Symptomatic Cytomegalovirus Infection Research Articles

Congenital Cytomegalovirus Infection: Update on Screening, Diagnosis and Treatment: Scientific Impact Paper No. 56.

Cytomegalovirus (CMV) is the most common cause of viral infection in newborn babies, and affects 1 in 200 of all live born infants in high-income countries; and 1 in 71 in low- and middle-income countries. It is a major cause of hearing loss and brain damage. Women may get CMV infection for the first time during pregnancy (primary infection) or may experience 'non-primary' infection, either by reactivation of previous CMV infection or by a new infection with a different strain of the virus. The most common source of infection to pregnant women is the saliva and urine of young children. Therefore, all pregnant women, especially those in regular contact with young children, should be informed about hygiene-based measures to reduce the risks, e.g. handwashing. The UK National Screening Committee recommends against universal antenatal or newborn screening for CMV. Testing for CMV is usually offered only to women who develop symptoms of influenza, glandular fever or hepatitis (liver inflammation) during pregnancy, or for those whom a routine ultrasound scan detects fetal anomalies that suggests possible CMV infection. The risk of harm to the fetus is greatest following primary CMV infection of the woman in early pregnancy, and appears to be very low following infection after 12 weeks of pregnancy. Babies with CMV infection at birth may have jaundice, a rash, enlarged liver or spleen, a small brain, or be small for their gestational age. Around 1 in 8 babies born with CMV infection will have clinically detectable signs at birth. The rest will not have any features detectable by clinical examination alone. Therefore, all infants with CMV infection at birth should be followed up at a minimum of up to 2 years of age or later, depending upon the disease status, to check hearing and brain development. Following primary CMV infection in the first 12 weeks of pregnancy, if the woman starts taking the antiviral medicine valaciclovir (valacyclovir) it reduces the risk of the baby becoming infected. Where CMV infection of the fetus in the womb has been confirmed (by amniocentesis, for example), regular ultrasound scans should be offered every 2-3 weeks until birth. Detailed assessment of the fetal brain is an essential part of these scans. Where maternal CMV infection occurs, but fetal infection is not confirmed, repeated ultrasound scans of the fetus should be offered every 2-3 weeks until birth. In infected fetuses, as well as ultrasound scans, an MRI scan of the brain should be offered at 28-32 weeks of gestation (and sometimes repeated 3-4 weeks later) to assess for any signs of harm to the fetal brain. All babies born to women with confirmed or suspected CMV infection should be tested for CMV with a urine or saliva sample within the first 21 days of life. In newborns with symptomatic CMV infection at birth, treatment with antiviral medicine (valganciclovir or ganciclovir) can reduce hearing loss in 5 out of 6 babies, and improve long-term brain development outcomes in some. There is no licensed vaccine for CMV.

Dynamics and Evolution of Donor-derived Cytomegalovirus Infection in 3 Solid Organ Transplant Recipients With the Same Multiorgan Donor.

Cytomegalovirus (CMV) infection poses a significant risk to immunosuppressed transplant recipients, manifesting through primary infection, reinfection, or reactivation. We analyzed the emergence of drug resistance in CMV infection in 3 patients who were later found to have received an allograft from a shared, deceased donor. The seronegative transplant recipients developed symptomatic CMV infections after bowel/pancreas, kidney, or lung transplantation. Prospective Sanger sequencing was used to identify mutations in the viral DNA polymerase (DP) and protein kinase (PK). DP and PK variants were retrospectively quantified by targeted next-generation sequencing. The impact of the novel DP-A505G substitution on drug susceptibility was assessed using a recombinant virus. Whole-genome sequencing of clinical CMV samples was enabled through target DNA enrichment. The DP-A505G substitution was found in all patient samples and could be associated with a natural polymorphism. A subsequent review of the patients' clinical histories revealed that they had all received organs from a single donor. The CMV infection exhibited divergent evolution among the patients: patient 1 developed resistance to ganciclovir and foscarnet because of 2 DP mutations (V715M and V781I), patient 2 showed no genotypic resistance, and patient 3 developed ganciclovir (PK-L595S) and maribavir resistance (PK-T409M). Interpatient variation across the entire CMV genome was minimal, with viral samples clustering in phylogenetic analysis. All 3 transplant recipients were infected with the same donor-derived CMV strain and readily developed different drug susceptibility profiles. This underscores the importance of judicious antiviral drug use and surveillance in preventing antiviral resistance emergence.

Contribution of fetal blood sampling to determining the prognosis of congenital cytomegalovirus infections: a case-cohort study in Switzerland

Cytomegalovirus is responsible for the most common congenital infection, affecting 0.5% to 1.0% of live births in Europe. Congenital cytomegalovirus infection can be diagnosed during pregnancy by viral DNA amplification in the amniotic fluid, but the prognosis of fetuses without severe brain abnormalities remains difficult to establish on the basis of prenatal imaging alone. To identify predictors of moderate to severe symptomatic cytomegalovirus infection among fetal blood parameters and to propose an algorithm on the basis of these parameters and on prenatal imaging that would provide the best positive and negative predictive values. Fetal blood sampling at 21-28 weeks gestation was performed in fetuses with congenital cytomegalovirus infection confirmed by amniocentesis after maternal infection in the first-trimester or periconceptional period. We compared the levels of hemoglobin, thrombocytes, γ-glutamyl transpeptidase, aspartate aminotransferase, alanine aminotransferase, β2-microglobulin, immunoglobulins G and M, and cytomegalovirus DNA viral loads in amniotic fluid and fetal blood between those with moderate to severe symptomatic infection and those with asymptomatic to mild infection (median follow-up of 36 months for live births). Among 58 fetuses included, 25 (43%) had a moderate to severe symptomatic infection: 16 with severe cerebral abnormalities, 5 with multiple signs or symptoms at birth, 2 with bilateral sensorineural hearing loss, and 2 with neurodevelopmental delay. The values of thrombocytes, aspartate aminotransferase, β2 microglobulin, Immunoglobulin M, and cytomegalovirus viral loads differed significantly between fetuses with moderate to severe symptomatic infection and those with asymptomatic to mild infection. The optimal strategy to predict moderate to severe symptomatic infection was to first perform fetal brain imaging, followed by fetal blood sampling with the following cutoffs: thrombocytes <120,000/mL, viremia ≥5 log10/mL, and β2 microglobulin ≥12 mg/L). This recursive algorithm had a negative predictive value of 100% for moderately to severely symptomatic infection. The combination of thrombocytes, β2-microglobulin, and cytomegalovirus viral load in fetal blood can be used for prognosis determination, particularly in cytomegalovirus-infected fetuses without severe brain abnormalities at the time of prenatal diagnosis. Future studies should evaluate whether these parameters remain useful in infected fetuses who have been treated with valacyclovir before fetal blood sampling.

Cytomegalovirus infection among people living with HIV in Sweden: Case profiles, treatment strategies and patient outcomes at Karolinska University Hospital 2010-2020.

In countries with access to early antiretroviral treatment (ART), opportunistic infections caused by cytomegalovirus (CMV) in people living with HIV (PLWH) are becoming increasingly rare. As potential complications are severe, it is critical to remain aware of this important diagnosis. However, clinical characteristics and prognosis of CMV infection in PLWH in the era of modern ART have not been well described. Here, we compiled the clinical presentation, management and outcome of CMV infection in PLWH treated at the infectious diseases clinic of Karolinska University Hospital during 2010-2020. We identified 51 cases of active CMV infection, based on detection of CMV-DNA, mainly diagnosed in patients with CD4 T-cell count <200 cells/μL (86%). Median time from HIV diagnosis to detection of CMV infection was 16 days. In 20 cases (39%), CMV infection was symptomatic with retinitis identified as a manifestation in 70% of cases. Symptomatic CMV infection was treated for 73 (20-313) days upon diagnosis, mostly using valganciclovir. One-year mortality was 22% and was associated with longer time to ART initiation from HIV diagnosis and with comorbidities, but not with CMV-DNA levels or CD4 count. Immune reconstitution was not significantly compromised in patients with symptomatic CMV, although CD4/8 ratio tended to be lower in patients with systemic CMV infection. Retinitis remains the most common manifestation of symptomatic CMV infection in PLWH. Recognizing CMV infection is important, especially in the management of 'late presenters'. Adequate duration of antiviral therapy and appropriate follow-up must be ensured to avoid complications.

Clinical Characteristics of Infants with Symptomatic Congenital and Postnatal Cytomegalovirus Infection-An 11-Year Multicenter Cohort Study in Taiwan.

(1) Background: Cytomegalovirus (CMV) infection is a prevalent viral disease among infants. The prevalence typically ranges from 0.2% to 2.4% among all newborns. There are limited data regarding the demographic characteristics of infants with symptomatic CMV infections. (2) Methods: In this retrospective cohort study using the Chang Gung Memorial Hospital multicenter database, infants with CMV infection determined by a positive urine culture, positive blood polymerase chain reaction assay or positive immunoglobulin M result for CMV from 2011 through 2021 were included. Clinical characteristics at initial diagnosis, management and outcomes were investigated. Congenital CMV (cCMV) infection is diagnosed within three weeks after birth; postnatal CMV (pCMV) is diagnosed when CMV is detected after the first 3 weeks of life. (3) Results: Among the 505 CMV-infected infants identified, 272 were included in the analysis. According to the age at initial presentation, 21 infants had cCMV infection and 251 had pCMV infection. Higher incidences of prematurity and being small for gestational age and a lower Z score for weight at diagnosis were observed in the cCMV group. While thrombocytopenia (61.9%) was the leading presentation in the cCMV group, hepatitis (59.8%) and prolonged jaundice (21.9%) were more common in the pCMV group. (4) Conclusions: Utilizing an 11-year multicenter database, we demonstrated the characteristics of infants with CMV infection in Taiwan and highlighted the demographic disparities and differing symptoms between the cCMV and pCMV groups. These findings emphasize the necessity for future research to refine screening policies, explore treatment options, and establish follow-up protocols for affected infants.

Symptomatic Cytomegalovirus (CMV) Infection and Antibody-Mediated Rejection (ABMR) of Kidney Allograft

Symptomatic Cytomegalovirus (CMV) Infection and Antibody-Mediated Rejection (ABMR) of Kidney Allograft

#2970 CYTOMEGALOVIRUS INFECTION AND RISK OF NEW-ONSET DIABETES AFTER TRANSPLANTATION: A RETROSPECTIVE STUDY

Abstract Background and Aims New-onset diabetes after transplantation (NODAT) is one of the common complications reported in patients with kidney transplant and is associated with risk of infection, poor allograft and patient survival. There is conflicting research literature regarding the role of cytomegalovirus (CMV) infection in increasing the risk of NODAT development. Aim To assess the risk of development of NODAT in kidney transplant patients with CMV infection Method A total of 59 kidney transplant patients were studied from March 2017 to February 2019. NODAT was defined as two readings of fasting plasma glucose of ≥126 mg/dL at three months post-transplant. CMV viral load was also documented. The 12 months post-transplant allograft and patient survival outcomes were also measured. Results Mean age was 43.4 ± 6.2 years. Nearly one-fourth, 14 (23.7%), of the patients had NODAT. CMV viral load and viremia were high in NODAT group; however, the result did not reach statistical significance. CMV DNA replication was statistically high during 1-6 months post-transplant for NODAT group (P&amp;lt;0.001). Only 7 (11.9%) recipients advanced to symptomatic CMV infection. Also, we found that high CMV viremia load was associated with poor kidney allograft function at 12 months. Conclusion In summary, this study showed that infection with CMV may not be a risk factor to develop NODAT in patients transplanted with kidney. An elevated CMV viral load may decrease the post-transplant allograft function at 12 months. The prompt diagnosis and timely 2 management of CMV infection could substantially lessen the risk to develop NODAT subsequent worsening of allograft and patient survival.

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

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

S2489 Differentiating CMV Colitis From GVHD in Post-Transplant Patients: A Case Study

Introduction: Cytomegalovirus (CMV) infection can complicate the clinical course of immunocompromised patients including allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients, where the infection can be serious. CMV can involve different organs including lungs, brain, eyes, and the GI tract. Signs and symptoms of CMV infection may overlap with other conditions including graft-versus-host disease (GVHD), a multisystem disorder commonly seen in allo-HSCT recipients. Case Description/Methods: A 57-year-old female presented with abdominal pain and diarrhea. Past medical history included relapsed acute myeloid leukemia, treated with azacitidine and venetoclax followed by allo-HSCT. She was recently hospitalized for suspected GVHD with skin, liver, and gastrointestinal involvement. She was also found to have a CMV viral load of 920 IU/mL. Endoscopy showed diffuse inflammation across the GI tract, with biopsies revealing apoptotic bodies consistent with acute GVHD. She was treated with ruxolitinib and prednisone for GVHD, and valganciclovir prophylactically for CMV viremia. At this presentation, labs were notable for lymphocytes of 39 x103/uL and platelets of 22 x 103/uL, and CMV viral load of 1,822,242 IU/mL. CT imaging revealed thickened distal small bowel loops, cecum, and right colon, and edematous gastric walls with submucosal enhancement. Infectious work-up, including stool culture, ova/parasite, and clostridium, was negative. She underwent endoscopic evaluation; EGD showed white discoloration that washed off in the esophagus and diffuse erythematous mucosa in the stomach (Figure). Biopsies from gastric mucosa and right colon mucosa revealed focal nuclear changes. Immunohistochemical stains were positive for CMV. She was diagnosed with refractory CMV colitis and treated with maribavir with improvement of symptoms and reduction of viral load, and prior course of steroids was tapered. Discussion: Immunosuppression for GVHD has been identified as an important risk factor for CMV reactivation. Differentiating CMV colitis and GI-GVHD poses a diagnostic challenge, and endoscopic evaluation is needed to address this. Endoscopy can identify cecal ulcers, a reliable finding for CMV colitis in patients with GVHD after allo-HSCT.1 It is important to timely identify CMV colitis to prevent post-transplant morbidity and mortality. This case also demonstrates effectiveness of maribavir, a novel antiviral, for refractory post-transplant CMV colitis.Figure 1.: EGD images showing white discoloration in the entire esophagus and diffuse erythematous mucosa in the entire examined stomach.

Factors associated with cytomegalovirus infection in antineutrophil cytoplasmic antibody-associated vasculitis: Anarrative review.

Patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV) are vulnerable to opportunistic infections, including cytomegalovirus (CMV) infection. This narrative review aims to identify factors associated with CMV infection in patients with AAV. The literature review was conducted on Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane, PubMed, Scopus, and Web of Science. The start date of the literature search was unrestricted and the end date was February 2022. CMV infection was defined as (a) CMV pp65 antigenemia or positive CMV DNA viral load by polymerase chain reaction or CMV detection on histological specimens, with associated signs and symptoms compatible with CMV infection; (b) presence of CMV clinical syndrome (defined as presence of compatible symptoms and signs and documentation of CMV by biopsy by virus isolation, rapid culture, immunohistochemistry, or DNA in biopsy material as defined by the CMV Drug Development Forum); and (c) CMV infection as coded by the International Statistical Classification of Diseases and Related Health Problems, 10th revision with at least one prescription for CMV treatment. We identified 4505 articles, of which three (2327 patients with AAV) were included. All studies were retrospective and only one of the three studies included only patients with AAV. Low or decreasing lymphocyte counts and higher prednisolone usage were associated with CMV infection in patients with AAV. Patients with AAV with lymphopenia and on high doses of prednisolone should be monitored closely for signs and symptoms of CMV infection, and might benefit from CMV prophylaxis. Prospective studies are urgently needed to better identify causes of CMV infections in patients with AAV.

Pitfalls in the Serological Evaluation of Maternal Cytomegalovirus Infection as a Potential Cause of Fetal and Neonatal Involvements: A Narrative Literature Review.

Cytomegalovirus (CMV) is the most common cause of intrauterine infection and serological assays are the primary tools for assessing CMV infections during pregnancy. CMV-specific immunoglobulin M (IgM) antibodies have been used as a diagnostic marker for primary CMV infection in pregnant women, although CMV-IgM has been detected in non-primary CMV infections. IgG avidity testing may aid the distinguishing of primary from non-primary CMV infection; however, there is no standardized assay for detecting this difference. Moreover, when maternal serology shows positive CMV-IgG with negative CMV-IgM findings, vertical transmission probability following primary CMV infection is often excluded. However, symptomatic congenital CMV infections in the context of negative findings for maternal CMV-IgM have been reported recently. The absence of CMV-IgM is recognized in both primary and non-primary CMV infections. Furthermore, maternal non-primary CMV infections during pregnancy may yield a greater proportion of symptomatic congenital CMV infections than previously thought. If universal prenatal screening is performed, ultrasonography for abnormal fetal findings should be conducted regardless of CMV-IgM antibody status. If not universally screened, CMV antibody screening should be performed whenever routine fetal ultrasound reveals abnormal findings. For suspected fetal CMV infection, amniotic fluid or postnatal infant urine CMV-DNA testing is required.

How to Provide Breast Milk for the Preterm Infant and Avoid Symptomatic Cytomegalovirus Infection with Possible Long-Term Sequelae.

Cytomegalovirus (CMV) is able to replicate in the breast milk of lactating mothers and thus the offspring might be affected by mild to severe symptoms of postnatal CMV disease in case of prematurity; not in term infants. Sepsis-like syndrome affects only very low birth infants; and few cases have been reported. The neurodevelopmental long-term outcome of those preterm infants revealed possible subtle deficiencies, but no major neurodevelopmental impairment. Neurodevelopmental sequelae are still in discussion and seem somewhat overestimated after careful evaluation of the published evidence. The main focus of postnatal CMV disease lies upon the extremely low birth weight of infants. Elimination of CMV is provided by short-term heating methods like the most widely used Holder pasteurization. Freezing and thawing methods leave a risk for CMV acquisition. The benefits of untreated breast milk have to be considered to outweigh the possible sequelae of postnatal CMV infection in the most vulnerable preterm infants.

Risk of New-Onset Diabetes after Transplantation among Kidney Transplant Recipients with Cytomegalovirus Infection: A Retrospective Analysis

Background: New-onset diabetes after transplantation (NODAT) is one of the common complications reported in patients with kidney transplant and is associated with risk of infection, poor allograft and patient survival. There is conflicting research literature regarding the role of cytomegalovirus (CMV) infection in increasing the risk of NODAT development. Objective: To assess the risk of development of NODAT in kidney transplant patients with CMV infection Methods: A total of 59 kidney transplant patients were studied from March 2017 to February 2019. NODAT was defined as two readings of fasting plasma glucose of ≥126 mg/dL at three months post-transplant. CMV viral load was also documented. The 12 months post-transplant allograft and patient survival outcomes were also measured. Results: Mean age was 43.4 ± 6.2 years. Nearly one-fourth, 14 (23.7%), of the patients had NODAT. CMV viral load and viremia were high in NODAT group; however, the result did not reach statistical significance. CMV DNA replication was statistically high during 1-6 months post-transplant for NODAT group (P&lt;0.001). Only 7 (11.9%) recipients advanced to symptomatic CMV infection. Also, we found that high CMV viremia load was associated with poor kidney allograft function at 12 months. Conclusions: In summary, this study showed that infection with CMV may not be a risk factor to develop NODAT in patients transplanted with kidney. An elevated CMV viral load may decrease the post-transplant allograft function at 12 months. The prompt diagnosis and timely management of CMV infection could substantially lessen the risk to develop NODAT subsequent worsening of allograft and patient survival. Keywords: Kidney; Transplant; NODAT; New-onset Diabetes; Cytomegalovirus

Efficacy and Tolerability of Valganciclovir 6 Months vs 6 Weeks in Symptomatic Cytomegalovirus Infection in Infants: An Open Level Randomized Controlled Trial

Congenital cytomegalovirus (CMV) infection is the most common transplacental infection affecting neurodevelopment in infant, commonly hearing and cognitive impairment. This study aimed to compare 6 weeks with 6 months duration of oral valganciclovir in respect of efficacy and tolerability. This randomized controlled trial was conducted in both outpatient and inpatient pediatrics department of a tertiary hospital, on123 infants aged 0-12 months with polymerase chain reaction proven congenital CMV infection over a period of 18 months. The children were divided into two groups, according to the treatment group they belonged to, one is 6 weeks group and other is 6 months group. The children were followed up for 12 months at 3-month interval to compare the virological clearance, psychological, visual, and hearing status, and side effects of drug. The viral load assessment was done at 6 weeks, 6 months, and 12 months of the initial treatment. Mean age of the infants of 6 weeks group is 7.33±1.74months and that of 6 months group is 6.70±2.23 months. Primary outcome is the clearance of virus, exhibited in both groups significantly at 12 weeks of follow up but 100% clearance of virus observed in 6 months group at 6 months of follow up. Whereas 5 patients at 12 weeks and 3 patients at 6 months have shown non clearance of virus among the 6 weeks treatment group. Total 50(80.6%) patients hearing return to normal at 12 months follow up in 6 months treatment group compared to 31(50.8%) in 6 weeks group (p=0.001). Visual improvement also observed among 58(93.5%) patients of 6 months group and 48(78.7%) in 6 weeks group and this difference is statistically significant (p=0.01). At 12 months of follow up 6 months group had shown better neurodevelopmental outcome (p=0.00). Both groups exhibit good tolerance to drug. &#x0D; Conclusion: 6 months duration treatment of valganciclovir in symptomatic CMV infection have shown better neurodevelopmental outcome and visual, auditory improvement compared to 6 weeks duration.

First-line noninvasive management of cytomegalovirus primary infection in pregnancy.

To introduce a first-line noninvasive antenatal management of maternal cytomegalovirus (CMV) primary infection based on ultrasound (US) and magnetic resonance imaging (MRI). Amniocentesis (AC) is used as a second-line tool in cases of abnormalities compatible with fetal CMV infection on US and/or MRI screening. Between January 2011 and October 2018, pregnant women referred with a CMV primary infection on antibody screening were followed up by monthly US scans and a brain MRI at approximately 32weeks. In cases with US and/or MRI abnormalities compatible with congenital CMV infection, AC was performed to confirm the diagnosis. Ninety pregnant women with a primary CMV infection were included (89 singleton and one twin pregnancy). The first-line screening by US and/or MRI was normal for 72 of 91 fetuses (79%). At birth, 19 of these 72 neonates (26%) had a positive urine sample for CMV but were asymptomatic. US and/or MRI abnormalities were identified in 19 fetuses (21%). AC confirmed a fetal CMV infection in 16 fetuses (84%); 12 pregnancies were terminated, and four were continued, with three symptomatic neonates at birth and one poor neurodevelopmental outcome at postnatal follow-up. First-line noninvasive management of maternal CMV primary infection based on serial US scans and brain MRI can be offered to identify fetuses with severe symptomatic congenital CMV infection and reduce the number of ACs without compromising the fetal outcome.

Cytomegalovirus Genotype and Virulence in Infants with Congenital Infection

Abstract Objective Cytomegalovirus (CMV) virulence may depend on genetic variability in several regions of the genome. This study aimed to assess specific CMV genotypes' association with the severity of symptomatic congenital CMV disease at birth. Methods CMV glycoprotein B (gB), glycoprotein N (gN), glycoprotein H (gH), and UL144 strains were identified by nested polymerase chain reaction, restriction fragment length polymorphism, and heteroduplex mobility assay single-stranded conformation polymorphism in 50 infants infected congenitally and 25 asymptomatic infants. Results gN1 (p = 0.010) and UL144-B (p = 0.034) genotypes were associated, by logistic regression, with reduced risk of developing symptomatic congenital CMV infection. gN1 (p = 0.020) and gN3 (p = 0.022) genotypes were associated with reduced risk of severe symptomatic disease. Conversely, gB1 (p = 0.018) was the most virulent genotype and was associated with severe symptoms. Conclusion An association among gB1, gN1, gN3, and UL144-B genotypes of CMV and severity of congenital CMV disease might exist. gB, gN, and UL144 genotypes could be important virological markers of infant infection.

Outcomes in symptomatic preterm infants with postnatal cytomegalovirus infection.

ABSTRACTPremature infants are at risk for developing symptomatic postnatal cytomegalovirus (CMV) disease, including sepsis-like syndrome. We performed a retrospective case–control study including infants born before 32 weeks of gestation and diagnosed with symptomatic postnatal CMV infection during the neonatal period. Neurodevelopmental outcome was evaluated using the Kyoto Scale of Psychological Development 2001 at 18 months of corrected age and at 3 years of age. Twenty-four infants were diagnosed with postnatal CMV infection; of them, 14 had sepsis-like symptoms and 10 had laboratory test abnormalities only. Home oxygen therapy was used significantly higher in the CMV-positive group compared with the control group at hospital discharge (52% vs 21%, P=0.032). The incidence of neurodevelopmental impairment was not significantly different between the two groups at 18 months of corrected age (29% vs 17%, P=0.48) and at 3 years of age (43% vs 29%, P=0.34). Postnatal CMV infection did not have a significant influence on neurodevelopmental outcomes of symptomatic preterm infants, although those in the CMV-positive group appeared worse. Larger studies with long-term follow-up are needed for a better understanding of continued neurodevelopmental outcomes in preterm infants with postnatal CMV infection.

The prevalence of Cytomegalovirus (CMV) infection among infants in Hospital Universiti Sains Malaysia

Background: The seroprevalence of Cytomegalovirus (CMV) infection in Malaysia ranges from 71.6 to 92%. The data on seroprevalence of CMV in Malaysia was scarce, particularly among infants in view of the limitation of the diagnostic methods available. Therefore, the aim of this study is to determine the prevalence of symptomatic CMV infection and its clinical demographics among infants in Hospital USM. Methods and materials: This is a hospital-based prospective cohort study conducted from 1st January until 31st December 2018. Infants serum for CMV IgM and IgG detection and plasma for CMV PCR (viral load monitoring) were collected for detection of CMV infection Maternal serum sample was also requested for serological study. Second serum sample was later requested from the symptomatic infants in between 2 and 4 weeks’ time. Acute infection among infants was defined as evidence of seroconversion of paired sera or positive CMV DNA from blood, urine or saliva. Those infants that were not fulfilling the criteria were regarded as possible passive immunity from the mother or inconclusive if no second sample sent. Results: The prevalence of acute symptomatic CMV infection among infants in Hospital USM was 20.9% (n = 41/196). There was a significant difference in the median age (in days) (p = < 0.01) between acute and non-acute (passive immunity and inconclusive) CMV infection. There were significant association (p < 0.05) for CMV hepatitis, presumed sepsis, rash and sensorineural hearing loss (SNHL) between acute or non-acute CMV infection in infants. Infants with CMV hepatitis were at 8.27 higher odds of being in acute CMV group. Infants without presumed sepsis were at 0.43 higher odds of correctly classified into acute or non-acute CMV infection). Infants presented with rash were at 4.97 higher odds of getting acute CMV infection. Infants with acute CMV infection were at 0.385 higher odds of getting SNHL. Conclusion: The prevalence of CMV infection among infants in Hospital USM was moderately low. CMV hepatitis, presumed sepsis, the presence of rash and SNHL was associated with acute CMV infection in infants.

Genetic and Functional Characterization of Toll-Like Receptor Responses in Immunocompetent Patients With CMV Mononucleosis.

Background: Human cytomegalovirus (CMV) modulates both innate and adaptive immune responses. However, limited data are available on the role of receptors of innate immunity, such as toll-like receptors (TLRs) in contributing to antiviral responses and inflammation.Objectives: The aim of this translational study was to characterize TLR responses in immunocompetent patients with primary and symptomatic CMV infection.Study Design: The study population consisted of 40 patients suffering from CMV mononucleosis and 124 blood donors included as controls. We evaluated the association between TLR2, 3, 4, 7 and 9 gene single nucleotide polymorphism (SNP) and susceptibility to symptomatic CMV infection in immunocompetent adults. Additionally, functional TLR-mediated cytokine responses in supernatants of short-term cultures of whole blood from patients with CMV mononucleosis and blood donors were evaluated.Results: TLR2 and TLR7/8 responses were altered in CMV infected patients as compared to healthy donors and were associated with the release of higher levels of the pro-inflammatory cytokines IL-6 and TNF-α, but not of the anti-inflammatory mediator IL-10. The analysis on the TLR SNPs indicated no difference between patients with CMV infection and the control group.Conclusions: No variation in the TLR2,3,4,7 and 9 genes was associated to the development of symptomatic CMV infection in immunocompetent adults. Nevertheless, TLR-mediated responses in CMV-infected patients appeared to be skewed toward a pro-inflammatory profile, which may contribute to the development of inflammatory symptoms during the CMV mononucleotic syndrome.

Diagnosis of cytomegalovirus infection from clinical whole genome sequencing

Rapid whole genome sequencing (rWGS) of peripheral blood has been used to detect microbial DNA in acute infections. Cytomegalovirus (CMV) is a herpesvirus capable of causing severe disease in neonates and immunocompromised patients. We identified CMV in patients undergoing diagnostic rWGS by matching reads that did not align to the human reference genome to a database of microbial genomes. rWGS was conducted on peripheral blood obtained from ill pediatric patients (age 1 day to 18 years). Reads not aligning to the human genome were analyzed using an in-house pipeline to identify DNA consistent with CMV infection. Of 669 patients who received rWGS from July 2016 through July 2019, we identified 28 patients (4.2%) with reads that aligned to the CMV reference genome. Six of these patients had clinical findings consistent with symptomatic CMV infection. Positive results were highly correlated (R2 > 0.99, p < 0.001) to a CMV-qPCR assay conducted on DNA isolated from whole blood samples. In acutely ill children receiving rWGS for diagnosis of genetic disease, we propose analysis of patient genetic data to identify CMV, which could impact treatment of up to 4% of children in the intensive care unit.