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1.
J Clin Pathol ; 73(1): 30-34, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31315894

RESUMO

AIMS: The purpose of the present study was to elucidate the presence of human herpesvirus 6A (HHV-6A), HHV-6B and HHV-7 in samples of the uterine cervix through detection of viral DNA. We analysed normal tissues, samples with low-grade squamous intraepithelial lesions (LSILs) and high-grade squamous intraepithelial lesions (HSILs). We correlated the presence of HHV-6 and HHV-7 with the finding of human papillomavirus (HPV) in mucosal samples. METHODS: Cervical samples were examined and grouped as follows: group 1 (n=29), normal cytology; group 2 (n=61), samples with LSIL; group 3 (n=35), samples with HSIL. Molecular biology examinations were performed in all samples to detect HHV-6, HHV-7 and HPV DNA and to typify HHV-6 species. RESULTS: Group 1: normal cytology and HPV (-): HHV-6: 6.8% (2/29), HHV-7: 79.3% (23/29); group 2: LSIL and HPV (-): HHV-6: 93.1% (27/29), HHV-7: 96.5% (28/29); LSIL and HPV (+): HHV-6: 0% (0/32), HHV-7: 90.6% (29/32); group 3: HSIL and HPV (-): HHV-6: 20% (2/10), HHV-7: 70% (7/10); HSIL HPV (+): HHV-6: 12% (3/25), HHV-7: 68% (17/25). HHV-6A DNA was not detected in any samples. CONCLUSIONS: (1) Both HHV-6 and HHV-7 infect the mucosal cells of the cervix with higher prevalence of HHV-7. (2) The higher prevalence of HHV-6 in LSIL HPV (-) samples compared with those with normal cytology indicates that it constitutes a possible risk factor for atypia production. (3) The presence of HHV-7 in all samples questions its role in the production of atypia. (4) The finding of HHV-6 and HHV-7 suggests that the cervical mucosa is a possible transmission pathway for these viruses.


Assuntos
Neoplasia Intraepitelial Cervical/diagnóstico , DNA Viral/genética , Herpesvirus Humano 6/genética , Herpesvirus Humano 7/genética , Técnicas de Diagnóstico Molecular , Infecções por Roseolovirus/diagnóstico , Lesões Intraepiteliais Escamosas Cervicais/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adolescente , Adulto , Argentina , Neoplasia Intraepitelial Cervical/genética , Neoplasia Intraepitelial Cervical/virologia , Feminino , Testes de DNA para Papilomavírus Humano , Humanos , Pessoa de Meia-Idade , Papillomaviridae/genética , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/virologia , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Infecções por Roseolovirus/genética , Infecções por Roseolovirus/transmissão , Infecções por Roseolovirus/virologia , Lesões Intraepiteliais Escamosas Cervicais/genética , Lesões Intraepiteliais Escamosas Cervicais/virologia , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/virologia , Adulto Jovem
2.
Klin Lab Diagn ; 64(9): 530-535, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31610104

RESUMO

HHV-7 (Human Herpes virus type 7) is a relatively recently discovered, ubiquitous beta herpes virus. In Russia, the diagnosis of HHV-7 infection is carried out by PCR, which determines the DNA in serum or plasma, if there are clinical indications. Laboratory serological tests for HHV-7 are not performed. Currently, in the scientific literature, information on clinical studies of HHV-7 infection, its epidemiology, and its role in the etiopathogenesis of various diseases is insufficient. This article presents the results of the development of a test kit "ELISA-HHV-7-IgG", designed to detect specific IgG to HHV-7 by enzyme-linked immunosorbent assay (ELISA). Studies of the sensitivity and specificity of the developed test kit, including potential cross-reactive samples positive for other herpesvirus infections, were carried out. In the context of serological diagnostics, we studied samples of the sera of children (n = 167) and old people (n = 238) for the presence of IgG to HHV-7 with confirmation of the results in the indirect immunofluorescence reaction and the immune blotting reaction. The research results are evidence of the possibility of using the developed test kit for serological diagnosis of HHV-7 infection.


Assuntos
Ensaio de Imunoadsorção Enzimática , Herpesvirus Humano 7 , Infecções por Roseolovirus/diagnóstico , Anticorpos Antivirais/sangue , Humanos , Imunoglobulina G/sangue , Federação Russa
3.
Transpl Infect Dis ; 21(3): e13073, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30875143

RESUMO

BACKGROUND: Human leukocyte antigen (HLA) mismatch and the administration of immunosuppressive agents are considered risks for human herpesvirus 6 (HHV-6) reactivation after stem cell transplantation (SCT). However, the incidence of HHV-6 reactivation in HLA-mismatched related SCT remains unknown. METHODS: We monitored plasma HHV-6 DNA loads weekly using real-time quantitative polymerase chain reaction for 5 weeks after SCT and compared serum IL-6 levels in HLA-mismatched SCT groups. RESULTS: Compared with detection in all 11 umbilical cord blood transplantation (CBT) patients (100%), plasma HHV-6 DNA was detected in only 3 of 42 haplo-SCT patients (7.1%) despite the use of methylprednisolone and antithymocyte globulin as graft-vs-host disease prophylaxis and a reduced-intensity conditioning regimen, respectively. Correspondingly, serum IL-6 levels in haplo-SCT patients were significantly lower than those in CBT patients. No HHV-6-associated encephalitis developed in either groups. CONCLUSIONS: Neither HLA disparity nor the use of methylprednisolone and antithymocyte globulin were risk factors for HHV-6 reactivation in our haplo-SCT patients. Rather than increasing risk, the administration of immunosuppressive agents potentially prevented HHV-6 reactivation after haplo-SCT by suppressing IL-6 production.


Assuntos
Corticosteroides/uso terapêutico , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Imunossupressores/uso terapêutico , Infecções por Roseolovirus/diagnóstico , Ativação Viral/efeitos dos fármacos , Adolescente , Adulto , Idoso , Soro Antilinfocitário/uso terapêutico , DNA Viral/sangue , Feminino , Antígenos HLA/genética , Herpesvirus Humano 6/fisiologia , Histocompatibilidade , Humanos , Incidência , Interleucina-6/sangue , Masculino , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Estudos Retrospectivos , Condicionamento Pré-Transplante , Adulto Jovem
4.
Transpl Infect Dis ; 21(1): e13003, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30256500

RESUMO

BACKGROUND: Human herpesvirus 6 (HHV6) is a cause of post-transplant acute limbic encephalitis (PALE). Seizures are associated with this disorder yet no predictive biomarkers have been identified. The objective of this study was to evaluate lab and neurodiagnostic biomarkers in patients with HHV6 associated PALE. METHODS: A retrospective chart review was performed at our institutions between 2000 and 2017. Patients were identified through a clinical database. Inclusion criteria included: age less than 18 years, HHV6 (quantitative real-time PCR or meningoencephalitis panel) tested in CSF and serum. Biomarkers of serum and CSF viral load, EEG, and MRI were reviewed along with clinical data. RESULTS: In total, 11 patients met inclusion criteria. All patients had undergone hematopoietic stem cell transplantation. Five of 11 patients had seizures as part of their clinical course, all being controlled with antiepileptic monotherapy. Seizure semiology was focal-onset in three cases and generalized in two. Neuroimaging was normal in all patients within seven days but six patients developed T2 signal intensities in the temporal lobes on repeat imaging between 14-28 days. The median CSF HHV6 viral load for all patients was 47 300 copies/mL although the median viral load was 2586 copies/mL in patients who had seizure compared to 473 969 copies/mL in those who had not (P = 0.02). Those with seizures tended to be younger (median 6.5 years compared to 11 years, P = 0.27). All patients with seizures had an EEG with 80% demonstrating abnormalities. CONCLUSION: In patients with post-hematopoietic stem cell transplant HHV6 associated PALE, lower CSF viral load may be associated with a higher likelihood to have seizures. This may indicate a primary infection as opposed to secondary reactivation phenomenon.


Assuntos
Encefalite Viral/diagnóstico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Herpesvirus Humano 6/isolamento & purificação , Encefalite Límbica/diagnóstico , Complicações Pós-Operatórias/diagnóstico , Infecções por Roseolovirus/diagnóstico , Convulsões/diagnóstico , Doença Aguda , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Criança , Eletroencefalografia , Encefalite Viral/complicações , Encefalite Viral/virologia , Feminino , Humanos , Encefalite Límbica/sangue , Encefalite Límbica/líquido cefalorraquidiano , Encefalite Límbica/virologia , Imagem por Ressonância Magnética , Masculino , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/líquido cefalorraquidiano , Complicações Pós-Operatórias/virologia , Estudos Retrospectivos , Infecções por Roseolovirus/complicações , Infecções por Roseolovirus/virologia , Convulsões/sangue , Convulsões/líquido cefalorraquidiano , Convulsões/virologia , Carga Viral
5.
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
6.
Transpl Infect Dis ; 21(1): e13024, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30414316

RESUMO

BACKGROUND: Human herpesvirus 6 (HHV-6) encephalitis is a known life-threatening complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, few studies have focused on the occurrence of HHV-6 encephalitis in patients receiving mycophenolate mofetil (MMF) combined with a calcineurin inhibitor as prophylaxis for graft-versus-host disease (GVHD). This study aimed to investigate the impact of MMF administered for GVHD prophylaxis in the occurrence of HHV-6 encephalitis after allo-HSCT and the characteristics of this condition. METHODS AND RESULTS: We retrospectively analyzed 73 patients who underwent allo-HSCT (83 transplants) at our hospital between April 2010 and December 2015. MMF (2-3 g/d) was administered along with a calcineurin inhibitor. Seven patients (8.0%) developed encephalitis due to HHV-6. The median period from allo-HSCT to the onset of HHV-6 encephalitis was 23 days (range, 17-98 days). The cumulative incidence of HHV-6 encephalitis on day 100 after treatment was 12% and 6% in patients who underwent cord blood transplantation (CBT) and non-CBT (ie, bone marrow transplantation and peripheral blood stem cell transplantation), respectively (P = 0.344). Neurological symptoms of encephalitis were more severe in non-CBT cases than those in CBT cases. All patients diagnosed with HHV-6 encephalitis were treated with ganciclovir or foscarnet. None of the enrolled patients died from HHV-6 encephalitis. CONCLUSIONS: Mycophenolate mofetil may have the potential to increase the frequency of severe HHV-6 encephalitis in patients undergoing CBT and non-CBT. Thus, MMF should be administered with caution, and patients should be monitored closely for HHV-6 encephalitis even those who did not undergo CBT.


Assuntos
Encefalite Viral/epidemiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Imunossupressores/efeitos adversos , Ácido Micofenólico/efeitos adversos , Infecções por Roseolovirus/epidemiologia , Adulto , Idoso , Antivirais/uso terapêutico , Inibidores de Calcineurina/efeitos adversos , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Encefalite Viral/diagnóstico , Encefalite Viral/tratamento farmacológico , Encefalite Viral/virologia , Feminino , Doença Enxerto-Hospedeiro/imunologia , Neoplasias Hematológicas/cirurgia , Herpesvirus Humano 6/isolamento & purificação , Humanos , Imunossupressão/efeitos adversos , Imunossupressão/métodos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Infecções por Roseolovirus/diagnóstico , Infecções por Roseolovirus/tratamento farmacológico , Infecções por Roseolovirus/virologia , Índice de Gravidade de Doença , Transplante Homólogo/efeitos adversos , Adulto Jovem
7.
Transpl Infect Dis ; 21(1): e13014, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30346638

RESUMO

BACKGROUND: In recent years, liver transplantation (LT) has become a well-accepted therapeutic modality for children with end-stage liver disease, with transplantation surgery being performed at a younger age. Human herpes virus 6 (HHV-6) infection occurs in most children within the first 2 years of life, therefore, data on primary HHV-6 infection in pediatric liver transplant recipients is scarce. OBJECTIVE: To describe the course of primary HHV-6 infection after pediatric LT. METHODS: Medical files, between the years 2015-2016, of post-LT pediatric patients with suspected primary HHV-6 infection were reviewed. Clinical and laboratory data for enrolled cases were evaluated. Primary infection was defined as DNAemia in children who were seronegative prior to transplantation or seroconversion from negative to positive IgG posttransplantation. RESULTS: Four cases of primary HHV-6 (type B) infection were identified among the 26 children who had undergone LT at our center during the study period. All patients were <1 year old and presented with fever, hepatitis, and elevated inflammatory markers, most (75%) within a short-period posttransplantation. All were initially treated with empiric antibiotics for a suspected bacterial infection and three underwent liver biopsy, one showing signs of rejection. Three were treated with antiviral therapy with a gradual resolution of symptoms. DISCUSSION: Primary HHV-6 should be taken into account in young children shortly after LT, especially when presenting with fever and elevated liver enzymes. Treatment with antiviral therapy should be considered. CONCLUSIONS: In young infants post-LT, a high index of suspicion may promote early detection of HHV-6 primary infection and prevent serious complications.


Assuntos
Febre/diagnóstico , Herpesvirus Humano 6/isolamento & purificação , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias/diagnóstico , Infecções por Roseolovirus/diagnóstico , Adolescente , Anticorpos Antivirais/sangue , Anticorpos Antivirais/isolamento & purificação , Antivirais/uso terapêutico , Biomarcadores/análise , Biópsia , Criança , Pré-Escolar , DNA Viral/sangue , DNA Viral/isolamento & purificação , Feminino , Febre/sangue , Febre/virologia , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/patologia , Herpesvirus Humano 6/genética , Herpesvirus Humano 6/imunologia , Humanos , Lactente , Fígado/patologia , Fígado/virologia , Masculino , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/virologia , Estudos Retrospectivos , Infecções por Roseolovirus/sangue , Infecções por Roseolovirus/tratamento farmacológico , Infecções por Roseolovirus/virologia
8.
J Pediatric Infect Dis Soc ; 7(suppl_2): S75-S78, 2018 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-30590622

RESUMO

Human herpesvirus 6B (HHV-6B) is a ubiquitous pathogen that infects most individuals before the age of three years. HHV-6B reactivates in approximately 40% of transplant recipients where it has been associated with a number of important outcomes, especially in allogeneic transplant recipients. This article will review the epidemiology, clinical manifestations, diagnosis, and treatment of HHV-6B infection.


Assuntos
Encefalite Viral/diagnóstico , Encefalite Viral/tratamento farmacológico , Herpesvirus Humano 6 , Infecções por Roseolovirus/diagnóstico , Infecções por Roseolovirus/tratamento farmacológico , Transplantados , Antivirais/uso terapêutico , Encefalite Viral/epidemiologia , Encefalite Viral/virologia , Foscarnet/uso terapêutico , Ganciclovir/uso terapêutico , Herpesvirus Humano 6/fisiologia , Humanos , Infecções por Roseolovirus/epidemiologia , Ativação Viral
9.
Viruses ; 10(12)2018 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-30572622

RESUMO

Herpesviruses are common components of the human microbiome that become clinically relevant when a competent immunosurveillance is compromised, such as in transplantation. Members of the beta and gamma subfamilies are associated with a wide diversity of pathologies, including end-organ disease and cancer. In this study, we developed a multiplex qPCR technique with high specificity, sensitivity, efficiency and predictability that allowed the simultaneous detection and quantification of beta and gamma human herpesviruses. The technique was tested in a cohort of 34 kidney- or liver-transplanted pediatric patients followed up for up to 12 months post-transplant. Viral load was determined in 495 leukocyte-plasma paired samples collected bi-weekly or monthly. Human herpesvirus (HHV) 7 was the herpesvirus most frequently found in positive samples (39%), followed by Epstein-Barr virus (EBV) (20%). Also, EBV and HHV7 were present in the majority of coinfection episodes (62%). The share of positive samples exclusively detected either in leukocytes or plasma was 85%, suggesting that these herpesviruses tended to take a latent or lytic path in an exclusive manner. Infection by human cytomegalovirus (HCMV) and HHV6, as well as coinfection by EBV/HHV7 and EBV/HHV6/HHV7, were associated with graft rejection (RR = 40.33 (p = 0.0013), 5.60 (p = 0.03), 5.60 (p = 0.03) and 17.64 (p = 0.0003), respectively). The routine monitoring of beta and gamma herpesviruses should be mandatory in transplant centers to implement preventive strategies.


Assuntos
Coinfecção/diagnóstico , Infecções por Vírus Epstein-Barr/diagnóstico , Rejeição de Enxerto/etiologia , Transplante de Órgãos/efeitos adversos , Infecções por Roseolovirus/diagnóstico , Adolescente , Criança , Coinfecção/virologia , Primers do DNA/genética , DNA Viral/sangue , Infecções por Vírus Epstein-Barr/virologia , Feminino , Rejeição de Enxerto/virologia , Herpesvirus Humano 4/genética , Herpesvirus Humano 6/genética , Herpesvirus Humano 7/genética , Humanos , Masculino , Reação em Cadeia da Polimerase Multiplex , Estudos Prospectivos , Infecções por Roseolovirus/virologia , Sensibilidade e Especificidade , Carga Viral
11.
Pediatr Transplant ; 22(7): e13239, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29862613

RESUMO

Differentiation between active and latent viral infection is critical for analysis of HHV-6-associated disease. HHV-6 infection has been associated with several clinical manifestations; however, the precise role of HHV-6 in pediatric LDLT remains unclear. This retrospective cohort study included 33 pediatric patients who received LDLT. All of the recipients were monitored for HHV-6 infection using viral isolation and real-time PCR. HHV-6 infection was observed in 14 of 33 (42.4%) recipients, and HHV-6B infection occurred within 2 weeks after LDLT in 10 of 14 (71.4%) recipients. HHV-6 was isolated from 10 of 33 (30.3%) recipients. Multivariate analysis showed that independent predictors of HHV-6B infection were age (OR 0.975; 95% CI 0.943-0.999; P = .041), PELD (OR 1.091; P = .038), and biliary atresia (OR 16.48; P = .035). The occurrence of unexplained fever was significantly higher in recipients with HHV-6B infection (11/14) compared with uninfected recipients (6/19) (P = .013). Additionally, ALT levels at 8 and 9 weeks after transplantation were significantly higher in the recipients with HHV-6B infection. Younger age, high MELD/PELD score, and biliary atresia as an underlying disease were identified as risk factors for viral infection.


Assuntos
Herpesvirus Humano 6 , Transplante de Fígado , Doadores Vivos , Complicações Pós-Operatórias/diagnóstico , Infecções por Roseolovirus/diagnóstico , Adolescente , Criança , Pré-Escolar , Feminino , Herpesvirus Humano 6/isolamento & purificação , Humanos , Lactente , Modelos Logísticos , Masculino , Complicações Pós-Operatórias/etiologia , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Fatores de Risco , Infecções por Roseolovirus/etiologia
12.
Clin Neurol Neurosurg ; 171: 106-108, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29902636

RESUMO

Central nervous system infection caused by Human Herpesvirus 6 (HHV-6) is well known in immunocompromised; however, data regarding immunocompetent patients is limited to case series. We describe a 29-year-old immunocompetent pregnant woman with meningoencephalitis due to HHV-6 and review current literature. HHV-6 should be kept in mind in patients with meningoencephalitis of unknown etiology.


Assuntos
Ceftriaxona/uso terapêutico , Encefalite Viral/tratamento farmacológico , Herpesvirus Humano 6/patogenicidade , Meningoencefalite/tratamento farmacológico , Infecções por Roseolovirus/tratamento farmacológico , Aciclovir/uso terapêutico , Adulto , Ampicilina/uso terapêutico , Encefalite Viral/diagnóstico , Feminino , Humanos , Imunocompetência/efeitos dos fármacos , Imunocompetência/imunologia , Hospedeiro Imunocomprometido/efeitos dos fármacos , Hospedeiro Imunocomprometido/imunologia , Meningoencefalite/virologia , Gravidez , Infecções por Roseolovirus/diagnóstico
13.
Methods Mol Biol ; 1768: 99-109, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29717439

RESUMO

Droplet digital™ polymerase chain reaction (ddPCR™) is a unique digital PCR technique that allows for absolute quantification of nucleic acid samples. This technique operates on the basis of amplification within water-oil emulsion droplets and can detect very small quantities of target molecules, yielding extremely precise data. Here, we describe in detail a ddPCR procedure for multiplexed detection of two clinically relevant herpesviruses, HHV-6A and HHV-6B.


Assuntos
Coinfecção/diagnóstico , DNA Viral/isolamento & purificação , Herpesvirus Humano 6/isolamento & purificação , Reação em Cadeia da Polimerase Multiplex/métodos , Infecções por Roseolovirus/diagnóstico , Coinfecção/virologia , Herpesvirus Humano 6/genética , Humanos , Reação em Cadeia da Polimerase Multiplex/instrumentação , Infecções por Roseolovirus/virologia
14.
Clin Infect Dis ; 67(7): 1125-1128, 2018 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-29635334

RESUMO

A review of 15 patients who tested positive for human herpesvirus 6 (HHV-6) on the FilmArray Meningitis/Encephalitis panel revealed that the majority were unlikely to have HHV-6 encephalitis. Criteria to assist interpretation of HHV-6 positive results are presented.


Assuntos
Herpesvirus Humano 6/isolamento & purificação , Meningite/virologia , Técnicas de Diagnóstico Molecular/métodos , Infecções por Roseolovirus/virologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Encefalite Viral/virologia , Feminino , Humanos , Hospedeiro Imunocomprometido , Lactente , Recém-Nascido , Masculino , Meningite/diagnóstico , Pessoa de Meia-Idade , Infecções por Roseolovirus/diagnóstico
15.
Pediatr Int ; 60(6): 547-552, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29542206

RESUMO

BACKGROUND: Patients undergoing hematopoietic stem cell transplantation (HSCT) frequently have HHV-6 reactivation typically during the early phase following HSCT. The long-term clinical complications and prognosis, however, remain unclear. METHODS: Between September 2010 and October 2012, whole blood samples from 105 patients collected weekly from prior to 6 weeks after HSCT underwent multiplex polymerase chain reaction (PCR) to screen for viral DNA, followed by real-time PCR for quantitative estimation. In 48 patients, only HHV-6 was detected in at least one sample. In 30 patients, no viral DNA was detected. Long-term clinical records were reviewed in March 2016. All 48 HHV-6-positive patients, and 24 patients in whom no viral DNA detected, were followed up. RESULTS: Median maximum HHV-6 DNA load in the blood of the HHV-6 reactivation group (n = 48) was 11 800 copies/µg peripheral blood leukocyte DNA (range, 52-310 000 000). Hemophagocytic syndrome (HPS) was diagnosed in two subjects with HHV-6 reactivation. Acute graft-versus-host disease (GVHD) developed more frequently in patients with HHV-6 reactivation than in patients without viral reactivation (P = 0.002), but there was no difference in incidence of chronic GVHD. There was no difference in engraftment of neutrophils and platelets between groups. There was also no difference in overall survival between groups. Onset of HPS, however, was associated with lower overall survival (P = 0.009). CONCLUSIONS: Human herpesvirus 6 reactivation was associated with acute GVHD, but not with chronic GVHD, engraftment or overall survival. Onset of HPS, however, predicts lower overall survival.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Herpesvirus Humano 6 , Infecções por Roseolovirus/etiologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Infecções por Roseolovirus/diagnóstico , Infecções por Roseolovirus/imunologia , Taxa de Sobrevida , Adulto Jovem
17.
J Neurovirol ; 24(3): 333-338, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29536269

RESUMO

Neurological manifestations associated with HHV-7 have been described in primary infection in children, and very occasionally in immunocompromised adult patients. However, the role of HHV-7 reactivation as a cause of central nervous system (CNS) diseases in immunocompetent adults has not yet been defined. We retrospectively analyzed clinical and microbiological features of adults with neurological symptoms who underwent lumbar puncture and a multiplex polymerase chain reaction (PCR) for herpesviruses (HHV-1-8) and enteroviruses performed in cerebrospinal fluid (CSF), during a 4-year period. A total of 251 subjects were included. Mean age was 55 years, ranging 15-89. Globally, HHV-7 DNA was detected in CSF in 14 patients (5.6%). It was detected in 1 of 36 patients with microbiologically confirmed CNS infections, and in 7 of 172 patients with diagnoses of non-infectious neurological disorders (Specificity 0.96, 95% confidence interval 0.93-0.99). Additionally, HHV-7 DNA was detected in 6 of 21 patients (28.6%) with probable CNS infections (compatible clinical syndrome and CSF changes) in the absence of other causative agent: four meningitis, one myelitis, and one encephalitis. Treatment with foscarnet was effective in achieving improvement of symptoms and clearance of HHV-7 DNA in CSF in the cases of encephalitis and myelitis, while ganciclovir was ineffective in the case of encephalitis. Our results show that HHV-7 reactivation may cause CNS disease in immunocompetent adults and that detection of HHV-7 DNA in CSF as a false-positive result or as asymptomatic reactivation in adult patients with neurological diseases is uncommon. Foscarnet seems the first-line treatment for HHV-7 CNS disease.


Assuntos
DNA Viral/genética , Encefalite Viral/diagnóstico , Herpesvirus Humano 7/genética , Meningite Viral/diagnóstico , Mielite/diagnóstico , Infecções por Roseolovirus/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/uso terapêutico , DNA Viral/líquido cefalorraquidiano , DNA Viral/isolamento & purificação , Encefalite Viral/líquido cefalorraquidiano , Encefalite Viral/tratamento farmacológico , Encefalite Viral/virologia , Feminino , Foscarnet/uso terapêutico , Ganciclovir/uso terapêutico , Herpesvirus Humano 7/isolamento & purificação , Humanos , Masculino , Meningite Viral/líquido cefalorraquidiano , Meningite Viral/tratamento farmacológico , Meningite Viral/virologia , Pessoa de Meia-Idade , Mielite/líquido cefalorraquidiano , Mielite/tratamento farmacológico , Mielite/virologia , Estudos Retrospectivos , Infecções por Roseolovirus/líquido cefalorraquidiano , Infecções por Roseolovirus/tratamento farmacológico , Infecções por Roseolovirus/virologia , Punção Espinal/métodos
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