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      A systematic literature review of the global seroprevalence of cytomegalovirus: possible implications for treatment, screening, and vaccine development

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          Abstract

          Background

          Cytomegalovirus (CMV) is a common pathogen that affects individuals of all ages and establishes lifelong latency. Although CMV is typically asymptomatic in healthy individuals, infection during pregnancy or in immunocompromised individuals can cause severe disease. Currently, treatments are limited, with no prophylactic vaccine available. Knowledge of the current epidemiologic burden of CMV is necessary to understand the need for treatment and prevention. A systematic literature review (SLR) was conducted to describe the most recent epidemiologic burden of CMV globally.

          Methods

          Medline, Embase, and LILACS were searched to identify data on CMV prevalence, seroprevalence, shedding, and transmission rates. The SLR covered the time period of 2010–2020 and focused geographically on Australia, Europe, Israel, Japan, Latin America (LATAM), and North America. Studies were excluded if they were systematic or narrative reviews, abstracts, case series, letters, or correspondence. Studies with sample sizes < 100 were excluded to focus on studies with higher quality of data.

          Results

          Twenty-nine studies were included. Among adult men, CMV immunoglobulin G (IgG) seroprevalence ranged from 39.3% (France) to 48.0% (United States). Among women of reproductive age in Europe, Japan, LATAM, and North America, CMV IgG seroprevalence was 45.6-95.7%, 60.2%, 58.3-94.5%, and 24.6-81.0%, respectively. Seroprevalence increased with age and was lower in developed than developing countries, but data were limited. No studies of CMV immunoglobulin M (IgM) seroprevalence among men were identified. Among women of reproductive age, CMV IgM seroprevalence was heterogenous across Europe (1.0-4.6%), North America (2.3-4.5%), Japan (0.8%), and LATAM (0-0.7%). CMV seroprevalence correlated with race, ethnicity, socioeconomic status, and education level. CMV shedding ranged between 0% and 70.2% depending on age group. No findings on CMV transmission rates were identified.

          Conclusions

          Certain populations and regions are at a substantially higher risk of CMV infection. The extensive epidemiologic burden of CMV calls for increased efforts in the research and development of vaccines and treatments.

          Trial registration

          N/A.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s12889-022-13971-7.

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          Most cited references78

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          Estimation of the worldwide seroprevalence of cytomegalovirus: A systematic review and meta-analysis

          Mohamed Zuhair, G Smit, Gabriel Wallis … (2019)
          Cytomegalovirus (CMV) infection does not usually produce symptoms when it causes primary infection, reinfection, or reactivation because these three types of infection are all controlled by the normal immune system. However, CMV becomes an important pathogen in individuals whose immune system is immature or compromised, such as the unborn child. Several vaccines against CMV are currently in clinical trials that aim to induce immunity in seronegative individuals and/or to boost the immunity of those with prior natural infection (seropositives). To facilitate estimation of the burden of disease and the need for vaccines that induce de novo immune responses or that boost pre-existing immunity to CMV, we conducted a systematic survey of the published literature to describe the global seroprevalence of CMV IgG antibodies. We estimated a global CMV seroprevalence of 83% (95%UI: 78-88) in the general population, 86% (95%UI: 83-89) in women of childbearing age, and 86% (95%UI: 82-89) in donors of blood or organs. For each of these three groups, the highest seroprevalence was seen in the World Health Organisation (WHO) Eastern Mediterranean region 90% (95%UI: 85-94) and the lowest in WHO European region 66% (95%UI: 56-74). These estimates of the worldwide CMV distribution will help develop national and regional burden of disease models and inform future vaccine development efforts.
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            Review of cytomegalovirus seroprevalence and demographic characteristics associated with infection.

            Michael J Cannon, D Scott Schmid, Terri B Hyde (2010)
            Cytomegalovirus establishes a lifelong latent infection following primary infection that can periodically reactivate with shedding of infectious virus. Primary infection, reactivation and reinfection during pregnancy can all lead to in utero transmission to the developing fetus. Congenital CMV infections are a major cause of permanent hearing loss and neurological impairment. In this literature review, we found that CMV infection was relatively common among women of reproductive age, with seroprevalence ranging from 45 to 100%. CMV seroprevalence tended to be highest in South America, Africa and Asia and lowest in Western Europe and United States. Within the United States, CMV seroprevalence showed substantial geographic variation as well, differing by as much as 30 percentage points between states, though differences might be explained by variation in the types of populations sampled. Worldwide, seroprevalence among non-whites tended to be 20-30 percentage points higher than that of whites (summary prevalence ratio (PR) = 1.59, 95% confidence interval (CI) = 1.57-1.61). Females generally had higher seroprevalences than males, although in most studies the differences were small (summary PR = 1.13, 95% CI = 1.11-1.14). Persons of lower socioeconomic status were more likely to be CMV seropositive (summary PR = 1.33, 95% CI = 1.32-1.35). Despite high seroprevalences in some populations, a substantial percentage of women of reproductive age are CMV seronegative and thus at risk of primary CMV infection during pregnancy. Future vaccine or educational campaigns to prevent primary infection in pregnant women may need to be tailored to suit the needs of different populations.
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              Review and meta-analysis of the epidemiology of congenital cytomegalovirus (CMV) infection.

              Aileen Kenneson, Michael J. Cannon (2015)
              We reviewed studies that reported results of systematic cytomegalovirus (CMV) screening on fetuses and/or live-born infants. The overall birth prevalence of congenital CMV infection was 0.64%, but varied considerably among different study populations. About 11% of live-born infants with congenital CMV infection were symptomatic, but the inter-study differences in definitions of symptomatic cases limit the interpretation of these data. Non-white race, low socioeconomic status (SES), premature birth, and neonatal intensive care unit admittance were risk factors for congenital CMV infection. Birth prevalence increased with maternal CMV seroprevalence. Maternal seroprevalence accounted for 29% of the variance in birth prevalence between study populations. Maternal seroprevalence and birth prevalence were both higher in study populations that were ascertained at birth rather than in the prenatal period. Thus, timing of ascertainment should be considered when interpreting birth prevalence estimates. Birth prevalence was inversely correlated with mean maternal age, but this relationship was not significant when controlling for maternal seroprevalence. The rate of transmission to infants born to mothers who had a primary infection or a recurrent infection during pregnancy was 32% and 1.4%, respectively. Possible maternal primary infections (i.e. seropositive mother with CMV IgM) resulted in congenital infections about 20% of the time, but are likely to represent a mixture of primary and recurrent infections. In summary, CMV is a common congenital infection worldwide that can lead to permanent disabilities. There is an urgent need for interventions that can reduce the substantial burden of this often overlooked disease.
              Article 0 comments Cited 216 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                John Diaz-Decaro: John.Diaz-Decaro@modernatx.com
                Journal
                Journal ID (nlm-ta): BMC Public Health
                Journal ID (iso-abbrev): BMC Public Health
                Title: BMC Public Health
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1471-2458
                Publication date (Electronic): 1 September 2022
                Publication date PMC-release: 1 September 2022
                Publication date Collection: 2022
                Volume: 22
                Electronic Location Identifier: 1659
                Affiliations
                [1 ]GRID grid.265892.2, ISNI 0000000106344187, University of Alabama at Birmingham, ; Birmingham, AL USA
                [2 ]Certara, Inc., Krakow, Poland
                [3 ]Certara, Inc., Lörrach, Germany
                [4 ]GRID grid.479574.c, ISNI 0000 0004 1791 3172, Moderna, Inc., ; 200 Technology Square, Cambridge, MA 02139 USA
                Article
                Publisher ID: 13971
                DOI: 10.1186/s12889-022-13971-7
                PMC ID: 9435408
                PubMed ID: 36050659
                SO-VID: 49867ebf-a71b-40e1-a989-8bfa7e4e12e6
                Copyright © © The Author(s) 2022
                License:

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                Date received : 28 January 2022
                Date accepted : 8 August 2022
                Funding
                Funded by: Moderna, Inc.
                Categories
                Subject: Research
                Custom metadata
                issue-copyright-statement © The Author(s) 2022

                ScienceOpen disciplines: Public health
                Keywords: cytomegalovirus,congenital cytomegalovirus,cmv,epidemiology,prevalence,seroprevalence,shedding
                Data availability:
                ScienceOpen disciplines: Public health
                Keywords: cytomegalovirus, congenital cytomegalovirus, cmv, epidemiology, prevalence, seroprevalence, shedding

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