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Fang M, Miao M, Lin X, Wang W, Wang Q, Liu L, Cheng C, Chi Y, Wei H, Chen W, Hu Z. Gastrointestinal cytomegalovirus infection in persons with HIV: a retrospective case series study. BMC Infect Dis 2025; 25:506. [PMID: 40217459 PMCID: PMC11992835 DOI: 10.1186/s12879-025-10926-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Accepted: 04/04/2025] [Indexed: 04/14/2025] Open
Abstract
BACKGROUND Gastrointestinal (GI) cytomegalovirus (CMV) infection remains an important cause of morbidity among persons with HIV (PWH), even in the late antiretroviral therapy (ART) era. However, its varied clinical presentations and outcomes are not fully understood. METHODS We conducted a retrospective review of 21 PWH with histologically confirmed GI-CMV infections admitted to a tertiary hospital in Nanjing, China, between September 2018 and September 2023. Clinical features, endoscopic findings, histology, treatment responses, and outcomes were examined. RESULTS Patients were predominantly male (95.2%) with a median age of 42 years. Over 80% had CD4 cell counts below 50 cells/µL; at admission, they were not on effective ART or had only recently initiated it, with a median HIV viral load of 5.2 log copies/mL (IQR: 4.9-5.7). Diarrhea (71.4%) was the most common presentation, followed by fever (52.4%), abdominal pain (47.6%), and GI bleeding (38.1%). The median symptom duration was 2.0 months (IQR: 1.0-5.0). Nearly half the patients had concurrent CMV end-organ disease-most commonly CMV retinitis-and 95.2% had at least one AIDS-defining illness; GI mycobacterial co-infection was found in three patients. The colon was the most frequently affected GI site, followed by the stomach and esophagus. Endoscopic findings included ulcers, erosions, proliferative lesions, and diffuse mucosal hemorrhage. All patients initially received intravenous ganciclovir and/or foscarnet for a median of 30 days (IQR: 20-39). The 9 patients with CMV retinitis were given oral ganciclovir maintenance. Gastrointestinal surgery was needed in 9.5% of cases. The 6-month mortality rate was 4.8%. CONCLUSION GI-CMV infection primarily affects PWH with profound immunosuppression (CD4 < 50 cells/µL) and inadequate or absent ART. These patients frequently have other AIDS-defining illnesses and CMV end-organ diseases, complicating their management. For PWH with GI-CMV infection, clinicians should address not only CMV itself but also coexisting conditions arising from advanced immunodeficiency to improve outcomes.
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Affiliation(s)
- Mingxia Fang
- Department of Infectious Diseases, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, 1-1 Zhongfu Road, Nanjing, Jiangsu, 210003, China
| | - Mengjiao Miao
- Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China
| | - Xiaoling Lin
- Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China
| | - Weixiao Wang
- Clinical Research Center, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, 1-1 Zhongfu Road, Nanjing, Jiangsu, 210003, China
| | - Qingqiang Wang
- Department of Gastroenterology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, 210003, China
| | - Lanxia Liu
- Department of Pathology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, 210003, China
| | - Cong Cheng
- Department of Infectious Diseases, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, 1-1 Zhongfu Road, Nanjing, Jiangsu, 210003, China
| | - Yun Chi
- Department of Infectious Diseases, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, 1-1 Zhongfu Road, Nanjing, Jiangsu, 210003, China
| | - Hongxia Wei
- Department of Infectious Diseases, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, 1-1 Zhongfu Road, Nanjing, Jiangsu, 210003, China
| | - Wei Chen
- Clinical Research Center, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, 1-1 Zhongfu Road, Nanjing, Jiangsu, 210003, China.
| | - Zhiliang Hu
- Department of Infectious Diseases, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, 1-1 Zhongfu Road, Nanjing, Jiangsu, 210003, China.
- Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
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Kaczmarek J, Marchelek-Myśliwiec M, Kosik-Bogacka D, Korycińska J, Lepczyńska M, Dutkiewicz G, Kabat-Koperska J. Blastocystis spp. Infection in Kidney Transplant Recipient. Pathogens 2025; 14:341. [PMID: 40333121 PMCID: PMC12030478 DOI: 10.3390/pathogens14040341] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2025] [Revised: 03/23/2025] [Accepted: 03/27/2025] [Indexed: 05/09/2025] Open
Abstract
The Blastocystis sp. is a common enteric parasite found in humans and various animals. Blastocystis spp. infections may be asymptomatic or symptomatic, with gastrointestinal and extra-intestinal symptoms, such as diarrhea, nausea, abdominal pain, bloating, vomiting, or anorexia. The disease leading to symptoms is usually observed in participants with immune deficiency. We report the case of weight loss and diarrhea in a Blastocystis sp. infection in a 64-year-old renal transplant recipient.
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Affiliation(s)
- Justyna Kaczmarek
- Department of Nephrology, Transplantology and Internal Medicine, Pomeranian Medical University, Powstańców Wielkopolskich 72, 70-111 Szczecin, Poland; (M.M.-M.); (G.D.); (J.K.-K.)
| | - Małgorzata Marchelek-Myśliwiec
- Department of Nephrology, Transplantology and Internal Medicine, Pomeranian Medical University, Powstańców Wielkopolskich 72, 70-111 Szczecin, Poland; (M.M.-M.); (G.D.); (J.K.-K.)
| | - Danuta Kosik-Bogacka
- Department of Biology, Parasitology and Pharmaceutical Botany, Pomeranian Medical University, Powstańców Wielkopolskich 72, 70-111 Szczecin, Poland;
| | - Joanna Korycińska
- Department of Medical Biology, School of Public Health, Collegium Medicum, University of Warmia and Mazury in Olsztyn (UWM), Żołnierska 14C, 10-561 Olsztyn, Poland; (J.K.); (M.L.)
| | - Małgorzata Lepczyńska
- Department of Medical Biology, School of Public Health, Collegium Medicum, University of Warmia and Mazury in Olsztyn (UWM), Żołnierska 14C, 10-561 Olsztyn, Poland; (J.K.); (M.L.)
| | - Grażyna Dutkiewicz
- Department of Nephrology, Transplantology and Internal Medicine, Pomeranian Medical University, Powstańców Wielkopolskich 72, 70-111 Szczecin, Poland; (M.M.-M.); (G.D.); (J.K.-K.)
| | - Joanna Kabat-Koperska
- Department of Nephrology, Transplantology and Internal Medicine, Pomeranian Medical University, Powstańców Wielkopolskich 72, 70-111 Szczecin, Poland; (M.M.-M.); (G.D.); (J.K.-K.)
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Purg D, Hojnik M, Kravos Tramšek NA. Cytomegalovirus Enterocolitis in a Patient Treated with Methylprednisolone for Amiodarone Hypersensitivity Pneumonitis. Diagnostics (Basel) 2024; 14:2633. [PMID: 39682543 DOI: 10.3390/diagnostics14232633] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Revised: 11/18/2024] [Accepted: 11/22/2024] [Indexed: 12/18/2024] Open
Abstract
Cytomegalovirus (CMV) is a common cause of infection in immunocompromised individuals, such as patients with hematological malignancies or AIDS, but can also occur in patients with other acquired immunodeficiencies. In tissue-invasive diseases, CMV diagnosis requires CMV DNA in the plasma and the histological confirmation of CMV in a tissue or organ. Evidence of CMV colitis requires a characteristic endoscopic picture with ulcers with a well-defined, convex appearance and CMV viral inclusions in the form of an "owl's eye" on mucosal sections stained with hematoxylin and eosin. CMV-specific immunohistochemistry is the gold standard for identifying CMV in tissue biopsies. It is important to consider a CMV infection in the diagnostic process, as it may delay the diagnosis and the treatment. We present the case of a 78-year-old patient with amiodarone interstitial lung disease who was treated with methylprednisolone. Two weeks after the start of his treatment, he was admitted to the hospital for acute gastroenterocolitis and Addisonian crisis. An examination had confirmed a tissue-invasive CMV disease. He was treated with valganciclovir for a total of six weeks. After the completion of treatment, the patient showed no clinical signs of CMV infection, and both laboratory and histological examinations revealed no residual CMV disease. Tissue-invasive CMV disease can occur in patients with acquired immunodeficiency, which may result from various causes, including glucocorticoid treatment.
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Affiliation(s)
- Darinka Purg
- Department of Gastroenterology, University Medical Centre Maribor, Ljubljanska Ulica 5, 2000 Maribor, Slovenia
| | - Marko Hojnik
- Department of Pathology, University Medical Centre Maribor, Ljubljanska Ulica 5, 2000 Maribor, Slovenia
| | - Nika Aleksandra Kravos Tramšek
- Department of Endocrinology and Diabetology, University Medical Centre Maribor, Ljubljanska Ulica 5, 2000 Maribor, Slovenia
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4
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Mihalić A, Železnjak J, Lisnić B, Jonjić S, Juranić Lisnić V, Brizić I. Immune surveillance of cytomegalovirus in tissues. Cell Mol Immunol 2024; 21:959-981. [PMID: 39134803 PMCID: PMC11364667 DOI: 10.1038/s41423-024-01186-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Accepted: 05/14/2024] [Indexed: 09/01/2024] Open
Abstract
Cytomegalovirus (CMV), a representative member of the Betaherpesvirinae subfamily of herpesviruses, is common in the human population, but immunocompetent individuals are generally asymptomatic when infected with this virus. However, in immunocompromised individuals and immunologically immature fetuses and newborns, CMV can cause a wide range of often long-lasting morbidities and even death. CMV is not only widespread throughout the population but it is also widespread in its hosts, infecting and establishing latency in nearly all tissues and organs. Thus, understanding the pathogenesis of and immune responses to this virus is a prerequisite for developing effective prevention and treatment strategies. Multiple arms of the immune system are engaged to contain the infection, and general concepts of immune control of CMV are now reasonably well understood. Nonetheless, in recent years, tissue-specific immune responses have emerged as an essential factor for resolving CMV infection. As tissues differ in biology and function, so do immune responses to CMV and pathological processes during infection. This review discusses state-of-the-art knowledge of the immune response to CMV infection in tissues, with particular emphasis on several well-studied and most commonly affected organs.
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Affiliation(s)
- Andrea Mihalić
- Center for Proteomics, Faculty of Medicine, University of Rijeka, Rijeka, Croatia
| | - Jelena Železnjak
- Center for Proteomics, Faculty of Medicine, University of Rijeka, Rijeka, Croatia
| | - Berislav Lisnić
- Center for Proteomics, Faculty of Medicine, University of Rijeka, Rijeka, Croatia
| | - Stipan Jonjić
- Center for Proteomics, Faculty of Medicine, University of Rijeka, Rijeka, Croatia
- Department of Biomedical Sciences, Croatian Academy of Sciences and Arts, Rijeka, Croatia
| | - Vanda Juranić Lisnić
- Center for Proteomics, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.
| | - Ilija Brizić
- Center for Proteomics, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.
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Manthey CF, Epple HJ, Keller KM, Lübbert C, Posovszky C, Ramharter M, Reuken P, Suerbaum S, Vehreschild M, Weinke T, Addo MM, Stallmach A, Lohse AW. S2k-Leitlinie Gastrointestinale Infektionen der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS). ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:1090-1149. [PMID: 38976986 DOI: 10.1055/a-2240-1428] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/10/2024]
Affiliation(s)
- Carolin F Manthey
- I. Medizinische Klinik und Poliklinik - Schwerpunkt Gastroenterologie; Sektionen Infektions- und Tropenmedizin, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Deutschland
- Gemeinschaftspraxis Innere Medizin Witten, Witten, Deutschland
| | - Hans-Jörg Epple
- Antibiotic Stewardship, Vorstand Krankenversorgung, Universitätsmedizin Berlin, Berlin, Deutschland
| | - Klaus-Michael Keller
- Klinik für Kinder- und Jugendmedizin, Helios Dr. Horst Schmidt Kliniken, Klinik für Kinder- und Jugendmedizin, Wiesbaden, Deutschland
| | - Christoph Lübbert
- Bereich Infektiologie und Tropenmedizin, Medizinische Klinik I (Hämatologie, Zelltherapie, Infektiologie und Hämostaseologie), Universitätsklinikum Leipzig, Leipzig, Deutschland
| | | | - Michael Ramharter
- I. Medizinische Klinik und Poliklinik - Schwerpunkt Gastroenterologie; Sektionen Infektions- und Tropenmedizin, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Deutschland
| | - Philipp Reuken
- Klinik für Innere Medizin IV (Gastroenterologie, Hepatologie, Infektiologie, Zentrale Endoskopie), Universitätsklinikum Jena, Jena, Deutschland
| | - Sebastian Suerbaum
- Universität München, Max von Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie, München, Deutschland
| | - Maria Vehreschild
- Medizinische Klinik II, Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - Thomas Weinke
- Klinik für Gastroenterologie und Infektiologie, Klinikum Ernst von Bergmann, Potsdam, Deutschland
| | - Marylyn M Addo
- I. Medizinische Klinik und Poliklinik - Schwerpunkt Gastroenterologie; Sektionen Infektions- und Tropenmedizin, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Deutschland
- Institut für Infektionsforschung und Impfstoffentwicklung Sektion Infektiologie, I. Med. Klinik, Zentrum für Innere Medizin, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Deutschland
| | - Andreas Stallmach
- Klinik für Innere Medizin IV (Gastroenterologie, Hepatologie, Infektiologie, Zentrale Endoskopie), Universitätsklinikum Jena, Jena, Deutschland
| | - Ansgar W Lohse
- I. Medizinische Klinik und Poliklinik - Schwerpunkt Gastroenterologie; Sektionen Infektions- und Tropenmedizin, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Deutschland
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Del Gaudio A, Di Vincenzo F, Petito V, Giustiniani MC, Gasbarrini A, Scaldaferri F, Lopetuso LR. Focus on Immune Checkpoint Inhibitors-related Intestinal Inflammation: From Pathogenesis to Therapeutical Approach. Inflamm Bowel Dis 2024; 30:1018-1031. [PMID: 37801695 PMCID: PMC11144981 DOI: 10.1093/ibd/izad229] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2023] [Indexed: 10/08/2023]
Abstract
Recently, antitumor immunotherapies have witnessed a breakthrough with the emergence of immune checkpoint inhibitors (ICIs) including programmed cell death-1 (PD-1), programmed cell death-ligand 1 (PD-L1), and cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibitors. Unfortunately, the use of ICIs has also led to the advent of a novel class of adverse events that differ from those of classic chemotherapeutics and are more reminiscent of autoimmune diseases, the immune-related adverse events (IRAEs). Herein, we performed an insight of the main IRAEs associated with ICIs, focusing on gastroenterological IRAEs and specifically on checkpoint inhibitor colitis, which represents the most widely reported IRAE to date. We comprehensively dissected the current evidence regarding pathogenesis, diagnosis, and management of ICIs-induced colitis, touching upon also on innovative therapies.
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Affiliation(s)
- Angelo Del Gaudio
- UOS Malattie Infiammatorie Croniche Intestinali, Centro di Malattie dell’Apparato Digerente (CEMAD), Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, 00168, Italy
- UOC di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, 00168, Italy
| | - Federica Di Vincenzo
- UOS Malattie Infiammatorie Croniche Intestinali, Centro di Malattie dell’Apparato Digerente (CEMAD), Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, 00168, Italy
- UOC di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, 00168, Italy
| | - Valentina Petito
- UOS Malattie Infiammatorie Croniche Intestinali, Centro di Malattie dell’Apparato Digerente (CEMAD), Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, 00168, Italy
- UOC di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, 00168, Italy
| | | | - Antonio Gasbarrini
- UOS Malattie Infiammatorie Croniche Intestinali, Centro di Malattie dell’Apparato Digerente (CEMAD), Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, 00168, Italy
- UOC di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, 00168, Italy
| | - Franco Scaldaferri
- UOS Malattie Infiammatorie Croniche Intestinali, Centro di Malattie dell’Apparato Digerente (CEMAD), Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, 00168, Italy
- UOC di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, 00168, Italy
| | - Loris Riccardo Lopetuso
- UOS Malattie Infiammatorie Croniche Intestinali, Centro di Malattie dell’Apparato Digerente (CEMAD), Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, 00168, Italy
- UOC di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, 00168, Italy
- Department of Medicine and Ageing Sciences, G. d’Annunzio University of Chieti-Pescara, Chieti, 66100, Italy
- Center for Advanced Studies and Technology (CAST), “G. d’Annunzio” University of Chieti-Pescara, Chieti, 66100, Italy
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Kojima K, Takada J, Kamei M, Kubota M, Ibuka T, Shimizu M. Steroid refractory severe ulcerative colitis after kidney transplantation successfully treated with infliximab. Clin J Gastroenterol 2023; 16:848-853. [PMID: 37715899 DOI: 10.1007/s12328-023-01857-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Accepted: 09/03/2023] [Indexed: 09/18/2023]
Abstract
A 54-year-old man underwent kidney transplantation at the age of 50 for end-stage renal failure owing to diabetic nephropathy. The patient was subsequently treated with three immunosuppressive drugs (tacrolimus, mycophenolate mofetil, and methylprednisolone) to prevent organ rejection, and no renal failure was noted. He visited our department with bloody stools and diarrhea, and a colonoscopy revealed mucosal edema and redness of the entire colon. After excluding infection and drug-induced enteritis based on the endoscopic and pathological findings, he was diagnosed with ulcerative colitis (UC). He was admitted and received a high dose of steroids, but did not demonstrate improvement. We initiated infliximab (IFX), and his symptoms improved within 3 days. After the second IFX treatment, the patient achieved clinical remission and was discharged. After the third IFX dose, the biomarker level became normal, and a colonoscopy after the fourth IFX dose revealed that all ulcers had become scarred and achieved endoscopic remission. The patient continued all medications to prevent organ rejection after the onset of UC and had no graft dysfunction or infection for 1 year.
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Affiliation(s)
- Kentaro Kojima
- Department of Gastroenterology and Internal Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu, 501-1194, Japan.
| | - Jun Takada
- Department of Gastroenterology and Internal Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu, 501-1194, Japan
| | - Makoto Kamei
- Department of Gastroenterology and Internal Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu, 501-1194, Japan
| | - Masaya Kubota
- Department of Gastroenterology and Internal Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu, 501-1194, Japan
| | - Takashi Ibuka
- Department of Gastroenterology and Internal Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu, 501-1194, Japan
| | - Masahito Shimizu
- Department of Gastroenterology and Internal Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu, 501-1194, Japan
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8
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Post CS, Cheng J, Pantanowitz L, Westerhoff M. Utility of Machine Learning to Detect Cytomegalovirus in Digital Hematoxylin and Eosin-Stained Slides. J Transl Med 2023; 103:100225. [PMID: 37527779 DOI: 10.1016/j.labinv.2023.100225] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2023] [Revised: 07/01/2023] [Accepted: 07/25/2023] [Indexed: 08/03/2023] Open
Abstract
Rapid and accurate cytomegalovirus (CMV) identification in immunosuppressed or immunocompromised patients presenting with diarrhea is essential for therapeutic management. Due to viral latency, however, the gold standard for CMV diagnosis remains to identify viral cytopathic inclusions on routine hematoxylin and eosin (H&E)-stained tissue sections. Therefore, biopsies may be taken and "rushed" for pathology evaluation. Here, we propose the use of artificial intelligence to detect CMV inclusions on routine H&E-stained whole-slide images to aid pathologists in evaluating these cases. Fifty-eight representative H&E slides from 30 cases with CMV inclusions were identified and scanned. The resulting whole-slide images were manually annotated for CMV inclusions and tiled into 300 × 300 pixel patches. Patches containing annotations were labeled "positive," and these tiles were oversampled with image augmentation to account for class imbalance. The remaining patches were labeled "negative." Data were then divided into training, validation, and holdout sets. Multiple deep learning models were provided with training data, and their performance was analyzed. All tested models showed excellent performance. The highest performance was seen using the EfficientNetV2BO model, which had a test (holdout) accuracy of 99.93%, precision of 100.0%, recall (sensitivity) of 99.85%, and area under the curve of 0.9998. Of 518,941 images in the holdout set, there were only 346 false negatives and 2 false positives. This shows proof of concept for the use of digital tools to assist pathologists in screening "rush" biopsies for CMV infection. Given the high precision, cases screened as "positive" can be quickly confirmed by a pathologist, reducing missed CMV inclusions and improving the confidence of preliminary results. Additionally, this may reduce the need for immunohistochemistry in limited tissue samples, reducing associated costs and turnaround time.
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Affiliation(s)
- Corey S Post
- Department of Pathology, Michigan Medicine, Ann Arbor, Michigan.
| | - Jerome Cheng
- Department of Pathology, Michigan Medicine, Ann Arbor, Michigan
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Anti-Cytomegalovirus Therapy: Whether and When to Initiate, Those Are the Questions. Pharmaceuticals (Basel) 2022; 15:ph15070797. [PMID: 35890096 PMCID: PMC9325238 DOI: 10.3390/ph15070797] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 06/23/2022] [Accepted: 06/24/2022] [Indexed: 11/30/2022] Open
Abstract
Cytomegalovirus (CMV) reactivation in patients with autoimmune bullous disease (AIBD) or severe drug eruption treated with immunosuppressive therapy was traditionally thought to be merely an epiphenomenon of the underlying immunosuppression. However, a detailed review of the clinical course of these patients revealed that CMV reactivation occurs upon rapid immune recovery, which is termed immune reconstitution inflammatory syndrome (IRIS), and that the timely initiation of anti-CMV therapy, when combined with maintenance doses of immunosuppressive agents, contributes to a rapid resolution of severe infectious complications thought to be refractory to conventional immunosuppressive therapies and unrelated to CMV reactivation. Thus, CMV reactivation resulting in fatal outcomes (CMV-IRIS) can be prevented by the timely detection of CMV DNA or antigens in the blood and by rapidly starting anti-CMV therapy while maintaining immunosuppressive therapy. Anti-CMV therapy is highly recommended for patients with CMV-IRIS or severe drug eruption who have risk factors for CMV reactivation resulting in fatal outcomes.
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Nourbakhsh SM, Daneshjoo K, Bahadoram M, Ataeepour M, Hassanzadeh S. Cytomegalovirus colitis in a child with leukemia: a case report. Future Microbiol 2022; 17:647-651. [PMID: 35414205 DOI: 10.2217/fmb-2021-0265] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
A 17-month-old boy with a known case of T-cell acute lymphoblastic leukemia was admitted to the authors' hospital because of blood-streaked diarrhea a week after his last chemotherapy session. Initially, he was treated with supportive care and an empiric regimen for opportunistic causes of diarrhea; however, this was not effective. Eventually, evaluation of his stool with PCR showed positivity for cytomegalovirus. Consequently, he responded dramatically to treatment with ganciclovir. Although cytomegalovirus colitis is rare, a few case reports suggest cytomegalovirus as a possible cause of colitis in children with leukemia, which can be fatal and should be considered as a differential diagnosis.
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Affiliation(s)
- Seyed Mk Nourbakhsh
- Department of Pediatric Hematology and Oncology, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, 1416753955, Iran
| | - Khadijeh Daneshjoo
- Department of Pediatric Hematology and Oncology, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, 1416753955, Iran
| | - Mohammad Bahadoram
- Thalassemia and Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, 15794 - 61357, Iran
| | - Mehdi Ataeepour
- Department of Pediatric Hematology and Oncology, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, 1416753955, Iran
| | - Shakiba Hassanzadeh
- Thalassemia and Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, 15794 - 61357, Iran
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11
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Li H, Fu ZY, Arslan ME, Cho D, Lee H. Differential diagnosis and management of immune checkpoint inhibitor-induced colitis: A comprehensive review. World J Exp Med 2021; 11:79-92. [PMID: 36246150 PMCID: PMC9553980 DOI: 10.5493/wjem.v11.i6.79] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Revised: 08/08/2021] [Accepted: 12/23/2021] [Indexed: 02/06/2023] Open
Abstract
Immune checkpoint inhibitors (ICIs) are a new class of cancer pharmacotherapy consisting of antibodies that block inhibitory immune regulators such as cytotoxic T lymphocyte antigen 4, programmed cell death 1 and programmed death-ligand 1. Checkpoint blockade by ICIs reactivates a tumor-specific T cell response. Immune-related adverse events can occur in various organs including skin, liver, and gastrointestinal tract. Mild to severe colitis is the most common side effect with some experiencing rapid progression to more serious complications including bowel perforation and even death. Prompt diagnosis and management of ICI-induced colitis is crucial for optimal outcome. Unfortunately, its clinical, endoscopic and histopathologic presentations are non-specific and overlap with those of colitis caused by other etiologies, such as infection, medication, graft-versus-host disease and inflammatory bowel disease. Thus, a definitive diagnosis can only be rendered after these other possible etiologies are excluded. Sometimes an extensive clinical, laboratory and radiologic workup is required, making it challenging to arrive at a prompt diagnosis. Most patients experience full resolution of symptoms with corticosteroids and/or infliximab. For ICI-induced colitis that is treatment-refractory, small scale studies offer alternative strategies, such as vedolizumab and fecal microbiota transplantation. In this review, we focus on the clinical features, differential diagnosis, and management of ICI-induced colitis with special attention to emerging treatment options for treatment-refractory ICI-induced colitis.
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Affiliation(s)
- Hua Li
- Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY 12208, United States
| | - Zhi-Yan Fu
- Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY 12208, United States
| | - Mustafa Erdem Arslan
- Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY 12208, United States
| | - Daniel Cho
- Schenectady Pathology Associates, Ellis Hospital, Schenectady, NY 12308, United States
| | - Hwajeong Lee
- Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY 12208, United States
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12
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Gugliesi F, Pasquero S, Griffante G, Scutera S, Albano C, Pacheco SFC, Riva G, Dell’Oste V, Biolatti M. Human Cytomegalovirus and Autoimmune Diseases: Where Are We? Viruses 2021; 13:260. [PMID: 33567734 PMCID: PMC7914970 DOI: 10.3390/v13020260] [Citation(s) in RCA: 48] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Revised: 02/03/2021] [Accepted: 02/05/2021] [Indexed: 12/14/2022] Open
Abstract
Human cytomegalovirus (HCMV) is a ubiquitous double-stranded DNA virus belonging to the β-subgroup of the herpesvirus family. After the initial infection, the virus establishes latency in poorly differentiated myeloid precursors from where it can reactivate at later times to cause recurrences. In immunocompetent subjects, primary HCMV infection is usually asymptomatic, while in immunocompromised patients, HCMV infection can lead to severe, life-threatening diseases, whose clinical severity parallels the degree of immunosuppression. The existence of a strict interplay between HCMV and the immune system has led many to hypothesize that HCMV could also be involved in autoimmune diseases (ADs). Indeed, signs of active viral infection were later found in a variety of different ADs, such as rheumatological, neurological, enteric disorders, and metabolic diseases. In addition, HCMV infection has been frequently linked to increased production of autoantibodies, which play a driving role in AD progression, as observed in systemic lupus erythematosus (SLE) patients. Documented mechanisms of HCMV-associated autoimmunity include molecular mimicry, inflammation, and nonspecific B-cell activation. In this review, we summarize the available literature on the various ADs arising from or exacerbating upon HCMV infection, focusing on the potential role of HCMV-mediated immune activation at disease onset.
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Affiliation(s)
- Francesca Gugliesi
- Department of Public Health and Pediatric Sciences, University of Turin, 10126 Turin, Italy; (F.G.); (S.P.); (S.S.); (C.A.); (S.F.C.P.); (V.D.)
| | - Selina Pasquero
- Department of Public Health and Pediatric Sciences, University of Turin, 10126 Turin, Italy; (F.G.); (S.P.); (S.S.); (C.A.); (S.F.C.P.); (V.D.)
| | - Gloria Griffante
- Department of Translational Medicine, Molecular Virology Unit, University of Piemonte Orientale Medical School, 28100 Novara, Italy;
| | - Sara Scutera
- Department of Public Health and Pediatric Sciences, University of Turin, 10126 Turin, Italy; (F.G.); (S.P.); (S.S.); (C.A.); (S.F.C.P.); (V.D.)
| | - Camilla Albano
- Department of Public Health and Pediatric Sciences, University of Turin, 10126 Turin, Italy; (F.G.); (S.P.); (S.S.); (C.A.); (S.F.C.P.); (V.D.)
| | - Sergio Fernando Castillo Pacheco
- Department of Public Health and Pediatric Sciences, University of Turin, 10126 Turin, Italy; (F.G.); (S.P.); (S.S.); (C.A.); (S.F.C.P.); (V.D.)
| | - Giuseppe Riva
- Otorhinolaryngology Division, Department of Surgical Sciences, University of Turin, 10126 Turin, Italy;
| | - Valentina Dell’Oste
- Department of Public Health and Pediatric Sciences, University of Turin, 10126 Turin, Italy; (F.G.); (S.P.); (S.S.); (C.A.); (S.F.C.P.); (V.D.)
| | - Matteo Biolatti
- Department of Public Health and Pediatric Sciences, University of Turin, 10126 Turin, Italy; (F.G.); (S.P.); (S.S.); (C.A.); (S.F.C.P.); (V.D.)
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13
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Gioco R, Puzzo L, Patanè M, Corona D, Trama G, Veroux P, Veroux M. Post-transplant colitis after kidney transplantation: clinical, endoscopic and histological features. Aging (Albany NY) 2020; 12:24709-24720. [PMID: 33353887 PMCID: PMC7803550 DOI: 10.18632/aging.202345] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2020] [Accepted: 11/16/2020] [Indexed: 12/19/2022]
Abstract
Chronic immunosuppression may increase the risk of post-transplant infection and medication-related injury and may also be responsible for the increased risk of gastrointestinal complications in kidney transplant recipients. Differentiating the various forms of post-transplant colitis is challenging, since most have similar clinical and histological features. This study evaluated the incidence of post-transplant gastrointestinal complications during screening colonoscopy. Kidney transplant recipients undergoing a colonoscopy for any reasons in the period 2014-2018 were included. Among the 134 patients completing the colonoscopy, 74 patients (56%) had an abnormal finding: an adenoma was found in 25 patients (18.6%), while 19 patients (14.1%) had colitis. Mycophenolic acid/related colitis was the most common colitis (6%), while 7 patients (5.2%) developed a de novo inflammatory bowel disease. Patients with post-transplant colitis were younger and with shorter time from transplant compared to patients without colitis. In conclusions, immunosuppression may predispose kidney transplant recipients to an increased risk of post-transplant colitis. Diagnostic colonoscopy should be encouraged in all transplant patients with refractory diarrhea and gastrointestinal symptoms to allow a prompt diagnosis and a timely treatment, finally improving the quality of life and long-term outcomes of affected patients.
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Affiliation(s)
- Rossella Gioco
- General Surgery Unit, University Hospital of Catania, Catania 95123, Italy
| | - Lidia Puzzo
- Pathology Unit, Department of Medical and Surgical Sciences and Advanced Technologies, University of Catania, Catania 95123, Italy
| | - Marco Patanè
- Organ Transplant Unit, University Hospital of Catania, Catania 95123, Italy
| | - Daniela Corona
- Department of Biomedical and Biotechnological Sciences, University of Catania, Catania 95123, Italy
| | - Giuseppe Trama
- Gastroenterology Unit, University Hospital of Catania, Catania 95123, Italy
| | | | - Massimiliano Veroux
- General Surgery Unit, University Hospital of Catania, Catania 95123, Italy.,Organ Transplant Unit, University Hospital of Catania, Catania 95123, Italy
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14
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Gioco R, Corona D, Ekser B, Puzzo L, Inserra G, Pinto F, Schipa C, Privitera F, Veroux P, Veroux M. Gastrointestinal complications after kidney transplantation. World J Gastroenterol 2020; 26:5797-5811. [PMID: 33132635 PMCID: PMC7579754 DOI: 10.3748/wjg.v26.i38.5797] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2020] [Revised: 05/28/2020] [Accepted: 08/25/2020] [Indexed: 02/06/2023] Open
Abstract
Gastrointestinal complications are common after renal transplantation, and they have a wide clinical spectrum, varying from diarrhoea to post-transplant inflammatory bowel disease (IBD). Chronic immunosuppression may increase the risk of post-transplant infection and medication-related injury and may also be responsible for IBD in kidney transplant re-cipients despite immunosuppression. Differentiating the various forms of post-transplant colitis is challenging, since most have similar clinical and histological features. Drug-related colitis are the most frequently encountered colitis after kidney transplantation, particularly those related to the chronic use of mycophenolate mofetil, while de novo IBDs are quite rare. This review will explore colitis after kidney transplantation, with a particular focus on different clinical and histological features, attempting to clearly identify the right treatment, thereby improving the final outcome of patients.
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Affiliation(s)
- Rossella Gioco
- General Surgery Unit, University Hospital of Catania, Catania 95123, Italy
| | - Daniela Corona
- Department of Biomedical and Biotechnological Sciences, University of Catania, Catania 95123, Italy
| | - Burcin Ekser
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, United States
| | - Lidia Puzzo
- Pathology Unit, Department of Medical and Surgical Sciences and Advanced Technologies, University of Catania, Catania 95123, Italy
| | - Gaetano Inserra
- Gastroenterology Unit, Department of Clinical and Experimental Medicine, University of Catania, Catania 95100, Italy
| | - Flavia Pinto
- General Surgery Unit, University Hospital of Catania, Catania 95123, Italy
| | - Chiara Schipa
- General Surgery Unit, University Hospital of Catania, Catania 95123, Italy
| | | | | | - Massimiliano Veroux
- General Surgery Unit, Organ Transplant Unit, University Hospital of Catania, Catania 95123, Italy
- Department of Medical and Surgical Sciences and Advanced Technologies, University Hospital of Catania, Catania 95123, Italy
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15
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New acetamide derivatives containing (ω-p-bromophenoxyalkyl)uracil moiety and their anticytomegalovirus activity. MENDELEEV COMMUNICATIONS 2020. [DOI: 10.1016/j.mencom.2020.09.016] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
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16
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Wei C, Kakazu T, Chuah QY, Tanaka M, Kato G, Sano M. Reactivation of cyprinid herpesvirus 2 (CyHV-2) in asymptomatic surviving goldfish Carassius auratus (L.) under immunosuppression. FISH & SHELLFISH IMMUNOLOGY 2020; 103:302-309. [PMID: 32439507 DOI: 10.1016/j.fsi.2020.05.020] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/03/2020] [Revised: 05/04/2020] [Accepted: 05/07/2020] [Indexed: 06/11/2023]
Abstract
Cyprinid herpesvirus 2 (CyHV-2) is a highly contagious pathogen of goldfish (Carassius auratus) and Prussian carp (Carassius auratus gibelio) causing herpesviral hematopoietic necrosis. Our previous study revealed that CyHV-2 can persistently infect the kidney and spleen of goldfish that recovered from a primary infection. In this study, we tried to identify the cells persistently infected with the virus in surviving fish and investigated virus reactivation in the survivors injected with immunosuppressants, namely dexamethasone (Dex) and cyclosporine A (CsA). Virus DNA was detected from the monocytes that were isolated from the trunk kidney of the asymptomatic survivors, suggesting that monocytes/macrophages are major cells that may be persistently infected with CyHV-2. A significant increase of virus DNA levels was detected in the group injected with Dex at 10 and 21 days post-injection (dpi). In the fish group injected with CsA, the virus DNA level was the same as that in the control group at 10 dpi but increased in some organs at 21 dpi. Compared with Dex-injected fish at 10 dpi, the group injected with both Dex and CsA showed a greater increase in virus DNA levels. The gene expression of phagocytosis-associated genes, major histocompatibility complex (MHC) class II and p47phox, and anti-virus antibody levels increased in the CsA group due to virus reactivation in the infected cells but not in the Dex and Dex & CsA groups, indicating that Dex effectively suppressed monocyte/macrophage function and antibody production. In addition, recombinant interferon γ (IFNγ) supplementation in the kidney leukocyte culture that was isolated from survivors showed a reduction of virus DNA. CsA may inhibit T-helper 1 (Th1) cells and consequently IFNγ production, causing a synergetic effect with Dex on virus reactivation. The results suggest that the activity of monocytes/macrophages stimulated by IFNγ can relate to virus latency and reactivation in asymptomatic virus carriers.
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Affiliation(s)
- Chang Wei
- Tokyo University of Marine Science and Technology, Tokyo, 108-8477, Japan
| | - Taichi Kakazu
- Tokyo University of Marine Science and Technology, Tokyo, 108-8477, Japan
| | - Qiu Yuan Chuah
- Tokyo University of Marine Science and Technology, Tokyo, 108-8477, Japan
| | - Mikio Tanaka
- Saitama Fisheries Research Institute, Saitama, 347-0011, Japan
| | - Goshi Kato
- Tokyo University of Marine Science and Technology, Tokyo, 108-8477, Japan
| | - Motohiko Sano
- Tokyo University of Marine Science and Technology, Tokyo, 108-8477, Japan.
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17
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Chaemsupaphan T, Limsrivilai J, Thongdee C, Sudcharoen A, Pongpaibul A, Pausawasdi N, Charatcharoenwitthaya P. Patient characteristics, clinical manifestations, prognosis, and factors associated with gastrointestinal cytomegalovirus infection in immunocompetent patients. BMC Gastroenterol 2020; 20:22. [PMID: 32000707 PMCID: PMC6990526 DOI: 10.1186/s12876-020-1174-y] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2019] [Accepted: 01/19/2020] [Indexed: 12/20/2022] Open
Abstract
Background Gastrointestinal (GI) cytomegaloviral (CMV) infection is common among patients with immunocompromised status; however, data specific to GI-CMV infection in immunocompetent patients are comparatively limited. Methods This retrospective study included patients diagnosed with GI-CMV infection at Siriraj Hospital (Bangkok, Thailand) during 2008–2017. Baseline characteristics, presentations, comorbid conditions, endoscopic findings, treatments, and outcomes were compared between immunocompetent and immunocompromised. Results One hundred and seventy-three patients (56 immunocompetent, 117 immunocompromised) were included. Immunocompetent patients were significantly older than immunocompromised patients (73 vs. 48.6 years, p < 0.0001). Significantly more immunocompetent patients were in the ICU at the time of diagnosis (21.0% vs. 8.6%, p = 0.024). GI bleeding was the leading presentation in immunocompetent, while diarrhea and abdominal pain were more common in immunocompromised. Blood CMV viral load was negative in significantly more immunocompetent than immunocompromised (40.7% vs. 12.9%, p = 0.002). Ganciclovir was the main treatment in both groups. Significantly more immunocompetent than immunocompromised did not receive any specific therapy (25.5% vs. 4.4%, p ≤ 0.01). Six-month mortality was significantly higher among immunocompetent patients (39.0% vs. 22.0%, p = 0.047). Independent predictors of death were old age and inpatient or ICU clinical setting. Treatment with antiviral agents was the only independent protective factor. Conclusion GI-CMV infection was frequently observed among immunocompetent elderly patients with comorbidities or severe concomitant illnesses. GI bleeding was the most common presentation. Blood CMV viral load was not diagnostically helpful. Significantly higher mortality was observed in immunocompetent than in immunocompromised patients, but this could be due to more severe concomitant illnesses in the immunocompetent group.
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Affiliation(s)
- Thanaboon Chaemsupaphan
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Julajak Limsrivilai
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
| | - Chenchira Thongdee
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Asawin Sudcharoen
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Ananya Pongpaibul
- Department of Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Nonthalee Pausawasdi
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Phunchai Charatcharoenwitthaya
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
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18
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Kagebayashi S, Yamamoto S, Seno H. Jejunal diaphragm disease associated with cytomegalovirus infection. Endosc Int Open 2019; 7:E533-E536. [PMID: 31041370 PMCID: PMC6447397 DOI: 10.1055/a-0848-8172] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2018] [Accepted: 11/26/2018] [Indexed: 11/15/2022] Open
Abstract
Background and study aims Diaphragm disease (DD) is a rare gastrointestinal disease featuring multiple thin, circumferential strictures in the intestine, related to prolonged intake of nonsteroidal anti-inflammatory drugs (NSAIDs). Here, we report a case of DD associated with cytomegalovirus (CMV) infection in a patient not taking NSAIDs. A 72-year-old man was referred to our hospital due to persistent epigastric pain. Push enteroscopy showed extensive mucosal detachment in the upper jejunum. Immunohistochemistry examination of biopsy specimens revealed CMV positivity. In addition, CMV antigenemia was positive. Antiviral treatment with ganciclovir improved his symptoms and the CMV antigenemia became negative. Wireless capsule enteroscopy performed 1 month after antiviral treatment showed regenerated mucosa and multiple diaphragm-like strictures in the jejunum, resulting in capsule retention. Balloon dilatation using double balloon enteroscopy (DBE) was performed and the capsule was retrieved endoscopically. DBE 6 months after antiviral therapy confirmed no recurrence of stenosis or inflammation. The patient had no history of long-term NSAID use. In a case of DD unassociated with NSAIDs, CMV infection should be considered in the differential diagnosis.
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Affiliation(s)
- Sumika Kagebayashi
- Department of Gastroenterology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Shuji Yamamoto
- Department of Gastroenterology, Kyoto University Graduate School of Medicine, Kyoto, Japan,Corresponding author Shuji Yamamoto, MD, PhD Department of GastroenterologyKyoto University Graduate School of Medicine54 Shogoin Kawahara-cho, SakyoKyoto 606-8507Japan+81-75-751-4338
| | - Hiroshi Seno
- Department of Gastroenterology, Kyoto University Graduate School of Medicine, Kyoto, Japan
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19
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Suri D, Jindal AK, Gupta A, Gupta A, Bajgai P, Singh R, Singh MP, Minz RW, Arora S, Singh S. Cytomegalovirus Disease in HIV-infected Children-A Single-Centre Clinical Experience over 23 Years. J Trop Pediatr 2018; 64:215-224. [PMID: 29873796 DOI: 10.1093/tropej/fmx052] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
BACKGROUND Cytomegalovirus (CMV) results in significant morbidity and mortality in Human Immunodeficiency Virus (HIV)-infected individuals. There is paucity of literature on paediatric CMV disease, especially from developing countries. METHODS A retrospective review of records of all HIV-infected children with evidence of CMV disease was done. RESULTS A total of 15 children were found to have CMV disease (retinitis in all, pneumonia in two and invasive gastrointestinal disease in one). Median CD4+ T cell count and percentage at diagnosis of CMV disease was 64.5 cells/µl and 3.6%, respectively. Intravenous ganciclovir was used in patients with active CMV disease. Of the 15 children, three died while two were lost to follow-up. Symptomatic patients had poor visual outcome and almost all children who were diagnosed on active screening attained normal vision. CONCLUSION Retinitis is the most common CMV disease in HIV-infected children. Early detection by active screening and initiation of systemic ganciclovir reduces the morbidity.
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Affiliation(s)
- Deepti Suri
- Pediatric Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Ankur K Jindal
- Pediatric Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Aman Gupta
- Pediatric Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Anju Gupta
- Pediatric Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Priya Bajgai
- Department of Ophthalmology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Ramandeep Singh
- Department of Ophthalmology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Mini P Singh
- Department Virology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Ranjana W Minz
- Department of Immunopathology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Sunil Arora
- Department of Immunopathology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Surjit Singh
- Pediatric Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
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20
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21
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Abstract
Cytomegalovirus (CMV), the largest of the herpesviruses, causes a wide range of clinical syndromes, from asymptomatic infection to severe disease in immunocompromised hosts. Laboratory methods for diagnosis include molecular testing, antigenemia, culture, serology, and histopathology. Treatment of CMV infection and disease is indicated in selected immunocompromised hosts, and preventive approaches are indicated in high-risk groups. This chapter reviews the epidemiology, clinical aspects, and the laboratory diagnosis and management of CMV in immunocompromised hosts.
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22
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Baniak N, Kanthan R. Cytomegalovirus Colitis: An Uncommon Mimicker of Common Colitides. Arch Pathol Lab Med 2017; 140:854-8. [PMID: 27472242 DOI: 10.5858/arpa.2015-0176-rs] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Cytomegalovirus latency, though ubiquitous in the human population, is known to cause colitis in both immunocompromised and immunocompetent hosts. Furthermore, the clinical, endoscopic, and histologic appearance of cytomegalovirus colitis can mimic that of inflammatory bowel disease, an extremely well-documented disease. In this context, though many reports have looked at inflammatory bowel disease with superimposed cytomegalovirus infection, less attention has been paid to cytomegalovirus as a primary cause of isolated colitis. Owing to the rarity of this phenomenon, it is important to consider this diagnosis and implement proper testing to avoid misdiagnosis and mismanagement.
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Affiliation(s)
| | - Rani Kanthan
- From the Department of Pathology and Laboratory Medicine, College of Medicine, University of Saskatchewan, Saskatoon, Canada
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23
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Gutiérrez-Delgado EM, Villanueva-Lozano H, García Rojas-Acosta MJ, Miranda-Maldonado IC, Ramos-Jiménez J. A case report of small bowel perforation secondary to cytomegalovirus related immune reconstitution inflammatory syndrome in an AIDS patient. Ann Med Surg (Lond) 2017; 13:20-23. [PMID: 28018589 PMCID: PMC5176126 DOI: 10.1016/j.amsu.2016.11.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2016] [Revised: 11/06/2016] [Accepted: 11/06/2016] [Indexed: 12/27/2022] Open
Abstract
Non-traumatic small bowel perforation is rare in adults but carries a high morbidity and mortality. The diagnosis is made on clinical suspicion, and the most common causes in developing countries are infectious diseases, being cytomegalovirus infection in immunocompromised patients the main etiology. We describe a patient with a recently diagnosed advanced stage HIV infection and an intestinal perforation associated with cytomegalovirus immune reconstitution inflammatory syndrome after highly active antiretroviral therapy initiation.
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Affiliation(s)
- Eva María Gutiérrez-Delgado
- Infectious Diseases Service, Internal Medicine Department, Hospital Universitario “Dr. José Eleuterio González”, Universidad Autónoma de Nuevo León, Monterrey, Mexico
| | - Hiram Villanueva-Lozano
- Infectious Diseases Service, Internal Medicine Department, Hospital Universitario “Dr. José Eleuterio González”, Universidad Autónoma de Nuevo León, Monterrey, Mexico
| | | | - Ivett C. Miranda-Maldonado
- Department of Pathological Anatomy and Cytopathology, Hospital Universitario “Dr. José Eleuterio González”, Universidad Autónoma de Nuevo León, Monterrey, Mexico
| | - Javier Ramos-Jiménez
- Infectious Diseases Service, Internal Medicine Department, Hospital Universitario “Dr. José Eleuterio González”, Universidad Autónoma de Nuevo León, Monterrey, Mexico
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24
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Cohen J. Vasculitis and Other Immunologically Mediated Diseases. Infect Dis (Lond) 2017. [DOI: 10.1016/b978-0-7020-6285-8.00085-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/21/2022] Open
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25
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Colomba C, Giuffrè M, La Placa S, Cascio A, Trizzino M, De Grazia S, Corsello G. Congenital cytomegalovirus related intestinal malrotation: a case report. Ital J Pediatr 2016; 42:105. [PMID: 27923378 PMCID: PMC5141648 DOI: 10.1186/s13052-016-0318-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2016] [Accepted: 11/30/2016] [Indexed: 11/10/2022] Open
Abstract
Background Cytomegalovirus is the most common cause of congenital infection in the developed countries. Gastrointestinal involvement has been extensively described in both adult and paediatric immunocompromised patients but it is infrequent in congenital or perinatal CMV infection. Case presentation We report on a case of coexistent congenital Cytomegalovirus infection with intestinal malrotation and positive intestinal Cytomegalovirus biopsy. At birth the neonate showed clinical and radiological evidence of intestinal obstruction. Meconium passed only after evacuative nursing procedures; stooling pattern was irregular; gastric residuals were bile-stained. Laparatomy revealed a complete intestinal malrotation and contextually gastrointestinal biopsy samples of the appendix confirmed the diagnosis of CMV gastrointestinal disease. Intravenous ganciclovir was initiated for 2 weeks, followed by oral valgancyclovir for 6 month. Conclusion CMV-induced proinflammatory process may be responsible of the interruption of the normal development of the gut or could in turn lead to a disruption in the normal development of the gut potentiating the mechanism causing malrotation. We suggest the hypothesis that an inflammatory process induced by CMV congenital infection may be responsible, in the early gestation, of the intestinal end-organ disease, as the intestinal malrotation. CMV infection should always be excluded in full-term infants presenting with colonic stricture or malrotation.
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Affiliation(s)
- Claudia Colomba
- Department of Sciences for Health Promotion and Mother-Child Care "G.D'Alessandro", Via del Vespro 129, 90127, Palermo, Italy.
| | - Mario Giuffrè
- Department of Sciences for Health Promotion and Mother-Child Care "G.D'Alessandro", Via del Vespro 129, 90127, Palermo, Italy
| | - Simona La Placa
- Department of Sciences for Health Promotion and Mother-Child Care "G.D'Alessandro", Via del Vespro 129, 90127, Palermo, Italy
| | - Antonio Cascio
- Department of Sciences for Health Promotion and Mother-Child Care "G.D'Alessandro", Via del Vespro 129, 90127, Palermo, Italy
| | - Marcello Trizzino
- Department of Sciences for Health Promotion and Mother-Child Care "G.D'Alessandro", Via del Vespro 129, 90127, Palermo, Italy
| | - Simona De Grazia
- Department of Sciences for Health Promotion and Mother-Child Care "G.D'Alessandro", Via del Vespro 129, 90127, Palermo, Italy
| | - Giovanni Corsello
- Department of Sciences for Health Promotion and Mother-Child Care "G.D'Alessandro", Via del Vespro 129, 90127, Palermo, Italy
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Ciccocioppo R, Racca F, Scudeller L, Piralla A, Formagnana P, Pozzi L, Betti E, Vanoli A, Riboni R, Kruzliak P, Baldanti F, Corazza GR. Differential cellular localization of Epstein-Barr virus and human cytomegalovirus in the colonic mucosa of patients with active or quiescent inflammatory bowel disease. Immunol Res 2016; 64:191-203. [PMID: 26659090 DOI: 10.1007/s12026-015-8737-y] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The role of human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) in the exacerbation of inflammatory bowel disease (IBD) is still uncertain. We prospectively investigated the presence of EBV and HCMV infection in both epithelial and immune cells of colonic mucosa of IBD patients, both refractory and responders to standard therapies, in comparison with patients suffering from irritable bowel syndrome who were considered as controls, by using quantitative real-time polymerase chain reaction, immunohistochemistry and in situ hybridization, in an attempt to assess viral localization, DNA load, life cycle phase and possible correlation with disease activity indexes. We obtained clear evidence of the presence of high DNA loads of both viruses in either enterocytes or immune cells of refractory IBD patients, whereas we observed low levels in the responder group and an absence of detectable copies in all cell populations of controls. Remarkably, the values of EBV and HCMV DNA in inflamed mucosa were invariably higher than in non-inflamed areas in both IBD groups, and the EBV DNA loads in the cell populations of diseased mucosa of refractory IBD patients positively correlated with the severity of mucosal damage and clinical indexes of activity. Moreover, EBV infection resulted the most prevalent either alone or in combination with HCMV, while immunohistochemistry and in situ hybridization did not allow us to distinguish between the different phases of viral life cycle. Finally, as regards treatment, these novel findings could pave the way for the use of new antiviral molecules in the treatment of this condition.
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Affiliation(s)
- Rachele Ciccocioppo
- Department of Internal Medicine, IRCCS Policlinico San Matteo Foundation, University of Pavia, Piazzale Golgi, 19, 27100, Pavia, Italy.
| | - Francesca Racca
- Department of Internal Medicine, IRCCS Policlinico San Matteo Foundation, University of Pavia, Piazzale Golgi, 19, 27100, Pavia, Italy
| | - Luigia Scudeller
- Biometry and Clinical Epidemiology Unit, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
| | - Antonio Piralla
- SS Virologia Molecolare - SC Virologia e Microbiologia, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
| | - Pietro Formagnana
- Department of Internal Medicine, IRCCS Policlinico San Matteo Foundation, University of Pavia, Piazzale Golgi, 19, 27100, Pavia, Italy
| | - Lodovica Pozzi
- Department of Internal Medicine, IRCCS Policlinico San Matteo Foundation, University of Pavia, Piazzale Golgi, 19, 27100, Pavia, Italy
| | - Elena Betti
- Department of Internal Medicine, IRCCS Policlinico San Matteo Foundation, University of Pavia, Piazzale Golgi, 19, 27100, Pavia, Italy
| | - Alessandro Vanoli
- Department of Human Pathology, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
| | - Roberta Riboni
- Department of Human Pathology, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
| | - Peter Kruzliak
- 2nd Department of Internal Medicine, St. Anne's University Hospital and Masaryk University, Pekarska 53, 656 91, Brno, Czech Republic. .,Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University, Odborarov 10, 832 32, Bratislava, Slovak Republic.
| | - Fausto Baldanti
- SS Virologia Molecolare - SC Virologia e Microbiologia, IRCCS Policlinico San Matteo Foundation, Pavia, Italy.,Department of Clinical Sciences, Surgery, Diagnostics and Pediatrics, University of Pavia, Pavia, Italy
| | - Gino Roberto Corazza
- Department of Internal Medicine, IRCCS Policlinico San Matteo Foundation, University of Pavia, Piazzale Golgi, 19, 27100, Pavia, Italy
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Traore L, Tao I, Bisseye C, Diarra B, Compaore TR, Nebie Y, Assih M, Ouedraogo A, Zohoncon T, Djigma F, Ouermi D, Barro N, Sanou M, Ouedraogo RT, Simpore J. Molecular diagnostic of cytomegalovirus, Epstein Barr virus and Herpes virus 6 infections among blood donors by multiplex real-time PCR in Ouagadougou, Burkina Faso. Pan Afr Med J 2016; 24:298. [PMID: 28154653 PMCID: PMC5267872 DOI: 10.11604/pamj.2016.24.298.6578] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2015] [Accepted: 07/15/2016] [Indexed: 12/21/2022] Open
Abstract
Introduction In most developing countries, Cytomegalovirus (CMV), Epstein Barr virus (EBV) and Herpes virus 6 (HHV-6) are not diagnosed in blood donors. The aim of this study is to determine the prevalence of these viruses in blood donors from the city of Ouagadougou, Burkina Faso. Methods The study included 198 blood donors of the Regional Blood Transfusion Centre of Ouagadougou. Multiplex real time PCR was used to diagnose the three viruses. Statistical analysis was performed with the software EpiInfo version 6 and SPSS version 17. P values ≤ 0.05 were considered significant. Results Of 198 samples tested, 18 (9.1%) were positive to at least one of the three viruses. In fact, 10 (5.1%) were positive for EBV, 10 (5.1%) positive for CMV and 12 (6.1%) positive for HHV-6. Viral infections were higher in women than in men, EBV (8,6% versus 4.3%), CMV (8.6% versus 3.7%) and HHV-6 (11.4% versus 4.9%). EBV / CMV / HHV-6 co-infection was found in 3.5% (7/198) of blood donors. Conclusion The prevalence recorded in this study is low compared to those found in previous studies from the sub-region among blood donors. The molecular diagnostic test used in our study could explain the differences with previous studies.
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Affiliation(s)
- Lassina Traore
- Biomolecular Research Center Pietro Annigoni Labiogene, UFR / SVT, University of Ouagadougou BP 364 Ouagadougou, Burkina Faso
| | - Issoufou Tao
- Biomolecular Research Center Pietro Annigoni Labiogene, UFR / SVT, University of Ouagadougou BP 364 Ouagadougou, Burkina Faso
| | - Cyrille Bisseye
- Biomolecular Research Center Pietro Annigoni Labiogene, UFR / SVT, University of Ouagadougou BP 364 Ouagadougou, Burkina Faso; Laboratory of Molecular and Cellular Biology, University of Sciences and Techniques of Masuku, P 943 Franceville, Gabon
| | - Birama Diarra
- Biomolecular Research Center Pietro Annigoni Labiogene, UFR / SVT, University of Ouagadougou BP 364 Ouagadougou, Burkina Faso
| | - Tegwindé Rebeca Compaore
- Biomolecular Research Center Pietro Annigoni Labiogene, UFR / SVT, University of Ouagadougou BP 364 Ouagadougou, Burkina Faso
| | - Yacouba Nebie
- Molecular Biology, Epidemiology and Monitoring of Communicable of Bacteria and Viruses Through Food, UFR / SVT, University of Ouagadougou, Burkina Faso
| | - Maleki Assih
- Biomolecular Research Center Pietro Annigoni Labiogene, UFR / SVT, University of Ouagadougou BP 364 Ouagadougou, Burkina Faso
| | - Alice Ouedraogo
- Biomolecular Research Center Pietro Annigoni Labiogene, UFR / SVT, University of Ouagadougou BP 364 Ouagadougou, Burkina Faso
| | - Theodora Zohoncon
- Biomolecular Research Center Pietro Annigoni Labiogene, UFR / SVT, University of Ouagadougou BP 364 Ouagadougou, Burkina Faso
| | - Florencia Djigma
- Biomolecular Research Center Pietro Annigoni Labiogene, UFR / SVT, University of Ouagadougou BP 364 Ouagadougou, Burkina Faso
| | - Djénéba Ouermi
- Biomolecular Research Center Pietro Annigoni Labiogene, UFR / SVT, University of Ouagadougou BP 364 Ouagadougou, Burkina Faso
| | - Nicolas Barro
- Molecular Biology, Epidemiology and Monitoring of Communicable of Bacteria and Viruses Through Food, UFR / SVT, University of Ouagadougou, Burkina Faso
| | - Mahamoudou Sanou
- Molecular Biology, Epidemiology and Monitoring of Communicable of Bacteria and Viruses Through Food, UFR / SVT, University of Ouagadougou, Burkina Faso
| | - Rasmata Traore Ouedraogo
- Molecular Biology, Epidemiology and Monitoring of Communicable of Bacteria and Viruses Through Food, UFR / SVT, University of Ouagadougou, Burkina Faso
| | - Jacques Simpore
- Biomolecular Research Center Pietro Annigoni Labiogene, UFR / SVT, University of Ouagadougou BP 364 Ouagadougou, Burkina Faso
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Wang HW, Kuo CJ, Lin WR, Hsu CM, Ho YP, Lin CJ, Su MY, Chiu CT, Wang CL, Chen KH. The clinical characteristics and manifestations of cytomegalovirus esophagitis. Dis Esophagus 2016; 29:392-399. [PMID: 25715747 DOI: 10.1111/dote.12340] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Esophagitis is the second most common gastrointestinal manifestation of cytomegalovirus (CMV) infection after colitis. CMV esophagitis has been reported in patients who have undergone transplantation, are on long-term renal dialysis, or who have the human immunodeficiency virus infection. This study aimed to investigate the clinical characteristics and manifestations of CMV esophagitis in patients who underwent diagnostic endoscopy. A total of 16 patients with histologically proven CMV infection were identified from 1539 patients with esophageal ulcers and analyzed retrospectively (January 2006 to December 2013). Patients' personal data (age, smoking, and alcohol consumption), underlying systemic diseases (diabetes mellitus, end-stage renal disease, and chronic obstructive pulmonary disease), malignancy, indication for esophagogastroduodenoscopy, endoscopic characteristics, and diagnostic methods (pathological or serological findings) were collected for further analysis. Among the patients with CMV esophagitis, the mean age was 59.94 years (range, 23-84 years). The male : female ratio was 1.67:1. Odynophagia and epigastralgia were common symptoms. Of the 16 patients, 3 (18.75%) were infected with the human immunodeficiency virus and 9 (56.25%) had an underlying malignancy, including lung cancer (6 patients), esophageal cancer (2 patients), gastric cancer (1 patient), ampulla of Vater cancer (1 patient), and lymphoma (1 patient). Six of the 9 patients (66.7%) with malignancy had been administered concurrent chemoradiotherapy (CCRT). In this study, patients with malignancy who had been administered CCRT were at increased risk for CMV esophagitis, which had not been reported before in the literature. CMV esophagitis should be considered as a potential treatment-related complication of CCRT.
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Affiliation(s)
- H-W Wang
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - C-J Kuo
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - W-R Lin
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - C-M Hsu
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Y-P Ho
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - C-J Lin
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - M-Y Su
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - C-T Chiu
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - C-L Wang
- Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - K-H Chen
- Department of Pathology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
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Canterino JE, McCormack M, Gurung A, Passarelli J, Landry ML, Golden M. Cytomegalovirus appendicitis in an immunocompetent host. J Clin Virol 2016; 78:9-11. [PMID: 26942831 DOI: 10.1016/j.jcv.2016.02.011] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2015] [Revised: 02/01/2016] [Accepted: 02/16/2016] [Indexed: 01/22/2023]
Abstract
Cytomegalovirus (CMV) is a common viral pathogen. Asymptomatic infection or a mononucleosis syndrome are the most common manifestations in otherwise healthy individuals. End-organ disease is rare in immunocompetent individuals. Here, we describe a case of CMV appendicitis in a patient without an immune-compromising condition.
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Affiliation(s)
- Joseph E Canterino
- Section of Infectious Diseases, Yale-New Haven Hospital, New Haven, CT 06510, USA.
| | - Michael McCormack
- Department of Surgery, Yale-New Haven Hospital, New Haven, CT 06510, USA.
| | - Ananta Gurung
- Department of Pathology, Royal Columbian Hospital, New Westminster, BC, Canada; Department of Pathology, Yale-New Haven Hospital, New Haven, CT, 06510, USA.
| | - James Passarelli
- Department of Surgery, Yale-New Haven Hospital, New Haven, CT 06510, USA.
| | - Marie L Landry
- Departments of Laboratory Medicine and Internal Medicine, Yale University School of Medicine, New Haven, CT 06510, USA.
| | - Marjorie Golden
- Section of Infectious Diseases, Yale-New Haven Hospital, New Haven, CT 06510, USA.
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Arnold M, Itzikowitz R, Young B, Machoki SM, Hsiao NY, Pillay K, Alexander A. Surgical manifestations of gastrointestinal cytomegalovirus infection in children: Clinical audit and literature review. J Pediatr Surg 2015; 50:1874-9. [PMID: 26265193 DOI: 10.1016/j.jpedsurg.2015.06.018] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2015] [Revised: 06/17/2015] [Accepted: 06/22/2015] [Indexed: 12/20/2022]
Abstract
INTRODUCTION Gastrointestinal sequelae of cytomegalovirus are rare, usually associated with significant immune compromise, and carry a high morbidity and mortality. Gastrointestinal disease frequently requires surgical intervention for diagnosis and management. AIM The aim of the study is to evaluate the incidence, presentation and management of gastrointestinal cytomegalovirus disease in a pediatric population. METHOD Between January 2003 and June 2011, a retrospective folder review was conducted of all symptomatic children with proven CMV disease, presenting to the surgical service. Eligible patients were identified using the surgical, histopathology and serology databases. RESULTS Thirty-eight patients (1.8/1000 surgical admissions) were identified with a median presenting age of 5months (range 3days-12years). Esophagitis (n=18) and small bowel disease (n=16) predominated, but CMV was seen throughout the gastrointestinal tract. Risk factors included HIV infection (n=21, 55%) and recent gastrointestinal surgery or infection (n=10, 26%). Characteristic multiple jejunoileal perforations were seen in six patients. Compared to upper GIT disease, intestinal involvement was associated with younger age and doubled mortality. In HIV-infected children, median CD4 (%) was lower in intestinal compared to upper gastrointestinal disease. Morbidities included anastomotic breakdowns (5), anastomotic strictures (3), relook laparotomies (10), resistant esophageal strictures (5) and prolonged parenteral nutrition (5). Anti-CMV drugs were given in 63%. Overall mortality was 32% (12/38) and was associated with lower GIT disease. CONCLUSION Invasive CMV gastrointestinal disease in our children was predominantly HIV-associated, or followed a major lower gastrointestinal inflammatory insult in infants younger than 6months. Successful therapy requires a high index of suspicion of active CMV disease to allow early implementation of CMV viral load control and aggressive treatment of the underlying immune impairment. Multiple surgical interventions are often required for both tissue diagnosis and management of acute and chronic complications. CMV-viral-load-tailored anti-CMV therapy is supported by recent literature.
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Affiliation(s)
- M Arnold
- Department of Paediatric Surgery, Red Cross War Memorial Children's Hospital, Cape Town, South Africa
| | - R Itzikowitz
- Department of Paediatric Surgery, Red Cross War Memorial Children's Hospital, Cape Town, South Africa
| | - B Young
- Department of Paediatric Surgery, Red Cross War Memorial Children's Hospital, Cape Town, South Africa
| | - S M Machoki
- Department of Paediatric Surgery, Red Cross War Memorial Children's Hospital, Cape Town, South Africa
| | - N Y Hsiao
- Division of Medical Virology, National Health Laboratory Service/University of Cape Town, Cape Town, South Africa
| | - K Pillay
- Department of Histopathology, NHLS, Red Cross War Memorial Children's Hospital, Cape Town, South Africa
| | - A Alexander
- Department of Paediatric Surgery, Red Cross War Memorial Children's Hospital, Cape Town, South Africa
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İlgen U, Atmiş V, Karaarslan Cengiz Ö, Çinar E, Aras S, Varli M, Atli T. A case of CMV esophagitis complicated by extensive thrombosis in older patient without HIV infection or transplantation. Eur Geriatr Med 2015. [DOI: 10.1016/j.eurger.2015.02.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Diagnostic utility of quantitative plasma cytomegalovirus DNA PCR for cytomegalovirus end-organ diseases in patients with HIV-1 infection. J Acquir Immune Defic Syndr 2015; 68:140-6. [PMID: 25590268 DOI: 10.1097/qai.0000000000000410] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE To investigate the diagnostic value of quantitative plasma cytomegalovirus (CMV)-DNA polymerase chain reaction (PCR) for CMV end-organ diseases (CMV-EOD) in patients with HIV-1 infection. DESIGN Single-center cross-sectional study. METHODS The study subjects were HIV-1-infected patients with CD4 ≤200 per microliter, who had undergone ophthalmologic examination with plasma CMV-DNA PCR measured within 7 days. CMV retinitis and other CMV-EOD were diagnosed according to the ACTG criteria. PCR value was converted into the WHO international standard. RESULTS CMV retinitis and all CMV-EOD were diagnosed in 23 (5%) and 37 (8%) of the 461 study patients, respectively. CMV-DNA was undetectable (<185 IU/mL) in 2 patients with CMV retinitis and 1 with encephalitis. The area under the receiver operating characteristic curve of CMV-DNA for CMV retinitis and all CMV-EOD were 0.80 [95% confidence interval (CI): 0.71 to 0.89] and 0.82 (0.75 to 0.89), respectively. The sensitivity, specificity, positive predictive value, and negative predictive value for each cutoff value of CMV-DNA were as follows: for CMV retinitis, ≥10,086 IU/mL: 26.1%, 94.1%, 18.8%, 96%; ≥2946 IU/mL; 56.5%, 86.8%, 18.3%, 97.4%; ≥959 IU/mL; 60.9%, 78.1%, 12.7%, 97.4%; detectable CMV-DNA (≥185 IU/mL): 91.3%, 48.2%, 8.5%, 99.1%; for all CMV-EOD: ≥10,086 IU/mL: 32.4%, 95.3%, 37.5%, 94.2%; ≥2946 IU/mL; 54.1%, 88%, 28.2%, 95.6%; ≥959 IU/mL; 62.2%, 79.5%, 20.9%, 96%; detectable CMV-DNA; 91.9%, 49.5%, 13.7%, 98.6%. CONCLUSIONS Plasma CMV-DNA PCR has a high diagnostic value for both CMV retinitis and all CMV-EOD in patients with advanced HIV-1 infection. A cutoff value of CMV-DNA ≥10,086 IU/mL and ≥2946 IU/mL yields high specificity, whereas undetectable CMV-DNA load (<185 IU/mL) likely rules out CMV-EOD.
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Ciccocioppo R, Racca F, Paolucci S, Campanini G, Pozzi L, Betti E, Riboni R, Vanoli A, Baldanti F, Corazza GR. Human cytomegalovirus and Epstein-Barr virus infection in inflammatory bowel disease: Need for mucosal viral load measurement. World J Gastroenterol 2015; 21:1915-1926. [PMID: 25684960 PMCID: PMC4323471 DOI: 10.3748/wjg.v21.i6.1915] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2014] [Revised: 10/03/2014] [Accepted: 11/19/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the best diagnostic technique and risk factors of the human Cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) infection in inflammatory bowel disease (IBD).
METHODS: A cohort of 40 IBD patients (17 refractory) and 40 controls underwent peripheral blood and endoscopic colonic mucosal sample harvest. Viral infection was assessed by quantitative real-time polymerase chain reaction and immunohistochemistry, and correlations with clinical and endoscopic indexes of activity, and risk factors were investigated.
RESULTS: All refractory patients carried detectable levels of HCMV and/or EBV mucosal load as compared to 13/23 (56.5%) non-refractory and 13/40 (32.5%) controls. The median DNA value was significantly higher in refractory (HCMV 286 and EBV 5.440 copies/105 cells) than in non-refractory (HCMV 0 and EBV 6 copies/105 cells; P < 0.05 and < 0.001) IBD patients and controls (HCMV and EBV 0 copies/105 cells; P < 0.001 for both). Refractory patients showed DNA peak values ≥ 103 copies/105 cells in diseased mucosa in comparison to non-diseased mucosa (P < 0.0121 for HCMV and < 0.0004 for EBV), while non-refractory patients and controls invariably displayed levels below this threshold, thus allowing us to differentiate viral colitis from mucosal infection. Moreover, the mucosal load positively correlated with the values found in the peripheral blood, whilst no correlation with the number of positive cells at immunohistochemistry was found. Steroid use was identified as a significant risk factor for both HCMV (P = 0.018) and EBV (P = 0.002) colitis. Finally, a course of specific antiviral therapy with ganciclovir was successful in all refractory patients with HCMV colitis, whilst refractory patients with EBV colitis did not show any improvement despite steroid tapering and discontinuation of the other medications.
CONCLUSION: Viral colitis appeared to contribute to mucosal lesions in refractory IBD, and its correct diagnosis and management require quantitative real-time polymerase chain reaction assay of mucosal specimens.
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Nausea, Vomiting, and Noninflammatory Diarrhea. MANDELL, DOUGLAS, AND BENNETT'S PRINCIPLES AND PRACTICE OF INFECTIOUS DISEASES 2015. [PMCID: PMC7173487 DOI: 10.1016/b978-1-4557-4801-3.00100-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
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Ganzenmueller T, Kluba J, Becker JU, Bachmann O, Heim A. Detection of cytomegalovirus (CMV) by real-time PCR in fecal samples for the non-invasive diagnosis of CMV intestinal disease. J Clin Virol 2014; 61:517-22. [PMID: 25453330 DOI: 10.1016/j.jcv.2014.10.009] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2014] [Revised: 10/09/2014] [Accepted: 10/14/2014] [Indexed: 12/18/2022]
Abstract
BACKGROUND Cytomegalovirus (CMV) infection of the gastrointestinal tract can cause CMV intestinal disease (CMV-ID), a severe complication in immunocompromised patients. Current gold standard for diagnosing CMV-ID requires the analysis of colon biopsies. Testing of fecal samples by CMV PCR might be a non-invasive diagnostic alternative, but data on this method is scarce. OBJECTIVES To evaluate the use of quantitative CMV real-time PCR in fecal samples for diagnosing CMV-ID. STUDY DESIGN Fecal samples and lower intestinal tract biopsies from 66 patients were analyzed by quantitative CMV PCR. To evaluate the diagnostic significance of CMV detection by PCR in fecal samples, patients were classified according to the etiology of their intestinal disease (based on results of endoscopy, histopathology and quantitative CMV DNA detection in biopsies) into three groups: "CMV-ID", "non-CMV-ID", and "equivocal". RESULTS 10/66 fecal samples were tested positive by quantitative CMV PCR, but CMV DNA loads were low (range <1000-11,000copies/ml). CMV detection by PCR in fecal samples was positive in 8/12 patients of the CMV-ID group, resulting in a sensitivity of 67% for diagnosing CMV-ID. With two exceptions, fecal CMV PCR was negative in the non-CMV-ID group (45/47) indicating a good specificity (96%). Moreover, CMV DNA detection in feces was associated with high CMV DNA levels in intestinal biopsies. CONCLUSIONS Negative CMV PCR results from fecal samples cannot exclude CMV-ID and thus have to be confirmed by analyzing intestinal biopsies. However, positive fecal PCR results are diagnostically useful and might help to circumvent invasive diagnostic procedures as endoscopy.
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Affiliation(s)
- Tina Ganzenmueller
- Institute of Virology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany.
| | - Jeanette Kluba
- Institute of Virology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany
| | - Jan Ulrich Becker
- Institute of Pathology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany
| | - Oliver Bachmann
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany; German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Germany
| | - Albert Heim
- Institute of Virology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany
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Kim JW, Boo SJ, Ye BD, Kim CL, Yang SK, Kim J, Kim SA, Park SH, Park SK, Yang DH, Jung KW, Kim KJ, Byeon JS, Myung SJ, Kim JH. Clinical utility of cytomegalovirus antigenemia assay and blood cytomegalovirus DNA PCR for cytomegaloviral colitis patients with moderate to severe ulcerative colitis. J Crohns Colitis 2014; 8:693-701. [PMID: 24405983 DOI: 10.1016/j.crohns.2013.12.014] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2013] [Revised: 12/16/2013] [Accepted: 12/17/2013] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Clinical usefulness of cytomegalovirus (CMV) antigenemia assay and blood CMV polymerase chain reaction (PCR) in patients with ulcerative colitis (UC) needs to be evaluated. METHODS Medical records of moderate to severe UC patients between January 2001 and December 2012 were reviewed retrospectively. Diagnostic performances of CMV antigenemia assay and blood PCR to predict CMV colitis, and clinical outcome according to the results were analyzed. CMV colitis was diagnosed by H&E staining and/or CMV immunohistochemistry. RESULTS Of the 229 study subjects, 83 patients (36.2%) had CMV colitis. The sensitivity and specificity of CMV antigenemia assay were 47.0% and 81.7%, and those of blood CMV DNA PCR were 44.3% and 87.9%, respectively. If either CMV antigenemia or PCR was positive in the presence of significant ulcers, the sensitivity and specificity of having CMV colitis were 67.3% and 75.7%, respectively, with the area under the receiver operating characteristic curve value of 0.717. Among patients with significant ulcers, positive CMV antigenemia (33/50 [66.0%] vs. 31/102 [30.4%]; p<0.001) and positive blood CMV PCR (25/37 [67.6%] vs. 24/86 [27.9%]; p<0.001) showed significantly higher probability of CMV colitis than blood test-negative patients. UC-CMV colitis patients with positive CMV antigenemia showed significantly higher rate of colectomy than those with negative antigenemia (13/39 [33.3%] vs. 5/44 [11.4%]; p=0.015). CONCLUSIONS Although CMV antigenemia and blood CMV PCR showed low sensitivity for diagnosing CMV colitis, the specificity values were high. Among UC-CMV colitis patients, CMV antigenemia showed significant association with subsequent colectomy.
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Affiliation(s)
- Jong Wook Kim
- Department of Internal Medicine, Inje University Ilsan Paik Hospital, Goyang, Republic of Korea
| | - Sun-Jin Boo
- Department of Internal Medicine, Jeju National University School of Medicine, Jeju, Republic of Korea
| | - Byong Duk Ye
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea; Inflammatory Bowel Disease Center, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
| | - Chang Lae Kim
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Suk-Kyun Yang
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea; Inflammatory Bowel Disease Center, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Jihun Kim
- Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Sun A Kim
- Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Sang Hyoung Park
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea; Inflammatory Bowel Disease Center, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Soo-Kyung Park
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Dong-Hoon Yang
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Kee Wook Jung
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Kyung-Jo Kim
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea; Inflammatory Bowel Disease Center, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Jeong-Sik Byeon
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Seung-Jae Myung
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Jin-Ho Kim
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
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Ciccocioppo R, Comoli P, Gallia A, Basso S, Baldanti F, Corazza GR. Autologous human cytomegalovirus-specific cytotoxic T cells as rescue therapy for ulcerative enteritis in primary immunodeficiency. J Clin Immunol 2014; 34:681-5. [PMID: 24888600 DOI: 10.1007/s10875-014-0060-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2013] [Accepted: 05/15/2014] [Indexed: 11/30/2022]
Abstract
PURPOSE Patients affected by primary immunodeficiency usually undergo a wide range of infections, including reactivation of latent ones. Here we report two cases suffering from late-onset combined immunodeficiency in which ulcerative enteritis due to human Cytomegalovirus caused a life-threatening malabsorption syndrome. METHODS The assessment of the viral load was carried out on both blood and mucosal samples by quantitative real-time polymerase chain reaction assay. The generation of autologous virus-specific cytotoxic T cell lines was performed according to Good Manufacturing Practice protocol after peripheral blood mononuclear cells were collected through a single leukapheresis. RESULTS In both patients, the viral load resulted negligible in peripheral blood, but very high in mucosal specimens (range 1.064 - 1.031.692 copies/10(5) cells). After two rounds of antiviral therapy proved unsuccessful, the generation of virus-specific cytotoxic T cell lines was carried out despite severe lymphopenia, and their infusion resulted safe and durably effective in healing intestinal ulcerations and resetting the viral load. CONCLUSIONS Virus-specific cellular therapy was useful in reconstituting specific immunity and treating severe human Cytomegalovirus-related enteritis in patients with primary immunodeficiency.
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Affiliation(s)
- Rachele Ciccocioppo
- Department of Internal Medicine, IRCCS Policlinico San Matteo Foundation - University of Pavia, Pavia, Italy,
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Yan Z, Wang L, Dennis J, Doern C, Baker J, Park JY. Clinical significance of isolated cytomegalovirus-infected gastrointestinal cells. Int J Surg Pathol 2014; 22:492-8. [PMID: 24891553 DOI: 10.1177/1066896914537681] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
BACKGROUND Cytomegalovirus (CMV) infection of the gastrointestinal (GI) tract is associated with high mortality in immunosuppressed patients. However, few studies have correlated blood CMV load with GI histopathological findings. Furthermore, there have been few studies determining the clinical significance of isolated CMV infection. DESIGN Cases were selected for the diagnosis of GI CMV infection by searching the information system of a tertiary hospital. The electronic medical record was reviewed for each case to determine blood viral load, clinicopathological features at the time of diagnosis and clinical outcomes after discharge. RESULTS In all, 30 patients with CMV-positive intestinal biopsies confirmed by immunohistochemistry (IHC) were identified. All were immunosuppressed. CMV inclusions were also recognized by hematoxylin and eosin stain in 27% of the cases, and the remaining cases were identified by IHC alone. CMV blood load was only positive in 17% of the cases; 8 cases had only isolated CMV-infected cells (0.1-0.5 IHC count/high-power field), with the following outcomes: worsening symptoms that responded to antiviral therapy (n = 5); clinical improvement without treatment (n = 1); death without treatment (n = 2). CONCLUSIONS CMV infection of the intestines is clinically significant but will not always present with classic viral cytopathic changes. IHC should be considered in any case where there is a clinical suspicion for CMV infection. Identification of isolated CMV infection by IHC should be considered clinically significant. Current blood viral load tests have poor sensitivity in detecting CMV intestinal infection. Future studies will investigate the predictive value of positive peripheral blood viral load in patients with intestinal symptoms.
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Affiliation(s)
- Zhen Yan
- Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA Department of Pathology, Children's Medical Center, Dallas, TX, USA
| | - Linlin Wang
- Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA Department of Pathology, Children's Medical Center, Dallas, TX, USA
| | - Jake Dennis
- Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA Department of Pathology, Children's Medical Center, Dallas, TX, USA
| | - Christopher Doern
- Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA Department of Pathology, Children's Medical Center, Dallas, TX, USA
| | - Jonathan Baker
- Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Jason Y Park
- Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA Department of Pathology, Children's Medical Center, Dallas, TX, USA Eugene McDermott Center for Human Growth and Development, Dallas, TX, USA
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Pasticci MB, Corsi S, Spigarelli F, Correnti S, Francisci D, Castronari R, Baldin P, Prosperini A, Baldelli F, Cenci E, Sensini A, Morelli O. Acute appendicitis due to Cytomegalovirus in an apparently immunocompetent patient: a case report. J Med Case Rep 2014; 8:92. [PMID: 24612821 PMCID: PMC3976169 DOI: 10.1186/1752-1947-8-92] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2013] [Accepted: 12/16/2013] [Indexed: 11/10/2022] Open
Abstract
Introduction In healthy subjects, Cytomegalovirus infection can be asymptomatic or manifest as mononucleosis syndrome, but organ disease has also been reported. However, in immunocompromised patients this infection can lead to its most significant and severe disease and even mortality. When Cytomegalovirus causes a gastrointestinal tract infection, it more commonly manifests with luminal tract disease and is usually characterized by ulcerative lesions. Appendicitis is a rare manifestation, and has been reported mainly in human immunodeficiency virus-infected patients or patients with other causes of immunocompromise. Case presentation The authors report on a case of acute primary Cytomegalovirus infection complicated with acute appendicitis due to Cytomegalovirus in an apparently immunocompetent 24-year-old Caucasian man also suffering from primary sclerosing cholangitis and ulcerative colitis. Diagnosis was based on clinical manifestations, serology results, as well as microbiological and histological findings. Treatment consisted of surgery and anti-Cytomegalovirus therapy. Conclusions Cytomegalovirus should be included among the etiologic agents of acute appendicitis in patients with primary sclerosing cholangitis and ulcerative colitis. Currently, there are no definitive data regarding the frequency of Cytomegalovirus appendicitis and the role of anti-Cytomegalovirus treatment in human immunodeficiency virus-negative and apparently immunocompetent subjects.
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Affiliation(s)
- Maria Bruna Pasticci
- Infectious Disease, Department Experimental Medicine and Biochemical Sciences, University of Perugia, 06100 Perugia, Italy.
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Pant C, Deshpande A, Larson A, O'Connor J, Rolston DDK, Sferra TJ. Diarrhea in solid-organ transplant recipients: a review of the evidence. Curr Med Res Opin 2013; 29:1315-28. [PMID: 23777312 DOI: 10.1185/03007995.2013.816278] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
OBJECTIVE To provide a comprehensive review of the literature as it relates to diarrhea in solid organ transplant (SOT) recipients. In this article, we review the epidemiology, pathogenesis, clinical manifestations, diagnosis and management of diarrhea in SOT recipients and discuss recent advances and challenges. METHODS Two investigators conducted independent literature searches using PubMed, Web of Science, and Scopus until January 1st, 2013. All databases were searched using a combination of the terms diarrhea, solid organ transplant, SOT, transplant associated diarrhea, and transplant recipients. Articles that discussed diarrhea in SOT recipients were reviewed and relevant cross-references also read and evaluated for inclusion. Selection bias could be a possible limitation of the approach used in selecting or finding articles for this article. FINDINGS Post-transplant diarrhea is a common and distressing occurrence in patients, which can have significant deleterious effects on the clinical course and well-being of the organ recipient. A majority of cases are due to infectious and drug-related etiologies. However, various other etiologies including inflammatory bowel disease must be considered in the differential diagnosis. A step-wise, informed approach to post-transplant diarrhea will help the clinician achieve the best diagnostic yield. The use of diagnostic endoscopy should be preceded by exclusion of an infectious or drug-related cause of diarrhea. Empiric management with antidiarrheal agents, probiotics, and lactose-free diets may have a role in managing patients for whom no cause can be determined even after an extensive investigation. CONCLUSIONS Physicians should be familiar with the common etiologies that result in post-transplant diarrhea. A directed approach to diagnosis and treatment will not only help to resolve the diarrhea but also prevent potentially life-threatening consequences including loss of the graft as well. Prospective studies are required to determine the etiology of post-transplant diarrhea in different clinical and geographic settings.
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Affiliation(s)
- Chaitanya Pant
- University of Oklahoma Health Sciences Center , Oklahoma City, OK , USA
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Detection of cytomegalovirus drug resistance mutations by next-generation sequencing. J Clin Microbiol 2013; 51:3700-10. [PMID: 23985916 DOI: 10.1128/jcm.01605-13] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023] Open
Abstract
Antiviral therapy for cytomegalovirus (CMV) plays an important role in the clinical management of solid organ and hematopoietic stem cell transplant recipients. However, CMV antiviral therapy can be complicated by drug resistance associated with mutations in the phosphotransferase UL97 and the DNA polymerase UL54. We have developed an amplicon-based high-throughput sequencing strategy for detecting CMV drug resistance mutations in clinical plasma specimens using a microfluidics PCR platform for multiplexed library preparation and a benchtop next-generation sequencing instrument. Plasmid clones of the UL97 and UL54 genes were used to demonstrate the low overall empirical error rate of the assay (0.189%) and to develop a statistical algorithm for identifying authentic low-abundance variants. The ability of the assay to detect resistance mutations was tested with mixes of wild-type and mutant plasmids, as well as clinical CMV isolates and plasma samples that were known to contain mutations that confer resistance. Finally, 48 clinical plasma specimens with a range of viral loads (394 to 2,191,011 copies/ml plasma) were sequenced using multiplexing of up to 24 specimens per run. This led to the identification of seven resistance mutations, three of which were present in <20% of the sequenced population. Thus, this assay offers more sensitive detection of minor variants and a higher multiplexing capacity than current methods for the genotypic detection of CMV drug resistance mutations.
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42
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Ozaki T, Yamashita H, Kaneko S, Yorifuji H, Takahashi H, Ueda Y, Takahashi Y, Kaneko H, Kano T, Mimori A. Cytomegalovirus disease of the upper gastrointestinal tract in patients with rheumatic diseases: a case series and literature review. Clin Rheumatol 2013; 32:1683-90. [PMID: 23942768 DOI: 10.1007/s10067-013-2363-7] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2013] [Accepted: 07/31/2013] [Indexed: 02/06/2023]
Abstract
Cytomegalovirus disease of the upper gastrointestinal tract (CMV-UGT) is a rare but significant complication in patients with rheumatic diseases. We reviewed records for January 2004 to December 2012 and investigated the occurrence of CMV-UGT in patients with rheumatic diseases to evaluate clinical characteristics, the value of the CMV antigenemia assay, and the association between immunosuppressive therapy and CMV-UGT. Ten CMV-UGT events (six gastric ulcer, two esophagitis, one gastritis, and one duodenal ulcer) in nine patients (three rheumatoid arthritis, three systemic lupus erythematosus, one dermatomyositis, one systemic sclerosis, and one overlap syndrome) were identified based on pathology. Mean age was 66.5 (range, 53-76) years. The CMV antigenemia assay was negative in five cases (50 %). All ten cases received glucocorticoids and six (60 %) received pulsed glucocorticoids. Mean prednisolone dose was 31.3 (range, 7.5-40) mg/day at diagnosis. Concomitant immunosuppressive agents were used in eight cases (80 %). Considering other published cases, the most common immunosuppressive drug was cyclophosphamide (ten cases; 45 %). Notably, two of our patients who were treated with low-dose glucocorticoids plus other milder immunosuppressive drugs (methotrexate and cyclosporine) also developed CMV-UGT. Life-threatening complications such as massive bleeding or perforated ulcer occurred in two patients. These results suggest that patients receiving intensive immunosuppressive therapy such as high-dose glucocorticoids and cyclophosphamide are at higher risk for developing CMV-UGT. Moreover, CMV-UGT can occur even with low-dose glucocorticoid therapy and relatively mild immunosuppressive agents. The value of the CMV antigenemia assay for predicting CMV-UGT appears to be limited.
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Affiliation(s)
- Takashi Ozaki
- Division of Rheumatic Diseases, National Center for Global Health and Medicine, 1-21-1, Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan,
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Novikov MS, Babkov DA, Paramonova MP, Khandazhinskaya AL, Ozerov AA, Chizhov AO, Andrei G, Snoeck R, Balzarini J, Seley-Radtke KL. Synthesis and anti-HCMV activity of 1-[ω-(phenoxy)alkyl]uracil derivatives and analogues thereof. Bioorg Med Chem 2013; 21:4151-7. [PMID: 23743443 PMCID: PMC7127185 DOI: 10.1016/j.bmc.2013.05.009] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2013] [Revised: 04/27/2013] [Accepted: 05/07/2013] [Indexed: 01/31/2023]
Abstract
HCMV infection represents a life-threatening condition for immunocompromised patients and newborn infants and novel anti-HCMV agents are clearly needed. In this regard, a series of 1-[ω-(phenoxy)alkyl]uracil derivatives were synthesized and examined for antiviral properties. Compounds 17, 20, 24 and 28 were found to exhibit highly specific and promising inhibitory activity against HCMV replication in HEL cell cultures with EC50 values within 5.5-12μM range. Further studies should be undertaken to elucidate the mechanism of action of these compounds and the structure-activity relationship for the linker region.
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Affiliation(s)
- Mikhail S. Novikov
- Department of Pharmaceutical & Toxicological Chemistry, Volgograd State Medical University, Pavshikh Bortsov Sq., 1, Volgograd 400131, Russia
| | - Denis A. Babkov
- Department of Pharmaceutical & Toxicological Chemistry, Volgograd State Medical University, Pavshikh Bortsov Sq., 1, Volgograd 400131, Russia
| | - Maria P. Paramonova
- Department of Pharmaceutical & Toxicological Chemistry, Volgograd State Medical University, Pavshikh Bortsov Sq., 1, Volgograd 400131, Russia
| | | | - Alexander A. Ozerov
- Department of Pharmaceutical & Toxicological Chemistry, Volgograd State Medical University, Pavshikh Bortsov Sq., 1, Volgograd 400131, Russia
| | - Alexander O. Chizhov
- Zelinsky Institute of Organic Chemistry, Russian Academy of Science, Leninsky pr., 47, Moscow 119991, Russia
| | - Graciela Andrei
- Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, Leuven B-3000, Belgium
| | - Robert Snoeck
- Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, Leuven B-3000, Belgium
| | - Jan Balzarini
- Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, Leuven B-3000, Belgium
| | - Katherine L. Seley-Radtke
- Department of Chemistry & Biochemistry, University of Maryland, Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, USA
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Hamada Y, Nagata N, Shimbo T, Igari T, Nakashima R, Asayama N, Nishimura S, Yazaki H, Teruya K, Gatanaga H, Kikuchi Y, Akiyama J, Ohmagari N, Uemura N, Oka S. Assessment of antigenemia assay for the diagnosis of cytomegalovirus gastrointestinal diseases in HIV-infected patients. AIDS Patient Care STDS 2013; 27:387-91. [PMID: 23799239 DOI: 10.1089/apc.2013.0115] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
Abstract
We conducted a single-center prospective study to evaluate the utility of cytomegalovirus (CMV) antigenemia assay for the diagnosis of CMV-gastrointestinal disease (GID). The study subjects were HIV-infected patients with CD4 count ≤200 μL/cells who had undergone endoscopy. A definite diagnosis of CMV-GID was made by histological examination of endoscopic biopsied specimen. CMV antigenemia assay (C10/C11 monoclonal antibodies), CD4 count, HIV viral load, history of HAART, and gastrointestinal symptoms as measured by 7-point Likert scale, were assessed on the same day of endoscopy. One hundred cases were selected for analysis, which were derived from 110 cases assessed as at high-risk for CMV-GID after endoscopy screening of 423 patients. Twelve patients were diagnosed with CMV-GID. Among the gastrointestinal symptoms, mean bloody stool score was significantly higher in patients with CMV-GID than in those without (2.5 vs. 1.7, p=0.02). The area under the receiver-operating characteristic curve of antigenemia was 0.80 (95%CI 0.64-0.96). The sensitivity, specificity, positive likelihood ratio (LR), and negative LR of antigenemia were 75.0%, 79.5%, 3.7, and 0.31, respectively, when the cutoff value for antigenemia was ≥1 positive cell per 300,000 granulocytes, and 50%, 92.0%, 5.5, and 0.55, respectively, for ≥5 positive cells per 300,000 granulocytes. In conclusion, CMV antigenemia seems a useful diagnostic test for CMV-GID in patients with HIV infection. The use of ≥5 positive cells per 300,000 granulocytes as a cutoff value was associated with high specificity and high positive LR. Thus, a positive antigenemia assay with positive endoscopic findings should allow the diagnosis of CMV-GID without biopsy.
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Affiliation(s)
- Yohei Hamada
- AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan
| | - Naoyoshi Nagata
- Department of Gastroenterology and Hepatology, National Center for Global Health, Tokyo, Japan
| | - Takuro Shimbo
- Department of Clinical Research and Informatics, International Clinical Research Center Research Institute, National Center for Global Health, Tokyo, Japan
| | - Toru Igari
- Department of Pathology Division of Clinical Laboratory, National Center for Global Health, Tokyo, Japan
| | - Ryo Nakashima
- Department of Gastroenterology and Hepatology, National Center for Global Health, Tokyo, Japan
| | - Naoki Asayama
- Department of Gastroenterology and Hepatology, National Center for Global Health, Tokyo, Japan
| | - So Nishimura
- Department of Gastroenterology and Hepatology, National Center for Global Health, Tokyo, Japan
| | - Hirohisa Yazaki
- AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan
| | - Katsuji Teruya
- AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan
| | - Hiroyuki Gatanaga
- AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan
- Center for AIDS Research, Kumamoto University, Kumamoto, Japan
| | - Yoshimi Kikuchi
- AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan
| | - Junichi Akiyama
- Department of Gastroenterology and Hepatology, National Center for Global Health, Tokyo, Japan
| | - Norio Ohmagari
- Division of Infectious Diseases, Disease Control and Prevention Center, National Center for Global Health, Tokyo, Japan
| | - Naomi Uemura
- Department of Gastroenterology and Hepatology, National Center for Global Health and Medicine, Kohnodai Hospital, Chiba, Japan
| | - Shinichi Oka
- AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan
- Center for AIDS Research, Kumamoto University, Kumamoto, Japan
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Nagata N, Shimbo T, Sekine K, Tanaka S, Niikura R, Mezaki K, Morino E, Yazaki H, Igari T, Ohmagari N, Akiyama J, Oka S, Uemura N. Combined endoscopy, aspiration, and biopsy analysis for identifying infectious colitis in patients with ileocecal ulcers. Clin Gastroenterol Hepatol 2013; 11:673-80.e2. [PMID: 23357489 DOI: 10.1016/j.cgh.2012.12.034] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2012] [Revised: 12/07/2012] [Accepted: 12/26/2012] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The ileocecal area is commonly involved in infection and inflammatory colonic diseases, but differential diagnosis can be difficult. We identified definitive endoscopic findings and a sample collection method for diagnosing infectious colitis. METHODS In a retrospective study, we analyzed data on 128 patients with ileocecal ulcer who underwent colonoscopy from 2007-2011 at the National Center for Global Health and Medicine in Tokyo, Japan. We collected information on location, size, number, and distinctive endoscopic findings and estimated diagnostic odds ratios (ORs). The sensitivities of microscopy, culture, polymerase chain reaction, and histologic methods in identifying patients with infection were compared with those of standard stool, endoscopic aspirated intestinal fluid, or biopsy analyses. RESULTS Of the 128 patients, 100 had infections, and 28 had Crohn's disease, Behçet's disease, or other inflammatory diseases. Predictive endoscopic findings were as follows: for amebiasis of the cecum (OR, 17.8), with exudates (OR, 13.9) and round-shaped ulcer (OR, 5.77); for tuberculosis (TB) with transverse-shaped ulcer (OR, 175), scar (OR, 34.6), linear-shaped ulcer (OR, 23.9), or ≥10 mm (OR, 14.0); for cytomegalovirus with round-shaped ulcer (OR, 4.09); and for Campylobacter with cecal valve lesion (OR, 58.3) or ≥10 mm (OR, 10.4). The sensitivity of endoscopic sample collection was significantly higher than that of standard stool sample collection for the diagnosis of amebiasis, TB, non-TB mycobacteria, and other bacteria (P < .05). The methods that detected infection with the highest levels of sensitivity were biopsy with histology for amebiasis, biopsy with culture for TB, biopsy with polymerase chain reaction for cytomegalovirus, and aspiration of intestinal fluid with culture for Campylobacter. CONCLUSIONS Combining results from endoscopic analysis with appropriate sample collection and pathogen detection methods enables infectious colitis to be differentiated from other noninfectious colonic diseases.
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Affiliation(s)
- Naoyoshi Nagata
- Department of Gastroenterology and Hepatology, International Clinical Research Center Research Institute, Tokyo, Japan.
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Becker SL, Vogt J, Knopp S, Panning M, Warhurst DC, Polman K, Marti H, von Müller L, Yansouni CP, Jacobs J, Bottieau E, Sacko M, Rijal S, Meyanti F, Miles MA, Boelaert M, Lutumba P, van Lieshout L, N'Goran EK, Chappuis F, Utzinger J. Persistent digestive disorders in the tropics: causative infectious pathogens and reference diagnostic tests. BMC Infect Dis 2013; 13:37. [PMID: 23347408 PMCID: PMC3579720 DOI: 10.1186/1471-2334-13-37] [Citation(s) in RCA: 50] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2012] [Accepted: 01/14/2013] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Persistent digestive disorders account for considerable disease burden in the tropics. Despite advances in understanding acute gastrointestinal infections, important issues concerning epidemiology, diagnosis, treatment and control of most persistent digestive symptomatologies remain to be elucidated. Helminths and intestinal protozoa are considered to play major roles, but the full extent of the aetiologic spectrum is still unclear. We provide an overview of pathogens causing digestive disorders in the tropics and evaluate available reference tests. METHODS We searched the literature to identify pathogens that might give rise to persistent diarrhoea, chronic abdominal pain and/or blood in the stool. We reviewed existing laboratory diagnostic methods for each pathogen and stratified them by (i) microscopy; (ii) culture techniques; (iii) immunological tests; and (iv) molecular methods. Pathogen-specific reference tests providing highest diagnostic accuracy are described in greater detail. RESULTS Over 30 pathogens may cause persistent digestive disorders. Bacteria, viruses and parasites are important aetiologic agents of acute and long-lasting symptomatologies. An integrated approach, consisting of stool culture, microscopy and/or specific immunological techniques for toxin, antigen and antibody detection, is required for accurate diagnosis of bacteria and parasites. Molecular techniques are essential for sensitive diagnosis of many viruses, bacteria and intestinal protozoa, and are increasingly utilised as adjuncts for helminth identification. CONCLUSIONS Diagnosis of the broad spectrum of intestinal pathogens is often cumbersome. There is a need for rapid diagnostic tests that are simple and affordable for resource-constrained settings, so that the management of patients suffering from persistent digestive disorders can be improved.
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Affiliation(s)
- Sören L Becker
- Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland
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47
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Papadimitriou G, Koukoulaki M, Vardas K, Florou E, Argyrakos T, Lakiotis G, Apostolou T, Drakopoulos S. Small bowel obstruction caused by inflammatory cytomegalovirus tumor in a renal transplant recipient: report of a rare case and review of the literature. Transpl Infect Dis 2012; 14:E111-E115. [PMID: 22931132 DOI: 10.1111/j.1399-3062.2012.00784.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2012] [Revised: 05/09/2012] [Accepted: 05/27/2012] [Indexed: 02/04/2023]
Abstract
Cytomegalovirus (CMV) infection in renal transplant recipients can present as asymptomatic viremia or CMV syndrome or, in more severe cases, as tissue-invasive disease. CMV enteritis, a common manifestation of CMV invasive disease, usually presents with fever, abdominal pain, anorexia, nausea, and diarrhea, and can be rarely complicated by colon perforation, hemorrhage, or megacolon. CMV infection occurs primarily in the first 6 months post transplantation, when immunosuppression is more intense. We describe the case of a female renal transplant recipient with small bowel obstruction caused by CMV disease 7 years post renal transplantation. The patient presented with diarrhea and abdominal pain. Because of elevated CMV viral load, she was initially treated with antiviral therapy with transient response. Endoscopy and imaging tests showed obstruction of the terminal ileum and, subsequently, the patient underwent exploratory laparotomy when a right hemicolectomy was performed. Biopsy results confirmed the diagnosis of CMV enteritis. Epidemiologic characteristics, clinical presentation, diagnostic workup, therapeutic options, and morbidity-mortality rates of CMV infection/disease, in renal transplant recipients, are reviewed.
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Affiliation(s)
- G Papadimitriou
- First Department of Surgery and Transplant Unit, Evangelismos General Hospital, Athens, Greece.
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48
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Abstract
Diarrhea is a common problem in patients with immunocompromising conditions. The etiologic spectrum differs from patients with diarrhea who have a normal immune system. This article reviews the most important causes of diarrhea in immunocompromised patients, ranging from infectious causes to noninfectious causes of diarrhea in the setting of HIV infection as a model for other conditions of immunosuppression. It also deals with diarrhea in specific situations, eg, after hematopoietic stem cell or solid organ transplantation, diarrhea induced by immunosuppressive drugs, and diarrhea in congenital immunodeficiency syndromes.
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Affiliation(s)
- Elisabeth Krones
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
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49
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Mokhtari M, Tavakkoli H, Rafiee A, Dibaj R. Assessment of relationship between active ulcerative colitis and cytomegalovirus infection among Iranian patients. Adv Biomed Res 2012; 1:19. [PMID: 23210078 PMCID: PMC3507017 DOI: 10.4103/2277-9175.98118] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2011] [Accepted: 02/18/2012] [Indexed: 12/16/2022] Open
Abstract
INTRODUCTION It has been previously reported that ulcerative colitis (UC) could be associated with cytomegalovirus (CMV) infection. There is controversy among different studies; however, this study is conducted in Isfahan. We evaluated the frequency distribution of CMV infection in Iranian patients with active UC comparison to normal individuals. MATERIALS AND METHODS This case-control study was conducted on 22 patients with active UC and 22 age- and sex-matched controls (F: M = 1). Samples were taken from colonoscopic specimens and tested with sensitive primers of the CMV using the polymerase chain reaction method, the most sensitive method for detecting CMV infection. RESULTS Patients and controls were similar in age (35.9 ± 11.03 years in the case and 40.8 ± 11.3 years in the control group) P=0.153. CMV DNA was found in 13.6% of the subjects in each group; therefore, total percentage of CMV infection was 13.6%. Six cases with CMV infection were three males and three females with age of 38.5 ± 11.02 years (compared to 38.3 ± 11.5 years in noninfected subjects P=0.968). CONCLUSION In our study, Iranian patients with active UC did not have a higher rate of CMV infection than controls.
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Affiliation(s)
- Mojgan Mokhtari
- Department of Pathology, Isfahan University of Medical Science, Isfahan, Iran
| | - Hamid Tavakkoli
- Department of Gastroenterology, Isfahan University of Medical Science, Isfahan, Iran
| | - Azita Rafiee
- Master Science of Medical Microbiology, Infectious and Tropical Diseases Research Center, Isfahan University of Medical Science, Isfahan, Iran
| | - Ramin Dibaj
- Department of Pathology, Isfahan University of Medical Science, Isfahan, Iran
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50
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Shah SK, Kreiner LA, Walker PA, Klein KL, Bajwa KS, Robinson EK, Millas SG, Souchon EA, Wray CJ. Cytomegalovirus enteritis manifesting as recurrent bowel obstruction and jejunal perforation in patient with acquired immunodeficiency syndrome: rare report of survival and review of the literature. Surg Infect (Larchmt) 2012; 13:121-4. [PMID: 22439782 DOI: 10.1089/sur.2010.098] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Cytomegalovirus (CMV) enteritis presenting with perforation in the setting of acquired immunodeficiency syndrome (AIDS) represents a particularly deadly combination. METHODS Case report and review of the pertinent literature. CASE REPORT The authors report a patient with AIDS and CMV enteritis presenting as recurrent small-bowel obstruction and leading to perforation of the jejunum with subsequent survival. CONCLUSION This is believed to represent the second case in the English-language literature of survival after CMV-induced small intestinal perforation in a patient with AIDS.
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Affiliation(s)
- Shinil K Shah
- Department of Surgery, The University of Texas Medical School at Houston, Houston, Texas, USA.
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