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1.
Clin Infect Dis ; 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32067040

RESUMO

BACKGROUND: Immune control of Epstein-Barr virus (EBV) infection is impaired in HIV-infected individuals. We explored maternal factors associated with EBV acquisition in HIV-exposed uninfected (HEU) infants and the relationship between EBV infection and serious adverse events (SAE) during the first year of life. METHODS: Two hundred and one HEU infants from Uganda enrolled in the ANRS12174 trial were tested for anti-viral capsid antigen (VCA) antibodies at week 50 of life. The date of infection was estimated by testing of EBV DNA at weeks 1, 6, 14, 26, 38 and 50 postpartum on dried blood spot (DBS). RESULTS: Eighty-seven (43%) infants were tested positive for anti-VCA IgG at week 50. Among the 59 infants positive for EBV DNA, 25% were infected within the first 26 weeks. Almost half of them (12%) were infected before week 14. Shedding of EBV in breast milk was associated with EBV DNA in maternal plasma (P=.009), HIV RNA detection (P=.039), lower CD4 count (P=.001) and was correlated with plasma EBV DNA levels (P=.002). EBV infant infection at week 50 was associated with shedding of EBV in breast milk (P=.009) and young maternal age (P=.029). Occurrence of a clinical SAE, including malaria and pneumonia, was associated with higher levels of EBV DNA in infants (P=.010). CONCLUSIONS: By assessing EBV infection in HEU infants we observed that infection during the first year of life is determined by HIV and EBV maternal factors and that EBV DNA levels was higher among infants with clinical SAE.

2.
Front Immunol ; 10: 1153, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31191532

RESUMO

Primary Sjögren's syndrome (pSS) is characterized by B cell hyperactivation, production of autoantibodies and increased risk of B cell lymphomas. Serological profile of Epstein-Barr virus (EBV) reactivation and increase EBV DNA levels in exocrine glands are observed in pSS, but whether these abnormalities are accompanied with disturbed systemic EBV control or have any association with pSS activity remains to be investigated. In this observational study, we initially explored anti-EBV antibodies and cell-free DNA in 395 samples from a cross-sectional plasma collection of pSS patients included in ASSESS French national cohort. Results were assessed in relation with disease activity. Further, to assess cell-associated EBV DNA we organized a case-control study including 20 blood samples from pSS patients followed in University Hospital Center of Montpellier. Results were compared with matched controls. Robust response against EBV early antigen (EA) was observed in pSS patients with anti-SSA/B (Sjögren's syndrome A and B) and anti-SSA autoantibodies compared to anti-SSA/B negatives (P < 0.01 and P = 0.01, respectively). Increased beta-2 microglobulin, kappa and lambda light chains, and immunoglobulin G levels were more frequently observed in anti-EA seropositive pSS subjects compared to anti-EA negative subjects (P < 0.001; P = 0.001; P = 0.003, respectively). Beta-2 microglobulin was independently associated with anti-EA positivity in multivariate analysis (P < 0.001). Plasma cell-free EBV DNA and EBV cellular reservoir was not different between pSS patients and controls. We conclude that serological evidence of EBV reactivation was more frequently observed and more strongly associated with anti-SSA/B status and B cell activation markers in pSS. However, serological profile of EBV reactivation was not accompanied by molecular evidence of systemic EBV reactivation. Our data indicated that EBV infection remains efficiently controlled in the blood of pSS patients.


Assuntos
Anticorpos Antinucleares/sangue , Anticorpos Antivirais/sangue , Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4/fisiologia , Síndrome de Sjogren/imunologia , Ativação Viral , Adulto , Idoso , Autoantígenos/imunologia , Linfócitos B/imunologia , Biomarcadores , Estudos de Casos e Controles , DNA Viral/análise , DNA Viral/sangue , Infecções por Vírus Epstein-Barr/virologia , Glândulas Exócrinas/virologia , Feminino , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/imunologia , Humanos , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Ribonucleoproteínas/imunologia , Síndrome de Sjogren/sangue , Síndrome de Sjogren/complicações , Síndrome de Sjogren/virologia , Microglobulina beta-2/análise
3.
PLoS One ; 12(8): e0183856, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28850597

RESUMO

BACKGROUND: Viral load monitoring and early Epstein-Barr virus (EBV) DNA detection are essential in routine laboratory testing, especially in preemptive management of Post-transplant Lymphoproliferative Disorder. Targeting the repetitive BamHI-W sequence was shown to increase the sensitivity of EBV DNA quantification, but the variability of BamHI-W reiterations was suggested to be a source of quantification bias. We aimed to assess the extent of variability associated with BamHI-W PCR and its impact on the sensitivity of EBV DNA quantification using the 1st WHO international standard, EBV strains and clinical samples. METHODS: Repetitive BamHI-W- and LMP2 single- sequences were amplified by in-house qPCRs and BXLF-1 sequence by a commercial assay (EBV R-gene™, BioMerieux). Linearity and limits of detection of in-house methods were assessed. The impact of repeated versus single target sequences on EBV DNA quantification precision was tested on B95.8 and Raji cell lines, possessing 11 and 7 copies of the BamHI-W sequence, respectively, and on clinical samples. RESULTS: BamHI-W qPCR demonstrated a lower limit of detection compared to LMP2 qPCR (2.33 log10 versus 3.08 log10 IU/mL; P = 0.0002). BamHI-W qPCR underestimated the EBV DNA load on Raji strain which contained fewer BamHI-W copies than the WHO standard derived from the B95.8 EBV strain (mean bias: - 0.21 log10; 95% CI, -0.54 to 0.12). Comparison of BamHI-W qPCR versus LMP2 and BXLF-1 qPCR showed an acceptable variability between EBV DNA levels in clinical samples with the mean bias being within 0.5 log10 IU/mL EBV DNA, whereas a better quantitative concordance was observed between LMP2 and BXLF-1 assays. CONCLUSIONS: Targeting BamHI-W resulted to a higher sensitivity compared to LMP2 but the variable reiterations of BamHI-W segment are associated with higher quantification variability. BamHI-W can be considered for clinical and therapeutic monitoring to detect an early EBV DNA and a dynamic change in viral load.


Assuntos
DNA Viral , Infecções por Vírus Epstein-Barr/virologia , Herpesvirus Humano 4/isolamento & purificação , Reação em Cadeia da Polimerase/métodos , Herpesvirus Humano 4/genética , Humanos , Sequências Repetitivas de Ácido Nucleico , Sensibilidade e Especificidade , Carga Viral
4.
Medicine (Baltimore) ; 95(27): e4005, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27399077

RESUMO

Epstein-Barr virus (EBV) in breast milk and subclinical mastitis (SCM) are both associated with human immunodeficiency virus (HIV) shedding and possibly with postnatal HIV transmission. The objective of this nested case-control study was to investigate the interplay between SCM and EBV replication in breast milk of HIV-infected mothers.The relationships between EBV deoxyribonucleic acid (DNA) shedding, HIV-1 ribonucleic acid (RNA) level, and SCM were explored in breast milk samples of Zambian mothers participating in the ANRS 12174 trial. Mammary gland inflammation was defined as a breast milk sodium to potassium ratio (Na/K) greater than 0.6 and further subclassified as either "possible SCM" (Na/K ratio 0.6-1.0) or SCM (Na/K ratio ≥ 1.0). Breast milk interleukin 8 (IL-8) was measured as a surrogate marker of mammary gland inflammation.EBV DNA was detected in breast milk samples from 42 out of 83 (51%) participants and was associated with HIV-1 shedding in breast milk (P = 0.006). EBV DNA levels were higher in samples with SCM and "possible SCM" compared to non-SCM breast milk samples (P = 0.06; P = 0.007). An EBV DNA level of >200 copies/mL was independently associated with SCM and "possible SCM" (OR: 2.62; 95%: 1.13-6.10). In patients with SCM, higher EBV replication in the mammary gland was associated with a lower induction of IL-8 (P = 0.013). Resistance to DNase treatment suggests that EBV DNA in lactoserum is encapsidated.SCM and decreased IL-8 responses are associated with an increased EBV shedding in breast milk which may in turn facilitate HIV replication in the mammary gland.


Assuntos
Infecções por HIV/transmissão , HIV-1/fisiologia , Herpesvirus Humano 4/fisiologia , Transmissão Vertical de Doença Infecciosa , Mastite/virologia , Leite Humano/virologia , Eliminação de Partículas Virais , Adulto , Contagem de Linfócito CD4 , DNA Viral/análise , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Recém-Nascido , RNA Viral/análise , Zâmbia
5.
J Clin Microbiol ; 54(6): 1641-1643, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27008874

RESUMO

The impact of HIV-1 DNA coamplification during HIV-1 RNA quantification on dried blood spots (DBS) was explored. False-positive HIV RNA detection (22/62, 35%) was associated with high HIV-1 DNA levels. Specificity of HIV-1 RNA assays on DBS should be evaluated following manufacturer protocols on samples with HIV-1 DNA levels of ≥1,000 copies/10(6) peripheral blood mononuclear cells.


Assuntos
DNA Viral/sangue , Erros de Diagnóstico , Infecções por HIV/virologia , HIV-1/isolamento & purificação , RNA Viral/sangue , Manejo de Espécimes/métodos , Carga Viral/métodos , Dessecação , Monitoramento de Medicamentos/métodos , Reações Falso-Positivas , Infecções por HIV/tratamento farmacológico , Humanos
6.
Infect Genet Evol ; 32: 161-4, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25791932

RESUMO

For the third time, teams belonging to the "Montpellier Infectious Diseases" network in the Rabelais BioHealth Cluster held their annual meeting on the 27th and 28th of November in Montpellier, France. While the 2012 meeting was focused on the cooperation between the local force tasks in biomedical and medical chemistry and presented the interdisciplinary research programs designed to fight against virus, bacteria and parasites, the 2014 edition of the meeting was focused on the translational research in infectious diseases and highlighted the bench-to-clinic strategies designed by academic and private research groups in the Montpellier area.


Assuntos
Doenças Transmissíveis/genética , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/genética , Infecções Bacterianas/microbiologia , Doenças Transmissíveis/tratamento farmacológico , Doenças Transmissíveis/epidemiologia , Doenças Transmissíveis Emergentes/epidemiologia , Congressos como Assunto , Desenho de Fármacos , Humanos , Doenças Parasitárias/epidemiologia , Doenças Parasitárias/genética , Doenças Parasitárias/parasitologia , Pesquisa Médica Translacional , Viroses/epidemiologia , Viroses/genética , Viroses/virologia
7.
Int J Cardiol ; 163(3): 320-325, 2013 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-23073279

RESUMO

OBJECTIVES: The aim of this cohort study was to retrospectively evaluate, in patients with chronic heart failure (CHF), the long term effect of trimetazidine (TMZ) on morbidity and mortality. BACKGROUND: Previous small studies in patients with CHF have shown that TMZ can improve left ventricular function, exercise capacity and NYHA class compared to placebo. However, no data on the effects of TMZ on survival in patients with CHF have ever been produced. METHODS: In this international multicentre retrospective cohort study data from 669 patients were analyzed. 362 patients were on TMZ due to symptom persistence despite up-titration of optimal CHF therapy, while the remaining patients continued conventional CHF therapy alone. Propensity score analysis was performed in order to minimize selection bias between the two groups. RESULTS: Kaplan-Meier analysis for global mortality showed 11.3% improved global survival (p=0.015) and 8.5% improved survival for cardiovascular (CVD) death (p=0.050) in the TMZ group. Cox regression analysis for global mortality showed a significant risk reduction for TMZ treated patients with a hazard ratio (HR)=0.189 (confidence interval - CI 95%: 0.017-0.454; p=0.0002). TMZ also showed a good risk reduction profile for CVD death causes (HR=0.072, CI 95%: 0.019-0.268, p=0.0001). The rate of hospitalization for cardiovascular causes was reduced by 10.4% at 5 years (p<0.0005) with increased hospitalization-free survival of 7.8 months. CONCLUSION: TMZ is effective in reducing mortality and event-free survival in patients with CHF. The addition of TMZ on top of optimal medical therapy improves long term survival in CHF patients.


Assuntos
Ácidos Graxos/antagonistas & inibidores , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/mortalidade , Trimetazidina/uso terapêutico , Vasodilatadores/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Ácidos Graxos/metabolismo , Feminino , Seguimentos , Insuficiência Cardíaca/metabolismo , Humanos , Internacionalidade , Masculino , Pessoa de Meia-Idade , Morbidade , Oxirredução/efeitos dos fármacos , Estudos Retrospectivos , Resultado do Tratamento , Trimetazidina/farmacologia , Vasodilatadores/farmacologia
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