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Vidovszky MZ, Surján A, Földvári G, Egyed L. Detection of DNA Viruses in Free-Ranging Rat Populations in Hungary. Viruses 2024; 16:1948. [PMID: 39772254 PMCID: PMC11680385 DOI: 10.3390/v16121948] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Revised: 12/14/2024] [Accepted: 12/16/2024] [Indexed: 01/11/2025] Open
Abstract
To address a gap in our understanding of viral infections in epidemiologically important rat species, we aimed to detect DNA viruses from the tissues of free-ranging rat populations in Hungary. DNA viruses were identified from the parenchymal organs of 230 Rattus norvegicus and Rattus rattus, using family-specific pan-PCR assays followed by sequencing of the PCR products. Adeno-, herpes-, circo-, and polyomaviruses were detected, while irido-, pox-, and dependoparvoviruses were not. Adenovirus DNA was present in 6.5% of the samples, herpesvirus and polyomavirus DNA in 12.2%, and circovirus DNA in 1.7%. All detected herpesviruses belonged to the β and γ subfamilies, with a majority being β herpesviruses. Some adenovirus and herpesvirus sequences were novel, while only the known Rattus norvegicus polyomavirus 1 was detected for polyomaviruses. The rare circovirus-positive samples revealed the presence of both rodent and bird circoviruses, indicating the ability of circoviruses to cross species barriers. Our findings show that rats host a variety of DNA viruses, many of which were previously uncharacterized, highlighting the need for further diagnostic studies.
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Affiliation(s)
- Márton Z. Vidovszky
- HUN-REN Veterinary Medical Research Institute, 1143 Budapest, Hungary; (M.Z.V.); (A.S.)
| | - András Surján
- HUN-REN Veterinary Medical Research Institute, 1143 Budapest, Hungary; (M.Z.V.); (A.S.)
| | - Gábor Földvári
- Institute of Evolution, HUN-REN Centre for Ecological Research, 1121 Budapest, Hungary
- Centre for Eco-Epidemiology, National Laboratory for Health Security, 1077 Budapest, Hungary
| | - László Egyed
- HUN-REN Veterinary Medical Research Institute, 1143 Budapest, Hungary; (M.Z.V.); (A.S.)
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Wu J, He YC, Huang QS, He Y, Zhao P, Chen Q, Zhu XL, Fu HX, Kong J, Wang FR, Zhang YY, Mo XD, Yan CH, Lv M, Wang Y, Xu LP, Liu KY, Huang XJ, Zhang XH. Clinical features and prognostic model for viral encephalitis after allogeneic haematopoietic stem cell transplantation. Br J Haematol 2024; 205:1477-1488. [PMID: 39099079 DOI: 10.1111/bjh.19683] [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: 03/10/2024] [Accepted: 07/21/2024] [Indexed: 08/06/2024]
Abstract
The objective of this study was to identify independent prognostic factors of viral encephalitis (VE) after allogeneic haematopoietic stem cell transplantation (allo-HSCT) and establish a prognostic model to identify post-transplant VE patients with a greater likelihood of mortality. Among 5380 patients in our centre from 2014 to 2022, 211 patients who developed VE after allo-HSCT were reviewed in this retrospective study. Prognostic factors were selected, and a prognostic model was constructed using Cox regression analysis. The model was subsequently validated and estimated using the area under the receiver operating characteristic curve (AUC), a calibration plot and decision curve analysis (DCA). Glasgow Coma Scale score <9, lesions >3 lobes on magnetic resonance imaging and severe thrombocytopenia were identified as independent prognostic risk factors for VE patients who underwent allo-HSCT. The prognostic model GTM (GTM is an abbreviation for a model composed of three risk factors: GCS score <9, severe thrombocytopenia [platelet count <20 000 per microliter], and lesions >3 lobes on MRI) was established according to the regression coefficients. The validated internal AUC was 0.862 (95% confidence interval [CI], 0.773-0.950), and the external AUC was 0.815 (95% CI, 0.708-0.922), indicating strong discriminatory ability. Furthermore, we constructed calibration plots that demonstrated good consistency between the predicted outcomes and the observed outcomes. DCA exhibited high accuracy in this system, leading to potential benefits for patients.
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Affiliation(s)
- Jin Wu
- Peking University People's Hospital, Peking University Institute of Haematology, Beijing, China
- Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
- Collaborative Innovation Centre of Haematology, Peking University, Beijing, China
- National Clinical Research Centre for Hematologic Disease, Beijing, China
| | - Yu-Chen He
- Peking University People's Hospital, Peking University Institute of Haematology, Beijing, China
- Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
- Collaborative Innovation Centre of Haematology, Peking University, Beijing, China
- National Clinical Research Centre for Hematologic Disease, Beijing, China
| | - Qiu-Sha Huang
- Peking University People's Hospital, Peking University Institute of Haematology, Beijing, China
- Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
- Collaborative Innovation Centre of Haematology, Peking University, Beijing, China
- National Clinical Research Centre for Hematologic Disease, Beijing, China
| | - Yun He
- Peking University People's Hospital, Peking University Institute of Haematology, Beijing, China
- Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
- Collaborative Innovation Centre of Haematology, Peking University, Beijing, China
- National Clinical Research Centre for Hematologic Disease, Beijing, China
| | - Peng Zhao
- Peking University People's Hospital, Peking University Institute of Haematology, Beijing, China
- Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
- Collaborative Innovation Centre of Haematology, Peking University, Beijing, China
- National Clinical Research Centre for Hematologic Disease, Beijing, China
| | - Qi Chen
- Peking University People's Hospital, Peking University Institute of Haematology, Beijing, China
- Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
- Collaborative Innovation Centre of Haematology, Peking University, Beijing, China
- National Clinical Research Centre for Hematologic Disease, Beijing, China
| | - Xiao-Lu Zhu
- Peking University People's Hospital, Peking University Institute of Haematology, Beijing, China
- Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
- Collaborative Innovation Centre of Haematology, Peking University, Beijing, China
- National Clinical Research Centre for Hematologic Disease, Beijing, China
| | - Hai-Xia Fu
- Peking University People's Hospital, Peking University Institute of Haematology, Beijing, China
- Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
- Collaborative Innovation Centre of Haematology, Peking University, Beijing, China
- National Clinical Research Centre for Hematologic Disease, Beijing, China
| | - Jun Kong
- Peking University People's Hospital, Peking University Institute of Haematology, Beijing, China
- Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
- Collaborative Innovation Centre of Haematology, Peking University, Beijing, China
- National Clinical Research Centre for Hematologic Disease, Beijing, China
| | - Feng-Rong Wang
- Peking University People's Hospital, Peking University Institute of Haematology, Beijing, China
- Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
- Collaborative Innovation Centre of Haematology, Peking University, Beijing, China
- National Clinical Research Centre for Hematologic Disease, Beijing, China
| | - Yuan-Yuan Zhang
- Peking University People's Hospital, Peking University Institute of Haematology, Beijing, China
- Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
- Collaborative Innovation Centre of Haematology, Peking University, Beijing, China
- National Clinical Research Centre for Hematologic Disease, Beijing, China
| | - Xiao-Dong Mo
- Peking University People's Hospital, Peking University Institute of Haematology, Beijing, China
- Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
- Collaborative Innovation Centre of Haematology, Peking University, Beijing, China
- National Clinical Research Centre for Hematologic Disease, Beijing, China
| | - Chen-Hua Yan
- Peking University People's Hospital, Peking University Institute of Haematology, Beijing, China
- Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
- Collaborative Innovation Centre of Haematology, Peking University, Beijing, China
- National Clinical Research Centre for Hematologic Disease, Beijing, China
| | - Meng Lv
- Peking University People's Hospital, Peking University Institute of Haematology, Beijing, China
- Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
- Collaborative Innovation Centre of Haematology, Peking University, Beijing, China
- National Clinical Research Centre for Hematologic Disease, Beijing, China
| | - Yu Wang
- Peking University People's Hospital, Peking University Institute of Haematology, Beijing, China
- Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
- Collaborative Innovation Centre of Haematology, Peking University, Beijing, China
- National Clinical Research Centre for Hematologic Disease, Beijing, China
| | - Lan-Ping Xu
- Peking University People's Hospital, Peking University Institute of Haematology, Beijing, China
- Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
- Collaborative Innovation Centre of Haematology, Peking University, Beijing, China
- National Clinical Research Centre for Hematologic Disease, Beijing, China
| | - Kai-Yan Liu
- Peking University People's Hospital, Peking University Institute of Haematology, Beijing, China
- Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
- Collaborative Innovation Centre of Haematology, Peking University, Beijing, China
- National Clinical Research Centre for Hematologic Disease, Beijing, China
| | - Xiao-Jun Huang
- Peking University People's Hospital, Peking University Institute of Haematology, Beijing, China
- Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
- Collaborative Innovation Centre of Haematology, Peking University, Beijing, China
- National Clinical Research Centre for Hematologic Disease, Beijing, China
| | - Xiao-Hui Zhang
- Peking University People's Hospital, Peking University Institute of Haematology, Beijing, China
- Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
- Collaborative Innovation Centre of Haematology, Peking University, Beijing, China
- National Clinical Research Centre for Hematologic Disease, Beijing, China
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Sattayalertyanyong O, Limsrivilai J, Phaophu P, Subdee N, Horthongkham N, Pongpaibul A, Angkathunyakul N, Chayakulkeeree M, Pausawasdi N, Charatcharoenwitthaya P. Performance of Cytomegalovirus Real-Time Polymerase Chain Reaction Assays of Fecal and Plasma Specimens for Diagnosing Cytomegalovirus Colitis. Clin Transl Gastroenterol 2023; 14:e00574. [PMID: 36854054 PMCID: PMC10208703 DOI: 10.14309/ctg.0000000000000574] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Accepted: 02/09/2023] [Indexed: 03/02/2023] Open
Abstract
INTRODUCTION Cytomegalovirus (CMV) viral load detected by real-time polymerase chain reaction (PCR) in plasma or stool may facilitate detection of CMV colitis. METHODS This prospective study enrolled 117 patients with clinically suspected CMV colitis. Patients presenting with gastrointestinal symptoms and having increased risk of CMV infection were eligible. All participants underwent colonoscopy with tissue biopsy. Five patients underwent colonoscopy twice because of clinical recurrence, resulting in a total of 122 colonoscopies. Stool CMV-PCR and plasma CMV-PCR were performed within 7 days before/after colonoscopy. Twenty asymptomatic volunteers also underwent the same protocol. RESULTS Twenty-seven (23.1%) of 122 colonoscopies yielded positive for CMV colitis. The sensitivity and specificity was 70.4% and 91.6% for stool CMV-PCR and 66.7% and 94.7% for plasma CMV-PCR, respectively. The sensitivity of either positive plasma or positive stool CMV-PCR was 81.5%, which is significantly higher than that of plasma CMV-PCR alone ( P = 0.045). However, positive results from both tests yielded a specificity of 95.8%, which is significantly higher than that of stool CMV-PCR alone ( P = 0.045). There was a good and significant correlation between stool CMV-PCR and plasma CMV-PCR ( r = 0.71, P < 0.01), and both tests significantly correlated with the cytomegalic cell count ( r = 0.62, P < 0.01 for stool and r = 0.64, P < 0.01 for plasma). There were no positive stool or plasma CMV-PCR assays among volunteers. DISCUSSION The results of this study strongly suggest that the combination of stool CMV-PCR and plasma CMV-PCR can be used to confidently rule in (both positive) or rule out (both negative) a diagnosis of CMV colitis.
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Affiliation(s)
- Onuma Sattayalertyanyong
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand;
- Siriraj GI Endoscopy Center, 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;
| | - Phutthaphorn Phaophu
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand;
| | - Nichcha Subdee
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand;
| | - Navin Horthongkham
- Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand;
| | - Ananya Pongpaibul
- Department of Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand;
| | - Napat Angkathunyakul
- Department of Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand;
| | - Methee Chayakulkeeree
- Division of Infectious Diseases and Tropical Medicine, Department of Medicine, 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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Sun YQ, Ma R, Huang XJ. Optimizing the treatment of cytomegalovirus infection in allo-HSCT recipients. Expert Rev Clin Immunol 2023; 19:227-235. [PMID: 36541485 DOI: 10.1080/1744666x.2023.2161510] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
INTRODUCTION Cytomegalovirus (CMV) infection continues to negatively impact the prognosis after allogeneic hematopoietic stem cell transplantation (allo-HSCT), even with active monitoring and preemptive strategies. Recent progress in pharmacology, immunotherapy, and vaccines has improved the strategy of CMV management. AREAS COVERED We summarized recent advances in managing CMV infection post allo-HSCT, including diagnosis, prophylaxis, and treatment. In this review, we mainly focused on approaches that have optimized or might optimize the management of CMV infection after allo-HSCT. EXPERT OPINION In our opinion, optimized management covers aspects including the serial monitoring of CMV-DNA and CMI, an accurate diagnosis, effective prophylaxis, and a rational preemptive therapy integrating antiviral drugs and cell therapies. Strategies based on the understanding of CMV pathogenesis and CMV-related immune reconstitution after allo-HSCT will be a direction in future studies.
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Affiliation(s)
- Yu-Qian Sun
- Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
| | - Rui Ma
- Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
| | - Xiao-Jun Huang
- Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
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Gu J, Ji H, Liu T, Chen C, Zhao S, Cao Y, Wang N, Xiao M, Chen L, Cai H. Detection of cytomegalovirus (CMV) by digital PCR in stool samples for the non-invasive diagnosis of CMV gastroenteritis. Virol J 2022; 19:183. [DOI: 10.1186/s12985-022-01913-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2022] [Accepted: 11/01/2022] [Indexed: 11/13/2022] Open
Abstract
Abstract
Background
CMV gastroenteritis is common in patients receiving allogeneic hematopoietic stem cell transplantation and it is difficult to distinguish from acute graft-versus-host disease (aGvHD), which has very similar symptoms but needs quite different treatment. CMV gastroenteritis is caused by local infection or reactivation of CMV in the gastrointestinal tract while aGvHD is due to immune rejection. The gold standard of diagnosis of CMV gastroenteritis and aGvHD is gastrointestinal biopsy under endoscopy, which is invasive and can potentially lead to severe side effects. Stool samples testing with quantitative polymerase chain reaction (qPCR) may be an alternative, while the application in trace level measurements and precision are not all satisfactory enough in reported research.
Methods
In this study, we designed a novel method that extracted the cell free DNA (cfDNA) from the fecal supernatant to perform digital PCR (dPCR) for the detection of CMV, analyzed the performance and compared it with the total DNA extracted by the current procedure.
Results
Twenty-two paired stool samples using two DNA extraction methods proved that the cfDNA extraction method had markedly higher DNA concentrations and control gene copy number, suggesting that cfDNA may be more informative and more useful for the detection of CMV DNA segment. The dPCR approach in detecting CMV DNA segment also exhibit good linearity (R2 = 0.997) and higher sensitivity (limit of detection at 50% was 3.534 copies/μL). Eighty-two stool samples from 44 immunocompromised patients were analyzed, CMV-positive rate was 28%, indicating that more than one-quarter of the gastrointestinal symptoms within these patients may be caused by CMV infection or reactivation.
Conclusion
The combined results suggest that detection of CMV by dPCR in cfDNA of stool supernatant is a powerful method to identify CMV gastroenteritis and helps in clinical treatment decision making.
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6
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[The Chinese consensus on the management of cytomegalovirus infection in allogeneic hematopoietic stem cell transplantation patients (2022)]. ZHONGHUA XUE YE XUE ZA ZHI = ZHONGHUA XUEYEXUE ZAZHI 2022; 43:617-623. [PMID: 36709144 PMCID: PMC9593016 DOI: 10.3760/cma.j.issn.0253-2727.2022.08.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Indexed: 01/30/2023]
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Utility of novel T-cell-specific extracellular vesicles in monitoring and evaluation of acute GVHD. Int J Hematol 2021; 113:910-920. [DOI: 10.1007/s12185-021-03113-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2020] [Revised: 02/17/2021] [Accepted: 02/18/2021] [Indexed: 01/08/2023]
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Bueno F, Albert E, Giménez E, Piñana JL, Pérez A, Gómez MD, Hernández‐Boluda JC, Gonzalez‐Barberá EM, Montoro J, Guerreiro M, Balaguer‐Roselló A, Hernani R, Sanz J, Solano C, Navarro D. Cytomegalovirus DNA load monitoring in stool specimens for anticipating the occurrence of intestinal acute graft‐versus‐host disease following allogeneic hematopoietic stem cell transplantation: Is it of any value? Transpl Infect Dis 2020; 22:e13440. [DOI: 10.1111/tid.13440] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Revised: 07/15/2020] [Accepted: 08/02/2020] [Indexed: 12/11/2022]
Affiliation(s)
- Felipe Bueno
- Microbiology Service Hospital Clínico UniversitarioInstitute for Research INCLIVA Valencia Spain
| | - Eliseo Albert
- Microbiology Service Hospital Clínico UniversitarioInstitute for Research INCLIVA Valencia Spain
| | - Estela Giménez
- Microbiology Service Hospital Clínico UniversitarioInstitute for Research INCLIVA Valencia Spain
| | - José Luis Piñana
- Hematology Department Hospital Universitari i Politècnic La Fe Valencia Spain
| | - Ariadna Pérez
- Hematology Service Hospital Clínico UniversitarioInstitute for Research INCLIVA Valencia Spain
| | - María Dolores Gómez
- Microbiology Service Hospital Universitari i Politècnic La Fe Valencia Spain
| | - Juan Carlos Hernández‐Boluda
- Hematology Service Hospital Clínico UniversitarioInstitute for Research INCLIVA Valencia Spain
- Department of Medicine School of Medicine University of Valencia Valencia Spain
| | | | - Juan Montoro
- Hematology Department Hospital Universitari i Politècnic La Fe Valencia Spain
| | - Manuel Guerreiro
- Hematology Department Hospital Universitari i Politècnic La Fe Valencia Spain
| | | | - Rafael Hernani
- Hematology Service Hospital Clínico UniversitarioInstitute for Research INCLIVA Valencia Spain
| | - Jaime Sanz
- Hematology Department Hospital Universitari i Politècnic La Fe Valencia Spain
| | - Carlos Solano
- Hematology Service Hospital Clínico UniversitarioInstitute for Research INCLIVA Valencia Spain
- Department of Medicine School of Medicine University of Valencia Valencia Spain
| | - David Navarro
- Microbiology Service Hospital Clínico UniversitarioInstitute for Research INCLIVA Valencia Spain
- Department of Microbiology School of Medicine University of Valencia Valencia Spain
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Cytomegalovirus and Inflammatory Bowel Diseases (IBD) with a Special Focus on the Link with Ulcerative Colitis (UC). Microorganisms 2020; 8:microorganisms8071078. [PMID: 32698383 PMCID: PMC7409252 DOI: 10.3390/microorganisms8071078] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Revised: 07/10/2020] [Accepted: 07/12/2020] [Indexed: 12/16/2022] Open
Abstract
Cytomegalovirus (CMV) infects approximately 40% of adults in France and persists lifelong as a latent agent in different organs, including gut. A close relationship is observed between inflammation that favors viral expression and viral replication that exacerbates inflammation. In this context, CMV colitis may impact the prognosis of patients suffering from inflammatory bowel diseases (IBDs), and notably those with ulcerative colitis (UC). In UC, the mucosal inflammation and T helper cell (TH) 2 cytokines, together with immunomodulatory drugs used for controlling flare-ups, favor viral reactivation within the gut, which, in turn, increases mucosal inflammation, impairs corticoid and immunosuppressor efficacy (the probability of steroid resistance is multiplied by more than 20 in the case of CMV colitis), and enhances the risk for colectomy. This review emphasizes the virological tools that are recommended for exploring CMV colitis during inflammatory bowel diseases (IBD) and underlines the interest of using ganciclovir for treating flare-ups associated to CMV colitis in UC patients.
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10
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Magdziak A, Szlak J, Mróz A, Wieszczy P, Zagórowicz E. A stool test in patients with active ulcerative colitis helps exclude cytomegalovirus disease. Scand J Gastroenterol 2020; 55:664-670. [PMID: 32552149 DOI: 10.1080/00365521.2020.1771760] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Objectives: In severe ulcerative colitis (UC) bowel biopsy is recommended to detect the cytomegalovirus (CMV) infection capable of complicating the course of the disease. Histopathology with immunohistochemistry (IHC) is time-consuming, and a blood polymerase chain reaction (PCR) for CMV DNA is used as an alternative, notwithstanding nothing more than a moderate correlation between the two. We aimed to detect CMV DNA in the stools of patients with active UC, and to compare the results with CMV IHC in bowel biopsies.Materials and methods: Measurement of CMV DNA in stools (copies/ml) entailed PCR, while biopsies assessed inflammation activity (Geboes scale), as well as counts of numbers of CMV IHC-positive cells/biopsy. The severity of UC was assessed using the Mayo score, stool calprotectin and concentrations of C-reactive protein in the blood.Results: 89 of the above pairs of tests for CMV were performed among 75 patients. CMV was detected in 36/89 stool specimens and 19/89 bowel biopsies. The sensitivity of the stool-CMV PCR was thus 84.7%, while specificity was of 71.4%. The negative predictive value was 94.3% and the positive predictive value 44.4%. No difference in the severity of UC was noted between the stool CMV DNA positive and negative groups. Similarly, there was no difference in the severity of UC between the CMV IHC positive and negative groups, except for the Geboes score, more often found to be higher in CMV IHC-positive patients (p = .002).Conclusions: CMV DNA was detected in the stools of 40.4% of patients with active UC. A negative test result may help to exclude bowel CMV disease.
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Affiliation(s)
- Agnieszka Magdziak
- The Maria Sklodowska-Curie National Research Institute of Oncology, Department of Microbiology, Warsaw, Poland
| | - Jakub Szlak
- The Maria Sklodowska-Curie National Research Institute of Oncology, Department of Gastroenterology, Warsaw, Poland
| | - Andrzej Mróz
- The Center of Postgraduate Medical Education, Department of Pathomorphology, Warsaw, Poland.,The Maria Sklodowska-Curie National Research Institute of Oncology, Department of Pathology and Laboratory Medicine, Warsaw, Poland
| | - Paulina Wieszczy
- The Maria Sklodowska-Curie National Research Institute of Oncology, Department of Cancer Prevention, Warsaw, Poland.,Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
| | - Edyta Zagórowicz
- The Maria Sklodowska-Curie National Research Institute of Oncology, Department of Gastroenterology, Warsaw, Poland.,The Center of Postgraduate Medical Education, Department of Gastroenterology and Hepatology and Clinical Oncology, Warsaw, Poland
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11
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Schmidt-Hieber M, Bierwirth J, Buchheidt D, Cornely OA, Hentrich M, Maschmeyer G, Schalk E, Vehreschild JJ, Vehreschild MJGT. Diagnosis and management of gastrointestinal complications in adult cancer patients: 2017 updated evidence-based guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO). Ann Hematol 2018; 97:31-49. [PMID: 29177551 PMCID: PMC5748412 DOI: 10.1007/s00277-017-3183-7] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2017] [Accepted: 11/11/2017] [Indexed: 12/15/2022]
Abstract
Cancer patients frequently suffer from gastrointestinal complications. In this manuscript, we update our 2013 guideline on the diagnosis and management of gastrointestinal complications in adult cancer patients by the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO). An expert group was put together by the AGIHO to update the existing guideline. For each sub-topic, a literature search was performed in PubMed, Medline, and Cochrane databases, and strengths of recommendation and the quality of the published evidence for major therapeutic strategies were categorized using the 2015 European Society for Clinical Microbiology and Infectious Diseases (ESCMID) criteria. Final recommendations were approved by the AGIHO plenary conference. Recommendations were made with respect to non-infectious and infectious gastrointestinal complications. Strengths of recommendation and levels of evidence are presented. A multidisciplinary approach to the diagnosis and management of gastrointestinal complications in cancer patients is mandatory. Evidence-based recommendations are provided in this updated guideline.
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Affiliation(s)
- M Schmidt-Hieber
- Clinic for Hematology, Oncology, Tumor Immunology and Palliative Care, HELIOS Klinikum Berlin-Buch, Berlin, Germany
| | - J Bierwirth
- Deutsches Beratungszentrum für Hygiene, BZH GmbH, Freiburg, Germany
| | - D Buchheidt
- 3rd Department of Internal Medicine - Hematology and Oncology - Mannheim University Hospital, University of Heidelberg, Heidelberg, Germany
| | - O A Cornely
- 1st Department of Internal Medicine, University of Cologne, Cologne, Germany
- German Center for Infection Research (DZIF), partner site Bonn-Cologne, Cologne, Germany
- Clinical Trials Centre Cologne, ZKS Köln, University of Cologne, Cologne, Germany
| | - M Hentrich
- Department III for Internal Medicine, Hematology and Oncology, Rotkreuzklinikum München, Munich, Germany
| | - G Maschmeyer
- Department of Hematology, Oncology and Palliative Care, Ernst-von-Bergmann Klinikum, Potsdam, Germany
| | - E Schalk
- Department of Hematology and Oncology, Medical Center, Otto-von-Guericke University, Magdeburg, Germany
| | - J J Vehreschild
- 1st Department of Internal Medicine, University of Cologne, Cologne, Germany
- German Center for Infection Research (DZIF), partner site Bonn-Cologne, Cologne, Germany
| | - Maria J G T Vehreschild
- 1st Department of Internal Medicine, University of Cologne, Cologne, Germany.
- German Center for Infection Research (DZIF), partner site Bonn-Cologne, Cologne, Germany.
- 1st Department of Internal Medicine, Hospital of the University of Cologne, Kerpener Str. 62, 50937, Köln, Germany.
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Yoshikawa T. Betaherpesvirus Complications and Management During Hematopoietic Stem Cell Transplantation. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2018; 1045:251-270. [PMID: 29896671 DOI: 10.1007/978-981-10-7230-7_12] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Two of the four betaherpesviruses, Cytomegalovirus (CMV) and human herpesvirus 6B (HHV-6B), play an important role in opportunistic infections in hematopoietic stem cell transplant (HSCT) recipients. These viruses are ubiquitous in humans and can latently infect mononuclear lymphocytes, complicating the diagnosis of the diseases they cause. Although the detection of viral DNA in a patient's peripheral blood by real-time PCR is widely used for monitoring viral infection, it is insufficient for the diagnosis of virus-associated disease. Theoretically, end-organ disease should be confirmed by detecting either viral antigen or significant amounts of viral DNA in a tissue sample obtained from the involved organ; however, this is often difficult to perform in clinical practice. The frequency of CMV-associated diseases has decreased gradually as a result of the introduction of preemptive or prophylactic treatments; however, CMV and HHV-6B infections remain a major problem in HSCT recipients. Measurement of viral DNA load in peripheral blood or plasma using real-time PCR is commonly used for monitoring these infections. Additionally, recent data suggest that an assessment of host immune response, particularly cytotoxic T-cell response, may be a reliable tool for predicting these viral infections. The antiviral drugs ganciclovir and foscarnet are used as first-line treatments; however, it is well known that these drugs have side effects, such as bone marrow suppression and nephrotoxicity. Further research is required to develop less-toxic antiviral drugs.
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Affiliation(s)
- Tetsushi Yoshikawa
- Department of Pediatrics, Fujita Health University School of Medicine, Toyoake, Japan.
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13
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Short article: Stool cytomegalovirus polymerase chain reaction for the diagnosis of cytomegalovirus-related gastrointestinal disease. Eur J Gastroenterol Hepatol 2017; 29:1059-1063. [PMID: 28509677 DOI: 10.1097/meg.0000000000000906] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVES The diagnosis of cytomegalovirus-related gastrointestinal disease (CMV-GI disease) still requires histopathology, but biopsy is considered invasive. Stool CMV PCR has been reported in adults as an alternative method to diagnose this condition; hence, the results between studies are discrepant. Moreover, no pediatric studies on stool CMV real-time PCR in CMV-GI disease have been carried out. Here, we evaluate the value of stool CMV real-time PCR in detecting CMV-GI disease among immunocompromised children. METHODS We enrolled immunocompromised patients aged younger than 20 years who presented with gastrointestinal symptoms at a teaching hospital during January 2015-March 2016. Stool samples were analyzed for CMV real-time PCR. All patients underwent esophagogastroduodenoscopy and colonoscopy with mucosal biopsy. RESULTS We performed stool CMV real-time PCR in 31 patients, but two could not undergo endoscopy. Therefore, 29 patients were analyzed. Two additional stool samples showed inhibitors that interfere with the PCR testing and were precluded from the final analysis. Among 27 patients, we found CMV-GI disease in seven (26%) patients. The sensitivity, specificity, and accuracy of stool CMV real-time PCR were 71, 85, and 82%, respectively. We also found that all patients with CMV-GI disease had positive plasma CMV real-time PCR (>150 copies/ml). A significant association between stool and plasma CMV real-time PCR was also noted (P<0.001). CONCLUSION Stool CMV real-time PCR may be used as a noninvasive tool in the diagnosis of CMV-GI disease. Plasma CMV real-time PCR shows a significant correlation with stool CMV real-time PCR and also represents high diagnostic values.
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Zhang XH, Zhang JM, Han W, Chen H, Chen YH, Wang FR, Wang JZ, Zhang YY, Mo XD, Chen Y, Wang Y, Chang YJ, Xu LP, Liu KY, Huang XJ. Viral encephalitis after haplo-identical hematopoietic stem cell transplantation: Causative viral spectrum, characteristics, and risk factors. Eur J Haematol 2017; 98:450-458. [PMID: 28129450 DOI: 10.1111/ejh.12855] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/22/2017] [Indexed: 12/25/2022]
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15
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Beswick L, Ye B, van Langenberg DR. Toward an Algorithm for the Diagnosis and Management of CMV in Patients with Colitis. Inflamm Bowel Dis 2016; 22:2966-2976. [PMID: 27763950 DOI: 10.1097/mib.0000000000000958] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
INTRODUCTION Concurrent cytomegalovirus (CMV) in inflammatory bowel disease-related colitis is an important yet complex clinical scenario associated with high rates of colectomy and other morbidity. This review aimed to examine the literature to produce a comprehensive diagnostic and treatment algorithm for the management of CMV in patients with colitis. METHODS A systematic literature review was conducted via PubMed/Medline databases until August 31, 2015, using multiple keywords in English language and where original data only presented. RESULTS This review discusses the concept of CMV reactivation which frequently occurs in inflammatory bowel disease-related colitis, most commonly in those presenting with steroid-refractory colitis. In this context, although signifying a poorer prognosis, in most cases, the virus is nonpathogenic and thus antiviral treatment is unhelpful. However, when reactivation gives rise to true CMV disease (colitis) as best discriminated by histology with immunohistochemistry (and the density of such) in colonic biopsy tissue, the patient does benefit from antivirals. CONCLUSION Diagnostic-based patient selection and treatment is integral to optimal outcomes in CMV, and therefore we propose an algorithm based on these concepts that now requires prospective evaluation.
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Affiliation(s)
- Lauren Beswick
- *Department of Gastroenterology, Eastern Health, Melbourne, Victoria, Australia; and †Eastern Health Clinical School, Monash University, Melbourne, Victoria, Australia
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Pillet S, Pozzetto B, Roblin X. Cytomegalovirus and ulcerative colitis: Place of antiviral therapy. World J Gastroenterol 2016; 22:2030-2045. [PMID: 26877608 PMCID: PMC4726676 DOI: 10.3748/wjg.v22.i6.2030] [Citation(s) in RCA: 65] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2015] [Revised: 11/19/2015] [Accepted: 12/21/2015] [Indexed: 02/06/2023] Open
Abstract
The link between cytomegalovirus (CMV) infection and inflammatory bowel diseases remains an important subject of debate. CMV infection is frequent in ulcerative colitis (UC) and has been shown to be potentially harmful. CMV reactivation needs to be diagnosed using methods that include in situ detection of viral markers by immunohistochemistry or by nucleic acid amplification techniques. Determination of the density of infection using quantitative tools (numbers of infected cells or copies of the genome) is particularly important. Although CMV reactivation can be considered as an innocent bystander in active flare-ups of refractory UC, an increasing number of studies suggest a deleterious role of CMV in this situation. The presence of colonic CMV infection is possibly linked to a decreased response to steroids and other immunosuppressive agents. Some treatments, notably steroids and cyclosporine A, have been shown to favor CMV reactivation, which seems not to be the case for therapies using anti-tumor necrosis factor drugs. According to these findings, in flare-ups of refractory UC, it is now recommended to look for the presence of CMV reactivation by using quantitative tools in colonic biopsies and to treat them with ganciclovir in cases of high viral load or severe disease.
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