Skip to main content

Advertisement

Log in

Evaluation of a Non-invasive Method to Detect Cytomegalovirus (CMV)-DNA in Stool Samples of Patients with Inflammatory Bowel Disease (IBD): A Pilot Study

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Background

A severe flare of colitis in patients with IBD treated with immunosuppressive therapy may be complicated by an underlying CMV infection. The aim of this pilot study was to investigate the diagnostic efficacy of quantitative polymerase chain reaction (PCR) to detect CMV DNA in stool samples of IBD patients.

Methods

Twenty-one patients with a severe flare of IBD, incompletely responding or refractory to either steroids or immunosuppressive agents, were included in the study. Nineteen patients completed the study according to the protocol undergoing an endoscopy with biopsies and collection of stool samples. Biopsy and stool samples were qualitatively and quantitatively analyzed for CMV DNA using real-time PCR.

Results

Thirty-two percent (6/19) of the patients had detectable CMV DNA in colonic biopsies and in five (83%) of those patients CMV DNA was detected in the stool. Thirteen patients had negative findings for CMV DNA in biopsy and stool samples. The sensitivity, specificity, and accuracy of the PCR-based stool test for detection of CMV DNA compared to PCR-based detection of CMV in mucosal biopsies were 83, 93, and 90%, respectively.

Conclusions

The pilot study suggests a high accuracy of this non-invasive testing method to detect CMV DNA in stool samples as compared to mucosal biopsies. This approach may offer a non-endoscopic testing modality for underlying CMV infection in patients with a severe flare of IBD, which could also be applied more broadly to determine the prevalence of CMV infections in patients with IBD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Galiatsatos P, Shrier I, Lamoureux E, Szilagyi A. Meta-analysis of outcome of cytomegalovirus colitis in immunocompetent hosts. Dig Dis Sci. 2005;50:609–616.

    Article  PubMed  Google Scholar 

  2. Buckner FS, Pomeroy C. Cytomegalovirus disease of the gastrointestinal tract in patients without aids. Clin Infect Dis. 1993;17:644–656.

    CAS  PubMed  Google Scholar 

  3. Minami M, Ohta M, Ohkura T, et al. Cytomegalovirus infection in severe ulcerative colitis patients undergoing continuous intravenous cyclosporine treatment in Japan. World J Gastroenterol. 2007;13:754–760.

    CAS  PubMed  Google Scholar 

  4. Kambham N, Vij R, Cartwright CA, Longacre T. Cytomegalovirus infection in steroid-refractory ulcerative colitis: a case-control study. Am J Surg Pathol. 2004;28:365–373.

    Article  PubMed  Google Scholar 

  5. Schulenburg A, Turetschek K, Wrba F, et al. Early and late gastrointestinal complications after myeloablative and nonmyeloablative allogeneic stem cell transplantation. Ann Hematol. 2004;83:101–106.

    Article  CAS  PubMed  Google Scholar 

  6. Shrestha BM, Parton D, Gray A, et al. Cytomegalovirus involving gastrointestinal tract in renal transplant recipients. Clin Transplant. 1996;10:170–175.

    CAS  PubMed  Google Scholar 

  7. Papadakis KA, Tung JK, Binder SW, et al. Outcome of cytomegalovirus infections in patients with inflammatory bowel disease. Am J Gastroenterol. 2001;96:2137–2142.

    Article  CAS  PubMed  Google Scholar 

  8. Cottone M, Pietrosi G, Martorana G, et al. Prevalence of cytomegalovirus infection in severe refractory ulcerative and Crohn’s colitis. Am J Gastroenterol. 2001;96:773–775.

    Article  CAS  PubMed  Google Scholar 

  9. Kaufman HS, Kahn AC, Iacobuzio-Donahue C, Talamini MA, Lillemoe KD, Hamilton SR. Cytomegaloviral enterocolitis: clinical associations and outcome. Dis Colon Rectum. 1999;42:24–30.

    Article  CAS  PubMed  Google Scholar 

  10. Wakefield AJ, Fox JD, Sawyerr AM, et al. Detection of herpesvirus DNA in the large intestine of patients with ulcerative colitis and Crohn’s disease using the nested polymerase chain reaction. J Med Virol. 1992;38:183–190.

    Article  CAS  PubMed  Google Scholar 

  11. Cooper HS, Raffensperger EC, Jonas L, Fitts WT Jr. Cytomegalovirus inclusions in patients with ulcerative colitis and toxic dilation requiring colonic resection. Gastroenterology. 1977;72:1253–1256.

    CAS  PubMed  Google Scholar 

  12. Matsuoka K, Iwao Y, Mori T, et al. Cytomegalovirus is frequently reactivated and disappears without antiviral agents in ulcerative colitis patients. Am J Gastroenterol. 2007;102:331–337.

    Article  PubMed  Google Scholar 

  13. Kojima T, Watanabe T, Hata K, Shinozaki M, Yokoyama T, Nagawa H. Cytomegalovirus infection in ulcerative colitis. Scand J Gastroenterol. 2006;41:706–711.

    Article  PubMed  Google Scholar 

  14. Dimitroulia E, Spanakis N, Konstantinidou AE, Legakis NJ, Tsakris A. Frequent detection of cytomegalovirus in the intestine of patients with inflammatory bowel disease. Inflamm Bowel Dis. 2006;12:879–884.

    Article  PubMed  Google Scholar 

  15. Krech U. Complement-fixing antibodies against cytomegalovirus in different parts of the world. Bull World Health Organ. 1973;49:103–106.

    CAS  PubMed  Google Scholar 

  16. de la Hoz RE, Stephens G, Sherlock C. Diagnosis and treatment approaches of CMV infections in adult patients. J Clin Virol. 2002;25 Suppl 2:S1–12.

    Google Scholar 

  17. Boeckh M, Boivin G. Quantitation of cytomegalovirus: methodologic aspects and clinical applications. Clin Microbiol Rev. 1998;11:533–554.

    CAS  PubMed  Google Scholar 

  18. Rowshani AT, Bemelman FJ, van Leeuwen EM, van Lier RA, ten Berge IJ. Clinical and immunologic aspects of cytomegalovirus infection in solid organ transplant recipients. Transplantation. 2005;79:381–386.

    Article  PubMed  Google Scholar 

  19. Cotte L, Drouet E, Bailly F, Vitozzi S, Denoyel G, Trepo C. Cytomegalovirus DNA level on biopsy specimens during treatment of cytomegalovirus gastrointestinal disease. Gastroenterology. 1996;111:439–444.

    Article  CAS  PubMed  Google Scholar 

  20. Kou T, Nakase H, Tamaki H, Kudo T, Nishio A, Chiba T. Cytomegalovirus infection in patients with ulcerative colitis diagnosed by quantitative real-time PCR analysis. Dig Dis Sci. 2006;51:1052–1055.

    Article  PubMed  Google Scholar 

  21. Numazaki K, Chiba S. Current aspects of diagnosis and treatment of cytomegalovirus infections in infants. Clin Diagn Virol. 1997;8:169–181.

    Article  CAS  PubMed  Google Scholar 

  22. Michel D, Marre E, Hampl W, et al. Intestinal cytomegalovirus disease in immunocompromised patients may be ruled out by search for cytomegalovirus DNA in stool samples. J Clin Microbiol. 1995;33:3064–3067.

    CAS  PubMed  Google Scholar 

  23. Chemaly RF, Yen-Lieberman B, Castilla EA, et al. Correlation between viral loads of cytomegalovirus in blood and bronchoalveolar lavage specimens from lung transplant recipients determined by histology and immunohistochemistry. J Clin Microbiol. 2004;42:2168–2172.

    Article  PubMed  Google Scholar 

  24. Chemaly RF, Yen-Lieberman B, Chapman J, et al. Clinical utility of cytomegalovirus viral load in bronchoalveolar lavage in lung transplant recipients. Am J Transplant. 2005;5:544–548.

    PubMed  Google Scholar 

  25. Boom R, Sol C, Weel J, et al. Detection and quantitation of human cytomegalovirus DNA in faeces. J Virol Methods. 2000;84:1–14.

    Article  CAS  PubMed  Google Scholar 

  26. Sanchez JL, Storch GA. Multiplex, quantitative, real-time pcr assay for cytomegalovirus and human DNA. J Clin Microbiol. 2002;40:2381–2386.

    Article  CAS  PubMed  Google Scholar 

  27. Powell RD, Warner NE, Levine RS, Kirsner JB. Cytomegalic inclusion disease and ulcerative colitis; report of a case in a young adult. Am J Med. 1961;30:334–340.

    Article  CAS  PubMed  Google Scholar 

  28. Domenech E, Vega R, Ojanguren I, et al. Cytomegalovirus infection in ulcerative colitis: A prospective, comparative study on prevalence and diagnostic strategy. Inflamm Bowel Dis. 2008;14:1373–1379.

    Article  PubMed  Google Scholar 

  29. Kishore J, Ghoshal U, Ghoshal UC, et al. Infection with cytomegalovirus in patients with inflammatory bowel disease: Prevalence, clinical significance and outcome. J Med Microbiol. 2004;53:1155–1160.

    Article  PubMed  Google Scholar 

  30. Kandiel A, Lashner B. Cytomegalovirus colitis complicating inflammatory bowel disease. Am J Gastroenterol. 2006;101:2857–2865.

    Article  CAS  PubMed  Google Scholar 

  31. Nakase H, Matsumura K, Yoshino T, Chiba T. Systematic review: Cytomegalovirus infection in inflammatory bowel disease. J Gastroenterol. 2008;43:735–740.

    Article  PubMed  Google Scholar 

  32. Hommes DW, Sterringa G, van Deventer SJ, Tytgat GN, Weel J. The pathogenicity of cytomegalovirus in inflammatory bowel disease: A systematic review and evidence-based recommendations for future research. Inflamm Bowel Dis. 2004;10:245–250.

    Article  PubMed  Google Scholar 

  33. Cotte L, Drouet E, Bissuel F, Denoyel GA, Trepo C. Diagnostic value of amplification of human cytomegalovirus DNA from gastrointestinal biopsies from human immunodeficiency virus-infected patients. J Clin Microbiol. 1993;31:2066–2069.

    CAS  PubMed  Google Scholar 

  34. Yoshino T, Nakase H, Ueno S, et al. Usefulness of quantitative real-time pcr assay for early detection of cytomegalovirus infection in patients with ulcerative colitis refractory to immunosuppressive therapies. Inflamm Bowel Dis. 2007;13:1516–1521.

    Article  PubMed  Google Scholar 

  35. D’Ovidio V, Vernia P, Gentile G, et al. Cytomegalovirus infection in inflammatory bowel disease patients undergoing anti-tnfalpha therapy. J Clin Virol. 2008;43:180–183.

    Article  PubMed  Google Scholar 

  36. Criscuoli V, Mocciaro F, Orlando A, Rizzuto MR, Renda MC, Cottone M. Cytomegalovirus disappearance after treatment for refractory ulcerative colitis in 2 patients treated with infliximab and 1 patient with leukapheresis. Inflamm Bowel Dis. 2009;15:810–811.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This study was funded by an unrestricted research grant from Procter and Gamble. Dr. Herfarth is supported by National Institutes of Health grant R21 DK080408-01 and the Crohn’s and Colitis Foundation of America (CCFA).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hans H. Herfarth.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Herfarth, H.H., Long, M.D., Rubinas, T.C. et al. Evaluation of a Non-invasive Method to Detect Cytomegalovirus (CMV)-DNA in Stool Samples of Patients with Inflammatory Bowel Disease (IBD): A Pilot Study. Dig Dis Sci 55, 1053–1058 (2010). https://doi.org/10.1007/s10620-010-1146-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-010-1146-0

Keywords

Navigation