Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 5.313
Filtrar
1.
Artigo em Inglês | MEDLINE | ID: mdl-33656138

RESUMO

Congenital cytomegalovirus infection causes lethal diseases with neurological, visual, auditory and systemic injuries, including the hemophagocytic syndrome. Hemophagocytic lymphohistiocytosis (HLH) can be caused by primary hereditary immunological defects, as well as several infectious triggering factors, such as viruses, bacteria and fungus, among them the cytomegalovirus (CMV). Here we present the case report of a male newborn male, delivered by cesarean at term (gestation age of 39 weeks), weighing 3,250 g, with suffusion skin lesions spread throughout the body, anemia, generalized edema, hepatosplenomegaly, thrombocytopenia associated with grunts and difficulty breathing, treated with ganciclovir after receiving the diagnosis of congenital CMV infection. After a few days of hospitalization, the patient presented with high fever, persistent hepatosplenomegaly and pancytopenia, in addition to elevated ferritin and triglycerides, receiving the diagnosis of HLH treated with immunosuppressive therapy, corticosteroids and intravenous human immunoglobulin. The present case report highlights the importance for health professionals to carry out the investigation of congenital diseases, especially in developing countries, as well as their complications, such as HLH.


Assuntos
Infecções por Citomegalovirus/congênito , Citomegalovirus/isolamento & purificação , Linfo-Histiocitose Hemofagocítica/diagnóstico , Administração Intravenosa , Corticosteroides/administração & dosagem , Cesárea , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/tratamento farmacológico , Feminino , Humanos , Imunoglobulinas/administração & dosagem , Lactente , Recém-Nascido , Linfo-Histiocitose Hemofagocítica/complicações , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Masculino , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Resultado do Tratamento
2.
Methods Mol Biol ; 2244: 39-50, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33555581

RESUMO

Primary human diploid fibroblasts are used routinely to study host/pathogen interactions of human cytomegalovirus (HCMV). Fibroblasts' ease of culture and tremendous permissiveness for infection allow the study of all facets of infection, an abbreviated list of which includes ligand-receptor interactions, activation of cell signaling responses, and dysregulation of the cell cycle and DNA repair processes. Another advantage to fibroblasts' permissiveness for HCMV is the capability to grow high titer stocks of virus in them. This chapter will discuss the production of viral stocks of HCMV in primary human fibroblasts, commencing with culturing and infection of cells and continuing through harvest, titration (determining the infectious capacity of a particular virus preparation), and storage of viral stocks for use in downstream experiments.


Assuntos
Técnicas de Cultura de Células/métodos , Citomegalovirus/genética , Fibroblastos/virologia , Linhagem Celular , Células Cultivadas , Citomegalovirus/classificação , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/virologia , Diploide , Fibroblastos/citologia , Humanos , Modelos Biológicos , Replicação Viral
3.
Methods Mol Biol ; 2244: 19-38, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33555580

RESUMO

Human cytomegalovirus is routinely isolated by inoculating fibroblast cultures with clinical specimens suspected of harboring HCMV and then monitoring the cultures for cytopathic effects characteristic of this virus. Initially, such clinical isolates are usually strictly cell-associated, but continued propagation in cell culture increases the capacity of an HCMV isolate to release cell-free infectious progeny. Once cell-free infection is possible, genetically homogenous virus strains can be purified by limiting dilution infections. HCMV strains can differ greatly with regard to the titers that can be achieved, the tropism for certain cell types, and the degree to which nonessential genes have been lost during propagation. As there is no ideal HCMV strain for all purposes, the choice of the most appropriate strain depends on the requirements of the particular experiment or project. In this chapter, we provide information that can serve as a basis for deciding which strain may be the most appropriate for a given experiment.


Assuntos
Técnicas de Cultura de Células/métodos , Citomegalovirus/genética , Tropismo Viral/genética , Citomegalovirus/classificação , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/virologia , Fibroblastos/citologia , Humanos , Projetos de Pesquisa , Tropismo Viral/fisiologia , Replicação Viral
4.
BMJ Case Rep ; 14(2)2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33608341

RESUMO

A 61-year-old male patient presented with decreased vision and recurrent redness in his right eye since the past 4 years. He had been diagnosed elsewhere as HLA-B27 positive anterior uveitis and was on oral methotrexate and topical corticosteroids for recurrent disease. He was on maximal medical therapy for glaucoma. Examination showed prominent inferior corneal oedema with pigmented keratic precipitates and elevated intraocular pressure. He underwent combined trabeculectomy with mitomycin C and cataract surgery. The aqueous sample tested positive for cytomegalovirus. He responded well to oral valganciclovir with resolution of uveitis, the intraocular pressure was well controlled and the corneal oedema resolved completely.


Assuntos
Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/diagnóstico , Erros de Diagnóstico , Epitélio Posterior/virologia , Glaucoma/complicações , Uveíte/complicações , Antivirais/uso terapêutico , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/tratamento farmacológico , Epitélio Posterior/efeitos dos fármacos , Epitélio Posterior/cirurgia , Antígeno HLA-B27 , Humanos , Masculino , Pessoa de Meia-Idade , Uveíte/diagnóstico , Uveíte/cirurgia , Valganciclovir/uso terapêutico
5.
Zhonghua Liu Xing Bing Xue Za Zhi ; 42(2): 316-320, 2021 Feb 10.
Artigo em Chinês | MEDLINE | ID: mdl-33626622

RESUMO

Objective: To study the prevalence and correlates of plasma cytomegalovirus (CMV) viremia among newly reported antiretroviral therapy (ART)-naive HIV/AIDS patients in Taizhou during 2017-2018. Methods: CMV DNA was measured in plasma specimens of newly reported ART-naive HIV/AIDS patients by quantitative PCR. Both univariable and multivariable logistic regression analyses were carried out to evaluate CMV viremia correlations among the individuals. Results: Of 612 HIV/AIDS patients, 480 (78.4%) were male, 125 (20.4%) were over 60 years old, 177 (28.9%) were infected via homosexual transmission, and 430 (70.3%) via heterosexual transmission. The prevalence of CMV viremia among HIV/AIDS patients was 13.4% (82/612). Multivariable logistic regression analysis showed that the risk of CMV viremia in CD4+ lymphocyte cells counts (CD4+) ≤200 cells/µl group was higher than CD4 counts >500 cells/µl (OR=5.10, 95%CI:1.74-14.96, P=0.003); The median CMV DNA level (log10) of 82 viremic patients was 1.57 (P25,P75:1.04,2.13); Viremic patients with CD4 counts ≤200 cells/µl had the highest CMV viral load (P<0.01). Conclusions: Among ART-naive HIV/AIDS patients, the prevalence of CMV viremia was significantly associated with immunodeficiency status. Further research is needed to evaluate the association between CMV viremia and the course of HIV infection.


Assuntos
Infecções por Citomegalovirus , Citomegalovirus , Infecções por HIV , Viremia , China/epidemiologia , Cidades/epidemiologia , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/epidemiologia , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Viremia/epidemiologia
6.
Viruses ; 13(1)2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33419104

RESUMO

Hearing loss, one of the most prevalent chronic health conditions, affects around half a billion people worldwide, including 34 million children. The World Health Organization estimates that the prevalence of disabling hearing loss will increase to over 900 million people by 2050. Many cases of congenital hearing loss are triggered by viral infections during different stages of pregnancy. However, the molecular mechanisms by which viruses induce hearing loss are not sufficiently explored, especially cases that are of embryonic origins. The present review first describes the cellular and molecular characteristics of the auditory system development at early stages of embryogenesis. These developmental hallmarks, which initiate upon axial specification of the otic placode as the primary root of the inner ear morphogenesis, involve the stage-specific regulation of several molecules and pathways, such as retinoic acid signaling, Sonic hedgehog, and Wnt. Different RNA and DNA viruses contributing to congenital and acquired hearing loss are then discussed in terms of their potential effects on the expression of molecules that control the formation of the auditory and vestibular compartments following otic vesicle differentiation. Among these viruses, cytomegalovirus and herpes simplex virus appear to have the most effect upon initial molecular determinants of inner ear development. Moreover, of the molecules governing the inner ear development at initial stages, SOX2, FGFR3, and CDKN1B are more affected by viruses causing either congenital or acquired hearing loss. Abnormalities in the function or expression of these molecules influence processes like cochlear development and production of inner ear hair and supporting cells. Nevertheless, because most of such virus-host interactions were studied in unrelated tissues, further validations are needed to confirm whether these viruses can mediate the same effects in physiologically relevant models simulating otic vesicle specification and growth.


Assuntos
Citomegalovirus/isolamento & purificação , Orelha Interna/embriologia , Orelha Interna/virologia , Perda Auditiva/virologia , Simplexvirus/isolamento & purificação , Animais , Diferenciação Celular , Inibidor de Quinase Dependente de Ciclina p27/genética , Citomegalovirus/patogenicidade , Perda Auditiva/congênito , Humanos , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética , Fatores de Transcrição SOXB1/genética , Transdução de Sinais , Simplexvirus/patogenicidade
7.
BMC Infect Dis ; 20(1): 828, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33176707

RESUMO

BACKGROUND: Severe and disseminated non-tuberculous mycobacterial (NTM) infections are frequently linked to a genetic predisposition but acquired defects of the interferon gamma (IFNγ) / interleukin 12 (IL-12) pathway need to be considered in adult patients with persistent or recurrent infections. Neutralizing anti-IFNγ autoantibodies disrupting IFNγ signalling have been identified as the cause of a severe and unique acquired immunodeficiency syndrome with increased susceptibility to NTM and other intracellular pathogens. CASE PRESENTATION: An adult Asian female with a previous history of recurrent NTM infections presented with persistent diarrhea, abdominal pain, night sweats and weight loss. Severe colitis due to a simultaneous infection with cytomegalovirus (CMV) and Salmonella typhimurium was diagnosed, with both pathogens also detectable in blood samples. Imaging studies further revealed thoracic as well as abdominal lymphadenopathy and a disseminated Mycobacterium intracellulare infection was diagnosed after a lymph node biopsy. Further diagnostics revealed the presence of high-titer neutralizing anti-IFNγ autoantibodies, allowing for the diagnosis of adult-onset immunodeficiency with anti-IFNγ autoantibodies (AIIA). CONCLUSIONS: We here present a severe case of acquired immunodeficiency with anti-IFNγ autoantibodies with simultaneous, disseminated infections with both viral and microbial pathogens. The case illustrates how the diagnosis can cause considerable difficulties and is often delayed due to unusual presentations. Histological studies in our patient give further insight into the pathophysiological significance of impaired IFNγ signalling. B-cell-depleting therapy with rituximab offers a targeted treatment approach in AIIA.


Assuntos
Autoanticorpos/imunologia , Infecções por Citomegalovirus/diagnóstico , Citomegalovirus/isolamento & purificação , Síndromes de Imunodeficiência/diagnóstico , Interferon gama/imunologia , Linfadenopatia/diagnóstico , Complexo Mycobacterium avium/isolamento & purificação , Infecção por Mycobacterium avium-intracellulare/diagnóstico , Infecções por Salmonella/diagnóstico , Salmonella typhimurium/isolamento & purificação , Adulto , Antibacterianos/uso terapêutico , Antivirais/uso terapêutico , Autoanticorpos/sangue , Biópsia , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/virologia , Diagnóstico Tardio , Feminino , Seguimentos , Humanos , Síndromes de Imunodeficiência/complicações , Síndromes de Imunodeficiência/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Interferon gama/metabolismo , Interleucina-12/metabolismo , Linfadenopatia/complicações , Linfadenopatia/tratamento farmacológico , Linfadenopatia/patologia , Infecção por Mycobacterium avium-intracellulare/complicações , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico , Infecção por Mycobacterium avium-intracellulare/microbiologia , Infecções por Salmonella/complicações , Infecções por Salmonella/tratamento farmacológico , Infecções por Salmonella/microbiologia , Resultado do Tratamento
8.
Z Gastroenterol ; 58(9): 868-871, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32947632

RESUMO

BACKGROUND: Concurrent cytomegalovirus (CMV) in inflammatory bowel disease (IBD)-related colitis is an important scenario associated with high rates of colectomy and other morbidity. Due to the low incidence of CMV, testing of all patients is associated with an unacceptably high consumption of resources and delay in treatment. Therefore, several predictive scores have been developed to identify patients at risk for a CMV infection. METHODS: We performed a retrospective single center study in a German University hospital including all IBD patients with available data on CMV-PCR analysis in whole blood between 2010 and 2018 and evaluated 2 prognostic scores for CMV infection for their diagnostic accuracy. RESULTS: In the study, 907 patients with IBD and CMV-PCR were identified. Of them, 21 patients (2.3 %) had a positive CMV-PCR (≥ 1000 copies/mL), 14 of them in ulcerative colitis and 7 in Crohn's disease. The Berlin Score identified 667 patients (73.1 %) as potentially CMV-positive, resulting in a positive predictive value of 2.5 % and a negative predictive value of 98.3 %. In contrast, the Münster Score identified 60 patients as potentially CMV-positive, resulting in a PPV of 20 % and an NPV of 99.4 %. CONCLUSIONS: Scoring systems can help to identify patients at risk for a CMV infection and minimize resource consumption and delay in treatment. Due to low incidence, a 2-step-algorithm, consisting of the Münster Score followed by a CMV-PCR if the score indicates a CMV infection, is preferable.


Assuntos
Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/diagnóstico , Citomegalovirus/isolamento & purificação , Doenças Inflamatórias Intestinais/complicações , Infecções Oportunistas/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Colite Ulcerativa , Citomegalovirus/genética , Infecções por Citomegalovirus/sangue , DNA Viral/análise , Feminino , Humanos , Doenças Inflamatórias Intestinais/patologia , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/sangue , Infecções Oportunistas/patologia , Reação em Cadeia da Polimerase , Valor Preditivo dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade
9.
Artigo em Inglês | MEDLINE | ID: mdl-32756824

RESUMO

Human cytomegalovirus (HCMV) infections remain a neglected public health issue. The aim of the present study was to evaluate the frequency of HCMV congenital infections in newborns up to 1 month in the Sao Paulo State, from 2010 to 2018. The molecular characterization of HCMV-positive samples was also undertaken. Urine samples from 275 potential congenital HCMV-infected patients were tested by real-time Polymerase Chain Reaction (qPCR). HCMV-positive samples were amplified by conventional PCR targeting the UL89 gene, sequenced and searched for mutations. A total of 32 (11.6%) positive-HCMV cases were detected (mean Ct 30.59); mean and median age of 10.3 and 6 days old, respectively. Children aged between 0-3 weeks had higher HCMV detection rates (84.4%; 27/32). UL89 gene was successfully sequenced in two samples, both classified as the human betaherpesvirus 5. No described resistance-associated mutations were identified. A routine screening in newborns coupled with the genetic characterization of key viral genes is vital to decrease sequels associated with congenital HCMV infections.


Assuntos
Infecções por Citomegalovirus/epidemiologia , Citomegalovirus/isolamento & purificação , DNA Viral , Brasil/epidemiologia , Criança , Citomegalovirus/genética , Infecções por Citomegalovirus/diagnóstico , Humanos , Lactente , Recém-Nascido , Programas de Rastreamento , Reação em Cadeia da Polimerase em Tempo Real
11.
Virology ; 548: 168-173, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32838938

RESUMO

Clinical significance of the cytomegalovirus (CMV) genotypes in patients undergoing allogeneic hematopoietic stem cell transplant (HSCT) has been evaluated mostly in adults. The studies of diverse CMV glycoprotein B (gB) and N (gN) genotype variants in transplanted children and adolescents are lacking. We analyzed the investment of gB and gN genotype variants in the HSCTed children and their relation to clinical complications and disease outcome. The cohort included forty two pediatric recipients of the HSCT. Patients positive for CMV DNAemia (24/42, 57.1%) were genotyped. The gB4 and gN1 genotype variants predominated and were evidenced in 7/18 (38.9%) and 9/19 (47.4%) patients, respectively. The graft-versus-host disease (GvHD) predominated in children with viremia (p < 0.05). Frequencies of the gB and gN genotypes contrasted those reported in recent studies. The GvHD scaled strongly with CMV reactivation whereas viral loads were uncorrelated to medical complications and treatment outcomes.


Assuntos
Infecções por Citomegalovirus/virologia , Citomegalovirus/isolamento & purificação , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Complicações Pós-Operatórias/virologia , Proteínas do Envelope Viral/genética , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Citomegalovirus/classificação , Citomegalovirus/genética , Citomegalovirus/metabolismo , Feminino , Genótipo , Doença Enxerto-Hospedeiro/virologia , Humanos , Masculino , Transplante Homólogo/efeitos adversos , Proteínas do Envelope Viral/metabolismo , Adulto Jovem
12.
BMC Infect Dis ; 20(1): 470, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32615937

RESUMO

BACKGROUND: Strongyloidiasis is a gastrointestinal parasitic infection caused by percutaneous infection with Strongyloides stercoralis. Digestive symptoms such as diarrhea and abdominal pain are the main manifestation, but serious infections such as septicemia, purulent meningitis, and bacterial pneumonia may occur in individuals harboring human T-lymphotropic virus type 1 (HTLV-1) or who are immunocompromised. Although coinfection with Strongyloides stercoralis and HTLV-1 can lead to chronic strongyloidiasis and a disseminated form of the disease, there is a high rate of response to the anthelmintic ivermectin. CASE PRESENTATION: We report a case of strongyloidiasis infection syndrome that was difficult to differentiate from immune reconstitution inflammatory syndrome (IRIS) for various reasons. The patient had been treated with the corticosteroids tacrolimus (Tac) and mycophenolate mofetil (MMF) for systemic lupus erythematosus (SLE) with lupus nephritis and pancytopenia. When the steroid was reduced, she developed cytomegalovirus (CMV) enteritis, and her respiratory status rapidly deteriorated immediately after the withdrawal of Tac and MMF. It was difficult to distinguish immune reconstitution inflammatory syndrome from strongyloidiasis infection syndrome because stool cultures were negative and eosinophils were not increased. Bronchoscopy revealed viable Strongyloides, leading to a diagnosis of strongyloidiasis infection syndrome, but the patient died despite treatment. CONCLUSIONS: Both corticosteroid therapy and HTLV-1 infection can be associated with a decrease of eosinophils, despite the presence of parasitic infection. In conclusion, even if multiple culture tests are negative, the risk of parasitic infection should be assessed in patients receiving immunosuppressants and steroids even in non-endemic areas.


Assuntos
Infecções por Citomegalovirus/complicações , Citomegalovirus/imunologia , Infecções por HTLV-I/complicações , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Imunossupressão/efeitos adversos , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Strongyloides stercoralis/isolamento & purificação , Estrongiloidíase/complicações , Idoso , Animais , Anti-Helmínticos/uso terapêutico , Antivirais/uso terapêutico , Coinfecção/tratamento farmacológico , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/virologia , Evolução Fatal , Feminino , Ganciclovir/uso terapêutico , Infecções por HTLV-I/diagnóstico , Infecções por HTLV-I/tratamento farmacológico , Infecções por HTLV-I/virologia , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Ivermectina/uso terapêutico , Estrongiloidíase/diagnóstico , Estrongiloidíase/tratamento farmacológico , Estrongiloidíase/parasitologia , Síndrome
13.
Cancer Invest ; 38(7): 394-405, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32643440

RESUMO

The study investigated the human cytomegalovirus (HCMV) and human papillomavirus (HPV) in gliomas. A retrospective study was conducted on 112 samples. HCMV was investigated by PCR, in situ hybridization (ISH) and immunohistochemistry. HPV was tested by PCR and DNA ISH. HCMV was identified in 60 gliomas, including 55 GBM. However, RNA ISH and immunohistochemistry failed to detect HCMV positivity. HPV was identified in 44 GBM. No significant relationship was identified between HCMV and HPV and tumour characteristics (p > 0.05). Our findings support the HCMV and HPV presence in gliomas. Further assays are required to more explore the potential efficient antiviral management.


Assuntos
Neoplasias Encefálicas/virologia , Citomegalovirus/isolamento & purificação , Glioma/virologia , Papillomaviridae/isolamento & purificação , Adulto , Idoso , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Citomegalovirus/genética , Infecções por Citomegalovirus/virologia , Feminino , Glioma/mortalidade , Glioma/patologia , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Papillomaviridae/genética , Infecções por Papillomavirus/virologia , Reação em Cadeia da Polimerase , Estudos Retrospectivos , Tunísia , Adulto Jovem
14.
Nat Commun ; 11(1): 3548, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32669541

RESUMO

Congenital CMV infection (cCMVi) affects 0.5-1% of all live births worldwide, making it the leading cause of sensorineural hearing loss (SNHL) in childhood. The majority of infants with cCMVi have normal hearing at birth, but are at risk of developing late-onset SNHL. Currently, we lack reliable biomarkers to predict the development of SNHL in these infants. Here, we evaluate blood transcriptional profiles in 80 infants with cCMVi (49 symptomatic, 31 asymptomatic), enrolled in the first 3 weeks of life, and followed for 3 years to assess emergence of late-onset SNHL. The biosignatures of symptomatic and asymptomatic cCMVi are indistinguishable, suggesting that immune responses of infants with asymptomatic and symptomatic cCMVi are not different. Random forest analyses of initial samples in infants with cCMVi, irrespective of their clinical classification, identify a 16-gene classifier signature associated with the development of SNHL with 92% accuracy, suggesting its potential value as a biomarker.


Assuntos
Infecções por Citomegalovirus/sangue , Citomegalovirus/imunologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/imunologia , Perda Auditiva Neurossensorial/epidemiologia , Infecções Assintomáticas , Biomarcadores/sangue , Estudos de Casos e Controles , Pré-Escolar , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/virologia , Feminino , Perda Auditiva Neurossensorial/genética , Perda Auditiva Neurossensorial/imunologia , Perda Auditiva Neurossensorial/virologia , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Estudos Prospectivos , Medição de Risco/métodos , Transcriptoma/genética
15.
Trop Doct ; 50(3): 282-284, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32437297

RESUMO

We retrospectively analysed the records of nine infants with polymerase chain reaction proven congenital cytomegalovirus (CMV) infection, of which 66% were born preterm. Microcephaly was a universal finding, followed by hepatosplenomegaly in 89%, while chorioretinitis was seen in only 44% cases. The mean age at diagnosis was 3.5 months. Neuroimaging was abnormal in 78%, with ventriculomegaly being the most common finding followed by T2/FLAIR white matter abnormalities, periventricular cysts and intracranial haemorrhage.


Assuntos
Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/patologia , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/epidemiologia , Feminino , Humanos , Índia/epidemiologia , Lactente , Recém-Nascido , Imagem por Ressonância Magnética , Masculino , Neuroimagem , Estudos Retrospectivos , Centros de Atenção Terciária
16.
J Infect Chemother ; 26(8): 790-794, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32273174

RESUMO

OBJECTIVES: This prospective cohort study aimed to evaluate the efficacy of the universal neonatal urine screening, followed by diagnosis, workup and antiviral therapy for symptomatic congenital cytomegalovirus (CMV) infection to reduce neurological impairments and sequelae. METHODS: Neonates born in three facilities underwent the universal urine screening of PCR analyses for CMV-DNA. Neonates with symptomatic congenital CMV infection (cCMV) received oral valganciclovir (VGCV) of 32 mg/kg/day for six weeks or six months, and were evaluated for neurological outcomes including developmental quotient (DQ) and hearing function at around 18 months of corrected age. RESULTS: cCMV was diagnosed in 56 (0.48%) of 11,736 neonates, consisting of 23 neonates with symptomatic and 33 with asymptomatic cCMV. The incidence of cCMV in the general perinatal medical center (0.69%) was higher than that in the primary maternity hospital (0.23%, p<0.01%). Twenty of the 23 infants with symptomatic cCMV received VGCV therapy, and 19 underwent neurological assessment. Eight neonates (42%) had severe sequelae of DQ < 70, bilateral hearing dysfunction, and/or epilepsy. Four neonates (21%) had mild sequelae of DQ 70-79 or unilateral hearing dysfunction only, and seven (37%) showed normal development without any impairment. CONCLUSIONS: This study on a large scale demonstrated that a series of universal neonatal urine screening, diagnosis, workup, and VGCV therapy for neonates with symptomatic cCMV may decrease neurological impairments, because 58% of the treated infants had normal development or mild sequelae. The universal urine screening likely identifies subclinical symptomatic cCMV. Mothers with fetuses of cCMV seem to be selectively transferred to perinatal medical centers before deliveries.


Assuntos
Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/urina , Citomegalovirus/isolamento & purificação , Triagem Neonatal/métodos , Antivirais/administração & dosagem , Estudos de Coortes , Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/tratamento farmacológico , DNA Viral/urina , Humanos , Recém-Nascido , Estudos Prospectivos , Resultado do Tratamento , Urina/virologia , Valganciclovir/administração & dosagem
17.
Nat Biomed Eng ; 4(6): 601-609, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32284553

RESUMO

In organ transplantation, infection and rejection are major causes of graft loss. They are linked by the net state of immunosuppression. To diagnose and treat these conditions earlier, and to improve long-term patient outcomes, refined strategies for the monitoring of patients after graft transplantation are needed. Here, we show that a fast and inexpensive assay based on CRISPR-Cas13 accurately detects BK polyomavirus DNA and cytomegalovirus DNA from patient-derived blood and urine samples, as well as CXCL9 messenger RNA (a marker of graft rejection) at elevated levels in urine samples from patients experiencing acute kidney transplant rejection. The assay, which we adapted for lateral-flow readout, enables-via simple visualization-the post-transplantation monitoring of common opportunistic viral infections and of graft rejection, and should facilitate point-of-care post-transplantation monitoring.


Assuntos
Sistemas CRISPR-Cas , Rejeição de Enxerto/virologia , Infecções Oportunistas/diagnóstico , Patologia Molecular/métodos , Biomarcadores/sangue , Biomarcadores/urina , Quimiocina CXCL9/sangue , Quimiocina CXCL9/urina , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Citomegalovirus/genética , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/diagnóstico , DNA Viral/sangue , DNA Viral/genética , DNA Viral/urina , Humanos , Rim , Nefropatias/virologia , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Testes Imediatos , Polyomavirus/genética , Polyomavirus/isolamento & purificação , Infecções por Polyomavirus/diagnóstico , Complicações Pós-Operatórias/diagnóstico , RNA Mensageiro , Infecções Tumorais por Vírus/diagnóstico
18.
JAMA ; 323(14): 1378-1387, 2020 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-32286644

RESUMO

Importance: Despite the use of a cytomegalovirus (CMV) prevention strategy of antiviral prophylaxis for high-risk CMV-seronegative liver transplant recipients with seropositive donors, high rates of delayed-onset postprophylaxis CMV disease occur. An alternate approach, preemptive therapy (initiation of antiviral therapy for early asymptomatic CMV viremia detected by surveillance testing), has not previously been directly compared with antiviral prophylaxis in these patients. Objective: To compare preemptive therapy with antiviral prophylaxis in CMV-seronegative liver transplant recipients with seropositive donors for the prevention of CMV disease. Design, Setting, and Participants: Randomized clinical trial of preemptive therapy vs antiviral prophylaxis in 205 CMV-seronegative liver transplant recipients with seropositive donors aged older than 18 years. The trial was conducted at 6 academic transplant centers in the United States between October 2012 and June 2017, with last follow-up in June 2018. Interventions: Patients were randomized 1:1 to receive either preemptive therapy (valganciclovir, 900 mg, twice daily until 2 consecutive negative tests a week apart) for viremia detected by weekly plasma CMV polymerase chain reaction for 100 days (n = 100) or valganciclovir, 900 mg, daily for 100 days as antiviral prophylaxis (n = 105). Main Outcomes and Measures: The primary outcome was incidence of CMV disease by 12 months, defined as CMV syndrome (CMV viremia and clinical or laboratory findings) or end-organ disease. Secondary outcomes included acute allograft rejection, opportunistic infections, graft and patient survival, and neutropenia. Results: Among 205 patients who were randomized (mean age, 55 years; 62 women [30%]), all 205 (100%) completed the trial. The incidence of CMV disease was significantly lower with preemptive therapy than antiviral prophylaxis (9% [9/100] vs 19% [20/105]; difference, 10% [95% CI, 0.5% to 19.6%]; P = .04]). The incidence of allograft rejection (28% vs 25%; difference, 3% [95% CI, -9% to 15%]), opportunistic infections (25% vs 27%; difference, 2% [95% CI, -14% to 10%]), graft loss (2% vs 2%; difference, <1% [95% CI, -4% to 4%]), and neutropenia (13% vs 10%; difference, 3% [95% CI, -5% to 12%]) did not differ significantly for the preemptive therapy vs antiviral prophylaxis group, respectively. All-cause mortality at last follow-up was 15% in the preemptive therapy vs 19% in the antiviral prophylaxis group (difference, 4% [95% CI, -14% to 6%]; P = .46). Conclusions and Relevance: Among CMV-seronegative liver transplant recipients with seropositive donors, the use of preemptive therapy, compared with antiviral prophylaxis, resulted in a lower incidence of CMV disease over 12 months. Further research is needed to replicate these findings and assess long-term outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT01552369.


Assuntos
Antibioticoprofilaxia , Antivirais/uso terapêutico , Infecções por Citomegalovirus/prevenção & controle , Citomegalovirus/isolamento & purificação , Transplante de Fígado , Valganciclovir/uso terapêutico , Viremia/tratamento farmacológico , Adulto , Idoso , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/transmissão , Infecções por Citomegalovirus/virologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Doadores de Tecidos , Carga Viral , Viremia/diagnóstico
19.
Arch Virol ; 165(5): 1099-1107, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32152788

RESUMO

To determine the status of human cytomegalovirus (HCMV) infection in human milk in China, a total of 510 human milk samples obtained from three provinces, including 211 donor human milk samples from human milk banks and 299 milk samples obtained from the mothers of premature infants, were tested to detect HCMV DNA. Overall, 46.4% of the donated milk samples and 59.2% of the samples obtained from mothers of premature infants were positive for HCMV DNA. The concentration of HCMV DNA was approximately 103 -104 copies/ml in the HCMV-DNA-positive human milk samples. Based on the nucleotide sequence of a 299- to 305-bp fragment of the glycoprotein B (gB) gene, three HCMV genotypes (gB1, gB2 and gB3) were identified in human milk samples. Mixed infection with genotypes gB1 and gB3 was also found in four milk samples from mothers. Genotype gB1 was the predominant genotype in the HCMV-DNA-positive human milk samples, and it could be subdivided into three lineages. There were also some characteristic nucleotides and amino acids in the three HCMV genotypes, which were helpful for distinguishing the genotypes. This is the first study to clarify the HCMV infection status and genetic characteristics of human milk obtained from banks in China, which will be helpful in preventing postnatal HCMV infections and ensuring the safety of human milk banks.


Assuntos
Citomegalovirus/classificação , Citomegalovirus/isolamento & purificação , Genótipo , Bancos de Leite , Leite Humano/virologia , China , Citomegalovirus/genética , DNA Viral/análise , DNA Viral/genética , Humanos , Prevalência , Análise de Sequência de DNA , Proteínas do Envelope Viral/genética
20.
Epidemiol Infect ; 148: e34, 2020 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-32070447

RESUMO

Cytomegalovirus (CMV) enters latency after primary infection and can reactivate periodically with virus excreted in body fluids which can be called shedding. CMV shedding during the early stage of pregnancy is associated with adverse pregnancy outcome. The shedding pattern in healthy seropositive women who plan to have babies has not been well characterised. Vaginal swabs, urine and blood were collected from 1262 CMV IgG-positive women who intended to have babies and tested for CMV DNA by fluorogenic quantitative PCR method. Serum IgM was also detected. The association between sociodemographic characteristics and CMV shedding prevalence was analysed. Among 1262 seropositive women, 12.8% (161/1262) were detected CMV DNA positive in at least one body fluid. CMV DNA was more frequently detected in vaginal secretion (10.5%) than in urine (3.2%) and blood (0.6%) also with higher viral loads (P < 0.00). CMV shedding was more likely detected in IgM-positive women than IgM-negative women (29.5% (13/44) vs. 12.2% (148/1218); OR 3.03, 95% CI 1.55-5.93; P = 0.001). CMV shedding in vaginal secretion was highly correlated with shedding in urine, the immune state of IgM, the adverse pregnant history and younger age. CMV shedding was more commonly detected in vaginal secretion than in urine or blood with higher viral loads among healthy seropositive women of reproductive age. Further studies are needed to figure out whether the shedding is occasional or continuous and whether it is associated with adverse pregnancy outcomes.


Assuntos
Infecções por Citomegalovirus/epidemiologia , Citomegalovirus/isolamento & purificação , Eliminação de Partículas Virais , Adulto , Anticorpos Antivirais/sangue , Sangue/virologia , China/epidemiologia , DNA Viral/análise , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Pessoa de Meia-Idade , Prevalência , Reação em Cadeia da Polimerase em Tempo Real , Urina/virologia , Vagina/virologia , Carga Viral , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...