BK Polyomavirus-associated nephropathy managed by screening policy in a real-life setting.

BACKGROUND: BK polyomavirus-associated nephropathy (PyVAN) is an important complication after kidney transplantation. Prevalence ranges from 1% to 10%, and graft loss occurs in approximately 50% of the cases. There is no effective treatment, so early viral detection with immunosuppression tapering is the current strategy to prevent PyVAN. AIMS: To verify the frequency of PyVAN in a single center and evaluate the response to immunosuppressive adjustments through graft survival analysis. METHODS: Retrospective evaluation of a cohort of kidney transplant recipients with biopsy-proven PyVAN, compared with no-PyVAN patients regarding clinical aspects, immunosuppression, and graft survival over at least 2 years. RESULTS: There were 1404 kidney transplants analyzed in the study period, 58 with biopsy-proven PyVAN. Cumulative incidence was 4.1%. Median time from transplantation to PyVAN diagnosis was 6 (1-41) months. PyVAN was associated with recipient male gender (P = .041) and deceased donation (P = .005). Graft survival was inferior for PyVAN compared to no-PyVAN patients, 81.8% vs 75.2%, P = .019. Thirteen (22.4%) PyVAN patients lost their grafts, nine (15.5%) losses attributed to BKPyV infection. Three patients with BKPyV-associated graft losses were submitted to a successful second kidney transplant, with no evidence of viral replication during follow-up. CONCLUSION: PyVAN still is an important cause of kidney graft failure. Even though implementing active vigilance and immunosuppressive adjustment, this real-life single-center study demonstrated inferior graft survival in PyVAN patients compared to non-PyVAN.

Variable sources of Bk virus in renal allograft recipients.

BK virus is the causative agent of polyomavirus-associated nephropathy, a major cause of kidney transplant failure affecting 1%-10% of recipients. Previous studies that investigated the viral source on the kidney recipient pointed that the donor is implicated in the origin of human polyomavirus BK (BKPyV) infection in recipients, but giving the low genetic variability of BKPyV this subject is still controversial. The aim of this study was to determine if BKPyV replicating in kidney recipients after transplantation is always originated from the donor. Urine and blood samples from 68 pairs of living donors and kidney recipients who underwent renal transplantation from August 2010-September 2011 were screened for BKPyV by real time polymerase chain reaction. Only three recipients presented viremia. When both donors and recipients were BKPyV positive, a larger fragment of VP1 region was obtained and sequenced to determine the level of similarity between them. A phylogenetic tree was built for the 12 pairs of sequences obtained from urine and high level of similarity among all sequences was observed, indicating that homology inferences for donor and recipient viruses must be cautiously interpreted. However, a close inspection on the donor-recipient pairs sequences revealed that 3 of 12 pairs presented considerably different viruses and 4 of 12 presented mixed infection, indicating that the source of BKPyV infection is not exclusively derived from the donor. We report that about 60% of the renal recipients shed BKPyV genetically distinct from the donor, confronting the accepted concept that the donor is the main source of recipients' infection.

Pilot Study of Early Monitoring Using Urinary Screening for BK Polyomavirus as a Strategy for Prevention of BKV Nephropathy in Kidney Transplantation.

BACKGROUND: Urine monitoring programs represent an important strategy for early diagnosis of reactivation of BK polyomavirus (BKV) in kidney transplant recipients. This study analyzes a BKV urine screening model in kidney transplant patients. METHODS: Urinary screening for BKV reactivation was performed by urinary decoy cell and polymerase chain reaction (PCR) tests in samples from 32 consecutive kidney transplant patients, collected in a 6-month follow-up period. PCR in plasma samples and BKV immunohistochemical studies to assess BKV renal disease, if a kidney biopsy was indicated, were performed. RESULTS: The urinary screening for BKV among 32 renal receptors was positive in 18 patients (56%) by the concomitant use of the decoy cells and/or qualitative PCR at some time during the study period. Transfusion before transplantation was significantly associated with urinary decoy cell positive screening (odds ratio = 11; 95% confidence interval = 1.47 to 82.4; P < .05); and so was male sex (odds ratio = 2.02; 95% confidence interval = 1.07 to 3.83; P < .05). The clinical management of screening positive cases consisted of decreasing or changing the immunosuppression regimen. Sixteen renal biopsies were performed. Immunohistochemistry for SV40 T antigen was negative in all biopsies. After 1 year of follow-up, no patient developed BKV-associated nephropathy, and there was no difference in renal function between patients positive and negative for BKV urinary screening. CONCLUSIONS: Early urinary monitoring is effective in detection of BKV replication and represents a good strategy to minimize the deleterious effects caused by the presence of the virus on preservation of graft function.

First epidemiologic study in Argentina of the prevalence of BK viruria in kidney transplant patients.

BACKGROUND: The worldwide seroprevalence of human BK polyomavirus (BKV) in adults is 80%. About 10%-60% of renal transplant recipients experience BKV infection, nephropathy of the graft may occur in 5% of the cases, and up to 45% lose the graft. The aim of this work was to describe the prevalence of BK viruria during the 1st year after transplantation. METHODS: An epidemiologic multicenter cross-sectional study was carried out in consecutive patients at each site with kidney transplantation from August 2011 to July 2012. Clinically significant viruria was defined as >10(7) copies/mL. Viral DNA was extracted with the use of silica columns. Quantification was performed with the use of real-time polymerase chain reaction with primers that amplify a fragment of the large T-antigen gene and with a specific Taqman-MGB probe for BKV. For each assay, a standard curve with a quantified plasmid was included. RESULTS: Of 402 renal transplant recipients at 18 renal transplant sites, we analyzed 382; median age was 46.33 years, and 46.40% were female. The median of the temporal distribution for urine samples was 153 days. BK virus was detected in 50/382 samples (13%), 18 with values >10(7) copies/mL (4.7%). The median of the distribution of positive values was 123 days and the highest frequency of positive values was in months 3-7. The conditions of recipient older than 34 years and donor older than 41 years were the only ones that showed statistically significant association with BK viruria. No association with any specific immunosuppressive drug was observed. CONCLUSIONS: This is the first multicenter study conducted in Argentina to determine the prevalence of BK viruria in renal transplant recipients. Because of the growing number of the population susceptible to this infection, it is important to register and describe data about its epidemiology and associated risk factors.

Human papillomavirus infection: etiopathogenesis, molecular biology and clinical manifestations.

Human papillomavirus (HPV) is a DNA virus that presents tropism for epithelial cells, causing infections of the skin and mucous membranes. Replication of HPV occurs in the nuclei of squamous cells and its life cycle is directly related to the differentiation program of the host cell. To date, nearly 100 different types of HPV have been characterized and there is a large number of other types that have not been sequenced yet. Besides being responsible for benign lesions of the skin and mucous membranes, HPV is also involved in the development of various mucocutaneous tumors: Bowen's disease, non-melanoma skin cancers and genital carcinomas. This review discusses the characteristics of HPV, malignant and benign mucous and skin manifestations caused by HPV, besides the main methods of detection and typing of the virus.

Infecção pelo papilomavírus humano: etiopatogenia, biologia molecular e manifestações clínicas / Human papillomavirus infection: etiopathogenesis, molecular biology and clinical manifestations

O papilomavírus humano (HPV) é um vírus DNA que apresenta tropismo por células epiteliais, causando infecções na pele e nas mucosas. A replicação do HPV ocorre no núcleo das células escamosas e o seu ciclo de vida é diretamente relacionado ao programa de diferenciação da célula hospedeira. Até o momento, foram completamente caracterizados cerca de 100 tipos diferentes de HPVs e há um grande número adicional de tipos ainda não sequenciados. Além de ser o responsável por lesões benignas de pele e mucosas, o HPV também está envolvido no desenvolvimento de diversos tumores cutaneomucosos: doença de Bowen, cânceres de pele não melanoma e carcinomas genitais. Esta revisão aborda as características do HPV, quadros cutâneos e mucosos benignos e malignos causados por ele e os principais métodos empregados em sua detecção e tipagem.

Human papillomavirus (HPV) is a DNA virus that presents tropism for epithelial cells, causing infections of the skin and mucous membranes. Replication of HPV occurs in the nuclei of squamous cells and its life cycle is directly related to the differentiation program of the host cell. To date, nearly 100 different types of HPV have been characterized and there is a large number of other types that have not been sequenced yet. Besides being responsible for benign lesions of the skin and mucous membranes, HPV is also involved in the development of various mucocutaneous tumors: Bowen's disease, non-melanoma skin cancers and genital carcinomas. This review discusses the characteristics of HPV, malignant and benign mucous and skin manifestations caused by HPV, besides the main methods of detection and typing of the virus.

Dietary intake and risk of persistent human papillomavirus (HPV) infection: the Ludwig-McGill HPV Natural History Study.

The association between dietary intake and persistence of type-specific human papillomavirus (HPV) infection, during a 12-month period, among 433 women participating in the Ludwig-McGill HPV Natural History Study was evaluated by use of a nested case-control design. Dietary intake was assessed by a food-frequency questionnaire at the month-4 visit. HPV status was assessed at months 0, 4, 8, and 12 by polymerase chain reaction (MY09/11). Only women who ever tested positive for HPV were included in the present study: 248 had transient HPV infections (1 of 4 positive tests or nonconsecutively positive), and 185 had persistent HPV infections (> or =2 consecutive tests positive for the same HPV type). Risk of type-specific, persistent HPV infection was lower among women reporting intake values of beta-cryptoxanthin and lutein/zeaxanthin in the upper 2 quartiles and intake values of vitamin C in the upper quartile, compared with those reporting intake in the lowest quartile. Consumption of papaya > or =1 time/week was inversely associated with persistent HPV infection.

Characterization of two infectious mouse mammary tumour viruses: superantigenicity and tumorigenicity.

Mouse mammary tumour virus (MMTV) is a type B retrovirus that causes mammary tumours in susceptible mice. MMTV encodes a superantigen (SAg) that has the property of stimulating T-cell populations expressing a particular variable region of the T-cell receptor (TCR) beta chain (Vbeta) and needs to be presented in the context of major histocompatibility complex (MHC) class II molecules. Previously, we described two exogenous MMTV, MMTV BALB14, which encodes a superantigen that induces the deletion of Vbeta14+ Tcells, and MMTV BALB2, which encodes a SAg that induces the deletion of Vbeta2+ Tcells. We now describe their biological activity: the deletions involve both CD4+ and CD8+ populations, are progressive and can be detected in blood, lymph nodes and spleen. Such deletions reflect, at least in part, those occurring during intrathymic development. Both BALB2 and BALB14 viral variants are capable of inducing a strong increase of Vbeta-specific T cells in BALB/c mice (I-A+, I-E+). However, when injected into the footpad, their initial stimulatory capacity differs in that the presence of MHC I-E molecules is essential only for the stimulation of Vbeta2+ T cells. Both viral variants are able to induce deletion even in the absence of the I-E molecule in which case, however, deletion appears later and is less pronounced. Both exogenous MMTVs induce, at the end of a year, 30-35% of pregnancy-dependent mammary adenocarcinomas.

Detection and typing of human papillomavirus DNA in benign and malignant tumours of laryngeal epithelium.

The role of human papillomaviruses (HPV) in laryngeal squamous cell carcinoma has not yet been established. Thirty-three cases of laryngeal squamous cell carcinoma were analysed for the presence of HPV DNA and compared with 25 cases of normal larynx and 29 cases of laryngeal squamous papilloma in their positivity index. The presence of HPV DNA was analysed by using L1 consensus primers and also by primers specific for the E7 gene of HPV types 16 and 18. Four normal laryngeal samples (16%) were positive for HPV DNA against the 24 samples (82%) (p < 0.001) found for laryngeal papilloma and 16 (48.5%) (p < 0.05) found for laryngeal squamous cell carcinoma. HPV 16 was the type most frequently found in laryngeal carcinoma samples. Our results support an etiologic role for this type of HPV in the pathogenesis of laryngeal carcinoma.

EBV-associated Kaposi's sarcoma in a pediatric renal transplant recipient.

A 7-year-old boy had undergone kidney transplantation for chronic renal failure secondary to bilateral renal hypoplasia. He developed acute and chronic rejection and received immunosuppressive therapy. A year later he died with EBV-associated hemophagocytic syndrome. The main pathologic findings disclosed visceral (lung and stomach) and abdominal lymph node involvement of Kaposi's sarcoma and EBV-positive immunoblasts in several organs. In the lungs and lymph nodes these had the features of polymorphous lymphoimmunoblastic lesions. Because of the peculiar distribution of Kaposi's sarcoma lesions a pathogenetic hypothesis is proposed based on the site of entry of the virus. This case contributes to expanding the relationship between Kaposi's sarcoma and kidney transplantation in the pediatric population.

Genital human papillomavirus infection in Panama City prostitutes.

Little is known of the natural history of genital human papillomavirus (HPV) infections in women from high-risk populations. Samples were collected from 183 Panama City prostitutes and assessed for HPV (filter in situ DNA hybridization) and for sexually transmitted agents. The cohort was followed for 8 mo; 51% of subjects completed four monthly return visits and 16% were sampled eight times. The proportion of women found infected with HPV increased significantly with increasing numbers of consecutive samples tested; 38 (21%) of 183 women were positive after one visit and 46 (82%) of 56 who completed six visits were infected. The pattern of viral detection over time was not random, which implied that most prostitutes were persistently infected with genital HPVs and that either scattered foci of infection or periodic reactivation of latent virus occurred. Our findings suggest that multiple sampling is necessary to accurately estimate HPV infection rates and to define whether patterns of DNA expression are present.