Congenital cytomegalovirus (CMV) infection is the leading cause of congenital viral infection and brain disease in children in developed countries, occurring in approximately 1% of all live births (from about 0.3% to 2.4%). Mother–child transmission is mainly the result of primary maternal CMV infection, which carries a risk of transmission varying from 14.2% to 52.4% (combined prevalence of 32.4%) [ 1 x 1 Kenneson, A and Cannon, MJ. Review and meta‐analysis of the epidemiology of congenital cytomegalovirus (CMV) infection. Rev Med Virol. 2007; 17: 253–276 Crossref | PubMed | Scopus (645) | Google Scholar See all References 1 ]. Ten per cent of congenitally infected newborns are symptomatic at birth, and permanent neurological injury occurs in up to 60% of these infants [ 2 x 2 Gaytant, MA, Steegers, EA, Semmekrot, BA, Merkus, HM, and Galama, JM. Congenital cytomegalovirus infection: review of the epidemiology and outcome. Obstet Gynecol Surv. 2002; 57: 245–256 Crossref | PubMed | Scopus (208) | Google Scholar See all References , 3 x 3 Ross, DS, Dollard, SC, Victor, M, Sumartojo, E, and Cannon, MJ. The epidemiology and prevention of congenital cytomegalovirus infection and disease: activities of the Centers for Disease Control and Prevention Workgroup. J Womens Health (Larchmt). 2006; 15: 224–229 Crossref | PubMed | Scopus (59) | Google Scholar See all References ]. Even with antiviral therapy, these injuries are often irreversible. Neurological outcomes may include cerebral palsy, mental retardation, sensorineural hearing loss, seizures, and visual impairments. Microcephaly, periventricular calcifications, hydrocephalus, cerebellar atrophy and polymicrogyria have been shown to be strong predictors of an adverse neurological outcome [ 4 x 4 van Gelder‐Hasker, MR, van Wezel‐Meijler, G, de Groot, L, van Geijn, HP, and de Vries, JI. Peri‐ and intraventricular cerebral sonography in second‐ and third‐trimester high‐risk fetuses: a comparison with neonatal ultrasound and relation to neurological development. Ultrasound Obstet Gynecol. 2003; 22: 110–120 Crossref | PubMed | Scopus (21) | Google Scholar See all References 4 ].

Congenital cytomegalovirus (CMV) infection is a leading cause of sensorineural hearing loss (SNHL). The mechanisms of pathogenesis of CMV-related SNHL are still unclear. The aim is to study congenital CMV-related damage in the fetal inner ear, in order to better understand the underlying pathophysiology behind CMV-SNHL. We studied inner ears and brains of 20 human fetuses, all at 21 week gestational age, with a high viral load in the amniotic fluid, with and without ultrasound (US) brain abnormalities. We evaluated histological brain damage, inner ear infection, local inflammatory response and tissue viral load. Immunohistochemistry revealed that CMV was positive in 14/20 brains (70%) and in the inner ears of 9/20 fetuses (45%). In the cases with inner ear infection, the marginal cell layer of the stria vascularis was always infected, followed by infection in the Reissner’s membrane. The highest tissue viral load was observed in the inner ear with infected Organ of Corti. Vestibular labyrinth showed CMV infection of sensory cells in the utricle and in the crista ampullaris. US cerebral anomalies were detected in 6 cases, and in all those cases, the inner ear was always involved. In the other 14 cases with normal brain scan, histological brain damage was present in 8 fetuses and 3 of them presented inner ear infection. CMV-infection of the marginal cell layer of the stria vascularis may alter potassium and ion circulation, dissipating the endocochlear potential with consequent SNHL. Although abnormal cerebral US is highly predictive of brain and inner ear damage, normal US findings cannot exclude them either.

Letermovir (LMV) inhibits HCMV replication by binding to components of the HCMV terminase complex showing a potential role in prevention of HCMV‐related complications in allogenic hematopoietic stem cell transplant recipients (allo‐HSCTRs). However, little is known about breakthrough HCMV infection and the relevance of HCMV DNAemia during prophylaxis. We reported the results of a multicenter prospective study involving five Italian centers in the management of HCMV DNAemia in 75 adult HCMV‐seropositive allo‐HSCTRs undergoing LMV prophylaxis. The aim of the present study was to characterize the presence of real HCMV reactivation during LMV prophylaxis. Then, the presence of circulating infectious HCMV particles was determined by virus isolation and degradation of free‐floating viral DNA. This report provide the first evidence that during LMV prophylaxis the clinical relevance of HCMV DNAemia should be critically considered.

We performed serological and molecular pretransplant screening in solid organ transplant (SOT) donors and recipients in north-central Italy and a surveillance program for human herpes virus 8 (HHV8) infection after transplant, aiming to establish an optimal management of HHV8 infection in SOT recipients. For pretransplant HHV8 screening in both donors and recipients, 6 serological (4 indirect immunofluorescent assays (IFA) and 2 enzyme-linked immunosorbent assays (ELISA) - both HHV8 lytic and latent antigen-based) and 2 molecular assays were used. A reference standard to identify HHV8-positive patients was defined by at least 2 positive assays. All transplant patients at risk to develop HHV8-related disease underwent virological posttransplant monitoring by quantitative real-time PCR assay. HHV8 seroprevalence was 4% (10/249) in donors and 18% (93/517) in organ recipients. The best performance was obtained by 2 lytic antigen-based IFAs that showed almost perfect agreement to the reference standard (0.943 and 0.931 Cohen’s kappa). HHV8-DNA was detected in 6.8% and 2.9% of HHV8-seropositive donor samples by in-house nested PCR and quantitative real-time PCR assays, respectively. After transplant, 3 out of 12 (25%) HHV8-mismatch patients (seropositive donor/seronegative recipient) developed a primary infection, 1 of whom developed a lethal nonmalignant illness. Two out of 93 HHV8-seropositive recipients (2.1%) had viral replication in posttransplant period, 1 of whom developed Kaposi’s sarcoma. Serological assays, specifically lytic IFAs, were the best methodological approach to identify HHV8-infected SOT donors and recipients. A very low incidence (1.9%) of posttransplant HHV8-related disease was observed.

Currently, no consensus has been reached on the optimal blood compartment to be used for surveillance of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) DNAemia. Although several comparative studies have been performed correlating CMV and EBV DNA loads in whole blood (WB) versus plasma, to our knowledge, no studies to date have analyzed the kinetics of both viruses in the 2 blood compartments. In this retrospective noninterventional multicenter cohort study, the kinetics of CMV and EBV DNA in 121 hematopoietic stem cell transplantation (HSCT) recipients were investigated by analyzing in parallel 569 and 351 paired samples from 80 and 58 sequential episodes of CMV and EBV DNAemia, respectively. Unlike previous studies, this study used a single automated molecular method that was CE-marked and Food and Drug Administration-approved for use in quantifying CMV and EBV DNA in both plasma and WB. Furthermore, the complete viral replication kinetics of all episodes (including both the ascending and the descending phases of the active infection) was examined in each patient. The previously observed overall correlation between CMV DNA levels in WB and plasma was confirmed (Spearman's ρ = .85; P < .001). However, although WB and plasma CMV DNAemia reached peak levels simultaneously, in the ascending phase, the median CMV DNA levels in plasma were approximately 1 log10 lower than WB. Furthermore, in patients who received preemptive therapy, CMV DNA showed a delayed decrease in plasma compared with WB. A lower correlation between EBV DNA levels in plasma versus WB was found (Spearman's ρ = .61; P < .001). EBV DNA kinetics was not consistent in the 2 blood compartments, mostly due to the lower positivity in plasma. Indeed, in 19% of episodes, EBV DNA was negative at the time of the EBV DNA peak in WB. Our results suggest a preferential use of WB for surveillance of CMV and EBV infection in HSCT recipients.