Skip to main content
Top
Published in: European Journal of Clinical Microbiology & Infectious Diseases 12/2018

01-12-2018 | Original Article

Real-time quantitative PCR analysis of endoscopic biopsies for diagnosing CMV gastrointestinal disease in non-HIV immunocompromised patients: a diagnostic accuracy study

Authors: Yasuhiro Tsuchido, Miki Nagao, Minoru Matsuura, Satoshi Nakano, Masaki Yamamoto, Yasufumi Matsumura, Hiroshi Seno, Satoshi Ichiyama

Published in: European Journal of Clinical Microbiology & Infectious Diseases | Issue 12/2018

Login to get access

Abstract

Cytomegalovirus gastrointestinal diseases (CMV-GIDs) are end-organ diseases of the gastrointestinal (GI) tract caused by CMV in immunocompromised patients. We aimed to evaluate the performance of quantitative polymerase chain reaction (qPCR) on endoscopic biopsies. We retrospectively reviewed the qPCR data on endoscopic biopsies in nonhuman immunodeficiency virus (HIV) immunocompromised patients between January 2009 and May 2015. The performance of the qPCR for CMV-GID was evaluated with the sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC). A total of 195 patients were included, and 28 patients with confirmed CMV-GID were identified. The AUROC of the qPCR was 0.935 (95% confidence interval [CI], 0.885 to 0.985), the sensitivity was 89.3% (95% CI, 71.8 to 97.7%), and the specificity was 85.6% (95% CI, 79.4 to 97.6%) with a cutoff value of 180 copies/μg DNA. The proportion of patients with inflammatory bowel disease in the histopathology-negative, PCR-positive group was smaller than that in the histopathology-positive group (10.7 vs 35.0%, p = 0.026), but other characteristics were not significantly different. The use of qPCR on endoscopic biopsies demonstrated good diagnostic performance for detecting CMV in non-HIV immunocompromised patients. It may increase the diagnostic yield when combined with a conventional histopathology.
Literature
1.
go back to reference Humar A, Snydman D, Practice AIDCo (2009) Cytomegalovirus in solid organ transplant recipients. Am J Transplant 9 Suppl 4:S78–S86CrossRef Humar A, Snydman D, Practice AIDCo (2009) Cytomegalovirus in solid organ transplant recipients. Am J Transplant 9 Suppl 4:S78–S86CrossRef
2.
go back to reference Mori T, Kato J (2010) Cytomegalovirus infection/disease after hematopoietic stem cell transplantation. Int J Hematol 91(4):588–595CrossRef Mori T, Kato J (2010) Cytomegalovirus infection/disease after hematopoietic stem cell transplantation. Int J Hematol 91(4):588–595CrossRef
3.
go back to reference Gallant JE, Moore RD, Richman DD, Keruly J, Chaisson RE (1992) Incidence and natural history of cytomegalovirus disease in patients with advanced human immunodeficiency virus disease treated with zidovudine. The Zidovudine Epidemiology Study Group. J Infect Dis 166(6):1223–1227CrossRef Gallant JE, Moore RD, Richman DD, Keruly J, Chaisson RE (1992) Incidence and natural history of cytomegalovirus disease in patients with advanced human immunodeficiency virus disease treated with zidovudine. The Zidovudine Epidemiology Study Group. J Infect Dis 166(6):1223–1227CrossRef
4.
go back to reference Ozaki T, Yamashita H, Kaneko S, Yorifuji H, Takahashi H, Ueda Y, Takahashi Y, Kaneko H, Kano T, Mimori A (2013) Cytomegalovirus disease of the upper gastrointestinal tract in patients with rheumatic diseases: a case series and literature review. Clin Rheumatol 32(11):1683–1690CrossRef Ozaki T, Yamashita H, Kaneko S, Yorifuji H, Takahashi H, Ueda Y, Takahashi Y, Kaneko H, Kano T, Mimori A (2013) Cytomegalovirus disease of the upper gastrointestinal tract in patients with rheumatic diseases: a case series and literature review. Clin Rheumatol 32(11):1683–1690CrossRef
5.
go back to reference Maconi G, Colombo E, Zerbi P, Sampietro GM, Fociani P, Bosani M, Cassinotti A, Casini V, Russo A, Ardizzone S, Porta M, Bianchi Porro G (2005) Prevalence, detection rate and outcome of cytomegalovirus infection in ulcerative colitis patients requiring colonic resection. Dig Liver Dis 37(6):418–423CrossRef Maconi G, Colombo E, Zerbi P, Sampietro GM, Fociani P, Bosani M, Cassinotti A, Casini V, Russo A, Ardizzone S, Porta M, Bianchi Porro G (2005) Prevalence, detection rate and outcome of cytomegalovirus infection in ulcerative colitis patients requiring colonic resection. Dig Liver Dis 37(6):418–423CrossRef
6.
go back to reference Ljungman P, Boeckh M, Hirsch HH, Josephson F, Lundgren J, Nichols G, Pikis A, Razonable RR, Miller V, Griffiths PD, Forum DDWGotCDD (2017) Definitions of cytomegalovirus infection and disease in transplant patients for use in clinical trials. Clin Infect Dis 64(1):87–91CrossRef Ljungman P, Boeckh M, Hirsch HH, Josephson F, Lundgren J, Nichols G, Pikis A, Razonable RR, Miller V, Griffiths PD, Forum DDWGotCDD (2017) Definitions of cytomegalovirus infection and disease in transplant patients for use in clinical trials. Clin Infect Dis 64(1):87–91CrossRef
7.
go back to reference Wilcox CM, Straub RF, Schwartz DA (1996) Prospective evaluation of biopsy number for the diagnosis of viral esophagitis in patients with HIV infection and esophageal ulcer. Gastrointest Endosc 44(5):587–593CrossRef Wilcox CM, Straub RF, Schwartz DA (1996) Prospective evaluation of biopsy number for the diagnosis of viral esophagitis in patients with HIV infection and esophageal ulcer. Gastrointest Endosc 44(5):587–593CrossRef
8.
go back to reference Mori T, Mori S, Kanda Y, Yakushiji K, Mineishi S, Takaue Y, Gondo H, Harada M, Sakamaki H, Yajima T, Iwao Y, Hibi T, Okamoto S (2004) Clinical significance of cytomegalovirus (CMV) antigenemia in the prediction and diagnosis of CMV gastrointestinal disease after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 33(4):431–434CrossRef Mori T, Mori S, Kanda Y, Yakushiji K, Mineishi S, Takaue Y, Gondo H, Harada M, Sakamaki H, Yajima T, Iwao Y, Hibi T, Okamoto S (2004) Clinical significance of cytomegalovirus (CMV) antigenemia in the prediction and diagnosis of CMV gastrointestinal disease after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 33(4):431–434CrossRef
9.
go back to reference Jang EY, Park SY, Lee EJ, Song EH, Chong YP, Lee SO, Choi SH, Woo JH, Kim YS, Kim SH (2009) Diagnostic performance of the cytomegalovirus (CMV) antigenemia assay in patients with CMV gastrointestinal disease. Clin Infect Dis 48(12):e121–e124CrossRef Jang EY, Park SY, Lee EJ, Song EH, Chong YP, Lee SO, Choi SH, Woo JH, Kim YS, Kim SH (2009) Diagnostic performance of the cytomegalovirus (CMV) antigenemia assay in patients with CMV gastrointestinal disease. Clin Infect Dis 48(12):e121–e124CrossRef
10.
go back to reference Boeckh M, Boivin G (1998) Quantitation of cytomegalovirus: methodologic aspects and clinical applications. Clin Microbiol Rev 11(3):533–554CrossRef Boeckh M, Boivin G (1998) Quantitation of cytomegalovirus: methodologic aspects and clinical applications. Clin Microbiol Rev 11(3):533–554CrossRef
11.
go back to reference Durand CM, Marr KA, Arnold CA, Tang L, Durand DJ, Avery RK, Valsamakis A, Neofytos D (2013) Detection of cytomegalovirus DNA in plasma as an adjunct diagnostic for gastrointestinal tract disease in kidney and liver transplant recipients. Clin Infect Dis 57(11):1550–1559CrossRef Durand CM, Marr KA, Arnold CA, Tang L, Durand DJ, Avery RK, Valsamakis A, Neofytos D (2013) Detection of cytomegalovirus DNA in plasma as an adjunct diagnostic for gastrointestinal tract disease in kidney and liver transplant recipients. Clin Infect Dis 57(11):1550–1559CrossRef
12.
go back to reference Fisher CE, Alexander J, Bhattacharya R, Rakita RM, Kirby KA, Boeckh M, Limaye AP (2016) Sensitivity of blood and tissue diagnostics for gastrointestinal cytomegalovirus disease in solid organ transplant recipients. Transpl Infect Dis 18(3):372–380CrossRef Fisher CE, Alexander J, Bhattacharya R, Rakita RM, Kirby KA, Boeckh M, Limaye AP (2016) Sensitivity of blood and tissue diagnostics for gastrointestinal cytomegalovirus disease in solid organ transplant recipients. Transpl Infect Dis 18(3):372–380CrossRef
13.
go back to reference Burston J, van Hal S, Dubedat S, Lee A (2017) Inclusions or bystanders? CMV PCR sensitivity and specificity in tissue samples. J Clin Virol 90:38–39CrossRef Burston J, van Hal S, Dubedat S, Lee A (2017) Inclusions or bystanders? CMV PCR sensitivity and specificity in tissue samples. J Clin Virol 90:38–39CrossRef
14.
go back to reference Tanaka N, Kimura H, Iida K, Saito Y, Tsuge I, Yoshimi A, Matsuyama T, Morishima T (2000) Quantitative analysis of cytomegalovirus load using a real-time PCR assay. J Med Virol 60(4):455–462CrossRef Tanaka N, Kimura H, Iida K, Saito Y, Tsuge I, Yoshimi A, Matsuyama T, Morishima T (2000) Quantitative analysis of cytomegalovirus load using a real-time PCR assay. J Med Virol 60(4):455–462CrossRef
15.
go back to reference Hajian-Tilaki K (2014) Sample size estimation in diagnostic test studies of biomedical informatics. J Biomed Inform 48:193–204CrossRef Hajian-Tilaki K (2014) Sample size estimation in diagnostic test studies of biomedical informatics. J Biomed Inform 48:193–204CrossRef
16.
go back to reference Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig L, Lijmer JG, Moher D, Rennie D, de Vet HC, Kressel HY, Rifai N, Golub RM, Altman DG, Hooft L, Korevaar DA, Cohen JF, Group S (2015) STARD 2015: an updated list of essential items for reporting diagnostic accuracy studies. Clin Chem 61(12):1446–1452CrossRef Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig L, Lijmer JG, Moher D, Rennie D, de Vet HC, Kressel HY, Rifai N, Golub RM, Altman DG, Hooft L, Korevaar DA, Cohen JF, Group S (2015) STARD 2015: an updated list of essential items for reporting diagnostic accuracy studies. Clin Chem 61(12):1446–1452CrossRef
17.
go back to reference Mills AM, Guo FP, Copland AP, Pai RK, Pinsky BA (2013) A comparison of CMV detection in gastrointestinal mucosal biopsies using immunohistochemistry and PCR performed on formalin-fixed, paraffin-embedded tissue. Am J Surg Pathol 37(7):995–1000CrossRef Mills AM, Guo FP, Copland AP, Pai RK, Pinsky BA (2013) A comparison of CMV detection in gastrointestinal mucosal biopsies using immunohistochemistry and PCR performed on formalin-fixed, paraffin-embedded tissue. Am J Surg Pathol 37(7):995–1000CrossRef
18.
go back to reference Kaplan JE, Benson C, Holmes KK, Brooks JT, Pau A, Masur H, (CDC) CfDCaP, Health NIo, America HMAotIDSo (2009) Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep 58(RR-4):1–207 quiz CE201–204 Kaplan JE, Benson C, Holmes KK, Brooks JT, Pau A, Masur H, (CDC) CfDCaP, Health NIo, America HMAotIDSo (2009) Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep 58(RR-4):1–207 quiz CE201–204
19.
go back to reference Laine L, Bonacini M, Sattler F, Young T, Sherrod A (1992) Cytomegalovirus and Candida esophagitis in patients with AIDS. J Acquir Immune Defic Syndr 5(6):605–609PubMed Laine L, Bonacini M, Sattler F, Young T, Sherrod A (1992) Cytomegalovirus and Candida esophagitis in patients with AIDS. J Acquir Immune Defic Syndr 5(6):605–609PubMed
20.
go back to reference Lawlor G, Moss AC (2010) Cytomegalovirus in inflammatory bowel disease: pathogen or innocent bystander? Inflamm Bowel Dis 16(9):1620–1627CrossRef Lawlor G, Moss AC (2010) Cytomegalovirus in inflammatory bowel disease: pathogen or innocent bystander? Inflamm Bowel Dis 16(9):1620–1627CrossRef
Metadata
Title
Real-time quantitative PCR analysis of endoscopic biopsies for diagnosing CMV gastrointestinal disease in non-HIV immunocompromised patients: a diagnostic accuracy study
Authors
Yasuhiro Tsuchido
Miki Nagao
Minoru Matsuura
Satoshi Nakano
Masaki Yamamoto
Yasufumi Matsumura
Hiroshi Seno
Satoshi Ichiyama
Publication date
01-12-2018
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Clinical Microbiology & Infectious Diseases / Issue 12/2018
Print ISSN: 0934-9723
Electronic ISSN: 1435-4373
DOI
https://doi.org/10.1007/s10096-018-3387-3

Other articles of this Issue 12/2018

European Journal of Clinical Microbiology & Infectious Diseases 12/2018 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.