{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T01:00:05Z","timestamp":1787792405565,"version":"build-2784847793"},"reference-count":49,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,4,23]],"date-time":"2021-04-23T00:00:00Z","timestamp":1619136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoF"],"abstract":"<jats:p>Background: Cytomegalovirus (CMV) and invasive aspergillosis (IA) cause high morbidity and mortality in solid organ transplant (SOT) recipients. There are conflicting data with respect to the impact of CMV on IA development in SOT recipients. Methods: A literature search was conducted from existence through to 2 April 2021 using MEDLINE, Embase, and ISI Web of Science databases. This review contained observational studies including cross-sectional, prospective cohort, retrospective cohort, and case-control studies that reported SOT recipients with post-transplant CMV (exposure) and without post-transplant CMV (non-exposure) who developed or did not develop subsequent IA. A random-effects model was used to calculate the pooled effect estimate. Results: A total of 16 studies were included for systematic review and meta-analysis. There were 5437 SOT patients included in the study, with 449 SOT recipients developing post-transplant IA. Post-transplant CMV significantly increased the risk of subsequent IA with pORs of 3.31 (2.34, 4.69), I2 = 30%. Subgroup analyses showed that CMV increased the risk of IA development regardless of the study period (before and after 2003), types of organ transplantation (intra-thoracic and intra-abdominal transplantation), and timing after transplant (early vs. late IA development). Further analyses by CMV definitions showed CMV disease\/syndrome increased the risk of IA development, but asymptomatic CMV viremia\/infection did not increase the risk of IA. Conclusions: Post-transplant CMV, particularly CMV disease\/syndrome, significantly increased the risks of IA, which highlights the importance of CMV prevention strategies in SOT recipients. Further studies are needed to understand the impact of programmatic fungal surveillance or antifungal prophylaxis to prevent this fungal-after-viral phenomenon.<\/jats:p>","DOI":"10.3390\/jof7050327","type":"journal-article","created":{"date-parts":[[2021,4,23]],"date-time":"2021-04-23T12:08:30Z","timestamp":1619179710000},"page":"327","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Does Post-Transplant Cytomegalovirus Increase the Risk of Invasive Aspergillosis in Solid Organ Transplant Recipients? A Systematic Review and Meta-Analysis"],"prefix":"10.3390","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9474-637X","authenticated-orcid":false,"given":"Nipat","family":"Chuleerarux","sequence":"first","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7279-1062","authenticated-orcid":false,"given":"Achitpol","family":"Thongkam","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kasama","family":"Manothummetha","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saman","family":"Nematollahi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Dioverti-Prono","sequence":"additional","affiliation":[{"name":"Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9507-6339","authenticated-orcid":false,"given":"Pattama","family":"Torvorapanit","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nattapong","family":"Langsiri","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Navaporn","family":"Worasilchai","sequence":"additional","affiliation":[{"name":"Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1622-1209","authenticated-orcid":false,"given":"Rongpong","family":"Plongla","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariya","family":"Chindamporn","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anawin","family":"Sanguankeo","sequence":"additional","affiliation":[{"name":"Department of Preventive and Social Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0749-7342","authenticated-orcid":false,"given":"Nitipong","family":"Permpalung","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/S1473-3099(04)01202-2","article-title":"Human cytomegalovirus: Clinical aspects, immune regulation, and emerging treatments","volume":"4","author":"Gandhi","year":"2004","journal-title":"Lancet Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1016\/S0140-6736(97)05535-9","article-title":"The Oral Ganciclovir International Transplantation Study Group. Randomised trial of efficacy and safety of oral ganciclovir in the prevention of cytomegalovirus disease in liver-transplant recipients","volume":"350","author":"Gane","year":"1997","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.1056\/NEJM199905133401903","article-title":"International Valacyclovir Cytomegalovirus Prophylaxis Transplantation Study Group. Valacyclovir for the prevention of cytomegalovirus disease after renal transplantation","volume":"340","author":"Lowance","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1111\/tid.12447","article-title":"It\u2019s not too late: A proposal to standardize the terminology of \u201clate-onset\u201d cytomegalovirus infection and disease in solid organ transplant recipients","volume":"17","author":"Razonable","year":"2015","journal-title":"Transpl. Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e13512","DOI":"10.1111\/ctr.13512","article-title":"Cytomegalovirus in solid organ transplant recipients-Guidelines of the American Society of Transplantation Infectious Diseases Community of Practice","volume":"33","author":"Razonable","year":"2019","journal-title":"Clin. Transplant."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.jcv.2006.01.015","article-title":"The impact of cytomegalovirus disease and asymptomatic infection on acute renal allograft rejection","volume":"36","author":"Reischig","year":"2006","journal-title":"J. Clin. Virol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2453","DOI":"10.1111\/j.1600-6143.2009.02824.x","article-title":"The \u2018indirect\u2019 effects of cytomegalovirus infection","volume":"9","author":"Freeman","year":"2009","journal-title":"Am. J. Transplant."},{"key":"ref_8","first-page":"727","article-title":"Alteration of direct and indirect effects of cytomegalovirus","volume":"5","author":"Kamar","year":"2007","journal-title":"Exp. Clin. Transplant."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"111","DOI":"10.2217\/fvl.09.64","article-title":"Clinical virology of cytomegalovirus infection following hematopoietic transplantation","volume":"5","author":"Solano","year":"2009","journal-title":"Future Virol."},{"key":"ref_10","first-page":"2761","article-title":"Infectious complications after small bowel transplantation in adults: An update","volume":"28","author":"Kusne","year":"1996","journal-title":"Transplant. Proc."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1053\/jlts.2002.36239","article-title":"Risk factors for invasive aspergillosis in liver transplant recipients","volume":"8","author":"Fortun","year":"2002","journal-title":"Liver Transplant."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1086\/430602","article-title":"Risk factors for invasive aspergillosis in solid-organ transplant recipients: A case-control study","volume":"41","author":"Gavalda","year":"2005","journal-title":"Clin. Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1086\/651262","article-title":"Invasive fungal infections among organ transplant recipients: Results of the Transplant-Associated Infection Surveillance Network (TRANSNET)","volume":"50","author":"Pappas","year":"2010","journal-title":"Clin. Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1111\/ajt.13186","article-title":"Emerging issues with diagnosis and management of fungal infections in solid organ transplant recipients","volume":"15","author":"Farmakiotis","year":"2015","journal-title":"Am. J. Transplant."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e13587","DOI":"10.1111\/ctr.13587","article-title":"Pneumocystis jiroveci in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice","volume":"33","author":"Fishman","year":"2019","journal-title":"Clin. Transplant."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e13339","DOI":"10.1111\/ctr.13339","article-title":"Cytomegalovirus infection and graft rejection as risk factors for pneumocystis pneumonia in solid organ transplant recipients: A systematic review and meta-analysis","volume":"32","author":"Krishnan","year":"2018","journal-title":"Clin. Transplant."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Permpalung, N., Kittipibul, V., Mekraksakit, P., Rattanawong, P., Nematollahi, S., Zhang, S.X., and Mehta Steinke, S. (2020). A Comprehensive Evaluation of Risk Factors for Pneumocystis Jirovecii Pneumonia in Adult Solid Organ Transplant Recipients: A Systematic Review and Meta-Analysis. Transplantation.","DOI":"10.1097\/TP.0000000000003576"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"g7647","DOI":"10.1136\/bmj.g7647","article-title":"Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: Elaboration and explanation","volume":"349","author":"Shamseer","year":"2015","journal-title":"BMJ Br. Med. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1093\/cid\/ciz1008","article-title":"Revision and Update of the Consensus Definitions of Invasive Fungal Disease From the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium","volume":"71","author":"Donnelly","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_20","unstructured":"Wells, G., Shea, B., O\u2019Connell, D., Peterson, J., Welch, V., Losos, M., and Tugwell, P. (2021, March 19). The Newcastle-Ottawa Scale (NOS) for Assessing the Quality of Nonrandomised Studies in Meta-Analyses. Published 2019. Available online: http:\/\/www.ohri.ca\/programs\/clinical_epidemiology\/oxford.asp."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1093\/ije\/dyn065","article-title":"Sensitivity of between-study heterogeneity in meta-analysis: Proposed metrics and empirical evaluation","volume":"37","author":"Patsopoulos","year":"2008","journal-title":"Int. J. Epidemiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1016\/S0895-4356(01)00377-8","article-title":"Funnel plots for detecting bias in meta-analysis: Guidelines on choice of axis","volume":"54","author":"Sterne","year":"2001","journal-title":"J. Clin. Epidemiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1136\/bmj.315.7109.629","article-title":"Bias in meta-analysis detected by a simple, graphical test","volume":"315","author":"Egger","year":"1997","journal-title":"BMJ"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1136\/bmj.327.7414.557","article-title":"Measuring inconsistency in meta-analyses","volume":"327","author":"Higgins","year":"2003","journal-title":"BMJ"},{"key":"ref_25","unstructured":"The United States Food and Drug Administration (US FDA) (2020, December 16). Vfend (Voriconazole) Tablets & Injection Approval Letter. Approval Date: 24 May 2002, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2002\/21-266_VFEND_Approv.pdf."},{"key":"ref_26","unstructured":"The United States Food and Drug Administration (US FDA) (2020, December 16). Valcyte (Valganciclovir) Approval Letter. Approval Date: 9 December 2003, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2003\/021304_S001_VALCYTE.pdf."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e90","DOI":"10.1097\/TXD.0000000000000584","article-title":"Prognosis of Invasive Aspergillosis in Kidney Transplant Recipients: A Case-Control Study","volume":"2","author":"Desbois","year":"2016","journal-title":"Transplant. Direct"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1093\/jac\/dkg450","article-title":"Prevention of invasive fungal infections in liver transplant recipients: The role of prophylaxis with lipid formulations of amphotericin B in high-risk patients","volume":"52","author":"Moreno","year":"2003","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3209","DOI":"10.3760\/cma.j.issn.0366-6999.20130252","article-title":"Pneumonia relevant to lung transplantation and pathogen distribution","volume":"126","author":"He","year":"2013","journal-title":"Chin. Med. J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1093\/cid\/civ103","article-title":"Invasive aspergillosis after kidney transplant: Case-control study","volume":"60","author":"Heylen","year":"2015","journal-title":"Clin. Infect. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1086\/514599","article-title":"Cytomegalovirus infection is a risk factor for invasive aspergillosis in lung transplant recipients","volume":"26","author":"Husni","year":"1998","journal-title":"Clin. Infect. Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1111\/tid.12187","article-title":"Itraconazole prophylaxis for invasive Aspergillus infection in lung transplantation","volume":"16","author":"Kato","year":"2014","journal-title":"Transpl. Infect. Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.cmi.2017.06.016","article-title":"Multinational case-control study of risk factors for the development of late invasive pulmonary aspergillosis following kidney transplantation","volume":"24","author":"Silva","year":"2018","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2148","DOI":"10.1111\/ajt.13735","article-title":"Risk Factors Associated With Early Invasive Pulmonary Aspergillosis in Kidney Transplant Recipients: Results From a Multinational Matched Case\u2013Control Study","volume":"16","author":"Silva","year":"2016","journal-title":"Am. J. Transplant."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1016\/S1053-2498(01)00364-3","article-title":"Nebulized amphotericin B prophylaxis for Aspergillus infection in lung transplantation: Study of risk factors","volume":"20","author":"Monforte","year":"2001","journal-title":"J. Heart Lung Transplant."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1111\/j.1600-6143.2004.00390.x","article-title":"Risk factors of invasive aspergillosis after heart transplantation: Protective role of oral itraconazole prophylaxis","volume":"4","author":"Munoz","year":"2004","journal-title":"Am. J. Transplant."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.jiac.2015.11.005","article-title":"Epidemiology of invasive fungal infections after liver transplantation and the risk factors of late-onset invasive aspergillosis","volume":"22","author":"Nagao","year":"2016","journal-title":"J. Infect. Chemother."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e12898","DOI":"10.1111\/tid.12898","article-title":"Epidemiology, risk factors and outcomes of invasive aspergillosis in solid organ transplant recipients in the Swiss Transplant Cohort Study","volume":"20","author":"Neofytos","year":"2018","journal-title":"Transpl. Infect. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1002\/lt.21099","article-title":"Risk factors for invasive aspergillosis in living donor liver transplant recipients","volume":"13","author":"Osawa","year":"2007","journal-title":"Liver Transplant."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1007\/s15010-008-8124-x","article-title":"A Risk Profile for Invasive Aspergillosis in Liver Transplant Recipients","volume":"37","author":"Rosenhagen","year":"2009","journal-title":"Infection"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1086\/345441","article-title":"Trends in risk profiles for and mortality associated with invasive aspergillosis among liver transplant recipients","volume":"36","author":"Singh","year":"2003","journal-title":"Clin. Infect. Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1097\/00007890-199602270-00029","article-title":"Incidence and significance of aspergillus cultures following liver and kidney transplantation","volume":"61","author":"Brown","year":"1996","journal-title":"Transplantation"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1097\/00005792-199903000-00003","article-title":"Invasive aspergillosis in transplant recipients","volume":"78","author":"Paterson","year":"1999","journal-title":"Medicine"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1111\/tid.12328","article-title":"Risk factors for invasive mold diseases in allogeneic hematopoietic cell transplant recipients","volume":"17","author":"Atalla","year":"2015","journal-title":"Transpl. Infect. Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/S0002-9343(97)80021-6","article-title":"The independent role of cytomegalovirus as a risk factor for invasive fungal disease in orthotopic liver transplant recipients. Boston Center for Liver Transplantation CMVIG-Study Group. Cytogam, MedImmune, Inc. Gaithersburg, Maryland","volume":"103","author":"George","year":"1997","journal-title":"Am. J. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2502","DOI":"10.1182\/blood.V90.6.2502","article-title":"Neutropenia in Allogeneic Marrow Transplant Recipients Receiving Ganciclovir for Prevention of Cytomegalovirus Disease: Risk Factors and Outcome","volume":"90","author":"Salzberger","year":"1997","journal-title":"Blood"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1111\/1469-0691.12222","article-title":"Risk factors of Ganciclovir-related neutropenia after allogeneic stem cell transplantation: A retrospective monocentre study on 547 patients","volume":"20","author":"Venton","year":"2014","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1046\/j.1365-2249.2001.01465.x","article-title":"The impact of CMV on the respiratory burst of macrophages in response to Pneumocystis carinii","volume":"123","author":"Laursen","year":"2001","journal-title":"Clin. Exp. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1766","DOI":"10.1056\/NEJMoa0802629","article-title":"Toll-like receptor 4 polymorphisms and aspergillosis in stem-cell transplantation","volume":"359","author":"Bochud","year":"2008","journal-title":"N. Engl. J. Med."}],"container-title":["Journal of Fungi"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2309-608X\/7\/5\/327\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:52:07Z","timestamp":1760161927000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2309-608X\/7\/5\/327"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,23]]},"references-count":49,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["jof7050327"],"URL":"https:\/\/doi.org\/10.3390\/jof7050327","relation":{},"ISSN":["2309-608X"],"issn-type":[{"value":"2309-608X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,23]]}}}