Epidemiology of cytomegalovirus infection and disease in solid organ transplant recipients in selected countries outside of North America and Europe: a systematic review
Monica Slavin1, Helio Tedesco-Silva2, Inderjeet Singh3, Anudeep Sandhu4, Dirk Demuth4, Jinzhen Cai5.
1Victorian Infectious Diseases Service, Royal Melbourne Hospital, Melbourne, Australia; 2Division of Nephrology , Hospital do Rim, Universidade Federal de São Paulo, São Paulo, Brazil; 3Takeda Pharmaceuticals India Pvt Ltd, Gurgaon, India; 4Takeda International AG – Singapore Branch, Singapore, Singapore; 5Affiliated Hospital of Qingdao University, Qingdao, People's Republic of China
Background: Cytomegalovirus (CMV), a highly prevalent herpes virus worldwide, can lead to a wide range of serious direct and indirect effects in solid organ transplant (SOT) recipients. As the seroprevalence of CMV varies across countries, a systematic review was undertaken to describe the epidemiology of CMV infection and disease in SOT recipients in selected countries outside of North America and Europe.
Methods: Information sources (search period: 01 Jan. 2011 – 21 Jul. 2021) included literature search (Ovid® MEDLINE and Embase, Cochrane Database of Systematic Reviews and World Health Organization database Global Index Medicus), pragmatic searches of the grey literature, and snowballing of references lists. Observational studies that included SOT (any organ) recipients (any age) from 15 selected countries in Asia-Pacific, Latin America, Russia and the Middle East and reported on the outcomes of interest (incidence, recurrence rates and risk factors of CMV infection and CMV disease, and CMV-related mortality at any time point) were included. The protocol was registered in PROSPERO (CRD42020205559).
Results: A total of 47 studies (range: 18 to 16,368 pts), most (89.4%, n=42) conducted in adults (≥ 18 years), were retained in the review (kidney: n=33 [70.2%]; liver: n=10 [21.3%]; lung: n=1 [2.1%]; mixed SOTs: n=3 [6.4%]). Reported incidence estimates of CMV infection varied greatly, ranging from 5.2% to 79.0%, according to type of organ transplanted (Figure 1) and country (Figure 2). For CMV disease, incidence estimates within one-year post-SOT ranged from 0% to 19%, in 21 of 23 studies, regardless of prevention strategy used or distribution of CMV serostatus in donor and recipients. Two studies conducted in Brazil reported higher incidence estimates of CMV disease: 30.0% in liver recipients and 34.8% in kidney recipients with a high-risk CMV serostatus (D+/R-). Data on recurrence of CMV infection were scarce (n=4 studies) but consistent rates were reported in 3 studies conducted in adults (35.4%, 35.7%, and 41.0%). Commonly reported risk factors for CMV infection or disease in kidney transplant recipients were high-risk CMV serostatus (D+/R-) (hazard ratio [HR]: 2.7-5.4), older age of recipients (HR: 1.02-2.24), and use of immunosuppressive agents (anti-thymocyte globulin, HR 2.90 or mycophelonate sodium, OR 1.67) and antirejection therapies (OR: 4.2-5.7). No data on risk factors in other SOT recipients were found. In 11 studies covering kidney and/or liver transplant recipients, reported CMV-related mortality rates were up to 5.3% (period of assessment not reported).
Conclusion: Heterogeneity in the incidence of CMV infection across organ types and countries outside of North America and Europe was found, despite most studies reporting on adult kidney recipients. High rates of CMV infection, CMV recurrence and CMV disease are likely to impact graft and patient outcomes post-transplantation and may contribute to greater disease burden post-SOT.
This review was funded by Takeda International AG – Singapore Branch. MS has received grants from F2G, Gilead, Merck and personal fees from Gilead, Pfizer, Takeda and Roche for work outside of this research. HT institution has received research grants to conduct clinical trials from Novartis, Pfizer, BMS, Natera and Astra Zeneca. He has also received consulting honoraria from Novartis, Pfizer, Takeda, MSD and CareDx. IS is an employee of Takeda Pharmaceuticals India Pvt Ltd. AS and DD are employees of Takeda International AG – Singapore Branch and hold stock options. JC has received grants from Takeda company. Literature retrieval, analysis and medical writing support were provided by Aurore Bergamasco, Camille Goyer, and Yola Moride of Yolarx Consultants and funded by Takeda International AG – Singapore Branch.
