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Bordetella and Mycoplasma Respiratory Infections in Dogs and Cats
UPDATE ON RESPIRATORY DISEASES
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BORDETELLA AND MYCOPLASMA RESPIRATORY INFECTIONS IN DOGS AND CATS David A. Bemis, PhD
Respiratory diseases of dogs and cats are often complicated by bacterial infections that require therapeutic intervention. Any of a variety of bacteria, including Escherichia, Pseudomonas, Klebsiella, Pasteurella, Staphylococcus, Streptococcus, Chlamydia, Mycoplasma, or Bordetella, may be involved in infections of the lower respiratory tract. 32 Most of these infections result from some compromise of the animal's innate defenses and are not highly contagious for healthy animals. Severity of disease and high numbers of organisms in lower respiratory tract tissues readily incriminate the organisms with disease. Systemic antimicrobial therapy usually is guided by culture and in vitro susceptibility test results. Unless an underlying primary defect can be corrected, supportive therapy and attention to nonspecific matters of hygiene are the only prophylactic measures that can be taken. Unlike many other bacteria that cause respiratory diseases in dogs and cats, Bordetella bronchiseptica and Mycoplasma sp. are well-suited to produce prolonged infections of the conducting airways. Diseases associated with these organisms are more often contagious, relatively mild or chronic. B. bronchiseptica and Mycoplasma sp, also are commonly recovered from the lower respiratory tract of asymptomatic animals .46• 52• 65 Selection of a suitable management strategy to control Bordetella and Mycoplasma infections can be confusing or controversial. From the Department of Microbiology, and the Clinical Bacteriology and Mycology Laboratory, Department of Environmental Practice, University of Tennessee College of Veterinary Medicine, Knoxville, Tennessee
VETERINARY CLINICS OF NORTH AMERICA: SMALL ANIMAL PRACTICE VOLUME 22 • NUMBER 5 • SEPTEMBER 1992
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BORDETELLA INFECTIONS Association with Disease
B. bronchiseptica has been associated with canine respiratory disease since early descriptions of its involvement in canine distemper by Ferry. 20 B. bronchiseptica has a predilection for ciliated airways and is therefore recovered commonly from dogs with rhinitis, sinusitis, tracheitis, bronchitis, and pneumonia. 2• 8• 13· 14• 50 Ascending otitis media appears to be rare in dogs, although this condition has been associated with B. bronchiseptica infections in other animals. 39 Canine tracheobronchitis, the disease syndrome with which B. bronchiseptica is most frequently associated, has been the subject of several reviews. 10• 19 • 22 In severely compromised dogs, B. bronchiseptica is occasionally isolated from tissues outside the respiratory tract. 20• 45 • 77 Reports linking B. bronchiseptica infection with feline diseases have been sparse. In early studies on distemper, McGowan45 isolated an organism matching the description of B. bronchiseptica from the respiratory tract of 65 cats, including 7 cats with bronchopneumonia. In 1973, Fisk and Soave21 and Snyder et al66 isolated B. bronchiseptica from lungs and trachea of 10 cats that had died from pneumonia . Reservoirs, Prevalence, and Transmission
Virtually all warm-blooded animals are susceptible to infection with B. bronchiseptica; infections have been reported in many wild and domestic animals and also in humans. 24• 79 On the basis of overall laboratory isolations and limited experimental evidence, it appears that some animals are more susceptible than others. Dogs, pigs, and guinea pigs are seemingly among the most highly susceptible; rats, rabbits and horses have moderate susceptibility, and chickens, mice, and humans are the least susceptible. The most significant natural reservoirs of B. bronchiseptica infections are presumed to be the respiratory tracts of infected animals. B. bronchiseptica generally does not survive well outside of the respiratory tract or outside of the animal. It is readily destroyed by phagocytosis, exposure to ultraviolet radiation, heat, low pH, detergents, and a great variety of chemicals. Nonetheless, in heavily contaminated environments, inanimate materials may become sources of infection. B. bronchiseptica does have relatively simple growth requirements, and one group of investigators53 recently demonstrated that B. bronchiseptica can grow in natural fresh and saltwater samples without additional nutrients. There are no reports of natural isolation of B. bronchiseptica from such environmental sources. It is difficult to obtain accurate estimates of the prevalence of B. bronchiseptica infections. Isolation rates vary within different subpopulations. Animals of all ages are susceptible to B. bronchiseptica infections.
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Isolation rates are generally higher in young animals, debilitated animals, and animals kept in close confinement. B. bronchiseptica infections in dogs usually are thought of as puppyhood infections that are invariably acquired by most dogs within the first year of life. Isolation rates within this age group may approach 100% in some facilities.12 In cases of canine distemper, isolation recovery rates commonly exceed 75% .20• 45• 77 Snyder et al66 found that the isolation rate of B. bronchiseptica from the upper respiratory tracts of cats obtained from commercial vendors and kept in close confinement rose from 10% to 48%66 within 3 weeks after purchase. Animals become reinfected with B. bronchiseptica, but the rate at which this occurs is unknown. B. bronchiseptica is one of the most frequently isolated organisms from dogs with chronic bronchitis/ however, because full clearance following primary infection may require more than 3 months, 13 it is difficult to define chronic B. bronchiseptica infection. Many infected animals remain asymptomatic. Snow45 recovered B. bronchiseptica by nasal swabs from 10 of 80 asymptomatic dogs and from 9 of 25 dogs with symptoms of upper respiratory disease. Although B. bronchiseptica is commonly thought of as a commensal, 46• 52· 65 there have not been any studies to determine its prevalence in well-defined adult populations. Ross66 recovered B. bronchiseptica from 1 of 22 healthy cats, and Yoda and colleagues81 made isolations from 12 of 226 and 4 of 126 presumably healthy dogs and cats, respectively. It is technically feasible to maintain Bordetella-free dogs through the use of barrier containment; some pet environments may be sufficiently isolated from sources of Bordetella to achieve the same results. B. bronchiseptica infection prevalence may vary from 0 to 100% depending on the population being tested. Transmission of B. bronchiseptica between different animal hosts has often been suspected68 but has never been clearly documented. Several investigators have demonstrated varying pathogenicity of B. bronchiseptica isolates for different animal hosts. 17• 60 A study of genetic lineages among B. bronchiseptica isolates has suggested that B. bronchiseptica clonal groups vary in the extent of their host ranges. 48 Clonal diversity was greatest for B. bronchiseptica isolates recovered from dogs, suggesting that dogs may have a higher likelihood of inter-host transmission than do pigs. B. bronchiseptica infections are spread by aerosol and direct contact. Transmission from experimentally infected to fully susceptible dogs was 100% within 1 to 4 days by both routes. 44 • 69 Actual doses inhaled from experimental aerosols, minimum infectious doses, and aerosol concentrations in contaminated environments have not been determined. Disease Symptomology, Pathology, and Pathogenesis
Most of our knowledge of B. bronchiseptica-induced disease in dogs has come from experimental infections.B· 69 Varying degrees of coughing
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and purulent nasal discharge are the prominent symptoms seen in experimentally infected dogs. Bacteria are found in high numbers at all levels of the conducting airways regardless of route of exposure (i.e., intranasat intratracheat aerosot or direct contact). B. bronchiseptica attaches to and replicates among cilia and produces cellular and extracellular products, which inhibit ciliary cell function, interfere wtih phagocytic cell function, and stimulate secretory cell activity. 10· 14 Neutrophilic invasion of ciliated mucosa is the most notable microscopic feature of infection. Varying degrees of exudation and mucus secretion also may be present but alveolar involvement is limited. Pneumonia usually is the result of bronchiectasis and purulent bronchiolitis. Maximum bacterial numbers in the lower respiratory tract and onset of clinical symptoms usually coincide at about 3 to 7 days postinoculation. By inference from a survey of practitioners in the United Kingdom, Thrusfield et aF1 estimated the mean incubation period for B. bronchiseptica infections to be 6.5 days. Symptoms last from a few days to several weeks. Mucosal antibodies may be detected as early as 4 days postinoculation, 15 but even in isolated environments, dogs may require 3 months to completely clear B. bronchiseptica from their respiratory tracts. 13 Although disease caused by B. bronchiseptica alone may occur naturally, 12 it is more frequently associated with other agents (distemper virus, parainfluenza virus, adenovirus, or Mycoplasma species in dogs and panleukopenia virus or rhinotracheitis virus in cats). Disease symptoms are more severe (pyrexia, dyspnea, anorexia) and often more chronic (e.g. , chronic sinusitis and chronic bronchitis) in such mixed infections and in animals with poor vaccination histories. Synergy has been demonstrated in experimental infections with canine parainfluenza virus and B. bronchiseptica. 75 B. bronchiseptica infections in natural diseases of dogs and cats may facilitate infections with other organisms (e. g., mycoplasmas) by their effects on ciliary motility and alveolar phagocytes. 10
Diagnosis of Infection
Isolation of B. bronchiseptica by culture is the most definitive way to diagnose infection. Serologic tests may provide some overall indication of infection in unvaccinated population s, but are not usually sensitive enough to detect infected individuals reliably. Tracheal swabs, transtracheal aspirates, tracheal washes, specimens representative of deep nasal tissue and lung tissue are the most satisfactory for detecting B. bronchiseptica infection. In healthy dogs and cats, such specimens frequently are sterile. High numbers of B. bronchiseptica, usually in pure culture and associated with neutrophilic exudate, are found in animals with acute disease. Careful consideration must be given to the physical examination and clinical history, because B. bronchiseptica may be isolated from asymptomatically infected ani-
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mals, convalescent carriers, chronically infected animals, and transiently colonized, immune animals. Although specimens with contamination external to the nasal cavity or from the oropharynx, are often unavoidable and more convenient, generally they are less efficient for detecting B. bronchiseptica infections. Selective media help overcome the effects of contamination but do not greatly improve the sensitivity of detection.
Antimicrobial Treatment Because many B. bronchiseptica infections are asymptomatic or produce only mild, self-limiting diseases, antimicrobial treatment is not always indicated. When symptoms persist (e.g., >14 days) or involve more severe, systemic signs, a number of antimicrobials can be used to prevent further spread and systemic invasion. Selection of antimicrobial agents should be based on results of in vitro culture and susceptibility tests Y Some discrepancies in susceptibility test results may occur as a result of methodologic as well as strain variations; 10• 79 however, B. bronchiseptica isolates have predictable susceptibilities to a number of agents (Table 1). The antipseudomonal penicillins (ticarcillin, piperacillin, azlocillin), aminoglycosides except streptomycin (kanamycin, gentamicin, amikacin, tobramycin), chloramphenicol, tetracyclines, guinolones (ciprofloxacin, enrofloxacin), and polymixins are effective in vitro against most isolates.30• 32• 61 • 67• 79 B. bronchiseptica isolates are consistently resistant to penicillin, nitrofurTable 1. PREDICTED ANTIMICROBIAL SUSCEPTIBILITIES OF B. BRONCHISEPTICA AND MYCOPLASMAS IN DOGS AND CATS Antimicrobial Agent
Streptomycin Gentamicin Penicillin G Ampicillin Extended spectrum penicillins First generation cephalosporins Tetracyclines Quinolones Chloramphenicol Erythromycin Tylosin Lincosamides Trimethoprimsulfadiazine Polymixins
B. bronchiseptica
Mycoplasma sp
resistant moderately susceptible resistant moderately susceptible or resistant moderately susceptible or resistant moderately susceptible or resistant moderately susceptible moderately susceptible susceptible moderately susceptible or resistant moderately susceptible resistant susceptible or resistant
resistant moderately susceptible resistant resistant
susceptible susceptible resistant
susceptible
resistant
resistant resistant moderately susceptible moderately susceptible moderately susceptible resistant
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ans, streptomycin, and many of the new generation cephalosporins (ceftaxime, ceftiofur). 32• 61 • 79• 80 Variable susceptibilities are reported for ampicillin, carbenicillin, cephalothin, sulfanomide, trimethoprim combinations, and erythromycin. 32· 6 1. 79 Sulfonamide resistance in B. bronchiseptica is most commonly R factor-mediated.26 Serious diseases caused by susceptible B. bronchiseptica isolates can be resolved by treatment with several different antimicrobials. 8 • 79 Reports demonstrating such clinical effectiveness are sparse, because marked clinical symptoms are difficult to reproduce in experimentally infected animals and antimicrobials are often prescribed for symptoms without verifying B. bronchiseptica as a major pathogen. Batey and Smits8 found that B. bronchiseptica pneumonias in dogs were effectively treated with oral trimethoprim-sulfadiazine (120 mg b.i.d.). Distribution of orally and parenterally administered antimicrobials into respiratory secretions may be insufficient to produce noticeable effect on B. bronchiseptica numbers or symptoms reflective of infections in the larger conducting airways. Standard treatments with erythromycin, chloramphenicol, ampicillin, tetracycline, or tylosin given orally and kanamycin or gentamicin given by a parenteral injection were unable to reduce bacterial numbers in the trachea and bronchi of experimentally infected dogs. 11 Many p11renteral and oral antimicrobials have been reported to be effective in ameliorating symptoms associated with infectious canine tracheobronchitis, 72 but only trimethoprin-sulfadiazine reduced B. bronchiseptica numbers in experimentally infected dogs. 42 Combined trimethoprim-sulfadiazine also prevented relapses of naturally occurring disease. 8 • 79 Clinical effectiveness of some agents might be improved by increasing dosages or shortening dosing intervals. Clavulanic acid combinations may increase the activity of broadspectrum penicillins against B. bronchiseptica. 67 In Europe, bromhexidine therapy improved the clinical effectiveness of oxytetracycline treatment in dogs with infectious tracheobronchitis, presumably by increasing drug levels in bronchial mucus.28 An alternative approach used with infectious canine tracheobronchitis is the administration of antimicrobials via intratracheal injections or aerosol.n· 34• 73 It is generally believed that such locally administered antimicrobials are no more effective for treating severe pneumonias than the same drugs administered orally or parenterally. 2· 76 Aerosol or intratracheal administration provides a means of more safely using drugs like the aminoglycosides or polymixins, which are poorly absorbed from mucosal surfaces and relatively toxic when administered parenterally. Aerosol treatment with kanamycin, gentamicin, polymyxin B, and colistin (250 mg, 50 mg, 166,666 IU, and 30 mg, respectively, nebulized from 3 mL suspensions for 10 minutes twice daily for 3 days) reduced clinical signs and B. bronchiseptica numbers in the trachea of experimentally infected dogs.n Antimicrobial aerosols may be of equal value in helping to hydrate and move mucous exudate from the bronchial tree. Mixed treatment with corticosteroids may not provide better results than treatment with antibiotics alone, 72 and in many
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instances topically administered corticosteroids offer no advantages over the same drugs administered orally. 2• 76 Vaccination
Most dogs do not remain persistently infected with B. bronchiseptica. Recovery from infection results in resistance to reinfection, which may last at least 6 months. 13 These observations fostered the hope that artificial immunization could be used to control B. bronchiseptica-induced diseases. Today, there are three different types of commercial vaccines for this purpose (Table 2). Live avirulent vaccines combined with modified live canine parainfluenza virus are administered intranasally. 16• 62 Inclusion of canine adenovirus type 2 has been advocated, but such three-way combinations have not become commercially available. 23 Intranasal vaccines elicit significant levels of secretory antibodies as soon as 4 days after inoculation15 and reduce both clinical disease and duration of shedding of wild-type and challenge strains of B. bronchiseptica. I. 16• 62• 70 Immunization with live organisms intranasally also may provide some degree of nonspecific colonization resistance. 10• 62 Production of active local immunity is not subject to maternal interference, and intranasal vaccines have been safely administered to pregnant bitches and newborn puppies. 1• 25 Dogs remain colonized with avirulent vaccine strains for at least 2 weeks, 62 but the duration of shedding and extent of dog-to-dog spread have not been studied. Reversion rates (from avirulent to Table 2. CANINE B. BRONCHISEPT/CA VACCINES Bordetella Antigen
Name
Live avirulent lntra-Trac II culture
Company Schering Plough (Kenilworth, NJ)
Naramune 2
Whole-cell bacterins
Extracted antigen
Bio Ceutic (St. Joseph, MO) Cough Guard B Smith Kline Beckman (Exton, PA) Smith Kline Vanguard SB Beckman (Exton, PA)
Bronchicine
Fermenta (Kansas City, MO)
Route intranasal
intranasal
parenteral*
Comment combined with MLV-paraininfluenza virus combined with MLV-parainfluenza virus monovalent
parenteral*
combined with MLV-distemper virus, Adenovirus type 2, parainfluenza virus, parvovirus subcutaneous monovalent
*Intramuscular injections recommended for puppies. Data from Compendium of Veterinary Products, ed 1. Port Huron, Ml, North American Compendiums, 1991 .
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virulent) appear to be very low; however, as with all live organisms, the possibility for clinically significant infections in compromised hosts always exists. Anecdotal reports of coughing following vaccination for infectious canine tracheobronchitis have appeared in the literature. 51 Early attempts to immunize dogs with parenterally administered whole-cell bacterins were not very successful. Although such products often produced high levels of agglutinating serum antibodies, they afforded little or no protection against disease and occasionally produced injection site abscesses. 13• 25• 41 Refinements in methods of bacterial inactivation, antigen dosages, and adjuvants have resulted in a much more effective and safer generation of whole cell bacterinsY· 44 • 64 B. bronchiseptica whole-cell bacterins are available as monovalent products or in combination with modified live virus vaccines. The extracted antigen-acellular B. bronchiseptica vaccine does not produce injection site toxicity when administered by the recommended subcutaneous route. 63 Two immunizations with this product significantly protected dogs from clinical disease following aerosol challenge and reduced nasal shedding of B. bronchiseptica. 63 Development of defined, nontoxic component vaccines for B. bronchiseptica is a current research interest of the veterinary biologics industry. Many boarding and other types of ~ommercial kennels require preboarding, pre-sale, and pre-training immunization against canine infectious tracheobronchitis. 54 It is important for practitioners to be aware of available products and their limitations in order to wisely direct their usage in the field. With respect to B. bronchiseptica immunization, each of the three different types of products provide significant protection against disease, but none completely prevents infection. Parenteral products produce highest levels of systemic immunity; intranasal products produce highest levels of mucosal immunity. There may be some advantages to combined vaccine usage with systemic priming and antibody levels being maintained by a parenteral product on an annual basis and mucosal antigen exposure to produce local immunity with an intranasal product prior to anticipated contact with wild-type B. bronchiseptica organisms.10 B. bronchiseptica immunization has not been attempted in cats nor does it appear to be indicated on the basis of prevalence observations.
MYCOPLASMA INFECTIONS Association with Disease
Eleven species of mycoplasma, three unclassified groups of mycoplasmas, acholeplasmas, and ureaplasmas have been isolated from the upper respiratory tract (oropharynx, nasopharynx, larynx) of dogs.3 • 5 • 37· 57· 59 Greater than 90% of all reported mycoplasma isolations from the lower respiratory tract are from dogs with pneumonia; lungs of healthy dogs rarely harbor mycoplasmas. 58 Seven species of mycoplasma have
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been associated with canine pneumonia: M. canis, M. spumans, M. cynos, M. edwardii, M. gateae, M. feliminutum , and M. bovigenitalium. 57 Several untypable mycoplasma species and ureaplasmas also have been recovered from pneumonic dog lungs. 3· 5· 37 Greig27 associated mycoplasmas with infectious tracheobronchitis but was unable to reproduce the disease experimentally. Outbreaks of canine infectious tracheobronchitis have been described in which B. bronchiseptica was noticeably absent, but mycoplasma isolations were not attempted. 4· 47· 49· 74 An investigation of a typical outbreak in a: closed colony of Labrador Retrievers resulted in the isolation of M. spumans and canine parainfluenza virus from trachea swabs and lung tissues of affected animals (Bemis DA, unpublished data). No other bacteria or viruses were recovered. In data based on 233 identified isolates of mycoplasma, M. spumans was the species most frequently isolated from pneumonia in dogs. 57 Rosenda!56 was unable to demonstrate the pathogenicity of M. spumans, M. canis, and M. gateae but did produce disease experimentally with M. cynos and M. bovigenitalium. Mycoplasma felis, M. gateae, M. feliminutum , M. arginini, acholeplasmas, and ureaplasmas hav~ been identified in the upper respiratory tract of cats.57 M . felis and M . arginini have been isolated from cats with pneumonia, but M. felis is more frequently associated with conjunctivitis.29· 57 Pulmonary abscesses have been associated with mycoplasma infections in cats. 18· 38· 78 Respiratory diseases have not been experimentally reproduced with mycoplasmas in cats. The high degree of association with diseased animals and pathologic findings similar to those of known mycoplasmal pathogens suggest a causal relationship between isolated mycoplasmas and pulmonary disease in dogs and cats. Reservoirs, Prevalence, and Transmission
Canine and feline mycoplasmas are frequent, if not consistent, inhabitants of the upper respiratory tract; infections of the lower respiratory tract generally are thought to be of endogenous origin. However, because virulence attributes of canine and feline mycoplasmas have not been well established, the possibility of exogenous transmission cannot be dismissed entirely. The distribution and relative numbers of individual mycoplasma species in the respiratory tract have not been determined. Some mycoplasma species associated with respiratory diseases are also found on mucous membranes of the urogenital system or gastrointestinal tract. Several mycoplasma species can be recovered from both dogs and cats or from other animals. 57 Disease Symptomology, Pathology, and Pathogenesis
There have been few clinical evaluations of respiratory mycoplasma infections in dogs and cats. Most isolations have been made from lung
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tissues of animals that had died with pneumonia (fever, emaciation, lethargy, dyspnea, chronic cough, and crackles were among the most commonly reported clinical symptoms). 37• 55• 57 Chronic mycoplasma colonization has been observed in dogs with primary ciliary dyskinesia (Edwards, personal communication, 1991). Kirchner et aP7 found macroscopic lesions suggestive of pneumonia in two dogs that had not apparently manifested clinical signs. A dog with mild, acute onset symptoms thought to be consistent with infectious canine tracheobronchitis was also observed to have macroscopic lesions of pneumonia when necropsied for unrelated purposes (Bemis DA, unpublished observations). Other dogs in the same kennel experienced similar symptoms and recovered uneventfully. Macroscopic lesions of pneumonia were produced experimentally in dogs inoculated with M. cynos, but clinical symptoms were not observed. 56 Microscopic pathology of natural and experimental mycoplasma pneumonia in dogs and cats consists of purulent bronchitis and bronchiolitis with varying degrees of bronchiectasis and epithelial damage in early stages of disease, followed by bronchial and bronchiolar epithelial hyperplasia, peribronchial and perivascular lymphoid h yperplasia, interstitial pneumonia, and bronchiolitis obliterans in later stages. 37• 56• 57 In contrast to B. bronchiseptica, mycoplasmas colonize both ciliated and nonciliated surfaces in the respiratory tract (Bemis DA, unpublished data) and are more frequently isolated from systemic body sites. 7· 3 L 33 Diagnosis
Most canine and feline mycoplasmas can be easily isolated by culture on appropriate mycoplasma media. Species identification requires immunologic testing with reference antisera. These reagents are not commercially available, and because the virulence is still unresolved, few clinical laboratories routinely speciate canine and feline mycoplasmas. Methods to distinguish different strains within each mycoplasma species, for epidemiological purposes, are at present limited. Serologic tests are not available for diagnosis of mycoplasma infections in dogs and cats. Antimicrobial Treatment
Antimicrobial susceptibility tests for mycoplasmas have not been standardized and are not widely available. Kato et aJ35 reported in vitro susceptibilities of 55 strains of M. canis, 11 strains of M. spumans, and 7 strains of M. maculosum to 22 antimicrobials. They found tylosin to be most active (MIC90 < 0.5fJ.g/mL); lincomycin, spriamycin, josamycin, and leukomycin were also quite active (MIC90 < 10f.lg/mL). Tetracycline (MIC90 < 10f.lg/mL), chloramphenicol (MIC90 < 10f.lg/mL) and kana-
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mycin (MIC90 < 50J..Lg/mL) were moderately active. Erythromycin, oleandomycin, and polymixin B had little or no effect on canine mycoplasmas. Spiramycin and tylosin have been used with clinical successes in mycoplasma pneumonias in dogs and cats.18 • 55 Cats with extrapulmonary abscesses caused by mycoplasmas responded well to tetracycline therapy. 36 A similar human lesion, suspected to have been transmitted by a cat scratch, responded to doxycycline after treatments with erythromycin, cloxacillin, and penicillin had failed. 40 Because mycoplasmas lack cell wells, beta-lactam antibiotics are uniformly ineffective against · mycoplasmas. In vitro susceptibility tests on fifteen different mycoplasma species from animals other than dogs and cats concluded that ciprofloxacin was highly active against animal mycoplasmas. 3° Clinical studies with enrofloxacin suggested that it was effective against mycoplasma infections in dogs and cats. 9 Macrolides .other than erythromycin (tylosin, tiamulin), lincosamides (lincomycin, clindamycin), tetracycline, chloramphenicol, and quinolones (ciprofloxacin, enrofloxacin) appear to be the best choices for antimicrobial therapy (see Table 1). Vaccination
There are no vaccines available to prevent canine and feline mycoplasmal diseases.6 Potential for development of such vaccines appears to be limited . Vaccines for other m ycoplasmal diseases (except contagious bovine pleuropneumonia) have not met with a great deal of success. 6 SUMMARY
The con sequences of B. bronchiseptica and mycoplasma infections in dogs and cats vary greatly. Only careful clinical judgment can dictate when to institute antimicrobial and other supportive treatments. Approaches to controlling diseases caused by these organisms should be tailored to meet individual needs. Management strategies that reduce natural exposure levels in the animal's en vironment and maintain active immunity to contagiou s components of disease have the highest likelihood of success. References 1. Alkire LT, Chladek DW: Field evaluation of an intranasally ad m inistered canine parainfluenza- Bordetella bronchiseptica vaccine. Vet Med/Small Anim Clin 75:1003, 1980 2. Amis TC: Chronic bronchitis in dogs. In Kirk RW (ed): Curren t Veterinary Therapy IX. Sm all Animal Practice. Philadelphia, WB Saunders, 1986, p . 247- 250
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3. Armstrong D, Tully JG, Yu B, et al: Previously uncharacterized mycoplasma isolates from an investigation of canine pneumonia. Infect Immun 1:1-7, 1970 4. Azetaka M, Konishi S: Kennel cough complex: Confirmation and analysis of the outbreak in Japan. Jpn J Vet Sci 50:851-858, 1988 5. Ball HJ, Bryson DG: Isolation of ureaplasmas from pneumonic dog lungs. Vet Rec 111:585, 1982 6. Barile MF: Immunization against mycoplasma infections. In Razin S, Barile MF (eds): The Mycoplasmas, vol 4. New York, Academic Press, 1985, pp 478, 451-483 7. Barton MD, Ireland L, Kirschner JL, et al: Isolation of Mycoplasma spumans from polyarthritis in a greyhound. Aust Vet J 62:206-207, 1985 8. Batey RG, Smits AF: The isolation of Bordetella bronchiseptica from an outbreak of canine pneumonia. Aust Vet J 52:184-186, 1976 9. Bauditz R: Results of clinical studies with Baytril in dogs and cats. Vet Med Rev 2:137- 140, 1987 10. Bemis DA: Current strategies for the control of canine infectious tracheobronchitis in canine cough. In Proceedings of the 5th Annual Eastern States Veterinary Conference, Orlando, FL, 1988, pp 22-35 11. Bemis DA, Appel MJG: Aerosol, parenteral and oral antibiotic treatment of Bordetella bronchiseptica infections in dogs. J Am Vet Med Assoc 170:1082-1086, 1977 12. Bemis DA, Carmichael LE, Appel MJG: Naturally occurring respiratory disease in a kennel caused by Bordetella bronchiseptica. Cornell Vet 67:282-293, 1977 13. Bemis DA, Greisen HA, Appel MGJ: Pathogenesis of canine bordetellosis. J Infect Dis 135:753-762, 1977 14. Bemis DA, Kennedy JR: An improved system for studying the effect of Bordetella bronchiseptica on the ciliary activity of canine tracheal epithelial cells. J Infect Dis 144:349-357, 1981 15. Bey RF, Shade FJ, Goodnow RA, et al: Intranasal vaccination of dogs with live avirulent Bordetella bronchiseptica: Correlation of serum agglutination titer and the formation of secretory IgA with protection against experimentally induced infectious tracheobronchitis. Am J Vet Res 42:1130- 1132, 1981 16. Chladek OW, Williams JM, Gerber DL: Canine parainfluenza- Bordetella bronchiseptica vaccine: Immunogenicity. Am J Vet Res 42:266-270, 1981 17. Collings LA, Rutter, JM: Virulence of Bordetella bronchiseptica in the porcine respiratory tract. J Med Microbial 19:247-258, 1985 18. Crisp MS, Birchard SJ, Lawrence AE: Pulmonary abscesses caused by a mycoplasma spin a cat. J Am Vet Med Assoc 191:340, 1987 · · 19. Dhein CR, Gorham JR: Canine respiratory infections. In Scott FW (ed): Contemporary Issues in Small Animal Practice, vol 3. Infectious Diseases. New York, Churchill Livingstone, 1986, p 177 20. Ferry NS: A preliminary report of the bacteriological findings in canine distemper. Am Vet Rev 37:499- 504, 1910 21. Fisk SK, Soave, OA: Bordetella bronchiseptica in laboratory cats from central California. Lab Anim Sci 23:33-35, 1973 22. Ford RB, Vaden SL: Canine infectious tracheobronchitis. In Greene CE (ed): Infectious Diseases of the Dog and Cat. Philadelphia, WB Saunders, 1990, p 259-260 23. Glickman LT, Appel MJ: Intranasal vaccine trial for canine infectious tracheobronchitis (kennel cough). Lab Anim Sci 31:397-399, 1981 24. Goodnow RA: Biology of Bordetella bronchiseptica. Microbial Rev 44:722- 738, 1980 25. Goodnow RA, Shade FJ: Control of canine bordetellosis. Mod Vet Pract 61:597- 598, 1980 26. Graham AC, Abruzzo GK: Occurrence and characterization of plasmids in field isolates of Bordetella bronchiseptica. Am J Vet Res 43:1852-1855, 1982 27. Greig AS: The significance of a pleuropneumonia-like organism in kennel cough. Can J Comp Med 18:275- 278, 1954 28. Hackett IJ: Intratracheal treatment. Vet Rec 122:119, 1988 29. Haesebrouck F, Devriese LA, van Rijssen B, et a!: Incidence and significance of isolation of Mycoplasma felis from conjunctival swabs of cats. Vet Microbial 26:95- 101, 1991 30. Hannan PCT, O'Hanlon PJ, Rogers NH: In vitro evaluation of various quinolone
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31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. 48. 49. 50. 51. 52. 53. 54. 55. 56. 57.
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antibacterial agents against veterinary mycoplasmas and porcine respiratory bacterial pathogens. Res Vet Sci 46:202-211, 1989 Henricks PM: Isolation of two mycoplasma sp from the peritoneal cavity of a dog. Can Vet J 28:437-438, 1987 Hirsch DC: Bacteriology of the lower respiratory tract. In Kirk RW (ed): Current Veterinary Therapy VIII. Small Animal Practice. Philadelphia, WB Saunders, 1986, pp 247-250 Hooper PT, Ireland LA, Carter A: Mycoplasma polyarthritis in a cat with probable severe immune deficiency. Aust Vet J 62:352, 1985 Hutchison RV: Intratracheal gentamicin and dexamethasone for treatment of infectious tracheobronchitis in the dog. Vet Med/Small Anim Clin 70:943-945, 1975 Kato H, Murakami T, Takase S, et al: Sensitivities in vitro to antibiotics ofmycoplasmas isolated from canine sources. Jpn J Vet Sci 34:197-206, 1972 Keane DP: Chronic abscesses in cats associated with an organism resembling mycoplasma. Can Vet J 24:289-291, 1983 Kirchner BK, Port CD, Magoc TJ, et al: Spontaneous bronchopneumonia in laboratory dogs infected with untyped mycoplasma sp. Lab Anim Sci 40:625-628, 1990 Malik R, Love ON, Hunt GB, et al: Pyothorax associated with a mycoplasma species in a kitten. J Small Anim Pract 32:31-34, 1991 Matsuda H, Tojo M, Fukui K, et al: The aerobic bacterial flora of the middle and external ears in normal dogs. J Small Anim Pract 25:269-274, 1984 McCabe SJ, Murray JF, Ruhnke HL: Mycoplasma infection of the hand acquired from a cat. J Hand Surg 12[Am]:1985, 1987 McCandlish lAP, Thompson H: Vaccination against Bordetella bronchiseptica infection in dogs using a heat-killed bacterial vaccine. Res Vet Sci 25:45-50, 1978 McCandlish lAP, Thompson H: Canine bordetellosis: Chemotherapy using a sulfadiazine-trimethoprin combination. Vet Rec 104:51-54, 1979 McCandlish lAP, Thompson H, Wright NG: Vaccination against canine bordetellosis using an aluminum hydroxide adjuvant vaccine. Res Vet Sci 25:51-58, 1978 McCandlish lAP, Thompson H, Wright NG: Vaccination against canine bordetellosis: Protection from contact challenge. Vet Rec 192:479- 483, 1978 McGowan JP: Some observations on a laboratory epidemic, principally among dogs and cats, in which the animals affected presented the symptoms of the disease called "distemper" . J Pathol Bacteriol 15:372-426, 1911 McKiernan BC, Smith AR, Kissil M: Bacterial isolates from the lower trachea of clinically healthy dogs. JAm Anim Hosp Assoc 20:139, 1984 Moloney MB, Pye D, Smith HV, et al: Isolation of parainfluenza virus from dogs. Aust Vet J 62:285-286, 1985 Musser JM, Bemis DA, Ishikawa H, et al: Clonal diversity and host distribution in Bordetella bronchiseptica. J Bacteriol 169:2793-2803, 1987 Noor F, Majid MS: Canine infectious tracheobronchitis in an animal facility: A bacteriological survey. Kajian Veterinar 14:1-4, 1982 van Oosterhout ICAM, Meij BP, Venker-van Haagen AJ, et al: Rhinoscopy in small animal clinics: an analysis of the results of 233 rhinoscopies and 97 bacterial cultures from nasal swabs. Tijdschrift voor Diergeneeskunde 114Sl:94-95, 1989 Ostle GN: Cough associated with canine vaccination? Vet Rec 125:446, 1989 Pecora DV: Bacteriologic cultural examination of the lower respiratory tract of laboratory dogs. Am J Vet Res 37:1511- 1513, 1976 Porter JF, Parton R, Wardlaw AC: Growth and survival of Bordetella bronchiseptica in natural waters and in buffered saline without added nutrients. Appl Environ Microbiol 57:1202- 1206, 1991 Praeger D: Tracheobronchitis, how some kennels are fighting back. Groom and Board July-Aug:24-25, 1985 Rosendal S: Mycoplasmas as a possible cause of enzootic pneumonia in dogs. Acta Vet Scand 13:137-139, 1972 Rosendal S: Canine mycoplasmas: Pathogenicity of mycoplasmas associated with distemper pneumonia. J Infect Dis 138:203-209, 1978 Rosendal S: Canine and feline mycoplasmas. In Barile MF, Razin S, Tully JG, et a! (eds): The Mycoplasmas, vol 2. New York, Academic, 1979, pp 217-234
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58. Rosendal S: Canine mycoplasmas: Their ecological niche and role in disease. J Am Vet Med Assoc 180:1212-1214, 1982 59. Rosendal S: Mycoplasmal infections. In Greene CE (ed): Infectious Diseases of the Dog and Cat. Philadelphia, WB Saunders, 1990, pp 446-452 60. Ross RF, Switzer WP, Duncan JR: Comparison of pathogenicity of various isolates of Bordete/la bronchiseptica in young pigs. Can J Comp Med 31:53-57, 1967 61. Roudebush P, Fales W: Antibacterial susceptibility of Bordetella bronchiseptica isolates from small companion animals with respiratory disease. J Am Anim Hosp Assoc 17:793-797, 1981 62. Shade FJ, Goodnow ·RA: Intranasal immunization of dogs against Bordetella bronchiseptica-induced tracheobronchitis (kennel cough) with modified live-Bordete/la bronchiseptica vaccine. Am J Vet Res 40:1241-1243, 1979 63. Shade FJ, Rapp VJ: Studies of a bacterin incorporating an extracted Bordetella bronchiseptica antigen for controlling canine bordetellosis. Vet Med/Small Anim Clin 77:1635-1639, 1982 64. Shelton ME, Draper DD, Farington DO: Control of a tracheobronchitis epizootic associated with Bordete/la bronchiseptica in a closed dog colony. Vet Med/Small Anim Clin 72:189-193, 1977 65. Snow HD, Donovan ML, Washington JO, et al: Canine respiratory disease in an animal facility. Viral and bacteriology survey. Arch Surg 99:126-128, 1969 66. Snyder SB, Fisk SK, Fox JG, et al: Respiratory tract disease associated with Bordetella bronchiseptica infection in cats. J Am Vet Med Assoc 163:293-294, 1973 67. Sparks SE, Jones RL, Kilgore WR: In vitro susceptibility of bacteria to a ticarcillinclavulanic acid combination. Am J Vet Res 49:2038-2040, 1988 68. Switzer WP, Mare CJ, Hubbard ED: Incidence of Bordetella bronchiseptica in wildlife and man in Iowa. Am J Vet Res 27:1134-1136, 1966 69. Thompson H, McCandlish lAP, Wright NG: Experimental respiratory disease in dogs due to Bordetella bronchiseptica. Res Vet Sci 20:16-23, 1976 70. Thrusfield MV, Aitken CGG, Muirhead RH: A field investigation of kennel cough: Efficacy of vaccination. J Small Anim Pract 30:550-560, 1989 71. Thrusfield MV, Aitken CGG, Muirhead RH: A field investigation of kennel cough: Incubation period and clinical signs. J Small Anim Pract 32:215-220, 1991 72. Thrusfield MV, Aitken CGG, Muirhead RH: A field investigation of kennel cough: Efficacy of different treatments. J Small Anim Pract 32:455-459, 1991 73. Turner T: Intratracheal treatment for kennel cough. Vet Rec 121:182-183, 1987 74. Ueland K: Serological, bacteriological and clinical observations on an outbreak of canine infectious tracheobronchitis in Norway. Vet Rec 126:481- 483, 1990 75. Wagnener JS, Sobonya R, Minnich L, et al: Role of canine parainfluenza virus and Bordetella bronchiseptica in kennel cough. Am J Vet Res 45:1862-1866, 1984 76. Williams HM Jr: Steroid and antibiotic aerosols. Am Rev Respir Dis 110:122-127, 1975 77. Winsser J: A study of Bordetel/a bronchiseptica. Proc Anim Care Panel 10:87-104, 1960 78. Wong WT, Noor F: Pyothorax in the cat-a report of two cases. Kajian Veterinar 16:15-17, 1984 79. Woolfrey BF, Moody JA: Human infections associated with Bordetel/a bronchiseptica. Clin Microbiol Rev 4:243-255, 1991 80. Yancey RJ Jr, Kinney ML, Roberts BJ, et a!: Ceftiofur sodium, a broad-spectrum cephalosporin: Evaluation in vitro and in vivo in mice. Am J Vet Res 48:1050- 1053, 1987 81. Yoda H, Nakayama K, Yusa T, et al: Bacteriological survey on Bordete/la bronchiseptica in various animal species. Experimental Animals 25:7-11, 1976
Address reprint requests to David A. Bemis, PhD Department of Microbiology University of Tennessee College of Veterinary Medicine Knoxville, TN 37996
0195-5616/92 $0.00 + .20
BORDETELLA AND MYCOPLASMA RESPIRATORY INFECTIONS IN DOGS AND CATS David A. Bemis, PhD
Respiratory diseases of dogs and cats are often complicated by bacterial infections that require therapeutic intervention. Any of a variety of bacteria, including Escherichia, Pseudomonas, Klebsiella, Pasteurella, Staphylococcus, Streptococcus, Chlamydia, Mycoplasma, or Bordetella, may be involved in infections of the lower respiratory tract. 32 Most of these infections result from some compromise of the animal's innate defenses and are not highly contagious for healthy animals. Severity of disease and high numbers of organisms in lower respiratory tract tissues readily incriminate the organisms with disease. Systemic antimicrobial therapy usually is guided by culture and in vitro susceptibility test results. Unless an underlying primary defect can be corrected, supportive therapy and attention to nonspecific matters of hygiene are the only prophylactic measures that can be taken. Unlike many other bacteria that cause respiratory diseases in dogs and cats, Bordetella bronchiseptica and Mycoplasma sp. are well-suited to produce prolonged infections of the conducting airways. Diseases associated with these organisms are more often contagious, relatively mild or chronic. B. bronchiseptica and Mycoplasma sp, also are commonly recovered from the lower respiratory tract of asymptomatic animals .46• 52• 65 Selection of a suitable management strategy to control Bordetella and Mycoplasma infections can be confusing or controversial. From the Department of Microbiology, and the Clinical Bacteriology and Mycology Laboratory, Department of Environmental Practice, University of Tennessee College of Veterinary Medicine, Knoxville, Tennessee
VETERINARY CLINICS OF NORTH AMERICA: SMALL ANIMAL PRACTICE VOLUME 22 • NUMBER 5 • SEPTEMBER 1992
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BORDETELLA INFECTIONS Association with Disease
B. bronchiseptica has been associated with canine respiratory disease since early descriptions of its involvement in canine distemper by Ferry. 20 B. bronchiseptica has a predilection for ciliated airways and is therefore recovered commonly from dogs with rhinitis, sinusitis, tracheitis, bronchitis, and pneumonia. 2• 8• 13· 14• 50 Ascending otitis media appears to be rare in dogs, although this condition has been associated with B. bronchiseptica infections in other animals. 39 Canine tracheobronchitis, the disease syndrome with which B. bronchiseptica is most frequently associated, has been the subject of several reviews. 10• 19 • 22 In severely compromised dogs, B. bronchiseptica is occasionally isolated from tissues outside the respiratory tract. 20• 45 • 77 Reports linking B. bronchiseptica infection with feline diseases have been sparse. In early studies on distemper, McGowan45 isolated an organism matching the description of B. bronchiseptica from the respiratory tract of 65 cats, including 7 cats with bronchopneumonia. In 1973, Fisk and Soave21 and Snyder et al66 isolated B. bronchiseptica from lungs and trachea of 10 cats that had died from pneumonia . Reservoirs, Prevalence, and Transmission
Virtually all warm-blooded animals are susceptible to infection with B. bronchiseptica; infections have been reported in many wild and domestic animals and also in humans. 24• 79 On the basis of overall laboratory isolations and limited experimental evidence, it appears that some animals are more susceptible than others. Dogs, pigs, and guinea pigs are seemingly among the most highly susceptible; rats, rabbits and horses have moderate susceptibility, and chickens, mice, and humans are the least susceptible. The most significant natural reservoirs of B. bronchiseptica infections are presumed to be the respiratory tracts of infected animals. B. bronchiseptica generally does not survive well outside of the respiratory tract or outside of the animal. It is readily destroyed by phagocytosis, exposure to ultraviolet radiation, heat, low pH, detergents, and a great variety of chemicals. Nonetheless, in heavily contaminated environments, inanimate materials may become sources of infection. B. bronchiseptica does have relatively simple growth requirements, and one group of investigators53 recently demonstrated that B. bronchiseptica can grow in natural fresh and saltwater samples without additional nutrients. There are no reports of natural isolation of B. bronchiseptica from such environmental sources. It is difficult to obtain accurate estimates of the prevalence of B. bronchiseptica infections. Isolation rates vary within different subpopulations. Animals of all ages are susceptible to B. bronchiseptica infections.
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Isolation rates are generally higher in young animals, debilitated animals, and animals kept in close confinement. B. bronchiseptica infections in dogs usually are thought of as puppyhood infections that are invariably acquired by most dogs within the first year of life. Isolation rates within this age group may approach 100% in some facilities.12 In cases of canine distemper, isolation recovery rates commonly exceed 75% .20• 45• 77 Snyder et al66 found that the isolation rate of B. bronchiseptica from the upper respiratory tracts of cats obtained from commercial vendors and kept in close confinement rose from 10% to 48%66 within 3 weeks after purchase. Animals become reinfected with B. bronchiseptica, but the rate at which this occurs is unknown. B. bronchiseptica is one of the most frequently isolated organisms from dogs with chronic bronchitis/ however, because full clearance following primary infection may require more than 3 months, 13 it is difficult to define chronic B. bronchiseptica infection. Many infected animals remain asymptomatic. Snow45 recovered B. bronchiseptica by nasal swabs from 10 of 80 asymptomatic dogs and from 9 of 25 dogs with symptoms of upper respiratory disease. Although B. bronchiseptica is commonly thought of as a commensal, 46• 52· 65 there have not been any studies to determine its prevalence in well-defined adult populations. Ross66 recovered B. bronchiseptica from 1 of 22 healthy cats, and Yoda and colleagues81 made isolations from 12 of 226 and 4 of 126 presumably healthy dogs and cats, respectively. It is technically feasible to maintain Bordetella-free dogs through the use of barrier containment; some pet environments may be sufficiently isolated from sources of Bordetella to achieve the same results. B. bronchiseptica infection prevalence may vary from 0 to 100% depending on the population being tested. Transmission of B. bronchiseptica between different animal hosts has often been suspected68 but has never been clearly documented. Several investigators have demonstrated varying pathogenicity of B. bronchiseptica isolates for different animal hosts. 17• 60 A study of genetic lineages among B. bronchiseptica isolates has suggested that B. bronchiseptica clonal groups vary in the extent of their host ranges. 48 Clonal diversity was greatest for B. bronchiseptica isolates recovered from dogs, suggesting that dogs may have a higher likelihood of inter-host transmission than do pigs. B. bronchiseptica infections are spread by aerosol and direct contact. Transmission from experimentally infected to fully susceptible dogs was 100% within 1 to 4 days by both routes. 44 • 69 Actual doses inhaled from experimental aerosols, minimum infectious doses, and aerosol concentrations in contaminated environments have not been determined. Disease Symptomology, Pathology, and Pathogenesis
Most of our knowledge of B. bronchiseptica-induced disease in dogs has come from experimental infections.B· 69 Varying degrees of coughing
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and purulent nasal discharge are the prominent symptoms seen in experimentally infected dogs. Bacteria are found in high numbers at all levels of the conducting airways regardless of route of exposure (i.e., intranasat intratracheat aerosot or direct contact). B. bronchiseptica attaches to and replicates among cilia and produces cellular and extracellular products, which inhibit ciliary cell function, interfere wtih phagocytic cell function, and stimulate secretory cell activity. 10· 14 Neutrophilic invasion of ciliated mucosa is the most notable microscopic feature of infection. Varying degrees of exudation and mucus secretion also may be present but alveolar involvement is limited. Pneumonia usually is the result of bronchiectasis and purulent bronchiolitis. Maximum bacterial numbers in the lower respiratory tract and onset of clinical symptoms usually coincide at about 3 to 7 days postinoculation. By inference from a survey of practitioners in the United Kingdom, Thrusfield et aF1 estimated the mean incubation period for B. bronchiseptica infections to be 6.5 days. Symptoms last from a few days to several weeks. Mucosal antibodies may be detected as early as 4 days postinoculation, 15 but even in isolated environments, dogs may require 3 months to completely clear B. bronchiseptica from their respiratory tracts. 13 Although disease caused by B. bronchiseptica alone may occur naturally, 12 it is more frequently associated with other agents (distemper virus, parainfluenza virus, adenovirus, or Mycoplasma species in dogs and panleukopenia virus or rhinotracheitis virus in cats). Disease symptoms are more severe (pyrexia, dyspnea, anorexia) and often more chronic (e.g. , chronic sinusitis and chronic bronchitis) in such mixed infections and in animals with poor vaccination histories. Synergy has been demonstrated in experimental infections with canine parainfluenza virus and B. bronchiseptica. 75 B. bronchiseptica infections in natural diseases of dogs and cats may facilitate infections with other organisms (e. g., mycoplasmas) by their effects on ciliary motility and alveolar phagocytes. 10
Diagnosis of Infection
Isolation of B. bronchiseptica by culture is the most definitive way to diagnose infection. Serologic tests may provide some overall indication of infection in unvaccinated population s, but are not usually sensitive enough to detect infected individuals reliably. Tracheal swabs, transtracheal aspirates, tracheal washes, specimens representative of deep nasal tissue and lung tissue are the most satisfactory for detecting B. bronchiseptica infection. In healthy dogs and cats, such specimens frequently are sterile. High numbers of B. bronchiseptica, usually in pure culture and associated with neutrophilic exudate, are found in animals with acute disease. Careful consideration must be given to the physical examination and clinical history, because B. bronchiseptica may be isolated from asymptomatically infected ani-
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mals, convalescent carriers, chronically infected animals, and transiently colonized, immune animals. Although specimens with contamination external to the nasal cavity or from the oropharynx, are often unavoidable and more convenient, generally they are less efficient for detecting B. bronchiseptica infections. Selective media help overcome the effects of contamination but do not greatly improve the sensitivity of detection.
Antimicrobial Treatment Because many B. bronchiseptica infections are asymptomatic or produce only mild, self-limiting diseases, antimicrobial treatment is not always indicated. When symptoms persist (e.g., >14 days) or involve more severe, systemic signs, a number of antimicrobials can be used to prevent further spread and systemic invasion. Selection of antimicrobial agents should be based on results of in vitro culture and susceptibility tests Y Some discrepancies in susceptibility test results may occur as a result of methodologic as well as strain variations; 10• 79 however, B. bronchiseptica isolates have predictable susceptibilities to a number of agents (Table 1). The antipseudomonal penicillins (ticarcillin, piperacillin, azlocillin), aminoglycosides except streptomycin (kanamycin, gentamicin, amikacin, tobramycin), chloramphenicol, tetracyclines, guinolones (ciprofloxacin, enrofloxacin), and polymixins are effective in vitro against most isolates.30• 32• 61 • 67• 79 B. bronchiseptica isolates are consistently resistant to penicillin, nitrofurTable 1. PREDICTED ANTIMICROBIAL SUSCEPTIBILITIES OF B. BRONCHISEPTICA AND MYCOPLASMAS IN DOGS AND CATS Antimicrobial Agent
Streptomycin Gentamicin Penicillin G Ampicillin Extended spectrum penicillins First generation cephalosporins Tetracyclines Quinolones Chloramphenicol Erythromycin Tylosin Lincosamides Trimethoprimsulfadiazine Polymixins
B. bronchiseptica
Mycoplasma sp
resistant moderately susceptible resistant moderately susceptible or resistant moderately susceptible or resistant moderately susceptible or resistant moderately susceptible moderately susceptible susceptible moderately susceptible or resistant moderately susceptible resistant susceptible or resistant
resistant moderately susceptible resistant resistant
susceptible susceptible resistant
susceptible
resistant
resistant resistant moderately susceptible moderately susceptible moderately susceptible resistant
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BEMIS
ans, streptomycin, and many of the new generation cephalosporins (ceftaxime, ceftiofur). 32• 61 • 79• 80 Variable susceptibilities are reported for ampicillin, carbenicillin, cephalothin, sulfanomide, trimethoprim combinations, and erythromycin. 32· 6 1. 79 Sulfonamide resistance in B. bronchiseptica is most commonly R factor-mediated.26 Serious diseases caused by susceptible B. bronchiseptica isolates can be resolved by treatment with several different antimicrobials. 8 • 79 Reports demonstrating such clinical effectiveness are sparse, because marked clinical symptoms are difficult to reproduce in experimentally infected animals and antimicrobials are often prescribed for symptoms without verifying B. bronchiseptica as a major pathogen. Batey and Smits8 found that B. bronchiseptica pneumonias in dogs were effectively treated with oral trimethoprim-sulfadiazine (120 mg b.i.d.). Distribution of orally and parenterally administered antimicrobials into respiratory secretions may be insufficient to produce noticeable effect on B. bronchiseptica numbers or symptoms reflective of infections in the larger conducting airways. Standard treatments with erythromycin, chloramphenicol, ampicillin, tetracycline, or tylosin given orally and kanamycin or gentamicin given by a parenteral injection were unable to reduce bacterial numbers in the trachea and bronchi of experimentally infected dogs. 11 Many p11renteral and oral antimicrobials have been reported to be effective in ameliorating symptoms associated with infectious canine tracheobronchitis, 72 but only trimethoprin-sulfadiazine reduced B. bronchiseptica numbers in experimentally infected dogs. 42 Combined trimethoprim-sulfadiazine also prevented relapses of naturally occurring disease. 8 • 79 Clinical effectiveness of some agents might be improved by increasing dosages or shortening dosing intervals. Clavulanic acid combinations may increase the activity of broadspectrum penicillins against B. bronchiseptica. 67 In Europe, bromhexidine therapy improved the clinical effectiveness of oxytetracycline treatment in dogs with infectious tracheobronchitis, presumably by increasing drug levels in bronchial mucus.28 An alternative approach used with infectious canine tracheobronchitis is the administration of antimicrobials via intratracheal injections or aerosol.n· 34• 73 It is generally believed that such locally administered antimicrobials are no more effective for treating severe pneumonias than the same drugs administered orally or parenterally. 2· 76 Aerosol or intratracheal administration provides a means of more safely using drugs like the aminoglycosides or polymixins, which are poorly absorbed from mucosal surfaces and relatively toxic when administered parenterally. Aerosol treatment with kanamycin, gentamicin, polymyxin B, and colistin (250 mg, 50 mg, 166,666 IU, and 30 mg, respectively, nebulized from 3 mL suspensions for 10 minutes twice daily for 3 days) reduced clinical signs and B. bronchiseptica numbers in the trachea of experimentally infected dogs.n Antimicrobial aerosols may be of equal value in helping to hydrate and move mucous exudate from the bronchial tree. Mixed treatment with corticosteroids may not provide better results than treatment with antibiotics alone, 72 and in many
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instances topically administered corticosteroids offer no advantages over the same drugs administered orally. 2• 76 Vaccination
Most dogs do not remain persistently infected with B. bronchiseptica. Recovery from infection results in resistance to reinfection, which may last at least 6 months. 13 These observations fostered the hope that artificial immunization could be used to control B. bronchiseptica-induced diseases. Today, there are three different types of commercial vaccines for this purpose (Table 2). Live avirulent vaccines combined with modified live canine parainfluenza virus are administered intranasally. 16• 62 Inclusion of canine adenovirus type 2 has been advocated, but such three-way combinations have not become commercially available. 23 Intranasal vaccines elicit significant levels of secretory antibodies as soon as 4 days after inoculation15 and reduce both clinical disease and duration of shedding of wild-type and challenge strains of B. bronchiseptica. I. 16• 62• 70 Immunization with live organisms intranasally also may provide some degree of nonspecific colonization resistance. 10• 62 Production of active local immunity is not subject to maternal interference, and intranasal vaccines have been safely administered to pregnant bitches and newborn puppies. 1• 25 Dogs remain colonized with avirulent vaccine strains for at least 2 weeks, 62 but the duration of shedding and extent of dog-to-dog spread have not been studied. Reversion rates (from avirulent to Table 2. CANINE B. BRONCHISEPT/CA VACCINES Bordetella Antigen
Name
Live avirulent lntra-Trac II culture
Company Schering Plough (Kenilworth, NJ)
Naramune 2
Whole-cell bacterins
Extracted antigen
Bio Ceutic (St. Joseph, MO) Cough Guard B Smith Kline Beckman (Exton, PA) Smith Kline Vanguard SB Beckman (Exton, PA)
Bronchicine
Fermenta (Kansas City, MO)
Route intranasal
intranasal
parenteral*
Comment combined with MLV-paraininfluenza virus combined with MLV-parainfluenza virus monovalent
parenteral*
combined with MLV-distemper virus, Adenovirus type 2, parainfluenza virus, parvovirus subcutaneous monovalent
*Intramuscular injections recommended for puppies. Data from Compendium of Veterinary Products, ed 1. Port Huron, Ml, North American Compendiums, 1991 .
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virulent) appear to be very low; however, as with all live organisms, the possibility for clinically significant infections in compromised hosts always exists. Anecdotal reports of coughing following vaccination for infectious canine tracheobronchitis have appeared in the literature. 51 Early attempts to immunize dogs with parenterally administered whole-cell bacterins were not very successful. Although such products often produced high levels of agglutinating serum antibodies, they afforded little or no protection against disease and occasionally produced injection site abscesses. 13• 25• 41 Refinements in methods of bacterial inactivation, antigen dosages, and adjuvants have resulted in a much more effective and safer generation of whole cell bacterinsY· 44 • 64 B. bronchiseptica whole-cell bacterins are available as monovalent products or in combination with modified live virus vaccines. The extracted antigen-acellular B. bronchiseptica vaccine does not produce injection site toxicity when administered by the recommended subcutaneous route. 63 Two immunizations with this product significantly protected dogs from clinical disease following aerosol challenge and reduced nasal shedding of B. bronchiseptica. 63 Development of defined, nontoxic component vaccines for B. bronchiseptica is a current research interest of the veterinary biologics industry. Many boarding and other types of ~ommercial kennels require preboarding, pre-sale, and pre-training immunization against canine infectious tracheobronchitis. 54 It is important for practitioners to be aware of available products and their limitations in order to wisely direct their usage in the field. With respect to B. bronchiseptica immunization, each of the three different types of products provide significant protection against disease, but none completely prevents infection. Parenteral products produce highest levels of systemic immunity; intranasal products produce highest levels of mucosal immunity. There may be some advantages to combined vaccine usage with systemic priming and antibody levels being maintained by a parenteral product on an annual basis and mucosal antigen exposure to produce local immunity with an intranasal product prior to anticipated contact with wild-type B. bronchiseptica organisms.10 B. bronchiseptica immunization has not been attempted in cats nor does it appear to be indicated on the basis of prevalence observations.
MYCOPLASMA INFECTIONS Association with Disease
Eleven species of mycoplasma, three unclassified groups of mycoplasmas, acholeplasmas, and ureaplasmas have been isolated from the upper respiratory tract (oropharynx, nasopharynx, larynx) of dogs.3 • 5 • 37· 57· 59 Greater than 90% of all reported mycoplasma isolations from the lower respiratory tract are from dogs with pneumonia; lungs of healthy dogs rarely harbor mycoplasmas. 58 Seven species of mycoplasma have
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been associated with canine pneumonia: M. canis, M. spumans, M. cynos, M. edwardii, M. gateae, M. feliminutum , and M. bovigenitalium. 57 Several untypable mycoplasma species and ureaplasmas also have been recovered from pneumonic dog lungs. 3· 5· 37 Greig27 associated mycoplasmas with infectious tracheobronchitis but was unable to reproduce the disease experimentally. Outbreaks of canine infectious tracheobronchitis have been described in which B. bronchiseptica was noticeably absent, but mycoplasma isolations were not attempted. 4· 47· 49· 74 An investigation of a typical outbreak in a: closed colony of Labrador Retrievers resulted in the isolation of M. spumans and canine parainfluenza virus from trachea swabs and lung tissues of affected animals (Bemis DA, unpublished data). No other bacteria or viruses were recovered. In data based on 233 identified isolates of mycoplasma, M. spumans was the species most frequently isolated from pneumonia in dogs. 57 Rosenda!56 was unable to demonstrate the pathogenicity of M. spumans, M. canis, and M. gateae but did produce disease experimentally with M. cynos and M. bovigenitalium. Mycoplasma felis, M. gateae, M. feliminutum , M. arginini, acholeplasmas, and ureaplasmas hav~ been identified in the upper respiratory tract of cats.57 M . felis and M . arginini have been isolated from cats with pneumonia, but M. felis is more frequently associated with conjunctivitis.29· 57 Pulmonary abscesses have been associated with mycoplasma infections in cats. 18· 38· 78 Respiratory diseases have not been experimentally reproduced with mycoplasmas in cats. The high degree of association with diseased animals and pathologic findings similar to those of known mycoplasmal pathogens suggest a causal relationship between isolated mycoplasmas and pulmonary disease in dogs and cats. Reservoirs, Prevalence, and Transmission
Canine and feline mycoplasmas are frequent, if not consistent, inhabitants of the upper respiratory tract; infections of the lower respiratory tract generally are thought to be of endogenous origin. However, because virulence attributes of canine and feline mycoplasmas have not been well established, the possibility of exogenous transmission cannot be dismissed entirely. The distribution and relative numbers of individual mycoplasma species in the respiratory tract have not been determined. Some mycoplasma species associated with respiratory diseases are also found on mucous membranes of the urogenital system or gastrointestinal tract. Several mycoplasma species can be recovered from both dogs and cats or from other animals. 57 Disease Symptomology, Pathology, and Pathogenesis
There have been few clinical evaluations of respiratory mycoplasma infections in dogs and cats. Most isolations have been made from lung
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tissues of animals that had died with pneumonia (fever, emaciation, lethargy, dyspnea, chronic cough, and crackles were among the most commonly reported clinical symptoms). 37• 55• 57 Chronic mycoplasma colonization has been observed in dogs with primary ciliary dyskinesia (Edwards, personal communication, 1991). Kirchner et aP7 found macroscopic lesions suggestive of pneumonia in two dogs that had not apparently manifested clinical signs. A dog with mild, acute onset symptoms thought to be consistent with infectious canine tracheobronchitis was also observed to have macroscopic lesions of pneumonia when necropsied for unrelated purposes (Bemis DA, unpublished observations). Other dogs in the same kennel experienced similar symptoms and recovered uneventfully. Macroscopic lesions of pneumonia were produced experimentally in dogs inoculated with M. cynos, but clinical symptoms were not observed. 56 Microscopic pathology of natural and experimental mycoplasma pneumonia in dogs and cats consists of purulent bronchitis and bronchiolitis with varying degrees of bronchiectasis and epithelial damage in early stages of disease, followed by bronchial and bronchiolar epithelial hyperplasia, peribronchial and perivascular lymphoid h yperplasia, interstitial pneumonia, and bronchiolitis obliterans in later stages. 37• 56• 57 In contrast to B. bronchiseptica, mycoplasmas colonize both ciliated and nonciliated surfaces in the respiratory tract (Bemis DA, unpublished data) and are more frequently isolated from systemic body sites. 7· 3 L 33 Diagnosis
Most canine and feline mycoplasmas can be easily isolated by culture on appropriate mycoplasma media. Species identification requires immunologic testing with reference antisera. These reagents are not commercially available, and because the virulence is still unresolved, few clinical laboratories routinely speciate canine and feline mycoplasmas. Methods to distinguish different strains within each mycoplasma species, for epidemiological purposes, are at present limited. Serologic tests are not available for diagnosis of mycoplasma infections in dogs and cats. Antimicrobial Treatment
Antimicrobial susceptibility tests for mycoplasmas have not been standardized and are not widely available. Kato et aJ35 reported in vitro susceptibilities of 55 strains of M. canis, 11 strains of M. spumans, and 7 strains of M. maculosum to 22 antimicrobials. They found tylosin to be most active (MIC90 < 0.5fJ.g/mL); lincomycin, spriamycin, josamycin, and leukomycin were also quite active (MIC90 < 10f.lg/mL). Tetracycline (MIC90 < 10f.lg/mL), chloramphenicol (MIC90 < 10f.lg/mL) and kana-
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mycin (MIC90 < 50J..Lg/mL) were moderately active. Erythromycin, oleandomycin, and polymixin B had little or no effect on canine mycoplasmas. Spiramycin and tylosin have been used with clinical successes in mycoplasma pneumonias in dogs and cats.18 • 55 Cats with extrapulmonary abscesses caused by mycoplasmas responded well to tetracycline therapy. 36 A similar human lesion, suspected to have been transmitted by a cat scratch, responded to doxycycline after treatments with erythromycin, cloxacillin, and penicillin had failed. 40 Because mycoplasmas lack cell wells, beta-lactam antibiotics are uniformly ineffective against · mycoplasmas. In vitro susceptibility tests on fifteen different mycoplasma species from animals other than dogs and cats concluded that ciprofloxacin was highly active against animal mycoplasmas. 3° Clinical studies with enrofloxacin suggested that it was effective against mycoplasma infections in dogs and cats. 9 Macrolides .other than erythromycin (tylosin, tiamulin), lincosamides (lincomycin, clindamycin), tetracycline, chloramphenicol, and quinolones (ciprofloxacin, enrofloxacin) appear to be the best choices for antimicrobial therapy (see Table 1). Vaccination
There are no vaccines available to prevent canine and feline mycoplasmal diseases.6 Potential for development of such vaccines appears to be limited . Vaccines for other m ycoplasmal diseases (except contagious bovine pleuropneumonia) have not met with a great deal of success. 6 SUMMARY
The con sequences of B. bronchiseptica and mycoplasma infections in dogs and cats vary greatly. Only careful clinical judgment can dictate when to institute antimicrobial and other supportive treatments. Approaches to controlling diseases caused by these organisms should be tailored to meet individual needs. Management strategies that reduce natural exposure levels in the animal's en vironment and maintain active immunity to contagiou s components of disease have the highest likelihood of success. References 1. Alkire LT, Chladek DW: Field evaluation of an intranasally ad m inistered canine parainfluenza- Bordetella bronchiseptica vaccine. Vet Med/Small Anim Clin 75:1003, 1980 2. Amis TC: Chronic bronchitis in dogs. In Kirk RW (ed): Curren t Veterinary Therapy IX. Sm all Animal Practice. Philadelphia, WB Saunders, 1986, p . 247- 250
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3. Armstrong D, Tully JG, Yu B, et al: Previously uncharacterized mycoplasma isolates from an investigation of canine pneumonia. Infect Immun 1:1-7, 1970 4. Azetaka M, Konishi S: Kennel cough complex: Confirmation and analysis of the outbreak in Japan. Jpn J Vet Sci 50:851-858, 1988 5. Ball HJ, Bryson DG: Isolation of ureaplasmas from pneumonic dog lungs. Vet Rec 111:585, 1982 6. Barile MF: Immunization against mycoplasma infections. In Razin S, Barile MF (eds): The Mycoplasmas, vol 4. New York, Academic Press, 1985, pp 478, 451-483 7. Barton MD, Ireland L, Kirschner JL, et al: Isolation of Mycoplasma spumans from polyarthritis in a greyhound. Aust Vet J 62:206-207, 1985 8. Batey RG, Smits AF: The isolation of Bordetella bronchiseptica from an outbreak of canine pneumonia. Aust Vet J 52:184-186, 1976 9. Bauditz R: Results of clinical studies with Baytril in dogs and cats. Vet Med Rev 2:137- 140, 1987 10. Bemis DA: Current strategies for the control of canine infectious tracheobronchitis in canine cough. In Proceedings of the 5th Annual Eastern States Veterinary Conference, Orlando, FL, 1988, pp 22-35 11. Bemis DA, Appel MJG: Aerosol, parenteral and oral antibiotic treatment of Bordetella bronchiseptica infections in dogs. J Am Vet Med Assoc 170:1082-1086, 1977 12. Bemis DA, Carmichael LE, Appel MJG: Naturally occurring respiratory disease in a kennel caused by Bordetella bronchiseptica. Cornell Vet 67:282-293, 1977 13. Bemis DA, Greisen HA, Appel MGJ: Pathogenesis of canine bordetellosis. J Infect Dis 135:753-762, 1977 14. Bemis DA, Kennedy JR: An improved system for studying the effect of Bordetella bronchiseptica on the ciliary activity of canine tracheal epithelial cells. J Infect Dis 144:349-357, 1981 15. Bey RF, Shade FJ, Goodnow RA, et al: Intranasal vaccination of dogs with live avirulent Bordetella bronchiseptica: Correlation of serum agglutination titer and the formation of secretory IgA with protection against experimentally induced infectious tracheobronchitis. Am J Vet Res 42:1130- 1132, 1981 16. Chladek OW, Williams JM, Gerber DL: Canine parainfluenza- Bordetella bronchiseptica vaccine: Immunogenicity. Am J Vet Res 42:266-270, 1981 17. Collings LA, Rutter, JM: Virulence of Bordetella bronchiseptica in the porcine respiratory tract. J Med Microbial 19:247-258, 1985 18. Crisp MS, Birchard SJ, Lawrence AE: Pulmonary abscesses caused by a mycoplasma spin a cat. J Am Vet Med Assoc 191:340, 1987 · · 19. Dhein CR, Gorham JR: Canine respiratory infections. In Scott FW (ed): Contemporary Issues in Small Animal Practice, vol 3. Infectious Diseases. New York, Churchill Livingstone, 1986, p 177 20. Ferry NS: A preliminary report of the bacteriological findings in canine distemper. Am Vet Rev 37:499- 504, 1910 21. Fisk SK, Soave, OA: Bordetella bronchiseptica in laboratory cats from central California. Lab Anim Sci 23:33-35, 1973 22. Ford RB, Vaden SL: Canine infectious tracheobronchitis. In Greene CE (ed): Infectious Diseases of the Dog and Cat. Philadelphia, WB Saunders, 1990, p 259-260 23. Glickman LT, Appel MJ: Intranasal vaccine trial for canine infectious tracheobronchitis (kennel cough). Lab Anim Sci 31:397-399, 1981 24. Goodnow RA: Biology of Bordetella bronchiseptica. Microbial Rev 44:722- 738, 1980 25. Goodnow RA, Shade FJ: Control of canine bordetellosis. Mod Vet Pract 61:597- 598, 1980 26. Graham AC, Abruzzo GK: Occurrence and characterization of plasmids in field isolates of Bordetella bronchiseptica. Am J Vet Res 43:1852-1855, 1982 27. Greig AS: The significance of a pleuropneumonia-like organism in kennel cough. Can J Comp Med 18:275- 278, 1954 28. Hackett IJ: Intratracheal treatment. Vet Rec 122:119, 1988 29. Haesebrouck F, Devriese LA, van Rijssen B, et a!: Incidence and significance of isolation of Mycoplasma felis from conjunctival swabs of cats. Vet Microbial 26:95- 101, 1991 30. Hannan PCT, O'Hanlon PJ, Rogers NH: In vitro evaluation of various quinolone
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antibacterial agents against veterinary mycoplasmas and porcine respiratory bacterial pathogens. Res Vet Sci 46:202-211, 1989 Henricks PM: Isolation of two mycoplasma sp from the peritoneal cavity of a dog. Can Vet J 28:437-438, 1987 Hirsch DC: Bacteriology of the lower respiratory tract. In Kirk RW (ed): Current Veterinary Therapy VIII. Small Animal Practice. Philadelphia, WB Saunders, 1986, pp 247-250 Hooper PT, Ireland LA, Carter A: Mycoplasma polyarthritis in a cat with probable severe immune deficiency. Aust Vet J 62:352, 1985 Hutchison RV: Intratracheal gentamicin and dexamethasone for treatment of infectious tracheobronchitis in the dog. Vet Med/Small Anim Clin 70:943-945, 1975 Kato H, Murakami T, Takase S, et al: Sensitivities in vitro to antibiotics ofmycoplasmas isolated from canine sources. Jpn J Vet Sci 34:197-206, 1972 Keane DP: Chronic abscesses in cats associated with an organism resembling mycoplasma. Can Vet J 24:289-291, 1983 Kirchner BK, Port CD, Magoc TJ, et al: Spontaneous bronchopneumonia in laboratory dogs infected with untyped mycoplasma sp. Lab Anim Sci 40:625-628, 1990 Malik R, Love ON, Hunt GB, et al: Pyothorax associated with a mycoplasma species in a kitten. J Small Anim Pract 32:31-34, 1991 Matsuda H, Tojo M, Fukui K, et al: The aerobic bacterial flora of the middle and external ears in normal dogs. J Small Anim Pract 25:269-274, 1984 McCabe SJ, Murray JF, Ruhnke HL: Mycoplasma infection of the hand acquired from a cat. J Hand Surg 12[Am]:1985, 1987 McCandlish lAP, Thompson H: Vaccination against Bordetella bronchiseptica infection in dogs using a heat-killed bacterial vaccine. Res Vet Sci 25:45-50, 1978 McCandlish lAP, Thompson H: Canine bordetellosis: Chemotherapy using a sulfadiazine-trimethoprin combination. Vet Rec 104:51-54, 1979 McCandlish lAP, Thompson H, Wright NG: Vaccination against canine bordetellosis using an aluminum hydroxide adjuvant vaccine. Res Vet Sci 25:51-58, 1978 McCandlish lAP, Thompson H, Wright NG: Vaccination against canine bordetellosis: Protection from contact challenge. Vet Rec 192:479- 483, 1978 McGowan JP: Some observations on a laboratory epidemic, principally among dogs and cats, in which the animals affected presented the symptoms of the disease called "distemper" . J Pathol Bacteriol 15:372-426, 1911 McKiernan BC, Smith AR, Kissil M: Bacterial isolates from the lower trachea of clinically healthy dogs. JAm Anim Hosp Assoc 20:139, 1984 Moloney MB, Pye D, Smith HV, et al: Isolation of parainfluenza virus from dogs. Aust Vet J 62:285-286, 1985 Musser JM, Bemis DA, Ishikawa H, et al: Clonal diversity and host distribution in Bordetella bronchiseptica. J Bacteriol 169:2793-2803, 1987 Noor F, Majid MS: Canine infectious tracheobronchitis in an animal facility: A bacteriological survey. Kajian Veterinar 14:1-4, 1982 van Oosterhout ICAM, Meij BP, Venker-van Haagen AJ, et al: Rhinoscopy in small animal clinics: an analysis of the results of 233 rhinoscopies and 97 bacterial cultures from nasal swabs. Tijdschrift voor Diergeneeskunde 114Sl:94-95, 1989 Ostle GN: Cough associated with canine vaccination? Vet Rec 125:446, 1989 Pecora DV: Bacteriologic cultural examination of the lower respiratory tract of laboratory dogs. Am J Vet Res 37:1511- 1513, 1976 Porter JF, Parton R, Wardlaw AC: Growth and survival of Bordetella bronchiseptica in natural waters and in buffered saline without added nutrients. Appl Environ Microbiol 57:1202- 1206, 1991 Praeger D: Tracheobronchitis, how some kennels are fighting back. Groom and Board July-Aug:24-25, 1985 Rosendal S: Mycoplasmas as a possible cause of enzootic pneumonia in dogs. Acta Vet Scand 13:137-139, 1972 Rosendal S: Canine mycoplasmas: Pathogenicity of mycoplasmas associated with distemper pneumonia. J Infect Dis 138:203-209, 1978 Rosendal S: Canine and feline mycoplasmas. In Barile MF, Razin S, Tully JG, et a! (eds): The Mycoplasmas, vol 2. New York, Academic, 1979, pp 217-234
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Address reprint requests to David A. Bemis, PhD Department of Microbiology University of Tennessee College of Veterinary Medicine Knoxville, TN 37996