Prevalence and Risk Factors of Cytomegalovirus Among Men Having Sex With Men Enrolled in a Pre-Exposure Prophylaxis Study.

Risk factors for cytomegalovirus (CMV) acquisition in men having sex with men remain unclear. Seroprevalence, incidence, risk factors and shedding of CMV were analyzed among participants enrolled in the HIV pre-exposure prophylaxis IPERGAY-ANRS trial. Among the 417 participants tested, 382 were seropositive at baseline (prevalence of 91.6%; 95%CI[88.5-94.1]) and 10/35 seroconverted during the study (incidence of 17.1 per 100 person-years; 95%CI[8.2-31.3]). A high number of sexual partners was independently associated with CMV seroprevalence. Shedding among CMV-seroconverters was reported for 6/9 and 2/9 at the oral and anal levels, respectively. Our data supports transmission of CMV during sexual contacts. Study part of the ANRS-IPERGAY Clinical trial: ClinicalTrials.gov number, NCT01473472.

Dynamic monitoring of viral gene expression reveals rapid antiviral effects of CD8 T cells recognizing the HCMV-pp65 antigen.

Introduction: Human Cytomegalovirus (HCMV) is a betaherpesvirus that causes severe disease in immunocompromised transplant recipients. Immunotherapy with CD8 T cells specific for HCMV antigens presented on HLA class-I molecules is explored as strategy for long-term relief to such patients, but the antiviral effectiveness of T cell preparations cannot be efficiently predicted by available methods. Methods: We developed an Assay for Rapid Measurement of Antiviral T-cell Activity (ARMATA) by real-time automated fluorescent microscopy and used it to study the ability of CD8 T cells to neutralize HCMV and control its spread. As a proof of principle, we used TCR-transgenic T cells specific for the immunodominant HLA-A02-restricted tegumental phosphoprotein pp65. pp65 expression follows an early/late kinetic, but it is not clear at which stage of the virus cycle it acts as an antigen. We measured control of HCMV infection by T cells as early as 6 hours post infection (hpi). Results: The timing of the antigen recognition indicated that it occurred before the late phase of the virus cycle, but also that virion-associated pp65 was not recognized during virus entry into cells. Monitoring of pp65 gene expression dynamics by reporter fluorescent genes revealed that pp65 was detectable as early as 6 hpi, and that a second and much larger bout of expression occurs in the late phase of the virus cycle by 48 hpi. Since transgenic (Tg)-pp65 specific CD8 T cells were activated even when DNA replication was blocked, our data argue that pp65 acts as an early virus gene for immunological purposes. Discussion: ARMATA does not only allow same day identification of antiviral T-cell activity, but also provides a method to define the timing of antigen recognition in the context of HCMV infection.

Clinical manifestations and immune markers of non-HIV-related CMV retinitis.

BACKGROUND: Since the HIV epidemic in the 1980s, CMV retinitis has been mainly reported in this context. CMV retinitis in persons living with HIV is usually observed when CD4 + cells are below 50 cells/mm3. This study aims to describe the immune markers of non-HIV-related CMV retinitis as well as to describe its clinical manifestations and outcomes. METHODS: Retrospective chart review of consecutive patients with CMV retinitis not related to HIV seen at the uveitis clinic of Jules Gonin Eye Hospital between 2000 and 2023. We reported the clinical manifestations and outcomes of the patients. We additionally assessed immune markers during CMV retinitis (leukocyte, lymphocyte, CD4 + cell and CD8 + cell counts as well as immunoglobulin levels). RESULTS: Fifteen patients (22 eyes) were included. Underlying disease was hematologic malignancy in 9 patients, solid organ transplant in 3 patients, rheumatic disease in 2 patients and thymoma in one patient. The median time between the onset of underlying disease and the diagnosis of retinitis was 4.8 years. Lymphopenia was observed in 8/15 patients (mild = 3, moderate = 4, severe = 1), and low CD4 counts were observed in 9/12 patients, with less than 100 cells/mm3 in 4 patients. Hypogammaglobulinemia was detected in 7/11 patients. Retinitis was bilateral in 7/15 patients, and severe visual loss was frequent (5/19 eyes). Disease recurrence was seen in 7/13 patients at a median time of 6 months after initial diagnosis. No differences in immune markers were observed in patients with vs. without recurrence. CONCLUSION: CMV retinitis is a rare disorder that can affect patients suffering any kind of immunodeficiency. It is associated with a high visual morbidity despite adequate treatment. CD4 + cell counts are usually higher than those in HIV patients, but B-cell dysfunction is common.

Exploring the implementation of an educational film within antenatal care to reduce the risk of cytomegalovirus infection in pregnancy: A qualitative study.

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). FINDINGS: 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. DISCUSSION: 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.

Seroreversion in HIV-Associated Bilateral CMV Retinitis: A Challenging Case Report.

PURPOSE: To report a case of seroreversion in a patient with HIV-associated bilateral CMV retinitis and the challenges associated with detection of this phenomenon in late stages of HIV. METHOD: Retrospective single case report. RESULTS: The clinical picture of the patient on presentation was suggestive of viral retinitis. PCR confirmed a diagnosis of CMV retinitis. Serology for HIV-1 & 2 was negative. A viral load of HIV and CD-4 count confirmed his sero status to be positive for HIV. Improvement in visual acuity and slow resolution of the lesion was noted with both anti-viral for CMV and HIV. A repeat HIV-1 testing was positive with an improvement in CD4 count. CONCLUSION: In highly suspicious individual, with a negative serology (post screening test) for HIV, the disease status should be confirmed by testing the individual for HIV viral load and CD4 count.

The battle between host antiviral innate immunity and immune evasion by cytomegalovirus.

Cytomegalovirus (CMV) has successfully established a long-lasting latent infection in humans due to its ability to counteract the host antiviral innate immune response. During coevolution with the host, the virus has evolved various evasion techniques to evade the host's innate immune surveillance. At present, there is still no vaccine available for the prevention and treatment of CMV infection, and the interaction between CMV infection and host antiviral innate immunity is still not well understood. However, ongoing studies will offer new insights into how to treat and prevent CMV infection and its related diseases. Here, we update recent studies on how CMV evades antiviral innate immunity, with a focus on how CMV proteins target and disrupt critical adaptors of antiviral innate immune signaling pathways. This review also discusses some classic intrinsic cellular defences that are crucial to the fight against viral invasion. A comprehensive review of the evasion mechanisms of antiviral innate immunity by CMV will help investigators identify new therapeutic targets and develop vaccines against CMV infection.

Cytomegalovirus Infection of the Gastrointestinal Tract in Patients on Hemodialysis: A Case Report and Literature Review.

Cytomegalovirus (CMV) infection is widespread in immunocompromised people, and several cases of CMV infections of the gastrointestinal (GI) tract have been reported in these individuals. We present a case of an immunocompetent patient on hemodialysis (HD) who developed CMV colitis. We also conducted a review of the literature on CMV GI tract infections among patients with chronic kidney disease undergoing dialysis. A 46-year-old man with a history of end-stage renal disease and undergoing HD developed severe diarrhea and hematochezia. A colonoscopy revealed ulcers, and CMV infection was identified in the biopsy sample. We successfully treated the patient with valganciclovir for 2 months. Our review of the literature yielded 21 articles and 24 cases of CMV GI tract infection in patients undergoing dialysis, including the current case. Hematochezia and diarrhea were purported to serve as indicators of CMV GI tract infection among patients on dialysis. Thus, clinicians should suspect CMV infection of the GI tract in dialysis patients, who experience unexplained bloody diarrhea, and promptly perform a GI endoscopy and biopsy.

Role of Endoscopic Techniques in the Diagnosis of Complications of Allogeneic Hematopoietic Stem Cell Transplantation: A Review of the Literature.

Allogeneic stem cell transplantation (Allo-SCT) implies that a donor and a recipient are not genetically identical. Allo-SCT is used to cure a variety of conditions, including hematologic malignancies using the graft versus tumor effect, nonmalignant hematologic, immune deficiencies, and, more recently, genetic disorders and inborn errors of metabolism. Given the immunosuppressive and myeloablative nature of some of the conditioning chemotherapy regimens used during the Allo-SCT, patients are often at high risk of infection, including viral infections affecting the gastrointestinal tract, following the transplant. Furthermore, other complications such as hepatic sinusoidal obstruction syndrome (SOS) or graft-versus-host disease may occur post-transplant and may require endoscopy to assist in the diagnosis. This review will provide newer insights into the importance of endoscopic techniques in the diagnosis of post-Allo-SCT complications with a focus on safety and timing.

Biliary stenosis after liver transplant is not associated with cytomegalovirus infection.

Background: Liver transplantation (LT) is the best treatment for end-stage liver disease; however, biliary complications (BCs) still pose a significant challenge. Among the post-transplant BC, strictures and biliary fistulas are the most common. Biliary strictures are classified as anastomotic and non-anastomotic. Some previous studies suggest an association between post-transplant biliary strictures and cytomegalovirus (CMV) infection. In this study, we aimed to identify whether there is an association between CMV infection and biliary strictures in patients undergoing LT. Methods: A retrospective study of 175 patients aged ≥18 years undergoing LT at Felicio Rocho Hospital between 2011 and 2017 was conducted. All included patients received grafts perfused with Institut Georges Lopez-1 (IGL-1) solution from brain-dead donors, survived post-transplantation for more than 120 days, and had a minimum follow-up of 12 months after LT. The diagnosis of CMV was made by antigenemia and biliary strictures by magnetic resonance cholangiopancreatography (MRCP). Results: The average age of the recipients was 54 years. Postoperative BCs occurred in 12% of transplants. The most common BC was stricture (9.1%), with a predominance of anastomotic strictures (AS) over non-AS (NAS) (87.5% vs. 12.5%, respectively). CMV infection was confirmed in 22.9% of patients. In the univariate analysis, post-transplant CMV infection correlated with the development of BCs (P=0.01), as well as biliary strictures (P=0.008). In the multivariate analysis, however, only model for end-stage liver disease (MELD) >21 was a risk factor for the development of BCs in general (P=0.02) and biliary strictures (P=0.01). Conclusions: CMV infection was not an independent risk factor for the development of non-anastomotic post-transplant biliary strictures in this study.

Shape of the art: TCR-repertoire after allogeneic hematopoietic cell transplantation.

The human adaptive immune repertoire is characterized by specificity and diversity to provide immunity against past and future tasks. Such tasks are mainly infections but also malignant transformations of cells. With its multiple lines of defense, the human immune system contains both, rapid reaction forces and the potential to capture, disassemble and analyze strange structures in order to teach the adaptive immune system and mount a specific immune response. Prevention and mitigation of autoimmunity is of equal importance. In the context of allogeneic hematopoietic cell transplantation (HCT) specific challenges exist with the transfer of cells from the adapted donor immune system to the immunosuppressed recipient. Those challenges are immunogenetic disparity between donor and host, reconstitution of immunity early after HCT by expansion of mature immune effector cells, and impaired thymic function, if the recipient is an adult (as it is the case in most HCTs). The possibility to characterize the adaptive immune repertoire by massively parallel sequencing of T-cell receptor gene rearrangements allows for a much more detailed characterization of the T-cell repertoire. In addition, high-dimensional characterization of immune effector cells based on their immunophenotype and single cell RNA sequencing allow for much deeper insights in adaptive immune responses. We here review, existing - still incomplete - information on immune reconstitution after allogeneic HCT. Building on the technological advances much deeper insights into immune recovery after HCT and adaptive immune responses and can be expected in the coming years.

Evaluation of the AltoStar AM16 system for the quantitation of AdV, CMV and HHV-6 DNA from clinical specimens.

The vulnerability of immunocompromised patients to common or opportunistic viral infections is particularly high. The quantitation of viral load in clinical specimens is important for the diagnosis and management of the infection and reactivation in this patient population, particularly transplant recipients. As the new regulation "IVDR" regarding in vitro diagnosis methods is about to come into effect in France, diagnostic laboratories have to implement methods and systems compatible with this new regulation. Technical performance of the AltoStar® Adenovirus (AdV), Cytomegalovirus (CMV) and human Herpesvirus-6 (HHV-6) DNA PCR Kits 1.5 was assessed on the AltoStar Automation system AM16 using reference kits in 146 clinical samples. Overall agreement in clinical specimens was 87.5 % (28/32), 96.8 % (62/64), 100 % (22/22), 100 % (28/28) and 92.8 % (26/28) for AdV, CMV (WB samples and other matrices), HHV-6 A&B respectively. Quantitative results were highly correlated and estimated to be equivalent within a 0.057-0.648 log-amount difference.We found that altona kits on The AltoStar AM16 system are suitable for clinical monitoring of AdV, CMV and HHV-6 in immunocompromised hosts.

Multicenter Analysis of Valganciclovir Prophylaxis in Pediatric Solid Organ Transplant Recipients.

Background: Valganciclovir is the only approved antiviral for cytomegalovirus (CMV) prevention in pediatric solid organ transplantation (SOT). Additional approaches may be needed to improve outcomes. Methods: A multicenter retrospective study from 2016 to 2019 was conducted of pediatric SOT recipients in whom at least 3 months of valganciclovir prophylaxis was planned. Episodes of CMV DNA in blood (DNAemia), CMV disease, drug-related toxicities, as well as other infections in the first year posttransplant and demographic and clinical data were collected. CMV DNAemia in the first year after prophylaxis or during prophylaxis (breakthrough) was analyzed by multivariate hazard models. Results: Among the 749 patients enrolled, 131 (17.5%) had CMV DNAemia at any time in the first year; 85 (11.4%) had breakthrough DNAemia, and 46 (6.1%) had DNAemia after prophylaxis. CMV disease occurred in 30 (4%). In a multivariate model, liver transplantation compared to kidney or heart, intermediate or high risk based on donor/recipient serologies, neutropenia, and valganciclovir dose modifications attributed to toxicity were associated with increased risk of total and/or breakthrough DNAemia. Bacteremia was also associated with increased hazard ratio for CMV DNAemia. In a separate multivariate analysis, rejection occurred more often in those with breakthrough CMV DNAemia (P = .002); liver transplants, specifically, had increased rejection if CMV DNAemia occurred in the first year (P = .004). These associations may be bidirectional as rejection may contribute to infection risk. Conclusions: CMV DNAemia in the first year posttransplantation occurs despite valganciclovir prophylaxis and is associated with medication toxicity, bacteremia, and rejection. Pediatric studies of newer antivirals, especially in higher-risk subpopulations, appear to be warranted.

Interactions of TTV with BKV, CMV, EBV, and HHV-6A and their impact on post-transplant graft function in kidney transplant recipients.

Background: Mono and combined reactivation of latent viruses occurs frequently under immunosuppressive therapy in kidney transplant patients. Recently, monitoring torque teno virus (TTV) reactivation came more into focus as a potential biomarker for immune status. The surrogate characteristics of TTV reactivation on acute rejection, and the combined reactivation with other latent viruses such as cytomegalovirus (CMV), human BK virus (BKV), Epstein-Barr virus (EBV), and human herpes virus-6A (HHV-6A) on allograft function, are unknown so far. Methods: Blood samples from 93 kidney transplant recipients obtained during the first post-transplant year were analyzed for TTV/BKV/CMV/EBV/HHV-6A load. Clinical characteristics, including graft function [glomerular filtration rate (GFR)], were collected in parallel. Results: TTV had the highest prevalence and viral loads at 100% and a mean of 5.72 copies/ml (cp/ml) (log10). We found 28.0%, 26.9%, 7.5%, and 51.6% of simultaneous reactivation of TTV with BKV, CMV, EBV, and HHV-6, respectively. These combined reactivations were not associated with a significantly reduced estimated GFR at month 12. Of interest, patients with lower TTV loads <5.0 cp/ml (log10) demonstrated not only a higher incidence of acute rejection, but also an unexpected significantly earlier occurrence and higher incidence of BKV and HHV-6A reactivation. Correlations between TTV loads, other latent viruses, and immunosuppressive medication were only significant from 6 months after transplant. Conclusion: We were able to observe and support previously introduced TTV load thresholds predicting kidney allograft rejection. However, due to a possible delayed relation between immunosuppressive medication and TTV viral load adaptation, the right time points to start using TTV as a biomarker might need to be further clarified by other and better designed studies.

Bridging the gap: assessing CMV DNAemia in kidney transplant recipients with previous solid organ transplants.

Cytomegalovirus (CMV) infection poses a significant threat to solid organ transplant (SOT) recipients and can lead to various complications and adverse outcomes. In an effort to prevent CMV infection, it is common to utilize prophylactic strategies, including antiviral medications such as valganciclovir, especially for high-risk patients. Risk factors for CMV infection in kidney transplant recipients (KTRs) include CMV mismatch between donor and recipient (i.e., donor positive, recipient negative), and intensity of immunosuppression, such as the use of T-cell depleting agents. However, little attention has been given to KTRs with a history of prior SOTs, despite their prolonged exposure to immunosuppressive regimens. The aim of this retrospective single-center study was to investigate the incidence and implications of CMV DNAemia in KTRs with prior SOTs. The study included 97 KTRs with prior SOTs and 154 KTRs with no prior transplants as a control group. In the study group, the most common SOT before the current kidney transplantation (KT), was a previous KT. Patients in the KTR group with prior SOTs were more sensitized than those in the control group [calculated panel-reactive antibody > 30%: 49 (50.5%) vs. 30 (19.45%) patients, p = 0.001]. There was a 39.2% incidence of CMV DNAemia in the previous SOT group compared to 48.7% in the control group [non-significant (NS)]. Patients with prior SOTs demonstrated a shorter post-transplant time to CMV DNAemia [median time 1.6 months (interquartile range, IQR 0.7-5.8) in the KTRs with prior SOTs vs. 2.6 months (IQR 1.5-8.1) in the control group (p = 0.001)]. Although the study highlights the need for tailored prophylaxis strategies and vigilant monitoring in KTRs with prior SOTs, its limitations, such as its retrospective nature and single-center design, call for further multicenter research to establish comprehensive guidelines for managing CMV DNAemia in this unique patient population. Despite these limitations, this study underscores the importance of recognizing the heightened risk of CMV infection or reactivation in KTRs overall and the potential benefits of proactive intervention to mitigate associated morbidity and mortality.

High burden of CMV infections after simultaneous pancreas-kidney transplantation-a nationwide cohort study.

Cytomegalovirus (CMV) infections remain a common problem after solid-organ transplantation. We characterized the burden of CMV infections, and adverse events of CMV prophylaxis after simultaneous pancreas-kidney transplantation (SPK). We included all SPK patients (n = 236) since 2010 in our country. Immunosuppression was ATG, tacrolimus, mycophenolate, and steroids. Valganciclovir prophylaxis was given to all CMV D+/R- patients for six months, and to seropositive SPK patients for three months since February 2019. CMV DNAemia was monitored with quantitative PCR from plasma. Among D+/R- SPK recipients, post prophylaxis CMV infection was detected in 41/60 (68%) during follow-up. In seropositive SPK recipients with no prophylaxis, CMV infection was detected in 53/95 (56%), vs. 28/78 (36%) in those who received 3 months of prophylaxis (P = 0.01). CMV was symptomatic in 35 (15%) patients, of which 10 required hospitalization. Mean duration of viremia was 28 days (IQR 21-41). Leukopenia was detected in 63 (46%) of the 138 patients with valganciclovir prophylaxis. 7/122 (6%) of the CMV infections detected were defined as refractory to treatment, and three patients had confirmed ganciclovir resistance. SPK recipients experience a high burden of CMV infections despite CMV prophylaxis. Leukopenia is common during valganciclovir prophylaxis.

Unravelling the potential of TIM-3 gene polymorphism in allogeneic hematopoietic stem cell transplantation - a preliminary study.

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.

Advancing Green Chemistry in Antiviral Therapeutics: A Comprehensive Review.

Cytomegalovirus (CMV) is a prevalent virus across the world that belongs to the family Herpesviridae but remains dormant in the body unless the immune system is compromised. In addition, when the bacterium is compromised without any health risks, the infection spreads from one person to another person through body fluids, such as saliva, blood, etc. Ganciclovir is an anti- viral medication used in treating viral infections, especially in the treatment of CMV in people with acquired immune deficiency syndrome and immunity at risk. The quality control of ganciclovir in industries is carried out by using anti-green solvents in large volumes; these solvents are not safe in consideration of environmental factors and analysts. Also, the waste generation by these solvents causes hazardous effects on the environment. Further, using 12 green analytical chemistry principles promotes the awareness of analytical judgments among the research groups. It is a revolutionary step in the analytical field to enhance the safety of the environment, and analysts, apart from safety, help to control waste production and conserve energy-reducing occupational hazards. Many works have been carried out for the quality control of ganciclovir using different solvents, such as acetonitrile, methanol, etc. Despite this, there are no existing methods with green solvents or procedures to reduce energy and waste generation. Therefore, the purpose of this review is to understand the drug profile of ganciclovir and the methods developed.

Feasibility, performances and predictive value of congenital CMV neonatal screening on saliva swabs.

BACKGROUND: Early diagnosis of congenital CMV infection (cCMVI) allows for early intervention and follow-up to detect delayed hearing loss. While CMV PCR in urine is the gold standard for cCMVI diagnosis, saliva testing is often performed. OBJECTIVES: Our aim was to determine (i) if swab saliva sampling needed standardization, (ii) if a threshold value in "virus copies per million cells (Mc)" in saliva samples could improve clinical specificity, and (iii) to establish a correlation between viral load in saliva and symptomatology/outcome of cCMVI. MATERIALS AND METHODS: In our institution, universal newborn screening is performed on saliva swabs at delivery or until day 3 of life. If positive, CMV PCR in urine is done within 2 weeks to confirm or exclude cCMVI. RESULTS: Cell quantification showed that saliva swab sampling was well performed as 95.4 % samples had more than 100 cells/10 µL. There was a good correlation between saliva viral load in copies/mL and in copies/Mc (Pearson's r = 0.96, p < 0.0001). However, threshold values, established to determine a viral load level at which we could confidently identify infected newborns, did not improve positive predictive value (21.8 % for copies/mL and 21 % for copies/Mc vs 25.4 % without threshold) but instead reduced sensitivity (88 % and 85% vs 100 % without threshold). Samples collected on day 2 or 3 had better positive predictive value (38.7 %) compared to those collected on day 1 (23.8 %). Symptomatology at birth was not significantly associated with viral load in saliva at diagnosis. However, sequelae occurrence was associated with viral load in saliva (copies/Mc). DISCUSSION: Our results confirm that saliva swab is a suitable sample for universal neonatal screening. However, identifying newborns that will develop sequelae remains an issue in the management of cCMVI.

Refractory/Resistant Cytomegalovirus Infection in Transplant Recipients: An Update.

Despite the significant progress made, CMV infection is one of the most frequent infectious complications in transplant recipients. CMV infections that become refractory or resistant (R/R) to the available antiviral drugs constitute a clinical challenge and are associated with increased morbidity and mortality. Novel anti-CMV therapies have been recently developed and introduced in clinical practice, which may improve the treatment of these infections. In this review, we summarize the treatment options for R/R CMV infections in adult hematopoietic cell transplant and solid organ transplant recipients, with a special focus on newly available antiviral agents with anti-CMV activity, including maribavir and letermovir.