Congenital Cytomegalovirus Infection

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Human Virology and Viral Diseases".

Deadline for manuscript submissions: closed (20 February 2023) | Viewed by 7912

Special Issue Editor

Department of Clinical Pathology, San Salvatore Hospital, 67100 L’Aquila, Italy
Interests: primary cytomegalovirus infection; pregnancy; CMV screening; hyperimmune globulin; antiviral strategies
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The relevance of congenital cytomegalovirus (CMV) infection has been well known for more than 50 years. However, this virus is still a major cause of severe and permanent disabilities in children, mostly after primary maternal infection, and is associated with severe neurological and hearing sequelae, which may be evidenced during pregnancy, at birth, or years after birth. Hygienic meaures can prevent CMV transmission, which mainly occurs following contact with children under 3 years of age when attending a nursery or daycare. In animal and human pregnancies, many studies have been conducted on the prevention of congenital CMV infection and disease using CMV-specific hyper immune globulin (HIG). A recent study has shown that high-dosage valaciclovir appears to be capable of decreasing the rates of congenital infection and disease. The implementation of CMV screening would enable primary prevention via hygiene counseling, an improvement in the understanding and awareness of congenital CMV infection, and an increase in our knowledge on the potential efficacy of preventive or therapeutic HIG or valaciclovir administration.

The aim of this Special Issue of Viruses is to compile the newest contributions on the prevention of congenital CMV infection and disease.

Prof. Dr. Giovanni Nigro
Guest Editor

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Keywords

  • primary cytomegalovirus infection
  • pregnancy
  • CMV screening
  • hyperimmune globulin
  • valaciclovir

Published Papers (5 papers)

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10 pages, 1280 KiB  
Article
Transient Decrease in Incidence Rate of Maternal Primary Cytomegalovirus Infection during the COVID-19 Pandemic in Japan
by Kuniaki Toriyabe, Asa Kitamura, Miki Hagimoto-Akasaka, Makoto Ikejiri, Shigeru Suga, Eiji Kondo, Masamichi Kihira, Fumihiro Morikawa and Tomoaki Ikeda
Viruses 2023, 15(5), 1096; https://doi.org/10.3390/v15051096 - 29 Apr 2023
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Abstract
This study evaluated the impact of the coronavirus disease 2019 (COVID-19) pandemic on the occurrence of maternal primary cytomegalovirus (CMV) infection in Japan. We performed a nested case-control study using data from maternal CMV antibody screening under the Cytomegalovirus in Mother and infant-engaged [...] Read more.
This study evaluated the impact of the coronavirus disease 2019 (COVID-19) pandemic on the occurrence of maternal primary cytomegalovirus (CMV) infection in Japan. We performed a nested case-control study using data from maternal CMV antibody screening under the Cytomegalovirus in Mother and infant-engaged Virus serology (CMieV) program in Mie, Japan. Pregnant women with negative IgG antibodies at ≤20 weeks of gestation who were retested at ≥28 weeks were enrolled. The study period was divided into 2015–2019 as the pre-pandemic and 2020–2022 as the pandemic period, and the study site included 26 institutions conducting the CMieV program. The incidence rate of maternal IgG seroconversion was compared between the pre-pandemic (7008 women enrolled) and pandemic (2020, 1283 women enrolled; 2021, 1100 women; and 2022, 398 women) periods. Sixty-one women in the pre-pandemic period and five, four, and five women during 2020, 2021, and 2022, respectively, showed IgG seroconversion. The incidence rates in 2020 and 2021 were lower (p < 0.05) than that in the pre-pandemic period. Our data suggest a transient decrease in the incidence of maternal primary CMV infection in Japan during the COVID-19 pandemic, which could be due to prevention and hygiene measures taken at the population level. Full article
(This article belongs to the Special Issue Congenital Cytomegalovirus Infection)
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11 pages, 1334 KiB  
Article
Revision of Cytomegalovirus Immunoglobulin M Antibody Titer Cutoff in a Maternal Antibody Screening Program in Japan: A Cohort Comparison Involving a Total of 32,000 Pregnant Women
by Asa Kitamura, Kuniaki Toriyabe, Miki Hagimoto-Akasaka, Kyoko Hamasaki-Shimada, Makoto Ikejiri, Toshio Minematsu, Shigeru Suga, Eiji Kondo, Masamichi Kihira, Fumihiro Morikawa and Tomoaki Ikeda
Viruses 2023, 15(4), 962; https://doi.org/10.3390/v15040962 - 13 Apr 2023
Cited by 1 | Viewed by 1609
Abstract
Cytomegalovirus (CMV) is associated with congenital infections. We aimed to validate the revised CMV immunoglobulin (Ig) M titer cutoff for IgG avidity measurements as a reflex test in maternal screening to identify women with primary CMV infection and newborn congenital cytomegalovirus (cCMV). We [...] Read more.
Cytomegalovirus (CMV) is associated with congenital infections. We aimed to validate the revised CMV immunoglobulin (Ig) M titer cutoff for IgG avidity measurements as a reflex test in maternal screening to identify women with primary CMV infection and newborn congenital cytomegalovirus (cCMV). We screened maternal CMV antibodies (the Denka assay) in Japan, from 2017 to 2019, using a revised IgM cutoff (≥4.00 index). Participants were tested for IgG and IgM antibodies, and for IgG avidity if IgM levels exceeded the cutoff. We compared these with corresponding results from 2013 to 2017 based on the original cutoff (≥1.21) and recalculated using the revised cutoff. Newborn urine CMV DNA tests were performed for women with low avidity (≤35.0%). Among 12,832 women screened in 2017–2019, 127 (1.0%) had IgM above the revised cutoff. Thirty-five exhibited low avidity, and seven infants developed cCMV. Of 19,435 women screened in 2013–2017, 184 (1.0%) had IgM above the revised cutoff, 67 had low avidity, and 1 had cCMV. The 2017–2019 results were not significantly different from the 2013–2017 results. The revised IgM cutoff improves maternal screening in identifying primary infection and newborn cCMV; however, further study related to other assays than Denka is required. Full article
(This article belongs to the Special Issue Congenital Cytomegalovirus Infection)
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15 pages, 2310 KiB  
Article
Cytokine Profiling of Amniotic Fluid from Congenital Cytomegalovirus Infection
by Nicolas Bourgon, Wendy Fitzgerald, Hugues Aschard, Jean-François Magny, Tiffany Guilleminot, Julien Stirnemann, Roberto Romero, Yves Ville, Leonid Margolis and Marianne Leruez-Ville
Viruses 2022, 14(10), 2145; https://doi.org/10.3390/v14102145 - 28 Sep 2022
Cited by 4 | Viewed by 1842
Abstract
Background: Congenital cytomegalovirus (cCMV) infection is frequent and potentially severe. The immunobiology of cCMV infection is poorly understood, involving cytokines that could be carried within or on the surface of extracellular vesicles (EV). We investigated intra-amniotic cytokines, mediated or not by EV, in [...] Read more.
Background: Congenital cytomegalovirus (cCMV) infection is frequent and potentially severe. The immunobiology of cCMV infection is poorly understood, involving cytokines that could be carried within or on the surface of extracellular vesicles (EV). We investigated intra-amniotic cytokines, mediated or not by EV, in cCMV infection. Methods: Forty infected fetuses following early maternal primary infection and forty negative controls were included. Infected fetuses were classified according to severity at birth: asymptomatic, moderately or severely symptomatic. Following the capture of EV in amniotic fluid (AF), the concentrations of 38 cytokines were quantified. The association with infection and its severity was determined using univariate and multivariate analysis. A prediction analysis based on principal component analysis was conducted. Results: cCMV infection was nominally associated with an increase in six cytokines, mainly soluble (IP-10, IL-18, ITAC, and TRAIL). EV-associated IP-10 was also increased in cases of fetal infection. Severity of fetal infection was nominally associated with an increase in twelve cytokines, including five also associated with fetal infection. A pattern of specific increase in six proteins fitted severely symptomatic infection, including IL-18soluble, TRAILsoluble, CRPsoluble, TRAILsurface, MIGinternal, and RANTESinternal. Conclusion: Fetal infection and its severity are associated with an increase in pro-inflammatory cytokines involved in Th1 immune response. Full article
(This article belongs to the Special Issue Congenital Cytomegalovirus Infection)
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16 pages, 340 KiB  
Opinion
Prevention of Congenital Cytomegalovirus Infection: Review and Case Series of Valaciclovir versus Hyperimmune Globulin Therapy
by Giovanni Nigro, Mario Muselli and on behalf of the Congenital Cytomegalic Disease Collaborating Group
Viruses 2023, 15(6), 1376; https://doi.org/10.3390/v15061376 - 15 Jun 2023
Cited by 3 | Viewed by 1397
Abstract
Cytomegalovirus (CMV) is the most common cause of congenital infections in developed countries because is capable of infecting the fetus after both primary and recurrent maternal infection, and because the virus may be spread for years through infected children. Moreover, CMV is the [...] Read more.
Cytomegalovirus (CMV) is the most common cause of congenital infections in developed countries because is capable of infecting the fetus after both primary and recurrent maternal infection, and because the virus may be spread for years through infected children. Moreover, CMV is the most serious congenital infection associated with severe neurological and sensorineural sequelae, which can occur at birth or develop later on. Hygienic measures can prevent CMV transmission, which mainly involve contact with children under 3 years of age and attending a nursery or daycare. In animal and human pregnancies, many observational and controlled studies have shown that CMV-specific hyperimmune globulin (HIG) is safe and can significantly decrease maternal–fetal transmission of CMV infection and, mostly, the occurrence of CMV disease. Recently, valaciclovir at the dosage of 8 g/day was also reported to be capable of decreasing the rates of congenital infection and disease. However, comparing the results of our two recent case series, the infants born to women treated with HIG showed significantly lower rates of CMV DNA positivity in urine (9.7% vs. 75.0%; p < 0.0001) and abnormalities after follow-up (0.0% vs. 41.7%; p < 0.0001). The implementation of CMV screening would enable primary prevention via hygiene counseling, improve the understanding and awareness of congenital CMV infection, and increase the knowledge of the potential efficacy of preventive or therapeutic HIG or antiviral administration. Full article
(This article belongs to the Special Issue Congenital Cytomegalovirus Infection)
6 pages, 3471 KiB  
Case Report
Four-Year Follow-Up of the Maternal Immunological, Virological and Clinical Settings of a 36-Year-Old Woman Experiencing Primary Cytomegalovirus Infection Leading to Intrauterine Infection
by Gabriella Forner, Alda Saldan, Carlo Mengoli, Sara Pizzi, Marny Fedrigo, Nadia Gussetti, Silvia Visentin, Annalisa Angelini, Erich Cosmi, Luisa Barzon and Davide Antonio Abate
Viruses 2023, 15(1), 112; https://doi.org/10.3390/v15010112 - 30 Dec 2022
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Abstract
The present study aims to provide the sequential immunological, clinical and virological events occurring in a CMV-infected pregnant woman experiencing intrauterine CMV transmission. In brief, a case of primary CMV infection occurred in a 36-year-old pregnant woman. The patient exhibited early-sustained viremia and [...] Read more.
The present study aims to provide the sequential immunological, clinical and virological events occurring in a CMV-infected pregnant woman experiencing intrauterine CMV transmission. In brief, a case of primary CMV infection occurred in a 36-year-old pregnant woman. The patient exhibited early-sustained viremia and viruria, detectable presence of CMV in saliva concomitant with a strong CMV-specific cell-mediated response (427 EliSpots). CMV was detected in the amniotic fluid at 15 weeks of pregnancy (>1 × 106 CMV copies/mL). The pregnancy was deliberately interrupted at 16 weeks of gestation. Fetal histological and pathological examinations revealed placentitis and fetal brain alterations as microcephaly and cortical dysplasia. Interestingly, this clinical report shows: (1) there was a rapid and sustained CMV-specific cell mediated immune response (Th1) in association with low IgG avidity (Th2) correlated with fetal CMV transmission. (2) The levels of CMV-specific cell-mediated immune response persisted at high levels up to 200 weeks after infection despite clinical and viral clearance. (3) The histological and pathological evidence suggests that a potent pro-inflammatory condition at the placental level may lead to cCMV. Full article
(This article belongs to the Special Issue Congenital Cytomegalovirus Infection)
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