Cytomegalovirus Infection In Children Research Articles

The clinical and laboratory algorithm for the diagnosis of acute cytomegalovirus infection in children

The aim. of the study is to optimize the Iaboratory diagnosis of cytomegaIovirus infection in chiIdren by finding cIinicaI and Iaboratory predictors corresponding to the acute stage of infection. MateriaIs and methods . The resuIts of 65 chiIdren age from 1 to 3 years outpatient of with cytomegaIovirus mono-nucIeosis are presented. Markers of herpes virus infections (CMV, EBV, HHV-6 type) were determined by PCR-reaI time (bIood, saIiva) and seroIogicaIIy (IgM, IgG). ResuIts. It has been estabIished. that acute cytomegaIovirus infection can occur both, in the form of infectious mononu-cIeosis and. be atypicaI accompanied, by proIonged fever and. severe Iymphadenopathy in most cases. Indirect Iaboratory markers of acute cytomegaIovirus infection are neutropenia and. hypoimmunogIobuIinemia IgA and. IgG. Acute cytomeg-aIovirus infection is accompanied by the virus shedding in both bIood and saIiva in aImost aII patients and the median vaIues of the viraI Ioad are different: 3,9 Ig DNA copies / mI for bIood, 4,9 Ig DNA copies / ml for saIiva. Using mathemati-caI modeIing, the “cut off" vaIue of viraI Ioad. for saIiva was determined, to be 4,1 Ig DNA copies / mI corresponding to 65.0% of the probabiIity of deveIoping acute CMV infection. ConcIusion. The study made it possibIe to substantiate the aIgorithm. for diagnosing acute cytomegaIovirus infection. in young chiIdren which. incIudes the most significant cIinicaI Iaboratory predictors, as weII as the caIcuIated. “cut off" vaIue of viraI Ioad. for saIiva equaI to 4,1 Ig DNA copies / mI. Determining the viraI Ioad in the saIiva of patients can be used, as an additionaI diagnostic criterion for the atypicaI form of acute cytomegaIovirus infection.

Organization of breastfeeding in neonatal intensive care units: discussion issues

научный биометрический журнал, который знакомит читателя с клиническими рекомендациями и особенностями применения лекарственных и вакцинных средств у детей, предоставляет исчерпывающую информацию о воздействии лекарственных средств на плод, о проводимых в

Challenges and Clinical Implications of the Diagnosis of Cytomegalovirus Lung Infection in Children.

Pulmonary cytomegalovirus (CMV) infection is a potential lethal disease in children, but it remains a diagnostic challenge. The differentiation between latent CMV infections with viral shedding and active infections is difficult and may lead to false positives in bronchoalvolar lavage (BAL) PCR detection. This review summarizes current diagnostic approaches for CMV lung infection in children including progress in the identification of underlying immune defects linked to this condition. There is increasing literature supporting that the combined assessment of host risk factors and lung disease pattern is essential for the diagnosis of pulmonary CMV infection in children. The most important host risk factor is an immunecompromised state that has expanded from primary or acquired immunodeficiency (e.g., HIV) to include a myriad of immune-dysregulation syndromes (e.g., CTLA4, PIK3 defects). Newborns, paricularly those born premature, are also a high-risk group. At the pulmonary level, active CMV infection is typically characterized by alveolar compromise leading to hypoxemia, ground-glass opacities, and intra-alveolar infiltrates with CMV inclusions in lung biopsy. The identification of active CMV lung infection should trigger additional evaluation of immune defects (primary or secondary) impairing T and NK cell function or innate antiviral responses as well as other immune dysregulation disorders. Lung CMV infections in children are more prevalent in immunocompromised hosts and premature newborns. Lung CMV infections should prompt further investigation into conditions altering immune mechanisms usually in place to contain CMV infections. Common clinical and radiological patterns such as hypoxemia and ground-glass pulmonary opacities may allow early identification and treatment of CMV lung infection and underlying causes in the pediatric population.

Cytomegalovirus infection and congenital heart disease in children

Congenital heart defects account for about 30% of all anomaly of development in children. Cytomegalovirus infection suffered by a woman during pregnancy claims one of the leading places among teratogenic factors.Aim: to study clinical and pathogenetic features of congenital heart diseases in children with active cytomegalovirus infection.Materials and methods: the survey included 240 children with congenital heart defects under 1 years old. The diagnosis was verified by enzyme immunoassay with detection of immunoglobulins of classes M and G to cytomegalovirus and by polymerase chain reaction, the material for which was blood and urine.Results. For congenital heart defects with the active forms of cytomegalovirus infection is characterized by a higher frequency of combined defects and the development of critical states. Children with cytomegalovirus infection in 40% suffered intrauterine myocarditis of cytomegalovirus etiology, which weighed the course of the underlying disease. The features characteristic of IUI was determined much more often (in the analysis of the noncardiac symptoms). Specific therapy of active forms of cytomegalovirus infection in children before surgery for correction of congenital heart defects has reduced the likelihood of postoperative complications.Summary. Cytomegalovirus infection has a direct teratogenic effect and can provoke the development of congenital heart defects. In addition, the virus has a cardiotropic and immune-mediated effect on the myocardium. This leads to the development of intrauterine myocarditis, which aggravates the course of the disease. The specific treatment of active forms of cytomegalovirus infection in children before surgery for the correction of congenital heart defects, reduces the likelihood of postoperative complications.

Frequency of cytomegalovirus infection in children with Nephrotic Syndrome

Frequency of cytomegalovirus infection in children with Nephrotic Syndrome

Results of catamnestic observation of cytomegalovirus infection in children

Aim. To study the characteristic features of cytomegalovirus excretion into the blood, saliva and urine of children aged 1-3 years with different forms of infectious process.
 Materials and methods. There were analyzed the results of observation of 65 children aged 1-3 years with acute cytomegalovirus infection, who received ambulatory treatment and were observed in catamnesis of 6 months. Cytomegalovirus infection markers were determined in blood, saliva and urine serologically (IgM, IgG) and using the method of quantitative PCR.
 Results. The maximum quantity of virus was found to be determined during the acute form of cytomegalovirus infection in the saliva, exceeding the value of 6.0 lg of CMV DNA copies/ml (median 4.9 lg of CMV DNA copies/ml). In the blood and urine of patients with the acute form of infection, the quantity of virus is within low and mean values of viral load (3.4 lg of CMV DNA copies/ml and 3.85 lg of CMV DNA copies/ml). Six month after the acute form of infection, no CMV DNA was determined in the blood, it decreased to 2.8 lg of CMV DNA copies/ml in the saliva and to 3.0 lg of CMV DNA copies/ml in the urine.
 Conclusions. Thus, the amount of cytomegalovirus DNA in the biological media of the body such as blood, saliva and urine is maximal during the acute form of disease that can be used as a diagnostic method.

Study of Incidence of Congenital Rubella and cytomegalo virus infections in Children’s, Attending in Tertiary care Hospital at New Delhi

Study of Incidence of Congenital Rubella and cytomegalo virus infections in Children’s, Attending in Tertiary care Hospital at New Delhi

Factors associated with cytomegalovirus infection in children undergoing allogeneic hematopoietic stem-cell transplantation.

While preemptive therapy with ganciclovir (GCV) for cytomegalovirus (CMV) infection is used following allogeneic hematopoietic stem-cell transplantation (HSCT), risk factors for CMV infection in children undergoing HSCT are poorly understood.We studied CMV reactivation following allogeneic HSCT by retrospectively analyzing pediatric patients who received allogeneic HSCT and preemptive GCV therapy between 1998 and 2016. The level of viremia requiring preemptive GCV therapy was >1 CMV antigen-positive cells per 5 × 105 leukocytes during the antigenemia assay era and >1000 copies/mL in the polymerase chain reaction era. Among 290 at-risk patients, 54 (18.6%) patients had primary CMV infection or CMV reactivation occurring at a median of 76 days (range, 7–234) following HSCT. CMV reactivation occurred in 28.2% (44/156) of CMV-seropositive transplant recipients at a median of 26 days posttransplant.Univariate and multivariate analyses revealed statistically significant relationships between CMV infection and grade III–IV acute graft-vs-host disease, seronegative donor/seropositive recipient combination, and unrelated/mismatched donors. The remaining demographic factors were not predictive of CMV infection.The seronegative donor/seropositive recipient combination for HSCT was associated with an incomplete response to antiviral therapy. Human leukocyte antigen identical donors were the best choice for patients undergoing allogeneic HSCT to reduce the incidence of CMV disease and mortality.

Early childhood CMV infection may decelerate the progression to clinical type 1 diabetes.

Evidence of the role of cytomegalovirus (CMV) infection in the pathogenesis of type 1 diabetes (T1D) has remained inconclusive. Our aim was to elucidate the possible role of CMV infection in the initiation of islet autoimmunity and in the progression to clinical T1D among children with human leukocyte antigen (HLA)-conferred T1D risk. A total of 1402 children from the prospective Type 1 Diabetes Prediction and Prevention (DIPP) study were analyzed for CMV-specific IgG antibodies during early childhood. All the children carried HLA-DQ genotypes associated with increased risk for T1D. The effect of CMV infection on the appearance of T1D-associated autoantibodies (insulin autoantibodies [IAA], glutamic acid decarboxylase [GADA], and insulinoma antigen-2 [IA-2A], n = 356) and on the progression rate to clinical T1D (n = 233) were analyzed with Kaplan-Meier survival analysis and Log-rank test. Early childhood CMV infection was inversely associated with the development of T1D during childhood. Cumulative progression to T1D was decreased in subjects with an early CMV infection (P = 0.035). In further analyses, the effect of early CMV infection on the initiation of islet autoimmunity and progression to clinical T1D were examined separately. Interestingly, early CMV infection did not affect the appearance of T1D-associated autoantibodies but a decelerating effect was observed on the progression rate from islet autoimmunity to clinical T1D (P = 0.015). Our results suggest that an early childhood CMV infection may decelerate the progression from islet autoimmunity to clinical T1D among at-risk children and may thus protect these children from progressing to T1D during childhood.

Cytomegalovirus infection in day care centres: A systematic review and meta-analysis of prevalence of infection in children.

Maternofetal transmission of cytomegalovirus (CMV) is the most common infectious cause of congenital malformation in developed countries. Maternal infection often results from close contact with infected children, and this may occur in day care centres (DCCs). A systematic review of observational studies was conducted to examine the prevalence of CMV infection among children attending DCCs. Meta-analysis using the random effect model was performed for studies including controls. Sources included PubMed, EMBASE (until August 2018), and references from identified publications. Inclusion criteria were studies reporting CMV infection prevalence among childcare children aged less than 7years of age. Controls were children without childcare exposure. CMV infection was defined as viral excretion detected by culture, polymerase chain reaction, or CMV seropositivity. Twenty-eight publications including 8347 participants met the eligibility criteria. The pooled prevalence of CMV infection among children in childcare from all studies was 32% (95% CI 23-41). Within case-controlled studies, prevalence among children attending DCCs was 34% (95% CI 25-44), whereas prevalence among those without childcare exposure was 22% (95% CI 15-30). Meta-analysis showed a significant association between DCC attendance and CMV infection (odds ratio 2.69, 95% CI 1.68-4.30; heterogeneity χ2 /df=8; I2 =84%, P<0.00001). Attendance at DCCs is significantly associated with increased risk of childhood CMV infection. Prevention strategies to reduce risk of CMV infection of pregnant women and children should involve review of DCC exposure and consideration of preventative hygiene strategies.

Detection of Cytomegalovirus in Liver Tissue by Polymerase Chain Reaction in Infants With Neonatal Cholestasis.

Cytomegalovirus (CMV) is associated with neonatal cholestasis (NC). Diagnosis of CMV infection is most often based on either positive blood CMV IgM or CMV blood polymerase chain reaction (PCR). Isolation of CMV in liver tissues in patients with NC has rarely been reported. This study was undertaken to see if CMV is present in liver tissues of patients with NC and evaluate the correlation between positive CMV PCR in liver tissue with the serology and blood PCR. This study was conducted in 31 infants with NC from June 2015 to December 2016. All patients underwent blood CMV IgM, blood CMV PCR and liver CMV PCR. Prevalence of CMV in NC based on positive liver CMV PCR was calculated. Sensitivity and specificity of the serologic markers and blood CMV PCR to identify CMV infection in the liver was determined. CMV IgM was positive in 13 (42%) patients, CMV IgG was positive in 26 (84%) patients and blood CMV PCR was positive in 23 (74%) patients. Liver CMV PCR was positive in 16 (52%) patients. Fifteen (48%) patients had biliary atresia (BA), 10 (32%) patients had neonatal hepatitis, 5 (16%) had paucity of bile ducts and 1 (3%) had ascending cholangitis. Of the 16 patients with positive liver CMV PCR, 8 (50%) had BA, 4 (25%) had neonatal hepatitis, 3 (19%) had paucity of bile ducts and 1 (6%) had ascending cholangitis. Sensitivity of blood CMV IgM in relation to liver CMV PCR was 69% and specificity was 61%. Sensitivity of blood CMV PCR was 61% and specificity was 71% when compared with liver CMV PCR. CMV is present in the liver tissues of more than half the patients with NC. Serology or blood CMV PCR is apparently not an accurate marker of CMV in the liver tissue. Also, CMV infection in children seems to be associated equally with BA or non-BA neonatal hepatitis.

Иммунопатогенетические аспекты неспецифических сиалоаденитов, ассоциированных с цитомегаловирусной инфекцией у детей

Иммунопатогенетические аспекты неспецифических сиалоаденитов, ассоциированных с цитомегаловирусной инфекцией у детей

Епштейн–Барр і цитомегаловірусна інфекція у дітей

Епштейн–Барр і цитомегаловірусна інфекція у дітей

Congenital Cytomegalovirus Infection in Children with Autism Spectrum Disorder: Systematic Review and Meta-Analysis.

Association of congenital cytomegalovirus (CMV) infection with autism spectral disorder (ASD) has been suggested since 1980s. Despite the observed association, its role as a risk factor for ASD remains to be defined. In the present review, we systematically evaluated the available evidence associating congenital CMV infection with ASD using PubMed, Web of Science, Cochrane Library, and Embase databases. Any studies on children with CMV infection and ASD were evaluated for eligibility and three observational studies were included in meta-analysis. Although a high prevalence of congenital CMV infection in ASD cases (OR 11.31, 95% CI 3.07-41.66) was indicated, too few events (0-2 events) in all included studies imposed serious limitations. There is urgent need for further studies to clarify this issue.

Real - Time Polymerase Chain Reaction Compared to Nested Polymerase Chain Reaction and Enzyme - Linked Immunosorbant Assays for Detecting Cytomegalovirus Infection in Children

Background: Patients with impaired immunity e.g. (use of immunosuppressant therapy, or chemotherapy) are at increased risk of Cytomegalovirus (CMV) infection. Diagnosis of this viral infection is faced with many difficulties in such patients. Objectives: This study aims to compare between ELISA, nested PCR, and real-time PCR in order to set up a highly sensitive applicable assay for detecting CMV in high risk children. Methodology: This study was conducted from September 2015 to May 2016. Two ml blood sample were collected from each of 366 children with suspected CMV infection. CMV specific IgM and IgG were determined in the sera using ELISA. CMV DNA was detected in the plasma using nested PCR. Quantitative real-time PCR was used to determine the viral load. Results: The highest prevalence (50%) of CMV IgM seropositivity was reported from patients suffering from fever of unknown origin. Using the molecular methods, CMV was detected only in patients suffering from malignant hematological disease and receiving chemotherapy, where 83.7% and 67.4% of patients with malignant hematological disease were positive for CMV by real-time and nested PCR respectively. In comparison to real time PCR, nested PCR was 80.5% sensitive and 100% specific; ELISA IgM was 22.2% sensitive and 84.24% specific, where ELISA IgG was 0% sensitive and 71.82% specific for the detection of CMV infection in high risk children. Conclusion: PCR is more sensitive and specific technique for detection of CMV infection in high risk children. Moreover, quantitative real-time PCR is superior to nested PCR as it can define threshold levels needed to guide treatment

Late cytomegalovirus infection in children: High incidence of allograft rejection and hepatitis in donor negative and seropositive liver transplant recipients.

The complications and outcome associated with late CMV infection and disease on the graft are poorly characterized in PLT recipients. We studied the overall incidence, risk factors, and outcome of late CMV infection and disease (infection 6months after transplant) in 180 PLT recipients admitted between 2008 and 2011 at the King's College Hospital. Antiviral prophylaxis of intravenous ganciclovir was given only to the D+R- group starting at day 7 post-transplant. The remaining groups (D-R+, D+R+, and D-R-) received pre-emptive therapy when they have CMV viremia above cut-off value and treatment for symptomatic CMV infection. The overall incidence of late CMV infection and disease was 9.4% (19/180) and 14.5% (19/130) in D+R-, D-R+, D+R- groups. The D-R+ group had the highest incidence of hepatitis (37.5%) and significantly increased incidence of CMV disease, and single and multiple acute rejection episodes when compared to the D+R- group, which received prophylaxis. The late CMV infection and disease in pediatric LT recipients was comparable to adult LT recipients despite variable duration of antiviral prophylaxis. Our results show that D-R+group had highest rate of hepatitis and rejection episodes, associated with high morbidity, and should be considered for antiviral prophylaxis.

The role of immunoglobulin prophylaxis for prevention of cytomegalovirus infection in pediatric hematopoietic stem cell transplantation recipients.

Following cessation of intravenous immunoglobulin (IVIg) administration for allogeneic hematopoietic stem cell transplantation (HSCT) recipients at our unit, we observed a sharp decline in the incidence of cytomegalovirus (CMV) infection. We conducted a retrospective study of the role of IVIg in the prevention of CMV infection in children and young adults who underwent HSCT from matched related donor. We included 109 patients (IVIg+/IVIg- ratio 82/27). Median age was 8.5 years. Patients were transplanted for malignant (59.7%) and nonmalignant diseases (40.3%) with myeloablative, reduced-intensity, and nonmyeloablative conditioning in 76, 22, and 2% of the transplants, respectively. Graft sources were peripheral blood stem cells, bone marrow, and cord blood in 58.7, 39.4, and 2%, respectively. The cumulative incidence of CMV infection at 1 year after HSCT was significantly higher in the cohort that did not receive IVIg compared with the one that did (44.4% vs. 13.4%, respectively, P = 0.001). Significant risk factor for CMV infection in the cohort not receiving IVIg was conditioning with total body irradiation (TBI) (87.5% in TBI+ vs. 26.3% in TBI-, P = 0.003). We conclude that children and young adults who undergo HSCT with TBI may need a preemptive regimen of anti-CMV treatment, if they do not get IVIg prophylaxis.

Association of TLR3 L412F Polymorphism with Cytomegalovirus Infection in Children.

Intracellular Toll-like receptor 3 (TLR3) recognizes viral double-stranded RNA (dsRNA) and activates antiviral immune responses through the production of type I interferons (IFNs) and inflammatory cytokines. This receptor binds to dsRNA molecules produced during human cytomegalovirus (HCMV) replication. TLR7 senses viral single-stranded RNA (ssRNA) in endosomes, and it can interact with endogenous RNAs. We determined the genotype distribution of single-nucleotide polymorphisms (SNPs) within the TLR3 and TLR7 genes in children with HCMV infection and the relationship between TLR polymorphisms and viral infection. We genotyped 59 children with symptomatic HCMV infection and 78 healthy individuals for SNPs in the TLR3 (rs3775290, c.1377C>T, F459F; rs3775291, c.1234C>T, L412F; rs3775296, c.-7C>A) and TLR7 (rs179008, c.32A>T, Q11L; rs5741880, c.3+1716G>T) genes. SNP genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and capillary electrophoresis. The HCMV DNA load was quantified by real-time PCR. We found an increased frequency of the heterozygous genotype TLR3 L412F in children with HCMV infection compared with uninfected cases. In individuals with a mutation present in at least one allele of the L412F SNP, an increased risk of HCMV disease was found, and this result remained highly significant after Bonferroni’s correction for multiple testing (Pc < 0.001). The heterozygous genotype of this SNP was associated with the increased risk of HCMV disease in an adjusted model that included the HCMV DNA copy number in whole blood and urine (P < 0.001 and P = 0.008, respectively). Moreover, those with a heterozygous genotype of rs3775296 showed an increased relative risk of HCMV infection (P = 0.042), but this association did not reach statistical significance after correction for multiple testing. In contrast, the rs3775290 SNP of TLR3 and TLR7 SNPs were not related to viral infection. A moderate linkage disequilibrium (LD) was observed between the SNPs rs3775291 and rs3775296 (r2 = 0.514). We suggest that the L412F polymorphism in the TLR3 gene could be a genetic risk factor for the development of HCMV disease.

Characteristics and prognosis of hepatic cytomegalovirus infection in children: 10 years of experience at a university hospital in Korea.

PurposeStudies on cytomegalovirus (CMV) infections in immunocompetent children are lacking, and minimal information is available in the medical literature on hepatic manifestations and complications of CMV. The aims of this study were to evaluate the clinical characteristics, laboratory data, and prognosis of children with CMV hepatitis, and to investigate its prevalence at a single medical center in Korea over a 10-year period.MethodsOne hundred thirty-two children diagnosed with CMV infection based on specific markers (anti-CMV IgM, CMV polymerase chain reaction in blood and urine, or CMV culture of urine) were included in the study. Clinical and biochemical characteristics, immunological markers, and outcomes of hepatic CMV infection were determined.ResultsThe median age of patients (n=132) was 8.5 months (range, 14 days–11.3 years). Peak total bilirubin and alanine aminotransferase levels in serum ranged from 0.11–21.97 mg/dL, and 5–1,517 IU/L, respectively. Alanine aminotransferase remained elevated from 2–48 weeks. Jaundice was the most common clinical feature of hepatic CMV infection during infancy. The hematologic findings revealed anemia, leukocytosis, and monocytosis in CMV-infected patients. All participants recovered without administration of ganciclovir.ConclusionIn children with CMV hepatitis, fever was the most common symptom at presentation, and jaundice was the most common clinical feature of hepatic CMV infection in infants younger than 3 months of age. Hepatic CMV infection in immunocompetent children is often a self-limited illness that does not require antiviral therapy, as most patients in this study had favorable outcomes.

Childhood Cytomegalovirus Infection: Case Series and Literature Review

Introduction and objectives: Early life Cytomegalovirus infection is an under-recognized disease. Infection can present as congenital, perinatal or acquired forms. Though mostly asymptomatic, it can lead to fatal complications. Case presentation: The clinical presentations of four Ethiopian children with acute Cytomegalovirus infections are reviewed. Three had neonatal disease while one had an acquired infection. Two of the neonatal infections involved preterm deliveries while all three presented with persistent direct hyperbilirubinemia. Serologic tests were used to diagnose their infections. Discussion: Childhood Cytomegalovirus infections involve multiple organs. Viral DNA detection and serologic tests are utilized to diagnose infection at different ages of childhood. Treatment was provided to one of our patients based on existing recommendations while the other three did not receive anti-viral drugs. Conclusions: Early diagnosis and management of pediatric Cytomegalovirus infections will prevent long-term hearing and neurologic disabilities.