The present AST‐IDCOP guidelines update information on BK polyomavirus (BKPyV) infection, replication, and disease, which impact kidney transplantation (KT), but rarely non‐kidney solid organ ...transplantation (SOT). As pretransplant risk factors in KT donors and recipients presently do not translate into clinically validated measures regarding organ allocation, antiviral prophylaxis, or screening, all KT recipients should be screened for BKPyV‐DNAemia monthly until month 9, and then every 3 months until 2 years posttransplant. Extended screening after 2 years may be considered in pediatric KT. Stepwise immunosuppression reduction is recommended for KT patients with plasma BKPyV‐DNAemia of >1000 copies/mL sustained for 3 weeks or increasing to >10 000 copies/mL reflecting probable and presumptive BKPyV‐associated nephropathy, respectively. Reducing immunosuppression is also the primary intervention for biopsy‐proven BKPyV‐associated nephropathy. Hence, allograft biopsy is not required for treating BKPyV‐DNAemic patients with baseline renal function. Despite virological rationales, proper randomized clinical trials are lacking to generally recommend treatment by switching from tacrolimus to cyclosporine‐A, from mycophenolate to mTOR inhibitors or leflunomide or by the adjunct use of intravenous immunoglobulins, leflunomide, or cidofovir. Fluoroquinolones are not recommended for prophylaxis or therapy. Retransplantation after allograft loss due to BKPyV nephropathy can be successful if BKPyV‐DNAemia is definitively cleared, independent of failed allograft nephrectomy.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Patients undergoing solid-organ transplantation (SOT) or allogeneic hematopoietic cell transplantation (HCT) are at increased risk for infectious complications. Community-acquired respiratory viruses ...(CARVs) pose a particular challenge due to the frequent exposure pre-, peri-, and posttransplantation. Although influenza A and B viruses have a top priority regarding prevention and treatment, recent molecular diagnostic tests detecting an array of other CARVs in real time have dramatically expanded our knowledge about the epidemiology, diversity, and impact of CARV infections in the general population and in allogeneic HCT and SOT patients. These data have demonstrated that non-influenza CARVs independently contribute to morbidity and mortality of transplant patients. However, effective vaccination and antiviral treatment is only emerging for non-influenza CARVs, placing emphasis on infection control and supportive measures. Here, we review the current knowledge about CARVs in SOT and allogeneic HCT patients to better define the magnitude of this unmet clinical need and to discuss some of the lessons learned from human influenza virus, respiratory syncytial virus, parainfluenzavirus, rhinovirus, coronavirus, adenovirus, and bocavirus regarding diagnosis, prevention, and treatment.
BackgroundThe replication of BK virus (BKV) and JC virus (JCV) is linked to polyomavirus-associated nephropathy, hemorrhagic cystitis, and multifocal leukoencephalopathy in immunodeficient patients, ...but the behavior of these viruses in immunocompetent individuals has hardly been characterized MethodsWe used EIA to study samples obtained from 400 healthy blood donors aged 20–59 years for BKV- and JCV-specific antibodies against virus-like particles. We also studied BKV and JCV loads in plasma and urine among these individuals by use of real-time polymerase chain reaction ResultsIgG seroprevalence was 82% (328 of 400 donors) for BKV and 58% (231 of 400) for JCV. As age increased (age groups were divided by decade), the seroprevalence of BKV decreased from 87% (87 of 100) in the youngest group (aged 20–29 years) to 71% (71 of 100) in the oldest group (aged 50–59 years) (P=.006), whereas the seroprevalence of JCV increased from 50% (50 of 100) in the youngest group to 68% (68 of 100) in the oldest group (P=.06). Asymptomatic urinary shedding of BKV and JCV was observed in 28 (7%) and 75 (19%) of 400 subjects, respectively, with median viral loads of 3.51 and 4.64 log copies/mL, respectively (P<.001). Unlike urinary BKV loads, urinary JCV loads were positively correlated with IgG levels. The shedding of JCV was more commonly observed among individuals who were seropositive only for JCV, compared with individuals who were seropositive for both BKV and JCV, suggesting limited cross-protection from BKV immunity. Noncoding control regions were of archetype architecture in all cases, except for 1 rearranged JCV variant. Neither BKV nor JCV DNA was detected in plasma ConclusionsOur study provides important data about polyomavirus infection and replication in healthy, immunocompetent individuals. These data indicate significant differences between BKV and JCV with respect to virus-host interaction and epidemiology
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Abstract Today the human polyomavirus (HPyV) family consists of 10 members, BK virus (BKV) and JC virus (JCV) isolated 40 years ago and the more recently identified KI virus (KIPyV), WU virus ...(WUPyV), Merkel cell polyomavirus (MCPyV), HPyV6, HPyV7, trichodysplasia spinulosa virus (TSPyV), HPyV9 and MWPyV. Serological studies suggest that HPyVs subclinically infect the general population with rates ranging from 35% to 90%. However, significant disease is only observed in patients with impaired immune functions. Thus, BKV has been linked to hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation and PyV-associated nephropathy (PyVAN) after kidney transplantation; JCV to progressive multifocal leukoencephalopathy (PML) in HIV-AIDS, hematological diseases and in autoimmune diseases treated with certain lymphocyte-specific antibodies. KIPyV and WUPyV have been found in the respiratory tract, HPyV6 and 7 in the skin, and HPyV9 in serum and skin, and MWPyV in stools and skin, but so far none of these PyVs have been linked to any disease. TSPyV, on the other hand, was identified in trichodysplasia spinulosa, a rare skin disease characterized by virus-induced lytic as well as proliferative tumor-like features that is observed in immune-suppressed transplant patients. In contrast to all the other HPyVs so far, MCPyV is unique in its association with a cancer, Merkel cell carcinoma, which is a rare skin cancer arising in the elderly and chronically immunosuppressed individuals. The discovery of the new HPyVs has revived interest in the Polyomaviridae and their association to human disease and cancer. In this review, we summarize knowledge about this expanding family of human pathogens.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
BK Polyomavirus Consensus Hirsch, Hans H; Mengel, Michael; Kamar, Nassim
Clinical infectious diseases,
11/2022, Volume:
75, Issue:
11
Journal Article
Peer reviewed
To the editor—BK polyomavirus (BKPyV) continues to challenge kidney transplantation (KT) outcomes with premature renal allograft failure, and evidence-based treatment approaches based on randomized ...clinical trials are sorely lacking. Imlay and coauthors 1 address this unmet need and note that “definitions of proven disease are variable.” The definition of proven BKPyV nephropathy has not changed since 2005 2, requiring cytopathic changes that reflect viral replication in the allograft such as enlarged nuclei and intranuclear inclusions in renal tubular epithelial cells and/or transitional cells plus markers specific for BKPyV 3. However, studies validating better histological and molecular markers are desirable to distinguish virus-specific and anti-donor immune responses and to predict outcomes. The authors also note that “definitions using surrogate markers do not incorporate allograft dysfunction or other clinically meaningful markers.” We are most concerned about this statement as it may result in loss of well-established grounds in the difficult terrain of identifying and treating BKPyV replication at an early stage of renal allograft damage, before declining allograft function, and that presently relies on reducing immunosuppression after careful consideration of risks 3. Indeed, proven BKPyV nephropathy with focal lesions and minimal inflammation is commonly seen without impaired allograft dysfunction 3. Thus, their proposal of “probable BKPyV nephropathy” based on significant BKPyV DNAemia plus evidence of allograft dysfunction defined as >20% rise in baseline renal allograft nephropathy is placing patients at risk of deferred intervention and worse outcomes.
Management of cytomegalovirus (CMV) in transplant patients relies on measuring plasma CMV‐loads using quantitative nucleic acid testing (QNAT). We prospectively compared the automated ...Roche‐cobas®6800‐CMV and Roche‐CAP/CTM‐CMV with laboratory‐developed Basel‐CMV‐UL54‐95bp, and Basel‐CMV‐UL111a‐77bp. Roche‐cobas®6800‐CMV and Roche‐CAP/CTM‐CMV were qualitatively concordant in 142/150 cases (95%). In‐depth comparison revealed higher CMV‐loads of the laboratory‐developed assay and correlated with smaller amplicon size. After calibration to the 1.WHO‐approved CMV international standard, differences were reduced but remained significant. DNase‐I pretreatment significantly reduced CMV‐loads for both automated Roche‐CAP/CTM‐CMV and Roche‐cobas®6800‐CMV assays, whereby 90% and 95% of samples became undetectable. DNase‐I pretreatment also reduced CMV‐loads quantified by Basel‐CMV‐UL54‐95bp and Basel‐CMV‐UL111a‐77bp, but remaining detectable in 20% and 35%, respectively. Differences were largest for 110 samples with low‐level CMV‐DNAemia being detectable but not‐quantifiable by Roche‐cobas®6800‐CMV, whereby the smaller amplicon sizes yielded higher viral loads for concordant positives. We conclude that non‐encapsidated fragmented CMV‐DNA is the major form of plasma CMV‐loads also measured by fully‐automated platforms. Amplicons of <150 bp and calibrators are needed for reliable and commutable QNAT‐results. We hypothesize that non‐encapsidated fragmented CMV‐DNA results from lysis of CMV‐replicating cells and represent a direct marker of viral cell damage, which contribute to delayed viral load responses despite effective antivirals.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Cytomegalovirus (CMV) infection and disease are important causes of morbidity and mortality in transplant recipients. For the purpose of developing consistent reporting of CMV outcomes in clinical ...trials, definitions of CMV infection and disease were developed and most recently published in 2002. Since then, there have been major developments in its diagnosis and management. Therefore, the CMV Drug Development Forum consisting of scientists, clinicians, regulators, and industry representatives has produced an updated version incorporating recent knowledge with the aim to support clinical research and drug development. The main changes compared to previous definitions are the introduction of a "probable disease" category and to incorporate quantitative nucleic acid testing in some end-organ disease categories. As the field evolves, the need for updates of these definitions is clear, and collaborative efforts between scientists, regulators, and industry can provide a platform for this work.
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