Cytomegalovirus Infection In Children Research Articles

Letermovir at a Prophylactic Dose for Cytomegalovirus Infection in Children Undergoing Allogeneic Hematopoietic Stem Cell Transplantation: A Single-Center Retrospective Study in Japan.

Cytomegalovirus (CMV) infection is a major complication of hematopoietic stem cell transplantation (HSCT). Previous studies in adults demonstrated that letermovir prophylaxis for 100 d after HSCT reduces the occurrence of CMV infection; however, studies in children are limited. In this study, we aimed to examine the incidence of CMV infection in children who underwent allogeneic HSCT with prophylactic letermovir therapy. A single-center retrospective study was conducted among patients aged ≤17 who underwent allogeneic HSCT. We compared the cumulative incidence of CMV infection, mainly monitored by pp65-antigenemia, after HSCT between patients with and without letermovir prophylaxis (10-12 or 5-6 mg/kg/d when co-administered with cyclosporine) using Gray's test. We analyzed 79 patients with a median follow-up period of 126 d. The median age of these patients was 8.3 years (Interquartile range, 3.7-12.4). Prophylactic letermovir was used in 25 patients. Twenty-five patients developed CMV infection, and the cumulative incidence was 38.9% (95% confidence intervals, 25.0-52.5). The cumulative incidence of CMV infection was not significantly different between the letermovir and no-letermovir groups (33.1 vs. 36.6%, p = 0.228). Meanwhile, the cumulative incidence of CMV infection up to 100 d following HSCT was significantly lower in the letermovir group than in the no-letermovir group (8.0 vs. 32.8%, p = 0.026). Most patients experienced no noticeable adverse effects associated with letermovir; however, one patient discontinued letermovir because of nausea and anorexia. In conclusion, the results of this study suggest that letermovir prophylaxis against CMV infection may be effective in children without severe adverse effects.

Long-term outcomes of congenital cytomegalovirus infection in children early identified by extended hearing-targeted screening

ObjectivesCongenital Cytomegalovirus (cCMV) has been associated with hearing, vision, and neurodevelopmental long-term sequelae. Despite the social burden associated with the disease, a universally accepted consensus on screening, diagnostic, therapeutic and follow-up approaches has not been reached. The present observational retrospective study aims at describing long-term sequelae and radiological abnormalities associated with cCMV in children early identified by extended hearing-targeted screening and evaluated by audiological follow-up in a single III Level Audiological Referral Center for at least 2 years. MethodsAudiological neonatal and follow-up data were available for all subjects. Data collection included clinical neonatal and virological assessment at birth. Ophthalmological, neurodevelopmental and neuroradiological follow-up abnormalities compatible with cCMV sequelae were collected by clinical reports. Spearman's rank correlation coefficient (rho-ρ) was used to evaluate possible correlations among the considered parameters. Results61 newborns were identified by extended hearing-targeted cCMV screening and diagnosed mostly (83.6 %) by PCR viral DNA extraction in urine collected within the 15° day of life. Seventeen babies were born preterm, with a mean gestational age of 33.5 weeks. Sixteen patients (26.2 %) were admitted to an Intensive or sub-Intensive Neonatal Care Unit. At birth, 35 newborns were symptomatic (57.3 %), and 19 of them received antiviral treatment by valganciclovir or ganciclovir. Overall, 20 children (32.7 %) were diagnosed with sensorineural hearing loss (SNHL), among them 17 (85 %) were refer at the newborn hearing screening while 3 (15 %) were Pass. 5/20 children (25 %) presented isolated SNHL, while in 15/20 (75 %) children SNHL was associated to other long-term sequelae. In 5 patients (25 %) a progression of the hearing threshold was observed, with a mean age of progression of 26 months of age. Risk factors for progression were a worse final hearing threshold (Spearman's ρ = 0.434; p = 0.0001) and a worse hearing threshold at birth (Spearman's ρ = 0.298; p = 0.020). Thirteen children were fitted with hearing aids, 8 of whom subsequently underwent cochlear implantation. Concerning long term impairments, 10/61 children (17 %) presented a variety of ophthalmological sequelae, while 16/40 cCMV patients (40 %) were diagnosed with neurodevelopmental abnormalities. Language delays were significantly associated with a worse hearing threshold (ρ = 0.582; p = 0.0001) and with other neurocognitive abnormalities (ρ = 0.677, p = 0.0001). 30 children underwent radiological brain evaluation by Magnetic Resonance Imaging, and 63.3 % of them presented abnormalities compatible with cCMV. Mean viral load at birth did not show significant associations with long-term sequelae. ConclusionsThe study highlights the diverse and significant long-term sequelae of cCMV infection detected through early screening. With a significant proportion of cCMV children developing sensorineural hearing loss, ophthalmological and neurodevelopmental issues, the results emphasize the importance of continuous, multidisciplinary follow-up. Early identification and tailored interventions are crucial for improving the long-term health and quality of life of children affected by cCMV.

CMV hyperimmune globulin as salvage therapy for recurrent or refractory CMV infection in children undergoing hematopoietic stem cell transplantation.

Cytomegalovirus (CMV) is a major cause of allogeneic hematopoietic stem cell transplant (HSCT)-related morbidity and mortality. Treatment failure continues to be a major issue in patients with CMV infection due to both drug resistance and intolerance. This single-center brief retrospective analysis of a case series aims to investigate the safety and efficacy of CMV-hyperimmune globulin as salvage therapy for CMV infection in children undergoing HSCT. Fifteen pediatric patients received human CMV-specific immunoglobulin (CMVIG) between July 2018 and December 2021 as a salvage therapy for refractory or recurrent CMV infection. At the time of CMVIG prescription, eight children presented with recurrent CMV infection and seven with refractory CMV infection. The overall response rate was 67% at 50 days from the CMVIG administration [95% confidence interval (CI): 44-88]. Overall survival (OS) from CMVIG administration at 100 days was 87% (95% CI: 56-96), and OS from HSCT at 1 year was 80% (95% CI: 50-93). Four patients died, three unrelated to CMV infection and one due to CMV pneumonia. CMVIG as salvage therapy was well tolerated, and no infusion-related adverse events were observed.

A great pediatrician and scholar devoting his whole life to pediatric infectious and digestive diseases—In memoriam of Professor Yongsui Dong

A great pediatrician and scholar devoting his whole life to pediatric infectious and digestive diseases—In memoriam of Professor Yongsui Dong

Toxoplasmosis and cytomegalovirus infection and their role in Egyptian autistic children

Autism is a neurodevelopmental disorder with a significantly increased incidence rate across the world over the past few years. Toxoplasmosis and cytomegalovirus (CMV) infection are globally prevalent and have been associated with diverse neurological and psychiatric disorders. A few studies have demonstrated the role of toxoplasmosis and CMV as potential etiological factors for autism. Accordingly, this study was performed to estimate the relationship between toxoplasmosis and CMV infection in children with autism as well as to assess their impact on the Childhood Autism Rating Scale (CARS) score. A total of 45 autistic children (6 girls, 39 boys) and 45 (21 girls, 24 boys) healthy control children were enrolled in our study. Their blood samples were collected and tested for the presence of Toxoplasma and CMV (IgG and IgM) antibodies and DNA by ELISA and real-time PCR (RT-PCR), respectively. Toxoplasmosis was detected in 11 (24.4%) autistic children through the ELISA [10 (22.2%) IgG + /IgM − and 1 (2.2%) IgG + /IgM +]; however, RT-PCR assay recorded only 1 positive case (2.2%), while it was detected in 10 (22.2%) control children through ELISA [9 (20%) IgG + /IgM − and 1 (2.2%) IgG + /IgM +] and 1 (2.2%) by RT-PCR. On the other hand, CMV infection was detected in all autistic children with 44 (97.8%) testing positive by ELISA [24 (53.3%) IgG + /IgM − , 18 (40%) IgG + /IgM + and 2 (4.4%) IgG − /IgM +] and 25 (55.6%) testing positive by RT-PCR assay. In addition, ELISA assay recorded 43 (95.6%) [19 (42.2%) IgG + /IgM + and 22 (48.9%) IgG + /IgM − and 2 (4.4%) IgG-/IgM +] and RT-PCR recorded 21 (46.7%) positive samples in control children with CMV. No significant difference was noted between autistic and control children for the overall prevalence of Toxoplasma or/and CMV infection. Similarly, the CARS score indicated a non-significant difference with Toxoplasma or/and CMV infection. Our data does not show an association between autism and toxoplasmosis or/and CMV infection. Nevertheless, considering that autistic children are at a high risk of contracting these infections, further studies with a larger sample size are recommended.

Clinical and immunological criteria for prediction of thechronic course of cytomegalovirus infection on the background of hypoxic-ischemic damage of the central nervous system in children in the first year of life

Objective. To develop prognostic criteria for the chronic course of cytomegalovirus infection by studying disorders of the regulation of the immune response in children of the first year of life against the background of hypoxic-ischemic CNS damage.Materials and methods. 108 newborns with cytomegalovirus infection occurring against the background of perinatal hypoxicischemic lesions of the central unequal system were examined. All observed patients at 1 and 3 months of life conducted an immunological examination, including the determination of T and B-lymphocytes. Determination of the population and subpopulation composition of peripheral blood lymphocytes, activation markers was carried out by the method of one- and twoparameter phenotyping using reagents from Immunotex (France), FITC (fluorescein isothiocynate) — labeled with CD3+, CD4+, CD8+, CD20+ and PE (phycoerythrin) — labeled CD28+, CD40+. The results were recorded on a BECKMAN COULTER EPICSXL-II flow cytometer (USA) using standard protocols. The observation groups consisted of 78 children (72.2%) with an acute course of the disease (Group 1) and 30 children (27.3%) with a chronic course (Group 2).Results. Of the totality of the studied parameters of the cellular and humoral parts of the immune system, statistically significant for the prognosis of the chronic course of cytomegalovirus infection in children of the first year of life against the background of hypoxic-ischemic CNS damage were found: CD8, CD40, CD3+CD28+, CD20+CD40+. Using the PolyAnalist 3.5 Pro CNS package, systems of inequalities were obtained and a formula for predicting the chronic course of cytomegalovirus infection in children in the first year against the background of perinatal hypoxic-ischemic CNS damage was calculated.Conclusion. A statistically significant relationship was found between the prognosis of the chronic course of cytomegalovirus infection against the background of perinatal hypoxic-ischemic CNS damage and the level of CD20, CD4, costimulatory molecules CD3+CD28–, CD20+CD40+. The proposed diagnostic rules can be considered screening markers for the prognosis of the chronic course of cytomegalovirus infection against the background of perinatal hypoxic-ischemic CNS damage in newborns, which makes it possible to start specific therapy in a timely manner.

The Viral Load of Human Cytomegalovirus Infection in Children following Hematopoietic Stem Cell Transplant by Chip Digital PCR.

Objective To detect viral load in human cytomegalovirus (HCMV) infection children after hematopoietic stem cell transplant (HSCT) by chip digital PCR (cdPCR). Methods The plasmid pUC57-UL83 containing the HCMV-UL83 gene and HCMV AD169 strain were used to evaluate the sensitivity of cdPCR. Either HSV-1, HSV-2, VZV, EBV, HHV-6, or HHV-7 was used to evaluate the specificity of HCMV cdPCR. The cdPCR was compared with quantitative PCR (qPCR) by detecting HCMV infection in 125 children's whole blood samples following HSCT. Results The limit of detection (LOD) of HCMV cdPCR was 103 copies/ml and the qPCR LOD was 297 copies/ml for plasmid pUC57-UL83. The result of HCMV cdPCR was 146 copies/ml for the HCMV AD169 strain, indicating that the sensitivity of cdPCR was higher than that of qPCR. There is no cross-reaction between HCMV cdPCR and other herpes viruses. The incidence of HCMV infection was 30.40% in 125 children following HSCT by cdPCR. The range of the HCMV viral load was from 107 copies/ml to 6600 copies/ml by cdPCR. Conclusions cdPCR is more sensitive than qPCR for detecting HCMV viral load. Furthermore, the cdPCR could be used to detect the viral load of HCMV infection before or after HSCT in children.

Clinical and diagnostic significance of determining the cytokine status in infants with chronic cytomegalovirus infection against the background of hypoxic-ischemic CNS damage

Objective: based on the production of cytokines, to identify the immunological features of the chronic course of cytomegalovirus infection in children of the first year of life against the background of hypoxic-ischemic CNS damage.Research methods:108 newborns with cytomegalovirus infection occurring against the background of perinatal hypoxic-ischemic lesions of the central unequal system were examined. All observed patients immediately after the diagnosis of cytomegalovirus infection underwent an immunological examination, including the determination of the levels of interferon-alpha (IFN-α) and interferon-gamma (IFN-γ), the level of interleukins — 2 and 4 (IL -2 and IL-4) necrosis factor human alpha tumors (TNF-α in blood serum was determined by enzyme immunoassay using a set of reagents ProCon IF2 plus, ProCon Ifgamma, ProCon TNFα (Protein contour LLC, Russia, St. Petersburg). At 1 and 6 months of life .The observation groups consisted of 78 children (72.2%) with an acute course of the disease (Group 1) and 30 children (27.3%) with a chronic course (Group 2). The control group consisted of 15 newborns without herpes virus infection.Results. Of the totality of the studied cytokines, statistically significant for the chronic course of cytomegalovirus infection in children of the first year of life against the background of hypoxic-ischemic CNS damage were found: IL-2, IFN-γ. It was found that in children with a persistent low level of IFN-γ and an increased level of IL-4 in the blood serum at the age of 6 months, there was a chronic course of cytomegalovirus infection against the background of perinatal hypoxic-ischemic CNS damage.A decrease in IFN-γ production indicates a congenital or acquired deficiency of the interferon system and can be considered as an indication for long-term interferon replacement therapy.

S3634 Menetrier Disease: A Case Report

Introduction: Menetrier disease is a rare form of protein-losing gastropathy that is characterized by enlarged mucosal folds in the proximal part of the stomach. Although it is generally self-limited in children, adult patients are at increased risk of malignancies, thromboembolic phenomenon, and gastric outlet obstruction. Considering the high risk of morbidity and mortality, prompt diagnosis and management are needed. We present a rare case of Menetrier disease, occurring in a postpartum female patient. Case Description/Methods: A 25-year-old female patient presented with nausea and abdominal cramping, diarrhea and weight loss of 9 kg five weeks after delivering her 3rd child. These symptoms were followed by anasarca. Her laboratory tests showed hypoalbuminemia of 1.5 g/dl, low total protein level of 3.4 g/dl, elevated urine protein-to-creatinine ratio of 0.8, and elevated random urine protein of 16 mg/dl with otherwise normal labs (e.g., complete blood count, comprehensive metabolic panel). An esophagogastroduodenoscopy revealed markedly diffuse thick folds in the gastric fundus, body and antrum (Figure A). Antral mucosa and antral-fundic transition zone mucosa showed foveolar hyperplasia with negative Helicobacter pylori and cytomegalovirus (CMV) staining (Figure B). She was treated with IV antiemetics, IV albumin and furosemide and started on a pureed, high-protein diet which resulted in a significant improvement in her symptoms. Discussion: Although the pathophysiology of Menetrier disease is unclear, it has been associated with CMV infection in children and H. Pylori in adults. One hypothesis contributes the etiopathogenesis to an overexpression of the transforming growth factor-alpha. It commonly presents in male adult patients with epigastric pain, fatigue, weight loss, edema or/and vomiting. The diagnosis can be made based on histopathology showing extreme foveolar hyperplasia and atrophic changes in glandular epithelium. Moreover, endoscopy or barium study showing markedly enlarged gastric rugae along with laboratory findings of lymphopenia and reduced globulin, albumin, alpha-1-antitrypsin, cholesterol, ceruloplasmin and fibrinogen levels are indicative of this disease. Supportive treatment involves high-protein diet, proton pump inhibitors, and replacement of micronutrients. Treatment of H. pylori, CMV, and medications like octreotide or cetuximab showed improvement in disease progression in some patients.Figure 1.: Marked enlarged gastric rugae on endoscopy (A) and foveolar hyperplasia on biopsy (B).

Letermovir Prophylaxis for Cytomegalovirus Infection in Children After Hematopoietic Cell Transplantation

Cytomegalovirus (CMV) infection is one of the major causes of morbidity following hematopoietic cell transplantation (HCT). Allogeneic HCT (allo-HCT) recipients are at the highest risk of clinically significant CMV reactivation. While letermovir has been approved for prophylactic use in CMV seropositive adults, reports on pediatric data are very limited. The objective of the study was to examine the use of letermovir for prophylaxis from CMV infection in children undergoing allo-HCT in a single center. This retrospective matched-pair analysis study included 39 CMV-seropositive pediatric patients undergoing allo-HCT receiving letermovir as a primary prophylaxis for CMV infection on a compassionate-use basis (LMV group, n=13) or not (control group, n=26). There were no differences in basic characteristics between the analyzed groups. Among patients of the study group, 12 received primary prophylaxis with letermovir from day +1 after HCT. One patient, previously treated with ganciclovir received secondary prophylaxis from day +18. Prophylactic dose of letermovir was adjusted to cyclosporine co-administration, varied in between 120-480 mg, and given orally, once daily. No CMV reactivation was observed during administration of letermovir. Cumulative incidence of CMV reactivation was significantly higher for the control group not receiving prophylaxis. Of the 13 patients of the study group, three died; however, deaths were not attributable to CMV infection. We did not observe any toxicities related to letermovir. Our data support letermovir prophylaxis efficacy and safety in pediatric patients after allo-HCT. Compared with the historical group, prophylactic use of letermovir decreased the number of CMV reactivations in children.

Characteristics of antibody production to individual cytomegalovirus proteins in children with keratitis and uveitis

The clinical diagnosis of cytomegalovirus (CMV) eye pathology in children needs laboratory confirmation. The disadvantages of determining antibodies to CMV in serum in enzyme-linked immunosorbent assay (ELISA) include the presence of false positive and false negative results.
 AIM: To determine the features of the synthesis of antibodies to the proteins of the tegument pp65, pp150, pp28 and the DNA-binding protein pp52 of cytomegalovirus, as well as to compare the diagnostic effectiveness of two laboratory methods of serodiagnostics of CMVI in children with uveitis and keratitis of different genesis: enzyme immunoassay and linear immunolysis.
 MATERIAL AND METHODS: A total of 30 children (age 516 years) with uveitis (n=14) and keratitis (n=16) were included in the study. The IgM and IgG antibodies to the immediate early (IE) and late antigens of the virus (serological markers of primary, chronic, and reactivation of chronic infection) were determined in the ELISA. The IgG antibodies to individual recombinant CMV antigens containing only immunodominant protein fragments of viral antigens were studied in the line immunoassay (LIA): the main nonstructural IE protein, DNA-binding phosphoprotein p52, and phosphoproteins of the tegument p150, p65, and p28. The results of LIA were evaluated visually.
 RESULTS: CMV infection (CMVI) in children with uveitis in ELISA was almost 2 times higher than that with keratitis (10/14%71% vs. 6/16%37.5%, p 0.05). Of the four positive results for detection of antibodies to IE antigen in ELISA, one was confirmed in LIA. In general, the discrepancy between the results of the determination of IgG antibodies to IE antigen in ELISA and LIA was noted in 13% of serum samples. LIA showed the increased frequency (p 0.05) and intensity (p 0.05) of antibody formation to viral antigens p65 and p52 in uveitis compared with keratitis, which confirmed the important role of CMVI in the pathogenesis of uveitis.
 CONCLUSION: Both methods revealed a higher level of CMVI in children with uveitis than those with keratitis. IgG antibodies to IE-antigen serological markers of the reactivation of chronic CMVI have clinical importance because they serve as the basis for the appointment of antiviral therapy. Discrepancies between the results of ELISA and LIA in the detection of antibodies to IE antigen indicate the expediency of confirming the results of ELISA in LIA.
 Thus, laboratory examination of sera in ELISA with subsequent analysis of antibodies to individual recombinant CMV antigens in LIA is an effective, highly sensitive, and highly specific method to verify CMVI and determine its activity. The most informative action is the determination of IgG antibodies to recombinant CMV antigens: IE antigens, p65, and p52.

Cytomegalovirus infection in liver-transplanted children.

Cytomegalovirus (CMV) infection is a common complication of liver trans-plantation in children. The CMV serostatus of recipients and donors is the primary risk factor, and prophylaxis or pre-emptive strategies are recommended for high-risk patients. Graft rejection, coinfection and Epstein-Bar virus reactivation, which can lead to post-transplant lymphoproliferative disease, are indirect effects of CMV infection. Assessment of CMV infection viral load should be routinely performed upon clinical suspicion. However, tissue-invasive CMV disease is not associated with CMV viraemia and requires confirmation by tissue pathology. Oral valganciclovir and intravenous ganciclovir are equivalent treatments, and the duration of treatment depends on factors including CMV viral load, tissue pathology, and clinical response. Risk stratification by donor and recipient status prior to transplantation and post-transplantation antiviral prophylaxis or pre-emptive therapy are recommended. Adult guidelines have been established but additional study of the effectiveness of the preventive guidelines in children is needed. This review summarizes the burden, risk factors, clinical manifestations, laboratory evaluation, treatment, and prevention of CMV infection in children after liver transplantation.

Cytomegalovirus Infection in Infancy May Increase the Risk of Subsequent Epilepsy and Autism Spectrum Disorder in Childhood.

Cytomegalovirus (CMV) is a ubiquitous virus, and CMV-associated diseases range from mild illness in immunologically normal hosts to life-threatening diseases in newborns and immunocompromised children. This study investigated the association between childhood CMV infection and subsequent epilepsy or neurodevelopmental disorders, attention deficit hyperactivity disorder (ADHD), and autism spectrum disorder (ASD). A retrospective analysis was performed on data for 69 children with confirmed CMV infections (CMV infection group) and 292 patients with other infections (control group) between 1 January 2006 to 31 December 2012. The results indicated that the CMV infection group had a higher risk of epilepsy in comparison to the control (odds ratio (OR), 16.4; 95% CI (confidence interval), 3.32–80.7; p = 0.001). Epilepsy risk increased in younger children (age 0–2) with CMV infection when compared to the control group (OR, 32.6; 95% CI, 3.84–276; p = 0.001). The ASD risk was also determined to be higher in the CMV infection group (OR, 17.9; 95% CI, 1.96–162; p = 0.01). The ADHD risk between the groups was not significant. This study suggests that CMV infection in infancy may increase the risk of subsequent epilepsy and ASD, especially in infants younger than 2 years, but is not associated with ADHD.

Cytomegalovirus Infections in Children with Primary and Secondary Immune Deficiencies.

Cytomegalovirus (CMV) is a human herpes virus that causes significant morbidity and mortality in immunosuppressed children. CMV primary infection causes a clinically mild disease in healthy children, usually in early childhood; the virus then utilises several mechanisms to establish host latency, which allows for periodic reactivation, particularly when the host is immunocompromised. It is this reactivation that is responsible for the significant morbidity and mortality in immunocompromised children. We review CMV infection in the primary immunodeficient host, including early identification of these infants by newborn screening to allow for CMV infection prevention strategies. Furthermore, clinical CMV is discussed in the context of children treated with secondary immunodeficiency, particularly paediatric cancer patients and children undergoing haematopoietic stem cell transplant (HSCT). Treatments for CMV are highlighted and include CMV immunotherapy.

Цитомегаловірусна інфекція у дітей: труднощі діагностики

У статті проведено аналіз даних літератури, що стосується проблеми цитомегаловірусної інфекції у дітей. Узагальнюються сучасні уявлення про варіанти перебігу та форми цитомегаловірусної інфекції в різних вікових групах, а також ускладнення та наслідки хвороби. Розглядаються методи раціональної діагностики захворювання у дітей на сучасному етапі. У статті описані випадки цитомегаловірусної інфекції у дітей раннього віку, показані труднощі діагностики в практиці лікаря-педіатра в зв’язку з різноманіттям клінічних проявів хвороби, тяжкою фоновою патологією хворих.

The effect of cytomegalovirus on clinical and paraclinical as well as immune parameters of children with rotavirus infection

The aim is to evaluate the effect of cytomegalovirus on clinical and paraclinical as well as immunological parameters in children with rotavirus infection (RVI). Materials and methods. 50 children aged one to three years, patients with moderate and severe intestinal infections of rotavirus etiology were examined. All children were examined for herpes virus infections types 1, 2, 4, 5, 6. Enzyme-linked immunosorbent assay (ELISA) was used to determine the level of specific Ig G and Ig M for herpes viruses types 1, 2, 4, 5, 6, and in the case of a positive test, polymerase chain reaction (PCR) determined the presence of DNA (qualitatively) of these herpesviruses. Group 1 (mono-RVI), which was taken as a reference, included 33 children in whom no infection with any of these viruses of the herpes group was detected. Group 2 included 17 patients who underwent RVI on the background of CMV infection, the presence of infection with other viruses of the herpes group was excluded. Immune response parameters (CD 3+, CD 4+, CD 8+, CD 16+, CD 22+, Ig A, Ig M, Ig G, IL 1β, 4, TNF-α) in the acute period of the disease and in the period of convalescence were analyzed. Qualitative indicators were given in the form of absolute and relative (%) value. Significance of differences was determined using Pearson’s χ2 test (Pearson’s Chi-squared test). Quantitative indicators were given in the form of median (Me) and values of lower (LQ) and upper (UQ) quartiles. The significance of differences in quantitative indicators in two unrelated groups was determined using the Mann–Whitney U-test. The threshold value of the confidence level was taken as 0.05. Results. The analysis of the obtained data allows to establish that in the acute period of RVI infection in children with CMV leads to lower figures of temperature reaction, lower vomiting rate, prolongation of hospitalization, along with decrease in leukocytes, CD 16+ (%) cells and immunoregulatory index (CD 4+/CD 8+) against the background of increased levels of monocytes, CD 8+ (%) T-lymphocytes, concentrations of IL-4 and TNF-α. During convalescence, the presence of CMV is associated with an increase in the duration of fever and diarrhea, an increase in monocytes, CD 8+ (%) T cells, concentrations of IL-4, TNF-α and lower figures of immunoregulatory index, CD 16+ (%), CD 22+ (%) T cells and Ig M. Conclusions. Latent cytomegalovirus infection in children with rotavirus gastroenteritis significantly affects a number of clinical and paraclinical as well as immune parameters, which leads to a decrease in the intensity of clinical manifestations in the acute period of the disease and the prolongation of some symptoms during convalescence.

Efficacy of small-dose ganciclovir on cytomegalovirus infections in children and its effects on liver function and miR-UL112-3p expression.

The aim of the study was to explore the efficacy of small-dose ganciclovir on cytomegalovirus infections as well as its effects on the liver function and miR-UL112-3p of children. A total of 141 children infected with cytomegalovirus admitted to the Affiliated Hospital of Weifang Medical University from May 2015 to August 2017 were enrolled, of which 74 children were treated with small-dose ganciclovir as an observation group (Obs group), and the rest were treated with conventional-dose ganciclovir as a control group (Con group). The two groups were compared in efficacy after treatment, changes of liver function indexes [total bilirubin (TB), alanine aminotransferase (ALT), and aspartate aminotransferase (AST)] and miR-UL112-3p before and after treatment, and adverse reactions after treatment. A receiver operating characteristic (ROC) curve was drawn to analyze the value of miR-UL112-3p in predicating efficacy on cytomegalovirus infections in children, and Pearson's correlation analysis was carried out to analyze the correlation between miR-UL112-3p expression and TB, ALT and AST. The MV-DNA level between the two groups after treatment was compared. The two groups showed no significant difference in efficacy and adverse reactions (both P>0.05), and before treatment, there was also no significant difference between the two groups in miR-UL112-3p, TB, ALT, and AST, while after treatment, both groups showed lower levels of miR-UL112-3p, TB, ALT, and AST, and the Obs group showed significantly lower levels thereof than the Con group (all P<0.05). In addition, the area under the curve (AUC), specificity, and sensitivity of miR-UL112-3p in the ROC curve of the Obs group were 0.866, 73.77 and 84.62%, respectively, while the AUC, specificity, and sensitivity of the ROC of the Con group were 0.837, 75.44, and 90.00%, respectively. Furthermore, miR-UL112-3p was positively correlated with TB, ALT, and AST, respectively. The CMV-DNA level in the Obs group was lower than that in the Con group, but the difference was not significant, and the level of CMV-DNA was positively correlated with that of miR-UL112-3p. In conclusion, small-dose ganciclovir can better improve the liver function of the children, and downregulate miR-UL112-3p in them. The AUC, specificity, and sensitivity of miR-UL112-3p for predicting the efficacy of small-dose ganciclovir were 0.866, 73.77 and 84.62%, respectively, and the AUC, specificity, and sensitivityfor predicting the efficacy of conventional-dose ganciclovir were 0.837, 75.44 and 90.00%, respectively.

Clinical features of the TORCH syndrome in newborns with congenital cytomegalovirus infection depending on birth body weight

Objective: to study the clinical features of TORCH syndrome in newborns with congenital cytomegalovirus infection depending on body weight at birthCharacteristics of children and research methods. The study included 70 patients (43 premature, 27 full-term) with with congenital acute cytomegalovirus infection, manifested form. Patient characteristics: Group 1: 21 premature children with extremely and very low body weight at birth; Group 2: 22 premature children with very low body weight; Group 3: 27 full-term children with body weight more than 2,500 g. The congenital cytomegalovirus infection was diagnosed on the presence of TORCH syndrome and etiological verification in the first 3 weeks of life.Results. The authors found that children with extremely and very low body weight significantly more often (p&lt;0.05) had hydrocephalus and interstitial pneumonia than children with low body weight. The full-term patients weighing more than 2,500 g suffered from hemolytic anemia, brain calcifications and congenital heart defects (p&lt;0.05) statistically significantly more often than preterm patients. Reduced duration of pregnancy in preterm labor contributes to the rare occurrence of hemolytic anemia and calcifications in the brain of premature babies. Periventricular localization of calcifications is characteristic of full-term infants. It is necessary to exclude congenital cytomegalovirus infection in newborns with congenital heart defects and other clinical manifestations of TORCH syndrome.Conclusion. The results of the study can be used to diagnose cytomegalovirus infection in children, depending on the birth weight.

Cytomegalovirus Infection and Guillain-Barré Syndrome: The First Case-Control Study in Iran.

Objectives Guillain-Barré syndrome (GBS) is an immune-mediated disease of the peripheral nervous system affecting all age groups around the world. Although the pathogenesis and optimal treatment of GBS have not yet been completely identified, one of the most common infectious diseases to trigger the syndrome is cytomegalovirus (CMV) infection. The GBS following CMV infection is rarely reported in childhood, and there have been no data on GBS with antecedent CMV infection in children in Iran. The current study aimed to evaluate the association between CMV infection and GBS in children in Iran. Materials & MethodsThe case-control study design was used for 30 GBS cases and 30 matched controls. All the serum samples were tested for the presence of anti-CMV immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies using a commercially available enzyme-linked immunosorbent assay (EUROIMMUN Medizinische, Germany). The CMV viral deoxyribonucleic acid (DNA) in the specimen was detected using polymerase chain reaction (PCR) (Cytomegalovirus PCR Detection Kit, CinnaGen Co., Iran).ResultsAnti-CMV IgG antibodies were detected in 97% of the GBS patients and 93% of the healthy controls. Anti-CMV IgM antibodies were demonstrated in 33% of the healthy controls (n=10) and 33% of the GBS children (n=10). The borderline level of anti-CMV IgM antibodies was observed in 23% of the healthy controls (n=7) and 13% of the GBS children (n=4) (P=0.57). None of the specimens from both controls and GBS cases was positive for CMV DNA using PCR. Conclusion The obtained data demonstrated the presence of anti-CMV antibodies in the majority of both GBS patients and controls. Moreover, no relation was observed between CMV infection and GBS. However, it is highly recommended to perform further studies with a large sample size.

Early-childhood cytomegalovirus infection and children's neurocognitive development.

Despite a clear association seen in congenitally infected children, the effect of postnatal cytomegalovirus (CMV) infection during early childhood on cognitive development has not yet been determined. CMV-infection status was obtained based on serological measurements when children were 7 years old. Using population-based longitudinal data, we employed multivariate Poisson regression with a robust variance estimator to characterize the relationship between childhood CMV infection and adverse neurocognitive outcomes in children. Suboptimal neurocognitive outcomes were compared between CMV-positive and CMV-negative children using various cognitive assessments from 8 to 15 years of age. Children were evaluated on the cognitive domains of language, reading, memory and general intelligence, with a suboptimal score being >2 standard deviations lower than the mean score. Approximate Bayes factor (ABF) analysis was used to determine the level of evidence for the observed associations. With adjustment for potential confounders, we observed that early-childhood CMV infection was associated with suboptimal total intelligence quotient (IQ) at 8 years of age [incidence-rate ratio (IRR) = 2.50, 95% confidence interval (CI) 1.35-4.62, ABF = 0.08], but not with suboptimal total IQ at 15 years of age (IRR = 0.97, 95% CI 0.43-2.19, ABF = 1.68). Suboptimal attentional control at 8 years (IRR = 1.74, 95% CI 1.13-2.68, ABF = 0.18) and reading comprehension at 9 years (IRR = 1.93, 95% CI 1.12-3.33, ABF = 0.24) were also associated with CMV infection. ABF analysis provided strong evidence for the association between CMV infection and total IQ at 8 years, and only anecdotal evidence for attentional control at 8 years and reading comprehension at 9 years. All other cognitive measures assessed were not associated with CMV infection. In this large-scale prospective cohort, we observed some evidence for adverse neurocognitive effects of postnatal CMV infection on general intelligence during early childhood, although not with lasting effect. If confirmed, these results could support the implementation of preventative measures to combat postnatal CMV infection.