Perinatal Cytomegalovirus Infection Research Articles

Prion protein alters viral control and enhances pathology after perinatal cytomegalovirus infection

Cytomegalovirus (CMV) infection poses risks to newborns, necessitating effective therapies. Given that the damage includes both viral infection of brain cells and immune system-related damage, here we investigate the involvement of cellular prion protein (PrP), which plays vital roles in neuroprotection and immune regulation. Using a murine model, we show the role of PrP in tempering neonatal T cell immunity during CMV infection. PrP-null mice exhibit enhanced viral control through elevated virus-specific CD8 T cell responses, leading to reduced viral titers and pathology. We further unravel the molecular mechanisms by showing CMV-induced upregulation followed by release of PrP via the metalloproteinase ADAM10, impairing CD8 T cell response specifically in neonates. Additionally, we confirm PrP downregulation in human CMV (HCMV)-infected fibroblasts, underscoring the broader relevance of our observations beyond the murine model. Furthermore, our study highlights how PrP, under the stress of viral pathogenesis, reveals its impact on neonatal immune modulation.

Pulmonary Complications of Cytomegalovirus Infection in Neonates and Infants: A Systematic Review of Case Reports and Pooled Analysis.

Cytomegalovirus (CMV) causes intrauterine infections in 0.67% of neonates, with 12.7% displaying symptoms at birth. CMV can lead to severe multiorgan involvement, and mortality in symptomatic cases is around 30%. Pulmonary complications are rare in infants with CMV. This review assesses pulmonary complications and outcomes in infants with CMV infection. A systematic literature search was conducted using PubMed, SCOPUS and Ovid SP to retrieve case reports on pulmonary complications in infants with congenital or perinatal CMV infection. Descriptive analysis and pooled analysis were conducted for the case reports. A total of 28 articles with 38 patients were included in this systematic review. The reported pulmonary complications in the case reports were CMV pneumonitis (34.2%), persistent pulmonary hypertension of the newborn (18.4%), emphysema and chronic lung disease (15.8%), diaphragmatic dysfunction (13.2%), lung cysts and calcifications (10.5%), Pneumocystis jirovecii infection (7.9%), pulmonary hypoplasia (5.3%) and bronchial atresia (2.6%). Seven (18.4%) of 38 patients passed away because of the pulmonary complications of CMV infection. Congenital transmission (P = 0.0108), maternal CMV (P = 0.0396) and presence of neonatal comorbidities (P = 0.0398) were independent risk factors for mortality. This systematic review demonstrated infrequent occurrence of severe pulmonary involvement in CMV infection but should be considered in infants with persistent or severe respiratory symptoms.

On the classification of cytomegalovirus infection in newborn children

Relevance: Cytomegalovirus (CMV) infection is the most common infection that is most commonly found in sick newborns and may be the leading cause of their morbidity and mortality. Current research and clinical observations confirm the likelihood of contracting CMV infection not only in the antenatal period but also in the perinatal and postnatal periods. The study aimed to comment on the current understanding of neonatal CMV infection, its clinical manifestations depending on the time of infection, perinatal outcomes, and long-term consequences to develop a functional classification of CMV infection in newborns. Materials and methods: A systematic review and analysis of the literature sources published by scientists in neonatology and perinatology, healthcare practitioners, and professional associations was carried out. Literature searches were conducted in PubMed, Embase, Scopus, and Euro-Peristat over the past decade by the study keywords. A total of 30 sources were included in the analysis. Results: Delayed sequelae, symptomatic and asymptomatic congenital and perinatal infections have been identified. A review shows that, to date, the incidence of asymptomatic congenital CMV infection has not been established. There is no systematization of the clinical manifestations and outcomes of congenital, perinatal, and postnatal CMV infection in newborns. Conclusion: Based on the literature review, we have developed a functional classification of CMV infection in newborns by the time of infection. Thus, CMV infection can be congenital, perinatal, or postnatal. The classification presents manifestations of symptomatic forms of CMV infection, perinatal and distant outcomes. However, there are no clear diagnostic criteria for asymptomatic forms of CMV infection. There is no clear rationale for etiopathogenetic therapy, prognostic and preventive criteria for various forms of CMV infection. All of the above tasks require further prospective cohort studies.

A Comparative Study Between Cytomegalovirus Immunoglobulin M-Positive and CMV Immunoglobulin M-Negative Biliary Atresia in Infants Attending a Tertiary Care Hospital in Bangladesh.

PurposePerinatal cytomegalovirus (CMV) infection can lead to biliary atresia (BA) in different entities. This study aimed to compare the clinical, hematological, biochemical, and histological features of infants with BA based on their CMV immunoglobulin M (IgM) status at presentation.MethodsThis cross-sectional descriptive study was carried out between January 2019 and June 2020 at the Department of Pediatric Gastroenterology and Nutrition at the Bangabandhu Sheikh Mujib Medical University (BSMMU) in Dhaka. Forty-three patients with BA were selected purposively and categorized into either the CMV IgM-positive or CMV IgM-negative BA group. Categorical variables were compared using Fisher’s exact test and chi-square tests, while the Student’s t-test and Mann–Whitney U-test were used to compare continuous variables. For all statistical tests, a p-value <0.05 was considered statistically significant.ResultsThirty-three (76.7%) of the cases were between 2 and 3 months of age on admission. The clinical, hematological, and biochemical parameters did not differ significantly between the CMV IgM-positive and CMV IgM-negative BA groups. Most (50.0%) of the CMV IgM-positive cases had fibrosis stage F2, while 43.5% of the CMV IgM-negative cases had fibrosis stage F3, with no significant difference between the groups (p=0.391).ConclusionOur data shows no significant distinction between CMV IgM-positive and CMV IgM-negative BA, suggesting that CMV does not contribute to BA pathogenesis.

Результаты патогенетической терапии препаратом Н-Пентоксиниал у детей с текущей латентной ЦМВ/ЭБВ инфекцией

In the perinatal and early postnatal period, congenital (antenatal) and intrauterine (intra- and perinatal) CMV are more often manifested by lesions of the liver, brain and organ of vision. Objective. To study the effect of pathogenetic therapy with the metabolic and hepatoprotective drug N-Pentoxinial on the course of persistent CMV/EBV infection of perinatal genesis in children. Material and Methods. The course of latent perinatal cytomegalovirus (CMV) and Epstein-Bar viral infections in children was studied against the background of antiviral treatment (specific against CMV/ EBV immunoglobulin - Neocytect and recombinant alpha-interferon - Viferon No. 10), followed (immediately after 5-7 days after antiviral) by the appointment of 1-2 courses of N-Pentoxinal for 10-20 days. The main group consisted of 20 children (average age 5.4±1.4 years), the control group consisted of 10 children (average age 5.1±1.7 years). All underwent general clinical and virological studies to confirm the diagnosis. Result and discussions. The results obtained indicate that the addition of N-pentoxynial to the basic antiviral therapy for CMV and EBV infection in children improves (accelerates) the elimination of the virus from biological fluids (blood and urine), as well as more rapid normalization of transaminases and alkaline phosphatase. There were no reliably proven allergic reactions. Conclusions. The drug N-Pentoxinial can be prescribed after antiviral therapy for perinatal CMV, EBV infection in order to consolidate the results of antiviral treatment and normalize liver function, especially bile secretion. Keywords: latent perinatal cytomegalovirus/Epstein-Barr viral infection, children, therapy.

Prevalence of cytomegalovirus DNAemia and genotypic distribution among childbearing mothers and neonates in Taiwan

BackgroundCongenital cytomegalovirus (CMV) infection is the leading cause of neurologic disabilities and sensorineural hearing loss in children. However, in Taiwan, there is limited information on the genotypic diversity and prevalence of perinatal CMV infection in both mothers and neonates. The aim of this study was to screen samples from both mothers and umbilical cord blood for CMV at the time of delivery and to determine the CMV genotypic distribution. MethodsBetween June 2012 and July 2015, residual maternal and umbilical cord blood samples were collected from consenting participants admitted to the Chang Bing Show Chwan Memorial Hospital in central Taiwan. The blood samples were screened for CMV DNA using real-time PCR assay, and the genotypic classification of the CMV UL55, UL144, and US28 genes was determined by sequencing and phylogenetic analysis. ResultsA total of 1282 mother-neonate paired samples were enrolled in the study, 95.3% of whom were Taiwanese. CMV DNA was detectable in 6.2% of the maternal blood samples, with a significantly higher rate noted in non-Taiwanese mothers (11.7%,p=0.027). For the 1,282 umbilical cord blood samples, CMV DNA was detectable in 5.3% of the samples. The presence of CMV DNA in maternal blood was positively associated with the presence of CMV DNA in umbilical cord blood (p=0.01). In addition, the UL55, UL144, and US28 genotypic distribution was similar between mothers and neonates. ConclusionThe prevalence of CMV DNAemia in childbearing mothers and neonates is similar and their genotypic distribution implies potential CMV infection during pregnancy.

Isolated thrombocytopenia in childhood: what if it is not immune thrombocytopenia?

Childhood immune thrombocytopenia (ITP) remains a diagnosis of exclusion when isolated thrombocytopenia is not part of another disease process. In practice, the diagnosis of ITP can only be confirmed when thrombocytopenia resolves or is excluded after the recognition of a primary cause. The records of 87 consecutive children with isolated thrombocytopenia seen over a nine-year period in a private paediatric haematology practice were reviewed retrospectively. Children in whom a primary cause was eventually found were the subjects of a further descriptive study. 9 (10%) children with isolated thrombocytopenia were not diagnosed with ITP because a primary disease was found. Of these nine cases, four had thrombocytopenia recognised during the neonatal period, consisting of perinatal cytomegalovirus infection (n = 2), meconium aspiration pneumonia (n = 1) and transient abnormal myelopoiesis associated with Down syndrome (n = 1). The remaining five children were each found to have familial thrombocytopenia, portal hypertension, cutaneous mastocytosis, May-Hegglin anomaly and systemic lupus erythematosus. Two of them had a history of failure of response to corticosteroid therapy. Secondary thrombocytopenia is not uncommon in a tertiary paediatric specialty practice with adequate evaluation. Thrombocytopenia occurring during the newborn period and failure of steroid therapy are predictive of secondary cases.

Patient perceptions of educational interventions for prevention of perinatal cytomegalovirus infection

Patient perceptions of educational interventions for prevention of perinatal cytomegalovirus infection

Congenital cytomegalovirus infection presenting with intrapulmonary calcifications on prenatal sonogram

Cytomegalovirus (CMV) is the most common congenital viral infection in developed countries. Although pneumonitis has been reported in infants with congenital CMV infection, involvement of the lung parenchyma is less common in congenital than in perinatal CMV infections. We report an infant with congenital cytomegalovirus (CMV) infection and multiple intrapulmonary calcifications on prenatal sonogram that had congenital pneumonia and persistent oxygen requirement after birth. To our knowledge, this is the first case report of a live-born infant with pulmonary calcifications due to CMV noted on prenatal sonograms.

A 5-year retrospective clinical study of perinatal cytomegalovirus infection

To investigate the incidence, clinical features, and treatment of perinatal cytomegalovirus (CMV) infection, as well as the factors affecting the therapeutic effect of ganciclovir. The clinical data of 237 infants who were hospitalized and diagnosed with perinatal CMV infection from 2008 to 2012 were retrospectively analyzed. The clinical features of infants with perinatal CMV infection and the proportion of such infants in all hospitalized infants showed no significant differences across the five years. In most infants, two or more systems were involved, and CMV hepatitis plus CMV pneumonia was most common (43.1%). The results of pathogen detection showed that the percentage of the infants with positive blood CMV-IgM and blood/urine CMV-DNA was 3.8%, while 90.3% of all infants had positive blood CMV-IgM alone and 5.9% had positive blood/urine CMV-DNA alone. A total of 197 infants were treated with ganciclovir, and the cure rate was 88.3%. An abnormal history of pregnancy (OR=6.191, 95% CI: 1.597-24.002) and liver involvement before medication (OR=3.705, 95% CI: 1.537-8.931) were the independent risk factors affecting the therapeutic effect of ganciclovir in infants with perinatal CMV infection. The epidemiological characteristics of perinatal CMV infection have remained generally stable for the last 5 years. CMV often involves several organs or systems, especially the liver and lung. Ganciclovir has a significant efficacy in the treatment of perinatal CMV infection, and an abnormal history of pregnancy and liver involvement before medication can increase the risk of ganciclovir resistance in infants with perinatal CMV infection.

Cytomegalovirus hepatitis in 49 pediatric patients with normal immunity.

Cytomegalovirus (CMV) hepatitis is generally asymptomatic or rarely can lead to severe complications in immunocompetent hosts. This study aims to evaluate CMV hepatitis in immunocompetent young children, which is discussed relatively rarely in the literature. A retrospective review of 49 pediatric patients with CMV hepatitis from January 2005 to December 2010 was performed. The median age of the patients was 5.81 ± 6.49 months and 57.1% were female. Complaints were prolonged jaundice, vomiting, diarrhea, and abdominal distension. Seventeen patients (34.6%) had congenital or probable congenital CMV infection, while 32/49 (65.3%) had perinatal CMV infection. CMV hepatitis was accompanied by other system findings in 22 patients (44.9%), and only liver involvement was present in 27/49 (55.1%). Alanine aminotransferase and aspartate aminotransferase were elevated together in all patients. Cholestatic hepatitis was present in 13 patients (26.5%). Four patients (8.16%) were treated with ganciclovir. Complete improvement of hepatitis occurred in 48/49 (97.95%). The recovery time of liver function tests was 7-180 days (mean: 53.92 ± 40.8). CMV hepatitis is usually mild and has a good outcome in immunocompetent individuals. However, cases should be carefully evaluated due to the important role of CMV in the etiology of infantile and neonatal hepatitis.

Cytomegalovirus-associated colitis with colonic stricture mimicking necrotizing enterocolitis in a newborn: a case report

Necrotizing enterocolitis is the most common gastrointestinal emergency in neonatal period. The etiology is considered multifactorial. Risk factors include prematurity, enteral feeding, hypoxia, and bacterial colonization. The etiologic role of viruses is unclear. Although cytomegalovirus (CMV) is a common congenital infection in neonates, most patients are asymptomatic. Gastrointestinal manifestation is unusual. In this report, we described a newborn with perinatal CMV infection presenting with symptoms mimicking necrotizing enterocolitis.

Perinatal Cytomegalovirus Infections: Epidemiology, Prevention, and Treatment

Mother-to-child transmission of cytomegalovirus (CMV) can lead to severe birth defects and neurologic impairment of infants. Congenital CMV is the most common congenital infection and the leading infectious cause of infant hearing loss and neurologic deficits, complicating up to 2% of all pregnancies globally. Although antiviral treatment of congenitally CMV-infected infants can ameliorate CMV-associated hearing loss and developmental delay, interventions that can effectively prevent congenital CMV infection and the associated neurologic impairments are still being evaluated. Moreover, an effective CMV vaccine to protect mothers against CMV acquisition during pregnancy is urgently needed to reduce the sizeable health and economic burden of this disease. Active and passive maternal and infant immunization strategies to prevent symptomatic perinatal CMV infection are a critical need in pediatric health.

Cytomegalovirus-associated colitis mimicking necrotizing enterocolitis – A near miss diagnosis of neonatal colonic stricture

Abstract Although cytomegalovirus (CMV) is a common congenital infection in neonates, most patients are asymptomatic. Gastrointestinal manifestation is unusual. In this report, we described a newborn with perinatal CMV infection presented with symptoms mimicking necrotizing enterocolitis. We hope to alert clinicians about this possible diagnosis when managing newborn gastrointestinal diseases.

Bronchiolitis obliterans caused by CMV in a previously healthy Asian infant

Cytomegalovirus (CMV) is currently the most common cause of congenital infection and the leading infectious cause of brain damage and hearing loss in children. Perinatal CMV infection rarely causes clinical manifestations in normal individuals and usually follows a benign course in immunocompetent infants. However, ~15-25% of infected preterm infants may develop pneumonia, hepatitis or sepsis-like illness, bradycardia, hepatosplenomegaly, distended bowel, anemia, or thrombocytopenia. Bronchiolitis obliterans (BO) is a rare, fibrosing form of chronic obstructive lung disease that follows severe insults to the lower respiratory tract and results in narrowing and/or complete obliteration of the small airways. In non-transplant children, the most common form of BO is a severe lower respiratory tract infection, especially of adenovirus. We experienced a case of a 37-day-old male who was diagnosed as BO on chest computed tomography (CT) after CMV pneumonia. To our best knowledge, this is the first case of BO caused by CMV pneumonia in a healthy infant.

Detection and gB genotyping of CMV in Mexican preterm infants in the context of maternal seropositivity.

Congenital (CI) and perinatal cytomegalovirus (CMV) infections (PI) can be linked to maternal CMV seropositivity, with fatal consequences in preterm newborns. GB genotyping has been used to analyze genotypic similarity in mothers and infants. The frequency of CMV infection in the context of maternal seropositivity and the viral gB genotypes as well as the genotypic similarity in mothers and preterm infants were investigated. Saliva samples and dry blood spots (DBS) were taken weekly from preterm newborns from birth until the first month of life, and breast milk samples were taken from their mothers weekly during the first month of lactation. CMV IgG seroprevalence of the mothers and CI or PI in the infants were established. The gB status and genotypic similarities were established retrospectively in DBS and in the breast milk samples. In total, 387 neonates and 375 mothers were enrolled. The maternal CMV-positive IgG serology was 97.3% (365/375). Neonatal CMV was found in 5.1% (20/387) of newborns, and one infant presented with CMV-compatible symptoms. CI was 2.5% and PI in the first month after birth was 11.8%. GB2 was the most prevalent genotype and was also the genotype preferentially transmitted to newborns by mothers with mixed infections. CMV PI and CI in preterm infants from highly seropositive mothers was high, but the rate of symptomatic infection was low. The prevalent genotype was gB2, and this genotype was preferentially transmitted to newborns by mothers with mixed infections.

Recurrent lymphadenopathy in children with Kikuchi-Fujimoto disease

Kikuchi-Fujimoto disease (KFD) is characterized by self-limiting regional lymphadenopathy with prolonged fever. Although the reported recurrence rate of KFD is known to be 3-4%, this rate appears to be higher in our clinical experience, and rates up to 38.5% have been previously reported. In this retrospective study, we reviewed medical records of children with pathologically confirmed KFD to investigate the factors associated with recurrent KFD. Enrolled children were divided into two groups according to the recurrence of KFD, and clinical and laboratory factors were compared between the two groups. The recurrence of KFD was determined based not on repeated pathologic confirmation but on the presence of clinical febrile lymphadenopathy. A total of 33 children with KFD, 26 boys (78.8%) and 7 girls (21.2%), with a median age of 12years (9months to 19years), were enrolled. Thirty-one children (93.9%) complained of fever, and most of the children (90.9%) complained of cervical lymphadenopathy. Neutropenia (<1,500/μL) or lymphopenia (<1,500/μL) was observed in 51.5%. Lactate dehydrogenase level, erythrocyte sedimentation rate, and C-reactive protein level were elevated in 90.9, 96.9, and 54.5% of children, respectively. Fourteen children (42.4%) experienced recurrent KFD, including ten children after biopsy and four children before and after biopsy. In a multivariate analysis, a past history of other systemic illnesses (p = 0.013) and a higher absolute lymphocyte count (p = 0.023) were significantly associated with recurrent KFD. These systemic illnesses were chronic idiopathic thrombocytopenic purpura, autoimmune thyroiditis, nephrotic syndrome, perinatal cytomegalovirus infection, and hemophagocytic lymphohistiocytosis. Our results suggest that recurrent KFD is more frequent than reported, and recurrent KFD should be considered in children with a history of other systemic illnesses such as immune disorders.

Cytomegalovirus-specific T-cell reactivity in biliary atresia at the time of diagnosis is associated with deficits in regulatory T cells

Biliary atresia (BA) is a progressive, inflammatory cholangiopathy that culminates in fibrosis of extrahepatic and intrahepatic bile ducts. A leading theory on the pathogenesis of BA is that the bile duct damage is initiated by a virus infection, followed by a bile duct-targeted autoimmune response. One mechanism of autoimmunity entails a diminished number or function of regulatory T cells (Tregs). The aim of this study was to identify potential virus-specific liver T cells from infants with BA at the time of diagnosis, implicating the virus involved in early bile duct damage. A subaim was to determine if the presence of virus infection was associated with quantitative changes in Tregs. Liver T cells from BA and control patients were cultured with antigen-presenting cells in the presence of a variety of viral or control proteins. 56% of BA patients had significant increases in interferon-gamma-producing liver T cells in response to cytomegalovirus (CMV), compared with minimal BA responses to other viruses or the control group CMV response. In addition, a positive correlation between BA plasma CMV immunoglobulin M (IgM) and liver T-cell CMV reactivity was identified. Investigation of peripheral blood Tregs revealed significant deficits in Treg frequencies in BA compared with controls, with marked deficits in those BA patients who were positive for CMV. Liver T-cell responses to CMV were identified in the majority of BA patients at diagnosis, suggesting perinatal CMV infection as a plausible initiator of bile duct damage. Deficiency of Tregs in BA implies decreased inhibition of inflammation and autoreactivity, potentially allowing for exaggerated bile duct injury.

598: Diagnosis of perinatal cytomegalovirus infection via serial daily rapid urine viral culture

598: Diagnosis of perinatal cytomegalovirus infection via serial daily rapid urine viral culture

The prevalence of congenital and perinatal cytomegalovirus infections among newborns of seropositive mothers

This study aimed to determine the prevalence of congenital and perinatal human cytomegalovirus (HCMV) infections among newborns in two major neonatal intensive care units (NICU) in Bahrain. One hundred newborns comprised of 84 preterm and 16 term babies admitted to the NICUs were enrolled in the study. During the first six weeks of life, urine and saliva was obtained from the babies weekly and serial breast milk samples were obtained from the mothers. Maternal serum HCMV IgG was measured. Virus isolation and detection was done by shell vial culture and nested PCR. Maternal HCMV IgG-seropositivity was 100%. Eight HCMV infections were detected comprising of three congenital and five perinatal infections. Congenital HCMV infection was found in preterm (2/84; 1.9%) and term (1/16; 6.3%) babies. HCMV DNA was detected in breast milk samples obtained during the first 10 days postpartum from all mothers whose babies had congenital HCMV. Forty-nine women provided breast milk samples between four and six weeks post-partum and HCMV DNA was detected in the breast milk of 11 women. Five (45.5%) of these eleven were mothers of babies with perinatal HCMV infection. There was no significant difference in the detection of HCMV using shell vial culture versus nested PCR method. The findings indicate occurrence of congenital and perinatal HCMV transmission in this setting of high maternal seropositivity. The use of shell vial culture and PCR amplification for HCMV screening in the NICU for rapid detection of infection during the early postnatal period is recommended.