Análise das condições bucais e microbiológicas salivar de pacientes infantis em programação para o transplante hepático e avaliação da qualidade de vida da saúde geral de seus doadores / Analysis of the oral conditions and salivary microbiology of pediatric patients in programming for liver transplantation and evaluation of the quality of life of their donors' general health

O transplante hepático (Tx) pediátrico é o tratamento definitivo e indicado para doenças hepáticas terminais. Nele, estão envolvidos dois cenários: o da criança receptora e do doador, que abrangem questões como a saúde geral e bucal, imunossupressão e qualidade de vida. A imunossupressão pode acarretar infecções oportunistas como os poliomavírus BK e JC que causam complicações clínicas no pós-transplante. Assim, esta pesquisa trata-se de um estudo longitudinal que se propôs avaliar três vertentes: i) as condições odontológicas das crianças no processo do transplante hepático; ii) avaliar a excreção oral e viremia dos poliomavírus BK e JC nas crianças antes e após o Tx; iii) avaliar o impacto da qualidade de vida (QV) dos doadores. Para analisar as vertentes relacionadas ao receptor, foram incluídas 84 crianças em programação para o transplante hepático no Hospital Municipal Infantil Menino Jesus em São Paulo, mas apenas 51 fizeram parte da amostra final. Foram utilizadas as categorias avaliativas do Bedside Oral Exam BOE para avaliar as condições bucais pré- e pós-transplante imediato. Juntamente com o exame clínico bucal, foram realizadas seis coletas, uma pré-transplante e cinco semanalmente no pós-transplante, de saliva e sangue para avaliar a presença dos poliomavírus. Em contrapartida, para avaliar a QV dos doadores, participaram desse estudo 25 adultos. Para essa avaliação foi utilizado o questionário SF-36 versão 2, que é autoaplicável e aborda oito domínios sobre a saúde física e emocional, sendo aplicado no pré-Tx (um dia anterior a cirurgia) e no pós-Tx (um mês após a cirurgia). As análises estatísticas utilizadas para cada objetivo foram: i) análise descritiva das condições bucais nos dois momentos e comparadas através do teste de Wilcoxon; ii) análise da variável dicotômica e o teste de McNemar para identificar a presença do BK e JC; iii) teste de Shapiro-Wilk, seguido pela comparação dos dados paramétricos pelo teste t pareado e dados não paramétricos pelo teste de Wilcoxon considerando significância estatística de p<0,05 para a avaliação da QV do doador. As análises foram realizadas através do software JAMOVI. Assim, os resultados encontrados para cada objetivo foram: i) no pré-transplante a característica mais frequente foi à alteração de cor nas mucosas (78.6% n=84) e no pós-transplante alteração nos lábios (27.4% n=51), na função deglutição (13.8% n=51) e na cor dos dentes (27.4% n=51); apesar disso as crianças apresentavam BOE escore 8, 9 ou 10 tanto no pré-transplante (92.8% n=84) como no pós-transplante (90.4% n=51); ii) em relação à excreção oral e viremia dos poliomavírus, apenas observamos a presença do BK na saliva em uma amostra (2%) na segunda e uma amostra (2%) na quinta semana pós-Tx; e no plasma em uma amostra (2%) na terceira e em uma amostra (2%) na quinta semana pós-Tx. O JC não foi detectado em nenhuma das amostras analisadas; iii) em relação à QV do doador, foi possível verificar uma diferença estatisticamente significativa nos domínios relacionados à capacidade funcional (média no pré-Tx= 85.4 e média no pós-Tx= 47.6; p<0.001), limitação por aspectos físicos (média no pré-Tx= 82.5 e média no pós-Tx= 52.5; p<0.001), dor (média no pré-Tx= 83.9 e média no pós-Tx= 60.5; p=0.002) e limitação por aspectos emocionais (média no pré-Tx= 82.5 e média no pós-Tx= 52.5; p<0.001). Conclui-se que as crianças possuíam uma boa condição bucal no pré e pós-transplante apesar de terem sido encontradas alterações na mucosa no pré-transplante e alterações em lábios e dentes no pós-transplante. A presença do poliomavírus BK é um evento raro em pacientes pediátricos no processo de transplante hepático. No que diz respeito ao impacto da QV nos doadores, houve uma piora no pós-transplante considerando os aspectos físicos e emocionais.

Caracterización clínica de la Nefropatía por Poliomavirus BK en pacientes trasplantados renales / Clinical characterization of Polyomavirus BK nephropathy in kidney transplanted patients

INTRODUCCIÓN. La nefropatía por poliomavirus BK resulta un problema emergente en el trasplante renal, pues contribuye a la pérdida temprana de los injertos renales. OBJETIVO. Caracterizar clínicamente a los pacientes trasplantados renales con nefropatía por poliomavirus BK. MATERIALES Y MÉTODOS. Estudio observacional, descriptivo, realizado en el Hospital de Especialidades Carlos Andrade Marín en el período 2013-2022, se obtuvo una base de datos anonimizada, 479 pacientes trasplantados renales, de estos se identificaron 37 pacientes que corresponde a un 7,7% con nefropatía por poliomavirus BK, se realizó un análisis con el programa estadístico SPSS v26®. RESULTADOS. La población estuvo caracterizada por pacientes del sexo masculino (56,8%), con una edad media de 48,2 años, el donante cadavérico fue el más frecuente (94,5%), la mayor parte del tratamiento de la nefropatía por poliomavirus BK consistió en cambio de micofenolato sódico a everolimus y se mantuvo con 50% de Tacrolimus y Prednisona (40,5%); al valorar el cambio de los valores de creatinina, los niveles más elevados fueros a los 12 meses cuando la pérdida renal fue temprana (p: 0,042), y de la misma manera a los 12 meses, fueron más elevados los niveles de creatinina cuando el diagnóstico histopatológico fue Nefropatía por Poliomavirus Clase 3 (p: 0,01). DISCUSIÓN. La prevalencia de la nefropatía se mantuvo por debajo del 10% reportado a nivel global, la creatinina empeoró en pacientes con pérdida temprana del injerto renal y con una clase patológica avanzada, hecho reportado en la fisiopatología de la enfermedad. CONCLUSIÓN. La pérdida del injerto renal temprano presentó una creatinina más alta que la tardía. Es recomendable un tamizaje adecuado para la detección temprana del virus BK siendo crucial para prevenir el deterioro de la función renal y limitar la posterior pérdida del injerto.

INTRODUCTION: BK polyomavirus nephropathy is emerging as a significant concern in kidney transplantation, as it contributes to the early loss of renal grafts. OBJECTIVE: The aim of this study was to clinically characterize renal transplant recipients with BK polyomavirus nephropathy. MATERIALS AND METHODS: An observational and descriptive study was conducted at Carlos Andrade Marín Specialties Hospital during the period of 2013 to 2022. An anonymized database comprising 479 renal transplant patients was utilized. Among these, 37 patients, constituting 7.7%, were identified with BK polyomavirus nephropathy. Data analysis was performed using the statistical program SPSS v26®. RESULTS: The study population was predominantly composed of male patients (56.8%) with a mean age of 48.2 years. Deceased donors accounted for the majority (94.5%) of cases. The primary approach for managing BK polyomavirus nephropathy involved transitioning from mycophenolate sodium to everolimus, alongside maintaining a regimen of 50% tacrolimus and 40.5% prednisone. When assessing changes in creatinine values, the highest levels were observed at 12 months, coinciding with early renal loss (p: 0.042). Similarly, at the 12-month mark, elevated creatinine levels were associated with a histopathological diagnosis of Polyomavirus nephropathy Class 3 (p: 0.01). DISCUSSION: The prevalence of nephropathy remained below the globally reported threshold of 10%. Creatinine levels worsened in patients experiencing early graft loss and an advanced pathological classification, aligning with established disease pathophysiology. CONCLUSION: Early renal graft loss was associated with higher creatinine levels compared to delayed loss. Adequate screening for early detection of BK virus is recommended, as it plays a crucial role in preventing renal function deterioration and limiting subsequent graft loss.

Haploidentical transplantation outcomes are comparable with those obtained with identical human leukocyte antigen allogeneic transplantation in Chilean patients with benign and malignant hemopathies

Abstract Introduction Patients with benign or malignant blood disorders, who require allogeneic stem cell transplantation and lack an identical human leukocyte antigen HLA identicalHL sibling donor, could be transplanted with hematopoietic stem cells from unrelated adult or umbilical cord donors. However, in our country, both approaches are costly and time-consuming options. Methods Over the last few years, haploidentical modalities have been investigated as an alternative donor source, showing similar results to those obtained with identical HLA donors. We started using T-cell-replete haploidentical with post-transplant cyclophosphamide in 2012 and we presented our experience with patients undergoing haploidentical ransplantation compared to SIB. Results Since January 2012 to date, 91 allogeneic transplants have been performed, of which 49 were haploidentical and 42 were HLA identical. The mean age of the patients was 35 years (range: 17-62). The mean CD34/kg × 106 infused per group was 5.93 and 5.89, respectively. Time to granulocyte and platelet engraftment was 11 and 15 days, respectively, for haploidentical, and 12 and 14 days, respectively, for HLA identical (p = 0.10). The 100-day cumulative incidence of global acute GVHD was 34% for haploidentical and 29% for SIHLA identical (p = 0.9). The 2-year overall global graft-versus-host disease was 43% for haploidentical and 41% for HLA identical (p = 0.8). Overall survival, relapse, and transplant and relapse-related mortality were similar between both groups. Conclusion Our experience showed that haploidentical has similar outcomes to those obtained with HLA idential and can be performed in our country safely.

Clinical manifestations of BK virus infection in pediatric kidney transplant patients / 소아과

BACKGROUND: Polyomavirus BK (BKV) infection is an important cause of graft loss in kidney transplant patients.PURPOSE: The purpose of this study was to evaluate clinical findings and risk factors for BKV in pediatric patients after kidney transplantation.METHODS: This retrospective single-center study included 31 pediatric kidney transplant recipients from January 2002 to December 2017. Two patients received 2 transplantations during the study period, and each transplant was analyzed independently. Total number of cases is 33 cases with 31 patients. BKV infection was confirmed from blood samples via periodic quantitative polymerase chain reaction.RESULTS: The mean age at kidney transplantation was 11.0±4.7 years, and the male-to-female ratio was 2.7:1. Three patients had a past medical history of high-dose chemotherapy and autologous stem-cell transplantation for solid tumors. Nine patients (27.3%) developed BKV infection. The median period from kidney transplantation to BKV detection in blood was 5.6 months. There was no statistically significant difference in estimated glomerular filtration rate between patients with and those without BKV infection. Among 9 patients with BKV viremia, 7 were treated by reducing their immunosuppressant dose, and BKV was cleared in 6 of these 7 patients. In the other 2 BKV-positive patients, viremia improved without immunosuppressant reduction.CONCLUSION: BKV infection is common in children with kidney transplantation and might not have affected short-term renal function in our patient sample due to early immunosuppressant reduction at the time of BKV detection.

Tricodisplasia espinulosa asociada a síndrome mielodisplásico e inmunosupresión / Trichodysplasia spinulosa: report of one case

Trichodysplasia spinulosa is a rare disease that occurs in the setting of immunosuppression, associated with tolerogenic therapy used in allograft recipients or patients with hematologic malignancies. Clinically, it is characterized by a centrofacial cutaneous eruption of erythematous papules with a central keratinous spicule, often associated with variable degrees of alopecia. Histologic findings are characteristic, and electron microscopy reveals the presence of trichodysplasia spinulosa associated polyomavirus. We report a 47-year-old woman with idiopathic autoimmune pancytopenia refractory to diverse immunosuppressant regimens, with clinical and pathologic findings compatible with the disease, in whom complementary studies were required to exclude other differential diagnoses.

Human polyomaviruses and cancer: an overview

The name of the family Polyomaviridae, derives from the early observation that cells infected with murine polyomavirus induced multiple (poly) tumors (omas) in immunocompromised mice. Subsequent studies showed that many members of this family exhibit the capacity of mediating cell transformation and tumorigenesis in different experimental models. The transformation process mediated by these viruses is driven by viral pleiotropic regulatory proteins called T (tumor) antigens. Similar to other viral oncoproteins T antigens target cellular regulatory factors to favor cell proliferation, immune evasion and downregulation of apoptosis. The first two human polyomaviruses were isolated over 45 years ago. However, recent advances in the DNA sequencing technologies led to the rapid identification of additional twelve new polyomaviruses in different human samples. Many of these viruses establish chronic infections and have been associated with conditions in immunosuppressed individuals, particularly in organ transplant recipients. This has been associated to viral reactivation due to the immunosuppressant therapy applied to these patients. Four polyomaviruses namely, Merkel cell polyomavirus (MCPyV), Trichodysplasia spinulosa polyomavirus (TSPyV), John Cunningham Polyomavirus (JCPyV) and BK polyomavirus (BKPyV) have been associated with the development of specific malignant tumors. However, present evidence only supports the role of MCPyV as a carcinogen to humans. In the present review we present a summarized discussion on the current knowledge concerning the role of MCPyV, TSPyV, JCPyV and BKPyV in human cancers.

Genomic analysis of Sheldrake origin goose hemorrhagic polyomavirus, China

Goose hemorrhagic polyomavirus (GHPV) is not a naturally occurring infection in geese in China; however, GHPV infection has been identified in Pekin ducks, a domestic duck species. Herein, we investigated the prevalence of GHPV in five domestic duck species (Liancheng white ducks, Putian black ducks, Shan Sheldrake, Shaoxing duck, and Jinyun Sheldrake) in China. We determined that the Jinyun Sheldrake duck species could be infected by GHPV with no clinical signs, whereas no infection was identified in the other four duck species. We sequenced the complete genome of the Jinyun Sheldrake origin GHPV. Genomic data comparison suggested that GHPVs share a conserved genomic structure, regardless of the host (duck or geese) or region (Asia or Europe). Jinyun Sheldrake origin GHPV genomic characterization and epidemiological studies will increase our understanding of potential heterologous reservoirs of GHPV.

Systematic review of the published data on the worldwide prevalence of John Cunningham virus in patients with multiple sclerosis and neuromyelitis optica / 한국역학회지

OBJECTIVES: John Cunningham virus (JCV) is a polyoma virus that infects humans, mainly in childhood or adolescence, and presents no symptomatic manifestations. JCV can cause progressive multifocal leukoencephalopathy (PML) in immunosuppressed individuals, including those undergoing treatment for multiple sclerosis (MS) and neuromyelitis optica (NMO). PML is a severe and potentially fatal disease of the brain. The prevalence of JCV antibodies in human serum has been reported to be between 50.0 and 90.0%. The aim of the present study was to review worldwide data on populations of patients with MS and NMO in order to establish the rates of JCV seropositivity in these individuals. METHODS: The present review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and used the following search terms: “JCV” OR “JC virus” AND “multiple sclerosis” OR “MS” OR “NMO” OR “neuromyelitis optica” AND “prevalence.” These terms were searched for both in smaller and in larger clusters of words. The databases searched included PubMed, MEDLINE, SciELO, LILACS, Google Scholar, and Embase. RESULTS: After the initial selection, 18 papers were included in the review. These articles reported the prevalence of JCV antibodies in the serum of patients with MS or NMO living in 26 countries. The systematic review identified data on 29,319 patients with MS/NMO and found that 57.1% of them (16,730 individuals) were seropositive for the anti-JCV antibody (range, 40.0 to 69.0%). CONCLUSIONS: The median worldwide prevalence of JCV among adults with MS or NMO was found to be 57.1%.

Systematic review of the published data on the worldwide prevalence of John Cunningham virus in patients with multiple sclerosis and neuromyelitis optica / 한국역학회지

OBJECTIVES: John Cunningham virus (JCV) is a polyoma virus that infects humans, mainly in childhood or adolescence, and presents no symptomatic manifestations. JCV can cause progressive multifocal leukoencephalopathy (PML) in immunosuppressed individuals, including those undergoing treatment for multiple sclerosis (MS) and neuromyelitis optica (NMO). PML is a severe and potentially fatal disease of the brain. The prevalence of JCV antibodies in human serum has been reported to be between 50.0 and 90.0%. The aim of the present study was to review worldwide data on populations of patients with MS and NMO in order to establish the rates of JCV seropositivity in these individuals.METHODS: The present review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and used the following search terms: “JCV” OR “JC virus” AND “multiple sclerosis” OR “MS” OR “NMO” OR “neuromyelitis optica” AND “prevalence.” These terms were searched for both in smaller and in larger clusters of words. The databases searched included PubMed, MEDLINE, SciELO, LILACS, Google Scholar, and Embase.RESULTS: After the initial selection, 18 papers were included in the review. These articles reported the prevalence of JCV antibodies in the serum of patients with MS or NMO living in 26 countries. The systematic review identified data on 29,319 patients with MS/NMO and found that 57.1% of them (16,730 individuals) were seropositive for the anti-JCV antibody (range, 40.0 to 69.0%).CONCLUSIONS: The median worldwide prevalence of JCV among adults with MS or NMO was found to be 57.1%.

Human polyomavirus infection: Cytological and molecular diagnosis / Infecção pelo poliomavírus humano: diagnóstico citológico e molecular

Summary Few studies directly compare urinary cytology with molecular methods for detecting BK and JC polyomaviruses. Reactivation of BKV infection is the main risk factor for the development of nephropathy in immunocompromised individuals. The limitation of the cytological method can be attributed to the stage where the infected cell does not have specific and sufficient morphological characteristics for a conclusive diagnosis and can be easily interpreted as degenerative alteration. Moreover, morphologically, it is not possible to differentiate the two types of viruses. Polymerase chain reaction (PCR), not only is a sensitive method, but also allows differentiation of viral types without quantification, and therefore is not indicative of nephropathy. According to the American Society of Nephrology, real-time PCR would be the gold standard to indicate nephropathy because it allows quantifying the number of viral copies.

Resumo Poucos estudos comparam diretamente a citologia urinária com métodos moleculares para detecção de poliomavírus BK e JC. A reativação da infecção por BKV é o principal fator de risco para o desenvolvimento de nefropatia em indivíduos imunocomprometidos. A limitação do método citológico pode ser atribuída ao estágio em que a célula infectada não possui características morfológicas específicas e suficientes para um diagnóstico conclusivo, podendo ser facilmente interpretada como alteração degenerativa. Além do mais, morfologicamente, não é possível diferenciar os dois tipos virais. A reação em cadeia pela polimerase (PCR), além de ser um método sensível, permite diferenciar os tipos virais sem quantificá-los, não sendo, portanto, indicativa de nefropatia. Segundo a American Society of Nephrology, a PCR em tempo real seria o padrão-ouro para indicar nefropatia, pois permite quantificar o número de cópias virais.

Polyomavirus en hospederos inmunocomprometidos: situación en Sudamérica / Polyomavirus in immunocompromised patients: the South America's situation

Resumen A 46 años de la identificación de los primeros polyomavirus en humanos (PyV), la preocupación por encontrar nuevos tipos relacionados a patologías de distintos órganos en pacientes inmunosuprimidos persiste. Hasta el momento de esta revisión, 15 PyV han sido descritos, muchos de ellos sin estar claramente asociados a enfermedades. En nuestro país, al igual que en gran parte de Sudamérica, el conocimiento y la pesquisa de estos agentes infecciosos son insuficientes por lo que sistematizamos aquello que se sabe sobre estos virus y su relación con los diferentes sistemas del cuerpo humano, con énfasis en los inmunosuprimidos y señalamos aquellos datos publicados en nuestro continente. Esperamos así incentivar un mayor estudio de estas infecciones virales.

Forty-six years after the identification of the first polyomaviruses in humans (PyV) still there are strong concerns to find new types related to pathologies of different organs in immunocompromised patients. At the time of this review, 15 PyV have been described, many of them without being clearly associated with diseases. In our country, as in much of South America, the knowledge and research of these infectious agents are insufficient, so we systematized what is known about these viruses and their relationship with different human systems with emphasis on immunocompromised and we pointed out data published in our continent. Thus, we hope to encourage the study of these infections.

A molecular epidemiological study of KI polyomavirus and WU polyomavirus in children with acute respiratory infection in Tianjin, China / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the relationship of KI polyomavirus (KIPyV) and WU polyomavirus (WUPyV) with acute respiratory infection in children in Tianjin, China.</p><p><b>METHODS</b>A total of 3 730 nasopharyngeal secretions were collected from hospitalized children with acute respiratory infection in Tianjin Children's Hospital from January 2011 to December 2013. Viral nucleic acid was extracted, and virus infection (KIPyV and WUPyV) was determined by PCR. Some KIPyV-positive and WUPyV-positive PCR products were subjected to sequencing. Sequencing results were aligned with the known gene sequences of KIPyV and WUPyV to construct a phylogenetic tree. Amplified VP1 fragments of KIPyV were inserted into the cloning vector (PUCm-T) transformed into E. coli competent cells. Positive clones were identified by PCR and sequencing. The nucleotide sequences were submitted to GenBank. In addition, another seven common respiratory viruses in all samples were detected by direct immunofluorescence assay.</p><p><b>RESULTS</b>In the 3 730 specimens, the KIPyV-positive rate was 12.14% (453/3 730) and the WUPyV-positive rate was 1.69% (63/3 730). The mean infection rate of KIPyV was significantly higher in June and July, while the mean infection rate of WUPyV peaked in February and March. Most of the KIPyV-positive or WUPyV-positive children were <3 years. The co-infections with KIPyV, WUPyV, and other respiratory viruses were observed in the children. The co-infection rate was 2.31% (86/3 730) and there were nine cases of co-infections with WUPyV and KIPyV. Thirty-five KIPyV-positive and twelve WUPyV-positive PCR products were sequenced and the alignment analysis showed that they had high homology with the known sequences (94%-100% vs 95%-100%). The VP1 gene sequences obtained from two KIPyV strains in this study were recorded in GenBank with the accession numbers of KY465925 and KY465926.</p><p><b>CONCLUSIONS</b>For some children with acute respiratory infection in Tianjin, China, the acute respiratory infection may be associated with KIPyV and WUPyV infections. KIPyV infection is common in summer, and WUPyV infection in spring. The epidemic strains in Tianjin have a high homology with those in other regions.</p>

Nefropatía por poliomavirus en un paciente inmunosuprimido por trasplante renal secundario a la enfermedad de arteritis de Takayasu / Poliomavirus nephropathy in an immunosuppressed patient with a renal transplant secondary to Takayasu arteritis

La nefropatía por poliomavirus es una enfermedad que predomina en los pacientes con trasplante renal por el tratamiento inmunosupresor para manutención del injerto renal. La prevalencia actual de esta enfermedad oscila entre el 1 y el 14%. La sospecha de la enfermedad se da por la presencia de decoy cells en el examen de orina y el diagnóstico, mediante el hallazgo de inclusiones virales en la biopsia renal. Se describe el caso de un paciente con trasplante renal secundario a arteritis de Takayasu, que presenta disfunción renal evidenciada por elevación progresiva de creatinina sérica, por lo que se le realiza una biopsia renal en donde se observaron inclusiones nucleares virales que permitieron concluir el diagnóstico.

Polyomavirus nephropathy is a disease that predominates in renal transplant patients due to the immunosuppressive treatment for the maintenance of the renal graft. The current prevalence of this disease ranges between 1-14%. The suspicion of the disease comes from the presence of decoy cells in urine samples and the gold standard for the diagnosis is the presence of viral inclusions in the renal biopsy. In this case report, we describe a patient with a renal transplant secondary to Takayasu arteritis who presented renal failure evidenced by progressive elevation of serum creatinine. The renal biopsy showed viral inclusions, confirming the diagnosis.

Infección por Poliomavirus en pacientes trasplantados renales del Hospital Carlos Andrade Marín, enero 2013 a diciembre 2014 / Polyomavirus infection in kidney transplant patients of the Carlos Andrade Marin Hospital from January 2013 to December 2014

Introducción: La nefropatía del poliomavirus tipo BK, o nefropatía por VBK, se asocia a disfunción del injerto renal teniendo como factor de riesgo del donante, la presencia de virus VBK activo, infección por Citomegalovirus. La presencia de células de Decoy en orina y de virus BK en el plasma son los marcadores de la replicación del virus del polioma. Materiales y métodos: Estudio retrospectivo observacional en pacientes sometidos a trasplante renal en el período: enero 2013 a diciembre 2014. Los métodos empleados para establecer el diagnóstico incluyeron la determinación de las características clínicas; el hallazgo de células de Decoy en orina; reacción en cadena de polimerasa (PCR) en sangre para detectar el virus BK; inmunohistoquímica en biopsia renal. Resultados: De 53 pacientes con trasplante renal, cinco desarrollaron nefropatía inducida por virus del polioma humano. De ellos, cuatro tuvieron donante cadavérico y uno, donante vivo relacionado. El deterioro de la función renal se estableció 3 a 7 meses postrasplante, en pacientes que recibieron terapia inmunosupresora a base de micofenolato de mofetilo o tacrolimus. De los cinco pacientes en uno se evidenció células de Decoy en orina positivo y todos tenían carga viral plasmática positiva. Discusión: La nefropatía por Virus BK en pacientes trasplantados renales constituye una infección secundaria relacionada con el rechazo, el diagnóstico se establece con el análisis de marcadores específicos.

Introduction: Polyomavirus type BK (BKV) nephropathy is associated with renal transplant dysfunction, since donos carrying the VBK hold a risk factor of the concurrent cytomegalovirus infection. The presence of Decoy cells in urine and the VBK in plasma are the markers of polioma virus replication. Methods: Retrospective observational study focused on patients who received renal transplants in the period between January 2013 to December 2014. In order to make the diagnosis more accurate, we tested for clinical characteristics; the presence of Decoy cells in urine; polymerase chain reaction (PCR) blood test to detect the BK virus and immune histochemical test on renal biopsies. Results: Of 53 renal transplant patients, five developed nephropathy induced by human polyoma virus. Four received transplants from cadaveric donors and one from a living donor. Renal function deterioration was seen between three to seven months after the renal transplant in those patients receiving immunosuppression with mycophenolate mofetil or tacrolimus. Of the five patients, one tested positive for decoy cells in urine, and they all tested positive for plasmatic viral load. Discusion: The presence of BKV nephropathy in renal transplant patients is a secondary infection that might cause organ rejection. The diagnosis is made with specific biomarkers.

Severe Crescentic BK Nephropathy: A Case Report / 대한이식학회지

A 44-year-old man was admitted for evaluation of asymptomatic graft dysfunction. An allograft biopsy revealed diffuse interstitial infiltration of lymphocytes (i3) with moderate tubulitis (t3) and SV40-positive renal tubular epithelial cells. The patient was diagnosed with BK virus nephropathy, and immunosuppression was modified with discontinuing mycophenolate and reducing tacrolimus. Leflunomide treatment was also started simultaneously. However, serum creatinine increased to 3.0 mg/dL; therefore, the patient underwent a second allograft biopsy, in which the crescent was no longer evident but tubulitis (t2) and fibrosis (i2) persisted. On day 20, leflunomide was switched to ciprofloxacin due to leukopenia. The serum creatinine increased to 3.3 mg/dL, and the third biopsy showed slightly improved tubulitis and interstitial inflammation. We then administered an intravenous infusion of immunoglobulin. On day 70, the renal function was stable and the BK serum viral load was low, and the patient was discharged. This is a case of severe crescentic BK nephropathy with successful outcome treated with aggressive treatment and this method will be useful in renal transplant patients.

Nefropatía asociada a poliomavirus BK en trasplante renal / BK polyomavirus-associated nephropathy in kidney transplant

El objetivo del presente reporte es dar a conocer los dos primeros casos de nefropatía del injerto asociada a poliomavirus BK (NPBK) ocurridos en el Hospital Edgardo Rebagliati Martins, EsSalud, Lima, Perú. El diagnóstico definitivo de la NPBK se corroboró mediante biopsia renal y estudio de microscopia electrónica. En el caso 1, el deterioro funcional renal no se controló a pesar de reducir la inmunosupresión y añadir drogas antivirales (leflunamide y ciprofloxacina), evolucionando a falla renal y su posterior acceso a retrasplante renal. En el caso 2, la alternativa terapéutica se basó en infusión de inmunoglobulina endovenosa asociada a reducción de la inmunosupresión, resultando en moderada mejora histológica y estabilización de la función renal. En ambos injertos renales hubo concomitantemente NPBK y lesiones histológicas compatibles con rechazo agudo celular pendientes de interpretar. En conclusión, la presencia del poliomavirus BK representa serio problema en el riñón trasplantado. La mejor conducta terapéutica se basa en el diagnóstico precoz y subsecuente reducción de la inmunosupresión. Es imprescindible disponer de metodología apropiada que posibilite un diagnóstico preciso. Se utiliza tamizaje de células señuelo o marcadoras (decoy cells) en orina, reacción de cadena polimerasa (PCR), biopsia renal o la microscopia electrónica como método valioso de ayuda en el diagnóstico etiológico viral. Se considera el retrasplante como opción ante la pérdida del injerto por NPBK (caso 1)...

Two documented cases of BK polyomavirus-associated nephropathy (BKVN) seen at Hospital Edgardo Rebagliati Martins, EsSalud, Lima, Peru are reported. Final BKVN diagnosis was confirmed by renal biopsy and electron microscopy study. Case 1: Renal functional deterioration was not controlled despite reduction of immunosuppression and addition of antiviral drugs (leflunomide and ciprofloxacin), evolving to renal failure and subsequent kidney retransplantation. Case 2: The therapeutical management consisted in intravenous immunoglobulin infusion linked to reduction of immunosuppression; this resulted in modest histological improvement and stabilization of renal function. Both renal grafts concomitantly presented BKVN and histological lesions consistent with acute rejection, pending interpretation. In conclusion presence of BK polyomavirus is a serious problem for transplanted kidneys. The best treatment is based on early diagnosis and subsequent reduction of immunosuppression. It is essential to have an appropriate methodology for precise diagnosis. Early electron microscopy is a valuable method for viral etiologic diagnosis. Retransplantation is considered a treatment option when faced with possible BKVN-related graft loss (Case 1)...

prevalence of human Bocavirus, human Coronavirus-NL63, human Metapneumovirus, human Polyomavirus KI and WU in respiratory tract infections in Kuwait

Objective: The aim of this study was to investigate the prevalence of human coronavirus [HCoV]-NL63, human metapneumovirus [hMPV], human bocavirus [Boca], human polyomavirus KI [KIV] and human polyomavirus WU [WUV] in respiratory tract infections [RTI] in Kuwait

Materials and Methods: Respiratory samples from 735 hospitalized patients with RTI from September 2010 to April 2013 were evaluated for the presence of HCoV-NL63, hMPV, Boca, KIV and WUV using molecular assays, polymerase chain reaction [PCR] and reverse-transcription PCR

Results: Of the 735 patients, 285 [38.8%] were diagnosed with viral RTI. The distribution of respiratory viruses was hMPV: 15 [5.3%], Boca: 14 [4.9%], WUV: 10 [3.5%] and KIV: 4 [1.4%]. HCoV-NL63 was not detected in any of the samples

Conclusions: These newly discovered viruses were associated with the development of RTI in Kuwait. The rapid identification of these viral infections could aid in the control of nosocomial transmission, reduce the use of antibiotics and improve treatment and management strategies

No Detection of Simian Virus 40 in Malignant Mesothelioma in Korea

BACKGROUND: Simian virus 40 (SV40), a polyomavirus, was discovered as a contaminant of a human polio vaccine in the 1960s. It is known that malignant mesothelioma (MM) is associated with SV40, and that the virus works as a cofactor to the carcinogenetic effects of asbestos. However, the reports about the correlation between SV40 and MM have not been consistent. The purpose of this study is to identify SV40 in MM tissue in Korea through detection of SV40 protein and DNA. METHODS: We analyzed 62 cases of available paraffin-blocks enrolled through the Korean Malignant Mesothelioma Surveillance System and performed immunohistochemistry for SV40 protein and real-time polymerase chain reaction (PCR) for SV40 DNA. RESULTS: Of 62 total cases, 40 had disease involving the pleura (64.5%), and 29 (46.8%) were found to be of the epithelioid subtype. Immunostaining demonstrated that all examined tissues were negative for SV40 protein. Sufficient DNA was extracted for real-time PCR analysis from 36 cases. Quantitative PCR of these samples showed no increase in SV40 transcript compared to the negative controls. CONCLUSIONS: SV40 is not associated with the development of MM in Korea.

Establishment of a real-time PCR assay for simultaneously detecting human BKV and CMV DNA and its application in renal transplantation recipients / 病毒学报

To establish a fluorescent quantitative PCR method (FQ-PCR) with TaqMan probe for simultaneous detection of polyomavirus (BKV) and cytomegalovirus (CMV) and to evaluate its clinical application in the renal transplantation recipients. The conservative sequences of BKV and CMV were targeted and amplified by nested PCR technique. The PCR products were cloned into the plasmids pcDNA3. 1(+). The recombinant plasmid containing target sequences of BKV and CMV were constructed as external standards. The TaqMan-based assay was optimized. For evaluating the assay, the sensitivity was determinated by diluted standard (5 X 103-10icopies/mL), and the specificity was verified by negative control and positive control, and the precision was assessed by intra-assay coefficient of variation (ICV) through detecting standard repeatedly (20 times). A total of 480 blood samples of renal transplantation recipients were used to detect BKV and CMV DNA simultaneously with FQ-PCR, and the concentrations of FK506 were measured by ELISA. The association of DNA copy and concentrations of FK506 was analyzed. The cloned target BKV and CMV DNA was confirmed by sequencing and analysis. The sensitivity of the FQ-PCR assay reached 5 X 103 copies/ml in detecting BKV or CMV DNA. Control DNA verified the assay specifically detecting target DNA. The precision of the assay to quantif target DNA copies was acceptable (Intra-assay CV was 3.44% for BKV and 2.23% for CMV; Inter-assay CV was 4. 98% for BKV and 3.76% for CMV;). Of 480 samples, 130 samples (27. 08%) were CMV DNA positive, significantly higher than the BKV DNA positive (13.33%, 64/480, P<0.05). The positive BKV or CMV DNA was found to be associated with high concentrations of FK506 (P<0. 05). In conclusion, the developed real-time PCR assay for detecting both CMV and BKV DNA simultaneously was s high sensitive, precise and time-effectiveand could be applied in the monitoring of the CMV and BKV infection in the renal transplantation recipients.