Association of BKV viremia and nephropathy with adverse alloimmune outcomes in kidney transplant recipients.

BACKGROUND: Immunosuppression reduction for BK polyoma virus (BKV) must be balanced against risk of adverse alloimmune outcomes. We sought to characterize risk of alloimmune events after BKV within context of HLA-DR/DQ molecular mismatch (mMM) risk score. METHODS: This single-center study evaluated 460 kidney transplant patients on tacrolimus-mycophenolate-prednisone from 2010-2021. BKV status was classified at 6-months post-transplant as "BKV" or "no BKV" in landmark analysis. Primary outcome was T-cell mediated rejection (TCMR). Secondary outcomes included all-cause graft failure (ACGF), death-censored graft failure (DCGF), de novo donor specific antibody (dnDSA), and antibody-mediated rejection (ABMR). Predictors of outcomes were assessed in Cox proportional hazards models including BKV status and alloimmune risk defined by recipient age and molecular mismatch (RAMM) groups. RESULTS: At 6-months post-transplant, 72 patients had BKV and 388 had no BKV. TCMR occurred in 86 recipients, including 27.8% with BKV and 17% with no BKV (p = .05). TCMR risk was increased in recipients with BKV (HR 1.90, (95% CI 1.14, 3.17); p = .01) and high vs. low-risk RAMM group risk (HR 2.26 (95% CI 1.02, 4.98); p = .02) in multivariable analyses; but not HLA serological MM in sensitivity analysis. Recipients with BKV experienced increased dnDSA in univariable analysis, and there was no association with ABMR, DCGF, or ACGF. CONCLUSIONS: Recipients with BKV had increased risk of TCMR independent of induction immunosuppression and conventional alloimmune risk measures. Recipients with high-risk RAMM experienced increased TCMR risk. Future studies on optimizing immunosuppression for BKV should explore nuanced risk stratification and may consider novel measures of alloimmune risk.

Molecular Epidemiology and Variation of the BK Polyomavirus in the Population of Central and Eastern Europe Based on the Example of Poland.

The BK polyomavirus (BKPyV) is a widespread pathogen in humans. Polymorphism of the region encoding the VP1 protein of BKPyV provides the basis for classifying the virus into types and subtypes, whose frequency varies depending on geographic location. The aim of our study was to determine the frequency of BKPyV in the Polish population and to assess its variation by analysing polymorphism in the typing region. The study was conducted on 168 healthy, Polish volunteers, whose blood (plasma) and urine were sampled. The virus was detected using PCR, products, sequenced and subjected to bioinformatic analysis. In addition, viral load was assessed by qPCR. The presence of the genetic material of the BK virus was noted in 61/168 urine samples but in none of the plasma sample. Sequencing and phylogenetic analysis confirmed that the BKPyV isolates were of types I and IV, dominant in Europe (63.93% and 36.07%, respectively). All isolates from genotype I belonged to subtype Ib-2, showing polymorphism at position 1809 with a frequency of 61.54% (G1809A) and 38.46% (G1809C). To the best of our knowledge, this is the first study of this magnitude on the genetic variation of BKPyV among healthy volunteers in Poland.

BK virus associated haemorrhagic cystitis in related donor haematopoietic stem cell transplant recipients: A developing country experience.

A retrospective cross sectional study was conducted at the Virology Department, Armed Forces Institute of Pathology (AFIP) and Armed Forces Bone Marrow Transplant Centre (AFBMTC), Rawalpindi, from January 2016 to July 2018. Medical records of 193 patients were examined to determine the number of patients developing Haemorrhagic Cystitis associated with BK virus (BKV). BKV PCR testing was done on the patients' urine samples. Cytomegalovirus reactivation was also assessed weekly from day 30 to day 100, by CMV quantitative PCR testing on blood samples. Out of 193 patients, 11 (5.6%) developed haemorrhagic cystitis and all these patients were positive for BKV on urine samples. The maximum number of positive cases, i.e. 5 (2.6%) was in the age group three months to 10 years. Primary disease in seven out of 11 cases was Beta-Thalassemia Major.

Effectiveness of hyperbaric oxygen therapy for virus-associated hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation.

Although some studies have suggested the effectiveness of hyperbaric oxygen (HBO) therapy for hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (HSCT), the role of HBO has not been established. We compared the treatment outcomes of 8 patients with viral HC (adenovirus [ADV], n = 2; BK virus [BKV], n = 6) treated with HBO (HBO[+]) and 8 patients (ADV, n = 2; BKV, n = 6) treated with conventional therapy (HBO[-]), such as urinary catheterization and intravenous cidofovir. HBO therapy was performed at 2.1 atmospheres for 90 min/day until clinical improvement was achieved. The median number of HBO treatments was 10 (range 8-12). The median duration of HBO treatment was 19.5 days (range 10-23 days). All 8 HBO(+) patients achieved complete remission (CR) at a median of 14.5 days (range 5-25 days). Of the 8 HBO(-) patients, 5 (62.5%) obtained CR and 3 remained symptomatic for 2-6 months. The cumulative incidence of transplant-related mortality at day 100 after allogeneic HSCT was significantly higher in the HBO(-) patients than in the HBO(+) patients (14.2 vs. 0%, P < 0.05). No severe HBO-related adverse effects were observed. In conclusion, HBO is a feasible option for treating viral HC after allogeneic HSCT.

Prospective analysis of BKV hemorrhagic cystitis in children and adolescents undergoing hematopoietic cell transplantation.

BK virus is one of the most common causes of hemorrhagic cystitis (HC) in children undergoing hematopoietic cell transplantation (HCT). Viruses can be found in urine and serum samples of immunocompromised patients. Malignant diseases, age, cell source, day of granulocyte reconstitution, conditioning regimen, or use of total body irradiation may play an important role in BKV epidemiology, development of hemorrhagic cystitis course, and outcome. The aim of this study was to evaluate the incidence, clinical course, and risk factors for BKV-HC in children undergoing HCT. A total number of 133 patients who were prospectively tested for BKV colonization/infection were enrolled into this multicenter analysis. Episodes of BKV-HC occurred in 36/133 (27%) enrolled subjects. In a univariate analysis for BKV-HC incidence, the following factors were significant: age >5 years, peripheral blood transplantation, matched unrelated donor (MUD) transplantation, busulfan-cyclophosphamide-melphalan conditioning regimen, and acute myeloblastic leukemia (AML) diagnosis. Presence of acute graft-versus-host disease (aGVHD) in liver and gut GVHD was a significant risk factor of BKV-HC. No BKV-attributed deaths were reported. In multivariate analysis, the incidence of HC was significantly higher in patients with AML, age >5 years, MUD transplants, and children with GVHD. HC is a frequent complication after HCT among children causes prolonged hospitalization but rarely contributes to death. We identified risk factors of BKV-HC development in children, with focus on aGVHD: we concluded that excessive immune reaction connected with GVHD and immunosuppression drugs might play a pivotal role in the development of BKV-HC.

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

Adenovirus (ADV)- or BK virus (BKV)-associated hemorrhagic cystitis (HC) is a common complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Several risk factors have been previously reported; however, it is unclear whether virus-associated HC can be transmitted. To clarify this point, we performed a retrospective cohort study on 207 consecutive patients who underwent allo-HSCT at Kyoto University Hospital between 2012 and 2018. We evaluated the incidence and risk factors of virus-associated HC and performed a phylogenetic analysis of the ADV partial sequence. The median age at transplantation was 50 (range, 17-68) years. Fifty-eight patients (28%) developed HC. ADVs were detected in 18 cases, BKVs were detected in 51, both were detected in 12, and only John Cunningham virus (JCV) was detected in 1 case. No factor was significantly associated with HC. However, both ADV- and BKV-HC occurred intensively between April 2016 and September 2017, which suggested possible nosocomial transmission of ADV and BKV. Genome sequencing of the hexon, E3, and penton regions of detected ADVs identified 7 cases of ADV type 11, 2 cases of type 35, and 3 cases of a type 79-related strain. A sequence analysis revealed that these strains in each type were almost identical, except for one case of a type 79-related strain. In conclusion, ADV-HCs with possible nosocomial transmission were described based on genotyping of the virus and partial sequencing of the viral genome. Although viral HC after allo-HSCT is thought to mainly be due to reactivation of a latent virus, nosocomial transmission of ADV or BKV should also be considered.

Tacrolimus intrapatient variability in BK virus nephropathy and chronic calcineurin toxicity in kidney transplantation.

Intrapatient variability (IPV) in tacrolimus has been increasingly acknowledged as a risk factor for poor graft survival after kidney transplantation. Although past studies have mainly accounted for IPV in acute or chronic rejection states as due to underimmunosuppression, this is not yet clear. So far, tacrolimus IPV for BK virus-associated nephropathy (BKVN) and chronic calcineurin inhibitor toxicity (CNIT) has not been investigated. Here, we evaluated IPV in tacrolimus for BKVN and chronic CNIT, which are mainly considered as overimmunosuppression states. In this case-control study, kidney allograft biopsies conducted between 1998 and 2018 were included, with patients grouped by biopsy results as BKVN alone group, CNIT alone group, and normal graft function (control group). IPV was estimated as mean absolute deviation. Our study groups included 25 kidney transplant recipients with BKVN alone, 91 patients with CNIT alone, and 60 patients with normal 5-year graft survival (control group). In analyses of IPV in tacrolimus six months before graft biopsy, IPV was highest in the BKVN group (P = 0.001). The BKVN group also had the highest IPV in tacrolimus at 12 months after biopsy (P = 0.001), with all pairwise comparisons statistically different between groups. At 12 months after biopsy, five patients (20%) in the BKVN group and 10 patients (10.9%) in the CNIT group had graft loss. Among other risk factors, BKVN and chronic CNIT are consequences related to high IPV. Quantification of IVP for tacrolimus in clinical practice would help to optimize kidney transplant outcomes.

Comparing Urine and Blood Screening Methods to Detect BK Virus After Renal Transplant.

OBJECTIVES: BK polyomavirus can infect healthy individuals; however, in renal transplant recipients, it can cause nephropathy, which can lead to renal allograftfailure. There are currently no effective antiviral agents against BK polyomavirus. Surveillance after kidney transplant for BK polyomavirus is the only means to prevent allograft failure. Transplant centers routinely screen for BK polyomavirus in either urine or blood. If BK polyomavirus replication occurs, itis usually detected first in urine, which is followed by detection in blood in a subset of cases. Screening for BK polyomavirus in urine has the potential for earlier detection of viralreactivation.However, not all patients with BK polyomavirus in urine will progress to BK viremia. Therefore, adding urine screening could increase the cost oftests without a clear clinical benefit. MATERIALS AND METHODS: We conducted an analysis of BK polyomavirus screening methods at 2 different centers and compared their clinical outcomes and efficiency of testing. RESULTS: We analyzed 209 patientswith BK polyomavirus reactivation after kidney transplant at 2 different institutions from 2008 to 2018. BK polyomavirus reactivation in blood was detected earlierifthe patient was screened by urine screening protocol. However, measurable clinical outcomes were similarin all groups with different screening methods. CONCLUSIONS: Although screening for BK polyomavirus in urine did detect viralreactivation earlier,there were no differences in graft or clinical outcomes when either the urine or blood screening method was used.

Incidence of BKV in the urine and blood samples of pediatric patients undergoing HSCT.

The aims were to investigate the incidence of BKV infection and the presence of HC in pediatric patients undergoing HSCT. Twenty-four children patients (M/F: 17/7) undergoing HSCT in a single center over a period of 1 year were included in the study. The presence of BKV DNA was determined by quantitative real-time PCR in plasma and urine samples at the following times: before transplantation, twice a week until engraftment time, and weekly for + 100 days. The mean age of the patients was 7.79 ± 5.03 years, the mean follow-up time was 95.6 ± 25.9 days, and the average number of samples per patient was 15.8 ± 3.2. BKV DNA was detected in at least one urine sample in 91.6% (n: 22) and at least one plasma sample in 75% (n:18) of the patients. The median time to the first BKV DNA positivity in urine and plasma samples was 11 (range: 1-80) and 32 days (range: 2-79), respectively. The median value of BKV DNA copies in urine and plasma were 1.7 × 106 (range: 2.8 × 101 -1.2 × 1014 ) and 1.9 × 103 copies/mL (range: 3-2.1 × 106 ), respectively. Thirteen patients (54.2%) had hematuria with BKV viruria; 8 (33.3%) patients had viremia. The median value of the BKV DNA copies in urine and plasma was 4.4 × 107 (range: 65-1 × 1011 ) and 2.9 × 103 (range: 7-7.8 × 104 ) copies/mL in these patients. Two (15.4%) of the 13 patients with BKV viruria and hematuria were diagnosed with BKV-related HC. BKV DNA viral load monitoring of urine and plasma in pediatric HSCT patients with a high risk for viral infections is valuable for understanding the development of BKV-related HC.

Incidence and risk factors for high-level BK viruria: a single center study in China.

BACKGROUND: BK virus allograft nephropathy is a serious complication after kidney transplantation, and the effect of pre-emptive intervention for high-level BK viruria has been verified, but protocols after kidney transplantation for early identification of high-level viruria are lacking. METHODS: This was a single-center study. The clinical data of the kidney transplant recipients and their donors in our center from January 1, 2015 to December 31, 2018, were collected. The patients were divided into the high-level BK viruria group (Group A) and a non-high-level BK viruria group (Group B) according to the qPCR results of BK virus DNA loads in urine samples. Significant variables were screened out by univariate analysis, and then the results were incorporated into a multivariate logistic regression model to analyze the independent risk factors for high-level BK viruria. RESULTS: A total of 262 recipients were included in the study. The incidence of high-level BK viruria was 13.4% (n = 35), and the median time of detection was 181 (range 91-1119) days. Univariate analysis showed that donor type ([Formula: see text] = 21.770, P < 0.001), history of ATG/ATG-F application ([Formula: see text] = 4.543, P = 0.033), acute rejection (AR) ([Formula: see text] = 8.313, P = 0.004) and delayed graft function (DGF) ([Formula: see text] = 21.170, P < 0.001) were related to high-level BK viruria. After the inclusion of the multivariate logistic regression model, the results showed deceased brain and cardiac donors (P = 0.032, OR = 3.927, 95% CI 1.122-13.746), AR (P = 0.022, OR = 4.709, 95% CI 1.253-17.697) and DGF (P = 0.001, OR = 6.682, 95% CI 2.288-19.518). CONCLUSIONS: Donation by deceased brain and cardiac patients, history of AR and DGF were independent risk factors for high-level BK viruria after kidney transplantation.

Prevalence of Human Polyomavirus JC and BK in Normal Population.

JC virus (JCV) , and BK virus (BKV) can remain latency in kidney and excrete via urine asymptomatically. JCV has been associated with colorectal and bladder cancers. BKV has been linked with lung, pancreas, liver, urogenital tract, head and neck cancers. Therefore, the frequency of JCV DNA and BKV DNA are essential to evaluate in urine samples of healthy individuals. MATERIALS AND METHODS: Hundred sixty four urine samples were collected from healthy subjects [96 females and 68 males]. DNA was extracted and detection of JCV DNA and BKV DNA was carried out by PCR . The analysis of sequencing and construction of phylogenetic tree were performed for the samples positive for JCV DNA and BKV DNA. RESULTS: Ten (6.09%) urine samples [5/96(5.2%) females and 5/68( 8.82) males] were tested positive for JCV DNA (P= 0.814). The results of sequencing and phylogenetic tree showed the isolated JCV DNA were cluster with 3A genotype. 21/164 (12.8%) samples were tested positive for BKV DNA [11/96(11.45%) females and males 10/68(14.7%)] ( P= 0.63). The results of sequencing and phylogenetic tree showed that the isolated BKV was cluster with genotype III. CONCLUSION: In the present study 6.09% and 12.8% of the healthy individuals showed positive for JCV DNA (genotype 3A) and BKV DNA(genotype III) respectively. With regard to life threating diseases by BKV and JCV in immunocomprsied patients , the screening BKV DNA and JCV DNA should be implemented for patients with cancer /autoimmune diseases /organ recipient/ multiple sclerosis (MS), prior to immunosuppression therapy or immunomodulatory agents treatment.
.

BK virus-associated nephropathy in a lung transplant patient: case report and literature review.

BACKGROUND: BK virus-associated nephropathy (BKVAN) is a relatively common cause of renal dysfunction in the first six months after renal transplantation. It arises from reactivation of the latent and usually harmless BK virus (BK virus) due to immunosuppression and other factors including some that are unique to renal transplantation such as allograft injury. BKVAN is much rarer in non-renal solid organ transplantation, where data regarding diagnosis and management are extremely limited. CASE PRESENTATION: We report a case of a 58-year-old man found to have worsening renal dysfunction nine months after bilateral sequential lung transplantation for chronic obstructive pulmonary disease (COPD). He had required methylprednisolone for acute allograft rejection but achieved good graft function. Urine microscopy and culture and renal ultrasound were normal. BK virus PCR was positive at high levels in urine and blood. Renal biopsy subsequently confirmed BKVAN. The patient progressed to end-stage renal failure requiring haemodialysis despite reduction in immunosuppression, including switching mycophenolate for everolimus, and the administration of intravenous immunoglobulin (IVIG). CONCLUSIONS: This very rare case highlights the challenges presented by BK virus in the non-renal solid organ transplant population. Diagnosis can be difficult, especially given the heterogeneity with which BKV disease has been reported to present in such patients, and the optimal approach to management is unknown. Balancing reduction in immunosuppression against prevention of allograft rejection is delicate. Improved therapeutic options are clearly required.

Epstein-Barr virus, cytomegalovirus and BK polyomavirus burden in juvenile systemic lupus erythematosus: correlation with clinical and laboratory indices of disease activity.

OBJECTIVES: Clinical and laboratory investigations have revealed that Epstein-Barr virus (EBV) is involved in altered immunological response of systemic lupus erythematosus (SLE). Higher seroprevalence rates of anti-EBV antibodies and increased viral load are demonstrated in adult SLE patients. The prevalence of BK polyomavirus (BKV) reactivation is also suggested to be higher in SLE. Herein, we aimed to evaluate the immune response of children with SLE to EBV antigens in addition to EBV and BKV DNA. We also tried to evaluate whether these serological results differ from another connective tissue disease - juvenile systemic sclerosis (jSS) - and healthy individuals. METHODS: Serum levels of EBV early antigen diffuse (EA-D) IgG, EBV nuclear antigen-1 IgG, EBV viral capsid antigen (VCA), cytomegalovirus (CMV) IgG, EBV DNA, CMV DNA and urinary BKV DNA were evaluated in healthy controls and in patients with a diagnosis of juvenile SLE (jSLE) and jSS. RESULTS: A total of 70 jSLE patients, 14 jSS patients and 44 sex-matched healthy individuals were involved in the study. EBV VCA was positive in 84.2% of jSLE patients, 85.7% of jSS patients and 36.3% of healthy controls. EBV EA-D IgG positivity was significantly higher in jSLE patients compared to jSS patients and healthy controls (20% vs. 7.1% and 0%, p = 0.005). EBV VCA positivity was associated with malar rash and immunological disorder, but there was no statistical significance in other antibody positivity in terms of clinical and haemogram findings and autoantibody positivity. CMV DNA positivity was present in only 2.8% of jSLE patients. None of the jSS patients or the healthy controls had CMV DNA positivity. EBV DNA and BKV DNA were also negative in all three groups. CONCLUSION: The results of our study assume a relationship between SLE and EBV, but we could not demonstrate an association between CMV and BKV. The negative DNA results in contrast to serological positivity can be interpreted as an altered and impaired immune system and increased viral susceptibility. These results suggest that EBV contributes to disease continuity, even if it does not directly cause development.

Prevalence of JC and BK viruses in Patients with Colorectal Cancer: A Systematic Review and Meta- Analysis.

INTRODUCTION: Polyomaviruses including BK virus (BKV) and JC virus (JCV) are widespread in human and have been associated with colorectal cancer (CRC) in some studies. The aim of present systematic review and meta-analysis article is to calculate the pooled prevalence of BKV and JCV in patients with CRC and assessing their association with this malignancy. MATERIALS AND METHODS: Domestic databases and Sciences Direct, PubMed, ProQuest, Web of Sciences and Scopus were searched for relevant articles up to 2nd  June 2019Two independent reviewers extracted the related data from eligible articles. The pooled prevalence and pooled odds ratio (POR) and their 95% confidence interval (95% CI) were calculated using "metaprop" and "metan" commands in Stata 14. Where I2 statistics were >50%, the random effect model was used. RESULTS: From 1461 relevant studies, 24 articles were eligible and included in the qualitative while 19 articles included in quantitative analysis. The pooled prevalence based on diagnostic methods varies from 29% using immunohistochemistry to 52% using nested-PCR method. The likelihood of being infected with JCV  was significantly higher in CRC patients compared to healthy (POR: 4.41, 95% CI: 2.13 - 9.13) controls, normal adjacent mucosa (POR: 2.79, 95% CI: 1.3-5.9) and colorectal adenoma (POR: 3.1, 95% CI: 1.5-6.5) but was not significant when non-CRC patients used as control group. CONCLUSION: The prevalence of JCV in colorectal patients was substantially variable by different methods and targets. The significant association between JCV and CRC that was observed in the present study is not indicative of causation and should be studied more in large-scale prospective designs.

BK Virus RNA in Renal Allograft Biopsies.

BK polyomavirus-associated nephropathy (BKpyVAN) remains a cause of graft loss in kidney transplant recipients on immunosuppressive therapy. Its diagnosis relies on the identification of BK virus (BKV) in the renal allograft biopsy by positive immunohistochemical (IHC) stain for the viral SV40 large T antigen, although in situ hybridization (ISH) for viral DNA is used in some centers. We examined tissue detection of BKV RNA by RNAscope, a novel, automated ISH test, in 61 allograft biopsies from 56 patients with BKpyVAN. We found good correlation between the estimate of BKV tissue load by RNAscope ISH and SV40 IHC (R2 = 0.65, p<0.0001). RNAscope ISH showed 88% sensitivity and 79% specificity and, as an alternative test, could confirm the presence of BKV tissue in presumed BKpyVAN and rule out BKV as the causative agent in JC virus nephropathy. We also used tissue BK viral load estimates by both RNAscope ISH and SV40 IHC to examine the relation between tissue and plasma BK levels and found significant correlation only between BK viremia and tissue BK measured by RNAscope ISH. Our findings suggest that the RNAscope ISH assay could be a reliable test for BKV detection in allograft biopsies.

Impact of extended infusional mesna prophylaxis on the incidence of BK viruria and hemorrhagic cystitis following post-transplantation cyclophosphamide and CTLA4Ig-based haploidentical transplantation.

Hemorrhagic cystitis (HC) has been reported with increased frequency following post-transplantation cyclophosphamide (PTCy)-based haploidentical hematopoietic cell transplantation (HCT) along with a strong association with BK viruria. We prospectively evaluated the incidence of BK viruria and HC in 115 patients (median age 20 years, 2-65) undergoing PTCy-based haploidentical HCT with (n = 71) or without (n = 44) CTLA4Ig. HC prophylaxis consisted of a continuous infusion of mesna 30 min prior and 48 h post-PTCy. The overall incidence of BK viruria was 65.7%. None with BK viruria < 104 copies/ml developed clinical symptoms (n = 65). The incidence of BK viruria ≥ 104 copies/ml was 7.1% (n = 8) and 75% developed HC. The incidence of HC was 5.4% at a median of 30 days. Both BK viruria ≥ 104 copies/ml and HC were strongly associated with acute GVHD (p < 0.001). A higher NRM was observed in those with BK viruria ≥ 104 copies/ml, related to GVHD and its complications (41.7% vs 12.6%, p = 0.04). The incidences of acute GVHD, vis-à-vis, overall BK viruria, BK viruria ≥ 104 copies/ml, and HC, tended to be lower in patients receiving CTLA4Ig. Thus, extended infusional mesna, coupled with significant reduction in alloreactivity along with possible preservation of antiviral immunity associated with the use of CTLA4Ig, was probably responsible for a much lower incidence of BK viruria and resultant HC than reported previously following PTCy-based haploidentical HCT.

Screening for BKV-DNAEMIA after renal transplantation in a resource limited setting.

Costs may hinder the implementation of BK polyomavirus (BKV)-DNAemia screening in resource-limited kidney transplant (KT) centers. We analyzed data from two studies to assess the performance and potential cost saving of a dual-step screening strategy based on the use of a preliminary qualitative semi-nested PCR (snPCR) assay followed by BKV-DNAemia quantification after KT. In the preliminary study, in which 130 samples from 33 KT recipients were screened for BKV-DNAemia, the estimated positive and negative predictive values of snPCR, as compared to quantitative PCR (qPCR), were 88% and 99%, respectively. In the second study, which included 84 KT recipients, BKV-DNAemia was detected by snPCR in 28/472 (5.9%) samples and confirmed by qPCR in 26 samples of 21 (25%) subjects. No graft loss occurred among KT recipients who developed BKV-DNAemia. Cost analyses suggested that this strategy might be a cost saving alternative for BKV-DNAemia screening for some resource-limited settings.

Systemic BK Virus Infection in a Pediatric Patient With Severe Combined Immunodeficiency.

Human BK virus (BKV) infection is known to occur mostly during childhood with the establishment of latent infection with no tissue damage or clinical manifestations. However, conditions causing immunosuppression can lead to increased virus replication and tissue damage. Although the tissues most commonly involved are the kidneys, bladder, ureters and, to some extent, brain tissue, there are some reports that suggest that BKV may cause multisystemic infections. In this case, a 12-month-old child was seen to suffer from multiple gastrointestinal infections. This prompted a search for immunodeficiencies, which revealed the presence of severe combined immunodeficiency. The child was eventually hospitalized and continued showing recurrent bouts of gastroenteritis as well as lower respiratory infection. After multiple antibiotic courses, he developed acute kidney injury, a hemophagocytic syndrome, and eventually respiratory failure, which led to his death a year later. Autopsy findings revealed the presence of a disseminated BKV infection involving the kidneys, ureters, leptomeninges, and pancreas. Analysis of the literature failed to show any previous case of BKV pancreatitis. The present case suggests that BKV can damage more tissues than previously reported and may be responsible for systemic infections in immunosuppressed patients.