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Wang Y, Fang Y, Yan Z, Xia R, Zeng W, Deng W, Xu J, Feng X, Peng J, Miao Y. Fatal BK polyomavirus-associated pneumonia: report of two cases with literature review. BMC Infect Dis 2023; 23:592. [PMID: 37697264 PMCID: PMC10494412 DOI: 10.1186/s12879-023-08577-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Accepted: 08/31/2023] [Indexed: 09/13/2023] Open
Abstract
BACKGROUND In immunocompromised populations, such as patients with AIDS and recipients of solid organ and hematopoietic stem cell transplants, BK polyomavirus (BKPyV) can reactivate and cause several diseases, which can lead to death in their severe forms. Unlike hemorrhagic cystitis and BKPyV-associated nephropathy, BKPyV-associated pneumonia is rare, with only seven known cases worldwide. However, the disease can rapidly progress with extremely high mortality. CASE PRESENTATION Herein, we report two cases of BKPyV-associated pneumonia following hematopoietic stem cell transplantation. Both patients had consistent infectious pneumonia and graft-versus-host disease after stem cell transplantation. The diagnosis of BKPyV-associated pneumonia was confirmed by metagenomic next-generation sequencing and polymerase chain reaction after the sudden worsening of the pulmonary infection signs and symptoms concomitant with renal dysfunction and systemic immune weakening. Both patients eventually died of systemic multi-organ failure caused by severe pneumonia. CONCLUSIONS Currently, BKPyV reactivation cannot be effectively prevented. Immunocompromised patients must actively manage their primary lung infections, pay close attention to pulmonary signs and imaging changes. Especially during and after steroid pulse therapy or immunosuppressive therapy for graft versus host diseases, BKPyV load in blood/urine needs to be regularly measured, and the immunosuppressive intensity should be adjusted properly after the BKPyV reactivation diagnosis. Clinical trials of new antiviral drugs and therapies for BKPyV are urgently needed.
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Affiliation(s)
- Yuchen Wang
- Department of Transplantation, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, 510515, China
| | - Yiling Fang
- Department of Transplantation, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, 510515, China
| | - Ziyan Yan
- Department of Transplantation, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, 510515, China
| | - Renfei Xia
- Department of Transplantation, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, 510515, China
| | - Wenli Zeng
- Department of Transplantation, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, 510515, China
| | - Wenfeng Deng
- Department of Transplantation, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, 510515, China
| | - Jian Xu
- Department of Transplantation, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, 510515, China
| | - Xiaoqin Feng
- Department of Pediatrics, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, 510515, China.
| | - Jie Peng
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, 510515, China.
| | - Yun Miao
- Department of Transplantation, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, 510515, China.
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Roy S, Mieczkowski PA, Weida C, Huo J, Roehrs P, Singh HK, Nickeleit V. BK polyomavirus nephropathy with systemic viral spread: Whole genome sequencing data from a fatal case of BKPyV infection. Transpl Infect Dis 2020; 22:e13269. [PMID: 32090422 DOI: 10.1111/tid.13269] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2019] [Revised: 01/26/2020] [Accepted: 02/16/2020] [Indexed: 12/25/2022]
Abstract
BK polyomavirus (BKPyV) infections with multi-organ involvement are rare. Here, we report for the first time whole genome sequencing data from a patient with systemic BKPyV disease. She presented post stem cell transplantation with graft-vs-host disease, suffered from profound immunosuppression, and developed fatal BKPyV disease of kidneys, lungs, and pancreas. The lytic infection was caused by an episomal BKPyV-Ib strain with canonical structural and receptor encoding gene sequences. However, DNA from all infected tissue sites showed diverse BKPyV-NCCR rearrangements (rr-NCCR) involving the P, Q, and R domains, while largely sparing O and S, carrying initiation sites for early and late BKPyV gene transcripts crucial for viral replication and assembly. Common to all rr-NCCR variants was a break point in Q (position 17-27) that can form the nidus for double DNA strand break formation and gene rearrangements. Metastatic clonal BKPyV spread from kidneys to other organs was not detected. We hypothesize that lack of immune surveillance and a specific NCCR break point promote profound gene rearrangements of NCCR-P, Q, and R with alterations of regulatory feedback loops. As a result, viral replication and pathogenicity are enhanced leading to severe, often fatal systemic disease not caused by the common archetypical BKPyV strains.
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Affiliation(s)
- Sanjeet Roy
- Division of Nephropathology, The University of North Carolina School of Medicine, Chapel Hill, NC, USA
| | - Piotr A Mieczkowski
- Department of Genetics, The University of North Carolina, Chapel Hill, NC, USA
| | - Carol Weida
- Carolinas Pathology Group, Charlotte, NC, USA
| | - Jeffrey Huo
- Division of Pediatric Hematology/Oncology/BMT, Levine Children's Hospital, Charlotte, NC, USA
| | - Philip Roehrs
- Division of Pediatric Hematology/Oncology/BMT, Levine Children's Hospital, Charlotte, NC, USA
| | - Harsharan K Singh
- Division of Nephropathology, The University of North Carolina School of Medicine, Chapel Hill, NC, USA
| | - Volker Nickeleit
- Division of Nephropathology, The University of North Carolina School of Medicine, Chapel Hill, NC, USA
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3
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Trang VD, Rockett R, Jeoffreys N, Trung NV, Hai An HP, Kok J, Dwyer DE. BK polyomavirus: a review of the virology, pathogenesis, clinical and laboratory features, and treatment. Future Virol 2017. [DOI: 10.2217/fvl-2017-0013] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BK polyomavirus (BKPyV) is a non-enveloped, circular dsDNA virus with a genome of approximately 5100 base pairs. It can be divided into four major genotypes, but the effects of different genotypes on clinical disease are uncertain. Primary BKPyV infection is generally acquired asymptomatically in childhood. It establishes low-level persistence in many tissues, particularly the genitourinary tract. Reactivation can lead to severe disease including BKPyV-associated nephropathy confirmed by renal biopsy, hemorrhagic cystitis and meningoencephalitis. Nucleic acid amplification testing of blood and urine is the main diagnostic and prognostic test for BKPyV infection. The treatment of BKPyV infection has concentrated on reduction in immunosuppressive therapy. Recent studies suggest that antiviral drugs have demonstrated only modest benefit, but adoptive T-cell therapies offer potential advances.
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Affiliation(s)
- Van Dinh Trang
- Clinical Laboratory, National Hospital of Tropical Diseases, 78-Giai Phong, Dong Da, Hanoi, Vietnam
- Western Clinical School, Westmead Hospital, The University of Sydney, NSW 2006, Australia
| | - Rebecca Rockett
- Center for Infectious Diseases & Microbiology Laboratory Services, Institute of Clinical Pathology & Medical Research, NSW Health Pathology, Westmead Hospital, Westmead NSW 2145, Australia
| | - Neisha Jeoffreys
- Center for Infectious Diseases & Microbiology Laboratory Services, Institute of Clinical Pathology & Medical Research, NSW Health Pathology, Westmead Hospital, Westmead NSW 2145, Australia
| | - Nguyen Vu Trung
- Clinical Laboratory, National Hospital of Tropical Diseases, 78-Giai Phong, Dong Da, Hanoi, Vietnam
- Department of Medical Microbiology, Hanoi Medical University, No. 1 Ton That Tung St, Dong Da, Hanoi, Vietnam
| | - Ha Phan Hai An
- Department of International Cooperation, Hanoi Medical University, No. 1 Ton That Tung St, Dong Da, Hanoi, Vietnam
- Kidney Diseases & Dialysis Department, Viet Duc Hospital, No. 40 Trang Thi St, Hoan Kiem, Hanoi, Vietnam
| | - Jen Kok
- Center for Infectious Diseases & Microbiology Laboratory Services, Institute of Clinical Pathology & Medical Research, NSW Health Pathology, Westmead Hospital, Westmead NSW 2145, Australia
| | - Dominic E Dwyer
- Western Clinical School, Westmead Hospital, The University of Sydney, NSW 2006, Australia
- Center for Infectious Diseases & Microbiology Laboratory Services, Institute of Clinical Pathology & Medical Research, NSW Health Pathology, Westmead Hospital, Westmead NSW 2145, Australia
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4
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Hemorrhagic Cystitis in a Liver Transplant Recipient Secondary to BK Virus. ACG Case Rep J 2017; 4:e67. [PMID: 28516112 PMCID: PMC5425281 DOI: 10.14309/crj.2017.67] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2017] [Accepted: 04/04/2017] [Indexed: 01/30/2023] Open
Abstract
The association between BK virus infection and hemorrhagic cystitis (HC) in hematopoietic stem cell transplant (HSCT) recipients is well established. However, BK virus-associated HC has not been described in liver transplant (LT) recipients. We present a case of BK virus-associated HC in a LT recipient. Our patient presented with worsening liver function tests 2 years after transplantation and was found to have acute cellular rejection. He was treated with increased immunosuppression and subsequently developed hematuria. He was eventually diagnosed with BK virus-associated HC.
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5
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Vigil D, Konstantinov NK, Barry M, Harford AM, Servilla KS, Kim YH, Sun Y, Ganta K, Tzamaloukas AH. BK nephropathy in the native kidneys of patients with organ transplants: Clinical spectrum of BK infection. World J Transplant 2016; 6:472-504. [PMID: 27683628 PMCID: PMC5036119 DOI: 10.5500/wjt.v6.i3.472] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2016] [Revised: 08/25/2016] [Accepted: 09/08/2016] [Indexed: 02/05/2023] Open
Abstract
Nephropathy secondary to BK virus, a member of the Papoviridae family of viruses, has been recognized for some time as an important cause of allograft dysfunction in renal transplant recipients. In recent times, BK nephropathy (BKN) of the native kidneys has being increasingly recognized as a cause of chronic kidney disease in patients with solid organ transplants, bone marrow transplants and in patients with other clinical entities associated with immunosuppression. In such patients renal dysfunction is often attributed to other factors including nephrotoxicity of medications used to prevent rejection of the transplanted organs. Renal biopsy is required for the diagnosis of BKN. Quantitation of the BK viral load in blood and urine are surrogate diagnostic methods. The treatment of BKN is based on reduction of the immunosuppressive medications. Several compounds have shown antiviral activity, but have not consistently shown to have beneficial effects in BKN. In addition to BKN, BK viral infection can cause severe urinary bladder cystitis, ureteritis and urinary tract obstruction as well as manifestations in other organ systems including the central nervous system, the respiratory system, the gastrointestinal system and the hematopoietic system. BK viral infection has also been implicated in tumorigenesis. The spectrum of clinical manifestations from BK infection and infection from other members of the Papoviridae family is widening. Prevention and treatment of BK infection and infections from other Papovaviruses are subjects of intense research.
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6
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Mathew J, Holanda D, Figanbaum T, Fraer M, Thomas C. Late-Onset BK Viral Nephropathy in a Kidney Transplant Recipient. Transplant Proc 2014; 46:2386-90. [DOI: 10.1016/j.transproceed.2014.06.047] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2014] [Accepted: 06/17/2014] [Indexed: 02/02/2023]
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BK Virus and Its Role in Hematopoietic Stem Cell Transplantation: Evolution of a Pathogen. Curr Infect Dis Rep 2014; 16:417. [PMID: 24942378 DOI: 10.1007/s11908-014-0417-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
We reviewed the literature regarding disease induced by BK virus (BKV) in the hematopoietic stem cell transplant (HSCT) population, particularly hemorrhagic cystitis (HC) and nephritis. The association between BKV and HC has been reported over the past four decades. BKV has been clinically implicated and widely accepted as an etiologic agent of HC and nephritis in HSCT and nephropathy in renal transplant patients. We discuss the potential benefit of early initiation of therapy in patients who fail supportive care alone as well as the different treatment strategies for HC induced by BKV. Treatments that have been used such as cidofovir and leflunomide are accompanied by risks, and the benefits are not as concrete as with other viral illness in the HSCT population.
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8
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Satyanarayana G, Marty FM, Tan CS. The polyomavirus puzzle: is host immune response beneficial in controlling BK virus after adult hematopoietic cell transplantion? Transpl Infect Dis 2014; 16:521-31. [PMID: 24834968 DOI: 10.1111/tid.12233] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2013] [Revised: 01/22/2014] [Accepted: 02/08/2014] [Indexed: 12/14/2022]
Abstract
BK virus (BKV), a ubiquitous human polyomavirus, usually does not cause disease in healthy individuals. BKV reactivation and disease can occur in immunosuppressed individuals, such as those who have undergone renal transplantation or hematopoietic cell transplantation (HCT). Clinical manifestations of BKV disease include graft dysfunction and failure in renal transplant recipients; HCT recipients frequently experience hematuria, cystitis, hemorrhagic cystitis (HC), and renal dysfunction. Studies of HCT patients have identified several risk factors for the development of BKV disease including myeloablative conditioning, acute graft-versus-host disease, and undergoing an umbilical cord blood (uCB) HCT. Although these risk factors indicate that alterations in the immune system are necessary for BKV pathogenesis in HCT patients, few studies have examined the interactions between host immune responses and viral reactivation in BKV disease. Specifically, having BKV immunoglobulin-G before HCT does not protect against BKV infection and disease after HCT. A limited number of studies have demonstrated BKV-specific cytotoxic T cells in healthy adults as well as in post-HCT patients who had experienced HC. New areas of research are required for a better understanding of this emerging infectious disease post HCT, including prospective studies examining BK viruria, viremia, and their relationship with clinical disease, a detailed analysis of urothelial histopathology, and laboratory evaluation of systemic and local cellular and humoral immune responses to BKV in patients receiving HCT from different sources, including uCB and haploidentical donors.
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Affiliation(s)
- G Satyanarayana
- Division of Infectious Disease, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA; Division of Infectious Disease, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA; Center for Virology and Vaccine Research, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
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9
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Rinaldo CH, Tylden GD, Sharma BN. The human polyomavirus BK (BKPyV): virological background and clinical implications. APMIS 2013; 121:728-45. [PMID: 23782063 DOI: 10.1111/apm.12134] [Citation(s) in RCA: 66] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2013] [Accepted: 04/27/2013] [Indexed: 12/13/2022]
Abstract
Polyomavirus BK (BKPyV) infects most people subclinically during childhood and establishes a lifelong infection in the renourinary tract. In most immunocompetent individuals, the infection is completely asymptomatic, despite frequent episodes of viral reactivation with shedding into the urine. In immunocompromised patients, reactivation followed by high-level viral replication can lead to severe disease: 1-10% of kidney transplant patients develop polyomavirus-associated nephropathy (PyVAN) and 5-15% of allogenic hematopoietic stem cell transplant patients develop polyomavirus-associated haemorrhagic cystitis (PyVHC). Other conditions such as ureteric stenosis, encephalitis, meningoencephalitis, pneumonia and vasculopathy have also been associated with BKPyV infection in immunocompromised individuals. Although BKPyV has been associated with cancer development, especially in the bladder, definitive evidence of a role in human malignancy is lacking. Diagnosis of PyVAN and PyVHC is mainly achieved by quantitative PCR of urine and plasma, but also by cytology, immunohistology and electron microscopy. Despite more than 40 years of research on BKPyV, there is still no effective antiviral therapy. The current treatment strategy for PyVAN is to allow reconstitution of immune function by reducing or changing the immunosuppressive medication. For PyVHC, treatment is purely supportive. Here, we present a summary of the accrued knowledge regarding BKPyV.
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Affiliation(s)
- Christine Hanssen Rinaldo
- Department of Microbiology and Infection Control, University Hospital of North Norway, Tromsø, Norway.
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10
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Risk Factors for BK Virus–Associated Hemorrhagic Cystitis in Allogeneic Stem Cell Transplant Recipients. INFECTIOUS DISEASES IN CLINICAL PRACTICE 2013. [DOI: 10.1097/ipc.0b013e318278f89a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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11
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Jennings SH, Wise AG, Nickeleit V, Maes RK, Cianciolo RE, Del Piero F, Law JM, Kim Y, McCalla AC, Breuhaus BA, Roberts MC, Linder KE. Polyomavirus-associated nephritis in 2 horses. Vet Pathol 2013; 50:769-74. [PMID: 23381926 DOI: 10.1177/0300985813476063] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Polyomaviruses produce latent and asymptomatic infections in many species, but productive and lytic infections are rare. In immunocompromised humans, polyomaviruses can cause tubulointerstitial nephritis, demyelination, or meningoencephalitis in the central nervous system and interstitial pneumonia. This report describes 2 Standardbred horses with tubular necrosis and tubulointerstitial nephritis associated with productive equine polyomavirus infection that resembles BK polyomavirus nephropathy in immunocompromised humans.
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Affiliation(s)
- S H Jennings
- North Carolina State University, College of Veterinary Medicine, Department of Population Health and Pathobiology, 1060 William Moore Rd, Raleigh, NC 27607, USA.
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12
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Smith SP, Crawley CR, See TC, Screaton NJ, Preller JM. A case of bilateral ureteric obstruction in an allogeneic stem cell transplant recipient. J Clin Virol 2013; 56:1-4. [DOI: 10.1016/j.jcv.2012.07.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2012] [Revised: 07/04/2012] [Accepted: 07/06/2012] [Indexed: 10/28/2022]
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13
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Akazawa Y, Terada Y, Yamane T, Tanaka S, Aimoto M, Koh H, Nakane T, Koh KR, Nakamae H, Ohsawa M, Wakasa K, Hino M. Fatal BK virus pneumonia following stem cell transplantation. Transpl Infect Dis 2012; 14:E142-6. [PMID: 22998078 DOI: 10.1111/tid.12011] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2011] [Revised: 05/14/2012] [Accepted: 06/14/2012] [Indexed: 12/16/2022]
Abstract
We report the case of a 39-year-old male patient who died of severe BK virus (BKV) pneumonia 168 days after hematopoietic stem cell transplantation (HSCT) for acute lymphoblastic leukemia. After suffering from BKV-associated late-onset hemorrhagic cystitis (HC) with long-term sustained BKV viremia, he died of rapidly progressive pneumonia. On autopsy, numerous viral intranuclear inclusions were seen in his lungs and bladder. An immunohistochemical examination of his lungs was positive for simian virus 40. Based on these pathological results and the high sustained BKV viral load in his blood, we reached a diagnosis of BKV pneumonia. Viral infection can occasionally become life threatening among HSCT recipients. It is widely known that BKV can cause late-onset HC, but BKV-associated pneumonia is rare. Because of its rapid progression and poor prognosis, it is difficult to make an antemortem diagnosis of BKV pneumonia. A treatment strategy for BKV pneumonia also needs to be formulated. Similar to other viral pathogens, BKV can cause pneumonia and the clinician should therefore be aware of it in immunocompromised patients.
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Affiliation(s)
- Y Akazawa
- Hematology, Graduate School of Medicine, Osaka City University, Osaka, Japan
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Yapa HMN, McLornan DP, Raj K, Streetly M, Kazmi M, Cuthill K, Laurie J, Menon PA, Macmahon E. Pneumonitis post-haematopoeitic stem cell transplant - cytopathology clinches diagnosis. J Clin Virol 2012; 55:278-81. [PMID: 22959064 DOI: 10.1016/j.jcv.2012.08.007] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2012] [Accepted: 08/03/2012] [Indexed: 12/17/2022]
Abstract
BACKGROUND Primary BK virus (BKV) infection is probably acquired by the respiratory route in childhood, and latent virus persists principally in the urinary tract. BKV reactivation is implicated in late onset haemorrhagic cystitis (HC) post Haematopoietic Stem Cell Transplant (HSCT). There is emerging evidence that BKV can cause life-threatening pneumonitis in immunocompromised individuals. OBJECTIVES To describe the first known case of BKV pneumonitis in an adult HSCT recipient. STUDY DESIGN/RESULTS A 19-year old male underwent an ABO-incompatible, volunteer unrelated donor allogeneic HSCT for high risk AML. The post-transplant period was complicated by moderate-severe cutaneous and gut acute graft-versus-host disease (aGVHD) and severe HC, attributable to BKV. Treatment encompassed intensification of immunosupression for aGVHD and weekly intravenous (IV) cidofovir (2.5mg/Kg) for BK viruria. He was readmitted with presumed septic shock and acute renal failure. After a transient improvement on broad spectrum antibacterials, he suffered significant respiratory deterioration. CT imaging revealed diffuse 'ground-glass' attenuation. Cytopathological assessment of a broncho-alveolar sample (BAL) was consistent with polyomavirus pneumonitis. No other cause was found to account for the respiratory deterioration. He did not respond to therapy and died of multi-organ failure. CONCLUSIONS BKV is implicated in haemorrhagic cystitis in HSCT recipients but not routinely considered as a cause of pneumonitis. There are just 5 other cases in the literature, including 3 patients with AIDS. BKV should be considered as a possible cause of pneumonitis in HSCT recipients.
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Affiliation(s)
- H Manisha N Yapa
- Department of Infectious Diseases, Guy's and St Thomas' NHS Foundation Trust, London, UK.
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Bennett SM, Broekema NM, Imperiale MJ. BK polyomavirus: emerging pathogen. Microbes Infect 2012; 14:672-83. [PMID: 22402031 PMCID: PMC3568954 DOI: 10.1016/j.micinf.2012.02.002] [Citation(s) in RCA: 78] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2012] [Revised: 02/03/2012] [Accepted: 02/07/2012] [Indexed: 02/07/2023]
Abstract
BK polyomavirus (BKPyV) is a small double-stranded DNA virus that is an emerging pathogen in immunocompromised individuals. BKPyV is widespread in the general population, but primarily causes disease when immune suppression leads to reactivation of latent virus. Polyomavirus-associated nephropathy and hemorrhagic cystitis in renal and bone marrow transplant patients, respectively, are the most common diseases associated with BKPyV reactivation and lytic infection. In this review, we discuss the clinical relevance, effects on the host, virus life cycle, and current treatment protocols.
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Affiliation(s)
- Shauna M. Bennett
- Program in Cellular and Molecular Biology, University of Michigan Medical School, 1150 West Medical Center Drive, 5724 Medical Science II, Ann Arbor, MI 48109-5620, USA
| | - Nicole M. Broekema
- Department of Microbiology and Immunology, University of Michigan Medical School, 1150 West Medical Center Drive, 5724 Medical Science II, Ann Arbor, MI 48109-5620, USA
| | - Michael J. Imperiale
- Program in Cellular and Molecular Biology, University of Michigan Medical School, 1150 West Medical Center Drive, 5724 Medical Science II, Ann Arbor, MI 48109-5620, USA
- Department of Microbiology and Immunology, University of Michigan Medical School, 1150 West Medical Center Drive, 5724 Medical Science II, Ann Arbor, MI 48109-5620, USA
- Comprehensive Cancer Center University of Michigan Medical School, 1150 West Medical Center Drive, 5724 Medical Science II, Ann Arbor, MI 48109-5620, USA
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Abedi Kiasari B, Vallely PJ, Klapper PE. Merkel cell polyomavirus DNA in immunocompetent and immunocompromised patients with respiratory disease. J Med Virol 2012; 83:2220-4. [PMID: 22012732 PMCID: PMC7166447 DOI: 10.1002/jmv.22222] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Merkel cell polyomavirus (MCPyV) was identified originally in association with a rare but aggressive skin cancer, Merkel cell carcinoma. The virus has since been found in the respiratory tract of some patients with respiratory disease. However, the role of MCPyV in the causation of respiratory disease has not been established. To determine the prevalence of MCPyV in 305 respiratory samples from immunocompetent and immunocompromised patients and evaluate their contribution to respiratory diseases, specimens were screened for MCPyV using single, multiplex, or real‐time PCR; co‐infection with other viruses was examined. Of the 305 samples tested, 10 (3.27%) were positive for MCPyV. The virus was found in two groups of patients: in 6 (2%) nasopharyngeal aspirate samples from children aged 26 days to 7 months who were immunocompetent; and in 4 (1.3%) of nasopharyngeal aspirate samples taken from patients aged 41 to 69 years who were severely immunosuppressed from leukemia or transplant therapy. Both groups had upper or lower respiratory tract infection. Co‐infections with other viruses were found in 30% of the MCPyV positive samples. The data present a pattern of infection similar to that seen with the polyomaviruses JC and BK in which the virus is acquired during childhood, probably by the respiratory route. The viruses then establish latency and become reactivated in the event of immunosuppression. J. Med. Virol. 83:2220–2224, 2011. © 2011 Wiley Periodicals, Inc.
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Motazakker M, Bagheri M, Imani M. Subtyping of BK Virus in Iranian Turkish Renal Transplant Recipients by RFLP-PCR. MAEDICA 2012; 7:10-13. [PMID: 23118813 PMCID: PMC3484789] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 11/23/2011] [Accepted: 03/26/2012] [Indexed: 06/01/2023]
Abstract
INTRODUCTION BK polyomavirus (BKV) as a member of polyomavirus family is prevalent in the human population. BKV persists in renal tissue after asymptomatic infection in childhood. The reactivation of BKV in renal transplant recipients sometimes can lead to BKV associated nephropathy. BKV isolates are classified into four serologically distinct subtypes. Present study was carried out to investigate the distribution pattern of BKV subtypes in Iranian Turkish renal transplant recipients. MATERIALS AND METHODS Urine samples from 12 kidney transplant recipients infected with BKV were analyzed by RFLP-PCR technique for classification of subtypes. RESULTS Our analysis showed that all samples were infected with BKV type I. BK virus types II, III, and IV were not detected in our patients. CONCLUSIONS Based on the results of the present study, BKV subtype I was the most frequently detected subtype in renal transplant recipients. To our knowledge, the present study provides the first data regarding distribution of BKV subtypes in Iranian renal transplant recipients.
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Affiliation(s)
- Morteza Motazakker
- Nephrology and Transplant Research Center, Clinical virology Laboratory, Urmia University of Medical Sciences, Urmia, Iran ; Division of Clinical Virology, Cellular and Molecular Research Center, Urmia University of Medical Sciences, Urmia, Iran
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18
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Haines HL, Laskin BL, Goebel J, Davies SM, Yin HJ, Lawrence J, Mehta PA, Bleesing JJ, Filipovich AH, Marsh RA, Jodele S. Blood, and not urine, BK viral load predicts renal outcome in children with hemorrhagic cystitis following hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2011; 17:1512-9. [PMID: 21385622 DOI: 10.1016/j.bbmt.2011.02.012] [Citation(s) in RCA: 75] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2011] [Accepted: 02/16/2011] [Indexed: 12/16/2022]
Abstract
BK virus is a significant cause of hemorrhagic cystitis after hematopoietic stem cell transplantation (HSCT). However, its role in nephropathy post-HSCT is less studied. We retrospectively evaluated clinical outcomes in pediatric HSCT patients with hemorrhagic cystitis. Although most of these patients had very high urine BK viral loads (viruria), patients with higher BK plasma loads (viremia) had significant renal dysfunction, a worse clinical course, and decreased survival. Patients with a peak plasma BK viral load of >10,000 copies/mL (high viremia) were more likely to need dialysis and aggressive treatment for hemorrhagic cystitis compared to patients with ≤ 10,000 copies/mL (low viremia). Conversely, most patients with low viremia had only transient elevations in creatinine, and less severe hemorrhagic cystitis that resolved with supportive therapy. Overall survival (OS) at 1 year post-HSCT was 89% in the low viremia group and 48% in the high viremia group. We conclude that the degree of BK viremia, and not viruria, may predict renal, urologic, and overall outcome in the post-HSCT population.
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Affiliation(s)
- Hilary L Haines
- Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA
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19
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Bergallo M, Costa C, Terlizzi ME, Astegiano S, Curtoni A, Solidoro P, Delsedime L, Cavallo R. Quantitative detection of the new polyomaviruses KI, WU and Merkel cell virus in transbronchial biopsies from lung transplant recipients. J Clin Pathol 2010; 63:722-5. [PMID: 20595181 DOI: 10.1136/jcp.2010.077966] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
BACKGROUND Recently, three new polyomaviruses-KI, WU and Merkel cell (MCV)-have been discovered and their detection has been reported in different types of specimens, including respiratory samples, suggesting their shedding in the airways. In lung graft recipients, viral agents are associated with events that may limit the success of transplantation, including organ infection/disease and allograft rejection. AIMS To evaluate the prevalence of KI, WU and MCV in transbronchial biopsies from lung transplant recipients and investigate the association with clinical and histopathological features. METHODS The quantitation of new polyomaviruses DNA by real-time PCR and association with clinical and histopathological findings were evaluated in 66 transbronchial biopsies from lung transplant recipients. Results KI, WU and MCV were detected in 9.2%, 12.3% and 33.8% of specimens, respectively; with mean viral load ranging from 81 copies/10(4) cells for WU to 258 for MCV, thus not differing from that previously reported in native lungs. No significant association with clinical and histopathological findings (including acute respiratory insufficiency, interstitial and organising pneumonia, acute and chronic rejection) was found. CONCLUSIONS Results showed a relatively high frequency of detection of the novel polyomaviruses in transbronchial biopsies from lung transplant recipients. It is likely that this accounted for the positive results found in some cases with different pathological background, although no significant association with a specific clinical and/or histopathological pattern was found.
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20
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Respiratory Epithelium: An Unlikely Reservoir for Latent Human Polyomavirus Infection but a Likely Portal of Entry. Transplantation 2010; 89:634-5. [DOI: 10.1097/tp.0b013e3181c7f255] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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21
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Kleinberg M. Viruses. MANAGING INFECTIONS IN PATIENTS WITH HEMATOLOGICAL MALIGNANCIES 2009. [PMCID: PMC7114983 DOI: 10.1007/978-1-59745-415-5_2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Viral infections are an important and often unrecognized component of disease in immunocompromised patients. The diagnosis and management of viral infections have expanded largely because of new quantitative molecular diagnostic assays. Well-recognized pathogens such as herpes simplex virus (HSV), cytomegalovirus (CMV), and respiratory viruses have been joined by newly recognized pathogens such as BK virus, human herpesvirus-6 (HHV-6), and human metapneumovirus in this highly susceptible patient population. The role of Epstein-Barr virus (EBV) and Human herpesvirus-8 (HHV-8) in lymphoproliferative diseases also continue to be clarified. As a result, the management of viral infections in patients with hematologic malignancies continues to be a growing challenge for the clinician.
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Affiliation(s)
- Michael Kleinberg
- School of Medicine, University of Maryland, S. Greene St. 22, Baltimore, 21201 U.S.A
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22
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Dropulic LK, Jones RJ. Polyomavirus BK infection in blood and marrow transplant recipients. Bone Marrow Transplant 2008; 41:11-8. [PMID: 17952131 PMCID: PMC3066131 DOI: 10.1038/sj.bmt.1705886] [Citation(s) in RCA: 148] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2007] [Accepted: 08/31/2007] [Indexed: 12/16/2022]
Abstract
The association of BK virus infection with hemorrhagic cystitis in blood and marrow transplant (BMT) recipients was first demonstrated two decades ago. During this time, therapeutic interventions focused on supportive measures such as hyperhydration, continuous bladder irrigation and topical administration of agents that alter the mucosal surface of the bladder wall. In recent years, PCR amplification of viral DNA in the urine and plasma has solidified the association of BK virus infection with hemorrhagic cystitis, demonstrating that higher urine and plasma viral loads occur in the setting of disease. The evaluation of virus-specific therapy has lagged behind assessment of the viral load and theories of pathogenesis. Extrapolating from successes in the treatment of BK virus nephropathy in the renal transplant population, cidofovir and leflunomide are identified as potential effective agents for the treatment of BK virus-associated hemorrhagic cystitis. The fluoroquinolone antibiotics may prove to be effective as prophylactic agents. Given the manifestation of BK virus infection in organs outside of the urinary tract in an increasing immunocompromised patient population and the availability of potential antiviral agents, therapeutic trials need to progress beyond the small case series in order to improve the morbidity and mortality caused by BK virus-associated hemorrhagic cystitis in the BMT population.
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Affiliation(s)
- L K Dropulic
- Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21205, USA.
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23
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Dropulic LK, Jones RJ. Polyomavirus BK infection in blood and marrow transplant recipients. Bone Marrow Transplant 2007. [PMID: 17952131 DOI: 10.1038/j.bmt.1705886] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The association of BK virus infection with hemorrhagic cystitis in blood and marrow transplant (BMT) recipients was first demonstrated two decades ago. During this time, therapeutic interventions focused on supportive measures such as hyperhydration, continuous bladder irrigation and topical administration of agents that alter the mucosal surface of the bladder wall. In recent years, PCR amplification of viral DNA in the urine and plasma has solidified the association of BK virus infection with hemorrhagic cystitis, demonstrating that higher urine and plasma viral loads occur in the setting of disease. The evaluation of virus-specific therapy has lagged behind assessment of the viral load and theories of pathogenesis. Extrapolating from successes in the treatment of BK virus nephropathy in the renal transplant population, cidofovir and leflunomide are identified as potential effective agents for the treatment of BK virus-associated hemorrhagic cystitis. The fluoroquinolone antibiotics may prove to be effective as prophylactic agents. Given the manifestation of BK virus infection in organs outside of the urinary tract in an increasing immunocompromised patient population and the availability of potential antiviral agents, therapeutic trials need to progress beyond the small case series in order to improve the morbidity and mortality caused by BK virus-associated hemorrhagic cystitis in the BMT population.
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Affiliation(s)
- L K Dropulic
- Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21205, USA.
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Fogeda M, Muñoz P, Luque A, Morales MD, Bouza E. Cross-sectional study of BK virus infection in pediatric kidney transplant recipients. Pediatr Transplant 2007; 11:394-401. [PMID: 17493219 DOI: 10.1111/j.1399-3046.2006.00671.x] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
BKV reactivation is associated with impaired graft function in adult kidney transplant patients. The clinical impact of BKV infection in the pediatric transplant population has not yet been fully evaluated. The objective of our study was to determine the prevalence of BKV infection in consecutive pediatric kidney transplant recipients in our center. Forty consecutive unselected pediatric kidney transplant recipients were studied. Mean age at screening was 15.6 +/- 5.3 yr and samples were obtained a median of 60.5 months after transplantation (3-123). BKV-DNA was analyzed in urine and plasma by qualitative nested-PCR. A review of the literature was performed. Prevalence of viruria and viremia was 50% and 12.5%, respectively. Viremia was associated with the presence of hematuria (p = 0.02). The mean creatinine level in children without BKV replication was 1.6 mg/dL, BKV viruria was 0.9 mg/dL, and BKV viremia was 0.8 mg/dL. A literature review showed that viruria and viremia were found in 28.2% and 8.5% of cases, respectively; BKV nephropathy was found in 3.8% and graft loss in 11% of the patients with BKV nephropathy and in 0.4% of the children studied. Recipient serostatus was the most important risk factor. The rate of BKV replication and nephropathy among pediatric kidney recipients is similar to that of adults, but the incidence of graft loss is significantly lower.
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Affiliation(s)
- Marta Fogeda
- Department of Clinical Microbiology-Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain
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25
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Abstract
PURPOSE OF REVIEW In many cases, the specific pathogen responsible for a respiratory infection is not identified and can lead to improper medical treatment, increased duration of illness, and possibly contributes to the development of antibiotic resistance. Molecular-based diagnostic methodologies have significantly improved our ability to identify common respiratory pathogens; these techniques are not useful, however, when a novel pathogen is responsible for the infection and clinicians must rely on differential diagnosis for the treatment of patients. RECENT FINDINGS New pathogens previously not associated with human infections have been identified in the past few years. In addition, new strains of bacteria and viruses have emerged as the causative agents of pneumonia and acute respiratory distress. Protozoans and saprophytic fungi, which are not normally associated with respiratory infection, have also emerged as respiratory pathogens particularly in individuals with AIDS or in those who are otherwise immunocompromised. SUMMARY This review discusses the recent literature on newly described respiratory pathogens as well as opportunistic pathogens that can infect the respiratory system of immunocompromised individuals. The studies referenced here reveal the need for expanded laboratory tests and highly trained microbiologists in clinical laboratories worldwide.
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Affiliation(s)
- John A Lednicky
- Life Sciences Division, Midwest Research Institute, Kansas City, Missouri, USA.
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26
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Krumbholz A, Zell R, Egerer R, Sauerbrei A, Helming A, Gruhn B, Wutzler P. Prevalence of BK virus subtype I in Germany. J Med Virol 2006; 78:1588-98. [PMID: 17063524 DOI: 10.1002/jmv.20743] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
The primary infection with human polyomavirus BK (BKV) occurs in early childhood and leads to viral latency within the urogenital tract. Up to 90% of the adult population are seropositive. In immunosuppressed patients, the BKV may be reactivated resulting in typical disease patterns like hemorrhagic cystitis and tubulointerstitial nephritis. Based on serological and molecular methods, BKV isolates were classified into four subtypes previously. Sixty specimens obtained from German renal and bone marrow transplant recipients were analyzed to gain data on the prevalence of BKV subtypes in Germany. With 90.9%, BKV subtype I was found to be predominant in both patient groups. 6.1% of BKV strains were classified as subtype IV. This pattern of phylogenetic distribution is similar to that demonstrated previously in England, Tanzania, the United States and Japan. Remarkably, there was one German BKV virus with a sequence which clusters together with strain SB in subtype II. The BKV subtype I was found to consist of at least three subgroups designated as Ia, Ib, and Ic. While the majority of the German sequences represent subgroup Ic, most of the Japanese sequences are clearly distinct. These findings support the hypothesis of distinct geographical prevalence of BKV subgroups. For the genotyping region, a relationship of BKV subgroups to disease patterns like hemorrhagic cystitis or tubulointerstitial nephritis could not be demonstrated.
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Affiliation(s)
- Andi Krumbholz
- Institute of Virology and Antiviral Therapy, Medical Center, Friedrich Schiller University Jena, Jena, Germany.
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27
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Abstract
This overview summarizes recent data on emerging viruses after hematopoietic cell transplantation (HCT), including adenovirus, BK virus, human metapneumovirus (hMPV), and human herpesvirus (HHV) 6. The increased recognition of these infections is due to improved molecular detection methods, increased surveillance and more profound immunosuppression in the host. Adenovirus can cause serious disease especially in T-cell depleted transplant recipients. Adenovirus viremia is an important risk factor for disease in this setting. BK virus has been associated with hemorrhagic cystitis in HCT recipients. BK viremia is significantly associated with hemorrhagic cystitis. hMPV shows a seasonal distribution and can cause fatal pneumonia in HCT recipients. hMPV may be the etiology of some cases previously categorized as idiopathic pneumonia syndrome. HHV-6 commonly leads to viremia in HCT recipients. HHV-6 has been strongly associated with encephalitis and delayed platelet engraftment. Prospective studies are needed to further examine epidemiology, disease associations, and management strategies for these viruses.
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Affiliation(s)
- Michael Boeckh
- Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
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28
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Hirsch HH. BK virus: opportunity makes a pathogen. Clin Infect Dis 2005; 41:354-60. [PMID: 16007533 DOI: 10.1086/431488] [Citation(s) in RCA: 230] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2005] [Accepted: 04/22/2005] [Indexed: 12/28/2022] Open
Abstract
More than 70% of the general population worldwide has serological evidence of exposure to Polyomavirus hominis type 1, better known as BK virus (BKV). BKV infection typically occurs during childhood, without specific symptoms, followed by a state of nonreplicative infection in various tissues, with the urogenital tract as the principal site. Asymptomatic reactivation and low-level replication with viruria is observed in 5% of healthy individuals. Persistent high-level BKV replication is the hallmark of polyomavirus-associated nephropathy in renal transplantation and of hemorrhagic cystitis in bone marrow transplantation. Since these manifestations are rare in other types of immunocompromised patients, the presence of specific cofactors is postulated. The role of BKV in autoimmune disease and cancer is a controversial topic and is difficult to determine, because the pathology no longer depends on BKV replication. This article discusses current views of pathogenesis, diagnosis, and treatment.
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Affiliation(s)
- Hans H Hirsch
- Department of Clinical Biological Sciences, University of Basel, University Hospital Basel, Basel, Switzerland.
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29
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Affiliation(s)
- Gordon Y Kim
- Department of Internal Medicine and Gastroenterology, The Ohio State University Medical Center, Columbus, Ohio, USA.
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30
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Abstract
Polyomavirus hominis 1, better known as BK virus (BKV), infects up to 90% of the general population. However, significant clinical manifestations are rare and limited to individuals with impaired immune functions. BKV has been associated with diverse entities such as haemorrhagic cystitis, ureteric stenosis, vasculopathy, pneumonitis, encephalitis, retinitis, and even multi-organ failure. In addition, BKV has been implicated in autoimmune disease and possibly cancer. Due to high prevalence and frequent reactivation, the role of BKV in some of these pathologies has been difficult to define. Development of BKV diseases is likely to require complementing determinants in the host, the target organ, and possibly the virus, that are subject to modulators such as immunosuppression. These complex aspects are highlighted in polyomavirus-associated nephropathy (PAN), an emerging disease in renal allograft recipients that may jeopardise the progress in renal transplantation accomplished in the past 10 years. Intervention is difficult due to the lack of specific antivirals and relies mostly on improving immune control. Diagnostic strategies using urine cytology and BKV load measurements in plasma have led to earlier diagnosis of PAN, which increased the success rate of intervention. Case series suggest that cidofovir might be effective, especially when combined with reduced immunosuppression.
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Affiliation(s)
- Hans H Hirsch
- Division of Infectious Diseases, Department of Internal Medicine, University Hospitals Basel, and Transplantation Virology Laboratory, Institute of Medical Microbiology, University of Basel, Switzerland.
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31
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Sabath BF, Major EO. Traffic of JC virus from sites of initial infection to the brain: the path to progressive multifocal leukoencephalopathy. J Infect Dis 2002; 186 Suppl 2:S180-6. [PMID: 12424695 DOI: 10.1086/344280] [Citation(s) in RCA: 101] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disorder of the human brain caused by infection with the human polyomavirus, JC. Up to 80% of humans express serum antibodies to JC virus (JCV), yet considerably fewer people develop PML-predominantly those under immunosuppressive conditions. Recent research showed JCV infection in multiple tissues throughout the body, suggesting sites for viral latency. These observations allow the proposal of pathways that JCV may use from sites of initial infection to the brain. Results from investigations into cell-surface receptors, intracellular DNA-binding proteins, and variant viral regulatory regions also suggest mechanisms that may regulate cellular susceptibility to JCV infection. Together, these data elucidate how JCV may establish infection in various cell types, persist latently or become reactivated, and ultimately reach the brain to cause PML.
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Affiliation(s)
- Bruce F Sabath
- Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Disorders and Stroke/NIH, 36 Convent Drive, Bldg. 36, Rm. 5W21, Bethesda, MD 20892, USA
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Petrogiannis-Haliotis T, Sakoulas G, Kirby J, Koralnik IJ, Dvorak AM, Monahan-Earley R, DE Girolami PC, DE Girolami U, Upton M, Major EO, Pfister LA, Joseph JT. BK-related polyomavirus vasculopathy in a renal-transplant recipient. N Engl J Med 2001; 345:1250-5. [PMID: 11680445 DOI: 10.1056/nejmoa010319] [Citation(s) in RCA: 101] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Affiliation(s)
- T Petrogiannis-Haliotis
- Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
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Reploeg MD, Storch GA, Clifford DB. Bk virus: a clinical review. Clin Infect Dis 2001; 33:191-202. [PMID: 11418879 DOI: 10.1086/321813] [Citation(s) in RCA: 177] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2000] [Revised: 12/07/2000] [Indexed: 12/18/2022] Open
Abstract
We present a review of the clinically oriented literature about BK virus, a relative of JC virus, which is the etiologic agent of progressive multifocal leukoencephalopathy (PML). The kidney, lung, eye, liver, and brain have been proposed as sites of BK virus-associated disease, both primary and reactivated. BK virus has also been detected in tissue specimens from a variety of neoplasms. We believe that BK virus is most often permissively present in sites of disease in immunosuppressed patients, rather than being an etiologic agent that causes symptoms or pathologic findings. There is, however, strong evidence for BK virus-associated hemorrhagic cystitis and nephritis, especially in recipients of solid organ or bone marrow transplants. Now that BK virus can be identified by use of specific and sensitive techniques, careful evaluation of the clinical and pathologic presentations of patients with BK virus will allow us to form a clearer picture of viral-associated pathophysiology in many organ systems.
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Affiliation(s)
- M D Reploeg
- Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.
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35
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Abstract
The BK virus (BKV) belongs to the family of the polyoma group, which contains three species: JC, which is responsible for progressive multifocal leukoencephalopathy in acquired immunodeficiency syndrome (AIDS); simian virus 40 (SV40), which is a simian virus of little pathologic significance in humans; and BKV, which is usually not pathogenic and is found in the urine of asymptomatic individuals. Recently BKV has been reported to cause symptomatic infection in renal transplant patients. The authors report a rare case of a 14-year-old boy with AIDS who developed a BKV infection of the lung and kidney that progressed to diffuse alveolar damage and death. The infected type II pneumocytes in the lung and the tubular epithelial cells in the kidney showed large, homogenous purple intranuclear inclusions. The absence of necrosis and destruction made it possible to distinguish BKV infection from herpes simplex. The size of the infected cells and the lack of a halo around the nuclear inclusion helped rule out cytomegalovirus as the cause of infection. Electron microscopy detected the presence of 40-nm intranuclear viral particles compatible with BKV, and in situ hybridization established the diagnosis.
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Affiliation(s)
- O Cubukcu-Dimopulo
- Department of Pathology, New York University Medical Center, NY 10016, USA
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