RESUMEN
AIMS: This study aims to evaluate the presence of EBV, HCMV, and BKV genomic sequences in the plasma samples (active infection/viremia) of kidney transplant recipients suspected of rejection and to investigate host and risk factors related to the activation of these viruses in these patients. METHODS: In this cross-sectional single-center study, plasma samples were collected from 98 suspected kidney transplant rejection patients at Labafinejad Hospital, Tehran, Iran, between December 2022 and June 2023. Quantitative real-time PCR assays for HCMV, EBV, and BK were performed using GeneProof Real-time PCR kits. ROC curve analysis was used to determine the viral load cutoff point for each virus. FINDINGS: HCMV active viremia was detected in 18 (18.36%) recipients, EBV active viremia in 7 (7.14%), and BKV active viremia in 5 (5.10%). ROC results indicated viral load cutoff points of 778, 661, and 457 points for HCMV, EBV, and BKV, respectively. The duration of time after transplantation significantly differed between active viremia and no viremia groups (120.5 vs. 46 months, P = 0.014). In the BKV active viremia group, the increase in creatinine compared to baseline creatinine was significantly higher than in the no viremia group (2.7 vs. 0.8, P = 0.017). The odds ratio of HCMV active viremia in patients taking tacrolimus was 2.84 times higher, and the odds of HCMV active viremia in patients taking antithymocyte globulin was 3.01 times higher than in patients not taking these drugs. CONCLUSION: Rapid and timely diagnosis of viral active infections in kidney transplant patients is crucial for effective disease management and implementation of appropriate treatment strategies. Identifying potential risk factors, including host and treatment-related factors that influence transplantation, can facilitate the development of suitable preventive strategies.
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Virus BK , Infecciones por Citomegalovirus , Citomegalovirus , Infecciones por Virus de Epstein-Barr , Rechazo de Injerto , Herpesvirus Humano 4 , Trasplante de Riñón , Infecciones por Polyomavirus , Carga Viral , Viremia , Humanos , Trasplante de Riñón/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Virus BK/aislamiento & purificación , Virus BK/genética , Adulto , Estudios Transversales , Infecciones por Polyomavirus/virología , Infecciones por Virus de Epstein-Barr/virología , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Citomegalovirus/virología , Citomegalovirus/aislamiento & purificación , Citomegalovirus/genética , Rechazo de Injerto/virología , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/aislamiento & purificación , Irán/epidemiología , Factores de Riesgo , Infecciones Tumorales por Virus/virología , Infecciones Tumorales por Virus/sangre , Anciano , Adulto Joven , Receptores de Trasplantes/estadística & datos numéricosRESUMEN
BACKGROUND: Overall, 20-30% of all cancers are estimated to be linked to infectious agents. Polyomaviruses are oncogenic cause in rodent models, readily transform their cells, and cause chromosomal instability in animal and human cells in-vitro. Some reports have indicated the presence of JCPyV and BKPyV in some human tumors. The JCPyV and BKPyV genome encodes some transforming proteins such as LT-Ag. Thus, these viruses could cause or promote some neoplasia, such as lymphomas, pancreatic, prostate, and colorectal cancers. Colorectal cancer (CRC) is the third most common cancer in the world. Risk factors for developing CRC are associated with personal features or habits, such as age, lifestyle, and gut microbiota. MATERIALS AND METHODS: In this study, we examined the prevalence of JCPyV and BKPyV in the 23 fecal samples of CRC patients and 24 healthy samples (control group). Virus DNA was extracted by a Favorgen DNA extraction kit. The large T antigen of JCPyV and VP1 of BKPyV were investigated by optimized multiplex PCR. RESULTS: One of the samples was positive for the JCPyV (4.3%), while in the samples of healthy individuals, the JCPyV was negative. Also, positive results for BKPyV PCR were obtained for five cases (21.7%) in the samples of the CRC group and one case (4.1%) in healthy individuals. CONCLUSION: The result showed no direct correlation between tumorigenesis and polyomavirus infections in CRC development. However, the exact role of BKPyV and JCPyV is still controversial and needs further study with larger sample size.
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Virus BK , Neoplasias Colorrectales , Virus JC , Reacción en Cadena de la Polimerasa , Humanos , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/virología , Virus BK/genética , Virus BK/aislamiento & purificación , Virus JC/genética , Virus JC/aislamiento & purificación , Masculino , Persona de Mediana Edad , Femenino , Anciano , Infecciones por Polyomavirus/diagnóstico , Infecciones por Polyomavirus/virología , Adulto , Heces/virologíaRESUMEN
BK polyomavirus-associated nephropathy (PyVAN) remains a serious threat for renal dysfunction and graft loss in kidney transplant recipients on immunosuppressive medication. In this study, a pilot cohort of 16 kidney transplant recipients were recruited of which eight were with significant BKPV viremia (sBKPV) and the rest were controls matched to age, gender, and time since transplant. We used next-generation sequencing to characterize the miRNA expression profile in urine samples. In total, the expression of 8 miRNAs (miR-16-5p,miR-200c-3p,bkv-miR-B1-3p,let-7b-3p,miR-1269b,bkv-miR-B1-5p,miR-193a-3p,miR-944) were upregulated whereas 21miRNAs (miR-134-5p,miR-4724-5p,miR-127-3p,miR-6500-3p,miR-507,miR-378b,miR-3911,miR-211-5p,miR-486-5p,miR-143-3p,miR-3195,miR-1307-5p,miR-29a-5p,miR-378f,miR-12136,miR-378g,miR-144-3p,miR-378a-3p,let-7i-5p,miR-204-5p,miR-146a-5p) were downregulated with fold change > 2. We found that bkv-miR-B1-5p and bkv-miR-B1-3p have 19-fold and 5-fold higher expression values in BKPV viremia patient samples, respectively. A few earlier studies have reported BKV miRNA in urine and serum samples using the RT- PCR from PyVAN patients. Our results corroborated findings from earlier studies and highlighted the need for additional evaluation of the role of sequencing approaches for monitoring BKPV specific and host miRNAs to better understand the viral reactivation and disease pathogenesis.
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Virus BK , Trasplante de Riñón , MicroARNs , Infecciones por Polyomavirus , Humanos , Trasplante de Riñón/efectos adversos , Virus BK/genética , Virus BK/aislamiento & purificación , MicroARNs/genética , MicroARNs/sangre , Infecciones por Polyomavirus/virología , Masculino , Persona de Mediana Edad , Femenino , Adulto , Infecciones Tumorales por Virus/virología , Proyectos PilotoRESUMEN
Since the significance of viral infections in children and adolescents with nephrotic syndrome (NS) is yet to be defined, this study intended to estimate the occurrence, pattern, and outcomes of some DNA viral infections in children with NS. METHODS: A prospective study was conducted to determine the genome identification of the viruses Epstein-Barr (EBV), human cytomegalovirus (HCMV), human herpesvirus 6 (HHV-6 type A and type B) and 7 (HHV-7), polyomavirus (BKV), and human adenovirus (HAdV) in plasma and urine samples of pediatric patients with NS. RESULTS: A total of 35 patients aged 1 to 18 years with NS and under immunosuppressant drugs participated in the study. Plasma and urine samples were collected at regular intervals during a median follow-up of 266 days (range 133-595), and DNA was analyzed to detect the selected DNA viruses. Eleven patients (31.4%) had active virus infections, and patterns were classified as coinfection, recurrent, and consecutive. Of these, six patients (54.5%) presented viral coinfection, six (54.5%) viral recurrence, and seven patients (63.3%) had viral consecutive infection. Ten of the eleven patients with active infection had a proteinuria relapse (91%) and eight (72.7%) were hospitalized (p = 0.0022). Active HCMV infection was the most frequent infection and was observed in six patients (54.5%), three of the eleven patients (27.2%) had suspected HCMV disease in the gastrointestinal tract, and one had HHV-7 coinfection. The frequency of other infections was: 9% for HHV-6, 45.5% for BKV, 27.3% for HHV-7, 18.2% for EBV, and 18.2% for HAdV. CONCLUSION: viral infections, especially HCMV, can be an important cause of morbidity and nephrotic syndrome relapse in children.
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Virus BK , Síndrome Nefrótico , Humanos , Síndrome Nefrótico/virología , Síndrome Nefrótico/complicaciones , Adolescente , Niño , Masculino , Femenino , Preescolar , Virus BK/genética , Virus BK/aislamiento & purificación , Lactante , Estudios Prospectivos , ADN Viral/genética , Herpesviridae/genética , Herpesviridae/clasificación , Herpesviridae/aislamiento & purificación , Coinfección/virología , Infecciones por Herpesviridae/virología , Adenoviridae/genética , Adenoviridae/aislamiento & purificación , Adenoviridae/clasificaciónRESUMEN
Guidelines recommend monitoring of Epstein-Barr virus (EBV) and BK virus (BKV) in solid organ and hematopoietic stem cell transplant patients. The majority of quantitative DNA testing for EBV and BKV employs unstandardized individual laboratory-developed testing solutions (LDTs), with implications for accuracy, reproducibility, and comparability between laboratories. The performance of the cobas EBV and cobas BKV assays was assessed across five laboratories, using the World Health Organization International Standards (WHO IS) for EBV and BKV, and the National Institute of Standards and Technology Quantitative Standard for BKV, and results were compared with the LDTs in use at the time. Methods were also compared using locally sourced clinical specimens. Variation was high when laboratories reported EBV or BKV DNA values using LDTs, where quantitative values were observed to differ by up to 1.5 log10 unit/mL between sites. Conversely, results from the cobas EBV and cobas BKV assays were accurate and reproducible across sites and on different testing days. Adjustment of LDTs using the international standards led to closer alignment between the assays; however, day-to-day reproducibility of LDTs remained high. In addition, BKV continued to show bias, indicating challenges with the commutability of the BKV International Standard. The cobas EBV and cobas BKV assays are automated, aligned to the WHO IS, and have the potential to reduce the variability in viral load testing introduced by differences in LDTs. Standardization of reporting values may eventually allow different centers to compare data to allow clinical decision thresholds to be established supporting improvements in patient management.IMPORTANCEThe application of center-specific cut-offs for clinical decisions and the variability of LDTs often hinder interpretation; thus, the findings reported here support the need for standardization in the field of post-transplant monitoring of EBV and BKV to improve patient management. Alongside the choice of assay, it is also important to consider which standard to use when deciding upon a testing methodology. This is a call to action for standardization, as treatment for EBV and BKV is driven by viral load test results, and the more accurate and comparable the test results are across institutions, the more informed and better the treatment decisions can be.
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Virus BK , Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Carga Viral , Humanos , Virus BK/aislamiento & purificación , Virus BK/genética , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/aislamiento & purificación , Carga Viral/normas , Carga Viral/métodos , Reproducibilidad de los Resultados , Infecciones por Virus de Epstein-Barr/diagnóstico , Infecciones por Virus de Epstein-Barr/virología , Infecciones por Polyomavirus/diagnóstico , Infecciones por Polyomavirus/virología , ADN Viral/genética , ADN Viral/análisis , Técnicas de Diagnóstico Molecular/normas , Técnicas de Diagnóstico Molecular/métodos , Infecciones Tumorales por Virus/diagnóstico , Infecciones Tumorales por Virus/virologíaRESUMEN
Polyomaviruses BK (BKPyV) and JC (JCPyV), belonging to the Polyomaviridae, are responsible for human pathologies. In kidney transplant recipients, BKPyV replication can lead to irreversible nephron damage whereas JCPyV replication remains asymptomatic. Concomitant replication is rare and potential competition between the infections has been described. The aim of this retrospective case-control study was to describe the molecular epidemiology and risk factors associated with BKPyV and JCPyV replication in a cohort of kidney transplant recipients. In total, 655 urine samples from 460 patients were tested for BKPyV and JCPyV DNA. Positive samples were submitted to strain genotyping. Demographic and clinical characteristics were also compared. Isolated JCPyV and BKPyV was found in 16.5% and 23.3% of patients, respectively; co-replication was rare (3.9%). BKPyV strains Ib-2, Ib-1, and IVc-2 were the most prevalent. JCPyV strains mostly belonged to genotypes 4 and 1B. During follow-up, JCPyV shedding significantly reduced the risk of BKPyV DNAuria, with an odds ratio of 0.57 (95% confidence interval: 0.35-0.99), and was associated with better prognosis than BKPyV replication, based on the estimated glomerular filtration rate. Molecular epidemiology of BKPyV and JCPyV strains in our region was similar to previous studies. This study suggests that JCPyV is benign and appears to limit damaging BKPyV replication. JCPyV DNAuria screening could thus be a useful strategy to predict BKPyV-related outcomes.
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Virus BK , Genotipo , Virus JC , Trasplante de Riñón , Epidemiología Molecular , Infecciones por Polyomavirus , Humanos , Virus BK/genética , Virus BK/aislamiento & purificación , Infecciones por Polyomavirus/epidemiología , Infecciones por Polyomavirus/virología , Infecciones por Polyomavirus/orina , Trasplante de Riñón/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Virus JC/genética , Virus JC/aislamiento & purificación , Estudios de Casos y Controles , Adulto , Esparcimiento de Virus , Anciano , Receptores de Trasplantes/estadística & datos numéricos , Infecciones Tumorales por Virus/epidemiología , Infecciones Tumorales por Virus/virología , Infecciones Tumorales por Virus/orina , ADN Viral/orina , ADN Viral/genética , Aloinjertos/virologíaRESUMEN
Little is known about the urinary virome and how it interacts with the host, particularly in renal transplant diseases. Using metagenomic sequencing, we characterized the urinary virome of 23 kidney transplant recipients longitudinally (11 BKV+ patients and 12 BKV- patients). We applied linear mixed effects models, PERMANOVA, k-means clustering, and MaAsLin2 algorithms to determine virome signatures associated with post-transplant time, BK viremia status, and patient sex. We found that the richness and alpha diversity of urinary virome were significantly different in renal transplant recipients with BKV+ over time in comparison to BKV- (richness P = 0.012, alpha P < 0.0001). Female BKV- patients had significantly higher virome richness than males (P = 0.0063). Virome beta diversity was significantly different between patients by BKV status (P < 0.001). Additionally, we identified underlying interactions between patient sex and BKV status, in terms of virome beta diversity (P = 0.008). BK polyomavirus infections were primarily of subtypes IA, IB1, and IB2. The non-BK dominant samples clustered into six urinary virome community states. BKV- samples had more anelloviruses than BKV+ samples though this difference was not statistically significant. Lastly, we identified specific viruses, associated with BKV+ and time in our samples. Our results indicate that dynamic alterations in the urinary virome over the post-transplant period in kidney transplant recipients can be shaped by BK viremia and patient sex. These findings advance our fundamental understanding of the urinary virome and support a new line of investigation in renal disease and transplantation. IMPORTANCE: The urinary microbiome is increasingly implicated in renal health and disease. While most research focuses on bacteria communities of the microbiome, factors that influence the urinary virome are not understood. Here, we investigated the urinary virome of 23 adult kidney transplant recipients longitudinally over 14 weeks post-transplant. We show that alterations in the urinary virome are associated with kidney transplant recipients with BK polyomavirus viremia that can lead to BK nephropathy and allograft rejection. By modeling the temporal dynamics post-transplant, we delineated specific profiles of the urinary virome associated with patient sex and urinary community states. These findings reveal fundamental aspects of the urinary virome that can be leveraged to better manage kidney diseases.
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Virus BK , Trasplante de Riñón , Infecciones por Polyomavirus , Receptores de Trasplantes , Viremia , Viroma , Humanos , Trasplante de Riñón/efectos adversos , Virus BK/aislamiento & purificación , Virus BK/genética , Masculino , Femenino , Infecciones por Polyomavirus/orina , Infecciones por Polyomavirus/virología , Viremia/orina , Persona de Mediana Edad , Adulto , Estudios Longitudinales , Infecciones Tumorales por Virus/orina , Infecciones Tumorales por Virus/virología , Anciano , Factores Sexuales , Orina/virologíaRESUMEN
BACKGROUND: Immunosuppression reduction for BK polyoma virus (BKV) must be balanced against risk of adverse alloimmune outcomes. We sought to characterize risk of alloimmune events after BKV within context of HLA-DR/DQ molecular mismatch (mMM) risk score. METHODS: This single-center study evaluated 460 kidney transplant patients on tacrolimus-mycophenolate-prednisone from 2010-2021. BKV status was classified at 6-months post-transplant as "BKV" or "no BKV" in landmark analysis. Primary outcome was T-cell mediated rejection (TCMR). Secondary outcomes included all-cause graft failure (ACGF), death-censored graft failure (DCGF), de novo donor specific antibody (dnDSA), and antibody-mediated rejection (ABMR). Predictors of outcomes were assessed in Cox proportional hazards models including BKV status and alloimmune risk defined by recipient age and molecular mismatch (RAMM) groups. RESULTS: At 6-months post-transplant, 72 patients had BKV and 388 had no BKV. TCMR occurred in 86 recipients, including 27.8% with BKV and 17% with no BKV (p = .05). TCMR risk was increased in recipients with BKV (HR 1.90, (95% CI 1.14, 3.17); p = .01) and high vs. low-risk RAMM group risk (HR 2.26 (95% CI 1.02, 4.98); p = .02) in multivariable analyses; but not HLA serological MM in sensitivity analysis. Recipients with BKV experienced increased dnDSA in univariable analysis, and there was no association with ABMR, DCGF, or ACGF. CONCLUSIONS: Recipients with BKV had increased risk of TCMR independent of induction immunosuppression and conventional alloimmune risk measures. Recipients with high-risk RAMM experienced increased TCMR risk. Future studies on optimizing immunosuppression for BKV should explore nuanced risk stratification and may consider novel measures of alloimmune risk.
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Virus BK , Rechazo de Injerto , Supervivencia de Injerto , Pruebas de Función Renal , Trasplante de Riñón , Infecciones por Polyomavirus , Infecciones Tumorales por Virus , Viremia , Humanos , Trasplante de Riñón/efectos adversos , Virus BK/inmunología , Virus BK/aislamiento & purificación , Femenino , Masculino , Infecciones por Polyomavirus/inmunología , Infecciones por Polyomavirus/virología , Infecciones por Polyomavirus/complicaciones , Persona de Mediana Edad , Rechazo de Injerto/etiología , Rechazo de Injerto/inmunología , Estudios de Seguimiento , Infecciones Tumorales por Virus/inmunología , Infecciones Tumorales por Virus/virología , Viremia/inmunología , Viremia/virología , Pronóstico , Factores de Riesgo , Tasa de Filtración Glomerular , Adulto , Complicaciones Posoperatorias , Inmunosupresores/uso terapéutico , Inmunosupresores/efectos adversos , Estudios Retrospectivos , Fallo Renal Crónico/cirugía , Fallo Renal Crónico/inmunología , Enfermedades Renales/virología , Enfermedades Renales/inmunología , Enfermedades Renales/cirugía , Receptores de TrasplantesRESUMEN
Transplant patients are at risk of infections due to long-term immunosuppression contributing to morbidity and mortality in this population. Post-transplant testing guidelines were established to monitor and guide therapeutic interventions in transplant recipients. We hypothesize that there are gaps in adherence to the recommended frequency of laboratory testing in post-transplant patients. We analyzed national reference laboratory data to compare viral post-transplant infection (PTI) testing frequency with their respective published guidelines to understand patient uptake and compliance. We evaluated the ordering patterns, positivity rates, and frequency of molecular infectious disease tests (MIDTs). We included 345 patients with International Classification of Diseases (ICD)-10 codes for transplant (Z940-Z942, Z944, Z9481, Z9483, Z9484) with at least two tests (within 7 days) in January 2019 and at least one test in December 2020 to find patients in the post-transplant period. We analyzed two cohorts: kidney transplant recipients (KTRs; 40%) and non-KTR (60%) then followed them longitudinally for the study period. In KTR cohort, high-to-low proportion of ordered MIDT was blood BK virus (bBKV) followed by cytomegalovirus (CMV); in non-KTR cohort, CMV was followed by Epstein-Barr virus (EBV). KTR cohort positivity was highest for urine BK virus (uBKV; 58%) followed by EBV (46%), bBKV (40%), and CMV (31%). Non-KTR cohort positivity was highest for uBKV (64%), EBV (51%), CMV (30%), bBKV (8%), and adenovirus (7%). All patients were tested at progressively longer intervals from the date of the first post-transplant ICD-10-coded test. More than 40% of the KTR cohort were tested less frequently for EBV and bBKV, and more than 20% of the non-KTR cohort were tested for EBV less frequently than published guidelines 4 months after transplant. Despite regular testing, the results of MIDT testing for KTR and non-KTR patients in the post-transplant period are not aligned with published guidelines.IMPORTANCEGuidance for post-transplant infectious disease testing is established, however, for certain infections it allows for clinician discretion. This leads to transplant center policies developing their own testing/surveillance strategies based on their specific transplant patient population (kidney, stem cell, etc.). The Organ Procurement and Transplant Network (OPTN) has developed a strategic plan to improve and standardize the transplant process in the US to improve outcomes of living donors and recipients. Publishing national reference lab data on the testing frequency and its alignment with the recommended guidelines for post-transplant infectious diseases can inform patient uptake and compliance for these strategic OPTN efforts.
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Trasplante de Riñón , Receptores de Trasplantes , Humanos , Trasplante de Riñón/efectos adversos , Masculino , Persona de Mediana Edad , Femenino , Receptores de Trasplantes/estadística & datos numéricos , Adulto , Anciano , Virus BK/aislamiento & purificación , Virus BK/genética , Virosis/epidemiología , Virosis/diagnóstico , Virosis/virología , Terapia de Inmunosupresión/efectos adversos , Citomegalovirus/aislamiento & purificación , Citomegalovirus/genética , Herpesvirus Humano 4/aislamiento & purificación , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/inmunología , Estudios RetrospectivosRESUMEN
BACKGROUND: Long-term allograft and patient survival after kidney transplantation (KTX) depends on the balance between over- and under-immunosuppression (IS). High levels of IS predispose to opportunistic infections. Plasma load of Torque Teno Virus (TTV), a non-pathogenic highly prevalent Annellovirus, is associated with its hosts immune status, especially after solid organ transplantation. OBJECTIVES: To investigate the association of plasma TTV load and opportunistic viral infections after pediatric KTX. STUDY DESIGN: This retrospective study includes all pediatric KTX patients followed at the Medical University of Vienna 2014-2020. PCR for Cytomegalovirus (CMV), Epstein-Barr virus (EBV), BK virus (BKV), and TTV was performed every 4-8 weeks at routine follow-up visits. RESULTS: 71 pediatric KTX patients were followed with TTV measurements for a median of 2.7 years. TTV plasma load was associated with CMV DNAemia at the next visit with an OR of 2.37 (95 % CI 1.15-4.87; p = 0.03) after adjustment for time after KTX and recipient age. For a cut-off of 7.68 log10 c/mL TTV a sensitivity of 100 %, a specificity of 61 %, a NPV 100 %, and a PPV of 46 % to detect CMV DNAemia at the next visit was calculated. TTV plasma loads were also associated with BKV DNAuria and BKV DNAemia at the next visit, but not with EBV DNAemia. CONCLUSIONS: This is the first study to analyse associations between TTV plasma loads and opportunistic viral infections in pediatric KTX. We were able to present a TTV cut-off for the prediction of clinically relevant CMV DNAemia that might be useful in clinical care.
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Virus BK , Infecciones por Citomegalovirus , Citomegalovirus , Infecciones por Virus ADN , Trasplante de Riñón , Infecciones por Polyomavirus , Torque teno virus , Carga Viral , Humanos , Trasplante de Riñón/efectos adversos , Torque teno virus/genética , Torque teno virus/aislamiento & purificación , Niño , Infecciones por Citomegalovirus/virología , Estudios Retrospectivos , Masculino , Virus BK/aislamiento & purificación , Virus BK/genética , Adolescente , Femenino , Infecciones por Polyomavirus/virología , Citomegalovirus/genética , Infecciones por Virus ADN/virología , Infecciones por Virus ADN/sangre , Infecciones por Virus ADN/epidemiología , Preescolar , ADN Viral/sangre , Infecciones Oportunistas/virología , Infecciones Oportunistas/diagnóstico , Receptores de Trasplantes/estadística & datos numéricos , LactanteRESUMEN
PURPOSE: This study aimed to investigate the prevalence and viral reactivations of clinical interest in the immunocompromised patient with particular focus on hematologic and solid organ transplant recipients. METHODS: Molecular screening data of CMV, EBV, JCV and BKV from 2011 to 2023 were analyzed. This extensive time span allowed the access to more than 100,000 samples from over 20,000 patients treated at Policlinico Umberto I. It was possible to temporally investigate patient attendance patterns, average age distribution, seasonality of infections, and positivity rates of the analyzed viruses. RESULTS: Between 2019 and 2022 a significant reduction in organ transplants performed and in the positive molecular detection of EBV, JCV and BKV was observed. Additionally, there has been a noteworthy decrease in CMV reactivations, with a reduction of up to 50% starting in 2019. A remarkable reduction of 39% in the rate of CMV viral reactivation has been also achieved in SOT between 2016 and 2023. CONCLUSION: The years following 2019 were profoundly impacted by the COVID-19 pandemic era. This period resulted in a substantial reduction in healthcare services and hospital visits. Furthermore, the introduction of the drug Letermovir in Italy in 2019 demonstrated remarkable efficacy, evidenced by a reduction in CMV reactivations. Additionally, the adoption of a novel clinical approach centered on personalized therapy facilitated improved management of immunocompromised patients.
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Hospitales Universitarios , Huésped Inmunocomprometido , Humanos , Italia/epidemiología , Hospitales Universitarios/estadística & datos numéricos , Masculino , Persona de Mediana Edad , COVID-19/epidemiología , COVID-19/virología , Femenino , Activación Viral , Virosis/epidemiología , Virosis/virología , Anciano , Adulto , Virus JC/genética , Virus JC/aislamiento & purificación , Virus JC/inmunología , Virus BK/genética , Virus BK/aislamiento & purificación , Infecciones por Citomegalovirus/epidemiología , Infecciones por Citomegalovirus/tratamiento farmacológico , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/inmunología , Prevalencia , Trasplante de Órganos/efectos adversos , Receptores de Trasplantes/estadística & datos numéricos , Citomegalovirus/genética , Citomegalovirus/inmunología , Infecciones por Polyomavirus/epidemiología , Infecciones por Polyomavirus/virologíaRESUMEN
The BK polyomavirus (BKPyV) is a widespread pathogen in humans. Polymorphism of the region encoding the VP1 protein of BKPyV provides the basis for classifying the virus into types and subtypes, whose frequency varies depending on geographic location. The aim of our study was to determine the frequency of BKPyV in the Polish population and to assess its variation by analysing polymorphism in the typing region. The study was conducted on 168 healthy, Polish volunteers, whose blood (plasma) and urine were sampled. The virus was detected using PCR, products, sequenced and subjected to bioinformatic analysis. In addition, viral load was assessed by qPCR. The presence of the genetic material of the BK virus was noted in 61/168 urine samples but in none of the plasma sample. Sequencing and phylogenetic analysis confirmed that the BKPyV isolates were of types I and IV, dominant in Europe (63.93% and 36.07%, respectively). All isolates from genotype I belonged to subtype Ib-2, showing polymorphism at position 1809 with a frequency of 61.54% (G1809A) and 38.46% (G1809C). To the best of our knowledge, this is the first study of this magnitude on the genetic variation of BKPyV among healthy volunteers in Poland.
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Virus BK/genética , Variación Genética , Infecciones por Polyomavirus/virología , Adulto , Anciano , Virus BK/clasificación , Virus BK/aislamiento & purificación , Virus BK/fisiología , Secuencia de Bases , ADN Viral/genética , Europa (Continente)/epidemiología , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Epidemiología Molecular , Filogenia , Polonia/epidemiología , Infecciones por Polyomavirus/epidemiología , Carga ViralRESUMEN
A retrospective cross sectional study was conducted at the Virology Department, Armed Forces Institute of Pathology (AFIP) and Armed Forces Bone Marrow Transplant Centre (AFBMTC), Rawalpindi, from January 2016 to July 2018. Medical records of 193 patients were examined to determine the number of patients developing Haemorrhagic Cystitis associated with BK virus (BKV). BKV PCR testing was done on the patients' urine samples. Cytomegalovirus reactivation was also assessed weekly from day 30 to day 100, by CMV quantitative PCR testing on blood samples. Out of 193 patients, 11 (5.6%) developed haemorrhagic cystitis and all these patients were positive for BKV on urine samples. The maximum number of positive cases, i.e. 5 (2.6%) was in the age group three months to 10 years. Primary disease in seven out of 11 cases was Beta-Thalassemia Major.
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Virus BK , Cistitis , Trasplante de Células Madre Hematopoyéticas , Hemorragia , Humanos , Virus BK/aislamiento & purificación , Estudios Transversales , Cistitis/virología , Países en Desarrollo , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Hemorragia/virología , Estudios Retrospectivos , Orina/virologíaRESUMEN
Although some studies have suggested the effectiveness of hyperbaric oxygen (HBO) therapy for hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (HSCT), the role of HBO has not been established. We compared the treatment outcomes of 8 patients with viral HC (adenovirus [ADV], n = 2; BK virus [BKV], n = 6) treated with HBO (HBO[+]) and 8 patients (ADV, n = 2; BKV, n = 6) treated with conventional therapy (HBO[-]), such as urinary catheterization and intravenous cidofovir. HBO therapy was performed at 2.1 atmospheres for 90 min/day until clinical improvement was achieved. The median number of HBO treatments was 10 (range 8-12). The median duration of HBO treatment was 19.5 days (range 10-23 days). All 8 HBO(+) patients achieved complete remission (CR) at a median of 14.5 days (range 5-25 days). Of the 8 HBO(-) patients, 5 (62.5%) obtained CR and 3 remained symptomatic for 2-6 months. The cumulative incidence of transplant-related mortality at day 100 after allogeneic HSCT was significantly higher in the HBO(-) patients than in the HBO(+) patients (14.2 vs. 0%, P < 0.05). No severe HBO-related adverse effects were observed. In conclusion, HBO is a feasible option for treating viral HC after allogeneic HSCT.
Asunto(s)
Cistitis/terapia , Cistitis/virología , Trasplante de Células Madre Hematopoyéticas , Hemorragia/terapia , Hemorragia/virología , Oxigenoterapia Hiperbárica , Adenoviridae/aislamiento & purificación , Infecciones por Adenoviridae/complicaciones , Adulto , Virus BK/aislamiento & purificación , Cistitis/etiología , Femenino , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Hemorragia/etiología , Humanos , Oxigenoterapia Hiperbárica/métodos , Masculino , Persona de Mediana Edad , Infecciones por Polyomavirus/complicaciones , Trasplante Homólogo/efectos adversos , Resultado del Tratamiento , Adulto JovenRESUMEN
BK virus is one of the most common causes of hemorrhagic cystitis (HC) in children undergoing hematopoietic cell transplantation (HCT). Viruses can be found in urine and serum samples of immunocompromised patients. Malignant diseases, age, cell source, day of granulocyte reconstitution, conditioning regimen, or use of total body irradiation may play an important role in BKV epidemiology, development of hemorrhagic cystitis course, and outcome. The aim of this study was to evaluate the incidence, clinical course, and risk factors for BKV-HC in children undergoing HCT. A total number of 133 patients who were prospectively tested for BKV colonization/infection were enrolled into this multicenter analysis. Episodes of BKV-HC occurred in 36/133 (27%) enrolled subjects. In a univariate analysis for BKV-HC incidence, the following factors were significant: age >5 years, peripheral blood transplantation, matched unrelated donor (MUD) transplantation, busulfan-cyclophosphamide-melphalan conditioning regimen, and acute myeloblastic leukemia (AML) diagnosis. Presence of acute graft-versus-host disease (aGVHD) in liver and gut GVHD was a significant risk factor of BKV-HC. No BKV-attributed deaths were reported. In multivariate analysis, the incidence of HC was significantly higher in patients with AML, age >5 years, MUD transplants, and children with GVHD. HC is a frequent complication after HCT among children causes prolonged hospitalization but rarely contributes to death. We identified risk factors of BKV-HC development in children, with focus on aGVHD: we concluded that excessive immune reaction connected with GVHD and immunosuppression drugs might play a pivotal role in the development of BKV-HC.
Asunto(s)
Virus BK/aislamiento & purificación , Cistitis/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Infecciones por Polyomavirus/etiología , Infecciones Tumorales por Virus/etiología , Adolescente , Niño , Preescolar , Cistitis/terapia , Femenino , Humanos , Incidencia , Lactante , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/terapia , Masculino , Infecciones por Polyomavirus/terapia , Estudios Prospectivos , Factores de Riesgo , Trasplante Homólogo/efectos adversos , Infecciones Tumorales por Virus/terapiaRESUMEN
Adenovirus (ADV)- or BK virus (BKV)-associated hemorrhagic cystitis (HC) is a common complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Several risk factors have been previously reported; however, it is unclear whether virus-associated HC can be transmitted. To clarify this point, we performed a retrospective cohort study on 207 consecutive patients who underwent allo-HSCT at Kyoto University Hospital between 2012 and 2018. We evaluated the incidence and risk factors of virus-associated HC and performed a phylogenetic analysis of the ADV partial sequence. The median age at transplantation was 50 (range, 17-68) years. Fifty-eight patients (28%) developed HC. ADVs were detected in 18 cases, BKVs were detected in 51, both were detected in 12, and only John Cunningham virus (JCV) was detected in 1 case. No factor was significantly associated with HC. However, both ADV- and BKV-HC occurred intensively between April 2016 and September 2017, which suggested possible nosocomial transmission of ADV and BKV. Genome sequencing of the hexon, E3, and penton regions of detected ADVs identified 7 cases of ADV type 11, 2 cases of type 35, and 3 cases of a type 79-related strain. A sequence analysis revealed that these strains in each type were almost identical, except for one case of a type 79-related strain. In conclusion, ADV-HCs with possible nosocomial transmission were described based on genotyping of the virus and partial sequencing of the viral genome. Although viral HC after allo-HSCT is thought to mainly be due to reactivation of a latent virus, nosocomial transmission of ADV or BKV should also be considered.
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Infección Hospitalaria/etiología , Cistitis/virología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Hemorragia/virología , Virosis/etiología , Adenoviridae/aislamiento & purificación , Adenoviridae/fisiología , Infecciones por Adenoviridae/epidemiología , Infecciones por Adenoviridae/etiología , Adolescente , Adulto , Anciano , Virus BK/aislamiento & purificación , Virus BK/fisiología , Estudios de Cohortes , Infección Hospitalaria/epidemiología , Cistitis/epidemiología , Cistitis/etiología , Femenino , Trasplante de Células Madre Hematopoyéticas/estadística & datos numéricos , Hemorragia/epidemiología , Hemorragia/etiología , Humanos , Virus JC/aislamiento & purificación , Virus JC/fisiología , Japón/epidemiología , Masculino , Persona de Mediana Edad , Infecciones por Polyomavirus/epidemiología , Infecciones por Polyomavirus/etiología , Estudios Retrospectivos , Factores de Riesgo , Trasplante Homólogo/efectos adversos , Trasplante Homólogo/estadística & datos numéricos , Infecciones Tumorales por Virus/epidemiología , Infecciones Tumorales por Virus/etiología , Infecciones Urinarias/epidemiología , Infecciones Urinarias/etiología , Virosis/epidemiología , Adulto JovenRESUMEN
Intrapatient variability (IPV) in tacrolimus has been increasingly acknowledged as a risk factor for poor graft survival after kidney transplantation. Although past studies have mainly accounted for IPV in acute or chronic rejection states as due to underimmunosuppression, this is not yet clear. So far, tacrolimus IPV for BK virus-associated nephropathy (BKVN) and chronic calcineurin inhibitor toxicity (CNIT) has not been investigated. Here, we evaluated IPV in tacrolimus for BKVN and chronic CNIT, which are mainly considered as overimmunosuppression states. In this case-control study, kidney allograft biopsies conducted between 1998 and 2018 were included, with patients grouped by biopsy results as BKVN alone group, CNIT alone group, and normal graft function (control group). IPV was estimated as mean absolute deviation. Our study groups included 25 kidney transplant recipients with BKVN alone, 91 patients with CNIT alone, and 60 patients with normal 5-year graft survival (control group). In analyses of IPV in tacrolimus six months before graft biopsy, IPV was highest in the BKVN group (P = 0.001). The BKVN group also had the highest IPV in tacrolimus at 12 months after biopsy (P = 0.001), with all pairwise comparisons statistically different between groups. At 12 months after biopsy, five patients (20%) in the BKVN group and 10 patients (10.9%) in the CNIT group had graft loss. Among other risk factors, BKVN and chronic CNIT are consequences related to high IPV. Quantification of IVP for tacrolimus in clinical practice would help to optimize kidney transplant outcomes.
Asunto(s)
Virus BK/aislamiento & purificación , Calcineurina/efectos adversos , Inmunosupresores/efectos adversos , Enfermedades Renales/inducido químicamente , Trasplante de Riñón , Infecciones por Polyomavirus/complicaciones , Tacrolimus/efectos adversos , Infecciones Tumorales por Virus/complicaciones , Infecciones Tumorales por Virus/epidemiología , Adulto , Anciano , Calcineurina/uso terapéutico , Estudios de Casos y Controles , Femenino , Rechazo de Injerto/epidemiología , Rechazo de Injerto/prevención & control , Supervivencia de Injerto , Humanos , Inmunosupresores/uso terapéutico , Riñón/patología , Enfermedades Renales/diagnóstico , Enfermedades Renales/epidemiología , Enfermedades Renales/cirugía , Fallo Renal Crónico/cirugía , Trasplante de Riñón/efectos adversos , Masculino , Persona de Mediana Edad , Nefritis Intersticial , Complicaciones Posoperatorias/virología , Estudios Retrospectivos , Factores de Riesgo , Tacrolimus/uso terapéutico , Resultado del Tratamiento , Infecciones Tumorales por Virus/virologíaRESUMEN
The aims were to investigate the incidence of BKV infection and the presence of HC in pediatric patients undergoing HSCT. Twenty-four children patients (M/F: 17/7) undergoing HSCT in a single center over a period of 1 year were included in the study. The presence of BKV DNA was determined by quantitative real-time PCR in plasma and urine samples at the following times: before transplantation, twice a week until engraftment time, and weekly for + 100 days. The mean age of the patients was 7.79 ± 5.03 years, the mean follow-up time was 95.6 ± 25.9 days, and the average number of samples per patient was 15.8 ± 3.2. BKV DNA was detected in at least one urine sample in 91.6% (n: 22) and at least one plasma sample in 75% (n:18) of the patients. The median time to the first BKV DNA positivity in urine and plasma samples was 11 (range: 1-80) and 32 days (range: 2-79), respectively. The median value of BKV DNA copies in urine and plasma were 1.7 × 106 (range: 2.8 × 101 -1.2 × 1014 ) and 1.9 × 103 copies/mL (range: 3-2.1 × 106 ), respectively. Thirteen patients (54.2%) had hematuria with BKV viruria; 8 (33.3%) patients had viremia. The median value of the BKV DNA copies in urine and plasma was 4.4 × 107 (range: 65-1 × 1011 ) and 2.9 × 103 (range: 7-7.8 × 104 ) copies/mL in these patients. Two (15.4%) of the 13 patients with BKV viruria and hematuria were diagnosed with BKV-related HC. BKV DNA viral load monitoring of urine and plasma in pediatric HSCT patients with a high risk for viral infections is valuable for understanding the development of BKV-related HC.
Asunto(s)
Virus BK/aislamiento & purificación , Cistitis/inmunología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Huésped Inmunocomprometido , Inmunosupresores/efectos adversos , Infecciones por Polyomavirus/inmunología , Adolescente , Niño , Preescolar , Cistitis/diagnóstico , Cistitis/epidemiología , Cistitis/virología , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Infecciones por Polyomavirus/diagnóstico , Infecciones por Polyomavirus/epidemiología , Infecciones por Polyomavirus/metabolismo , Carga Viral , Adulto JovenRESUMEN
OBJECTIVES: BK polyomavirus can infect healthy individuals; however, in renal transplant recipients, it can cause nephropathy, which can lead to renal allograftfailure. There are currently no effective antiviral agents against BK polyomavirus. Surveillance after kidney transplant for BK polyomavirus is the only means to prevent allograft failure. Transplant centers routinely screen for BK polyomavirus in either urine or blood. If BK polyomavirus replication occurs, itis usually detected first in urine, which is followed by detection in blood in a subset of cases. Screening for BK polyomavirus in urine has the potential for earlier detection of viralreactivation.However, not all patients with BK polyomavirus in urine will progress to BK viremia. Therefore, adding urine screening could increase the cost oftests without a clear clinical benefit. MATERIALS AND METHODS: We conducted an analysis of BK polyomavirus screening methods at 2 different centers and compared their clinical outcomes and efficiency of testing. RESULTS: We analyzed 209 patientswith BK polyomavirus reactivation after kidney transplant at 2 different institutions from 2008 to 2018. BK polyomavirus reactivation in blood was detected earlierifthe patient was screened by urine screening protocol. However, measurable clinical outcomes were similarin all groups with different screening methods. CONCLUSIONS: Although screening for BK polyomavirus in urine did detect viralreactivation earlier,there were no differences in graft or clinical outcomes when either the urine or blood screening method was used.
Asunto(s)
Virus BK , Trasplante de Riñón , Infecciones por Polyomavirus/diagnóstico , Virus BK/aislamiento & purificación , Humanos , Riñón , Trasplante de Riñón/efectos adversos , Infecciones por Polyomavirus/sangre , Infecciones por Polyomavirus/orina , Viremia/diagnóstico , Activación ViralRESUMEN
BACKGROUND: BK virus allograft nephropathy is a serious complication after kidney transplantation, and the effect of pre-emptive intervention for high-level BK viruria has been verified, but protocols after kidney transplantation for early identification of high-level viruria are lacking. METHODS: This was a single-center study. The clinical data of the kidney transplant recipients and their donors in our center from January 1, 2015 to December 31, 2018, were collected. The patients were divided into the high-level BK viruria group (Group A) and a non-high-level BK viruria group (Group B) according to the qPCR results of BK virus DNA loads in urine samples. Significant variables were screened out by univariate analysis, and then the results were incorporated into a multivariate logistic regression model to analyze the independent risk factors for high-level BK viruria. RESULTS: A total of 262 recipients were included in the study. The incidence of high-level BK viruria was 13.4% (n = 35), and the median time of detection was 181 (range 91-1119) days. Univariate analysis showed that donor type ([Formula: see text] = 21.770, P < 0.001), history of ATG/ATG-F application ([Formula: see text] = 4.543, P = 0.033), acute rejection (AR) ([Formula: see text] = 8.313, P = 0.004) and delayed graft function (DGF) ([Formula: see text] = 21.170, P < 0.001) were related to high-level BK viruria. After the inclusion of the multivariate logistic regression model, the results showed deceased brain and cardiac donors (P = 0.032, OR = 3.927, 95% CI 1.122-13.746), AR (P = 0.022, OR = 4.709, 95% CI 1.253-17.697) and DGF (P = 0.001, OR = 6.682, 95% CI 2.288-19.518). CONCLUSIONS: Donation by deceased brain and cardiac patients, history of AR and DGF were independent risk factors for high-level BK viruria after kidney transplantation.