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Download Bacterial Pathogens Associated With Bovine Respiratory Disease
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Bacterial Pathogens Associated With Bovine Respiratory Disease Complex Pneumonia is an inflammation of the tissues of the lungs that results from the response of the animal to an infectious agent, either a virus or bacteria, or in most cases both. Common viruses that can initiate pneumonia in cattle include: IBR (infectious bovinerhinotracheitis virus; a herpes virus), BRSV (bovine respiratory syncytial virus), PI3 (parainfluenza 3 virus), and BVD (bovine virus diarrhea virus). Often the virus infection will cause damage to the lung tissue and then bacteria will invade the compromised tissues. Lung damage from bacterial pneumonia, in the form of lesions, is generally the precipitating factor in BRDC related mortality. The four main bacterial pathogens involved in BRDC are opportunistic pathogens, normally residing in the respiratory tracts of healthy cattle, and becoming pathogenic when stress and secondary infection impairs immune function1. Three of the main bacterial pathogens (Mannheimia haemolytica, Pasturella multocida, and Histophilis somni) frequently associated with BRDC are all generally susceptible to the same types of antibiotics2. However, Mycoplasma bovis is a more genetically distinct bacterial pathogen involved in BRD. It lacks cell walls and is therefore not susceptible to some common types of antibiotics, like penicillin3. The importance of knowing the bacteria involved in BRDC is that it can influence treatment options. Mannheimia haemolytica Mannheimia haemolytica (formerly named Pasturella haemolytica ) is commonly isolated from the lungs of cattle with pneumonia2. Mannheimia haemolytica is comprised of 12 capsular serotypes, with serotype A1 involved in most cases of pneumonia. Serotype A1 alone can cause pneumonia, but pneumonia symptoms are difficult to replicate without adding environmental stress or viral infection4. The switch from commensal to pathogenic organism is considered density dependent, because virulence factors are stimulated when M. haemolytica is able to grow rapidly in the lung5. One important virulence factor, leukotoxin, is excreted during the log phase of bacterial growth6. Leuktoxin is thought to play a major role in lung injury 7 due to its ability to damage white blood cells 8 and elicit a vigorous inflammatory response9. Pasturella multocida Pasturella multocida subsp. multocida ranks only below Mannheimia heamolytica in involvement in fatal cases of BRDC2,10, but the involvement of P. multocida in BRDC has risen in recent years2. The presence of P. multocida in the upper respiratory tract is not always associated with disease11,12. It is not clear if commensal P. multocida converts to a pathogen in a density dependent manner, or if differences in the lung environment after viral infection favor the growth of more pathogenic isolates13. P. multocida does generate a density dependent signal similar to M. haemolytica5, but no toxins are known to be secreted from P. multocida involved in pneumonia14,15. Other virulence factors, such molecules on the bacterial surface, may be important for P. multocida pathogenicity15. Pasturella multocida is the only common BRDC pathogen that is zoonotic, or infectious to humans. P. multocida is generally transmitted to humans by animal bite, scratch, or lick16. Histophilis somni Histophilis somni (formerly named Haemophilus somnus) is commonly isolated from the lungs of cattle with BRDC2. In addition to being associated with of BRDC, H. somni is involved in bovine infertility, abortion, septicemia, arthritis, myocarditis, and thrombotic meningoencephalitis 17. H. somni infections are characterized by inflammatory destruction of blood vessels18. H. somni virulence stems from molecules embedded on the bacterium’s cell surface. A primary virulence factor is lipoologosaccaride (LOS) which, along with other molecules on the cell surface, can mimic eukaryotic cell coatings, and may help hide the bacteria from the bovine immune system17,19. LOS can also damage endothelial cells and activate platelets, inducing vascular inflammation and coagulation20,21. Vascular inflammation is further exacerbated by the ability of H. somni to produce histamine22. Mycoplasma bovis For dairy calves, there are limited data on the prevalence of M. bovis. This bacterium has been the subject of considerable investigation; however, its primary role in bovine bacterial pneumonia is controversial23. M. bovis has been isolated from up to 45% of grossly and histologically normal bovine lungs 24. The nasal prevalence of M. bovis in Californian dairy calves up to 8 months of age was 34% in herds with M. bovis-associated disease and 6% in nondiseased herds25. A longitudinal study showed that almost all calves in diseased herds became infected with M. bovis26. M. bovis is also associated with bovine mastitis, arthritis, and ear infections. M. bovis is the predominant cause of ear infections in cattle27, and infected animals may display ear droop, head tilt, and ear drainage due to infection of the middle ear28. Arthritis and lameness generally occur after prolonged M. bovis infections29. M. bovis should be suspected in cases of pneumonia that are unresponsive to antibiotic treatments, especially if accompanied by ear infection or arthritis30. Because mycoplasmas lack a cell wall, the β-lactam antimicrobials are not effective against these pathogens. Similarly, mycoplasmas do not synthesize folic acid and are therefore intrinsically resistant to sulfonamides. Mycoplasmas as a class are generally susceptible to drugs that interfere with protein (tetracyclines, macrolides, linosamides, and florfenicol) or DNA (fluoroquinolones) synthesis. However, M. bovis is resistant to erythromycin31. Unlike the other bacterial pathogens associated with BRDC, M. bovis is shed in the milk of infected cows. Feeding calves unpasteurized milk is thought to play a role in the transmission of M. bovis32. Treatment of Bacterial Pneumonia Early detection and treatment of BRD is a priority to quickly reduce the impact on infected bovine. Initial clinical signs include an elevated temperature, nasal and eye discharge, walking with a stiff gait, a crusty muzzle, salivation and mild diarrhea. Rapid shallow breathing and coughing are also early signs. Affected animals will often hang their heads and look lethargic. Their unwillingness to eat is closely tied to fever and depression. Evaluating calves for treatment using a screening system, such as the calf respiratory scoring chart which was developed at the University of Wisconsin, (http://www.vetmed.wisc.edu/dms/fapm/fapmtools/8calf/group_pen_respiratory_scoring_chart.pdf), and is based on rectal temperature, character of nasal discharge, eye or ear appearance and presence of coughing, has been recommended for dairy calves33. Cases of bacterial pneumonia resulting from BRDC are typically treated with antibiotics, sometimes in conjunction with non-steroidal anti-inflammatories (NSAIDs). Success of antibiotic treatment is dependent on proper timing and dosage of drug administration and susceptibility of the bacterial pathogen(s) to the administered antibiotic. It is important to follow labeling instructions and veterinary guidelines as to the proper usage of antibiotics. Vaccination Against Bacterial Pneumonia USDA approved vaccines are available to help protect cattle against the four main bacterial pathogens involved in BRDC34. The practice of vaccination against bacterial BRDC pathogens is common, but less so than vaccination against viral BRDC pathogens35. However, the efficacy of vaccination in preventing or reducing the severity of BRDC is not well established36. No decrease in treatments for respiratory disease was observed in young dairy calves vaccinated with a modified-live Mannheimia haemolytica and Pasteurella multocida vaccine37. Therefore vaccination should be considered only one element of BRDC prevention, along with efforts to minimizing calf stress, colostrum feeding, and hygiene. Consult your veterinarian to determine a vaccination protocol that matches the needs of your herd with location-specific disease pressures. Further reading and internet resources: Mycoplasma: Calf to Cow. http://www.vetmed.ucdavis.edu/vetext/INF-DA/Wust-mycoplasma.pdf Calf notes by Dr. Jim Quigley: English http://www.calfnotes.com Spanish/Español http://www.calfnotes.com/CNnotasterneros.htm Calf facts by Dr. Sam Leadley: English and Spanish/Español http://atticacows.com/ University of Wisconsin Dairy Calf Clinical Information and Forms including respiratory scoring chart http://www.vetmed.wisc.edu/dms/fapm/fapmtools/calves.htm 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. Griffin, D., Chengappa, M., Kuszak, J. & McVey, D.S. Bacterial pathogens of the bovine respiratory disease complex. Veterinary Clinics of North America: Food Animal Practice 26, 381-394 (2010). Welsh, R.D., Dye, L.B., Payton, M.E. & Confer, A.W. Isolation and antimicrobial susceptibilities of bacterial pathogens from bovine pneumonia: 1994–2002. Journal of Veterinary Diagnostic Investigation 16, 426 (2004). Caswell, J.L., Bateman, K.G., Cai, H.Y. & Castillo-Alcala, F. Mycoplasma bovis in respiratory disease of feedlot cattle. Veterinary Clinics of North America: Food Animal Practice 26, 365-379 (2010). Frank, G.H. Pasteurellosis of cattle. in Pasteurella and pasteurellosis (ed. Adlam C. F., R.J.M.) (Academic Press, London, 1989). Malott, R.J. & Lo, R.Y.C. Studies on the production of quorum‐sensing signal molecules in Mannheimia haemolytica A1 and other Pasteurellaceae species. FEMS microbiology letters 206, 25-30 (2002). Shewen, P. & Wilkie, B. Evidence for the Pasteurella haemolytica cytotoxin as a product of actively growing bacteria. American Journal of Veterinary Research 46, 1212–1214 (1985). Highlander, S.K. et al. Inactivation of Pasteurella (Mannheimia) haemolytica leukotoxin causes partial attenuation of virulence in a calf challenge model. Infection and immunity 68, 3916 (2000). Shewen, P.E. & Wilkie, B.N. Cytotoxin of Pasteurella haemolytica acting on bovine leukocytes. Infection and immunity 35, 91 (1982). Czuprynski, C.J. Host response to bovine respiratory pathogens. Animal Health Research Reviews 10, 141143 (2009). Lillie, L. The bovine respiratory disease complex. The Canadian Veterinary Journal 15, 233 (1974). Fulton, R.W. et al. Evaluation of health status of calves and the impact on feedlot performance: assessment of a retained ownership program for postweaning calves. Canadian Journal of Veterinary Research 66, 173 (2002). Allen, J. et al. The microbial flora of the respiratory tract in feedlot calves: associations between nasopharyngeal and bronchoalveolar lavage cultures. Canadian Journal of Veterinary Research 55, 341 (1991). Dabo, S., Taylor, J. & Confer, A. Pasteurella multocida and bovine respiratory disease Animal Health Research Reviews 8, 129-150 (2007). Fuller, T.E., Kennedy, M.J. & Lowery, D.E. Identification of Pasteurella multocida virulence genes in a septicemic mouse model using signature-tagged mutagenesis. Microbial pathogenesis 29, 25-38 (2000). 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. Harper, M., Boyce, J.D. & Adler, B. Pasteurella multocida pathogenesis: 125 years after Pasteur. FEMS microbiology letters 265, 1-10 (2006). Kawashima, S., Matsukawa, N., Ueki, Y., Hattori, M. & Ojika, K. Pasteurella multocida meningitis caused by kissing animals: a case report and review of the literature. Journal of neurology 257, 653-654 (2010). Corbeil, L.B. Histophilus somni host-parasite relationships. Animal Health Research Reviews 8, 151-160 (2007). Gogolewski, R., Leathers, C., Liggitt, H. & Corbeil, L. Experimental Haemophilus somnus pneumonia in calves and immunoperoxidase localization of bacteria. Veterinary Pathology Online 24, 250 (1987). Sandal, I. & Inzana, T.J. A genomic window into the virulence of Histophilus somni. Trends in microbiology 18, 90-99 (2010). Kuckleburg, C.J., McClenahan, D.J. & Czuprynski, C.J. Platelet activation by Histophilus somni and its LOS induces endothelial cell pro-inflammatory responses and platelet internalization. Shock (Augusta, Ga.) 29, 189 (2008). Kuckleburg, C.J. et al. Bovine platelets activated by Haemophilus somnus and its LOS induce apoptosis in bovine endothelial cells. Microbial pathogenesis 38, 23-32 (2005). Ruby, K.W., Griffith, R.W. & Kaeberle, M.L. Histamine production by Haemophilus somnus. Comparative immunology, microbiology and infectious diseases 25, 13-20 (2002). Confer, A.W. Update on bacterial pathogenesis in BRD. Anim Health Res Rev 10, 145-8 (2009). Gagea, M.I. et al. Diseases and pathogens associated with mortality in Ontario beef feedlots. Journal of Veterinary Diagnostic Investigation 18, 18-28 (2006). Bennett, R.H. & Jasper, D.E. Nasal Prevalence of Mycoplasma-Bovis and Iha Titers in Young Dairy Animals. Cornell Veterinarian 67, 361-373 (1977). Maunsell, F.P., Donovan, G.A., Risco, C. & Brown, M.B. Field evaluation of a Mycoplasma bovis bacterin in young dairy calves. Vaccine 27, 2781-2788 (2009). Lamm, C.G., Munson, L., Thurmond, M.C., Barr, B.C. & George, L.W. Mycoplasma otitis in California calves. Journal of veterinary diagnostic investigation 16, 397 (2004). Maeda, T. et al. Mycoplasma bovis-associated suppurative otitis media and pneumonia in bull calves. Journal of Comparative Pathology 129, 100-110 (2003). Nicholas, R. & Ayling, R. Mycoplasma bovis: disease, diagnosis, and control. Research in veterinary science 74, 105-112 (2003). Maunsell, F.P. & Donovan, G.A. Mycoplasma bovis infections in Young Calves. Veterinary Clinics of North America: Food Animal Practice 25, 139-177 (2009). Maunsell, F.P. et al. Mycoplasma bovis Infections in Cattle. Journal of Veterinary Internal Medicine 25, 772-783 (2011). Caswell, J.L. & Archambault, M. Mycoplasma bovis pneumonia in cattle. Animal Health Research Reviews 8, 161-186 (2007). McGuirk, S.M. Disease Management of Dairy Calves and Heifers. The Veterinary clinics of North America. Food animal practice 24, 139-153 (2008). USDA. Veterinary Biological Products. (United States Department of Agriculture Center for Veternary Biologics, Ames, IA 2011). NAHMS. Vaccination Practices for Respiratory Pathogens in U.S. Feedlots. (ed. USDA) (Fort Collins, CO, 2000). Taylor, J.D., Fulton, R.W., Lehenbauer, T.W., Step, D.L. & Confer, A.W. The epidemiology of bovine respiratory disease: What is the evidence for preventive measures? The Canadian Veterinary Journal 51, 1351 (2010). Aubry, P., Warnick, L.D., Guard, C.L., Hill, B.W. & Witt, M.F. Health and performance of young dairy calves vaccinated with a modified-live Mannheimia haemolytica and Pasteurella multocida vaccine. Journal of the American Veterinary Medical Association 219, 1739-+ (2001). The “Integrated Program for Reducing Bovine Respiratory Disease Complex (BRDC) in Beef and Dairy Cattle” Coordinated Agricultural Project is supported by Agriculture and Food Research Initiative Competitive Grant no. 2011-68004-30367 from the USDA National Institute of Food and Agriculture.”