection Call 8:30-5 EST 1-800-444-5644 rates, disease frequency, pilin gene rearrangement, and

24 Iowa State University Veterinarian