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The emergence of Clostridium difficile as a pathogen of food animals

Published online by Cambridge University Press:  28 February 2007

J. Glenn Songer
J. Glenn Songer*
Affiliation:
Department of Veterinary Science and Microbiology, University of Arizona, Tucson, AZ 85721, USA
*
E-mail: [email protected]
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Abstract

Clostridium difficile causes pseudomembranous colitis in humans, usually after disruption of the bowel flora by antibiotic therapy. Factors mediating the frank disease include the dose and toxigenicity of the colonizing strain, its ability to adhere to colonic epithelium, the concurrent presence of organisms that affect multiplication and toxin production or activity, and the susceptibility of the host. Toxins A (an enterotoxin) and B (a cytotoxin) play the major role in pathogenesis and the detection of toxins in gut contents is the gold standard for diagnosis. Disease in horses takes the form of often-fatal foal hemorrhagic enteritis. Nosocomial, antibiotic-associated, disease is increasingly common in adult horses. Enteric clinical signs are reported in ostriches, companion animals and recently calves. Clostridium difficile colitis is now a common diagnosis in neonatal pigs in the USA and elsewhere. Clinical features include onset at 1–5 days of age, sometimes with dyspnea, mild abdominal distension and scrotal edema, and commonly with yellow, pasty diarrhea. There is mesocolonic edema grossly, with microscopic diffuse colitis, mucosal edema, crypt distension, epithelial necrosis and superficial mucosal erosion. Neutrophil infiltration of the lamina propria is common, and fibrin and numerous rod-shaped bacteria are observed on the surface. About two-thirds of litters and one-third of piglets will be affected (based upon positive toxin tests), although this appears to vary with the season. The case fatality rate is probably low if considering only direct effects of C. difficile infection. The significance of toxin-positive non-diarrheic pigs and the nature of the interaction of toxins A and B with enterocytes are unknown. Given the widespread occurrence of the disease, there is substantial effort to develop immunoprophylactic products.

Keywords

Clostridium difficilepathogensfood animalspigs
Type
Research Article
Information
Animal Health Research Reviews , Volume 5 , Issue 2 , December 2004 , pp. 321 - 326
Copyright
Copyright © CAB International 2004

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References

Aktories, K (1997a). Bacterial toxins that target Rho proteins. Journal of Clinical Investigation 99: 827–829.CrossRefGoogle ScholarPubMed
Aktories, K (1997b). Rho proteins: targets for bacterial toxins. Trends in Microbiology 5: 282–288.CrossRefGoogle ScholarPubMed
Aldeen, WE, Bingham, M, Aiderzada, A, Kucera, J, Jense, S and Carroll, KC (2000). Comparison of the TOX A/B test to a cell culture cytotoxicity assay for the detection of Clostridium difficile in stools. Diagnostic Microbiology and Infectious Disease 36: 211–213.CrossRefGoogle ScholarPubMed
Alfa, MJ, Kabani, A, Lyerly, D, Moncrief, S, Neville, LM, Al-Barrak, A, Harding, GK, Dyck, B, Olekson, K and Embil, JM (2000). Characterization of a toxin A-negative, toxin B-positive strain of Clostridium difficile responsible for a nosocomial outbreak of Clostridium difficile -associated diarrhea. Journal of Clinical Microbiology 38: 2706–2714.CrossRefGoogle ScholarPubMed
Allo, M, Silva, J, Fekety, R, Rifkin, GD and Waskin, H (1979). Prevention of clindamycin-induced colitis in hamsters by Clostridium sordellii antitoxin [sound recording]. Gastroenterology (Glendale, Calif.) 76: 351–355.Google ScholarPubMed
Aronsson, B, Granstrom, M, Mollby, R and Nord, CE (1985). Serum antibody response to Clostridium difficile toxins in patients with Clostridium difficile diarrhoea. Infection 13: 97–101.CrossRefGoogle ScholarPubMed
Barbut, F, Richard, A, Hamadi, K, Chomette, V, Burghoffer, B and Petit, JC (2000). Epidemiology of recurrences or reinfections of Clostridium difficile -associated diarrhea. Journal of Clinical Microbiology 38: 2386–2388.CrossRefGoogle ScholarPubMed
Bartlett, JG (1992). Antibiotic-associated diarrhea. Clinical Infectious Diseases 15: 573–581.CrossRefGoogle ScholarPubMed
Bartlett, JG, Onderdonk, AB and Cinseros, RL (1977). Clindamycin-associated colitis due to a toxin-producing species of clostridium in hamsters. Journal of Infectious Diseases 136: 701–705.Google Scholar
Bartlett, JG, Chang, TTW, Gurwith, M, Gorbach, SL and Onderdonk, AB (1978). Antibiotic-associated pseudomembranous colitis due to toxin-producing clostridia. New England Journal of Medicine 298: 531–534.Google Scholar
Bongaerts, GP and Lyerly, DM (1994). Role of toxins A and B in the pathogenesis of Clostridium difficile disease. Microbial Pathogenesis 17: 1–12.CrossRefGoogle Scholar
Borriello, SP and Wilcox, MH (1998). Clostridium difficile infections of the gut: the unanswered questions. Journal of Antimicrobial Chemotherapy 41 Supplement C: 67–69.Google Scholar
Braun, V, Hundsberger, T, Leukel, P, Sauerborn, M and von Eichel-Streiber, C (1996). Definition of the single integration site of the pathogenicity locus in Clostridium difficile. Gene 181: 29–38.CrossRefGoogle ScholarPubMed
Corthier, G, Muller, MC, Wilkins, TD, Lyerly, D, L'Haridon, R (1991). Protection against experimental pseudomembranes colitis in gnotobiotic mice by use of monoclonal antibodies against Clostridium difficile toxin A. Infection and Immunity 59: 1192–1195.CrossRefGoogle ScholarPubMed
Fekety, R and Shah, AB (1993). Diagnosis and treatment of Clostridium difficile colitis. Journal of the American Medical Association 269: 71–75.CrossRefGoogle ScholarPubMed
Fekety, R, Kim, KH, Brown, D, Batts, DH, Cudmore, M, Silva, J Jr (1981). Epidemiology of antibiotic-associated colitis: isolation of Clostridium difficile from the hospital environment. American Journal of Medicine 70: 906–908.CrossRefGoogle ScholarPubMed
Fekety, R, McFarland, LV, Surawicz, CM, Greenberg, RN, Elmer, GW and Mulligan, ME (1997). Recurrent Clostridium difficile diarrhea: characteristics of and risk factors for patients in a prospective, randomized, double-blinded trial. Clinical Infectious Diseases 24: 324–333.CrossRefGoogle Scholar
Frey, SM and Wilkins, TD (1992). Localization of two epitopes recognized by monoclonal antibody PCG-4 on Clostridium difficile toxin A. Infection and Immunity 60: 2488–2492.CrossRefGoogle ScholarPubMed
Giannasca, PJ, Zhang, Z-X, Lei, W-D, Boden, JA, Giel, MA, Monath, TP, Thomas, WD Jr (1999). Serum antitoxin antibodies mediate systemic and mucosal protection from Clostridium difficile disease in hamsters. Infection and Immunity 67: 527–538.CrossRefGoogle ScholarPubMed
Johnson, D, Clabots, CR and Linn, FV (1990). Nosocomial Clostridium difficile colonisation and disease. Lancet 336: 97–100.Google Scholar
Johnson, S and Gerding, DN (1998). Clostridium difficile -associated diarrhea. Clinical Infectious Diseases 26: 1027–1036.Google Scholar
Johnson, S, Samore, MH and Farrow, KA (1999). Epidemics of diarrhea caused by a clindamycin-resistant strain of Clostridium difficile in four hospitals. New England Journal of Medicine 341: 1645–1651.Google Scholar
Jones, MA and Hunter, D (1983). Isolation of Clostridium difficile from pigs. Veterinary Record 112: 253.CrossRefGoogle Scholar
Kelly, CP and LaMont, JT (1998). Clostridium difficile infection. Annual Review of Medicine 49: 375–390.Google Scholar
Kelly, CP, Pothoulakis, C, Orellana, J and LaMont, JT (1992). Human colonic aspirates containing immunoglobulin A antibody to Clostridium difficile toxin A inhibit toxin A–receptor binding. Gastroenterology 102: 35–40.Google Scholar
Kelly, CP, Pothoulakis, C and LaMont, JT (1994). Clostridium difficile colitis. New England Journal of Medicine 330: 257–262.Google Scholar
Kelly, CP, Pothoulakis, C and Vavva, F (1996). Anti- Clostridium difficile bovine immunoglobulin concentrate inhibits cytotoxicity and enterotoxicity of C. difficile toxins. Antimicrobial Agents and Chemotherapy 40: 373–379.Google Scholar
Kelly, CP, Chetham, S and Keates, S (1997). Survival of anti- Clostridium difficile bovine immunoglobulin concentrate in the human gastrointestinal tract. Antimicrobial Agents and Chemotherapy 41: 236–241.Google Scholar
Ketley, JM, Mitchell, TJ, Candy, DC, Burdon, DW and Stephen, J (1987). The effects of Clostridium difficile crude toxins and toxin A on ileal and colonic loops in immune and non-immune rabbits. Journal of Medical Microbiology 24: 41–52.CrossRefGoogle ScholarPubMed
Kim, PH, Iaconis, JP and Rolfe, RD (1987). Immunization of adult hamsters against Clostridium difficile-associated ileocecitis and transfer of protection to infant hamsters. Infection and Immunity 55: 2984–2992.CrossRefGoogle ScholarPubMed
Kink, JA and Williams, JA (1998). Antibodies to recombinant Clostridium difficile toxins A and B are an effective treatment and prevent relapse of C. difficile -associated disease in a hamster model of infection. Infection and Immunity 66: 2018–2025.CrossRefGoogle Scholar
Klipfel, AA, Schein, M, Fahoum, B and Wise, L (2000). Acute abdomen and Clostridium difficile colitis: still a lethal combination. Digestive Surgery 17: 160–163.CrossRefGoogle Scholar
Kyne, L, Warny, M, Qamar, A and Kelly, CP (2000). Asymptomatic carriage of Clostridium difficile and serum levels of IgG antibody against toxin A. New England Journal of Medicine 342: 390–397.CrossRefGoogle ScholarPubMed
Kyne, L, Warny, M and Qamar, A (2001). Association between antibody response to toxin A and protection against recurrent Clostridium difficile diarrhoea. Lancet 357: 189–193.Google Scholar
Larson, HE, Parry, JV, Price, AB, Davies, DR and Tyrrell, DA (1977). Underdescribed toxin in pseudomembranous colitis. British Medical Journal 1: 1246–1248.CrossRefGoogle Scholar
Leung, DY, Kelly, CP and Boguniewicz, M (1991). Treatment with intravenously administered gamma globulin of chronic relapsing colitis induced by Clostridium difficile toxin. Journal of Pediatrics 118: 633–637.Google Scholar
Limaye, AP, Turgeon, DK, Cookson, BT and Fritsche, TR (2000). Pseudomembranous colitis caused by a toxin A(–) B(+) strain of Clostridium difficile. Journal of Clinical Microbiology 38: 1696–1697.Google Scholar
Lyerly, DM, Frey, SM and Wilkins, TD (1990). Vaccination against lethal Clostridium difficile enteritis with a nontoxigenic recombinant peptide of toxin A. Current Microbiology 21: 29–33.CrossRefGoogle Scholar
Lyerly, DM, Bostwick, EF, Binion, SB and Wilkins, TD (1991). Passive immunization of hamsters against disease caused by Clostridium difficile by use of bovine immunoglobulin G concentrate. Infection and Immunity 59: 2215–2218.Google Scholar
McFarland, LV, Mulligan, ME, Kwok, RY and Stamm, WE (1989). Nosocomial acquisition of Clostridium difficile infection. New England Journal of Medicine 320: 204–210.Google Scholar
Moncrief, JS, Barroso, LA and Wilkins, TD (1997). Positive regulation of Clostridium difficile toxins. Infection and Immunity 65: 1105–1108.Google Scholar
Moncrief, JS, Zheng, L, Neville, LM and Lyerly, DM (2000). Genetic characterization of toxin A–negative, toxin B–positive Clostridium difficile isolates by PCR. Journal of Clinical Microbiology 38: 3072–3075.CrossRefGoogle ScholarPubMed
O'Connor, D, Hynes, P, Cormican, M, Collins, E, Corbett-Feeney, G and Cassidy, M (2001). Evaluation of methods for detection of toxins in specimens of feces submitted for diagnosis of Clostridium difficile-associated diarrhea. Journal of Clinical Microbiology 39: 2846–2849.CrossRefGoogle ScholarPubMed
Olson, MM, Shanholtzer, CJ, Lee, JT and Gerding, DN Jr (1994). Ten years of prospective Clostridium difficile-associated disease surveillance and treatment at the Minneapolis VA Medical Center, 1982–1991. Infection Control and Hospital Epidemiology 15: 371–381.CrossRefGoogle ScholarPubMed
Post, KW and Songer, JG (2001). Antimicrobial susceptibility of Clostridium difficile isolated from neonatal pigs with enteritis, In: Proceedings, 44th Annual Meeting of the American Association of Veterinary Laboratory Diagnosticians p. 65Google Scholar
Post, KW, Glock, RD, Holtcamp, A, Jost, BH and Glenn Songer, J (2000). Reproduction of Clostridium difficile associated enteritis by experimental inoculation of piglets. In: Proceedings, 43rd Annual Meeting of the American Association of Veterinary Laboratory DiagnosticiansBirmingham AL.Google Scholar
Post, KW, Songer, JG, Jost, BH, Glock, RD and Holtcamp, A (2001). The emergence of Clostridium difficile as a cause of porcine neonatal enteritis. In: Proceedings, 32nd Annual Meeting of the American Association of Swine VeterinariansNashville TN.Google Scholar
Post, KW, Jost, BH and Songer, JG (2002). Evaluation of the Clostridium difficile TOX A/B test for the diagnosis of neonatal swine enteritis. Journal of Veterinary Diagnostic Investigation 14: 258–259.CrossRefGoogle Scholar
Pothoulakis, C and LaMont, JT (1993). Clostridium difficile colitis and diarrhea. Gastroenterology Clinics of North America 22: 623–637.Google Scholar
Poxton, IR, McCoubrey, J and Blair, G (2001). The pathogenicity of Clostridium difficile. Clinical Microbiology and Infection 7: 421–427.CrossRefGoogle ScholarPubMed
Price, AB and Davies, DR (1977). Pseudomembranous colitis. Journal of Clinical Pathology 30: 1–12.CrossRefGoogle ScholarPubMed
Riegler, M, Pothoulakis, C and Hamilton, G (1995). Clostridium difficile toxin B is more potent than toxin A in damaging human colonic epithelium in vitro. Journal of Clinical Investigation 95: 2004–2011.CrossRefGoogle ScholarPubMed
Ryan, ET, Butterton, JR, Smith, RN, Carroll, PA, Crean, TI and Calderwood, SB (1997). Protective immunity against Clostridium difficile toxin A induced by oral immunization with a live, attenuated Vibrio cholerae vector strain. Infection and Immunity 65: 2941–2949.Google Scholar
Salcedo, J, Keates, S and Pothoulakis, C (1997). Intravenous immunoglobulin therapy for severe Clostridium difficile colitis. Gut 41: 366–370.CrossRefGoogle ScholarPubMed
Schellenberg, D, Bonington, A, Champion, CM, Lancaster, R, Webb, S and Main, J (1994). Treatment of Clostridium difficile diarrhoea with brewer's yeast. Lancet 343: 171–172.CrossRefGoogle ScholarPubMed
Songer, JG (1996). Clostridial enteric diseases of domestic animals: a review. Clinical Microbiology Reviews 9: 216–234.CrossRefGoogle Scholar
Songer, JG (2001). A practical approach to clostridial infections. In: Emerging Infections and Molecular Pathogenesis. Annual Meeting of the American College of Veterinary Pathologists, Salt Lake City, UT, December 2–5.Google Scholar
Songer, JG, Post, KW, Larson, DJ, Jost, BH and Glock, RD (2000a). Clostridium difficile as a cause of porcine neonatal enteritis. In: Proceedings, 43rd Annual Meeting of the American Association of Veterinary Laboratory DiagnosticiansBirmingham AL.Google Scholar
Songer, JG, Post, KW, Larson, DJ, Jost, BH and Glock, RD (2000b). Enteric infection of neonatal swine with Clostridium difficile. Swine Health and Production 8: 185–189.Google Scholar
Teasley, DG, Gerding, DN and Olson, MM (1983). Prospective randomized trial of metronidazole versus vancomycin for Clostridium difficile-associated diarrhea and colitis. Lancet 2: 1043–1046.Google Scholar
Tjellstrom, B, Stenhammar, L, Eriksson, S and Magnusson, KE (1993). Oral immunoglobulin A supplement in treatment of Clostridium difficile enteritis [letter]. Lancet 341: 701–702.Google Scholar
Viscidi, R, Laughon, BE and Yolken, R (1983). Serum antibody response to toxins A and B of Clostridium difficile. Journal of Infectious Diseases 148: 93–100.CrossRefGoogle Scholar
von Eichel-Streiber, C, Boquet, P, Sauerborn, M and Thelestam, M (1996). Large clostridial cytotoxins: a family of glycosyltransferases modifying small GTP-binding proteins. Trends in Microbiology 4: 375–382.CrossRefGoogle ScholarPubMed
Ward, SJ, Douce, G, Dougan, G and Wren, BW (1999a). Local and systemic neutralizing antibody responses induced by intranasal immunization with the nontoxic binding domain of toxin A from Clostridium difficile. Infection and Immunity 67: 5124–5132.CrossRefGoogle ScholarPubMed
Ward, SJ, Douce, G, Fingueiredo, D, Dougan, G and Wren, BW (1999b). Immunogenicity of a Salmonella typhimurium aroD vaccine expressing a nontoxic domain of Clostridium difficile toxin A. Infection and Immunity 67: 2145–2152.CrossRefGoogle ScholarPubMed
Warny, M, Vaerman, JP, Avesani, V and Delmee, M (1994). Human antibody response to Clostridium difficile toxin A in relation to clinical course of infection. Infection and Immunity 62: 384–389.Google Scholar
Warny, M, Fatimi, A and Bostwick, EF (1999). Bovine immunoglobulin concentrate– Clostridium difficile retains C. difficile toxin neutralising activity after passage through the human stomach and small intestine. Gut 44: 212–217.Google Scholar
Waters, EH, Orr, JP, Clark, EG and Schaufele, CM (1998). Typhlocolitis caused by Clostridium difficile in suckling piglets. Journal of Veterinary Diagnostic Investigation 10: 104–108.Google Scholar
Whittier, S, Shapiro, DS and Kelly, WF (1993). Evaluation of four commercially available enzyme immunoassays for laboratory diagnosis of Clostridium difficile-associated diseases. Journal of Clinical Microbiology 31: 2861–2865.Google Scholar
Wilcox, MH (1996). Cleaning up Clostridium difficile infection. Lancet 348: 767–768.CrossRefGoogle ScholarPubMed
Wilcox, MH, Fawley, WN, Settle, CD and Davidson, A (1998). Recurrence of symptoms in Clostridium difficile infection: relapse or reinfection? Journal of Hospital Infection 38: 93–100.CrossRefGoogle ScholarPubMed
Wren, BW, Russell, RR and Tabagchali, S (1991). Antigenic cross-reactivity and functional inhibition by antibodies to Clostridium difficile toxin A, Streptococcus mutans glucan-binding protein and a synthetic peptide. Infection and Immunity 59: 3151–3155.CrossRefGoogle Scholar
Yaeger, M (2001). Clostridium difficile and other emerging enteric diseases. In: Iowa Swine Disease Conference, Iowa State UniversityAmes, IANovember 9–10, 2001.Google Scholar
Yaeger, M, Funk, N and Hoffman, L (2002). A survey of agents associated with neonatal diarrhea in Iowa swine including Clostridium difficile and porcine reproductive and respiratory syndrome virus. Journal of Veterinary Diagnostic Investigation 14: 281–287.Google Scholar