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1.
Rev Med Virol ; 34(4): e2555, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39031854

ABSTRACT

Congenital cytomegalovirus (cCMV) is among the most common congenital infections globally. Of 85%-90% cCMV-infected infants without symptoms at birth, 10%-15% develop sequelae, most commonly sensorineural hearing loss (SNHL); their childhood neurodevelopmental outcomes are less well understood. Embase and MEDLINE were searched for publications from 16th September 2016 to 9th February 2024 to identify studies reporting primary data on neurodevelopmental outcomes in children with asymptomatic cCMV (AcCMV), measured using assessment tools or as evaluated by the study investigators, clinicians, educators, or parents. The Newcastle-Ottawa scale was applied to studies to assess risk of bias. Of 28 studies from 18 mostly high-income countries, there were 5-109 children with AcCMV per study and 6/28 had a mean or median age at last follow-up of ≥5 years. Children with AcCMV had better neurodevelopmental outcomes than children with symptomatic cCMV in 16/19 studies. Of 9/28 studies comparing AcCMV with CMV-uninfected children, six reported similar outcomes whilst three reported differences limited to measures of full-scale intelligence and receptive vocabulary among children with AcCMV and SNHL, or more generally in motor impairment. Common limitations of studies for our question were a lack of cCMV-uninfected controls, heterogeneous definitions of AcCMV, lack of focus on neurodevelopment, selection bias and inadequate follow-up. There was little evidence of children with AcCMV having worse neurodevelopmental outcomes than CMV-uninfected children, but this conclusion is limited by study characteristics and quality; findings highlight the need for well-designed and standardised approaches to investigate long-term sequelae.


Subject(s)
Asymptomatic Infections , Cytomegalovirus Infections , Humans , Cytomegalovirus Infections/congenital , Cytomegalovirus Infections/virology , Cytomegalovirus Infections/complications , Cytomegalovirus Infections/diagnosis , Asymptomatic Infections/epidemiology , Infant, Newborn , Neurodevelopmental Disorders/virology , Child , Infant , Child, Preschool , Hearing Loss, Sensorineural/virology , Cytomegalovirus
2.
Cancer Med ; 13(14): e7402, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39034465

ABSTRACT

BACKGROUND: Viral reactivations are frequent in hematologial patients due to their cancer-related and drug-induced immunosuppressive status. Daratumumab, an anti-CD38 monoclonal antibody, is used for multiple myeloma (MM) treatment, and causes immunosuppression by targeting CD38-expressing normal lymphocytes. In this single-center two-arm real-life experience, we evaluated incidence of cytomegalovirus (CMV) reactivation in MM patients treated with daratumumab-based regimens as first- or second-line therapy. METHODS: A total of 101 consecutive MM patients were included in this study and were divided into two cohorts: daratumumab and nondaratumumab-based (control) regimens. Patients treated with >2 lines of therapies were excluded to reduce the confounding factor of multi-treated cases. Primary endpoint was the CMV reactivation rate. RESULTS: CMV reactivation rate was significantly higher in the daratumumab cohort compared to control group (33% vs. 4%; p < 0.001), also with higher CMV-DNA levels (>1000 UI/mL in 12% of cases; p < 0.05). However, only one subject developed a CMV disease with severe pneumonia, while 12% of patients were successfully treated with preemptive therapy with valganciclovir. No subjects in the control cohort required anti-CMV agents (p = 0.02). CONCLUSION: Our single-center retrospective experience showed that daratumumab might significantly increase the risk of CMV reactivation in MM, while currently underestimated and related to morbility and mortality in MM patients under treatments. However, further validation on larger and prospective clinical trials are required.


Subject(s)
Antibodies, Monoclonal , Cytomegalovirus Infections , Cytomegalovirus , Multiple Myeloma , Virus Activation , Humans , Multiple Myeloma/drug therapy , Male , Female , Virus Activation/drug effects , Aged , Cytomegalovirus Infections/virology , Cytomegalovirus Infections/drug therapy , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal/adverse effects , Cytomegalovirus/physiology , Middle Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Retrospective Studies , Valganciclovir/therapeutic use , Aged, 80 and over , Antiviral Agents/therapeutic use
3.
Nat Commun ; 15(1): 6007, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39030218

ABSTRACT

An influenza vaccine approach that overcomes the problem of viral sequence diversity and provides long-lived heterosubtypic protection is urgently needed to protect against pandemic influenza viruses. Here, to determine if lung-resident effector memory T cells induced by cytomegalovirus (CMV)-vectored vaccines expressing conserved internal influenza antigens could protect against lethal influenza challenge, we immunize Mauritian cynomolgus macaques (MCM) with cynomolgus CMV (CyCMV) vaccines expressing H1N1 1918 influenza M1, NP, and PB1 antigens (CyCMV/Flu), and challenge with heterologous, aerosolized avian H5N1 influenza. All six unvaccinated MCM died by seven days post infection with acute respiratory distress, while 54.5% (6/11) CyCMV/Flu-vaccinated MCM survived. Survival correlates with the magnitude of lung-resident influenza-specific CD4 + T cells prior to challenge. These data demonstrate that CD4 + T cells targeting conserved internal influenza proteins can protect against highly pathogenic heterologous influenza challenge and support further exploration of effector memory T cell-based vaccines for universal influenza vaccine development.


Subject(s)
CD4-Positive T-Lymphocytes , Cytomegalovirus , Influenza A Virus, H1N1 Subtype , Influenza Vaccines , Macaca fascicularis , Animals , Influenza Vaccines/immunology , Influenza Vaccines/administration & dosage , CD4-Positive T-Lymphocytes/immunology , Influenza A Virus, H1N1 Subtype/immunology , Cytomegalovirus/immunology , Orthomyxoviridae Infections/immunology , Orthomyxoviridae Infections/prevention & control , Influenza A Virus, H5N1 Subtype/immunology , Lung/immunology , Lung/virology , Lung/pathology , Genetic Vectors/genetics , Genetic Vectors/immunology , Male , Female , Memory T Cells/immunology , Immunologic Memory/immunology , Vaccination
4.
BMC Infect Dis ; 24(1): 691, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38992583

ABSTRACT

BACKGROUND: Hemorrhagic varicella (HV) is a particular form of chicken pox.,with high mortality in adults. This form of the disease is rare, to date, approximately 4 cases have been reported. Occasional cases of HV have been documented in adults with hematologic disorders or other diseases. While there is one reported case of simultaneous reactivation of cytomegalovirus in an adult with chickenpox, there is a lack of information regarding changes in liver function indicators for such patients. This is unfortunate, as CMV reactivation can further exacerbate liver failure and increase mortality. In this report, we present a case of hemorrhagic varicella reactivation with cytomegalovirus and provide some relevant discussions. CASE PRESENTATION: We present the case of a 25-year-old male with HV, who had a history of nephrotic syndrome generally controlled with orally administered prednisone at a dosage of 50 mg per day for two months. The patient arrived at the emergency room with complaints of abdominal pain and the presence of hemorrhagic vesicles on his body for the past 3 days. Despite medical evaluation, a clear diagnosis was not immediately determined. Upon admission, the leukocyte count was recorded as 20.96 × 109/L on the first day, leading to the initiation of broad-spectrum antibiotic treatment. Despite the general interpretation that a positive IgG and a negative IgM indicate a previous infection, the patient's extraordinarily elevated IgG levels, coupled with a markedly increased CMV DNA quantification, prompted us to suspect a reactivation of the CMV virus. In light of these findings, we opted for the intravenous administration of ganciclovir as part of the treatment strategy. Unfortunately,,the patient succumbed to rapidly worsening symptoms and passed away. Within one week of the patient's demise, chickenpox gradually developed in the medical staff who had been in contact with him. In such instances, we speculate that the patient's diagnosis should be classified as a rare case of hemorrhagic varicella. CONCLUSION: Swift identification and timely administration of suitable treatment for adult HV are imperative to enhance prognosis.


Subject(s)
Chickenpox , Coinfection , Cytomegalovirus Infections , Cytomegalovirus , Humans , Male , Adult , Cytomegalovirus Infections/drug therapy , Cytomegalovirus Infections/complications , Cytomegalovirus Infections/virology , Cytomegalovirus Infections/diagnosis , Cytomegalovirus/isolation & purification , Chickenpox/drug therapy , Chickenpox/complications , Chickenpox/virology , Chickenpox/diagnosis , Coinfection/virology , Coinfection/drug therapy , Antiviral Agents/therapeutic use , Antiviral Agents/administration & dosage , Hemorrhage/virology , Hemorrhage/etiology , Herpesvirus 3, Human/isolation & purification , Virus Activation
5.
J Med Virol ; 96(7): e29814, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39015038

ABSTRACT

Novel biomarkers reflecting the degree of immunosuppression in transplant patients are required to ensure eventual personalized equilibrium between rejection and infection risks. With the above aim, Torque Teno Virus (TTV) viremia was precisely examined in a large cohort of transplanted immunocompromised patients (192 hematological and 60 solid organ transplant recipients) being monitored for Cytomegalovirus reactivation. TTV load was measured in 2612 plasma samples from 448 patients. The results revealed a significant increase in TTV viral load approximately 14 days following CMV reactivation/infection in solid organ transplant (SOT) patients. No recognizable difference in TTV load was noted among hematological patients during the entire timeframe analyzed. Furthermore, a temporal gap of approximately 30 days was noted between the viral load peaks reached by the two viruses, with Cytomegalovirus (CMV) preceding TTV. It was not possible to establish a correlation between CMV reactivation/infection and TTV viremia in hematological patients. On the other hand, the SOT patient cohort allowed us to analyze viral kinetics and draw intriguing conclusions. Taken together, the data suggest, to our knowledge for the first time, that CMV infection itself could potentially cause an increase in TTV load in the peripheral blood of patients undergoing immunosuppressive therapy.


Subject(s)
Cytomegalovirus Infections , Cytomegalovirus , DNA Virus Infections , Immunocompromised Host , Torque teno virus , Viral Load , Viremia , Humans , Cytomegalovirus/immunology , Cytomegalovirus/physiology , Cytomegalovirus Infections/virology , Cytomegalovirus Infections/immunology , Cytomegalovirus Infections/blood , Male , DNA Virus Infections/virology , DNA Virus Infections/blood , DNA Virus Infections/immunology , Middle Aged , Female , Adult , Immunosuppression Therapy/adverse effects , Virus Activation , Transplant Recipients/statistics & numerical data , Aged , Cohort Studies
6.
Rom J Ophthalmol ; 68(2): 166-169, 2024.
Article in English | MEDLINE | ID: mdl-39006321

ABSTRACT

Aim: To report a case of cytomegalovirus (CMV) neuroretinitis observed in an immunocompetent patient. Materials and methods: The patient presented with a complaint of diminution of vision in both eyes (BE) and had a traumatic cataract in the right eye (RE). Fundus examination of the left eye (LE) revealed an active white, fluffy lesion with an overlying retinal hemorrhage patch with a macular star. The diagnosis of CMV neuroretinitis was established, and the patient commenced treatment with valganciclovir. Results: The patient exhibited no underlying risk factors. Subsequently, a positive response to oral valganciclovir treatment was observed. Discussion: Cytomegalovirus (CMV) neuroretinitis is typically associated with immunocompromised individuals, such as those with HIV/AIDS. The patient's presentation with a traumatic cataract in the right eye and a distinctive fundus appearance in the left eye posed a diagnostic challenge. The absence of common risk factors for CMV infection necessitated a thorough examination and consideration of rare infectious etiologies. The positive response to valganciclovir reinforces its efficacy in managing CMV-related ocular conditions. This case emphasized the necessity for ophthalmologists to maintain a high index of suspicion for CMV and other unusual pathogens when faced with neuroretinitis in patients who do not present with typical systemic immunosuppressive conditions. Early diagnosis and appropriate antiviral therapy prevent potential complications and preserve vision in such atypical presentations. Conclusion: This case underscores the importance of considering rare infectious agents in immunocompetent patients when encountering neuroretinitis, particularly in the absence of typical symptoms or signs of the disease. Abbreviations: CMV = Cytomegalovirus, BE = Both eyes, RE = Right eye, LE = Left eye, CBC = Complete Blood Count, ESR = Erythrocyte Sedimentation Rate, VDRL = Venereal Disease Research Laboratory, FTA-ABS = Fluorescent Treponemal Antibody Absorption, PPD = Purified Protein Derivative, ANA = Anti-Nuclear Antibodies, RF = Rheumatoid Factor, ACE = Anti Converting Enzyme, Ig G = Immunoglobulin G, HSV = Herpes simplex virus.


Subject(s)
Antiviral Agents , Cytomegalovirus Retinitis , Cytomegalovirus , Immunocompetence , Humans , Cytomegalovirus Retinitis/diagnosis , Cytomegalovirus Retinitis/drug therapy , Antiviral Agents/therapeutic use , Cytomegalovirus/isolation & purification , Male , Eye Infections, Viral/diagnosis , Eye Infections, Viral/virology , Eye Infections, Viral/drug therapy , Visual Acuity , Fluorescein Angiography/methods , Valganciclovir/therapeutic use , Fundus Oculi , Tomography, Optical Coherence/methods
7.
Front Immunol ; 15: 1414830, 2024.
Article in English | MEDLINE | ID: mdl-39007131

ABSTRACT

Introduction: Cytomegalovirus (CMV) infection remains a challenge following kidney transplantation (KTx). Currently, CMV-IgG serostatus at transplantation is used to individualize CMV preventive strategies. We assessed the clinical utility of CMV-IGRA for predicting CMV infection following KTx. Methods: We performed a nationwide prospective cohort study from August 2016 until December 2022. Data from all adult KTx recipients in Norway, n=1,546 (R+; n=1,157, D+/R-; n=260, D-/R-; 129), were included with a total of 3,556 CMV-IGRA analyses (1,375 at KTx, 1,188 at eight weeks, 993 one-year after KTx) and 35,782 CMV DNAemia analyses. Results: In R+ recipients CMV-IGRA status, measured at any of the time-points, could not identify any differential risk of later CMV infection. D+/R- recipients remaining CMV-IGRA negative 1-year after transplantation (regardless of positive CMV DNAemia and/or CMV IgG status at that time) had increased risk of developing later CMV infection compared to D+/R- recipients who had become CMV-IGRA positive (14% vs. 2%, p=0.01). Conclusion: Knowledge of pre-transplant CMV-IGRA status did not provide additional information to CMV-IgG serostatus that could improve current post-transplant CMV treatment algorithms. However, D+/R- recipients with a persisting negative CMV-IGRA one-year after transplantation remained at increased risk of experiencing later CMV infection. Therefore we advocate post-transplant CMV-IGRA monitoring in these patients.


Subject(s)
Cytomegalovirus Infections , Cytomegalovirus , Immunity, Cellular , Kidney Transplantation , Humans , Kidney Transplantation/adverse effects , Cytomegalovirus Infections/immunology , Cytomegalovirus/immunology , Male , Female , Middle Aged , Adult , Prospective Studies , Antibodies, Viral/blood , Aged , Norway/epidemiology , Risk Factors , Immunoglobulin G/blood
9.
Crit Care ; 28(1): 243, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39014504

ABSTRACT

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.


Subject(s)
Critical Illness , Cytomegalovirus Infections , Immunocompromised Host , Humans , Retrospective Studies , Male , Female , Cytomegalovirus Infections/immunology , Middle Aged , Aged , Spain/epidemiology , Cohort Studies , Intensive Care Units/statistics & numerical data , Intensive Care Units/organization & administration , France/epidemiology , Adult , Israel/epidemiology , Hospital Mortality , Cytomegalovirus/immunology , Cytomegalovirus/pathogenicity , Risk Factors
10.
J Pak Med Assoc ; 74(7): 1402-1404, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39028091

ABSTRACT

A number of complications are associated with COVID-19 due to reduced immunity. Of these, opportunistic infections are of great significance because of their atypical presentation and low detection rates. Co-infection of various parts of the gastrointestinal system with cytomegalovirus (CMV) is a common occurrence in COVID- 19 patients. Dysphagia and odynophagia are the main complaints of oesophagitis caused by CMV. Colitis due to CMV presents with melena, diarrhoea, or constipation. However, gastritis due to the same agent can be asymptomatic or associated with atypical symptoms like fever and epigastric pain. Cytomegalovirus gastritis can be fatal if not detected early. Hence, continued monitoring of routine baseline investigations is imperative until the complete resolution of COVID-19, as prompt diagnosis improves the outcomes.


Subject(s)
COVID-19 , Cytomegalovirus Infections , Gastritis , SARS-CoV-2 , Humans , Cytomegalovirus Infections/diagnosis , Cytomegalovirus Infections/complications , COVID-19/complications , COVID-19/diagnosis , Gastritis/virology , Gastritis/diagnosis , Male , Asymptomatic Infections , Immunocompetence , Middle Aged , Cytomegalovirus/immunology , Cytomegalovirus/isolation & purification , Coinfection/diagnosis , Female
11.
Egypt J Immunol ; 31(3): 113-122, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38995716

ABSTRACT

End-stage renal disease (ESRD) patients are considered immunocompromised, putting them at high risk for infections, including cytomegalovirus (CMV). CMV can affect hematological parameters, causing further complications in ESRD patients. This study intended to determine the seropositivity of CMV infection in hemodialysis patients and its effect on different blood parameters in ESRD patients to help decrease the overall dialysis associated morbidity and mortality. Blood samples were collected from 45 ESRD patients and 45 controls. A complete blood count was performed using an automated cell counter. CMV-specific IgM and IgG levels were measured using immunochemistry testing. The seropositivity for CMV-IgG was 42.2% in ESRD patients which was significantly higher than in control group (22.2%) (p=0.042). The seropositivity for CMV-IgM was 6.7% in ESRD patients with no difference with the control group (4.4%). The prevalence of anemia was significantly higher in CMV seropositive (77.3%) compared to CMV seronegative (47.8%) ESRD patients. Other studied blood parameters were not different between CMV seronegative and seropositive ESRD patients. In conclusion, CMV infection is a significant concern for dialysis patients and can affect hematological parameters, leading to further complications. Early detection and treatment of CMV infection and monitoring of CMV IgM and IgG levels are critical to prevent further complications and improve clinical outcomes.


Subject(s)
Antibodies, Viral , Cytomegalovirus Infections , Cytomegalovirus , Immunoglobulin G , Immunoglobulin M , Kidney Failure, Chronic , Renal Dialysis , Humans , Renal Dialysis/adverse effects , Cytomegalovirus Infections/blood , Cytomegalovirus Infections/immunology , Cytomegalovirus Infections/epidemiology , Female , Male , Cytomegalovirus/immunology , Kidney Failure, Chronic/therapy , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/immunology , Middle Aged , Immunoglobulin M/blood , Antibodies, Viral/blood , Immunoglobulin G/blood , Adult , Anemia/blood , Anemia/immunology
12.
Sci Rep ; 14(1): 15210, 2024 07 02.
Article in English | MEDLINE | ID: mdl-38956212

ABSTRACT

This retrospective cohort study investigated patients with cytomegalovirus anterior uveitis (CMV AU) and compared treatment outcomes between regional and systemic antiviral therapies. Treatment modalities included topical (2% ganciclovir [GCV] eye drops or 0.2% GCV eye gel) and systemic (intravenous GCV or oral valganciclovir) groups. The comparison parameters included response rates, time to response, recurrence rates, time to recurrence, and complications. Forty-four patients (54.5% male) with a mean age of 56 ± 9.87 years were enrolled, with 31 eyes in the topical group and 13 eyes in the systemic group. The median response time was significantly slower in the topical group (63 days [IQR 28-112]) compared to the systemic group (28 days [IQR 24-59]) (p = 0.04). Treatment response rates were 87.1% (27/31) in the topical group and 100% (13/13) in the systemic group (p = 0.30), while recurrence rates were 37% (10/27) and 69.2% (9/13) (p = 0.056), with a median time to recurrence of 483 days [IQR 145-1388] and 392 days [IQR 203.5-1907.5] (p = 0.20), respectively. In conclusion, both topical and systemic GCV treatments demonstrated favorable outcomes for CMV AU. Systemic GCV showed rapid control of intraocular inflammation.


Subject(s)
Antiviral Agents , Cytomegalovirus Infections , Ganciclovir , Uveitis, Anterior , Humans , Male , Female , Middle Aged , Cytomegalovirus Infections/drug therapy , Cytomegalovirus Infections/virology , Uveitis, Anterior/drug therapy , Uveitis, Anterior/virology , Antiviral Agents/therapeutic use , Antiviral Agents/administration & dosage , Retrospective Studies , Treatment Outcome , Ganciclovir/therapeutic use , Ganciclovir/administration & dosage , Aged , Cytomegalovirus , Adult , Valganciclovir/therapeutic use , Recurrence , Ophthalmic Solutions
13.
Virol J ; 21(1): 149, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38956615

ABSTRACT

OBJECTIVES: This study aimed to characterize incidences of CMV reactivations within one year post-allo-SCT and identify risk factors for CMV second reactivation episode in population with high seropositivity where first CMV reactivation episode deemed to be high. METHODS: This retrospective cohort study analyzed data from 359 allo-SCT patients aged 14 and older admitted to a tertiary academic hospital. Data on demographic and clinical factors, CMV serostatus, conditioning regimens, graft-versus-host disease prophylaxis, engraftment time, and CMV reactivations were collected. RESULTS: First and second CMV reactivations occurred in 88.9% and 18.4% of post-allo-SCT patients respectively. Patients were stratified into two groups based on primary disease necessitating allo-SCT, patients with malignant (Group 1) and non-malignant (Group 2) hematological disease. Factors associated with the second reactivation included cord blood as a stem cell source, human leukocyte antigen mismatch, acute graft-versus-host disease, and hematological malignancies. Patients with non-malignant hematological disease displayed better outcomes, including a higher rate of spontaneous clearance of first CMV reactivation (70% versus 49.4%) and lower rates of second CMV reactivation (9.6% versus 31%) than those with malignant hematological disease. The one-year overall survival rate was 87.7% (95.5% in non-malignant hematological disease and 78.13% in malignant hematological disease). CONCLUSION: Our findings are concordant with previous local study in regard to high rate of first CMV reactivation post-allo-SCT. It appears that patients with nonmalignant hematological disease had better outcomes, such as lower second CMV reactivation and higher survival rates compared to patients with malignant hematological disease. Further investigation is needed to identify other factors affecting recurrent CMV reactivations in allo-SCT in patients with malignant hematological disease.


Subject(s)
Cytomegalovirus Infections , Cytomegalovirus , Transplantation, Homologous , Virus Activation , Humans , Male , Female , Cytomegalovirus Infections/virology , Cytomegalovirus Infections/epidemiology , Middle Aged , Adult , Retrospective Studies , Young Adult , Cytomegalovirus/immunology , Adolescent , Risk Factors , Aged , Transplantation, Homologous/adverse effects , Recurrence , Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Stem Cell Transplantation/adverse effects , Incidence
14.
Viruses ; 16(7)2024 Jul 02.
Article in English | MEDLINE | ID: mdl-39066229

ABSTRACT

Pediatric solid organ transplant (SOT) recipients face a challenging balance between immunosuppression and graft rejection. While Epstein-Barr Virus (EBV) and cytomegalovirus (HCMV) are known contributors to post-transplant lymphoproliferative disease and graft rejection, respectively, the roles of herpesvirus 6 and 7 (HHV6 and HHV7) and the impact of these herpesviruses on cytokine levels remain unclear, leading to gaps in clinical practice. In this associative study, we measured 17 cytokines using a Bio-Plex assay in a meticulously curated plasma sample pool (N = 158) from pediatric kidney and liver transplant recipients over a one-year follow-up period. The samples included virus-negative and virus-positive cases, either individually or in combination, along with episodes of graft rejection. We observed that the elevation of IL-4, IL-8, and IL-10 correlated with graft rejection. These cytokines were elevated in samples where HCMV or HHV6 were detected alone or where EBV and HHV7 were co-detected. Interestingly, latent EBV, when detected independently, exhibited an immunomodulatory effect by downregulating cytokine levels. However, in co-detection scenarios with ß-herpesviruses, EBV transitioned to a lytic state, also associating with heightened cytokinemia and graft rejection. These findings highlight the complex interactions between the immune response and herpesviruses in transplant recipients. The study advocates for enhanced monitoring of not only EBV and HCMV but also HHV6 and HHV7, providing valuable insights for improved risk assessment and targeted interventions in pediatric SOT recipients.


Subject(s)
Cytokines , Cytomegalovirus , Graft Rejection , Herpesvirus 6, Human , Herpesvirus 7, Human , Kidney Transplantation , Liver Transplantation , Humans , Kidney Transplantation/adverse effects , Cytokines/blood , Cytokines/metabolism , Child , Herpesvirus 6, Human/immunology , Male , Female , Child, Preschool , Liver Transplantation/adverse effects , Cytomegalovirus/immunology , Graft Rejection/virology , Graft Rejection/immunology , Herpesvirus 4, Human/immunology , Adolescent , Infant , Herpesviridae Infections/virology , Herpesviridae Infections/immunology , Transplant Recipients , Epstein-Barr Virus Infections/virology , Epstein-Barr Virus Infections/immunology , Cytomegalovirus Infections/virology , Cytomegalovirus Infections/immunology , Herpesviridae
15.
Viruses ; 16(7)2024 Jul 05.
Article in English | MEDLINE | ID: mdl-39066247

ABSTRACT

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.


Subject(s)
Antiviral Agents , Cytomegalovirus Infections , Cytomegalovirus , Drug Resistance, Viral , Transplant Recipients , Humans , Cytomegalovirus Infections/drug therapy , Cytomegalovirus Infections/virology , Cytomegalovirus Infections/etiology , Antiviral Agents/therapeutic use , Cytomegalovirus/drug effects , Cytomegalovirus/physiology , Hematopoietic Stem Cell Transplantation/adverse effects , Organ Transplantation/adverse effects , Acetates , Dichlororibofuranosylbenzimidazole/analogs & derivatives , Quinazolines
16.
Viruses ; 16(7)2024 Jul 11.
Article in English | MEDLINE | ID: mdl-39066272

ABSTRACT

Cytomegalovirus (CMV) infection is a significant clinical concern in newborns, immunocompromised patients with acquired immunodeficiency syndrome (AIDS), and patients undergoing immunosuppressive therapy or chemotherapy. CMV infection affects many organs, such as the lungs, digestive organs, the central nerve system, and eyes. In addition, CMV infection sometimes occurs in immunocompetent individuals. CMV ocular diseases includes retinitis, corneal endotheliitis, and iridocyclitis. CMV retinitis often develops in infected newborns and immunocompromised patients. CMV corneal endotheliitis and iridocyclitis sometimes develop in immunocompetent individuals. Systemic infections and CMV ocular diseases often require systemic treatment in addition to topical treatment.


Subject(s)
Cytomegalovirus Infections , Cytomegalovirus , Iridocyclitis , Humans , Iridocyclitis/virology , Iridocyclitis/drug therapy , Cytomegalovirus Infections/virology , Cytomegalovirus Infections/drug therapy , Cytomegalovirus Infections/complications , Cytomegalovirus Retinitis/drug therapy , Cytomegalovirus Retinitis/virology , Antiviral Agents/therapeutic use , Endothelium, Corneal/virology , Endothelium, Corneal/pathology , Eye Infections, Viral/virology , Eye Infections, Viral/drug therapy , Immunocompromised Host , Keratitis/virology , Keratitis/drug therapy
17.
Viruses ; 16(7)2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39066300

ABSTRACT

Cytomegalovirus (CMV) is the leading infectious cause of brain defects and neurological dysfunctions, including sensorineural hearing loss (SNHL). Targeted screening in neonates failing the hearing screen is currently recommended in Italy according to national guidelines. However, SNHL may not be present at birth; also, congenital CMV (cCMV) may manifest with subtle signs other than SNHL. Therefore, the inclusion of additional criteria for cCMV screening appears clinically valuable. Starting January 2021, we have implemented expanded targeted cCMV screening at our center, with testing in case of maternal CMV infection during pregnancy, inadequate antenatal care, maternal HIV infection or immunosuppression, birthweight and/or head circumference < 10th centile, failed hearing screen, and prematurity. During the first three years of use of this program (2021-2023), 940 (12.3%) of 7651 live-born infants were tested. The most common indication was birthweight < 10th centile (n = 633, 67.3%). Eleven neonates were diagnosed as congenitally infected, for a prevalence of 1.17% (95%CI 0.48-1.86) on tested neonates and of 0.14% (95%CI 0.06-0.23) on live-born infants. None of the cCMV-infected newborns had a failed hearing screen as a testing indication. Implementation of an expanded cCMV screening program appears feasible and of clinical value.


Subject(s)
Cytomegalovirus Infections , Cytomegalovirus , Neonatal Screening , Pregnancy Complications, Infectious , Humans , Cytomegalovirus Infections/congenital , Cytomegalovirus Infections/diagnosis , Infant, Newborn , Female , Neonatal Screening/methods , Pregnancy , Italy/epidemiology , Cytomegalovirus/genetics , Cytomegalovirus/isolation & purification , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/virology , Male , Hearing Loss, Sensorineural/virology , Hearing Loss, Sensorineural/diagnosis , Prevalence
18.
Zhonghua Er Ke Za Zhi ; 62(8): 721-726, 2024 Aug 02.
Article in Chinese | MEDLINE | ID: mdl-39039873

ABSTRACT

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.


Subject(s)
Antiviral Agents , Cytomegalovirus Infections , Hearing Loss, Sensorineural , Humans , Cytomegalovirus Infections/congenital , Cytomegalovirus Infections/complications , Male , Female , Infant, Newborn , Prospective Studies , Hearing Loss, Sensorineural/virology , Hearing Loss, Sensorineural/etiology , Antiviral Agents/therapeutic use , Risk Factors , Cytomegalovirus , Infant , Logistic Models
19.
Int J Mol Sci ; 25(14)2024 Jul 09.
Article in English | MEDLINE | ID: mdl-39062747

ABSTRACT

Salivary glands' neoplasms are hard to diagnose and present a complex etiology. However, several viruses have been detected in these neoplasms, such as HCMV, which can play a role in certain cancers through oncomodulation. The co-infections between HCMV with betaherpesviruses (HHV-6 and HHV-7) and polyomaviruses (JCV and BKV) has been investigated. The aim of the current study is to describe the frequency of HCMV and co-infections in patients presenting neoplastic and non-neoplastic lesions, including in the salivary gland. Multiplex quantitative polymerase chain reaction was used for betaherpesvirus and polyomavirus quantification purposes after DNA extraction. In total, 50.7% of the 67 analyzed samples were mucocele, 40.3% were adenoma pleomorphic, and 8.9% were mucoepidermoid carcinoma. Overall, 20.9% of samples presented triple-infections with HCMV/HHV-6/HHV-7, whereas 9.0% were co-infections with HCMV/HHV-6 and HCMV/HHV-7. The largest number of co-infections was detected in pleomorphic adenoma cases. All samples tested negative for polyomaviruses, such as BKV and JCV. It was possible to conclude that HCMV can be abundant in salivary gland lesions. A high viral load can be useful to help better understand the etiological role played by viruses in these lesions. A lack of JCV and BKV in the samples analyzed herein does not rule out the involvement of these viruses in one or more salivary gland lesion subtypes.


Subject(s)
Coinfection , Cytomegalovirus Infections , Cytomegalovirus , Salivary Gland Neoplasms , Salivary Glands , Humans , Coinfection/virology , Cytomegalovirus Infections/virology , Cytomegalovirus Infections/diagnosis , Cytomegalovirus/genetics , Cytomegalovirus/isolation & purification , Male , Female , Salivary Gland Neoplasms/virology , Middle Aged , Adult , Aged , Salivary Glands/virology , Salivary Glands/pathology , Adenoma/virology , Aged, 80 and over , Carcinoma/virology , DNA, Viral/genetics , DNA, Viral/analysis , Young Adult , Adolescent
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