Congenital Cytomegalovirus Infection Research Articles

Cytomegalovirus infection of the fetal brain: intake of aspirin during pregnancy blunts neurodevelopmental pathogenesis in the offspring.

Congenital cytomegalovirus (CMV) infections represent one leading cause of human neurodevelopmental disorders. Despite their high prevalence and severity, no satisfactory therapy is available and pathophysiology remains elusive. The pathogenic involvement of immune processes occurring in infected developing brains has been increasingly documented. Here, we have used our previously validated rat model of CMV infection of the fetal brain in utero to test whether the maternal administration of four different drugs with immunomodulatory properties would have an impact on the detrimental postnatal outcome of CMV infection. CMV infection of the rat fetal brain was done intracerebroventricularly. Each of the drugs, including acetylsalicylic acid (aspirin, ASA), a classical inhibitor of cyclooxygenases Cox-1 and Cox-2, the two key rate-limiting enzymes of the arachidonic acid-to-prostaglandins (PG) synthesis pathway, was administered to pregnant dams until delivery. ASA was selected for subsequent analyses based on the improvement in postnatal survival. A combination of qRT-PCR, mass spectrometry-based targeted lipidomics, immunohistochemistry experiments, monitoring of neurologic phenotypes and electrophysiological recordings was used to assess the impact of ASA in CMV-infected samples and pups. The postnatal consequences of CMV infection were also analyzed in rats knocked-out (KO) for Cox-1. Increased PGE2 levels and increased proportions of Cox-1+ and Cox-2+ microglia were detected in CMV-infected developing brains. Maternal intake of ASA led to decreased proportion of Cox-1+ fetal, but not neonatal, microglia, while leaving the proportions of Cox-2+ microglia unchanged. Maternal intake of ASA also improved the key postnatal in vivo phenotypes caused by CMV infection and dramatically prevented against the spontaneous epileptiform activity recorded in neocortical slices from CMV-infected pups. In contrast with maternal intake of ASA, Cox-1 KO pups displayed no improvement in the in vivo phenotypes after CMV infection. However, as with ASA administration, the spontaneous epileptiform activity was dramatically inhibited in neocortical slices from CMV-infected, Cox-1 KO pups. Overall, our data indicate that, in the context of CMV infection of the fetal brain, maternal intake of ASA during pregnancy improved CMV-related neurodevelopmental alterations in the offspring, likely via both Cox-1 dependent and Cox-1 independent mechanisms, and provide proof-of-principle for the use of ASA against the detrimental outcomes of congenital CMV infections.

A case of congenital cytomegalovirus infection in a child with Prader–Willi syndrome

A possible manifestation of intrauterine infection with herpes viruses can be severe eye damage. Various visual disturbances with negative consequences have been described in Prader–Willi syndrome. The article describes bilateral chorioretinitis in a child with Prader–Willi syndrome, which developed against the background of congenital herpetic infection of CMV etiology.

Progress and Challenges in the Management of Congenital Cytomegalovirus Infection

Congenital cytomegalovirus (CMV) infection is the most common intrauterine viral infection with a significant impact on the foetus and newborn. Current diagnostic practice includes serological testing for specific antibodies, but there are no global screening protocols. Maternal CMV screening is often performed in conjunction with antenatal ultrasound. While most infections are asymptomatic, severe cases can lead to long-term disability or death. Antiviral therapies, mainly ganciclovir and valganciclovir, are reserved for symptomatic patients, especially those with central nervous system involvement. Although effective, these treatments are associated with significant side effects such as neutropenia and hepatotoxicity. Foscarnet and cidofovir are used as alternatives, but their efficacy and safety require further study in paediatric patient populations. The effectiveness of passive prophylaxis is still uncertain. The lack of universally accepted guidelines for diagnosis, treatment, and prevention and the risk of serious side effects highlight the need for continued research. This review evaluates current therapeutic strategies, discusses their efficacy and associated risks, and highlights the need for innovative approaches to improve outcomes for affected neonates.

Auditory Development of Young Children with Profound Hearing Loss, Cochlear Implants, and Congenital CMV Infection

Background/Objectives: The aim of this study was to assess auditory development in young children with profound hearing loss, cochlear implants (CIs), and congenital cytomegalovirus (cCMV) infection and to determine the effect of comorbidities on their development. Methods: The study group (cCMV group) consisted of 47 CI children—18 girls and 29 boys—who had been diagnosed as having prelingual hearing loss due to cCMV infection (with or without comorbidities); the mean age at CI activation was 15.2 months (range: 9.7–23.8; SD = 3.5). The reference group (no cCMV) consisted of 117 similar children (57 girls and 60 boys) who had profound sensorineural hearing loss not caused by cCMV infection; they had no comorbidities. The mean age at CI activation in the second group was 14.3 months (range: 7.9–23.5; SD = 4.0). Auditory development in all children was assessed with the LittlEARS Auditory Questionnaire (LEAQ) at CI activation and at about 1, 5, 9, 14, and 24 months of CI use. Results: The mean LEAQ total score increased over a similar time frame from 9.8 pts to 28.9 pts in the cCMV group without comorbidities, from 4.5 pts to 18.5 pts in the cCMV group with comorbidities, and from 9.2 to 31.6 pts in the reference group with no cCMV infection. Conclusions: Early cochlear implantation in children with sensorineural hearing loss due to congenital CMV infection and no comorbidities promotes their early auditory development in a similar way to children without cCMV infection.

CD4+ but not CD8+ T cells are required for protection against severe guinea pig cytomegalovirus infections.

Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus and the leading cause of infectious disease related birth defects worldwide. How the immune response modulates the risk of intrauterine transmission of HCMV after maternal infection remains poorly understood. Maternal T cells likely play a critical role in preventing infection at the maternal-fetal interface and limiting spread across the placenta, but concerns exist that immune responses to infection may also cause placental dysfunction and adverse pregnancy outcomes. This study investigated the role of CD4+ and CD8+ T cells in a guinea pig model of primary cytomegalovirus infection. Monoclonal antibodies specific to guinea pig CD4 and CD8 were used to deplete T cells in non-pregnant and in pregnant guinea pigs after mid-gestation. CD4+ T cell depletion increased the severity of illness, caused significantly elevated viral loads, and increased the rate of congenital guinea pig cytomegalovirus (GPCMV) infection relative to animals treated with control antibody. CD8+ T cell depletion was comparably well tolerated and did not significantly affect the weight of infected guinea pigs or viral loads in their blood or tissue. However, significantly more viral genomes and transcripts were detected in the placenta and decidua of CD8+ T cell depleted dams post-infection. This study corroborates earlier findings made in nonhuman primates that maternal CD4+ T cells play a critical role in limiting the severity of primary CMV infection during pregnancy while also revealing that other innate and adaptive immune responses can compensate for an absent CD8+ T cell response in α-CD8-treated guinea pigs.

National survey on Congenital Cytomegalovirus Awareness and Screening Practices among Healthcare Professionals

ObjectivesCongenital cytomegalovirus (CMV) infection, resulting from maternal-fetal transmission of CMV, poses a substantial risk to maternal and child health. It is the most prevalent congenital viral infection, and the prevention and management of this condition rely heavily on the knowledge and awareness of healthcare professionals. MethodsThis cross-sectional survey was conducted between March 1, 2023, and August 31, 2023, across multiple tertiary centers in various Saudi Arabian cities. It assessed the understanding and awareness of congenital CMV infection among 400 healthcare professionals from diverse specialties. The study utilized a structured questionnaire to evaluate knowledge levels, obtain demographic data, and identify factors influencing awareness. ResultsThe study revealed significant disparities in knowledge levels, with around 84 % of participants categorized as having “low" knowledge. Obstetricians and gynecologists exhibited better knowledge. Factors like specialization, age, and professional experience significantly affected knowledge levels. Additionally, many healthcare professionals perceived a lack of information and awareness regarding CMV among their peers. ConclusionCongenital CMV infection is a major public health concern with potential severe consequences. The study identified knowledge disparities, particularly among non-specialist healthcare practitioners, emphasizing the need for targeted educational programs and focused awareness initiatives. Key factors, such as expertise, age, and experience, underscore the importance of addressing ongoing knowledge gaps, highlighting the need for continuous efforts to mitigate challenges associated with CMV infection.

Testing for genetic and viral etiologies in congenital hearing loss based on a survey of cochlear implant centers: proposed HEARRING group consensus and future directions

Background In cases of congenital sensorineural hearing loss, testing for genetic etiologies and congenital cytomegalovirus (cCMV) infection have become common practice. Aims/Objectives The purpose of this study is to determine which specific testing methodologies should be used and when. Material and methods We surveyed 20 practicing otolaryngologists across eighteen institutions in thirteen countries about their approach to cCMV, GJB2, and wider genetic testing. Results We found 90% of respondents employ all three tests, either in routine or special cases. cCMV testing is widely used, with 95% of respondents incorporating it into their clinical practice. GJB2 testing was employed by 90%. In cases with negative GJB2 test results, a majority of respondents proceeded to wider genetic screening. Test reimbursement was also examined for each test. For cCMV testing, 63.1% reported reimbursement, 68.4% reported reimbursement for GJB2 variant testing and 52.6% reported reimbursement for wider genetic screening. Conclusions and significance A common approach is to perform cCMV and GJB2 testing as the first tests, followed by wider genetic testing. This study offers insight into the prevalence, methodologies, and reimbursement status of these testing methodologies across multiple hearing centers and countries. Current consensus and future directions are described based on the current survey.

Congenital Cytomegalovirus Infection: Update on Screening, Diagnosis and Treatment: Scientific Impact Paper No. 56.

Cytomegalovirus (CMV) is the most common cause of viral infection in newborn babies, and affects 1 in 200 of all live born infants in high-income countries; and 1 in 71 in low- and middle-income countries. It is a major cause of hearing loss and brain damage. Women may get CMV infection for the first time during pregnancy (primary infection) or may experience 'non-primary' infection, either by reactivation of previous CMV infection or by a new infection with a different strain of the virus. The most common source of infection to pregnant women is the saliva and urine of young children. Therefore, all pregnant women, especially those in regular contact with young children, should be informed about hygiene-based measures to reduce the risks, e.g. handwashing. The UK National Screening Committee recommends against universal antenatal or newborn screening for CMV. Testing for CMV is usually offered only to women who develop symptoms of influenza, glandular fever or hepatitis (liver inflammation) during pregnancy, or for those whom a routine ultrasound scan detects fetal anomalies that suggests possible CMV infection. The risk of harm to the fetus is greatest following primary CMV infection of the woman in early pregnancy, and appears to be very low following infection after 12 weeks of pregnancy. Babies with CMV infection at birth may have jaundice, a rash, enlarged liver or spleen, a small brain, or be small for their gestational age. Around 1 in 8 babies born with CMV infection will have clinically detectable signs at birth. The rest will not have any features detectable by clinical examination alone. Therefore, all infants with CMV infection at birth should be followed up at a minimum of up to 2 years of age or later, depending upon the disease status, to check hearing and brain development. Following primary CMV infection in the first 12 weeks of pregnancy, if the woman starts taking the antiviral medicine valaciclovir (valacyclovir) it reduces the risk of the baby becoming infected. Where CMV infection of the fetus in the womb has been confirmed (by amniocentesis, for example), regular ultrasound scans should be offered every 2-3 weeks until birth. Detailed assessment of the fetal brain is an essential part of these scans. Where maternal CMV infection occurs, but fetal infection is not confirmed, repeated ultrasound scans of the fetus should be offered every 2-3 weeks until birth. In infected fetuses, as well as ultrasound scans, an MRI scan of the brain should be offered at 28-32 weeks of gestation (and sometimes repeated 3-4 weeks later) to assess for any signs of harm to the fetal brain. All babies born to women with confirmed or suspected CMV infection should be tested for CMV with a urine or saliva sample within the first 21 days of life. In newborns with symptomatic CMV infection at birth, treatment with antiviral medicine (valganciclovir or ganciclovir) can reduce hearing loss in 5 out of 6 babies, and improve long-term brain development outcomes in some. There is no licensed vaccine for CMV.

The value of magnetic resonance imaging in congenital cytomegalovirus infection: a systematic review.

Congenital cytomegalovirus (cCMV) infection can lead to severe neurodevelopmental and hearing impairments. Imaging techniques can be used both pre- and postnatally to assess early signs of infection. The objective was to provide a systematic review of current literature regarding magnetic resonance imaging (MRI) and its value to predict clinical outcome in children with cCMV. PubMed, Embase, and Web of Science were searched for studies investigating MRI in cCMV between 2016-2024. Risk of bias was assessed using Newcastle-Ottawa quality assessment scales. Descriptive synthesis was performed. Twenty studies were included. MRI detected brain abnormalities in 5.0-53.0% of infected patients prenatally and 26.9-69.0% postnatally. The three most frequently detected abnormalities included white matter lesions, subependymal cysts, and ventricular dilatation. Symptoms at birth, first trimester seroconversion, and high viral load were associated with abnormal MRI; however, brain abnormalities were still found in 33-37% of clinically asymptomatic patients. Prenatal MRI had a negative predictive value of 94-100% and a positive predictive value of 12-60% for predicting adverse clinical outcome. Five in six studies found an association between MRI abnormalities and neurodevelopmental impairments, five in eight with (congenital) hearing loss. MRI detected additional abnormalities in 5.6-19.4% of children with normal ultrasound.In conclusion,MRI can detect a wide range of brain abnormalities, both pre- and postnatally, in symptomatic and asymptomatic patients. MRI can be a helpful tool in the prediction of clinical impairments and seems complementary to ultrasound. Therefore, both fetal and neonatal MRI should be considered in the standard work-up of all cCMV-infected children.

Hoyeraal-Hreidarsson syndrome: a case report of dyskeratosis congenita with a novel PARN gene mutation

Introduction and importance: Dyskeratosis congenita (DC) is a rare multisystem disorder primarily characterized by bone marrow failure due to telomere shortening. Typical clinical features include oral leukoplakia, skin hyperpigmentation, and nail dystrophy, along with an increased risk of malignancies. Hoyeraal-Hreidarsson Syndrome (HH), a severe variant of DC, is associated with profound neurological and immunological complications, emphasizing the importance of early diagnosis and genetic evaluation to guide appropriate management. Case Presentation: We present a case of a 2-year-old girl diagnosed with Hoyeraal-Hreidarsson Syndrome, linked to a newly discovered mutation in the poly (A)-specific ribonuclease (PARN) gene. The patient exhibited intrauterine growth retardation (IUGR), congenital cytomegalovirus (CMV) infection, immunodeficiency, microcephaly, and cerebellar hypoplasia. Whole exome sequencing (WES) identified a novel mutation in the PARN gene. Clinical Discussion: Hoyeraal-Hreidarsson Syndrome, a severe form of DC, manifests with multisystem involvement and is genetically heterogeneous. Early genetic testing through techniques such as WES can aid in diagnosing rare syndromes like HH and guide treatment strategies, including bone marrow transplantation. Conclusion: This case underscores the importance of genetic evaluation in complex, rare syndromes like HH. Whole exome sequencing plays a crucial role in identifying pathogenic mutations and tailoring management. The patient’s prognosis is being closely monitored following bone marrow transplantation.

Antiviral Therapy for Congenital Cytomegalovirus Infection: Does It Prevent Late-Onset Sensorineural Hearing Loss?

Abstract Background Congenital cytomegalovirus (CMV) infection is the leading non-genetic cause of sensorineural hearing loss (SNHL) in children. While SNHL is often present at birth, as many as 20% of infants with congenital CMV infection may develop late-onset hearing loss beyond the neonatal period. Antiviral therapy improves hearing outcomes, but its effect on the occurrence of late-onset SNHL is not fully known. The objective is to describe the prevalence of SNHL at birth and late SNHL among infants and children with congenital CMV infection and assess the impact of antiviral treatment on the occurrence of late-onset SNHL. Methods From 2013 to 2022, infants with congenital CMV infection referred to the NEO-ID Clinic at Nationwide Children’s Hospital (NCH), Columbus, OH underwent complete evaluation including hearing testing. Pertinent demographic, clinical, audiologic, laboratory, and radiographic data were obtained and stored using an electronic database (REDCap). Infants with SNHL at birth or who developed late-onset SNHL beyond a month of age were identified and compared with respect to receipt of antiviral therapy in the neonatal period. Results During the 10-year study period, we enrolled 204 infants with congenital CMV infection: 75% (154/204) had symptomatic disease, while 25% (50/204) had clinically inapparent infection (normal physical examination, growth parameters, and evaluation). Overall, 30% (n=62) had SNHL at birth or on follow-up audiologic evaluation with the majority (95%, 59/62) having symptomatic disease. Of the 62 infants with SNHL, 29% (n=18) had late-onset SNHL in one (n=10) or both (n=8) ears at a median age of 19 months (IQR, 8.5-42 months). Of the 122 infants who received antiviral therapy initiated in the first month of age, 12 (10%) developed late-onset SNHL in one (n=7) or both (n=5) ears. All 12 had symptomatic congenital CMV infection, and 2 received cochlear implants in one ear. Of the 82 infants who did not receive any antiviral therapy, 6 (7%) developed late-onset SNHL (3, unilateral [2, symptomatic]; 3, bilateral [1, symptomatic]) and 2 received cochlear implant. There was no difference in the occurrence of late-onset SNHL in treated (10%) vs. untreated (7%) infants with congenital CMV infection (p=0.6). Conclusion In this cohort of mostly symptomatic infants with congenital CMV infection, antiviral treatment did not reduce the occurrence of late-onset SNHL. Further study on the impact of early antiviral therapy on severity of the SNHL is urgently needed to inform optimal treatment management.

Antiviral Treatment and Risk of Hearing Loss in Asymptomatic and Mild Symptomatic Infants With Congenital Cytomegalovirus.

To assess hearing outcomes at 24 months of age in infants with mild congenital cytomegalovirus (cCMV) infection, depending on whether they have received antiviral treatment or not. A retrospective study within the European Registry of Children with cCMV was performed. Included children had cCMV diagnosed in utero/in the first 21 days of life, with normal physical examination, alanine aminotransferase <80 U/L and platelets >100,000 cs/mm3 and absence of hearing loss (HL) at birth. Cranial ultrasound (cUS) and/or cranial magnetic resonance imaging was normal or with minor findings (isolated lenticulostriate vasculopathy and/or germinolysis/caudothalamic or subependymal cysts, and/or focal/multifocal white matter involvement). The main outcome was the presence of HL at 24 months of age. One hundred ninety-six patients met inclusion criteria. A total of 34.7% received antiviral treatment with valganciclovir/ganciclovir. Children treated had lower gestational age, birth weight and head circumference, and maternal primary infection was less frequent. Among treated children, 21.3% presented minor findings in cUS versus 6.3% in nontreatment group (P = 0.003). Nine patients (4.6%) developed HL at 24 months. Among children with HL, 20% presented minor findings in cUS versus 11.3% in non-HL group (P = NS). HL rate was similar in treated and nontreated groups (4.6% vs. 6.3%; P = 0.6). One-third of the children were treated with antivirals and infants with minor neuroimaging findings at birth were more likely to receive antiviral. There were no differences in the prevalence of HL at 2 years of age between treated and not-treated children. Minor neuroimaging findings were not clearly associated with an increased risk of delayed onset HL.

Outcome of Children with Congenital Cytomegalovirus Infection: A Retrospective Observational Study

Abstract Objective Congenital cytomegalovirus (CMV) infection is a common intrauterine infection and the leading cause of nonhereditary sensorineural hearing loss. This study aims to assess the long-term outcome of the infection and to identify infants at risk of developing long-term sequelae. Methods This retrospective single-center observational study includes infants born between 2003 and 2019 with confirmed congenital CMV (based on current criteria). Brain imaging (ultrasound and magnetic resonance imaging [MRI]), clinical monitoring of neurosensory development, and auditory brainstem evoked responses were performed, as well as long-term neurodevelopmental follow-up to assess sequelae. Results A total of 66 infants with congenital CMV were included in the study. Median gestational age at birth was 38.6 weeks (interquartile range: 36.9–40.1). Clinical findings included intrauterine growth restriction (39%), microcephaly (29%), thrombocytopenia (17%), and jaundice (11%). Brain abnormalities were observed on ultrasound (30%) and MRI (42%). Neurodevelopmental scores were abnormal in 21 subjects (43%) and associate with the vacuolization of anterior temporal lobe and ventricular septations on MRI (both p = 0.05). Fourteen patients (21%) had sensorineural hearing loss, which was more common in patients with abnormal cerebral images at birth, determined by ultrasound (p = 0.06). Microcephaly (p = 0.05) and abnormal MRI (p = 0.03) at birth were associated with poor long-term outcomes. Conclusion Early detection of congenital CMV infection is important to prevent long-term complications in affected infants. Understanding the predictors of poor outcomes may help improving management and treatment strategies for this condition.

Prenatal and postnatal antiviral therapies for the prevention and treatment of congenital cytomegalovirus infections.

Congenital cytomegalovirus infection (cCMV) is the leading infectious cause of sensorineural hearing loss and lifelong neurodevelopmental disabilities. Studies suggest antiviral therapy can prevent fetal infection after maternal primary infection, as well as halt the progression of hearing loss and neurodevelopmental disabilities in newborns with symptomatic cCMV. With growing worldwide momentum on early detection and diagnosis of cCMV, this review describes the exciting recent advances in antiviral therapies in CMV infected pregnant mothers and babies, as well as emerging evidence on anti-CMV vaccines. New opportunities for prenatal and neonatal interventions have driven a rising interest in screening and identification of asymptomatic CMV infection. Routine screening of pregnant women to identify primary infection in first trimester is now advocated in Western Europe but has yet to be examined from a public health perspective in other regions. Evidence is emerging for maternal valaciclovir therapy to prevent fetal infection after a maternal primary CMV infection in the first trimester of pregnancy. For those infants who are born with symptomatic cCMV, a 6-month course of valganciclovir, started within the first 4 weeks of life, and possibly up to 13 weeks of life, is the current recommended therapy. However, there is unclear evidence for the benefit of treatment for asymptomatic cCMV and cCMV with isolated hearing loss. Research to identify more effective antivirals and an effective CMV vaccine continues. More research is needed to determine the region-specific applicability of the new European recommendations for routine CMV screening in pregnancy. Areas of uncertainty in postnatal management include timing of initiation, duration of treatment and identifying pediatric subgroups that benefit from modification of the standard treatment recommendations.

Audiological and Vestibular Follow-Up for Children with Congenital Cytomegalovirus Infection: From Current Limitations to Future Directions.

Currently, the guidelines for audiological and vestibular follow-up in children with congenital cytomegalovirus (CMV) are not well-defined. The general recommendation is to evaluate hearing in all children with congenital CMV at the same intervals: once every 3-6 months up to 1 year of age, once every 6 months from 1 to 3 years of age, and once a year from 3 to 6 years of age. Additionally, there are no universally accepted protocols for the vestibular follow-up of children with congenital CMV, although video head impulse test (v-HIT) and cervical vestibular-evoked myogenic potentials (cVEMPs) are sometimes used. This narrative review critically evaluates existing audiological and vestibular follow-up approaches for children with congenital CMV, highlighting the need for personalized protocols. Tailoring follow-up schedules with different timing and methods based on risk factors, such as the trimester of maternal infection, CMV PCR results in amniotic fluid, and valganciclovir use, would indeed allow for more precise evaluations, timely interventions, and optimized resource allocation. This strategy would also alleviate the logistical and emotional burdens on families by ensuring that high-risk children receive more frequent and appropriate assessments and early interventions, while lower-risk children avoid unnecessary testing.

Serological and Molecular Detection of Cytomegalovirus in Aborted Women in Diyala Province, Iraq

Background: Cytomegalovirus (CMV) is a common virus that can infect individuals of all ages. In pregnant women, CMV infection can lead to complications such as congenital CMV infection, which can cause miscarriage, stillbirth, or significant fetal abnormalities. Objective: To evaluate the prevalence of CMV infection in women with and without a history of miscarriage in Diyala Province, Iraq. Methods: A total of 120 women were recruited and divided into three groups: 40 pregnant women with a history of miscarriage, 40 non-pregnant women with a history of miscarriage, and 40 healthy women without a history of miscarriage (control group). Blood samples were collected from each participant and analyzed for the presence of CMV-specific IgG and IgM antibodies using enzyme-linked immunosorbent assay (ELISA). Some positive results were retested to detect the MIE gene region IE-2 (UL122) by real-time PCR and the IE1 (UL123) gene by conventional PCR. Demographic data of study groups were recorded, and statistical analysis was performed using SPSS Version 29. Results: The serological analysis revealed the following prevalence of CMV IgG antibodies: 100% in both pregnant and non-pregnant women with a history of miscarriage, and 95% in the control group of healthy women without a history of miscarriage. For CMV IgM antibodies, the prevalence was 47.5% in pregnant women with a history of miscarriage, 40% in non-pregnant women with a history of miscarriage, and 7.5% in the control group of healthy women without a history of miscarriage. The PCR results showed that 9 of the samples were positive for both the UL122 and UL123 genes. Conclusion: The study indicates a high prevalence of CMV infection among women with a history of miscarriage in Diyala Province, Iraq. Routine screening for CMV in pregnant women, especially those with a history of miscarriage, is recommended to reduce potential risks and improve pregnancy outcomes.

T cell responses and clinical symptoms among infants with congenital cytomegalovirus infection.

BACKGROUNDCongenital cytomegalovirus (cCMV) infection can cause developmental impairment and sensorineural hearing loss (SNHL). To determine the relationship between immune responses to cCMV infection and neurologic sequelae, T cell responses were compared for their connection to clinical symptoms at birth and neurodevelopmental outcomes.METHODSThirty cCMV-infected and 15 uninfected infants were enrolled in a single-center prospective observational case-control study. T cell pp65-specific cytokine responses; CD57, CD28, and PD-1 expression; and memory subsets were compared.RESULTSInfected neonates (73% symptomatic at birth) lacked pp65-specific cytokine-secreting T cells, with elevated frequencies of CD57+, CD28-, and PD-1+CD8+ T cells and effector memory subsets. Though frequencies overlapped between cCMV symptom groups, asymptomatic infants had higher frequencies of CD57+PD-1+CD8+ T cells. Neonates with subsequent developmental delay lacked detectable CMV-specific T cell responses, with patterns resembling those of uninfected infants. Two children with progressive SNHL had high frequencies of PD-1+CD8+ T cells over the first year compared with children without progressive SNHL.CONCLUSIONSimilar to published reports, neonatal viral antigen-specific cytokine-secreting T cell responses were not detected, but overall patterns indicate that globally differentiated memory CD8+ T cell populations were induced by cCMV infection, with higher frequencies of terminally differentiated PD-1+CD8+ T cells potentially associated with asymptomatic infection. In this cohort, a lack of in utero T cell differentiation was associated with developmental delay, and high frequencies of PD-1+CD8+ T cells persisted only in children with progressive SNHL. Further work is needed to define the specificity of these T cells and their mechanistic connection to these outcomes.FUNDINGThis study was funded through an intramural research award at Nationwide Children's Hospital, the Pediatric Infectious Disease Society Fellowship Award funded by Stanley and Susan Plotkin and Sanofi Pasteur, the Abigail Wexner Research Institute at Nationwide Children's Hospital, and the Pichichero Family Foundation Vaccines for Children Initiative Research Award from the Pediatric Infectious Diseases Society Foundation.

Congenital CMV infection - what we know about the symptoms, treatment and prevention? - Review of literature

Introduction: Cytomegalovirus (CMV) is a double-strand DNA virus, member of the viral family known as Herpesviridae which is wide-spread. CMV infection is the most common congenital infection worldwide. Disease is mostly asymptomatic for healthy people, therefore is detected late, when the children start presenting symptoms. Unfortunately the congenital CMV infection leads to the serious health problems for infants. Detection of the virus is typically done through quantitative PCR assays. Infection especially affects nervous system and can present infant’s deafness. Earlier it was equivalent with the children being deaf till the end of life, but nowadays thanks to the development of laryngological methods (ex. cochlear implantation) patients have chance to grow up correctly. Material and methods: A literature search was conducted using Google Scholar, PubMed, and Web of Science databases. We searched articles by entering key words in the appropriate configuration: “CMV”, “Congenital CMV infection”, “valganciclovir”, “infant’s deafness”. Scientific articles published between 1991–2023 were analyzed from all over the world and guidelines of Polish Society of Epidemiology and Infectious Diseases.Conclusions: Currently we haven’t got prevention towards congenital CMV, only the treatment for infants: valganciclovir. It stops development of severe symptoms. There are available analysis, where using valganciclovir during pregnancy reduces the possibility or soften the course of the congenital CMV infection , but it’s not the obligatory guidelines. In many countries researchers want to conduct screening test for CMV IgG among the pregnant women.

Cystic leukoencephalopathy in congenital cytomegalovirus infection.

Cystic leukoencephalopathy in congenital cytomegalovirus infection.

Changes of CD8+CD28- Tregs and Gamma-Delta-T-cells in a Neonate with Intrauterine Cytomegalovirus Infection: A Case Report

BackgroundCongenital cytomegalovirus (cCMV) infection can lead to a range of adverse outcomes. The majority of cCMV neonates with clinical symptoms are infected postnatally; however, established cases of intrauterine infection are uncommon, resulting in a paucity of reports on clinical findings and lymphocytes expression in CMV-infected neonates.Case presentationWe followed a neonate with cCMV infection from the onset of hospitalization to several months of follow-up. This infant was intrauterine CMV-positive in the amniotic fluid of the mother at 21 weeks’ gestation and received intravenous ganciclovir infusion and sequential oral valganciclovir after birth. The typical clinical signs manifested in the nervous system, liver, and peripheral blood and were documented during the hospitalizaion period and up to the follow-up visit. Flow cytometry was employed to examine the expression of T cells, their subsets, and the associated cytokines in peripheral blood samples at various time points. The flow data for the cCMV neonate were compared with those of the controls at each time point. Following treatment, clinical symptoms improved and the infant became CMV negative. However, developmental delays occurred later in life. The proportion of CD8+CD28− Tregs in the peripheral blood of the neonate with congenital CMV infection was higher than that in the controls at the three time points. The expression levels of perforin and granzyme B secreted by γδ T cells (Vδ1 and Vδ2 T cells), increased during the course of hospitalization until follow-up and were higher than those in the controls at the three time points.ConclusionsDespite the alleviation of clinical symptoms, developmental delay in later life remains inevitable in this intrauterine cCMV neonate. CD8+CD28− Tregs and Vδ1 and Vδ2 T cells secreting perforin and granzyme B may be involved in congenital CMV infection, although this hypothesis requires validation in a larger study. This report may contribute to our understanding of the effect of current treatment and the immune status of intrauterine cCMV-infected neonates.