Prospects for Development and Potential Impact of a Vaccine Against Congenital Cytomegalovirus (CMV) Infection

A 22-year-old pregnant woman was referred to our fetal medicine unit due to severe fetal growth restriction at 26 weeks of gestation. An extensive detailed ultrasound revealed signs of bilateral periventricular hyperechogenicity, suggesting fetal infection potentially due to cytomegalovirus (CMV). Doppler ultrasound showed a high peak systolic velocity in the middle cerebral artery. Percutaneous umbilical cord blood sampling confirmed fetal CMV infection and severe fetal anaemia. We present this case to highlight the importance of fetal anaemia, which can be fatal regardless of whether it is associated with generalised oedema or hydrops fetalis.

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Clinical and ultrasound features associated with congenital cytomegalovirus infection as potential predictors for targeted newborn screening in high-risk pregnancies

Scientific Reports ◽

10.1038/s41598-020-76772-1 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Hitomi Imafuku ◽

Hideto Yamada ◽

Akiko Uchida ◽

Masashi Deguchi ◽

Tokuro Shirakawa ◽

...

Keyword(s):

Preterm Delivery ◽

Medical Center ◽

Clinical Manifestations ◽

High Sensitivity ◽

Clinical Findings ◽

Youden Index ◽

Cmv Infection ◽

Fetal Abnormality ◽

Congenital Cytomegalovirus ◽

Fetal Abnormalities

AbstractThis prospective cohort study aimed to determine clinical factors associated with congenital cytomegalovirus (CMV) infection in pregnancy. Newborns born at a perinatal medical center received PCR analyses for CMV-DNA in their urine with informed consent. Clinical data, including age, maternal fever or flu-like symptoms, complications, ultrasound fetal abnormality, gestational weeks at delivery, and birth weight, were collected. Logistic regression analyses determined clinical findings associated with congenital CMV infection (cCMV). cCMV was diagnosed in 32 of 4380 pregnancies. Univariate and multivariable analyses revealed that age < 25 years old (OR 2.7, 95% CI 1.1–6.6; p < 0.05), the presence of maternal fever or flu-like symptoms (5.4, 2.6–11.2; p < 0.01), ultrasound fetal abnormalities (12.7, 5.8–27.7; p < 0.01), and preterm delivery at less than 34 gestational weeks (2.6, 1.1–6.0; p < 0.05) were independent clinical findings associated with cCMV. A combination of maternal fever/flu-like symptoms, ultrasound fetal abnormalities, or preterm delivery at less than 34 gestational weeks as optimal predictive factors showed 90.6% sensitivity, 66.4% specificity, and a maximum Youden index of 0.57. CMV-DNA tests in the urine of newborns born to mothers with these clinical manifestations may be an effective method in detecting cCMV as a targeted screening with a high sensitivity.

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Congenital Cytomegalovirus Infection: A Cause of Renal Dysplasia?

Pediatric and Developmental Pathology ◽

10.2350/06-06-0099.1 ◽

2007 ◽

Vol 10 (4) ◽

pp. 300-304 ◽

Cited By ~ 5

Author(s):

Maren Chan ◽

Jonathan L. Hecht ◽

Theonia Boyd ◽

Seymour Rosen

Keyword(s):

Viral Infections ◽

Tissue Injury ◽

Clinical Manifestations ◽

Renal Dysplasia ◽

Cmv Infection ◽

Congenital Cytomegalovirus Infection ◽

Congenital Cytomegalovirus ◽

Wide Range ◽

The Central Nervous System ◽

Multicystic Dysplasia

Cytomegalovirus (CMV) infection is one of the most frequently encountered viral infections of the fetus and induces a wide range of histologic and clinical manifestations. Congenital abnormalities are typically restricted to the central nervous system despite evidence of CMV inclusions occurring in most epithelial cells. Although tissue injury and even glomerulonephritis have been observed in congenital CMV infections, renal multicystic dysplasia has not been reported. Herein, we describe a case of unilateral renal dysplasia in a 19-week fetus with concurrent CMV infection. We believe the present case to be the first description of a virus apparently inducing renal multicystic dysplasia.

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The obstetrician, congenital cytomegalovirus, clinical and diagnostic approaches to the pregnant woman

Microbiology Australia ◽

10.1071/ma15067 ◽

2015 ◽

Vol 36 (4) ◽

pp. 194

Author(s):

Antonia W Shand

Keyword(s):

Magnetic Resonance Imaging ◽

Pregnant Woman ◽

Fetal Mri ◽

Maternal Infection ◽

Resonance Imaging ◽

Cmv Infection ◽

Serological Screening ◽

Congenital Cytomegalovirus ◽

Fetal Infection ◽

Diagnostic Approaches

There is low awareness of congenital cytomegalovirus (CMV) in Australia. Routine pregnancy serological screening for CMV is not recommended, but all pregnant women should be given advice about CMV prevention. Obstetricians may be asked to see a pregnant woman when serology suggests CMV infection or when features of fetal infection are present on ultrasound. If maternal CMV infection is confirmed, the timing of infection (pre-pregnancy or gestation of pregnancy), must be determined to predict the fetal risks. In addition, it is important to establish whether maternal infection is primary or reactivation. If there is fetal infection, ultrasound can be used to attempt to establish whether the fetus may have been affected. Serial serology, CMV IgG avidity, maternal viraemia (using serum PCR), amniotic fluid CMV PCR, serial fetal ultrasounds, and possibly fetal MRI (magnetic resonance imaging) are investigations that may be useful to predict neonatal outcomes. Timely and accurate counselling is important to optimise maternal and neonatal management.

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Should You Follow the Better-Hearing Ear for Congenital Cytomegalovirus Infection and Isolated Sensorineural Hearing Loss?

Otolaryngology ◽

10.1177/0194599819880348 ◽

2019 ◽

Vol 162 (1) ◽

pp. 114-120 ◽

Cited By ~ 1

Author(s):

Vanessa Torrecillas ◽

Chelsea M. Allen ◽

Tom Greene ◽

Albert Park ◽

Winnie Chung ◽

...

Keyword(s):

Hearing Loss ◽

Sensorineural Hearing Loss ◽

Early Onset ◽

Medical Center ◽

Antiviral Treatment ◽

Sensorineural Hearing ◽

Cmv Infection ◽

Congenital Cytomegalovirus ◽

Delayed Onset ◽

Hearing Thresholds

Objective To describe the progression of sensorineural hearing loss (SNHL) in the better- and poorer-hearing ears in children with asymptomatic congenital cytomegalovirus (CMV) infection with isolated SNHL. Study Design Longitudinal prospective cohort study. Setting Tertiary medical center. Subjects and Methods We analyzed hearing thresholds of the better- and poorer-hearing ears of 16 CMV-infected patients with isolated congenital/early-onset or delayed-onset SNHL identified through hospital-based CMV screening of >30,000 newborns from 1982 to 1992. Results By 12 months of age, 4 of 7 patients with congenital/early-onset SNHL developed worsening thresholds in the poorer-hearing ear, and 1 had an improvement in the better-hearing ear. By 18 years of age, all 7 patients had worsening thresholds in the poorer-hearing ear and 3 patients had worsening thresholds in the better-hearing ear. Hearing loss first worsened at a mean age of 2 and 6 years in the poorer- and better-hearing ears, respectively. Nine patients were diagnosed with delayed-onset SNHL (mean age of 9 years vs 12 years for the poorer- and better-hearing ears), 6 of whom had worsening thresholds in the poorer-hearing ear and 1 in both ears. Conclusion In most children with congenital CMV infection and isolated SNHL, the poorer-hearing ear worsened earlier and more precipitously than the better-hearing ear. This study suggests that monitoring individual hearing thresholds in both ears is important for appropriate interventions and future evaluation of efficacy of antiviral treatment.

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Congenital Cytomegalovirus Infection Masquerading as Antenatal Ventriculomegaly With Intraventricular Hemorrhage in a Term Neonate

The Neurohospitalist ◽

10.1177/1941874419846044 ◽

2019 ◽

Vol 10 (1) ◽

pp. 55-57

Author(s):

Deepanjan Bhattacharya ◽

B. N. Anil Kumar ◽

Inusha Panigrahi ◽

Anupriya Kaur

Keyword(s):

Intraventricular Hemorrhage ◽

Term Neonate ◽

Preterm Neonates ◽

Cmv Infection ◽

Congenital Cytomegalovirus Infection ◽

Positive Polymerase Chain Reaction ◽

Congenital Cytomegalovirus ◽

Left Lateral Ventricle ◽

Polymerase Chain ◽

Occipital Horn

Intraventricular hemorrhage is an uncommon manifestation of congenital cytomegalovirus (CMV) infection and has been described in preterm neonates. We discuss a term neonate, who was referred because of intracranial hemorrhage and hydrocephalous detected in the antenatal ultrasound. She had cholestatic jaundice, hepatitis, and thrombocytopenia, with positive polymerase chain reaction for CMV. Neuroimaging revealed reduced sulcation, mildly enlarged ventricles, and multiple periventricular cysts, along with residual hemorrhage in occipital horn of left lateral ventricle. She was started on ganciclovir, following which there was improvement in platelet count, jaundice, as well as transaminase levels.

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Neonatal screening for congenital cytomegalovirus infection in Tehran, Iran, using Guthrie cards

Iranian Journal of Microbiology ◽

10.18502/ijm.v12i3.3236 ◽

2020 ◽

Author(s):

Samileh Noorbakhsh ◽

Mohammad Farhadi ◽

Faezeh Haghighi ◽

Sara Minaeian ◽

Morteza Haghighi Hasanabad

Keyword(s):

Early Stage ◽

Limited Data ◽

Cmv Infection ◽

Congenital Cytomegalovirus ◽

Congenital Cmv Infection ◽

Effective Counseling ◽

Total Dna ◽

Guthrie Cards ◽

Congenital Cmv

Background and Objectives: Cytomegalovirus (CMV) constitutes the most common viral cause of congenital infections in newborns worldwide. There are a significant number of asymptomatic newborns with congenital CMV infection in Iran, which may develop long-term sequelae of infection. Unfortunately, limited data exsists from Iran on the rate of congenital CMV infection among neonates. The current study was aimed to investigate the prevalence of congenital CMV infection among Iranian neonates by testing Guthrie cards. Materials and Methods: Guthrie cards were collected from infants within 2 weeks of life, and total DNA was extracted from samples by thermal shock and evaluated for CMV DNA using nested-PCR assay. CMV infection in newborns was confirmed through a commercial CMV PCR kit. Infected infants underwent further evaluation at the hospital. Results: CMV infection was identified in four of 1174 infants (0.34%) which is approximately 3 cases per 1000 live births. Infected infants were asymptomatic at birth and had a normal hearing status similar to other children. There were no factors in relation with CMV infection among newborns. Conclusion: According to the results of this study, infected infants with congenital CMV infection could identify at early stage by testing Guthrie cards (within 21 days of life). Furthermore, since there is a lack of CMV knowledge in our popula- tion, educating and effective counseling by obstetricians/ gynecologists to the pregnant women are recommended.

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Cytokine Profiles in Infants with Congenital Cytomegalovirus (CMV) Infection† 814

Pediatric Research ◽

10.1203/00006450-199804001-00835 ◽

1998 ◽

Vol 43 ◽

pp. 141-141

Author(s):

Suresh B Boppana ◽

Lisa Rivera

Keyword(s):

Cmv Infection ◽

Congenital Cytomegalovirus ◽

Cytokine Profiles

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Potential Impact of Different Cytomegalovirus (CMV) IgM Assays on an Algorithm Requiring IgM Reactivity as a Criterion for Measuring CMV IgG Avidity

Clinical and Vaccine Immunology ◽

10.1128/cvi.00106-14 ◽

2014 ◽

Vol 21 (6) ◽

pp. 813-816 ◽

Cited By ~ 5

Author(s):

Harry E. Prince ◽

Mary Lapé-Nixon ◽

Andrew Brenner ◽

Nancy Pitstick ◽

Marc Roger Couturier

Keyword(s):

Cmv Infection ◽

Serum Samples ◽

Immunofluorescent Assay ◽

Negative Results ◽

Igg Avidity ◽

Positive Serum ◽

Chemiluminescent Immunoassay ◽

Potential Impact ◽

The Impact ◽

Positive Results

ABSTRACTThe measurement of cytomegalovirus (CMV) IgG avidity is a powerful tool for identifying individuals with recent CMV infection. Because such patients are expected to be positive for CMV IgM, several investigators have suggested that CMV IgG-positive sera first be screened for CMV IgM and then only the IgM-reactive sera be tested for avidity. We investigated the impact of different CMV IgM assays on such a reflexing algorithm using a panel of 369 consecutive IgG-positive serum samples submitted for avidity testing. A bead-based immunofluorescent assay (BIFA) identified 105 IgM-positive serum samples, whereas an IgM-capture enzyme immunoassay (EIA) identified 48 IgM-positive serum samples; this marked difference led us to evaluate additional CMV IgM assays. An enzyme-linked immunofluorescent assay (ELFA) and a chemiluminescent immunoassay (CIA) were used to test all sera with discordant BIFA/EIA results, all sera with concordant positive results, and selected sera with concordant negative results. The findings indicated that the ELFA would identify 74 CMV IgM-positive samples and the CIA would identify 64. Of the 23 low-avidity serum samples, 2 were IgM negative by BIFA, 3 by ELFA and CIA, and 4 by EIA; of the 23 intermediate-avidity serum samples, 6 were IgM negative by BIFA, 10 by ELFA, and 15 by EIA and CIA. In both these avidity groups, BIFA IgM-negative sera were also negative by the other 3 assays. These findings demonstrate that an algorithm requiring CMV IgM reactivity as a criterion for CMV IgG avidity testing does not identify all low-avidity sera and thus misses some cases of acute CMV infection.

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Early high CMV seroprevalence in pregnant women from a population with a high rate of congenital infection

Epidemiology and Infection ◽

10.1017/s0950268812002695 ◽

2012 ◽

Vol 141 (10) ◽

pp. 2187-2191 ◽

Cited By ~ 17

Author(s):

A. Y. YAMAMOTO ◽

R. A. C. CASTELLUCCI ◽

D. C. ARAGON ◽

M. M. MUSSI-PINHATA

Keyword(s):

Pregnant Women ◽

Primary Infection ◽

Congenital Infection ◽

High Rate ◽

Cmv Infection ◽

Congenital Cytomegalovirus ◽

Younger Age ◽

Congenital Cmv Infection ◽

Stratified Sample ◽

Congenital Cmv

SUMMARYCongenital cytomegalovirus (CMV) infection rates increase with maternal seroprevalence due to transmission from maternal non-primary infection. CMV seroprevalence estimates of pregnant women are needed for planning strategies against congenital CMV transmission. We aimed to determine the age-specific prevalence of serum antibodies for CMV in a representative age-stratified sample of unselected pregnant women from a Brazilian population. A total of 985 pregnant women, aged 12–46 years (median 24 years), were enrolled. Overall CMV seroprevalence was 97% (95% confidence interval 95·8–98·0), with age-specific (years) prevalence as follows: 12–19 (96·3%), 20–24 (97·7%), 25–29 (97·1%), and 30–46 (96·7%). CMV seroprevalence is almost universal (97%) and is found at similar levels in pregnant women of ages ranging from 12 to 46 years. Because high CMV seroprevalence is found even in women of a younger age in this population, this finding suggests that the majority of primary CMV infections occur early, in infancy or childhood. As a consequence, vaccines currently under development to prevent primary infection may not be a solution for the prevention of congenital CMV infection in this population.

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