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Objective: Rare coexistence of disease or pathology Background: Cytomegalovirus (CMV) is a common herpesvirus that often causes asymptomatic or mild infections. In immunocompromised patients, CMV can lead to severe complications, including Guillain-Barré syndrome (GBS) and encephalitis. While these conditions have been described in the immunocompetent population, simultaneous presentation of CMV-associated GBS and encephalitis in such individuals has not been previously reported. Case Report: We present a case of a 58-year-old woman with poorly controlled diabetes who developed concurrent GBS and encephalitis following a CMV infection. The patient experienced bilateral ascending paraparesis 1 week after self-limited gastrointestinal symptoms. Despite initial treatment with plasma exchange therapy, her condition deteriorated with altered mental status and generalized tonic-clonic seizures, necessitating orotracheal intubation. Laboratory analysis revealed the presence of CMV in her cerebrospinal fluid. After treatment with further sessions of plasma exchange therapy and ganciclovir, her muscular strength in the extremities improved. However, she developed acute lung edema and failed extubation, leading to cardiorespiratory arrest with neurological sequelae. Palliative care was institutionalized, and she died 2 weeks later due to pneumonia. Conclusions: This case highlights an unusual clinical presentation of overlapping CMV-associated GBS and encephalitis in an immunocompetent individual, with diabetes as the only identified risk factor. It underscores the importance of considering CMV as a potential etiological factor in such complex cases and the need for prompt diagnosis to improve patient outcomes. Further research is warranted to explore the underlying mechanisms and implications of this rare overlapping neurological manifestation. [ABSTRACT FROM AUTHOR]

Background: Cytomegalovirus (CMV) infection represents a major issue worldwide, since it constitutes the most common viral congenital infection, with a prevalence of 0.58% and 1–5% in developed and developing countries, respectively. According to recent studies, prenatal treatment significantly decreases the risk of vertical CMV transmission, and early intervention may even prevent the termination of pregnancy. This study aimed to investigate the level of awareness of CMV among pregnant patients through a semi-systematic review. Methods: We included all of the original articles investigating knowledge and awareness about CMV infection among pregnant women. Our research included the PubMed database. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement, the Covidence system automatically guided us to screen the titles and/or abstracts, and then full-texts, followed by data extraction from the eligible studies. Results: We screened 764 studies altogether, with 13 studies included in this analysis. Knowledge about the existence of CMV infection risk varied between the articles, ranging from 11.4% in a study performed in Ireland to 60% reported in a study on the French population. Studies analyzing the impact of educational interventions on patients' knowledge about preventive measures reported significant improvement compared to their level of awareness before the intervention. Conclusions: Patients' awareness and knowledge about CMV seemed to be generally low or very low during the last decade before the development of effective secondary prevention methods. Educational interventions seem to be effective, and therefore their wide use could be of potential benefit. In the era of available secondary prevention of vertical transmission, it is crucial to concentrate the efforts of different stakeholders to increase the awareness of cCMV among pregnant women. [ABSTRACT FROM AUTHOR]

Objective: Rare disease Background: Gaucher disease is a rare autosomal recessive disorder characterized by mutations in the glucocerebrosidase gene, resulting in deficient enzyme activity and accumulation of glucocerebroside in macrophages, which leads to pathological changes in affected organs. The atypical clinical manifestations of Gaucher disease often contribute to delays in diagnosis and treatment. Case Report: We present the case of a 4-month-old female infant admitted to the Department of Pediatrics with progressive hepatosplenomegaly since birth. Concurrently, she had cytomegalovirus infection and sensory neurological hearing loss. Gaucher disease diagnosis was confirmed through whole-exome sequencing and validated by a glucocerebrosidase activity test, revealing the mutation site as c.1448T>C. This report outlines the differential diagnosis process for Gaucher disease in this infant before confirmation, contributing valuable insights for early diagnosis. Conclusions: Our case underscores the challenge of diagnosing Gaucher disease due to its atypical presentation. The coexistence of cytomegalovirus infection complicates the clinical picture, emphasizing the need for careful differential diagnosis. Unfortunately, delayed diagnosis is all too common in rare diseases like Gaucher disease, even when the clinical presentation is seemingly typical. This highlights the need for increased awareness and education within the medical community to facilitate early recognition, which is essential for prompt intervention and improved outcomes. This report contributes valuable clinical and genetic information, aiming to enhance awareness and deepen the understanding of Gaucher disease in infants, particularly those with concurrent infections. [ABSTRACT FROM AUTHOR]

Background: Health-state utility values (HSUVs) for post-transplant refractory cytomegalovirus (CMV) infection (with or without resistance [R/R]) were determined using a time trade-off (TTO) survey completed by 1,020 members of the UK general public. Methods: Existing literature and qualitative interviews with clinicians experienced in treating R/R CMV were used to develop initial draft vignettes of health states. The vignettes were refined to describe three clinical states of R/R CMV: clinically significant and symptomatic (CS-symptomatic CMV); clinically significant and asymptomatic (CS-asymptomatic CMV); and non-clinically significant (non-CS CMV). Each clinical state was valued independently and combined with three events of interest: graft-versus-host disease; kidney graft loss; and lung graft loss to generate twelve vignettes. The final vignettes were evaluated by a sample of the UK general public using an online TTO survey. Exclusion criteria were applied to the final data to ensure that responses included in the analysis met pre-defined quality control criteria. Results: Overall, 738 participants met the inclusion criteria and were included in the analysis. The sample was representative of the UK general population in terms of age and sex. Non-CS CMV had the highest mean HSUV (95% confidence interval) (0.815 [0.791, 0.839]), followed by CS-asymptomatic CMV (0.635 [0.602, 0.669]), and CS-symptomatic CMV (0.443 [0.404, 0.482]). CS-symptomatic CMV with lung graft loss had the lowest mean HSUV (0.289), with none of the health states considered on average worse than dead. Conclusions: Post transplant R/R CMV has substantial impact on the health-related quality of life of patients. The utility values obtained in this study may be used to support economic evaluations of therapies for R/R CMV infection. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) is a significant cause of morbidity and mortality in pediatric transplantation. However, currently utilized CMV prevention paradigms have limitations, leading to research aimed at novel strategies for mitigation of CMV infection. Cell-mediated immunity (CMI) is crucial in controlling CMV infection and the use of CMV-specific CMI assays to guide prevention and treatment of CMV infection in both solid organ transplant and hematopoietic cell transplant recipients shows great promise. In this article, we review the immune response to CMV infection to highlight the rationale for CMI assays, describe available commercial assays and strategies for their use, and summarize relevant literature regarding the use of CMI assays in transplant recipients. [ABSTRACT FROM AUTHOR]

Introduction: In this single-center retrospective cohort study, we investigated the efficacy of letermovir in preventing Cytomegalovirus (CMV) infection in patients with aplastic anemia (AA) who have undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: Based on whether or not letermovir was used for preventing CMV infection, the patients were categorized into two groups: letermovir and control groups. The overall survival (OS) rate and cumulative incidence of CMV infection during the first 100 days after allo-HSCT were evaluated. The study included 21 matched pairs of patients, identified through propensity score matching analysis, to compare CMV infection rates, treatment efficacy, and regression. Results: The incidence of CMV infection within 100 days after transplantation was significantly lower in the letermovir group than in the control group (26.5 vs. 77.4%, respectively; P < 0.001), among a total of 87 patients who underwent the transplant. In the matched cohort of 21 patients with AA, the letermovir group also showed a significantly reduced cumulative incidence of CMV infection (14.3 vs. 90.5% in the control group; P < 0.001). Compared to the control group, patients with CMV infection in the letermovir group had lower CMV-DNA load and a shorter clearance time. However, there was no significant difference in OS between both groups (P = 0.34). Conclusions: Letermovir effectively prevents CMV infection in allo-HSCT recipients with AA and demonstrates a high safety profile. [ABSTRACT FROM AUTHOR]

Background: Pneumocystis jirovecii pneumonia (PJP) is a common and troublesome complication of kidney transplantation. In the era of prophylaxis, the peak incidence of PJP after kidney transplantation and specific characteristics of late-onset PJP have always been debated. Methods: We performed a retrospective study by analysing the data of post-transplantation pneumonia in adult kidney transplantation recipients between March 2014 and December 2021 in The Affiliated First Hospital of University of Science and Technology of China (USTC). A total of 361 patients were included and divided into early-onset PJP, late-onset PJP and non-PJP groups. The characteristics of each group and related risk factors for the late-onset patients were investigated. Results: Some patients developed PJP 9 months later with a second higher occurrence between month 10 and 15 after transplantation. Compared with non-PJP, ABO-incompatible and cytomegalovirus (CMV) viremia were significantly associated with late onset of PJP in multivariate analysis. The use of tacrolimus, CMV viremia, elevated CD8(+) T cell percent and hypoalbuminemia were risk factors for late PJP. Receiver operating characteristic curve analysis demonstrated that a combination of those factors could increase the sensitivity of prediction remarkably, with an area under the curve of 0.82, a sensitivity of 80% and a specificity of 83%. Conclusions: PJP could occur months after kidney transplantation. ABO-incompatible transplant recipients are at high risk of PJP. In the later stages of transplantation, CMV viremia, T lymphocyte subsets percentage and serum albumin levels should be monitored in patients using tacrolimus. [ABSTRACT FROM AUTHOR]

Congenital cytomegalovirus (CMV) is the most common cause of congenital infection worldwide, the most common nongenetic cause of sensorineural hearing loss in children, and a cause of neurodevelopmental disorders in the brain. Infants with symptomatic congenital CMV infection may benefit from hearing and neurodevelopmental outcomes, particularly if antiviral treatment is initiated within the first month of life. Infants with life-threatening symptoms are recommended to receive 2-6 weeks of intravenous ganciclovir and then switch to oral valganciclovir, and those without life-threatening symptoms are recommended to use oral valganciclovir during the entire 6-month period. During antiviral drug treatment, absolute neutrophil count, platelet count, blood urea nitrogen, creatinine, and liver function tests were performed to identify neutropenia, thrombocytopenia, renal failure, and liver failure. This review investigated the evidence to date of treating congenital CMV infection. [ABSTRACT FROM AUTHOR]

Cytomegalovirus hepatitis is a liver disease caused by human cytomegalovirus infection and is one of the most common liver diseases in children and immunocompromised individuals. This disease has no specific clinical manifestations and is easily confused with other types of viral hepatitis, which may lead to delayed treatment or mistreatment. Therefore, the early diagnosis of cytomegalovirus hepatitis is of vital importance, and patients should be given timely and effective treatment with appropriately selected antiviral drugs and course of treatment. This article reviews the recent research advances in the etiology, epidemiology, pathogenesis, clinical manifestations, diagnosis, treatment, and prevention of cytomegalovirus hepatitis. [ABSTRACT FROM AUTHOR]

To investigate the risk factors for CMV infection and to clarify the cut-off count of CMV pp65 antigenemia predicting clinical symptoms related to CMV infection in patients with rheumatic disease. We retrospectively analyzed 261 patients with rheumatic disease who were treated with immunosuppressive therapy. CMV infection was defined as positive > 1 CMV-positive cell per two slides (CMV pp65 antigenemia C10/C11). Patients with CMV infection were divided into two groups based on the presence of antiviral treatment for CMV disease. We determined a cut-off value of CMV-positive cells for the diagnosis of CMV disease. CMV infection was observed in 141 cases (54%). In a multivariate analysis, CMV infection was associated with three following factors: Age > 60 years (OR 1.87 [95% CI 1.04–3.36]); lymphocyte counts < 1000/μL (OR 3.34 [95% CI 1.88–6.05]); steroid pulse therapy (OR 2.60 [95% CI 1.27–5.55]). The cut-off level of CMV pp65 antigenemia indicating CMV disease was five positive cells average two slides by using receiver operating characteristic curve analysis (AUC 0.95, sensitivity 0.94, specificity 0.80). Age > 60 years, lymphocytopenia (< 1000/μL) and steroid pulse therapy are risk factors of CMV infection. We recommend that CMV pp65 antigenemia of > 5 cells average two slides (C10/C11) in patients with rheumatic disease should be the treated with antiviral drugs. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) reactivation has been linked to adverse clinical outcomes in critically ill patients, with emerging evidence suggesting a potential connection with severe COVID-19. Mechanisms driving this association may include primary lung injury, amplification of systemic inflammation, and secondary immunosuppression. Diagnostic challenges in detecting and assessing CMV reactivation necessitate a comprehensive approach to improve accuracy and inform treatment decisions. Currently, there is limited evidence on the efficacy and safety of CMV pharmacotherapy in critically ill COVID-19 patients. Although insights from non-COVID-19 critical illness studies suggest a potential role for antiviral treatment or prophylaxis, the risks and benefits must be carefully balanced in this vulnerable patient population. Understanding the pathophysiological role of CMV in the context of COVID-19 and exploring the advantages of antiviral treatment are crucial for optimizing care in critically ill patients. This review provides a comprehensive synthesis of available evidence, emphasizing the need for additional investigation to establish the role of CMV treatment or prophylaxis in the management of severe COVID-19 and to develop a framework for future research on this topic. [ABSTRACT FROM AUTHOR]

Background: Life-long immunosuppressive treatment after liver transplantation (LT) prevents graft rejection but predisposes the LT recipient to infections. Herpesvirus infections are associated with morbidity and mortality among LT recipients. Among those, especially cytomegalovirus (CMV) and varicella-zoster virus (VZV) pose challenges after LT. The aim of this study is to provide an in-depth characterization of the cellular immune response against CMV and VZV infections in LT recipients and identify potential risk factors for infection. Methods: The Herpesvirus Infections in Solid Organ Transplant Recipients – Liver Transplant Study (HISTORY) consists of an epidemiological and immunological substudy. The epidemiological substudy is a retrospective observational cohort study that includes all patients who underwent LT in Denmark between 2010 and 2023 (N ≈ 500). Using data from nationwide hospital records and national health registries, the incidence of and clinical risk factors for CMV and VZV infections will be determined. The immunological substudy is an explorative prospective observational cohort study including patients enlisted for LT in Denmark during a 1.5-year period (N > 80). Participants will be followed with scheduled blood samples until 12 months after LT. CMV- and VZV-derived peptides will be predicted for their likelihood to be presented in participants based on their HLA type. Peptide-MHC complexes (pMHC) will be produced to isolate CMV- and VZV-specific T cells from peripheral blood mononuclear cells before and after CMV and VZV infection. Their frequency, T cell receptor sequences, and phenotypic characteristics will be examined, and in a subset of participants, CMV- and VZV-specific T cells will be expanded ex vivo. Discussion: This study will provide novel insight into T cell immunity required for viral control of CMV and VZV and has the potential to develop a prediction model to identify LT recipients at high risk for infection based on a combination of clinical and immunological data. Furthermore, this study has the potential to provide proof-of-concept for adoptive T cell therapy against CMV and VZV. Combined, this study has the potential to reduce the burden and consequence of CMV and VZV infections and improve health and survival in LT recipients. Trial registration: ClinicalTrials.gov (NCT05532540), registered 8 September 2022. [ABSTRACT FROM AUTHOR]

HIV patients are at higher risk of contracting and developing into an asymptomatic form of CMV infection. This review aimed to evaluate the efficacy and safety of preemptive therapy for preventing CMV disease in HIV patients. The electronic search was conducted in MEDLINE/PubMed and CENTRAL from inception until 9 September 2022. Studies were included if they assessed the efficacy or safety of anti-CMV preemptive therapy compared to placebo or no therapy. Risk of bias were assessed using the Cochrane Risk of Bias tool for randomized trials version 2 or the Cochrane Collaboration Risk of Bias in Non-randomized Studies of Interventions. The random-effects model was used to calculate effect sizes. We identified six RCTs (2135 participants) and four observational studies (395 participants), with five RCTs were performed before highly active antiretroviral therapy (HAART) era. Preemptive therapy did not reduce the incidence of CMV disease (RR 0.84, 95% CI: 0.59–1.18), yet reduced the RR of all-cause mortality rate by 26% (RR 0.85, 95% CI: 0.74–0.97) with a low quality of evidence. The incidence of neutropenia as an adverse event increased significantly (RR 2.47, 95% CI: 1.12–5.45) with moderate quality of evidence. With the advent of HAART, a limited number of studies have been performed to explore anti-CMV preemptive therapy due to the improved outcomes of HIV patients with CMV viremia. Therefore, optimal HAART should take precedence over anti-CMV preemptive therapy. The protocol for this review was registered in the Prospective Register of Systematic Reviews (CRD42020145765). [ABSTRACT FROM AUTHOR]

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

Background: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome of systemic hyper-inflammation, caused by an excessive cytokine secretion, secondary to an uncontrolled proliferation of lymphocytes and macrophages, and leading to vascular endothelial injury and multi-organ failure. HLH is either primary/familial due to genetic mutations in the genes coding for the CD8+ and NK T cells cytotoxic proteins or is secondary to infection, malignancy, or autoimmune disorders. Timely diagnosis using the HLH-2004 criteria and prompt initiation of treatment for HLH is essential for the survival of affected patients. Adults with HLH have poor outcomes even with aggressive treatment. Case Report: Our patient was a 48-year-old man who presented with altered mental status. He was tachycardic and tachypneic, and quickly developed acute hypoxemic respiratory failure requiring mechanical ventilation. Computed tomography (CT) of the chest and abdomen showed bilateral pleural effusion, ascites, and heterogeneous splenomegaly. Laboratory workup revealed anemia, thrombocytopenia, severe hyperferritinemia, hypofibrinogenemia, and hypertriglyceridemia. Pleural fluid analysis showed a lymphocytic exudate, with T cell predominance on flow cytometry. A T cell rearrangement study of the pleural fluid was positive. Bone marrow biopsy showed histiocytes with hemophagocytic activity. The diagnosis of HLH secondary to T cell lymphoma was made, and the patient was treated with dexamethasone and etoposide. A few hours later, the patient had a cardiac arrest, and laboratory findings suggestive of tumor lysis syndrome (TLS) were discovered. The patient died of refractory shock one day later, and the cytomegalovirus (CMV) PCR result was positive during that day. Conclusions: Adults with HLH have poor outcomes even with aggressive treatment. Additional focus on the management of HLH should shift towards preventing complications such as TLS. More studies should focus on post-treatment outcomes of HLH secondary to malignancy to improve the management and prognosis. [ABSTRACT FROM AUTHOR]

Gastric perforation as a multi-etiological disease is a full-thickness injury of the stomach wall. In this case report, we presented a 60-year-old woman with a history of suicidal behavior referred to the emergency unit with a decreased level of consciousness due to the multidrug consumption (amphetamine and benzodiazepine). Passing 3 days of admission in the intensive care unit, the patient represented severe abdominal distension, lack of defecation, and the absence of bowel sound, which suggested the gastrointestinal (GI) complication. Abdominal-pelvic sonography followed by laparotomy confirmed the gastric perforation, which finally led to the patient's death. Pathological analysis showed that the vast involvement of cytomegalovirus (CMV) in the patient's GI tract resulted in several peptic ulcers. The first report of gastric perforation-related death arises from the partnership of CMV infection and drug poisoning. [ABSTRACT FROM AUTHOR]

Objective: To describe a rare case of cardiac tamponade in a pediatric patient with systemic lupus erythematosus (SLE) and cytomegalovirus (CMV) infection, and to discuss the relationship between these morbidities, the diagnostic approach, and the possible treatments. Case description: A 9-year-old girl presented to the emergency department with severe dyspnea, muffled heart sounds, jugular vein distention, hemodynamic instability, and intense pallor. She had previously been followed up at the outpatient clinic for a sixmonth history of mild respiratory distress, polyarthritis, fever, and various cutaneous manifestations. Doppler echocardiogram revealed pericardial effusion. The patient was submitted to pericardiocentesis followed by water seal pleuropericardial drainage, with no complications. The investigation continued, with fulfillment of clinical and laboratory SLE criteria plus CMV antigenemia of 15/200,000 cells. Medications to control CMV infection and SLE were then initiated, with good clinical and laboratory response. Comments: Pediatric SLE commonly manifests in a more severe form, accounting for high morbimortality. Cardiac tamponade could be one of the first manifestations of SLE, which can also be precipitated by infectious agents, such as CMV, leading to diagnostic confusion and misleading the treatment. Changes in therapeutics must also be considered in the presence of both conditions. This study presents a juvenile SLE case aggravated by a CMV infection with the unusual manifestation of cardiac tamponade. [ABSTRACT FROM AUTHOR]

Objective: To investigate the spectrum and frequency of abnormalities on brain MRI in a large cohort of live newborns with congenital CMV (cCMV) infection. Methods: Institutional review board approval and informed consent for neonatal MRI and data collection were obtained. Between January 2010 and January 2018, brain MRI was performed in 196 live newborns diagnosed with cCMV. Images were independently reviewed by 2 pediatric radiologists, blinded to clinical data. Results: cCMV infection was clinically symptomatic in 26/191 newborns (13.6%). Brain MRI showed abnormalities in 76/196 patients (38.8%). MRI was abnormal in 20/26 clinically symptomatic patients (76.9%): 76.9% showed white matter lesions, 61.5% subependymal cysts, 46.2% ventriculomegaly, 26.9% ventricular adhesions, 26.9% gyral abnormalities, 24.0% calcifications, 15.4% cerebellar anomalies. MRI was abnormal in 55/165 (33.3%) clinically asymptomatic patients: 30.9% had white matter lesions, 15.8% subependymal cysts, 4.2% ventriculomegaly, 2.4% ventricular adhesions, 1.2% gyral abnormalities, 0.6% calcifications, none had cerebellar anomalies. Concomitant brain lesions were seen in all patients with gyral abnormalities, cerebellar anomalies, and calcifications and nearly all patients with subependymal cysts and ventriculomegaly. In all but 4 patients with other detected brain lesions, white matter abnormalities were simultaneously present. In 33/74 patients (45.2%), white matter lesions were seen as a sole abnormality. Conclusion: White matter lesions were the most common detected abnormality on brain MRI in newborns with congenital CMV. Since brain abnormalities were seen in more than 30% of clinically asymptomatic and 75% of clinically symptomatic newborns, MRI should be advised in all newborns diagnosed with cCMV. Key Points: • Neonatal brain MRI showed abnormalities in more than 30% of clinically asymptomatic and 75% of symptomatic newborns with congenital cytomegalovirus infection. • White matter lesions were by far the most common detected abnormality, followed by subependymal cysts and ventricular dilatation. • Lesions in cCMV were often multiple, with many patients showing concomitant lesions. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to investigate a potential association between whole blood and lymphocyte Cyclosporin A (CyA) levels and the occurrence and frequency of infectious complications in kidney transplant patients. Methods: The study involves 130 kidney transplant recipients who received CyA in addition to Mycophenolate Mofetil and steroids. CyA whole blood trough and maximum level (CyA BL0 and CyA BLm) as well as the corresponding levels in the lymphocytes (CyA L0 and CyA Lm) were measured for 6 months post-transplantation. Results: Cytomegalovirus (CMV) as well as urinary tract infections (UTIs) were the most commonly diagnosed with an incidence of 24.6% and 26.2%, respectively. Only CyA L0 showed a significant association with CMV infection occurrence (adjusted OR = 1.051, 95% CI.997–1.025, P -value 0.046). A positive linear correlation was found between CyA BL0, CyA BLm and CyA Lm and the number of CMV episodes per patient. Conclusion: We showed an association between the CMV infections occurrence and the trough lymphocyte level of CyA (CyA L0). Both lymphocyte CyA levels also correlated with the frequency of CMV infections. Further studies are needed to establish the optimal range of both CyA blood and lymphocyte levels and decrease the risk of opportunistic infections in high risk patients. [ABSTRACT FROM AUTHOR]

Objective: Rare disease. Background: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease characterized by an intense immunologic response that results in multiorgan dysfunction. It typically manifests as a result of a familial genetic immunodeficiency disorder or secondary to a trigger such as an infection, malignancy, or autoimmune disease. The major factors involved in the development of the disease are an individual's genetic propensity to develop HLH, such as rare associated mutations, or inflammatory processes that trigger the immune system to go haywire. Case Report: Before the COVID-19 pandemic, a 22-year-old woman with a history of congenital absence of the right kidney, right-sided hearing loss, and leukopenia presented with a 3-week history of generalized malaise, fever, chest pain, cough, and shortness of breath. She developed an acute systemic cytomegalovirus infection further complicated by HLH. Based on her history and clinical course, an underlying primary immunodeficiency was suspected. An immunodeficiency gene panel revealed a monoallelic mutation in GATA2, a gene that encodes zinctranscription factors responsible for the regulation of hematopoiesis. Conclusions: GATA2 deficiency encompasses a large variety of mutations in the GATA2 gene and leads to disorders associated with hematologic and immunologic manifestations of monocytopenia and B-, and natural killer-cell deficiency. Over time, affected individuals are at high risk of developing life-threatening infections and serious hematologic complications, such as myelodysplastic syndromes and/or leukemias. We aimed to illustrate the importance of identifying an underlying genetic disorder associated with secondary HLH to help guide acute and long-term management. [ABSTRACT FROM AUTHOR]

Some HLA alleles have been shown to be associated with susceptibility to cytomegalovirus (CMV) disease incidence in vitro. The objective of this study was to identify correlations between donor HLA allotypes and CMV disease incidence in patients with acute myeloid leukemia who had undergone allogeneic hematopoietic stem cell transplantation (HSCT). Methods and materials we retrospectively analyzed the medical records of 613 donors and recipients with acute myeloid leukemia who had received an allogeneic HSCT from matched sibling (n = 260), unrelated (n = 168), or haploidentical (n = 186) donors, from 2012 to 2017. The HLA‐A, ‐B, ‐C, and ‐DRB1 allotypes in the donors were determined using sequence‐based typing. Overall, CMV disease incidence was significantly associated with three genotype alleles, HLA‐A*30:04:01G, ‐B*51:01:01G, and ‐DRB1*09:01:02G. In the donor CMV IgG seropositive subgroup, CMV disease incidence was significantly associated with HLA‐B*51:01:01G and ‐DRB1*09:01:02G. In the IgG seropositive donors in the unrelated allo‐HSCT subgroup CMV disease incidence was also significantly associated with HLA‐B*51:01:01G. In the CMV seropositive donors in the haploidentical allo‐HSCT subgroup, the incidence of CMV disease was significantly associated with HLA‐A*24:02:01G and ‐DRB1*09:01:02G. HLA‐DRB1*13:02:01G was a protective marker among IgG seropositive donors in the unrelated allo‐HSCT recipient category. Discussion and conclusions The incidence of CMV disease among HSCT recipients varies according to donor HLA alleles and the donor CMV IgG serostatus. Certain donor HLA alleles can be considered to be risk or protective markers. Donors' HLA types and CMV IgG serostatus should be considered in donor selection. [ABSTRACT FROM AUTHOR]

Patient: Male, 35-year-old Final Diagnosis: CMV infection Symptoms: Fever Medication: -- Clinical Procedure: -- Specialty: Gastroenterology and Hepatology, Infectious Diseases Objective: Challenging differential diagnosis Background: Cytomegalovirus (CMV) is a member of Herpesviridae family with its name derived from the fact that it causes enlargement of the infected cell resulting in the characteristic inclusion bodies seen on microscopy. CMV virus has an incubation period of about 4 to 6 weeks. Symptoms of CMV infection vary and depend on factors including the age and immune status of the patient. It usually presents as asymptomatic infection in immunocompetent individuals whereas severe disease is usually seen in immunocompromised patients. Here we present a case of an immunocompetent patient who presented with acute CMV hepatitis. Case Report: A 35-year-old male with no significant prior medical history who presented to the Emergency Department with a 2-week history of low-grade fever. Acute CMV infection was diagnosed by positive CMV antibody and polymerase chain reaction (PCR) testing. The patient was treated with valganciclovir that resulted in rapid improvement in clinical status as well as normalization of the liver enzymes. Conclusions: This article presents a rare case of immunocompetent young male with acute CMV hepatitis who responded favorably to antiviral therapy. [ABSTRACT FROM AUTHOR]

Introduction. Cytomegalovirus is the most common cause of infections in the post-transplantation period. A reliable and timely laboratory diagnosis of cytomegalovirus infection in patients on dialysis and in the post-transplantation period is significant because of the possibility of preventing or mitigating the effects of cytomegalovirus disease. The main objective of this study was to compare serological and molecular polymerase chain reaction methods to determine the presence of cytomegalovirus in the blood of dialysis patients. Material and Methods. The study included 28 dialysis patients, potential renal transplant recipients. All patients were evaluated for the presence of cytomegalovirus in the blood by a quantitative polymerase chain reaction method as well as in the serum for the presence of anti-cytomegalovirus Immunoglobulin G and Immunoglobulin M antibodies. Results. According to the comparative enzyme-linked immunosorbent assay for detecting antibodies in dialysis patients, 96.4% were once exposed to the virus, while 7.1% showed current infection not confirmed by polymerase chain reaction test. No statistically significant association was found between the positive finding of anti-cytomegalovirus Immunoglobulin M antibodies and the findings of the polymerase chain reaction cytomegalovirus method when Chi-square (χ 2) and Fisher's correlation tests were conducted (p > 0.05). Conclusion. Due to 7.1% false positives results for the presence of anti-cytomegalovirus Immunoglobulin M antibodies in the serum of immunocompromised dialysis patients, not confirmed by polymerase chain reaction test, serological techniques are not reliable in detecting active cytomegalovirus infection causing positive finding of anti-cytomegalovirus Immunoglobulin M, so confirmation of cytomegalovirus deoxyribonucleic acid by polymerase chain reaction method is required. [ABSTRACT FROM AUTHOR]

Background and aims: The impact of cytomegalovirus (CMV) colitis on long-term outcomes of ulcerative colitis (UC) flares remains controversial. Methods: A total of 257 UC patients with moderate-to-severe flares were observed for a mean follow-up of 41.2 months. CMV colitis was defined as histopathologic confirmation of CMV inclusions obtained from macroscopic endoscopic lesions in patients with UC flares. An independent gastrointestinal pathologist prospectively reviewed all specimens. A poor outcome was defined as any of hospitalization, colectomy or death during the follow-up period. Results: The prevalence of CMV colitis was 14% (36/257) over the 10-year study period (2007–2016). When compared to the controls, patients with CMV colitis were characterized by older age, higher disease activity, endoscopic deep ulcerations and more frequent use of immunosuppressive drugs (all p <.05). In total, 57 outcome events (50 hospitalizations, seven colectomies) were observed among the study population (44.7% in patients with CMV colitis vs. 18.9% in controls). The cumulative probability of a poor outcome was significantly greater in the patients with CMV colitis than in the controls (log-rank test p <.001). In a multivariable analysis, CMV colitis remained as an independent predictor of a poor outcome (hazard ratio; 2.27; 95% confidence interval: 1.12–4.60). Despite a generally favorable response to antiviral therapy (79%), the risk of recurrent CMV colitis remained quite high (57%). Most of the recurrences developed within 8 months (75%). Conclusions: True CMV colitis is a poor prognostic indicator among patients with UC flares. An effective strategy for managing recurrent CMV colitis is urgently needed (KCT0003296). [ABSTRACT FROM AUTHOR]

Objectives: Antiviral resistance in cytomegalovirus (CMV) may result from mutations in the molecular targets of antiviral agents. The aim of this study was to investigate both the prevalence of resistance-associated mutations and the factors associated with antiviral resistance in solid organ transplant (SOT) patients with repeated high CMV loads during antiviral treatment.Methods: SOT patients were selected retrospectively, based on CMV loads of >30000 IU/mL at least twice in a period during which treatment was given. Patient samples were tested for antiviral resistance by Sanger sequencing the UL97 and UL54 genes of CMV, which code for the viral kinase and polymerase. Factors predisposing to and resulting from the development of antiviral resistance mutations were analysed.Results: Multiple samples from 113 SOT patients were tested, showing resistance-associated mutations in 25 patients (22%). A further 20 (18%) patients showed mutations that were not known to be associated with antiviral resistance. Several factors were associated with development of resistance-associated mutations in UL97 as well as UL54, including human leucocyte antigen (HLA) mismatch, which occurred more frequently in the group of patients with resistance mutations. High-level resistance mutations were most frequently seen in UL97.Conclusions: This study shows that by selecting patients solely on the basis of virological response to treatment, more patients with antiviral resistance mutations are identified. In this study we confirm findings by other groups that primary infections are associated with resistance development. Moreover, we show that HLA mismatch is associated with the development of antiviral resistance, which suggests a role for host immunity in the development of resistance. [ABSTRACT FROM AUTHOR]

Background: Congenital cytomegalovirus (cCMV) is the leading cause of nongenetic congenital hearing loss in much of theworld and a leading cause of neurodevelopmental disabilities. Infected babies can be born towomenwho are seropositive and seronegative prior to pregnancy, and the incidence is approximately 0.6%-0.7% in the United States. Symptoms vary from mild to severe, and hearing loss can be delayed in onset and progressive. Methods: We reviewed the literature to summarize the epidemiology, clinical manifestations, diagnosis, treatment, and future directions of cCMV. Results: The best way to diagnose the infection is with polymerase chain reaction of urine or saliva within 3 weeks after birth, followed by a repeat confirmatory test if positive. Moderately to severely symptomatic neonates should be treated for 6 months with valganciclovir, and some practitioners also choose to treat infants who have isolated hearing loss only. Treatment is not recommended for asymptomatic infants. All infected infants should be screened for hearing loss and neurodevelopmental sequelae. Universal and targeted screening may be cost effective. Currently, no vaccine is commercially available, although multiple candidates are under study. Conclusion: Congenitally acquired cytomegalovirus is found in all communities around the world with a disease burden that is greater thanmany other well-known diseases. Advances are beingmade in prevention and treatment; however, improved awareness of the disease among clinicians and patients is needed. [ABSTRACT FROM AUTHOR]

Background Congenital cytomegalovirus (CMV) infection is a major cause of sensorineural hearing loss. By law, newborns in Connecticut who fail newborn hearing screening are tested for infection with CMV. This targeted screening is controversial, because most children with congenital CMV infection are asymptomatic, and CMV-related hearing loss can have a delayed onset. Our hospital uses a saliva polymerase chain reaction (PCR) assay (confirmed by a urine PCR assay) to detect CMV. Here, we report the results of the first year of our screening program. Methods We reviewed the medical records of newborns in the Yale New Haven Health System who failed the newborn hearing screening test between January 1 and December 31, 2016. Results Of 10964 newborns, 171 failed newborn hearing screening, and 3 of these newborns had positive saliva CMV PCR test results. Of these 3 newborns, 2 had positive results on the confirmatory test (for 1 of them the confirmatory test was not performed until the infant was 10 weeks old), and 1 had a negative result on the confirmatory test. Three additional newborns with congenital CMV infection were tested because of clinical indications (1 for ventriculomegaly on prenatal ultrasound and 2 for CMV infection of the mother). Results of audiology follow-up were available for 149 (87.1%) of the 171 newborns who failed newborn hearing screening; 127 (85.2%) had normal results. Conclusion Our targeted screening program for congenital CMV infection had a low yield. Consideration should be given to other strategies for identifying children at risk of hearing loss as a result of congenital CMV infection. [ABSTRACT FROM AUTHOR]

Abstract Background Cytomegalovirus (CMV)-specific T-cells are crucial to prevent CMV disease. CMV seropositive recipients transplanted with stem cells from a CMV seronegative allogeneic donor (R+D−) may be at risk for CMV disease due to absence of donor CMV-specific memory T-cells in the graft. Methods We analyzed the duration of CMV reactivations and the incidence of CMV disease in R+D− and R+D+ patients after alemtuzumab-based T-cell depleted allogeneic stem cell transplantation (TCD alloSCT). To determine the presence of donor-derived primary CMV-specific T-cell responses we analyzed the origin of CMV-specific T-cells in R+D− patients. Results The duration of CMV reactivations (54 versus 38 days, respectively, p = 0.048) and the incidence of CMV disease (0.14 versus 0.02, p = 0.003 at 1 year after alloSCT) were higher in R+D− patients compared to R+D+ patients. In R+D− patients, CMV-specific CD4+ and CD8+ T-cells were mainly of recipient origin. However, in 53% of R+D− patients donor-derived CMV-specific T-cells were detected within the first year. Conclusions In R+D− patients, immunity against CMV was predominantly mediated by recipient T-cells. Nevertheless, donor CMV serostatus significantly influenced the clinical severity of CMV reactivations indicating the role of CMV-specific memory T-cells transferred with the graft, despite the ultimate formation of primary donor-derived CMV-specific T-cell responses in R+D− patients. Highlights • Incidence of CMV disease higher after transplantion with CMV negative donor (R+D−). • In R+D− patients CMV-specific T-cells mainly of recipient origin after transplantation. • Donor-derived CMV-specific T-cell response detectable within the first year. [ABSTRACT FROM AUTHOR]

Currently in Portugal, universal screening of pregnant women for Cytomegalovirus (CMV) infection is not performed. However, it is recommended to screen all women attending preconception care. We aimed to assess women's attendance to preconception care and if their serologic status regarding CMV was known and/or investigated in that consultation. In this cross-sectional study, we interviewed 240 women admitted to the obstetrical ward of a hospital in the Metropolitan Area of Porto (Portugal) about their adherence to preconception care and collected data regarding their CMV serologic status and its investigation. We found that 71.3% of the women who attended preconception care were not screened for CMV infection. Among primigravida, the screening rate was only of 30.4% (upper limit of CI 95%: 44.8%). There were no statistically significant differences between the private and public sectors of healthcare. We observed attendance to preconception care is high (73.1%). For the population subgroup of the metropolitan area of Porto, attendance to preconception care is at least 66%, with a 95% confidence level. Portuguese guidelines stating a woman's serologic status regarding CMV should be investigated in preconception care are not properly implemented. This suggests guidelines should assure the screening of previously non-screened women during pregnancy. [ABSTRACT FROM AUTHOR]

Objective：To investigate the effect of cytomegalovirus (CMV) infection on the pregnancy outcomes of IVF/ICSI treatment. Methods：The data of 59 536 patients who underwent ART treatment in our center between August 2005 and January 2018 were retrospectively analyzed. These patients were divided into two groups: the CMV IgG positive group (n=94) and the CMV IgG negative group (n=26 483). The pregnancy outcomes were compared accordingly. Results：There were no significantly differences in the age, infertile duration, body mass index, base level of FSH between the two groups (all P＞0.05). The number of retrieved oocytes, the number of 2PN after IVF, the rate of biochemical pregnancy, and the rate of clinical pregnancy in the CMV IgG positive group were significantly lower than those in the CMV IgG negative group (all P＜0.05). Conclusions：The number of retrieved oocytes, the number of 2PN after IVF, the rate of biochemical pregnancy, and the rate of clinical pregnancy could be lowered in those patients with the history of CMV infection. The CMV positive infection may affect the clinical outcomes of IVF/ICSI treatment. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) remains a significant contributor to morbidity and death after pediatric solid and stem cell transplantation. Decisions regarding prevention and treatment often lack pediatric-specific data to drive decision making. We present here a case-based discussion around some of these specific topics and focus on approaches to CMV prevention, post-CMV secondary prophylaxis options, and identification and treatment of resistant CMV infection, including emerging antiviral agents and the use of cytotoxic CMV-specific T-cells, in the setting of pediatric hematopoietic stem cell transplantation. [ABSTRACT FROM AUTHOR]

Infection by cytomegalovirus has worldwide distribution with high prevalence in developing countries, where it reaches almost 100% of the population. Cutaneous manifestations are rare. Moreover, unspecific presentation of dermatological lesions may contribute to subdiagnosis of the disease. We report a case of a 24 years-old female patient, severely immunocompromised, with ulcerations on the skin with 4 months of evolution, diagnosed with human immunodeficiency virus type 1 infection two months after the onset of lesions. In the third week of hospitalization she developed an acute cytomegalovirus retinitis, and despite initiation of anti-retroviral and anti- cytomegalovirus treatment initiation, she died after three months with an acute pericarditis. [ABSTRACT FROM AUTHOR]

Background Micro-RNAs are implicated in various physiological and pathologic processes. In this study, we tested whether Micro-RNA gene variants of host-genome affect clinical manifestation of symptomatic HCMV infection. Methodology HCMV infection was detected by fluorescent PCR and immuno-histochemistry. The detection of genetic variants of four studied Micro-RNA tag-SNPs was done through PCR-RFLP assay and validated with DNA sequencing. Results We observed an increased risk ranged from 3-folds to 5-folds among symptomatic HCMV cases for mutant genotype of rs2910164 (crude OR = 3.11, p = 0.009 and adjusted OR = 3.25, p = 0.007), rs11614913 (crude OR = 3.20, p = 0.006 and adjusted OR = 3.48, p = 0.004) and rs3746444 (crude OR = 4.91, p = 0.002 and adjusted OR = 5.28, p = 0.002) tag-SNPs. Interestingly, all the tag-SNPs that were significant after multiple comparisons at a FDR of 5% in symptomatic HCMV cases remained significant even after bootstrap analysis, providing internal validation to these results. Multifactor Dimensionality Reduction (MDR) analysis revealed 5-folds increased risk for symptomatic HCMV cases under the four-factor model (rs2910164, rs2292832, rs11614913 and rs3746444). Conclusions These results suggest that Micro-RNA gene variants of host-genome may affect clinical manifestation of symptomatic HCMV infection. [ABSTRACT FROM AUTHOR]

The cytomegalovirus infection is prevalent in developed countries. The natural history of disease includes three phases: primoinfection (majority is asymptomatic), latency and reactivation. In certain immunosuppressive states, as in the case of transplantation and HIV infection, the virus can reactivate, occurring cutaneous manifestations, of what stands out the occurrence of genital ulcers. In these, co-infection with other etiologic agents is common, particularly with the herpes simplex virus, leading to more severe manifestations and difficulty in the differential diagnosis. In this context, it is relevant to know the pathogenesis of this virus and the diagnostics means available in order to optimize its therapy. [ABSTRACT FROM AUTHOR]

Background: Children with congenital cytomegalovirus (CMV) infection face a bigger risk of neurological deficits and developmental delays associated with sensorineural hearing loss (SNHL). Their rehabilitation with a cochlear implant (CI) may therefore be inferior to the paediatric population in general. This study describes post-implant outcomes in children with CMV-related deafness and compares them to children with genetic deafness caused by GJB2 mutation (connexin 26) rehabilitated at the Centro Hospitalar e Universitário de Coimbra, Portugal. Material and method: We conducted a revision of 11 children with profound hearing loss caused by congenital CMV infection rehabilitated with a CI in our institution. The children were divided into 3 groups according to age of implantation (<2 years, 2-3 years, >3 years) and their performance was compared to a group of children with genetic hearing loss caused by GJB2 mutation. To compare performance the following tests were applied: SIR, CAP, vocal characteristics evaluation grid (VCEG), MAIS, and MUSS. Results: We found no differences between the two groups in terms of hearing thresholds obtained with a CI. In spite of a wider spread of results in the CMV group, there were no significant statistical differences in the SIR and VCEG tests or in the MAIS and MUSS questionnaires. There was a significant difference in the CAP test (p=0.049) where the GJB2 group had superior results. Conclusions: The present study has shown that the CMV group had poorer results for the CAP test and a wider spread of results in the other tests. However, the CMV group attained results comparable to children with profound hearing loss and no other deficit, and benefited from rehabilitation with a cochlear implant. [ABSTRACT FROM AUTHOR]

We report a pediatric patient admitted with abdominal pain, diffuse lower extremity edema and watery diarrhea for two months. Laboratory findings including complete blood count, serum albumin, lipid and immunoglobulin levels were compatible with protein losing enteropathy. Colonoscopic examination revealed diffuse ulcers with smooth raised edge (like "punched out holes") in the colon and terminal ileum. Histopathological examination showed active colitis, ulcerations and inclusion bodies. Immunostaining for cytomegalovirus was positive. Despite supportive management, antiviral therapy, the clinical condition of the patient worsened and developed disseminated cytomegalovirus infection and the patient died. Protein losing enteropathy and disseminated cytomegalovirus infection a presenting of feature in steroid-naive patient with inflammatory bowel disease is very rare. Hypogammaglobulinemia associated with protein losing enteropathy in Crohn's disease may predispose the cytomegalovirus infection in previously healthy children. [ABSTRACT FROM AUTHOR]

Objective. To determine the seroprevalence and detection of primary infection by cytomegalovirus (CMV) with immunoglobulin G (IgG) avidity test during the first quarter of pregnancy in the General Hospital in Morelia, Michoacan. Materials and methods. A total of 177 patients were studied employing a modified Elisa test using a chemilumines-centmicroparticleimmunoassay (CMIA) for the detection of CMV antibodies (IgG and immunoglobulin M [IgM]),and IgG avidity. Results. 90.4% were positive for IgG, and of these, 2.3% were also reactive for IgM, and in this group the IgG avidity test reported low avidity for 1.1% and higher avidity in the same percentage. 9.6% were seronegative. Conclusions. Similarity was found with published studies in Mexico. Health professionals should know the clinical algorithms for diagnosis and proper management of CMV infection using the IgG avidity test. [ABSTRACT FROM AUTHOR]

Congenital Cytomegalovirus (CMV) infection and alpha 1-antitrypsin (A1AT) deficiency are separately well described entities, but their simultaneous occurrence can pose a special challenge to a clinician, especially dealing with optimal diagnostic as well as therapeutic approach. Congenital CMV infection is the most common vertically transmitted infection in developed countries. In 85-95% of newborns it runs asymptomatic, while in others it is presented with jaundice, petechias, hepatosplenomegaly and central nervous system damage. A1AT deficiency is on the other hand, the most common genetic liver disease in children, and the clinical spectrum varies from the accidentally detected increased levels of transaminases through to the severe infant cholestasis that can progress to cirrhosis. The following case report describes a two-month old male with severe clinical presentation of congenital CMV infection probably exacerbated due to A1AT deficiency comorbidity. The clinical manifestations and unusually difficult clinical signs this infant presented lead to assumption that the additional liver damage exists. Extensive laboratory analyses were performed, including PCR for CMV DNA, A1AT serum concentration, A1AT genotyping, followed and confirmed with phenotyping. Patient was treated parenteral with ganciclovir, what continued with oral valganciclovir and supportive therapy. Intensive and thorough supportive treatment of the infant resulted in satisfactory progress and excellent outcome. Patient was followed-up till the age of 18 months. The presented case provides excellent example about successful overcoming obstacles in differential diagnosis of A1AT in neonates and infants. Medical charts analysis was the methodology used in making this report. [ABSTRACT FROM AUTHOR]

Rha B, Redden D, Benfield M, Lakeman F, Whitley RJ, Shimamura M. Correlation and clinical utility of pp65 antigenemia and quantitative polymerase chain reaction assays for detection of cytomegalovirus in pediatric renal transplant patients. Abstract: qPCR and pp65 antigenemia assays are used to monitor CMV infection in renal transplant recipients, but correlation of assays in a pediatric population has not been evaluated. Paired CMV real-time qPCR and pp65 antigenemia tests from 882 blood samples collected from 115 pediatric renal transplant recipients were analyzed in this retrospective cohort study for the strength of association and clinical correlates. The assays correlated well in detecting infection (κ = 0.61). Higher qPCR values were demonstrated with increasing levels of antigenemia (p < 0.01). Discordant test results were associated with antiviral treatment (OR 4.33, p < 0.01) and low-level viremia, with odds of concordance increasing at higher qPCR values (OR 3.67, p < 0.01), and no discordance occurring above 8500 genomic equivalents/mL. Among discordant samples, neither test preceded the other in detecting initial infection or in returning to negative while on treatment. Only two cases of disease occurred during the two-yr study period. With strong agreement in the detection of CMV infection, either qPCR or pp65 antigenemia assays can be used effectively for monitoring pediatric renal transplant patients for both detection and resolution of infection. [ABSTRACT FROM AUTHOR]

Abstract: Ample evidence suggests that infection with cytomegalovirus (CMV) leads to accelerated aging of the immune system and may contribute to poor responsiveness to influenza vaccination in older persons. The objective of this study was to investigate whether CMV infection, acquired earlier in life, affects the response to influenza vaccination in a randomized controlled trial among older persons in long-term care facilities. During the 1997–1998 influenza season, 731 residents (median age 83 [interquartile range 78–88], 75.4% female) in 14 long-term care facilities in the Netherlands were randomly assigned to receive 15 or 30μg of inactivated influenza vaccine, followed by a 15μg booster vaccine or a placebo vaccine at day 84. Blood samples were collected at day 0, day 25, day 84 and day 109. Seroresponses to influenza vaccination were measured by hemagglutination-inhibition tests to the A/H3N2 strain at all time points. Subsequently, baseline levels of IgG anti-CMV antibodies were measured using an automated chemiluminescent microparticle immunoassay. Participants with CMV antibody level ≥6AU/mL were considered to harbor CMV infection. At baseline, no differences in pre-vaccination geometric mean antibody titers (GMT) were observed between participants with (n =571, 78.1%) or without CMV infection (n =160, 21.9%). During follow-up, participants with and without CMV infection had similar responses to influenza vaccination as measured with changes in GMT (linear mixed model, adjusted for gender, age, pre-vaccination GMT and vaccination strategy, p =0.46). Analogously, no association was found between CMV infection and a more than 4-fold increase in antibody titer (Generalized Estimating Equations, adjusted OR 1.14 [95%CI 0.80;1.64]) or an antibody titer ≥40 (adjusted OR 1.24 [95%CI 0.86;1.80]). In conclusion, CMV infection did not explain poor responsiveness to influenza vaccination in residents of long-term care facilities. [Copyright &y& Elsevier]

Objective: Between January 2008 and December 2009 the Microbiology and Clinical Microbiology Department, Serology/ ELISA Laboratory evaluated the detection of three infectious agents and we aimed to evaluate the algorithmic position of avidity index (AI) test results in the clinician-laboratory collaboration. Methods: Toxoplasma gondii, cytomegalovirus (CMV) and rubella serological tests were evaluated retrospectively in the serum samples of the 126 cases between January 2008 and December 2009. IgM and IgG antibodies and IgG AI were investigated in the serum samples of the cases by ELISA method. Results: T. gondii, CMV and rubella IgG AI tests were performed in 40, 53 and 33 of 126 cases, respectively. Low AI results were detected in 7 T. gondii, 5 CMV and 1 rubella tests and high AI test results were detected in 29 (72.5%), 45 (84.9%) and 30 (90.9%) of Toxoplasma, CMV and rubella tests, respectively. We detected low avidity test results in 8 (7.3%) of 110 cases which required the triple test. IgM and IgG were positive in 2 of 8 cases. IgM was negative and IgG was positive in 6 of 8 cases. We detected high AI test results in 96 (87.3%) cases. Primarily, direct dual test (IgM and IgG) was required and 90 cases were IgM-negative and IgG-positive, and 6 cases were both IgG and IgM-positive. Later the dual test and AI test were required. Of 16 cases, 5 (31.3%) showed low AI, and 8 showed high AI. Conclusions: With respect to clinician-laboratory collaboration, avidity tests were required primarily together with serologic tests for the detection of these three infectious agents. Although avidity tests have a high cost, it is advisable to perform them if there is a potentially high clinical risk. [ABSTRACT FROM AUTHOR]

Purpose. Drug interactions and toxicities associated with the antiviral management of cytomegalovirus (CMV) infection are described. Summary. The use of current antiviral treatments for CMV in patients undergoing solid organ or hematopoietic stem cell transplantation is categorically characterized by high-toxicity profiles and drug--drug interactions. The consequences of hematologic toxicities may be manifested clinically in several ways, including increased rates of infections and bleeding, more pronounced bone marrow suppression, and the development of anemia. Moreover, patients undergoing solid organ or stem cell transplantation have difficulty tolerating the nephrotoxic effects of current treatments, because their renal function is often already compromised by infection, sepsis, or the administration of other commonly used nephrotoxic drugs. Patients undergoing transplantation have an especially high risk of drug interactions, because multiple drugs are often administered to prevent allograft rejection, to treat or prevent infection, to control pain, and to treat a number of possible comorbid conditions. Commonly used antiviral agents for the management of CMV infection include cidofovir, CMV i.v. immunoglobulin, foscarnet, ganciclovir, and valganciclovir. Drug interactions associated with the use of ganciclovir and foscarnet sodium are numerous and potentially dangerous. At this time, such toxicities are managed by dosage adjustments, temporary discontinuations of medications, and careful monitoring of the patient. Conclusion. Clinically important drug--drug interactions can occur in immunocompromised transplant recipients who are treated for CMV infection. Because of the high toxicity and narrow therapeutic range of the antiviral medications available for CMV management, patients should be carefully monitored for any potential adverse effects from such interactions. [ABSTRACT FROM AUTHOR]

Pediatric Menetrier disease is a rare clinical event with unknown etiology, which has a different course from that in adults. It is characterized by gastric hypertrophy and hypoalbuminemia secondary to protein loss throughout the gastric mucosa. Menetrier disease is usually self-limiting in children. In particular, in patients with immune deficiency, one of the most important cause for Menetrier disease is cytomegalovirus (CMV) infection. This infection can also be observed in immunocompetent children. A girl aged two and a half years with a one-week history of generalized edema, weakness, and decreased urine output was admitted at the Pediatric Department of Şişli Hamidiye Etfal Training and Research Hospital. Periorbital and pretibial edema, abdominal distension, and ascites were detected and laboratory studies revealed hypoalbuminemia and elevated fecal alpha-1 antitrypsin excretion. According to the serological investigations, anti-CMV IgM antibodies were detected positive and CMV DNA values were found to be 1170 copies/mL. The patient was treated with intravenous albumin infusion, PPI therapy, and a high-protein and low-salt diet. On the 10th day of treatment, her condition gradually improved without any antiviral drug. We prepared this presentation because we determined CMV as an etiological agent of protein-losing gastropathy in a child with a healthy immune system. (JAREM 2016; 6: 56-8) [ABSTRACT FROM AUTHOR]

The article examines the prevalence and effect on patient outcome of active human cytomegalovirus infections in patients with prolonged treatment in an intensive care unit. Active cytomegalovirus infection was diagnosed in 35 of 255 patients. Patients with and without active the infection were not significantly different in parameters, such as sex, age, admission category or comorbidities. Mortality rate in patients with cytomegalovirus infection was increased.

The human immune system evolved to defend the organism against pathogens, but is clearly less well able to do so in the elderly, resulting in greater morbidity and mortality due to infectious disease in old people, and higher healthcare costs. Many age-associated immune alterations have been reported over the years, of which probably the changes in T cell immunity, often manifested dramatically as large clonal expansions of cells of limited antigen specificity together with a marked shrinkage of the T cell antigen receptor repertoire, are the most notable. It has recently emerged that the common herpesvirus, cytomegalovirus (CMV), which establishes persistent, life-long infection, usually asymptomatically, may well be the driving force behind clonal expansions and altered phenotypes and functions of CD8 cells seen in most old people. In those few who are not CMV-infected, another even more common herpesvirus, the Epstein-Barr virus, appears to have the same effect. These virus-driven changes are less marked in “successfully aged” centenarians, but most marked in people whom longitudinal studies have shown to be at higher risk of death, that is, those possessing an “immune risk profile” (IRP) characterized by an inverted CD4:8 ratio (caused by the accumulation primarily of CD8+ CD28− cells). These findings support the hypothesis that persistent herpesviruses, especially CMV, act as chronic antigenic stressors and play a major causative role in immunosenescence and associated mortality. [ABSTRACT FROM AUTHOR]

Abstract: In France, screening for cytomegalovirus infection (CMV) during pregnancy is not recommended in routine. The transmission of CMV through breastmilk from mothers to preterm infants is frequent (15–20%). The frequency of neuro-sensorial handicap related to congenital CMV infection in very preterm infants is not well documented. We report the case of a female infant born at 30 weeks of gestation. At 15 days, she developed cholestatic jaundice. Urine cultures were positive for CMV. Diagnostic procedure showed no other cause for jaundice. At 40 days, the infant presented with hepato-splenomegaly, purpura and abnormal skin color related to a symptomatic, secondary CMV infection, probably transmitted through breastmilk. Ganciclovir was begun for 21 days. At 12 months, she presents with normal development. This observation raises questions about breastfeeding in very preterm infants. Unexplained prematurity could reflect recent infection or reactivation in the mother. Thus, because of the well-known risks of prematurity on one hand, and CMV infection on the other, we suggest that detection of CMV seropositive mothers should be considered before allowing breastfeeding. If the mother has serologic evidence of recent infection or reactivation, freezing breastmilk at –20 °C for 3 days may be an option in order to reduce virolactia, especially during early lactation. This may reduce the risk of postnatal vertical virus transmission with minimal logistical difficulties and without interrupting breastfeeding. [Copyright &y& Elsevier]

Purpose. The mechanism of action, pharmacokinetics, and other advantages and disadvantages of ganciclovir and valganciclovir are discussed. Summary. Shortcomings of oral ganciclovir include low bioavailability, large pill burden, patient nonadherence, and the emergence of resistance. Valganciclovir, an oral prodrug of ganciclovir, has a nearly tenfold greater absolute bioavailability than ganciclovir. Dosage adjustment is required for both drugs in patients with renal impairment. Conclusion. The pharmacokinetic profile of valganciclovir offers significant advantages for its use in cytomegalovirus (CMV) prophylaxis. [ABSTRACT FROM AUTHOR]

Purpose. The novel and traditional risk factors for cytomegalovirus (CMV) infection and disease in solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients, the current strategies for the prevention of CMV disease, the emerging syndrome of late-onset CMV disease, and the risk factors for antiviral drug resistance are described. Summary. The evolution of transplantation practices, the changes in the characteristics of donors and recipients, the introduction of novel immunosuppressive drugs, and the widespread use of antiviral drugs for CMV prevention have collectively influenced the natural history of CMV infection and disease in SOT and HSCT recipients. Strategies for CMV prevention with the use of antiviral drugs, whether as prophylaxis or as preemptive therapy, are effective in reducing the incidence of CMV disease in transplant recipients. However, late-onset CMV disease is now emerging as a serious problem. Donor and recipient CMV serostatus and other traditional risk factors for early-onset CMV disease appear to contribute to the occurrence of late-onset CMV disease during the first year after transplantation. Conclusion. The epidemiology of CMV infection and disease has changed after transplantation. Strategies to prevent late-onset CMV disease include the prolonged use of antiviral prophylaxis, but this practice can lead to the emergence of antiviral drug resistance, which has been associated with high rates of morbidity and mortality. [ABSTRACT FROM AUTHOR]

Purpose. A historical perspective and the epidemiology, pathogenesis, and typical patient presentation of cytomegalovirus (CMV) disease in transplant patients; the implications of clinical trials of prophylactic antiviral drug therapy; and unanswered questions about the optimal duration of prophylaxis and the risk of antiviral drug resistance are discussed. Summary. CMV infection and disease are common in transplant patients. They often are the result of transplantation from a CMV-seropositive donor to a CMV-seronegative recipient or reactivation of latent virus in a CMV-seropositive recipient. Reactivation in transplant recipients may be the result of a blunted cytotoxic T-lymphocyte response and an imbalance in the release of pro-inflammatory and anti-inflammatory cytokines. CMV disease develops in many infected patients and frequently involves the graft. Antiviral drug therapies reduce the risk of and delay the onset of CMV disease in transplant recipients. They also reduce the risk of graft injury. Conclusion. The optimal duration of antiviral drug prophylaxis in transplant patients remains to be determined; however, it is clear that antiviral prophylaxis can prevent CMV disease as well as many of the complications associated with CMV disease. [ABSTRACT FROM AUTHOR]

Valganciclovir (Valcyte™) is an orally administered prodrug of the standard anti-cytomegalovirus (CMV) drug ganciclovir. Valganciclovir is as effective as intravenous ganciclovir for the treatment of AIDS-related CMV retinitis, and oral ganciclovir for the prophylaxis of CMV infection and disease in high-risk solid organ transplant recipients. The drug is generally well tolerated and has a similar tolerability profile to that of oral or intravenous ganciclovir, but is devoid of adverse events related to intravenous or indwelling catheter access associated with the use of intravenous ganciclovir, cidofovir and foscarnet. The simple and convenient once-daily valganciclovir regimen offers potential for improved patient compliance. It provides greater systemic ganciclovir exposure than oral ganciclovir, thus reducing the risk of viral resistance when used for prophylaxis in high-risk solid organ transplant recipients. Furthermore, the use of valganciclovir instead of intravenous ganciclovir may provide significant cost savings, based on data comparing oral versus intravenous regimens for the treatment of AIDS-related CMV retinitis. Overall, valganciclovir appears to have some advantages over ganciclovir. Therefore, when used as prophylaxis against CMV infection and disease in high-risk solid organ transplant recipients or as induction and maintenance therapy of CMV retinitis in patients with AIDS, oral valganciclovir is an attractive alternative to other available anti-CMV drugs. [ABSTRACT FROM AUTHOR]