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Journal of Medical Virology May 2023Studies analyzing the relationship between BK polyomavirus (BKV) or JC polyomavirus (JCV) infection and kidney transplant (KT) long term clinical outcomes are scarce....
Studies analyzing the relationship between BK polyomavirus (BKV) or JC polyomavirus (JCV) infection and kidney transplant (KT) long term clinical outcomes are scarce. Therefore, we evaluated this relationship in a single-center retrospective cohort of 288 KT patients followed for 45.4(27.5; 62.5) months. Detection of BKV viremia in two consecutive analyses led to discontinuation of antimetabolite and initiation of mammalian target of rapamycin inhibitor. Outcome data included de novo BKV and/or JCV viremia and/or viruria after KT, death-censored graft survival and patient survival. BKV viruria and viremia were detected in 42.4% and 22.2% of KT recipients, respectively. BKV viremic patients had higher urinary BKV viral loads at the onset of viruria, when compared to nonviremic patients (7 log vs. 4.9 log cp/mL, p < 0.001). JCV viruria was identified in 38.5% of KT patients; the 5.9% of KT recipients who developed JCV viremia had higher JCV urinary viral loads at the onset of viruria, when compared to non-viremic patients (5.3 vs. 3.7 log cp/mL, p = 0.034). No differences were found in estimated glomerular filtration rate at the end of follow up, when comparing BKV or JCV viruric or viremic patients with nonviremic patients. No association was found between JCV or BKV viruria or viremia and death/graft failure. Therefore, higher BKV urinary viral loads at the onset could serve as an early maker of over immunosuppression. JCV and BKV replication was not associated with inferior clinical outcomes in KT patients with the above-mentioned immunosuppression strategy.
Topics: Humans; Kidney Transplantation; Retrospective Studies; BK Virus; Viremia; JC Virus; Kidney Diseases; Polyomavirus Infections; Tumor Virus Infections; DNA, Viral
PubMed: 37218583
DOI: 10.1002/jmv.28800 -
Annals of Clinical and Translational... Mar 2021Based on publicly available data, we reevaluated current algorithms for stratifying the risk of progressive multifocal leukoencephalopathy (PML) in natalizumab-treated...
Based on publicly available data, we reevaluated current algorithms for stratifying the risk of progressive multifocal leukoencephalopathy (PML) in natalizumab-treated patients with multiple sclerosis, and found that there are a number of issues. First and foremost, our analysis highlights the necessity of separate PML incidence assessments for the U.S. versus Europe, and indicates that the risk in John Cunningham virus (JCV) antibody-negative patients may be higher than previously communicated. Additionally, we advocate introducing a low-risk JCV index threshold of 0.45 for individuals with prior exposure to an immunosuppressant, and setting the low-risk threshold at 0.6 instead of 0.9 for those without such pretherapies. On the other hand, the risk of PML on natalizumab, in general, appears to not only plateau but to actually decrease after about 5 years of continuous dosing.
Topics: Algorithms; Antibodies, Viral; Canada; Europe; Humans; Immunologic Factors; JC Virus; Leukoencephalopathy, Progressive Multifocal; Multiple Sclerosis; Natalizumab; Risk Assessment; United States
PubMed: 33539683
DOI: 10.1002/acn3.51130 -
Current Hematologic Malignancy Reports Aug 2019Infectious diseases contribute significantly to morbidity and mortality in recipients of allogeneic haematopoietic stem cell transplantation (aHSCT), particularly in the... (Review)
Review
PURPOSE OF REVIEW
Infectious diseases contribute significantly to morbidity and mortality in recipients of allogeneic haematopoietic stem cell transplantation (aHSCT), particularly in the era of highly immunosuppressive transplant regimens and alternate donor transplants. Delayed cellular immune recovery is a major mechanism for the increased risk in these patients. Adoptive cell therapy with ex vivo manipulated pathogen-specific T cells (PSTs) is increasingly taking its place as a treatment strategy using donor-derived or third party-banked cells.
RECENT FINDINGS
The majority of clinical trial data in the form of early-phase studies has been in the prophylaxis or treatment of cytomegalovirus (CMV), Epstein-Barr virus (EBV) and adenovirus (AdV). Advancements in methods to select and enrich PSTs offer the opportunity to target the less common viral pathogens as well as fungi with this technology. Early clinical studies of PSTs targeting polyomaviruses (BK virus and JC virus), human herpesvirus 6 (HHV6), varicella zoster virus (VZV) and Aspergillus spp. have shown promising results in small numbers of patients. Other potential targets include herpes simplex virus (HSV), respiratory viruses and other invasive fungal species. In this review, we describe the burden of disease of this wider spectrum of pathogens, the progress in the development of manufacturing capability, early clinical results and the opportunities and challenges for implementation in the clinic.
Topics: Adenoviridae; Animals; Antigens, Viral; Cytomegalovirus; Epitopes, T-Lymphocyte; Hematopoietic Stem Cell Transplantation; Herpesvirus 4, Human; Host-Pathogen Interactions; Humans; Immune Reconstitution; Immunocompromised Host; Immunotherapy, Adoptive; Opportunistic Infections; T-Lymphocytes; Transplantation, Homologous; Treatment Outcome; Virus Diseases
PubMed: 31228095
DOI: 10.1007/s11899-019-00521-z -
Virus Research Mar 2020Polyomaviridae family consists of small circular dsDNA viruses. Out of the 14 human polyomaviruses described so far, BKPyV and JCPyV have been studied extensively since... (Review)
Review
Polyomaviridae family consists of small circular dsDNA viruses. Out of the 14 human polyomaviruses described so far, BKPyV and JCPyV have been studied extensively since their discovery in 1971. Reportedly, both BKPyV and JCPyV are widely distributed across the globe with the frequency of 80-90 % in different populations. The primary infection of these viruses is usually asymptomatic and latent which is activated as a consequence of immunosuppression. Activated BKPyV and JCPyV viruses lead to the development of BK Virus Associated Nephropathy and Progressive Multifocal Leukoencephalopathy, respectively. Immense progress has been made during the last few decades regarding the molecular understanding of polyomaviruses. Epidemiology of polyomaviruses has also been studied extensively. However, most of the epidemiological studies have focused on European and American populations. Therefore, limited data is available regarding the geographical distribution of these potentially oncogenic viruses in Asian countries. In this article, we have presented a compendium of latest advances in the molecular understanding of polyomaviruses and their pathobiology. We also present a comprehensive review of published literature regarding the epidemiology and prevalence of BKPyV and JCPyV in Asian regions. For this purpose, a thorough search of available online resources was performed. As a result, we retrieved 24 studies for BKPyV and 22 studies for JCPyV, that describe their prevalence in Asia. These studies unanimously report high occurrence of both BKPyV and JCPyV in Asian populations. The available data from these studies was categorized into two groups: on the basis of prevalence (low, medium and high) and disease development (healthy and diseased). Altogether, Korean population hasbeen evidenced to possess highest frequency of BKPyV (66.7 %), while JCPyV was found to be most prevalent in Taiwan (88 %). Due to high and ubiquitous distribution of these viruses, frequent studies are required to develop a better understanding regarding the epidemiology and pathobiology of these viruses in Asia.
Topics: Asia; BK Virus; Genome, Viral; Humans; JC Virus; Latent Infection; Polyomavirus Infections; Prevalence; Tumor Virus Infections; Viral Tropism; Virus Activation
PubMed: 31911182
DOI: 10.1016/j.virusres.2020.197860 -
Journal of Clinical Immunology Oct 2022Mutations in the ARPC1B isoform component of human actin-related protein 2/3 complex have been recently associated with an inborn error of immunity characterized by...
Mutations in the ARPC1B isoform component of human actin-related protein 2/3 complex have been recently associated with an inborn error of immunity characterized by combined immunodeficiency, allergies, autoinflammation, and platelet abnormalities. Currently, indications on the management of this novel disease and information on its outcome are lacking. We report the first case series of 7 children with a homozygous mutation in ARPC1B gene who underwent allogeneic-HSCT (allo-HSCT). All patients presented an early clinical onset, characterized by recurrent infections, failure to thrive and gastrointestinal bleeding episodes complicated with neonatal hemorrhagic enteritis in 3 cases, and macrophage activating syndrome in 2. Allo-HSCT was performed at the median age of 1.83 years after a myeloablative conditioning regimen in all cases. Engraftment occurred in all patients with full donor chimerism in 6 out of 7. The clinical course after engraftment was uneventful in 3 out of 7 children; 2 patients developed a grade 1-2 acute graft-versus-host disease (GvHD), and 1 patient a grade 1 chronic-GvHD. JC virus-related progressive multifocal leukoencephalopathy was diagnosed in one patient 13 months after haploidentical-HSCT and successfully managed with donor-derived viral-specific T-cell infusion. Only one patient had a fatal outcome 3 months after HSCT because of sepsis, after veno-occlusive disease, and transplant-associated microangiopathy. At a median follow-up of 19 months (range 3-110), 6 out of 7 patients are alive and disease-free. The severity of the clinical phenotype at diagnosis and the high survival rate, with limited transplant-related morbidity, strongly support the indication to allo-HSCT for patients with this diagnosis.
Topics: Humans; Infant, Newborn; Actin-Related Protein 2-3 Complex; Disease-Free Survival; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Transplantation Conditioning; Infant; Transplantation Chimera
PubMed: 35767111
DOI: 10.1007/s10875-022-01305-6 -
Journal of Water and Health Feb 2024The objective of this study was to assess the occurrence and seasonal frequency of human adenovirus (HAdV), human polyomavirus (HPyV), and human papillomavirus (HPV) in...
The objective of this study was to assess the occurrence and seasonal frequency of human adenovirus (HAdV), human polyomavirus (HPyV), and human papillomavirus (HPV) in urban sewage. The detection of these viruses was carried out by polymerase chain reaction (PCR), and then the viral concentrations in the positive samples were quantified by quantitative PCR (qPCR). Additionally, HAdV and HPyV genotyping was also performed by PCR. A total of 38/60 (63.3%) positive samples were found. HAdV was the most prevalent virus (26/60; 43.3%), followed by HPyV (21/60; 35%) and HPV (21/60; 35%). The viral concentrations ranged from 3.56 × 10 to 7.55 × 10 genome copies/L. The most common dual viral agents was found between HAdV and HPyV, in eight samples (8/38, 21%). HAdV types 40 and 41 as well as HPyV types JC and BK were identified, with HAdV-40 and HPyV JC being the most prevalent types. Furthermore, the detection rates of HAdV, HPyV, and HPV were higher during the winter season than the other seasons. The high prevalence of HAdV and HPyV supports their suitability as viral indicators of sewage contamination. Furthermore, this study demonstrates the advantages of environmental surveillance as a tool to elucidate the community-circulating viruses.
Topics: Humans; Adenoviridae; Sewage; Polyomavirus; Papillomavirus Infections; Adenoviruses, Human
PubMed: 38421633
DOI: 10.2166/wh.2024.322 -
Viruses Sep 2020In the fifty years since the discovery of JC polyomavirus (JCPyV), the body of research representing our collective knowledge on this virus has grown substantially. As... (Review)
Review
In the fifty years since the discovery of JC polyomavirus (JCPyV), the body of research representing our collective knowledge on this virus has grown substantially. As the causative agent of progressive multifocal leukoencephalopathy (PML), an often fatal central nervous system disease, JCPyV remains enigmatic in its ability to live a dual lifestyle. In most individuals, JCPyV reproduces benignly in renal tissues, but in a subset of immunocompromised individuals, JCPyV undergoes rearrangement and begins lytic infection of the central nervous system, subsequently becoming highly debilitating-and in many cases, deadly. Understanding the mechanisms allowing this process to occur is vital to the development of new and more effective diagnosis and treatment options for those at risk of developing PML. Here, we discuss the current state of affairs with regards to JCPyV and PML; first summarizing the history of PML as a disease and then discussing current treatment options and the viral biology of JCPyV as we understand it. We highlight the foundational research published in recent years on PML and JCPyV and attempt to outline which next steps are most necessary to reduce the disease burden of PML in populations at risk.
Topics: Animals; History, 20th Century; History, 21st Century; Humans; JC Virus; Polyomavirus Infections; Tumor Virus Infections
PubMed: 32882975
DOI: 10.3390/v12090969 -
Neurotherapeutics : the Journal of the... Jul 2020Progressive multifocal leukoencephalopathy (PML) is a viral disease of the brain associated with immunodeficiency, immune suppressing medications, and malignancy. In the... (Review)
Review
Progressive multifocal leukoencephalopathy (PML) is a viral disease of the brain associated with immunodeficiency, immune suppressing medications, and malignancy. In the absence of effective anti-viral therapy for the causative JC virus, immune restoration has emerged as the critical therapeutic alternative. The evolving treatment of PML (and other rare JC virus-associated neurologic syndromes) requires consideration of baseline immune functioning and comorbid diseases while selecting from a number of therapeutic options to restore an effective immune response. This review focuses on the current options for management of PML in typical situations where this disease presents, including several where immune restoration is a standard therapeutic approach such as in PML associated with HIV/AIDS and in multiple sclerosis associated with natalizumab. Other circumstances in which PML occurs including associated with primary immunodeficiencies, malignancies, and transplants present greater challenges to immune reconstitution, but emerging concepts may enhance therapeutic options for these situations. Particular attention is focused on recent experience with checkpoint inhibitors, guidance for MS drug discontinuation, and strategies to monitor and facilitate immune restoration.
Topics: Animals; Antibodies, Monoclonal, Humanized; Humans; Immune Reconstitution; Immunosuppressive Agents; Leukoencephalopathy, Progressive Multifocal; Natalizumab; Treatment Outcome
PubMed: 32166631
DOI: 10.1007/s13311-020-00848-z -
Journal of Neurovirology Oct 2023Our study aims to report on the demographic, incidence rate (IR), clinical, and microbiological characteristics of PML patients diagnosed in our tertiary-care hospital... (Review)
Review
Our study aims to report on the demographic, incidence rate (IR), clinical, and microbiological characteristics of PML patients diagnosed in our tertiary-care hospital over the past 12 years. In this retrospective observational study, we reviewed all requests for JCPyV PCR in CSF from patients with suspected PML. We collected demographic, clinical, and microbiological data of patients diagnosed with PML. Since 2018, real-time quantitative PCR has been used, whereas prior to 2018, samples were sent to our National Reference Center for qualitative diagnosis. Thirteen patients were diagnosed with PML, with 10 of them having a definitive diagnosis and 3 classified as a possible diagnosis with negative PCR results. Eleven patients had advanced HIV, one had non-Hodgkin's lymphoma, and one had systemic lupus erythematosus. Most of the white matter lesions were located at the cerebral level, although the parenchyma and cerebellum were also affected. The most frequent symptoms were behavioral disorders and hemiparesis. The viral load of JCPyV in cerebrospinal fluid was < 1000 copies/mL in three patients. Six patients received compassionate treatment, and all six patients with definitive PML diagnosis died. Although advanced HIV patients were the most affected by PML in our study, it should also be considered in patients with other underlying diseases. While current PCR tests offer high sensitivity and specificity, false negatives can occur. The prognosis of the disease remains poor, and early multidisciplinary diagnosis-including clinical, microbiological, and neuroimaging assessments-remains crucial for improving neurological damage and prognosis.
Topics: Humans; Leukoencephalopathy, Progressive Multifocal; Retrospective Studies; JC Virus; HIV Infections; Tertiary Care Centers; Real-Time Polymerase Chain Reaction; Observational Studies as Topic
PubMed: 37470903
DOI: 10.1007/s13365-023-01158-8 -
Multiple Sclerosis and Related Disorders Sep 2023Progressive multifocal leukoencephalopathy (PML) is a rare viral central nervous system (CNS) demyelinating disease primarily associated with a compromised immune... (Review)
Review
Radiological abnormalities in progressive multifocal leukoencephalopathy: Identifying typical and atypical imaging patterns for early diagnosis and differential considerations.
Progressive multifocal leukoencephalopathy (PML) is a rare viral central nervous system (CNS) demyelinating disease primarily associated with a compromised immune system. PML is seen mainly in individuals with human immunodeficiency virus, lymphoproliferative disease, and multiple sclerosis. Patients on immunomodulators, chemotherapy, and solid organ or bone marrow transplants are predisposed to PML. Recognition of various PML-associated typical and atypical imaging abnormalities is critical for early diagnosis and differentiating it from other conditions, especially in high-risk populations. Early PML recognition should expedite efforts at immune-system restoration, allowing for a favorable outcome. This review aims to provide a practical overview of radiological abnormalities in PML patients and address differential considerations.
Topics: Humans; Leukoencephalopathy, Progressive Multifocal; Natalizumab; Immune Reconstitution Inflammatory Syndrome; Multiple Sclerosis; Early Diagnosis; JC Virus
PubMed: 37418930
DOI: 10.1016/j.msard.2023.104830