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1.
Mikrobiyol Bul ; 54(1): 110-119, 2020 Jan.
Artigo em Turco | MEDLINE | ID: mdl-32050882

RESUMO

Anti-HCV and HCV RNA tests are used in laboratory diagnosis of hepatitis C virus (HCV) infections. False positive results are frequently observed in anti-HCV tests used as screening tests in societies with low prevalence of HCV. The HCV RNA test, which is a confirmatory test, is not performed in every laboratory because it is a high-cost and high-tech test, which can lead to delay in the diagnosis and treatment of patients. In this study, it was aimed to obtain an optimal anti-HCV S/CO value in our laboratory for demonstrating true antibody positivity and viremia in patients by analyzing the relationship between anti-HCV, alanine aminotransferase (ALT) and HCV RNA using retrospective data. Between July 2014 and July 2017, 754.190 anti-HCV tests were performed. Patients aged 18 years or older who were reactive with anti-HCV and those with simultaneous HCV RNA and ALT prompts were included in the study. The second generation CMIA (Abbott, USA) method was used for anti-HCV detection. For quantitative HCV RNA analysis, viral nucleic acid extraction was performed with the QIAsymphony SP/AS (Qiagen, Germany) using the QIAsymphony DSP Virus/Pathogen Midi Kit; and PCR was performed by Rotor-Gene Q (Qiagen, Germany) using Artus HCV QS-RGQ kit. ARCHITECT c and AEROSET systems (Abbott, USA) were used for ALT measurement. HCV genotype determination (622 cases) was performed using GenoSen's HCV Genotyping 1/2/3/4 RG qualitative real time PCR kit (Corbett Research, Australia) and GEN-C 2.0 Reverse Hybridization Strip Assay (NLM Diagnostics, Italy) kit at different periods covered by our study. The optimal threshold value for the relationship between anti-HCV, ALT and HCV RNA was selected based on ROC analysis. Statistical significance was accepted as p<0.05. Of the anti-HCV test results, 10.679 were found to be reactive. 1754 data of 1290 cases with anti-HCV reactivity who were simultaneously tested for HCV RNA and ALT in the same serum were evaluated. Of these, 742 (42%) were found to be HCV RNA positive and 1012 (58%) were found to be HCV RNA negative. ALT and anti-HCV levels of those who were positive for HCV RNA were significantly higher than those with negative HCV RNA (p= 0.001). The threshold point for anti-HCV S/CO according to HCV RNA was found to be 7.13 (sensitivity of 97.4%, specificity of 50.3%, positive predictive value 58.9%, negative predictive value 96.4%), and the cut-off point for ALT was found to be 27.5 IU/L (sensitivity of 77.6%, specificity of 80.8%). For HCV RNA positivity, the area under the ROC curve for anti-HCV and ALT was significantly higher than 0.5 (p= 0.001). No statistically significant difference was found between HCV genotypes in terms of ALT and anti-HCV levels. By using our new threshold in the laboratory workflow, the need to verify with HCV RNA can be reduced, especially in some patients who have been screened for antiHCV for screening purposes. Anti-HCV values below 7.13 S/CO, considering the high negative predictive value of this threshold; a false positive result in a patient presenting for screening can be predicted without waiting for the HCV RNA result. In anti-HCV reactivities determined above 7.13, the possibility of absence of viremia should be considered due to the low positive predictive value.


Assuntos
Hepacivirus , Hepatite C , Viremia , Adolescente , Adulto , Técnicas e Procedimentos Diagnósticos/normas , Alemanha , Hepacivirus/genética , Hepatite C/diagnóstico , Anticorpos Anti-Hepatite C/metabolismo , Humanos , RNA Viral/genética , Estudos Retrospectivos , Viremia/diagnóstico
2.
Afr Health Sci ; 19(2): 1988-1992, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31656481

RESUMO

Background: Previous trials have investigated the effect of hepatitis C on lung functions; however, the role of viral load levels is unclear. The aim of this study was to investigate the effect of HCV viremia status on lung functions. Methods: This study was in 60 patients with chronic hepatitis C (CHC). Patients were classified into three groups (non-viremic, low-viremic and high-viremic) based on serum HCV RNA levels. Spirometric parameters (FEV1, FVC, FEV1/FVC) and the proportion of patients with spirometric abnormalities were compared between three groups. Results: High-viremic and low-viremic patients showed a significantly higher prevalance of spirometric abnormality than observed in non-viremic patients (p=0.02). Moreover, there was a significant moderate correlation between viremia level and the percentage of spirometric abnormalities (Cramer's U value=0.452, p=0.002). High-viremic patients were 14.2 times more likely to exhibiting pulmonary dysfunction than non-viremic patients. Additionally, spirometric parameters FEV1 and FVC were significantly reduced in high-viremic and low-viremic patients compared to those in non-viremic patients (p=0.013 and p<0.001 respectively). Conclusion: These results indicate that persistent HCV infection may be associated with reduced pulmonary functions, especially in patients with high viremia levels. Therefore, these patients should be carefully monitored for lung function.


Assuntos
Hepacivirus/isolamento & purificação , Anticorpos Anti-Hepatite C/análise , Hepatite C Crônica/diagnóstico , Pulmão/fisiologia , RNA Viral/sangue , Viremia/diagnóstico , Adulto , Feminino , Hepatite C Crônica/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Testes de Função Respiratória , Espirometria , Carga Viral , Viremia/epidemiologia , Viremia/virologia
3.
Medicine (Baltimore) ; 98(39): e16997, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574798

RESUMO

This study aimed to determine the association between different lymphocyte subsets and cytomegalovirus (CMV) infection status in patients with systemic lupus erythematosus (SLE). We performed a retrospective study among SLE patients with CMV infection and collected patient socio-demographic and clinical characteristics, as well as their recorded circulating lymphocyte subsets. Univariate and multivariable logistic regression analyses examined the relationship between CMV infection status and lymphocyte subset counts. We included 125 hospitalized patients with SLE, consisting of 88 with documented CMV infection and 37 without any evidence of CMV or other infections. Among the 88 CMV-infected patients, 65 (73.8%) patients developed CMV disease and 23 (26.2%) presented as CMV viremia. Compared to uninfected patients (1520 ±â€Š101 cells/µL), lymphocytes remained stable among those with CMV viremia (1305 ±â€Š272 cells/µL, P = .995). However, compared to their uninfected counterparts, there was a marked decrease in lymphocytes among patients with CMV disease (680 ±â€Š513 cells/µL, P < .001). Analysis of lymphocyte subsets via flow cytometry showed that CD4+ T cell, CD8+ T cell, and natural killer cell counts were lower among those with CMV disease compared to those with CMV viremia and those without infection. Further, multivariable analysis showed that total lymphocyte (odds ratio [OR] 0.999, 95% confidence interval [CI] 0.998-1.000, P = .007) and CD4+ T cell counts (OR 0.99, 95% CI 0.992-0.998, P = .003) were negatively associated with CMV disease. Our findings support a potential inverse relationship between lymphopenia, specifically CD4+ T-cell lymphopenia, and CMV disease among hospitalized SLE patients.


Assuntos
Infecções por Citomegalovirus/diagnóstico , Lúpus Eritematoso Sistêmico/imunologia , Subpopulações de Linfócitos , Viremia/diagnóstico , Adulto , Sedimentação Sanguínea , Estudos de Casos e Controles , Feminino , Humanos , Contagem de Linfócitos , Linfopenia/complicações , Masculino , Projetos Piloto , Estudos Retrospectivos
4.
Microbiol Immunol ; 63(11): 449-457, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31373399

RESUMO

Hepatitis C virus (HCV) infection is a major public health problem with about 1.75 million new HCV cases and 71 million chronic HCV infections worldwide. The study aimed to evaluate clinical, serological, molecular, and liver markers to develop a mathematical predictive model for the quantification of the HCV viral load in chronic HCV infected patients. In this cross-sectional study, blood samples were taken from 249 recently diagnosed HCV-infected subjects and were tested for liver condition, viral genotype, and HCV RNA load. Receiver operating characteristics (ROC) curves and multiple linear regression analysis were used to predict the HCV-RNA load. Genotype 3 followed by genotype 1 were the most prevalent genotypes in Mashhad, Northeastern Iran. The maximum levels of viral load were detected in the mixed genotype group, and the lowest levels in the undetectable genotype group. The log of the HCV viral load was significantly associated with thrombocytopenia and higher serum levels of alanine transaminase (ALT). In addition, the log HCV RNA was significantly higher in patients with arthralgia, fatigue, fever, vomiting, or dizziness. Moreover, genotype 3 was significantly associated with icterus. A ROC curve analysis revealed that the best cut-off points for serum levels of aspartate aminotransferase (AST), ALT, and alkaline phosphatase (ALP) were >31, >34, and ≤246 IU/L, respectively. Sensitivity, specificity, and positive predictive values for AST were 87.7%, 84.36%, and 44.6%, for ALT they were 83.51%, 81.11%, and 36%, and for ALP were 72.06%, 42.81%, and 8.3%, respectively. A mathematical regression model was developed that could estimate the HCV-RNA load. Regression model: log viral load = 7.69 - 1.01 × G3 - 0.7 × G1 + 0.002 × ALT - 0.86 × fatigue.


Assuntos
Hepacivirus/genética , Hepatite C Crônica/virologia , Fígado/patologia , RNA Viral/sangue , Viremia/diagnóstico , Adulto , Biomarcadores/sangue , Estudos Transversais , Feminino , Genótipo , Humanos , Irã (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Testes Sorológicos/métodos , Carga Viral/métodos
6.
Transfus Clin Biol ; 26(3): 155-159, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31255509

RESUMO

INTRODUCTION: Different evaluations conducted on blood safety between 2004 and 2013 in Africa showed some progress in most countries. This paper describes the current status of the availability and access to safe blood in the Region. METHODS: A cross-sectional survey was conducted from January to December 2018. Data were collected through a questionnaire prepared using key indicators of blood safety and analysis was done using Excel 2010 and results were compared to those of the 2013. RESULTS: A total of 2,678 blood centres were reported including 244 (9%) stand-alone and 2,434 (91%) hospital based. Amongst these countries, 90.2% had a blood policy, 60.1% participated in an External Quality Assessment Scheme for Transfusion Transmissible Infections screening, 12% had accredited blood services, 73.2% had national guidelines on clinical use of blood and 78% had a government budget. The total number of blood units collected was 4,899,913 and the average proportion of voluntary blood donations was 71%. Plasma-derived medicinal products were included in the national essential medicines list in 52.6% of countries. The average proportion of units of blood tested for infections was 99.5% for HIV, 92.3% for HBV, 98.9% for HCV, 98.8% for syphilis. The percentage of whole blood separated into blood components was 63.4%. CONCLUSION: Countries in the region continue to improve availability and access to safe blood, but challenges still remain and call for concrete actions required to reach universal access to quality and safe blood for transfusion throughout the region.


Assuntos
Segurança do Sangue , Transfusão de Sangue/estatística & dados numéricos , África/epidemiologia , Bancos de Sangue/normas , Bancos de Sangue/estatística & dados numéricos , Doadores de Sangue/estatística & dados numéricos , Segurança do Sangue/normas , Segurança do Sangue/estatística & dados numéricos , Transfusão de Sangue/normas , Estudos Transversais , Pesquisas sobre Serviços de Saúde , Humanos , Utilização de Procedimentos e Técnicas/estatística & dados numéricos , Sífilis/prevenção & controle , Sífilis/transmissão , Reação Transfusional/epidemiologia , Reação Transfusional/prevenção & controle , Viremia/diagnóstico , Viremia/epidemiologia , Viroses/prevenção & controle , Viroses/transmissão , Organização Mundial da Saúde
7.
Transpl Infect Dis ; 21(4): e13133, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31233669

RESUMO

Trichodysplasia spinulosa (TS) is a rare disease associated with immunosuppression and induced by a polyomavirus denominated Tricodisplasia Polyomavirus (TSPyV). We report a case of TS 6 months after kidney transplantation in a 65 years-old woman under immunosuppression therapy with prednisone, mycophenolate and tacrolimus. The patient developed follicular papules on the face with a thickening of the skin and alopecia of the eyebrows, leading to distortion of the face and a leonine appearance characteristic of the disease. The skin biopsy confirmed the clinical diagnosis and the presence of TSPyV DNA in the skin was detected. Staining for SV40 was positive. Immunosuppression was changed: mycophenolate was withdrawn, tacrolimus reduced and everolimus added. Intravenous cidofovir and later on leflunomide were added. Although the literature has reported clinical success with topical cidofovir, we were unable to use it because this drug is not available. There was an improvement of skin lesions and on cosmetic appearance. The patient had three rejections (one clinically diagnosed and two other biopsy proven), progressed with renal failure and graft loss. Retrospective analysis of stored urine and blood samples detected TSPyV DNA in some of those samples two months before the TS clinical development. This case highlights the TSPyV detection in blood and urine samples before the development of skin lesions.


Assuntos
Doenças do Cabelo/virologia , Transplante de Rim/efeitos adversos , Infecções por Polyomavirus/diagnóstico , Viremia/diagnóstico , Viremia/tratamento farmacológico , Idoso , DNA Viral , Feminino , Doenças do Cabelo/tratamento farmacológico , Humanos , Imunossupressão/efeitos adversos , Imunossupressores , Rim/patologia , Infecções por Polyomavirus/urina , Estudos Retrospectivos , Pele/patologia , Pele/virologia , Transplantados
8.
J Infect Chemother ; 25(10): 820-824, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31027885

RESUMO

The BK virus (BKV) is a member of the polyomaviridae family of DNA viruses. BKV reactivates under a highly immunosuppressed state and causes renal dysfunction. In renal transplant patients, BKV infection leads to tubular impairment and loss of transplanted kidney grafts. However, few studies have reported on the relationship between BKV and lung transplantation. Adjustment of the dosage of immunosuppressants is needed in some cases, but the treatment method has not been established. Here, we report a case of BKV-associated viruria and viremia in a patient with lymphangioleiomyomatosis (LAM) after lung re-transplantation. A 44-year-old female refractory LAM patient who had undergone lung re-transplantation 3 months earlier was diagnosed with BKV-associated viruria and viremia. Urine cytology indicated decoy cells and the urine and serum polymerase chain reaction test was positive for BKV. As scheduled after re-transplantation surgery, immunosuppressive drugs were progressively reduced. This patient was considered to have experienced spontaneous BKV-associated viremia and viruria. Review of the literature suggested that 17%-42% of BKV-associated viruria cases have been reported after lung transplantation, but cases of BKV-associated nephropathy are rarely reported. Based on the present case, doctors involved in lung transplantation should monitor patients for BKV infection. Decoy cell monitoring by urine cytology is a useful screening method in the follow-up observation after lung transplantation. Early-stage interventions may prevent BKV-associated nephropathy even in patients who have developed BKV viremia, and sirolimus can be administered to patients with histories of BKV infection if they are carefully monitored.


Assuntos
Vírus BK/isolamento & purificação , Transplante de Pulmão/efeitos adversos , Infecções Urinárias/diagnóstico , Viremia/diagnóstico , Adulto , Vírus BK/imunologia , DNA Viral/isolamento & purificação , Feminino , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Humanos , Imunossupressores/efeitos adversos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/cirurgia , Linfangioleiomiomatose/imunologia , Linfangioleiomiomatose/cirurgia , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/cirurgia , Infecções por Polyomavirus/diagnóstico , Infecções por Polyomavirus/imunologia , Infecções por Polyomavirus/virologia , Reoperação/efeitos adversos , Fatores de Risco , Infecções Tumorais por Vírus/diagnóstico , Infecções Tumorais por Vírus/imunologia , Infecções Tumorais por Vírus/virologia , Infecções Urinárias/imunologia , Infecções Urinárias/virologia , Carga Viral , Viremia/imunologia , Viremia/virologia
9.
BMC Nephrol ; 20(1): 29, 2019 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-30704432

RESUMO

BACKGROUND: Anti-glomerular basement membrane (anti-GBM) disease is characterized by circulating IgG glomerular basement membrane antibodies and is clinically expressed as a rapidly progressive crescentic glomerulonephritis (GN), with 30-60% of patients also developing pulmonary hemorrhage. Classically, the renal biopsy shows glomerular crescent formation, bright linear staining of glomerular basement membranes (GBM) for IgG on direct immunofluorescence (IF), and the serologic presence of circulating anti-GBM antibodies. Recently, patients with linear IgG IF staining, undetectable circulating anti-GBM antibodies and glomerular changes atypical for anti-GBM disease have been described as "atypical anti-GBM disease", with a distinctly more benign clinical course than typical anti-GBM disease. We present a case report of a patient with negative anti-GBM serology but positive linear IgG staining by IF, severe diffuse crescentic and endocapillary proliferative glomerulonephritis, and renal failure, complicated by severe pulmonary hemorrhage after immunosuppression, likely due to cytomegalovirus (CMV) pneumonitis. CASE PRESENTATION: A 24-year-old man was admitted to hospital with hemoptysis and renal failure. Investigations for anti-GBM serology by addressable laser bead immunoassay (ALBIA) was negative for anti-GBM antibodies. Renal biopsy showed diffuse endocapillary proliferative glomerulonephritis with membranoproliferative features and diffuse circumferential crescents. Direct IF showed strong linear staining for IgG along GBMs. The patient's hemoptysis improved with immunosuppression, but 1 month later he was readmitted with gross hemoptysis, which was refractory to further cyclophosphamide, plasma exchange and rituximab. Bronchoalveolar lavage (BAL) and blood work confirmed CMV pneumonitis, and the patient's hemoptysis resolved with ganciclovir, though he became dialysis dependent. CONCLUSIONS: This case demonstrates an atypical presentation of anti-GBM disease with both crescents and endocapillary hypercellularity and negative serology. The patient is dialysis dependent, unlike most previously described patients with atypical anti-GBM disease. The course was complicated by CMV pneumonitis, which contributed to the severity of the pulmonary manifestations and added diagnostic difficulty.


Assuntos
Doença Antimembrana Basal Glomerular/complicações , Infecções por Citomegalovirus/complicações , Hemoptise/etiologia , Pneumonia Viral/complicações , Viremia/complicações , Doença Antimembrana Basal Glomerular/terapia , Antivirais/uso terapêutico , Autoanticorpos/análise , Terapia Combinada , Ciclofosfamida/uso terapêutico , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/tratamento farmacológico , Diagnóstico Tardio , Progressão da Doença , Ganciclovir/uso terapêutico , Hemorragia/etiologia , Humanos , Imunoglobulina G/análise , Glomérulos Renais/química , Glomérulos Renais/imunologia , Pneumopatias/etiologia , Masculino , Plasma , Troca Plasmática , Pneumonia Viral/tratamento farmacológico , Recidiva , Viremia/diagnóstico , Viremia/tratamento farmacológico , Adulto Jovem
10.
J Vet Diagn Invest ; 31(2): 284-288, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30734651

RESUMO

We investigated the potential for viremic sera from cattle persistently infected with bovine viral diarrhea virus to create false-negative antibody results when testing pools of 10 sera by indirect or blocking ELISAs. Seronegative viremic sera ( n = 23) were each added to a series of artificially constructed pools containing various percentages (0-90%) of antibody-positive sera, and the resulting pools were assayed for antibody. In all 23 cases, a negative antibody result was obtained in the pool containing no seropositive sera. In contrast, all pools containing ≥10% seropositive serum, representing a single seropositive animal in a pool of 10 samples, returned a positive result in both antibody ELISAs. We concluded that the likelihood of a false-negative antibody result occurring as a result of the presence of serum from a viremic animal was low, and therefore did not preclude the use of pooled sera for serosurveillance.


Assuntos
Anticorpos Antivirais/sangue , Doença das Mucosas por Vírus da Diarreia Viral Bovina/diagnóstico , Vírus da Diarreia Viral Bovina/isolamento & purificação , Ensaio de Imunoadsorção Enzimática/veterinária , Viremia/veterinária , Animais , Doença das Mucosas por Vírus da Diarreia Viral Bovina/virologia , Bovinos , Reações Falso-Negativas , Estudos Soroepidemiológicos , Viremia/diagnóstico , Viremia/virologia
11.
Int J Food Microbiol ; 292: 144-149, 2019 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-30599454

RESUMO

Although hepatitis E virus (HEV) transmission has been demonstrated after consumption of products containing infected pig liver, human cases can be also associated with other pig meat products, such as sausages. Data on HEV viremia and dissemination in muscle meat of infected animals are still sparse, especially during long-term infection. Previously, we have shown that experimental co-infection of pigs with HEV and porcine reproductive and respiratory syndrome virus (PRRSV) lengthens HEV infection up to 49 days and increases the likelihood of the presence of HEV RNA in the liver of the pig at a later stage of infection. In the present study, we show that during experimental HEV-PRRSV co-infection, prolonged HEV viremia, up to 49 days post-inoculation (dpi), is detected. The long-term viremia observed was statistically associated with the absence of HEV seroconversion. HEV RNA was also frequently detected, at a late stage of infection (49 dpi), in the three different types of muscle tested: femoral biceps, psoas major or diaphragm pillar. The HEV RNA load could reach up to 1 ·â€¯106 genome copies per gram of muscle. Detection of HEV in muscle meat was statistically associated with high HEV loads in corresponding liver and fecal samples. The presence of HEV in pig blood, femoral biceps and major psoas, corresponding to ham and tenderloin muscles respectively, is of concern for the food industry. Hence, these results indicate new potential risks for consumers and public health regarding pork products.


Assuntos
Coinfecção/virologia , Contaminação de Alimentos , Vírus da Hepatite E/isolamento & purificação , Músculo Esquelético/virologia , Vírus da Síndrome Respiratória e Reprodutiva Suína/isolamento & purificação , Carne Vermelha/virologia , Viremia/diagnóstico , Animais , Coinfecção/diagnóstico , Fezes/virologia , Microbiologia de Alimentos , Hepatite E/diagnóstico , Hepatite E/transmissão , Produtos da Carne/virologia , Síndrome Respiratória e Reprodutiva Suína/diagnóstico , Síndrome Respiratória e Reprodutiva Suína/transmissão , RNA Viral/isolamento & purificação , Fatores de Risco , Suínos/virologia , Doenças dos Suínos/virologia
13.
Transpl Infect Dis ; 21(1): e13005, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30276937

RESUMO

Primary effusion lymphoma (PEL) is a rare mature B-cell non-Hodgkin's lymphoma arising in body cavities and presenting with effusions. It has been described predominantly in patients with impaired immunity from the acquired immunodeficiency syndrome and is associated with the Human Herpesvirus-8 (HHV-8). Seldom has PEL been diagnosed in persons negative for the human immunodeficiency virus (HIV), and in such cases it has occurred primarily in the setting of posttransplant immunosuppression. We report an instructive case of a Caribbean-American HIV-negative orthotopic heart transplant recipient with a history of HHV-8-associated Kaposi's sarcoma who developed HHV-8 viremia and PEL of the pleural space early in the posttransplant course. This case highlights the importance of considering PEL in the differential diagnosis of a new pleural effusion in a transplant recipient at risk for HHV-8-associated disease.


Assuntos
Transplante de Coração/efeitos adversos , Herpesvirus Humano 8/isolamento & purificação , Linfoma de Efusão Primária/diagnóstico , Complicações Pós-Operatórias/diagnóstico , Viremia/diagnóstico , Diagnóstico Diferencial , Humanos , Imunossupressão/efeitos adversos , Imunossupressão/métodos , Linfoma de Efusão Primária/imunologia , Linfoma de Efusão Primária/patologia , Linfoma de Efusão Primária/virologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/virologia , Cavidade Pleural/patologia , Cavidade Pleural/virologia , Complicações Pós-Operatórias/imunologia , Complicações Pós-Operatórias/virologia , Sarcoma de Kaposi/imunologia , Sarcoma de Kaposi/patologia , Sarcoma de Kaposi/virologia , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/virologia , Viremia/imunologia , Viremia/virologia
14.
J Virol ; 93(3)2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30429336

RESUMO

Human herpesvirus 6B (HHV-6B) DNA is frequently detected in human samples. Diagnostic assays distinguishing HHV-6B reactivation from latency are limited. This has impaired strategies to diagnose and treat HHV-6B-associated diseases. We used RNA sequencing to characterize and compare the HHV-6B transcriptome in multiple sample types, including (i) whole blood from hematopoietic cell transplant (HCT) recipients with and without HHV-6B plasma viremia, (ii) tumor tissue samples from subjects with large B cell lymphoma infected with HHV-6B, (iii) lymphoblastoid cell lines (LCLs) from subjects with inherited chromosomally integrated HHV-6B or latent infection with HHV-6B, and (iv) HHV-6B Z29 infected SupT1 CD4+ T cells. We demonstrated substantial overlap in the HHV-6B transcriptome observed in in vivo and in vitro samples, although there was variability in the breadth and quantity of gene expression across samples. The HHV-6B viral polymerase gene U38 was the only HHV-6B transcript detected in all next-generation RNA sequencing (RNA-seq) data sets and was one of the most highly expressed genes. We developed a novel reverse transcription-PCR assay targeting HHV-6B U38, which identified U38 mRNA in all tested whole-blood samples from patients with concurrent HHV-6B viremia. No HHV-6B U38 transcripts were detected by RNA-seq or reverse transcription-real-time quantitative PCR (RT-qPCR) in whole-blood samples from subjects without HHV-6B plasma detection or from latently infected LCLs. A RT-qPCR assay for HHV-6B U38 may be useful to identify lytic HHV-6B infection in nonplasma samples and samples from individuals with inherited chromosomally integrated HHV-6B. This study also demonstrates the feasibility of transcriptomic analyses for HCT recipients.IMPORTANCE Human herpesvirus 6B (HHV-6B) is a DNA virus that infects most children within the first few years of life. After primary infection, HHV-6B persists as a chronic, latent infection in many cell types. Additionally, HHV-6B can integrate into germ line chromosomes, resulting in individuals with viral DNA in every nucleated cell. Given that PCR to detect viral DNA is the mainstay for diagnosing HHV-6B infection, the characteristics of HHV-6B infection complicate efforts to distinguish between latent and active viral infection, particularly in immunocompromised patients who have frequent HHV-6B reactivation. In this study, we used RNA sequencing to characterize the HHV-6B gene expression profile in multiple sample types, and our findings identified evidence-based targets for diagnostic tests that distinguish between latent and active viral infection.


Assuntos
Herpesvirus Humano 6/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Infecções por Roseolovirus/diagnóstico , Transcriptoma , Proteínas Virais/genética , Viremia/diagnóstico , Ativação Viral , Latência Viral , Adulto , Idoso , Biomarcadores/análise , Estudos de Casos e Controles , Citocinas/sangue , DNA Viral , Feminino , Humanos , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/virologia , Masculino , Pessoa de Meia-Idade , Infecções por Roseolovirus/genética , Infecções por Roseolovirus/virologia , Viremia/genética , Viremia/virologia
15.
Pediatr Transplant ; 23(1): e13324, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30447046

RESUMO

BACKGROUND: BKPyV is an important cause of premature graft failure after KT. Most clinical studies describe BKPyV infection in adult KT patients. We studied the prevalence of post-transplant BKPyV viremia, serology, and graft function in pediatric KT recipients. METHODS: Forty-six pediatric patients transplanted between 2009 and 2014 were followed up for BKPyV DNAemia by plasma PCR for median 2.3 (range: 1-6) years. BKPyV-specific antibodies were retrospectively analyzed using virus-like particle ELISA. GFR was measured annually by 51 Cr-EDTA clearance, and serum samples were screened for DSAs by Luminex assay. RESULTS: BKPyV viremia was demonstrated in nine patients at a median of 6 months post-KT. Early BKPyV viremia at 3 months post-KT associated with decreased concomitant GFR and tendency for decreased subsequent graft function. Three of nine patients with BKPyV viremia developed DSA, all against class II antigens. PyVAN developed to four patients and responded to judicious reduction in IS. One graft was lost later due to ABMR. BKPyV-IgG was found in 18 of 31 patients (58%) tested at transplantation, and seven recipients seroconverted after transplantation with a significant increase in IgG levels with IgM. Finally, BKPyV-IgG was detectable in 31 of 40 patients (78%) at the end of the study. CONCLUSIONS: Post-transplant BKPyV viremia in pediatric KT patients may alter graft function and contribute to progression of chronic allograft injury. BKPyV-IgG predicts past exposure. Low or absent BKPyV-specific antibody levels were seen pretransplant in 42% of tested patients, but were not predictive of prolonged replication or poor outcome.


Assuntos
Anticorpos Antivirais/sangue , Vírus BK , Transplante de Rim , Infecções por Polyomavirus/etiologia , Complicações Pós-Operatórias , Infecções Tumorais por Vírus/etiologia , Viremia/etiologia , Adolescente , Formação de Anticorpos , Vírus BK/imunologia , Vírus BK/isolamento & purificação , Biomarcadores/sangue , Criança , Pré-Escolar , Feminino , Finlândia , Seguimentos , Sobrevivência de Enxerto/imunologia , Sobrevivência de Enxerto/fisiologia , Humanos , Lactente , Masculino , Infecções por Polyomavirus/diagnóstico , Infecções por Polyomavirus/epidemiologia , Infecções por Polyomavirus/imunologia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/imunologia , Prevalência , Estudos Retrospectivos , Infecções Tumorais por Vírus/diagnóstico , Infecções Tumorais por Vírus/epidemiologia , Infecções Tumorais por Vírus/imunologia , Viremia/diagnóstico , Viremia/epidemiologia , Viremia/imunologia
16.
JAMA Pediatr ; 173(1): 52-59, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30476967

RESUMO

Importance: The evolution of fetal brain injury by Zika virus (ZIKV) infection is not well described. Objectives: To perform longitudinal neuroimaging of fetuses and infants exposed to in utero maternal ZIKV infection using concomitant magnetic resonance imaging (MRI) and ultrasonography (US), as well as to determine the duration of viremia in pregnant women with ZIKV infection and whether the duration of viremia correlated with fetal and/or infant brain abnormalities. Design, Setting, and Participants: A cohort of 82 pregnant women with clinical criteria for probable ZIKV infection in Barranquilla, Colombia, and Washington, DC, were enrolled from June 15, 2016, through June 27, 2017, with Colombian women identified by community recruitment and physician referral and travel-related cases of American women recruited from a Congenital Zika Program. Interventions and Exposures: Women received 1 or more MRI and US examinations during the second and/or third trimesters. Postnatally, infants underwent brain MRI and cranial US. Blood samples were tested for ZIKV. Main Outcomes and Measures: The neuroimaging studies were evaluated for brain injury and cerebral biometry. Results: Of the 82 women, 80 were from Colombia and 2 were from the United States. In 3 of 82 cases (4%), fetal MRI demonstrated abnormalities consistent with congenital ZIKV infection. Two cases had heterotopias and malformations in cortical development and 1 case had a parietal encephalocele, Chiari II malformation, and microcephaly. In 1 case, US results remained normal despite fetal abnormalities detected on MRI. Prolonged maternal polymerase chain reaction positivity was present in 1 case. Of the remaining 79 cases with normal results of prenatal imaging, postnatal brain MRI was acquired in 53 infants and demonstrated mild abnormalities in 7 (13%). Fifty-seven infants underwent postnatal cranial US, which detected changes of lenticulostriate vasculopathy, choroid plexus cysts, germinolytic/subependymal cysts, and/or calcification in 21 infants (37%). Conclusions and Relevance: In a cohort of pregnant women with ZIKV infection, prenatal US examination appeared to detect all but 1 abnormal fetal case. Postnatal neuroimaging in infants who had normal prenatal imaging revealed new mild abnormalities. For most patients, prenatal and postnatal US may identify ZIKV-related brain injury.


Assuntos
Encéfalo/diagnóstico por imagem , Imagem por Ressonância Magnética , Malformações do Sistema Nervoso/diagnóstico por imagem , Neuroimagem/métodos , Complicações Infecciosas na Gravidez , Ultrassonografia Pré-Natal , Infecção por Zika virus/diagnóstico por imagem , Adulto , Biomarcadores/sangue , Encéfalo/anormalidades , Encéfalo/embriologia , Encéfalo/virologia , Colômbia , District of Columbia , Feminino , Desenvolvimento Fetal , Humanos , Recém-Nascido , Estudos Longitudinais , Masculino , Malformações do Sistema Nervoso/embriologia , Malformações do Sistema Nervoso/virologia , Gravidez , Complicações Infecciosas na Gravidez/sangue , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/virologia , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Estudos Prospectivos , Doença Relacionada a Viagens , Viremia/sangue , Viremia/diagnóstico , Infecção por Zika virus/sangue , Infecção por Zika virus/embriologia , Infecção por Zika virus/virologia
17.
BMC Infect Dis ; 18(1): 622, 2018 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-30514229

RESUMO

BACKGROUND: Nucleic acid tests performed on blood samples collected on Dried Blood Spot (DBS) and detection of HCV core antigen (HCVcAg) are two approaches that may facilitate access to HCV diagnosis in low and middle incomes countries. In this study we evaluate HCV RNA and HCV antigen testing on DBS in HIV/HCV co-infected peoples who inject drugs in Vietnam. METHOD: One hundred and four HIV/HCV seropositive patients managed in outpatient care at the Haiphong Viet Tiep hospital were included in this study from February to March, 2014 (ANRS 12262 study). RESULTS: Eighty-six subjects were tested positive for HCV RNA in serum, median (IQR): 6.9 log10 IU/ml (5.6-7.4 log10 IU/ml). Genotypes consisted of 57 G1 (69%), 3 G3 (4%), and 22 G6 (27%). HCV RNA was detected on DBS specimens in 79 out 86 subjects with chronic hepatitis C (sensitivity 92.5%; 95% CI: 85.1-96.9%). HCV RNA level on DBS and serum was moderately correlated (r = 0.24; p = 0.05) suggesting a degradation of HCV RNA due to transportation and storage conditions. HCVcAg was detected in 75/86 dB specimens (sensitivity: 87.2%; 95% CI: 78.3-93.4%), with a strong positive relationship between DBS HCVcAg and serum HCV RNA levels (r = 0.80; P < 0.0001). CONCLUSIONS: Quantification of HCVcAg on DBS appears to benefit from substantial stability under prolonged storage conditions but with a lower analytical sensitivity compared to DBS HCV RNA testing. Detection of HCV RNA on DBS is an interesting approach for confirming viral replication in HCV seropositive persons but the impact of pre-analytical conditions on the integrity of HCV RNA needs to be controlled.


Assuntos
Teste em Amostras de Sangue Seco/métodos , Infecções por HIV/virologia , Hepatite C/virologia , RNA Viral/análise , Abuso de Substâncias por Via Intravenosa/virologia , Proteínas do Core Viral/análise , Viremia/diagnóstico , Adulto , Coinfecção , Estudos Transversais , Testes Diagnósticos de Rotina , Usuários de Drogas , Feminino , Genótipo , HIV/genética , Infecções por HIV/sangue , Infecções por HIV/complicações , Hepacivirus/genética , Hepatite C/sangue , Hepatite C/complicações , Hepatite C/diagnóstico , Humanos , Testes Imunológicos , Injeções , Masculino , RNA Viral/sangue , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Abuso de Substâncias por Via Intravenosa/sangue , Abuso de Substâncias por Via Intravenosa/complicações , Vietnã , Proteínas do Core Viral/sangue , Proteínas do Core Viral/genética , Viremia/sangue , Viremia/genética
18.
J Clin Virol ; 109: 29-34, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30388664

RESUMO

BACKGROUND: In Cambodia, access to hepatitis B surface antigen (HBsAg) screening is low for pregnant women and Hepatitis B Virus (HBV) DNA quantification is poorly accessible. OBJECTIVES: To evaluate the performance of a serial algorithm using two HBV rapid diagnostic tests (RDTs), in which samples positive for HBsAg were further tested for HBeAg as a surrogate marker for HBV DNA quantification. STUDY DESIGN: In 2015, we prospectively collected plasma samples from 250 pregnant women consulting for antenatal care in one hospital in Phnom Penh including 128 with a known positive HBsAg status. All specimens were tested with the SD BIOLINE HBsAg RDT and HBsAg ELISA assay. In ELISA-positive samples, HBeAg status was determined using the SD BIOLINE HBeAg RDT and HBV DNA quantification was assessed. RESULTS: Sensitivity and specificity of HBsAg RDT were 99.2% (97.7-99.9) and 100% (97.0-100), respectively. Among the 128 ELISA-positive samples, 29 (23%) tested HBeAg positive and 34 (26.5%) had HBV DNA > 5.3 Log10 IU/mL. Sensitivity and specificity of HBeAg RDT in identifying viremic samples were 76.5% (62.2.0-90.7) and 96.8% (93.3-100) for HBV DNA > 5.3 Log10 IU/mL and 89.3% (77.8-100) and 96.0% (92.2-99.8) for HBV DNA > 7.3 Log10IU/mL. Among the 99 negative HBeAg RDT women, 8 had HBV DNA > 5.3 Log10 IU/mL and 7 of them harbored BCP/PC HBV mutants. CONCLUSIONS: A combination of HBsAg and HBeAg RDTs could be a low-cost strategy to identify HBV-infected pregnant women at risk of perinatal transmission in a country were HBV DNA quantification is not routinely available.


Assuntos
Antígenos de Superfície da Hepatite B/sangue , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/isolamento & purificação , Hepatite B/diagnóstico , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Complicações Infecciosas na Gravidez/diagnóstico , Algoritmos , Camboja , DNA Viral/sangue , Testes Diagnósticos de Rotina , Feminino , Hepatite B/sangue , Vírus da Hepatite B/imunologia , Humanos , Projetos Piloto , Gravidez , Complicações Infecciosas na Gravidez/virologia , Gestantes , Sensibilidade e Especificidade , Viremia/diagnóstico
19.
Lancet Gastroenterol Hepatol ; 3(12): 856-864, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30274834

RESUMO

BACKGROUND: Direct-acting antivirals for chronic hepatitis C (HCV) infection have reduced the need for on-treatment HCV RNA monitoring. We assessed the accuracy and cost implications of using HCV core antigen testing to replace HCV RNA testing for confirmation of diagnosis, on-treatment monitoring, and determination of sustained virological response (SVR). METHODS: In a retrospective screening cohort study, de-identified residual serum from unselected samples were obtained from commercial laboratories in Ontario, Canada. Samples from each 5-year age-sex band from birth years 1945-74 collected from Aug 1, 2014, to Feb 28, 2015, were included. All samples that tested positive for HCV antibodies, and 10% of samples that tested negative for HCV antibodies, were tested for HCV core antigen and HCV RNA. A retrospective clinical cohort study was also done using blood samples from patients with confirmed HCV infection collected at four tertiary academic centres: one in Canada, two in Germany, and one in the USA. For assessment of SVR, we included samples from patients who started direct-acting antiviral-based treatment (excluding telaprevir and boceprevir) with or without peginterferon, ribavirin, or both, from Jan 1, 2014, to March 31, 2015. To ensure inclusion of adequate numbers for analysis, patients who relapsed after any treatment regimen were included. Serum samples included in the study were from baseline, week 4 on-treatment (only for patients treated with direct-acting antivirals), end of treatment, and week 12 or 24 of follow-up. The sensitivity and specificity of core antigen testing as a diagnostic tool was assessed in the screening cohort, using HCV RNA as a reference. The sensitivity and specificity of core antigen testing as well as its concordance with HCV RNA testing in the clinical cohort was assessed at baseline, week 4 on-treatment, and at weeks 12 or 24 after the end of treatment in patients undergoing therapy with direct-acting antivirals. The cost-effectiveness of core antigen testing with and without confirmatory HCV RNA testing for negative samples was also assessed. FINDINGS: From 10 006 samples in the screening cohort, 75 of 80 viraemic (HCV RNA-positive) samples tested positive for HCV core antigen (sensitivity 94%, 95% CI 86-98), and none of the 993 HCV RNA-negative samples tested positive for HCV core antigen (specificity 100%, 95% CI 94-100). The five viraemic samples that tested negative for HCV core antigen had low corresponding HCV RNA concentrations. In the clinical cohort, two (1%) of 202 baseline samples tested negative for HCV core antigen; one had a low HCV RNA concentration (468 IU/mL), the other had a high HCV RNA concentration (>2 000 000 IU/mL). By week 4 of treatment, HCV core antigen concentrations decreased in all patients but were not predictive of SVR. Although there was good concordance between HCV RNA and HCV core antigen results at 12 weeks after the end of treatment (r=0·97; p<0·0001), three of the 148 patients who achieved SVR at 12 weeks tested HCV core antigen positive. 12 weeks after the end of treatment, HCV core antigen was undetectable in one (1%) of 71 samples from patients who were identified as having relapsed according to HCV RNA detection. On-treatment and end-of-treatment testing of core antigen or HCV RNA provided little clinical value. The use of HCV core antigen testing as a confirmatory diagnostic strategy was cost saving relative to HCV RNA testing, with a reduction of CAD$0·29-3·70 per patient screened depending on whether HCV RNA testing was used to confirm HCV core antigen-negative results. INTERPRETATION: These data support the use of HCV core antigen testing to document HCV viraemia in a cost-saving diagnostic algorithm. In a treatment setting, HCV core antigen testing can be used instead of HCV RNA testing for diagnosis and documentation of treatment adherence, but it might not be adequate to determine SVR. This approach might improve access to care, particularly in low-income and middle-income countries. FUNDING: Abbott Diagnostics and Toronto Centre for Liver Disease.


Assuntos
Antivirais/uso terapêutico , Monitoramento de Medicamentos/economia , Monitoramento de Medicamentos/métodos , Antígenos da Hepatite C/sangue , Hepatite C Crônica/sangue , Hepatite C Crônica/tratamento farmacológico , RNA Viral/sangue , Proteínas do Core Viral/sangue , Adulto , Idoso , Redução de Custos , Feminino , Hepatite C/genética , Hepatite C/imunologia , Hepatite C Crônica/diagnóstico , Humanos , Masculino , Programas de Rastreamento/economia , Programas de Rastreamento/métodos , Adesão à Medicação , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Viremia/sangue , Viremia/diagnóstico , Viremia/tratamento farmacológico
20.
Front Immunol ; 9: 2147, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30319615

RESUMO

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis can be caused by a broad range of pathogens; however, bacterial infections represent the majority of sepsis cases. Up to 42% of sepsis presentations are culture negative, suggesting a non-bacterial cause. Despite this, diagnosis of viral sepsis remains very rare. Almost any virus can cause sepsis in vulnerable patients (e.g., neonates, infants, and other immunosuppressed groups). The prevalence of viral sepsis is not known, nor is there enough information to make an accurate estimate. The initial standard of care for all cases of sepsis, even those that are subsequently proven to be culture negative, is the immediate use of broad-spectrum antibiotics. In the absence of definite diagnostic criteria for viral sepsis, or at least to exclude bacterial sepsis, this inevitably leads to unnecessary antimicrobial use, with associated consequences for antimicrobial resistance, effects on the host microbiome and excess healthcare costs. It is important to understand non-bacterial causes of sepsis so that inappropriate treatment can be minimised, and appropriate treatments can be developed to improve outcomes. In this review, we summarise what is known about viral sepsis, its most common causes, and how the immune responses to severe viral infections can contribute to sepsis. We also discuss strategies to improve our understanding of viral sepsis, and ways we can integrate this new information into effective treatment.


Assuntos
Carga Global da Doença , Hospedeiro Imunocomprometido/imunologia , Viremia/imunologia , Vírus/imunologia , Antibacterianos/uso terapêutico , Antivirais/uso terapêutico , Humanos , Prevalência , Viremia/diagnóstico , Viremia/tratamento farmacológico , Viremia/epidemiologia , Vírus/isolamento & purificação
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