Primary cytomegalovirus infection during pregnancy has a high risk of vertical transmission, with severe fetal sequelae mainly associated with first-trimester infections. We conducted a retrospective analysis of 200 IU/kg cytomegalovirus-specific hyperimmune globulin (HIG), used in first-trimester maternal primary infections for congenital infection prevention. The primary outcome was vertical transmission, defined as neonatal viruria or positive amniocentesis if pregnancy was discontinued. HIG, initially administered monthly and since 2019 biweekly, was discontinued in negative amniocentesis cases. Women declining amniocentesis and positive amniocentesis cases with normal sonography were offered monthly HIG until delivery as a treatment strategy. The total transmission rate was 29.9% (32/107; 10 pregnancy terminations with positive amniocentesis, 18 completed pregnancies with positive amniocentesis and 4 declining amniocentesis). Maternal viremia was the only factor associated with fetal transmission (OR 4.62, 95% CI 1.55-13.74). The transmission rate was not significantly different whether HIG was started during the first or second trimester (28.2% vs. 33.3%; p = 0.58), or between monthly and biweekly subgroups (25.7% vs. 37.8%, p = 0.193). Pre-treatment maternal viremia could inform decisions as a predictor of congenital infection.

Ganciclovir (GCV) and its prodrug valganciclovir (VGCV) are antiviral medications primarily used to treat infections caused by cytomegalovirus (CMV), particularly in immunocompromised individuals such as solid organ transplant (SOT) recipients. Therapy with GCV is associated with significant side effects, including bone marrow suppression. Therefore, therapeutic drug monitoring (TDM) is mandatory for an appropriate balance between subtherapeutic and toxic drug levels. This study aimed to develop and validate three novel methods based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) for GCV determination in serum (reference methodology), dried serum spots (DSS), and VAMS-Mitra™ devices. The methods were optimized and validated in the 0.1-25 mg/L calibration range. The obtained results fulfilled the EMA acceptance criteria for bioanalytical method validation. Assessment of DSS and VAMS techniques extended GCV stability to serum for up to a minimum of 49 days (at room temperature, with desiccant). Developed methods were effectively evaluated using 80 clinical serum samples from pediatric renal transplant recipients. Obtained samples were used for DSS, and dried serum VAMS samples were manually generated in the laboratory. The results of GCV determination using serum-, DSS- and VAMS-LC-MS/MS methods were compared using regression analysis and bias evaluation. The conducted statistical analysis confirmed the interchangeability between developed assays. The DSS and VAMS samples are more accessible and stable during storage, transport and shipment than classic serum samples.

BACKGROUND: Road traffic injuries (RTIs) are among the most important issues worldwide. Several studies reported that infection with the neurotropic parasite Toxoplasma gondii (T. gondii) increased the risk of car accidents. In this study, our objective was to investigate the possible associations among latent T. gondii, Cytomegalovirus (CMV), and Herpes Simplex Virus (HSV) infections with the risk of motorcycle accidents in Jahrom (Fars Province), which is a county with a high rate of motorcycle accidents in Iran.
METHODS: In the setting of a case-control study; 176 motorcyclist men, including 88 survivors of motorcycle accidents and 88 motorcyclist without accidents, were considered as case and control groups, respectively. Rates of latent infections with T. gondii, CMV, and HSV were assessed by an enzyme-linked immunosorbent assay (ELISA).
RESULTS: Eleven of 88 (12.5%) in the case group and 22 of 88 (25.0%) in controls were positive for anti-T. gondii IgG antibodies, this difference was statistically significant (OR = 0.42; CI: 0.19-0.95, p = 0.03). The general seroprevalence of CMV (94.3% in the case group vs. 87.5% in the control group, OR = 2.37; CI: 0.78-7.13, p = 0.12) and HSV (63.6% in the case group vs. 62.5% in the control group, OR = 1.05; CI: 0.57-1.94, p = 0.87) were not significantly different between the case and control groups.
CONCLUSIONS: Although latent toxoplasmosis has been associated with traffic accidents in recent reports, we found a negative association between latent toxoplasmosis and motorcycle accidents among survivors of these accidents. As such, latent CMV and HSV infections did not differ significantly between the cases compared to the control groups.

BACKGROUND: Congenital cytomegalovirus (CMV) infection is a leading cause of sensorineural hearing loss and neuro-disability in childhood. In the absence of a licensed vaccine, adoption of hygiene-based measures may reduce the risk of CMV infection in pregnancy, however these measures are not routinely discussed with pregnant women as part of National Health Service (NHS) antenatal care in the United Kingdom (UK).
METHODS: An exploratory qualitative study was conducted, underpinned by Normalization Process Theory (NPT), to investigate how an educational intervention comprising of a short film about CMV may best be implemented, sustained, and enhanced in real-world routine antenatal care settings. Video, semi-structured interviews were conducted with participants who were recruited using a purposive sample that comprised of midwives providing antenatal care from three NHS hospitals (n = 15) and participants from professional colleges and from organisations or charities providing, or with an interest in, antenatal education or health information in the UK (n = 15).
RESULTS: Midwives were reluctant to include CMV as part of early pregnancy discussions about reducing the risk of other infections due to lack of time, knowledge and absence of guidance or policies relating to CMV in antenatal education. However, the educational intervention was perceived to be a useful tool to encourage conversations and empower women to manage risk by all stakeholders, which would overcome some identified barriers. Macro-level challenges such as screening policies and lack of official guidelines to legitimise dissemination were identified.
CONCLUSIONS: Successful implementation of education about CMV as part of routine NHS care in the UK will require an increase in awareness and knowledge about CMV amongst midwives. NPT revealed that \'coherence\' and \'cognitive participation\' between service members are vital to imbed CMV education in routine practice. \'Collective action\' and \'reflexive monitoring\' is required to sustain service changes.

OBJECTIVE: To understand parental perspectives regarding universal newborn screening (UNS) for congenital cytomegalovirus (cCMV) in Canada.
METHODS: A qualitative, patient-led study using the Patient and Community Engagement Research approach consisting of online focus groups and in-depth individual interviews to understand parental preferences regarding UNS for cCMV. Data were analysed iteratively using inductive thematic analysis and narrative story analysis.
METHODS: Canada-wide study conducted via video conference from October to December 2023.
METHODS: 12 participants from five Canadian provinces who self-identified as 18 years of age or older and as having parental lived experience with cytomegalovirus (CMV) or cCMV participated in the study.
RESULTS: We identified three themes: (1) attitudes about UNS for cCMV, including participants\' unanimous support for UNS and confirmation that parental anxiety is not a deterrent for screening, (2) cCMV diagnosis, including the importance of coupling cCMV diagnosis with access to treatment and medical support and (3) awareness of cCMV, where participants shared their frustration about the lack of public and pregnant people\'s awareness of cCMV.
CONCLUSIONS: Parental anxiety is not a deterrent for UNS for cCMV. Children with cCMV and their families deserve every opportunity to attain their best possible outcomes. UNS offers children with cCMV access to early intervention if they need it, and also helps to raise awareness and education to prevent future CMV infections.

To explore the impacts of cytomegalovirus (CMV) infection and antiviral treatment (AVT) on native liver survival (NLS) in biliary atresia (BA) infants. This retrospective cohort study included infants diagnosed as BA between January 2015 and December 2021 at Hunan Children\'s Hospital. CMV infection was defined by DNA polymerase chain reaction alone (DNA data set) and combination of DNA and immunoglobulin M (CMV data set). In the DNA data set of 330 patients, 234 patients (70.9%) survived with their native liver in 2 years, with 113 (73.9%) in the DNA- cohort, 70 (65.4%) in the DNA+ and AVT- cohort and 51 (72.9%) in the DNA+ and AVT+ cohort, without significant differences by log-rank tests. In patients administrated between 2015 and March 2019, there were 206 evaluable patients in the DNA data set, with rates of 5-year NLS of 68.3% in the DNA- cohort, similar to that in the DNA+ and AVT+ cohort (62.2%, p = 0.546), but significantly higher than that in the DNA+ and AVT- cohort (51.4%, p = 0.031). Similar trends were also observed in the CMV data set, although statistically insignificant. CMV infection before or on the day of HPE can reduce the rate of 5-year NLS and AVT was recommended for CMV-infected BA infants.

Objective: To assess the clinical features and effectiveness of antiviral therapy in newborns with sensorineural hearing loss (SNHL) caused by congenital congenital cytomegalovirus (cCMV) infection, and to speculate the risk factors for poor hearing outcomes. Methods: A multicenter prospective cohort study wasconducted, enrolling 176 newborns diagnosed with cCMV at four research centers in Zhejiang Province from March 1, 2021, to April 30, 2024. Clinical characteristics at birth were recorded and hearing was followed up. The children were divided into groups based on their condition at birth, specifically into asymptomatic, mild symptom, and moderate to severe symptom groups. Additionally, they were divided into SNHL and normal hearing groups based on the results of air conduction brainstem audiometry at birth. And they were also divided into treatment and untreated groups according to antiviral treatment. Mann Whitney U test, and chi square test were used for inter group comparison to analyze the differences in clinical features between different disease groups, and to analyze the effects of clinical features, antiviral therapy, and other factors on hearing improvement. Logistic regression analysis was employed to identify the risk factors influencing hearing outcomes. Results: Among the cohort of 176 children diagnosed infection with cCMV, 90 cases were male and 86 cases were female. Of these, 79 cases were asymptomatic, 12 cases classified as mild cCMV and 85 cases as moderate to severe cCMV. Fifty cases belonged to SNHL group, with different degrees of severity, including 30 cases of mild, 9 cases of moderate, 5 cases of severe, and 6 cases of extremely severe SNHL. Among the 121 cases in the normal hearing group, 2 cases (1.7%) exhibited late-onset hearing loss despite having normal hearing at birth. Among 81 cases (46.0%) who completed the hearing follow-up, 71 cases (87.7%) had good hearing outcomes and 10 cases (12.3%) had poor hearing outcomes. Among the 81 children, 29 cases (35.8%) had SNHL at birth. During follow-up, the hearing threshold improved in 19 cases (65.5%), remained stable in 7 cases (24.1%) and progressed in 3 cases (10.3%). A total of 26 cases in the treatment group and 55 cases in the untreated group completed the hearing follow-up assessment. The rate of hearing improvement in the treatment group was found to be higher compared to the untreated group (13 cases (50.0%) vs. 6 cases (10.9%), χ2=15.00, P<0.01), with individuals in the treatment group having a 4.58 times greater likelihood of experiencing hearing improvement (RR=4.58,95%CI 1.96-10.70, P<0.05). However, no statistically significant difference was observed in hearing outcomes between the antiviral treatment group and the untreated group (RR=0.90, 95%CI 0.57-1.41, P=0.517). Multivariate analysis further confirmed SNHL (OR=11.58, 95%CI 2.10-63.93, P=0.005) and preterm birth (OR=4.98, 95%CI 1.06-23.41, P=0.042) as independent risk factors for poor hearing outcomes. Conclusions: SNHL resulting from cCMV infection presents symptoms at birth and can be improved by antiviral therapy. Poor hearing outcomes are associated with SNHL and prematurity.
目的： 探讨新生儿先天性巨细胞病毒（cCMV）感染所致感音神经性耳聋（SNHL）患儿的临床特征、抗病毒治疗情况，并推测听力结局不良的危险因素。 方法： 多中心前瞻性队列研究，纳入2021年3月1日至2024年4月30日浙江省4家医院176例cCMV感染的新生儿为研究对象，记录出生时临床特征并随访听力。根据出生时cCMV感染情况分为无症状组、轻度症状组和中重度症状组；根据出生时气导脑干听结果分为SNHL组和听力正常组；根据抗病毒治疗情况分为治疗组和未治疗组。采用Mann-Whitney U检验、χ2检验进行组间比较，分析临床特征在不同病情分组间的差异，并分析临床特征、抗病毒治疗等对听力改善的影响。采用Logistic回归分析法筛选影响听力结局的危险因素。 结果： 176例cCMV感染患儿中男90例、女86例。无症状组79例、轻度症状组12例、中重度症状组85例。SNHL组50例，其中听力水平轻度30例、中度9例、重度5例、极重度6例；听力正常组121例，其中2例（1.7%）出生时听力正常的患儿出现晚发型听力损伤。81例（46.0%）患儿完成听力随访，听力结局良好者71例（87.7%）、听力结局不良者10例（12.3%）；81例患儿中29例（35.8%）出生时存在SNHL，随访听力阈值好转19例（65.5%），维持稳定7例（24.1%），进展3例（10.3%）。治疗组40例，均为中重度cCMV。完成听力随访的治疗组26例，未治疗组55例。完成听力随访的治疗组听力好转率高于未治疗组［13例（50.0%）比6例（10.9%），χ2=15.00，P<0.01］；治疗组听力好转可能性是未治疗组的4.58倍（RR=4.58，95%CI 1.96~10.70，P<0.05）；抗病毒治疗组和未治疗组的听力结局差异无统计学意义（RR=0.90，95%CI 0.57~1.41，P=0.517）。Logistic多因素分析示SNHL（OR=11.58，95%CI 2.10~63.93，P=0.005）、早产（OR=4.98，95%CI 1.06~23.41，P=0.042）均为听力结局不良的独立危险因素。 结论： cCMV感染所致SNHL在出生时均为症状性感染，抗病毒治疗能改善SNHL。出生时存在SNHL及早产提示听力结局不良。.

BACKGROUND: Cytomegalovirus (CMV) infection in patients with cellular immune deficiencies is associated with significant morbidity and mortality. However, data on CMV end-organ disease (CMV-EOD) in critically ill, immunocompromised patients are scarce. Our objective here was to describe the clinical characteristics and outcomes of CMV-EOD in this population.
METHODS: We conducted a multicenter, international, retrospective, observational study in adults who had CMV-EOD and were admitted to any of 18 intensive care units (ICUs) in France, Israel, and Spain in January 2010-December 2021. Patients with AIDS were excluded. We collected the clinical characteristics and outcomes of each patient. Survivors and non-survivors were compared, and multivariate analysis was performed to identify risk factors for hospital mortality.
RESULTS: We studied 185 patients, including 80 (43.2%) with hematologic malignancies, 55 (29.7%) with solid organ transplantation, 31 (16.8%) on immunosuppressants, 16 (8.6%) with solid malignancies, and 3 (1.6%) with primary immunodeficiencies. The most common CMV-EOD was pneumonia (n = 115, [62.2%] including 55 [47.8%] with a respiratory co-pathogen), followed by CMV gastrointestinal disease (n = 64 [34.6%]). More than one organ was involved in 16 (8.8%) patients. Histopathological evidence was obtained for 10/115 (8.7%) patients with pneumonia and 43/64 (67.2%) with GI disease. Other opportunistic infections were diagnosed in 69 (37.3%) patients. Hospital mortality was 61.4% overall and was significantly higher in the group with hematologic malignancies (75% vs. 51%, P = 0.001). Factors independently associated with higher hospital mortality were hematologic malignancy with active graft-versus-host disease (OR 5.02; 95% CI 1.15-27.30), CMV pneumonia (OR 2.57; 95% CI 1.13-6.03), lymphocytes < 0.30 × 109/L at diagnosis of CMV-EOD (OR 2.40; 95% CI 1.05-5.69), worse SOFA score at ICU admission (OR 1.18; 95% CI 1.04-1.35), and older age (OR 1.04; 95% CI 1.01-1.07).
CONCLUSIONS: Mortality was high in critically ill, immunocompromised patients with CMV-EOD and varied considerably with the cause of immunodeficiency and organ involved by CMV. Three of the four independent risk factors identified here are also known to be associated with higher mortality in the absence of CMV-EOD. CMV pneumonia was rarely proven by histopathology and was the most severe CMV-EOD.

BACKGROUND: T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) molecule is a key regulator of the immune response by exerting an inhibitory effect on various types of immune cells. Understanding the role of TIM-3 in hematopoietic stem cell transplantation (HSCT) may improve transplant outcomes. Our study evaluated the potential association between TIM-3 polymorphisms, namely rs1036199 (A > C) or rs10515746 (C > A), changes which are located in exon 3 and the promoter region of the TIM-3 gene, and post-HSCT outcomes.
METHODS: One-hundred and twenty allogeneic HSCT patients and their respective donors were enrolled and genotyped for TIM-3 single nucleotide polymorphisms (SNPs) using real-time PCR with TaqMan assays.
RESULTS: We found that the presence of the rare alleles and heterozygous genotypes of studied SNP in recipients tended to protect against or increase the risk for acute graft-versus-host disease (aGvHD). For the rs1036199 polymorphism, recipients with the AC heterozygous genotype (p = 0.0287) or carrying the rarer C allele (p = 0.0334) showed a lower frequency of aGvHD development along all I-IV grades. A similar association was detected for the rs10515746 polymorphism as recipients with the CA genotype (p = 0.0095) or the recessive A allele (p = 0.0117) less frequently developed aGvHD. Furthermore, the rarer A allele of rs10515746 SNP was also associated with a prolonged aGvHD-free survival (p = 0.0424). Cytomegalovirus (CMV) infection was more common in patients transplanted with TIM-3 rs10515746 mismatched donors (p = 0.0229) and this association was also found to be independent of HLA incompatibility and pre-transplant CMV-IgG status. Multivariate analyses confirmed the role of these recessive alleles and donor-recipient TIM-3 incompatibility as an independent factor in aGvHD and CMV development.
CONCLUSIONS: Polymorphism of TIM-3 molecule may affect the immune response in HSCT patients. The recessive alleles of rs1036199 and rs10515746 SNPs decreased the risk of developing aGvHD. TIM-3 donor-recipient genetic matching may also affect the risk of post-transplant CMV infection, indicating the potential value of genetic profiling in optimizing transplant strategies.

OBJECTIVE: Efficacy and safety of letermovir as prophylaxis for clinically significant cytomegalovirus infections (csCVMi) was evaluated in randomised controlled trials while most of the real-world studies are single-centre experiences.
METHODS: We performed a retrospective, multi-centre case-control study at six German university hospitals to evaluate clinical experiences in patients receiving CMV prophylaxis with letermovir (n = 200) compared to controls without CMV prophylaxis (n = 200) during a 48-week follow-up period after allogeneic hematopoietic cell transplantation (aHCT).
RESULTS: The incidence of csCMVi after aHCT was significantly reduced in the letermovir (34%, n = 68) compared to the control group (56%, n = 112; p < 0.001). Letermovir as CMV prophylaxis (OR 0.362) was found to be the only independent variable associated with the prevention of csCMVi. Patients receiving letermovir showed significantly better survival compared to the control group (HR = 1.735, 95% CI: 1.111-2.712; p = 0.014). Of all csCMVi, 46% (n = 31) occurred after discontinuation of letermovir prophylaxis. Severe neutropenia (<500 neutrophils/µL) on the day of the stem cell infusion was the only independent variable for an increased risk of csCMVi after the end of letermovir prophylaxis.
CONCLUSIONS: Our study highlights the preventive effects of letermovir on csCMVi after aHCT. A substantial proportion of patients developed a csCMVi after discontinuation of letermovir. In particular, patients with severe neutropenia require specific attention after drug discontinuation.