Possible nosocomial transmission of virus-associated hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation

Onda, Yoshiyuki; Kanda, Junya; Hanaoka, Nozomu; Watanabe, Mizuki; Arai, Yasuyuki; Hishizawa, Masakatsu; Kondo, Tadakazu; Yamashita, Kouhei; Nagao, Miki; Fujimoto, Tsuguto

doi:10.1007/s00277-021-04414-1

Cited by 11 publications

(8 citation statements)

References 27 publications

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“…The lack of differences in BKV‐HC‐related HSCT characteristics between the periods may be partially explained by the cluster being caused by nosocomial infections. The nosocomial transmission of adenovirus‐associated HC has also been reported based on genotyping and partial sequencing of viral genomes 35 …”

Section: Discussionmentioning

confidence: 99%

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A cluster of BK polyomavirus‐associated hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation

Hosoi

Murata

Suzuki

et al. 2021

Transplant Infectious Dis

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Background BK polyomavirus (BKV) can cause hemorrhagic cystitis (HC) in immunocompromised patients after hematopoietic stem cell transplantation (HSCT). It remains unclear whether nosocomial BKV infections occur. During a 9‐month period, an increase in BKV‐associated HC (BKV‐HC) cases was observed at our institution. Aim The BKV‐HC cluster population was compared with populations of HSCT patients from before and after the BKV‐HC cluster to evaluate whether nosocomial BKV transmission had occurred. Methods A retrospective analysis was carried out to assess the risk of patients developing BKV‐HC after HSCT. The background data of the cluster patients were compared with those of the patients who underwent HSCT before or after the cluster, and the collected BKV isolates were serotyped. Results BKV‐HC involving grade ≥2 hematuria occurred in six of 15 HSCT recipients during a 9‐month period. The incidence of BKV‐HC was significantly higher in this period than in the other periods (p = 0.0014). There were no significant differences in the patients’ background data between the cluster and non‐cluster periods, including in terms of risk factors for BKV‐HC. Serotype analyses of BKV revealed that the BKV detected in the urine samples from four of the six BKV‐HC patients belonged to subtype Ic. The gene sequences of these four BKV exhibited >99.5% homology. Conclusion Our study suggests that nosocomial BKV infections may occur after HSCT. Although many cases of BKV‐HC are caused by the reactivation of a latent virus, it is necessary to employ appropriate hygiene measures when cases of BKV‐HC occur.

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Section: Discussionmentioning

confidence: 99%

“…The nosocomial transmission of adenovirus-associated HC has also been reported based on genotyping and partial sequencing of viral genomes. 35 BKV is detected in the urine of >80% of HSCT recipients, while only 10% develop BKV-HC. 1,12,19,20 No treatment is needed when mild HC symptoms occur.…”

Section: Discussionmentioning

confidence: 99%

A cluster of BK polyomavirus‐associated hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation

Hosoi

Murata

Suzuki

et al. 2021

Transplant Infectious Dis

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“…Indeed, pre-PCR studies relied on directly visualizing cell-free polyomavirus particles in urine of immunocompromised patients by negative staining and electron microscopy [ 6 , 31 , 35 , 36 ]. Thus, high-level BKPyV replication can produce urine viral loads >10 million c/mL containing a significant fraction of infectious units and hence a source of virus transmission, especially among HCT patients [ 12 , 37 , 38 ]. Third, BKPyV genome fragmentation leads to underestimating the genetic variation by NGS in an amplicon-size–dependent manner.…”

Section: Discussionmentioning

confidence: 99%

Molecular Characterization of BK Polyomavirus Replication in Allogeneic Hematopoietic Cell Transplantation Patients

Leuzinger

Kaur

Wilhelm

et al. 2022

The Journal of Infectious Diseases

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Background High-level BK polyomavirus (BKPyV) replication in allogeneic hematopoietic cell transplantation (HCT) predicts failing immune control and BKPyV-associated hemorrhagic cystitis (BKPyV-HC). Methods To identify molecular markers of BKPyV-replication and disease, we scrutinized BKPyV-DNA loads in longitudinal urine and plasma pairs from 20 HCT-patients using quantitative nucleic-acid-testing (QNAT), DNase-I treatment prior to QNAT, next-generation-sequencing (NGS) and tested cell-mediated immunity. Results We found that larger QNAT amplicons led to under-quantification and false-negatives results (p < 0.001). DNase-I reduced urine and plasma BKPyV-loads by >90% (p < 0.001) indicating non-encapsidated BKPyV-genomes. DNase-resistant urine BKPyV-loads remained infectious in cell culture. BKPyV-genome fragmentation of ≤250 bp impaired NGS-coverage of genetic variation using 1000 bp and 5000 bp targets. Conversely, 250bp-amplicons captured viral minority variants. We identified genotype-specific and genotype-independent changes in capsid-Vp1 or large T-antigen predicted to escape from antibody neutralization or HLA-presentation to CD8 T-cells, respectively. Genotype-specific changes in immunodominant 9mers were associated with reduced or absent CD8 T-cell responses. Thus, failure to control BKPyV-replication in HCT-patients may involve insufficient genotype-specific cytotoxic CD8 T-cell responses potentially predictable by low neutralizing antibodies as well as genotype-independent immune escape of variants. Conclusion Our results provide new insights for patient evaluation and for designing immune protection through neutralizing antibodies, adoptive T-cell therapy or vaccines.

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“…Another possibility is that replication may be induced by the mutation or rearrangements in NCCR region or alternatively viral replication may be result of the transmission of BKPyV from the donor to the recipient [ 77 ]. There are also studies suggesting replication of BKPyV as a result of the nosocomial transmission via medical personnel, medical instruments, or common toilets [ 78 , 79 ].…”

Section: Pathogenesis Of Bkpyv Infectionsmentioning

confidence: 99%

“…TAg has also been shown to activate the DNA methyltransferasy1 gene, causing hypermethylation of tumour suppressor genes, which facilitates their inactivation [ 85 ]. In experiments in mice, inactivation of pRB and p53 by TAg in the epithelium of the urinary tract caused a tumour reminiscent of cancer in humans [ 78 ]. Moreover, TAg has been detected in bladder cancer cells in transplant patients, and a correlation has been demonstrated between a large number of BKPyV viral particles in the urine and cases of bladder cancer [ 81 ].…”

Section: Pathogenesis Of Bkpyv Infectionsmentioning

confidence: 99%

BK Polyomavirus—Biology, Genomic Variation and Diagnosis

Furmaga

Kowalczyk

Zapolski

et al. 2021

Viruses

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The BK polyomavirus (BKPyV), a representative of the family Polyomaviridae, is widespread in the human population. While the virus does not cause significant clinical symptoms in immunocompetent individuals, it is activated in cases of immune deficiency, both pharmacological and pathological. Infection with the BKPyV is of particular importance in recipients of kidney transplants or HSC transplantation, in which it can lead to the loss of the transplanted kidney or to haemorrhagic cystitis, respectively. Four main genotypes of the virus are distinguished on the basis of molecular differentiation. The most common genotype worldwide is genotype I, with a frequency of about 80%, followed by genotype IV (about 15%), while genotypes II and III are isolated only sporadically. The distribution of the molecular variants of the virus is associated with the region of origin. BKPyV subtype Ia is most common in Africa, Ib-1 in Southeast Asia, and Ib-2 in Europe, while Ic is the most common variant in Northeast Asia. The development of molecular methods has enabled significant improvement not only in BKPyV diagnostics, but in monitoring the effectiveness of treatment as well. Amplification of viral DNA from urine by PCR (Polymerase Chain Reaction) and qPCR Quantitative Polymerase Chain Reaction) is a non-invasive method that can be used to confirm the presence of the genetic material of the virus and to determine the viral load. Sequencing techniques together with bioinformatics tools and databases can be used to determine variants of the virus, analyse their circulation in populations, identify relationships between them, and investigate the directions of evolution of the virus.

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Possible nosocomial transmission of virus-associated hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation

Abstract: The full-text file will be made open to the public on

Cited by 11 publications

References 27 publications

A cluster of BK polyomavirus‐associated hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation

A cluster of BK polyomavirus‐associated hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation

Molecular Characterization of BK Polyomavirus Replication in Allogeneic Hematopoietic Cell Transplantation Patients

BK Polyomavirus—Biology, Genomic Variation and Diagnosis

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