Acquired Cytomegalovirus Infection Research Articles

Handling of human milk to prevent acquired cytomegalovirus infection in Japanese neonatal intensive care units: The first nationwide survey.

Human milk (HM) has been proven to provide immunological and nutritional advantages to neonates; however, acquired cytomegalovirus (CMV) infection can be associated with raw HM. In Japan, there are no standardized guidelines concerning HM handling. This cross-sectional survey was performed to reveal specific trends in HM handling in neonatal intensive care units (NICUs) in Japan. A questionnaire was sent to 255 NICUs participating in the Japanese Neonatologist Association in May 2020. It involved HM handling practices, such as maternal screening, pasteurization, storage, and the workforce. Of 255 NICUs, 174 (67.8%) responded to the survey. Maternal CMV screening was carried out in 37 units (22.2%), and CMV inactivation in HM was performed in 44 units (26.5%). For CMV inactivation, a freeze-thawing method was employed in about 90% of units. In 70% of units providing CMV inactivation, CMV inactivation was conducted regardless of bodyweight and corrected gestational age of infants until the infants' discharge. Acquired CMV infection in preterm neonates was observed in 43 units (25.7%) in the survey period. A wide range of HM handling practices are used in Japanese NICUs. A national guideline for handling HM in NICUs should be created to promote the infection control of CMV.

Effectiveness and safety of prenatal valacyclovir for congenital cytomegalovirus infection: systematic review and meta-analysis.

Universal screening for cytomegalovirus (CMV) infection in pregnancy is not recommended in most countries. One of the major deterrents is the lack of effective prenatal therapy. The role of valacyclovir therapy in reducing the risk of vertical transmission, symptomatic congenital CMV infection and adverse outcome is controversial. The main aim of this systematic review and meta-analysis was to investigate the safety and effectiveness of prenatal valacyclovir therapy in pregnancies with maternal CMV infection. MEDLINE, EMBASE and Cochrane databases and ClinicalTrials.gov were searched. The inclusion criteria were pregnancy with confirmed maternal CMV infection, treated or untreated with valacyclovir. The primary outcome was the incidence of congenital CMV infection confirmed by a positive CMV polymerase chain reaction result of the amniotic fluid. The secondary outcomes were symptomatic and asymptomatic infection, perinatal death, termination of pregnancy, anomalies detected on follow-up ultrasound, on fetal magnetic resonance imaging or at birth, severe and mild-to-moderate symptoms due to congenital CMV infection, neurological, visual and hearing symptoms, and adverse events related to valacyclovir. Risk of bias was assessed using the revised Cochrane risk-of-bias tool for randomized trials (RoB 2) or Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool, as appropriate. Head-to-head meta-analyses were used to compare the risk of each of the explored outcomes according to whether pregnancies with maternal CMV infection were treated with prenatal valacyclovir therapy. Eight studies (620 women) were included. Pregnancies treated with valacyclovir had a significantly lower risk of congenital CMV infection compared with those not receiving valacyclovir (three studies; 325 fetuses; pooled odds ratio (OR), 0.37 (95% CI, 0.21-0.64); I2 = 0%; P < 0.001). When stratifying the analysis according to gestational age at maternal infection, the risk of vertical transmission was significantly lower in pregnancies receiving valacyclovir following first-trimester maternal infection (three studies; 184 fetuses; pooled OR, 0.34 (95% CI, 0.15-0.74); I2 = 20.9%; P = 0.001), while there was no significant difference between the two groups in those acquiring CMV infection in the periconceptional period or in the third trimester of pregnancy. Only one study reported on the risk of vertical transmission in women infected in the second trimester, demonstrating a lower risk of congenital infection in women taking valacyclovir, although this was based on a small number of cases. Pregnancies treated with valacyclovir therapy had an increased likelihood of asymptomatic congenital CMV infection compared with those not receiving valacyclovir (two studies; 132 fetuses; pooled OR, 2.98 (95% CI, 1.18-7.55); I2 = 0%; P = 0.021), while there was no significant difference between the two groups in the risk of perinatal death (P = 0.923), termination of pregnancy (P = 0.089), anomalies detected at follow-up imaging assessment during pregnancy or at birth (P = 0.934) and symptoms due to CMV infection in the newborn (P = 0.092). The occurrence of all adverse events in pregnant individuals taking valacyclovir was 3.17% (95% CI, 1.24-5.93%) (six studies; 210 women), with 1.71% (95% CI, 0.41-3.39%) experiencing acute renal failure, which resolved after discontinuation of the drug. On GRADE assessment, the quality of evidence showing that valacyclovir reduced the risk of congenital CMV infection and adverse perinatal outcome was very low. Prenatal valacyclovir administration in pregnancies with maternal CMV infection reduces the risk of congenital CMV infection. Further evidence is needed to elucidate whether valacyclovir can affect the course of infection in the fetus and the risk of symptomatic fetal or neonatal infection. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Effects of Perinatally Acquired Cytomegalovirus Infection on Growth Hormone Axis

Cytomegalovirus (CMV) is one of the most common causes of perinatally acquired infection worldwide. It affects almost every organ system with varied type of clinical manifestation. In this case series, effect of perinatally acquired cytomegalovirus infection was studied on relatively unexplored area i.e, on growth hormone axis. Effect of standard antiviral treatment was also studied in these children. Five children were diagnosed to have perinatally acquired cytomegalovirus infection and it was found that all of these children were suffering from growth hormone deficiency (as evidenced by low insulin-like growth factor 1 and insulin-like growth factor binding protein 3 level as well). Some of the children were also found to have other endocrine manifestations like hypothyroidism and hypoglycaemia. They were treated with intravenous Ganciclovir followed by oral Valganciclovir and most of them responded well.

A Case of Erythema Multiforme Associated with Acute Acquired Cytomegalovirus Infection

Erythema multiforme (EM) is an acute self-limiting disease that is characterized by target-like lesions and may exhibit cutaneous and mucosal involvement. It is known to be caused most commonly by infections, although several factors have been impeached for etiology. In this manuscript, a case of EM caused by cytomegalovirus (CMV) infection, which is a rare agent in etiology, is reported. In the literature, immunocompetent children with CMV infection are known to not admit commonly with cutaneous symptoms. Pediatric CMV infection usually is asymptomatic, although it may also lead to different clinical manifestations. CMV infection should be considered in determining the etiology of EM.

Correlation between serum IgM antibody and viral load with clinical symptoms in neonates infected with cytomegalovirus

To investigate the correlation between serum cytomegalovirus (CMV) IgM antibody/viral load and infection-related clinical symptoms in neonates infected with CMV, and provide basis for clinical assessment and monitoring of neonatal CMV infection. A total of 70 neonates with CMV infection admitted to neonatology in Women's Hospital, School of Medicine Zhejiang University, from January 2014 to December 2020 were included in this study. Using real-time quantitative PCR as the diagnostic criteria, congenital cytomegalovirus-infected neonates (n=29) was diagnosed within the first 3 weeks of life, otherwise, it was postnatally acquired cytomegalovirus infection (n=41). The differences in general information and clinical indicators between IgM antibody positive and negative patients were analyzed, combined with the PCR result, the correlation between the IgM/viral load and the occurrence of symptoms were analyzed. T-test and non-parametric test were used to compare the differences of indicators between groups, logistic regression was used for multivariate analysis, and ROC curve was used to evaluate the auxiliary diagnostic value of relevant indicators. In the congenital CMV infection group and the postnatally acquired CMV infection group, viral load and the proportion of symptomatic patients in IgM positive group were significantly higher than IgM negative group (Z=-2.616, P=0.008; 80% vs. 21%, P=0.005) (Z=-2.405, P=0.016; 56% vs. 19%, P=0.025). Logistic regression analysis of the included population showed the risk factors of CMV infection-related symptoms were IgM positive (OR 4.562, 95%CI:1.461-14.246,P=0.009) and viral load (OR 1.728, 95%CI:1.068-2.798,P=0.026). Regressive analysis for single symptom with correction showed IgM antibody positive was associated with hearing dysfunction(OR 3.954, 95%CI:1.066-14.677,P=0.040),the CMV viral load was associated with thrombocytopenia (OR 2.228, 95%CI:1.124-4.413,P=0.022), and brain imaging abnormalities (OR 3.956, 95%CI:1.421-11.011, P=0.008). Receiver operating characteristic (ROC) analysis showed the area under ROC curve of CMV viral load for brain imaging abnormalities was 0.883 (P<0.001), with a sensitivity of 75.0% and specificity of 90.3%. For neonates infected with CMV, the risk of infection-related clinical symptoms and hearing dysfunction may be increased when IgM antibody was positive. Meanwhile, the higher the CMV viral load at diagnosis, the higher the risk of thrombocytopenia and abnormal brain imaging.

Maternal-Fetal Infections (Cytomegalovirus, Toxoplasma, Syphilis): Short-Term and Long-Term Neurodevelopmental Outcomes in Children Infected and Uninfected at Birth.

(1) Background: Infections in pregnancy can lead to miscarriage, premature birth, infections in newborns, and developmental disabilities in babies. Infected infants, symptomatic at birth, can have long-term sequelae, and asymptomatic babies are also at increased risk of developing long-term sensorineural outcomes. Targeted therapy of the pregnant mother can reduce fetal and neonatal harm. (2) Aim of the study: To explore the association between symptoms and time of onset of long-term sequelae in infected children born from mothers who contracted an infection during pregnancy, by a long-term multidisciplinary follow-up. (3) Methods: For up to 2-4 years, we evaluated cognitive, motor, audiological, visual, and language outcomes in infants with symptomatic and asymptomatic congenital infections and in uninfected infants. (4) Results: 186 infants born from women who acquired Cytomegalovirus infection (n = 103), Toxoplasma infection (n = 50), and Syphilis (n = 33) during pregnancy were observed. Among them, 119 infants acquired the infection in utero. Infected infants, symptomatic at birth, obtained lower scores on the Cognitive and Motor Scale on Bayley-III compared to asymptomatic and uninfected infants (p = 0.026; p = 0.049). Many severe or moderate sequelae rose up within the first year of life. At 24 months, we observed sequelae in 24.6% (14/57) of infected children classified as asymptomatic at birth, compared to 68.6% (24/35) of symptomatic ones (χ2 = 15.56; p &lt; 0.001); (5) Conclusions: Infected babies symptomatic at birth have a worse prognosis than asymptomatic ones. Long-term sequelae may occur in infected children asymptomatic at birth after the first year of life. Multidisciplinary follow-up until 4-6 years of age should be performed in all infected children, regardless of the presence of symptoms at birth.

Identification of the causative mutation in the ITGB2 gene in a LAD1 patient by whole exome sequencing

Leukocyte adhesion deficiency type 1 (LAD1) is a rare congenital immunodeficiency disease. The cause of disease is determined to be the mutations in the ITGB2 gene that codes for CD18, the beta chain of beta-2 integrins, leads to decreased expression or functioning of CD18. This deficiency leads to severe impairment of leukocyte adhesion to the vascular wall and leukocyte migration to sites of infection and inflammation. LAD1 has also been associated with inhibition of interleukin-23 and interleukin-17 resulting in a hyperinflammatory and chronic inflammation. Patients with LAD1 typically present in early infancy with recurrent, life threatening infections that are frequently fatal before 2 years of age without hematopoietic stem cell transplant (HSCT). However, LAD1 is difficult to diagnose and many LAD1 patients die at a young age despite intensive antibiotic therapy. Accurate diagnosis requires detailed clinical information (delayed umbilical cord loss, severe periodontitis, delayed wound healing and sores, skin abscesses, and recurrent infection), and confirmation the absence of integrins by flow cytometric analysis. A better understanding of the molecular characteristics of this disease is needed to raise awareness and definitive diagnosis infants with LAD1. To definitive diagnosis, whole exome sequencing and Sanger sequencing were performed in an eighteen-month-old boy with severe leukocytosis, recurrent infections, delayed wound healing, and hepatosplenomegaly associated with an acquired cytomegalovirus infection. Two variants: One previously reported mutation (c.533C&gt;T, p.Pro178Leu) and one novel variant (c.59-1G&gt;A), in the ITGB2 gene were detected. These results can be used for definitive genetic diagnosis, genetic counseling, as well as a prenatal diagnosis in LAD1 patients.

Cytomegalovirus acquisition in infancy and the risk of tuberculosis disease in childhood: a longitudinal birth cohort study in Cape Town, South Africa

SummaryBackgroundThe risk of tuberculosis disease after recent exposure is greatest before age 5 years; however, the mechanisms explaining this increased risk are not well elucidated. Acquisition of viral infections, such as cytomegalovirus, in early life might modulate the immune system. We aimed to evaluate the acquisition of cytomegalovirus infection in infancy and the development of tuberculosis disease in children.MethodsIn this prospective, birth cohort study we enrolled pregnant women who were between 20 and 28 weeks of gestation attending antenatal care in Paarl, a periurban setting outside of Cape Town, South Africa. Participants were recruited from two clinics (TC Newman and Mbekweni). Infants were given Bacillus Calmette–Guérin vaccination at birth as per national policy. Nasopharyngeal swabs for cytomegalovirus detection using qPCR were done for infants at birth, age 3 and 6 weeks, and age 3, 6, 12, and 24 months. Children were prospectively followed up for tuberculosis disease until age 9 years using tuberculin skin testing, radiographic examinations, GeneXpert, and sputum testing. Tuberculin skin tests were done at the 6-month visit and then at age 12, 24, 36, 48, and 60 months, and at the time of lower respiratory tract infection. We compared tuberculosis disease incidence after age 1 year or after age 6 months in children with and without cytomegalovirus infection using Cox regression and hazard ratios (HRs) with 95% CIs.FindingsBetween March 5, 2012, and March 31, 2015, 1225 pregnant women were recruited and enrolled in the birth cohort. 88 (7%) women were excluded because of loss to antenatal follow-up or pregnancy losses. Of 1143 livebirths, 68 (6%) mother–infant pairs were excluded. In total, 963 children were serially tested for cytomegalovirus (7186 cytomegalovirus measurements taken; median six tests per child, IQR 2–11). The prevalence of congenital cytomegalovirus at age younger than 3 weeks was 2% (18 of 816). Cytomegalovirus positivity increased continuously with age from 3% (27 of 825) by age 6 weeks to 21% (183 of 882) by 3 months, 35% (315 of 909) by 6 months, and 42% (390 of 933) by 12 months. Mother–infant pairs were followed up for a median of 6·9 years (IQR 6·0–7·8). The risk of tuberculosis disease in children after age 1 year was higher in those with cytomegalovirus infection by age 6 weeks (adjusted HR 4·1, 95% CI 1·2–13·8; p=0·022), 3 months (2·8, 1·4–5·8; p=0·0040), 6 months (3·6, 1·7–7·3; p<0·0001), 12 months (3·2, 1·6–6·4; p=0·0010), and 24 months (4·2, 2·0–8·8; p<0·0001). The risk of microbiologically confirmed tuberculosis disease was also higher among children acquiring cytomegalovirus infection before age 3 months (adjusted HR 3·2, 95% CI 1·0–10·6; p=0·048), 6 months (3·9, 1·2–13·0; p=0·027), 12 months (4·4, 1·2–16·3; p=0·027), and 24 months (6·1, 1·3–27·9; p=0·020). In children older than 1 year, the risk of tuberculosis disease was consistently greater in those with high cytomegalovirus loads than in those with low cytomegalovirus loads that were acquired before age 3 months (adjusted HR 2·0 vs 3·7; ptrend=0·0020; both groups compared with cytomegalovirus negative reference) and before age 12 months (2·7 vs 3·7; ptrend=0·0009).InterpretationInfants that acquire cytomegalovirus in the first year of life are at high risk of subsequently developing tuberculosis disease. Efforts to prevent tuberculosis in early childhood in high-burden countries might need to deter or delay acquisition of cytomegalovirus perinatally or in the first months of life.FundingBill & Melinda Gates Foundation, MRC South Africa, National Research Foundation South Africa, and Wellcome Trust.

Epidemiology of cytomegalovirus infection in pregnancy in Israel: Real-world data from a large healthcare organization.

Congenital cytomegalovirus infection (cCMVi) is the leading cause of nonhereditary sensorineural hearing loss among newborns. Women newly acquiring cytomegalovirus infection (CMVi) during pregnancy have the highest risk of vertical transmission. This study aimed to describe the epidemiology of CMVi in pregnancy in a large healthcare database. A retrospective cohort study was performed using the Maccabi Healthcare Services database (Israel). Women aged 18-44 years old on July 1, 2013 with no record of pregnancy in the prior 6 months were followed through December 31, 2017 for first pregnancy occurrence. Pregnancy outcomes (live birth, spontaneous/therapeutic abortions, stillbirth, and uncertain outcomes) were captured. CMV test results were obtained to assess serostatus at the start of pregnancy (SoP) and primary CMV infection (CMVi) during pregnancy. Associations of demographic and reproductive factors with pCMVi were investigated (multivariable logistic regression). The study included 84 699 pregnant women (median age = 31 years; interquartile range = 28-35). Live birth, fetal loss, and uncertain pregnancy outcomes accounted for 76.8%, 18.2%, and 5.0%, respectively. The seroprevalence of CMV at the start of pregnancy in this cohort was 63.4% (95% confidence interval [CI]: 63.1-63.7). Among seronegative women with available test results (n = 10 657), CMVi incidence was 14.5 per 1000 (95% CI = 12.2-16.7). In multivariate logistic regression models adjusting for maternal age, CMVi was significantly associated with having one or more prior live births (odds ratio [OR]: 3.8 [95% CI: 2.6-5.4]) and having a child less than 6 years of age (OR: 4.3 [95%CI: 3.0-6.1]). One in three pregnant women in Israel is at risk for primary CMVi. This study demonstrates that real-world electronic healthcare data can be leveraged to support clinical management and development of interventions for congenital CMV by identifying women at high risk for CMVi during pregnancy.

Acute Febrile Illness as a Manifestation of Cytomegalovirus Infection in Extremely Low-Birth Weight Babies—A Case Series

Cytomegalovirus (CMV) infection in extremely low-birth weight infants (ELBW) is associated with significant morbidity and mortality. Our case series elaborates the profile and outcomes of 5 ELBW neonates with likely postnatal CMV infection. All babies were on mothers’ own milk and had a history of receiving leuko-reduced packed red blood cells. The mean age at diagnosis was 64 days. Hepatosplenomegaly was present in 4 cases. Along with other features warranting testing for CMV, unusually all the 5 neonates had fever spikes at the time of deterioration. Three cases had thrombocytopenia. Atypical clinical feature in the form of papular lesions, which healed with hyperpigmentation, was noted in a neonate. The fever subsided after starting treatment with valganciclovir. All babies developed bronchopulmonary dysplasia requiring prolonged respiratory support. Two babies expired. Duration of treatment with valganciclovir ranged from 6 weeks to 6 months. Survivors were developmentally normal on follow-up with normal hearing and ophthalmic examination. Febrile spikes with worsening of pre-existing morbidities could be an important clue to acquired CMV infection.

Cytomegalovirus-Associated Autoantibody against TAF9 Protein in Patients with Systemic Lupus Erythematosus

Background: Evidence indicates a causal link between cytomegalovirus (CMV) infection and the triggering of systemic lupus erythematosus (SLE). Animal studies have revealed that CMV phosphoprotein 65 (pp65) induces autoantibodies against nuclear materials and causes the autoantibody attack of glomeruli. IgG eluted from the glomeruli of CMVpp65-peptide-immunized mice exhibited cross-reactivity against dsDNA and TATA-box-binding protein associated factor 9 (TAF9). Whether the elevation of anti-TAF9 IgG is associated with anti-CMV reactivity in human lupus remains unclear. Methods: The sera from patients with rheumatic diseases, including ankylosing spondylitis (AS), gout, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Sjögren syndrome (SS) were examined using ELISA for antibodies of CMV, CMVpp65, and TAF9. Results: In total, 83.8% of the rheumatic patients had acquired CMV infections. The SLE patients had a high prevalence of anti-CMV IgM. The highest seropositivity rates for anti-HCMVpp65 and anti-TAF9 IgG were observed in the SLE patients. Purified anti-CMVpp65 IgG from CMVpp65/TAF9 dual-positive SLE sera reacted to both TAF9 and dsDNA. An increased prevalence of proteinuria and low hemoglobin levels were found in CMV IgG- and CMVpp65 IgG-positive SLE patients. Conclusions: This observation suggests that immunity to CMVpp65 is associated with cross-reactivity with TAF9 and dsDNA and that it is involved in the development of clinical manifestations in SLE.

Literature Review and an Italian Hospital Experience about Post-Natal CMV Infection Acquired by Breast-Feeding in Very Low and/or Extremely Low Birth Weight Infants

Breastfeeding is recommended for all neonates due to a known variety of beneficial effects, but infants can be infected by cell-associated bacteria and viruses from breast milk, such as cytomegalovirus (CMV). The majority of CMV-seropositive breastfeeding women have a viral, self-restricted reactivation, can shed the virus in the milk for about 12 weeks after delivery, and can transmit the infection to their offspring. Post-natal CMV-infected term infants are mainly asymptomatic, while very low birth weight (VLBW, <1500 g) and extremely low birth weight (ELBW, <1000 g) infants may present with severe disease, short-term sequelae ranging from abnormalities in laboratory indexes to sepsis-like syndrome, and long-term sequelae such as developmental problems. Thus, the use of thermally treated maternal milk for VLBW/ELBW infants may be indicated to prevent/reduce the risk of CMV transmission. Different techniques, with varying efficacy in eradicating CMV and maintaining the activity of biological compounds in milk are available: long/short pasteurization, freeze-thawing, the use of microwaves, and ultraviolet-C irradiation. In our NICU, the use of maternal raw milk is always strongly recommended for term/preterm infants, but to reduce risk of CMV transmission, freeze-thawing mother’s own milk is used in neonates with GA ≤ 30 weeks or/and weight ≤ 1000 g, usually regardless of serological maternal condition, as CMV screening is not routinely offered to pregnant women and the milk of seroimmune mothers is not evaluated for CMV reactivation, as its rate is similar to seroprevalence. Over the last 4 years, we had 10 VLBW/ELBW newborns in our NICU with late-onset sepsis and negative cultures. In these cases, the research of CMV DNA in neonatal urine or saliva, for the diagnosis of post-natal symptomatic infection (once congenital transmission has been excluded) may be useful and not invasive. The take-home message we would like to share is that acquired CMV infection should be considered in VLBW/ELBW infants breastfed by seropositive mothers and presenting severe symptoms—particularly sepsis with negative cultures. This could allow pediatricians to make better-quality diagnoses, perform supportive therapy, provide antiviral treatment if needed, or establish a “pre-emptive” therapy for these high-risk neonates.

Incidence of Postnatal CMV Infection among Breastfed Preterm Infants: a Systematic Review and Meta-analysis.

BackgroundWe performed a systematic review and meta-analysis to evaluate the incidence of breast milk-acquired cytomegalovirus (CMV) infection in preterm infants born to CMV-seropositive mothers.MethodsPubMed, Embase, and Cochrane Library databases were searched using the terms: (“breast feeding” or “breast milk” or “human milk” or “breast”) and (“HCMV” or “cytomegalovirus”) and (“infant, extremely premature” or “premature birth” or “newborn” or “neonate” or “low birth weight” or “very low birth weight” or “premature” or “preterm infant”). Studies that had information on CMV status and breast feeding were included in the meta-analysis.ResultsA total of 2,502 newborns from 19 studies were included in this meta-analysis. The rate of postnatally acquired CMV infection among breastfed infants with CMV-seropositive mothers was 16.5% (95% confidence interval [CI], 0.10–0.26; P < 0.001). The infection rate was 26% with fresh breast milk, 8% with a combined diet of fresh and freeze–thawed breast milk, and 11% with freeze–thawed breast milk. Among cases where the CMV status of breast milk was determined, CMV shedding into breast milk occurred in 80.5% (95% CI, 0.71–0.87; P < 0.001) of CMV seropositive mothers. The breast milk-acquired CMV infection rate among infants fed CMV-positive breast milk was 20.7% (95% CI, 0.14–0.30; P < 0.001).ConclusionThis meta-analysis examined the rate of breast milk-acquired CMV infections in preterm infants with CMV-seropositive mothers; the CMV infection rate was higher in preterm infants fed fresh breast milk. Until further data are available, we cautiously suggest the use of freeze–thawed breast milk, rather than fresh breast milk, for preterm infants or very low birth weight infants.

Clinical Features, Treatment Courses, and Distribution of Cytomegalovirus Genotypes among Thrombocytopenia Patients Aged Younger than 12 Months.

The aims of this study were to evaluate the clinical characteristics, laboratory data, and treatment of the cytomegalovirus (CMV)-associated thrombocytopenia in infants aged younger than 12 months and to investigate the possible relationship between genotypes of glycoprotein B (gB) and glycoprotein H (gH) and CMV-associated thrombocytopenia. Infants with positive identification of cytomegalovirus (CMV) and thrombocytopenia, being treated at Hubei Maternal and Child Health Hospital from January 2015 to June 2019 were included. Genotype of gB and gH analysis were done by nested polymerase chain reaction (nPCR) and restrictions length polymorphism. The prevalence of CMV congenital, perinatal, and postnatal infection were 1.4% (76/5428), 29.1% (378/1301), and 41.8% (243/581), respectively. A total of 29 immunocompetent patients with CMV-associated thrombocytopenia were analyzed, including 7 (9.2%, 7/76) congenital infections, 14 (3.7%, 14/378) perinatal infections, and 8 (3.3%, 8/243) postnatal infections. Platelet count at diagnosis <20 × 109/L was the common hematologic finding of CMV-associated thrombocytopenia in perinatal infection (1/7 congenital infection vs. 10/14 perinatal infection vs. 3/8 postnatal infection, Chi-square (χ2) = 6.616, p = 0.037). Notably, significantly higher frequency of hepatobiliary symptoms was found in congenital and perinatal infections groups (4/7 congenital infection vs. 10/14 perinatal infection vs. 1/8 postnatal infection, χ2 = 7.188, p = 0.027). Intravenous immunoglobulin was prescribed for 24 (82.8%, 24/29) patients, and antiviral agents were prescribed for 9 (31.0%, 9/29) patients. The most prevalent genotypes of CMV in the study were gB1 (60.7%, 17/28) and gH2 (57.1%, 16/28). There was a substantial percentage of symptomatic CMV infection in patients aged younger than 12 months. Thrombocytopenia is one of the common clinical manifestations in congenital CMV infection. The gB1 genotype had more virulence in infants with acquired CMV infection. There might be an association between gH2 genotype of CMV and CMV-associated thrombocytopenia.

Curative effect of rat nerve growth factor combined with early rehabilitation intervention in the treatment of hearing injury caused by cytomegalovirus infection

Objective To explore the effect of rat nerve growth factor combined with early rehabilitation intervention in the treatment of hearing injury caused by cytomegalovirus (CMV) infection. Methods 106 cases of hearing impairment caused by cytomegalovirus infection diagnosed in our hospital from January 2012 to February 2018 were randomly divided into observation group and control group, 53 cases in each group. The control group were treated only with ganciclovir and comprehensive rehabilitation therapy, while the treatment group was treated with nerve growth factor on the basis of the control group. Before and after treatment, the children in both groups underwent multi-frequency steady-state evoked potential test, cytomegalovirus antibody DNA fluorescence quantification, and their mothers underwent cytomegalovirus antibody test. The total effective rate of the two groups and the effective rate of the observation group with different degrees of hearing impairment were compared, and the therapeutic effect of the observation group with congenital and acquired CMV infection was compared. Results The total effective rate was 80.7% in the observation group, which was higher than 65.9% in the control group (P<0.05). The effective rate of mild to moderate hearing loss in observation group was higher than that in severe hearing impairment (P<0.05). The efficacy of the rat nerve growth factor in the treatment of hearing loss after CMV infection was higher than that of hearing loss caused by congenital cytomegalovirus infection (P<0.05). Conclusions Rat nerve growth factor combined with early comprehensive rehabilitation intervention is an effective method to treat acoustic nerve injury caused by CMV infection. The effect of rat nerve growth factor on mild and moderate hearing impairment was better than that of severe hearing impairment. The therapeutic effect of acquired CMV infection on hearing damage was better than that of by congenital infection. Key words: Nerve growth factor; Rehabilitation; Cytomegalovirus infections; Hearing disorders

Detection of leukocyte adhesion deficiency type 1 in an infant by high-throughput targeted exome sequencing

Leukocyte adhesion deficiency type 1 (LAD-I) characterized by immune-deficiency and leukocytosis is rare in infant patients. A 43-day-old boy with severe leukocytosis, recurrent infections, defective wound healing and hepatosplenomegaly associated with an acquired cytomegalovirus infection. To establish the diagnosis definitively, a high-throughput targeted exome sequencing was performed, which yielded the diagnosis of LAD-I. A homozygous mutation in integrin subunit beta 2 (ITGB2), c.817G>A (p.G273R) was identified. Though LAD-I has been thoroughly-studied, with more than 300 detailed cases and 96 mutations in ITGB2, establishing a definitive diagnosis of LAD-I in infancy is challenging because of the lack of typical clinical presentations. Better understanding the molecular characterization of this disease is necessary to increase awareness and identification of infants with LAD-I.

Detection of cytomegalovirus in saliva from infants undergoing sepsis evaluation in the neonatal intensive care unit: the VIRIoN-C study.

Objective To determine the frequency of detection of cytomegalovirus (CMV) among infants evaluated for late-onset sepsis in the neonatal intensive care unit (NICU). Methods This study was a prospective cohort study. Results During the 13-month study, 84 infants underwent 116 sepsis evaluations, and CMV DNA was detected in saliva in three (4%) infants (median: gestational age 28 weeks, birth weight 950 g), representing 5% (n=6) of all sepsis evaluations. One infant had CMV DNA detected in saliva in all four sepsis evaluations. Two infants had acquired CMV infection, while the timing of CMV acquisition could not be determined in one infant. Two of the three infants had concomitant Gram-negative bacteremia and urinary tract infections (UTIs), two developed severe bronchopulmonary dysplasia (BPD) and none died. Conclusion Detection of CMV DNA in saliva occurred in 4% of infants and 5% of sepsis evaluations. Persistence of CMV DNA shedding in saliva made attribution of clinical illness difficult to ascertain.

Pre-Transplant Cytomegalovirus Immunoglobulin G Antibody Levels Could Prevent Severe Cytomegalovirus Infections Post-Transplant in Liver Transplant Recipients: Experience from a Tertiary Care Liver Centre

Background: Humoral immune responses in cytomegalovirus (CMV) are not studied well. Pre-transplant CMV immunoglobulin G (IgG) antibody levels (Pre-Tx IgG) could influence the occurrence of post-transplant CMV infections. Objective: Correlation between pre-Tx IgG and post-Tx risk of acquiring CMV infection was investigated. Materials and Methods: A total of 146 liver Tx recipients, not on CMV prophylaxis, were included. Pre-Tx IgG in donor (D) and recipient (R) were estimated and all the recipients were followed up for 1 year for CMV infections. Results: D+ R+ serostatus was seen in 142 (97.3%) and D− R+ in 4 (2.7%). A total of 113 (77.4%) recipients had pre-Tx IgG of ≥250 AU/ml. Overall, post-Tx CMV infections were seen in 54 (36.9%) recipients. In 32 (59.2%) patients, CMV infection was seen during the 1st month after TX. Incidences of post-Tx CMV infection in recipients with pre-Tx IgG <250 AU/mL and ≥250 AU/mL were 42.4% and 34.5%, respectively (P = 0.99). Median viral load was significantly higher in patients with pre-Tx IgG <250 AU/ml: 4log10 (R: 2.8–6.6 log 10) copies/ml than those with ≥250 AU/ml: 2.2 log10 (R: 1.6–3.8 log10) copies/ml, P = 0.04. There was no difference in the time of occurrence of CMV infection in both the groups. Concurrent occurrence of rejection and CMV infection was seen in significantly more patients 18/54 (32.7%) than in patients without CMV infection (12/99, 12%, P = 0.002). Conclusions: Higher pre-Tx CMV IgG levels might prevent severe CMV infections post-Tx. Recipients with low pre-Tx CMV titre might be benefitted by CMV prophylaxis or aggressive pre-emptive treatment.

The Serological Evidence of Cytomegalovirus Infection as a Potent Aetiological Factor for Cleft Lip/Palate, Mental Retardation and Deafness.

Congenital Cytomegalovirus (CCMV) infection is estimated to occur in 0.5% to 2% of all deliveries across the world. According to the available literature about Human Cytomegalovirus (HCMV) infected children, 0.5% to 1% acquire Cytomegalovirus (CMV) in utero, 40% acquire the infection within the first decade of life, between 15% to 70% acquire CMV infection in group day care settings and continue to shed the virus for 6 to 48 months after primary infection. Although, 90% of the infected infants are clinically asymptomatic at birth, shreds of evidence show that these infants are at risk for audiological, neurological, and developmental sequelae. Despite this, HCMV still remains undetected due to silent or asymptomatic nature of the virus. The present study was aimed to test the hypothesis that HCMV can be a potential aetiologic factor in the development of cleft lip/palate, mental retardation and deafness. The study was carried out in a controlled setting under strict aseptic conditions. Blood samples were collected from 80 children, who were selected strictly adhering to the inclusion criteria and were divided into four groups containing 20 children each. Group 1: 20 children with cleft lip/palate, Group 2: 20 mentally retarded children, Group 3: 20 completely deaf children and Group 4: 20 normal Children (control). The samples were tested for HCMV-specific Immunoglobulin G (IgG) and Immunoglobulin M (IgM) antibodies by using solid phase enzyme-linked immunosorbent assay and the obtained data were analysed statistically using ANOVA and Post-Hoc Tukey's tests. In the study group (Group1, 2 and 3) children, the overall positivity for HCMV- specific IgG was 100% and 5% borderline to IgM antibodies whereas in the control group (Group 4) it was 80% negative to HCMV- specific IgG and 100% negative to IgM antibodies. From the observations noted in the present study, HCMV could be suggested as the potent aetiologic factor in the development of cleft lip/palate, mental retardation and deafness.

Cytomegalovirus and Epstein-Barr Virus Infections.

1. Swetha Pinninti, MD* 2. Catherine Hough-Telford, MD† 3. Sunil Pati, PhD† 4. Suresh Boppana, MD† 1. *Department of Pediatrics, University of Nebraska Medical Center/Children’s Hospital and Medical Center, Omaha, NE. 2. †Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL. 1. Although most infants with symptomatic congenital cytomegalovirus (cCMV) infection are at risk of developing sensorineural hearing loss, 10% to 15% of asymptomatic infants also develop hearing loss and require audiologic screening at regular intervals in the first few years after birth. 2. Unlike with other congenital infections, CMV seropositivity is not protective for fetal transmission. An estimated 75% of infants with cCMV are born in the United States following nonprimary maternal infections. 3. Most individuals with Epstein-Barr virus-associated infectious mononucleosis recover with supportive therapy; contrary to common belief, corticosteroid use is not the mainstay of treatment because airway compromise and splenic rupture can be rare complications. After completing this article, the reader should be able to: 1. Recognize routes of acquisition of cytomegalovirus (CMV) in the neonatal and postneonatal periods. 2. Recognize differences in presentations of congenital CMV infection, childhood infections, and infections in the immunocompromised individual. 3. Plan the diagnostic evaluation for congenital or acquired CMV infection in immunocompetent and immunocompromised children of various ages. 4. Understand management and long-term follow-up plans for infants with congenital CMV infection. 5. Describe the management and treatment of CMV infections in the immunocompromised host. 6. Explain the epidemiology of Epstein-Barr virus (EBV) infections and identify the clinical features associated with EBV infection in immunocompetent and immunocompromised children of various ages. 7. Recognize the potential complications of EBV infection in immunocompetent and immunocompromised children of various ages. 8. Plan management of children with uncomplicated infectious mononucleosis. Cytomegalovirus (CMV) is the most common cause of congenital infection and the leading nongenetic cause of sensorineural hearing loss (SNHL). CMV is also a significant cause of morbidity in preterm neonates who acquire infection postnatally …