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1.
Ann Rheum Dis ; 78(12): 1669-1676, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31570366

RESUMO

OBJECTIVES: Maintenance of remission has become central in the management of systemic lupus erythematosus (SLE). The importance of interferon-alpha (IFN-α) in the pathogenesis of SLE notwithstanding, its expression in remission has been poorly studied as yet. To study its expression in remission and its prognostic value in the prediction of a disease relapse, serum IFN-α levels were determined using an ultrasensitive single-molecule array digital immunoassay which enables the measurement of cytokines at physiological concentrations. METHODS: A total of 254 SLE patients in remission, according to the Definition of Remission in SLE classification, were included in the study. Serum IFN-α concentrations were determined at baseline and patients were followed up for 1 year. Lupus flares were defined according to the Safety of Estrogens in Lupus Erythematosus: National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index Flare Index, whereas the Kaplan-Meier analysis and Cox regression analysis were used to estimate the time to relapse and to identify baseline factors associated with time to relapse, respectively. RESULTS: Of all patients in remission, 26% displayed abnormally high IFN-α serum levels that were associated with the presence of antibodies specific for ribonucleoprotein (RNP), double stranded (ds)DNA and Ro/SSA60, as well as young age. Importantly, elevated-baseline IFN-α serum levels and remission duration were associated in an independent fashion, with shorter time to relapse, while low serum levels of complement component 3 and anti-dsDNA Abs were not. CONCLUSION: Direct serum IFN-α assessment with highly sensitive digital immunoassay permits clinicians to identify a subgroup of SLE patients, clinically in remission, but at higher risk of relapse.

2.
Ocul Immunol Inflamm ; : 1-9, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31642720

RESUMO

Objective: To report the clinical features and treatment outcomes in immunocompetent patients with anterior segment inflammation (ASI) related to human cytomegalovirus (HCMV) depending on their ethnic origin. Material and Methods: Multicenter retrospective study of 38 patients with at least one test, either HCMV-positive PCR or GWc. Results: Features of Posner-Schlossman syndrome were observed in 50% of the eyes, Fuchs heterochromic iridocyclitis in 13% of the eyes, chronic nonspecific anterior uveitis in 21% of the eyes, and corneal endotheliitis in 18% of the eyes. PCR and GWc were positive for HCMV in 50% and 96.2% of the eyes, respectively. Glaucoma was diagnosed in 50% of eyes. Treatment was oral valganciclovir in about half of the patients. Other treatments were intravenous ganciclovir and/or ganciclovir topical ointment and/or intravitreal ganciclovir. Conclusions: No obvious association of specific clinical features with individual ethnicity could be identified. We found a high rate of glaucoma in all ethnic groups. There was a delay in diagnosis and specific treatment of HCMV in most patients.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31508378

RESUMO

Tuberculosis (TB) remains one of the leading causes of mortality worldwide, and a lack of understanding of basic disease pathogenesis is hampering development of new vaccines and treatments. Multiple studies have previously established a role for type I interferon (IFN) in TB disease. Type I IFNs are critical immune mediators for host responses to viral infection, yet their specific influence in bacterial infection remains unclear. As IFN-stimulated genes (ISGs) can have both stimulatory and inhibitory effects on immune function, clarifying the role of type I interferon in TB remains an important question. The quantification of interferon proteins in the circulation of patients has been restricted until the recent development of digital ELISA. To test the hypothesis that patients with active TB disease have elevated circulating type I IFN we quantified plasma IFNα and ß proteins with Simoa digital ELISA in patients with active disease and asymptomatic M. tuberculosis infection. Strikingly no differences were observed between these two groups, while plasma from acute influenza infection revealed significantly higher plasma levels of both IFNα and IFNß proteins. These results suggest a discordance between ISG mRNA expression by blood leukocytes and circulating type I IFN in TB.

4.
PLoS One ; 14(6): e0217651, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31199828

RESUMO

OBJECTIVES: During winter, after excluding obvious sites of infection, the most important diagnoses of isolated fever or influenza-like illness (ILI) to rule out are listeriosis and influenza, because of their severe potential outcomes and the straightforward management available for each. While awaiting laboratory results, the recommended management strategy is usually hospitalization for intravenous antibiotic therapy against potential listeria. This study sought to assess the effect of the use of a rapid test on hospitalization and antibiotic therapy rates. METHODS: The study included all pregnant women who consulted for ILI or isolated fever after clinical and laboratory investigations and had a molecular diagnostic assay for influenza during two time periods, both during influenza epidemics: before introduction of the rapid molecular assay use (period 1) and after this (period 2). RESULTS: The study included 38 women during period 1 and 124 during period 2. The influenza diagnosis was confirmed for 24 of 38 (63.2%) women during period 1 and 65 of 124 (52.4%) women during period 2 (P = 0.24). The hospitalization rate fell significantly from period 1 to period 2, both in the total population (71.0% versus 44.3%, P = 0.004) and among women with confirmed influenza (83.3% versus 38.5%, P<0.001), as did the antibiotic therapy rate in both groups (respectively, 86.8% versus 56.1%, P = 0.001 and 91.7% versus 44.7%, P<0.001). CONCLUSION: The use of a rapid molecular assay for the diagnosis of influenza improved the management of pregnant women with an isolated fever or ILI by reducing the rates of unnecessary hospitalization and antibiotic therapy.

5.
J Exp Med ; 216(9): 2038-2056, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31217193

RESUMO

Autosomal recessive IRF7 and IRF9 deficiencies impair type I and III IFN immunity and underlie severe influenza pneumonitis. We report three unrelated children with influenza A virus (IAV) infection manifesting as acute respiratory distress syndrome (IAV-ARDS), heterozygous for rare TLR3 variants (P554S in two patients and P680L in the third) causing autosomal dominant (AD) TLR3 deficiency. AD TLR3 deficiency can underlie herpes simplex virus-1 (HSV-1) encephalitis (HSE) by impairing cortical neuron-intrinsic type I IFN immunity to HSV-1. TLR3-mutated leukocytes produce normal levels of IFNs in response to IAV. In contrast, TLR3-mutated fibroblasts produce lower levels of IFN-ß and -λ, and display enhanced viral susceptibility, upon IAV infection. Moreover, the patients' iPSC-derived pulmonary epithelial cells (PECs) are susceptible to IAV. Treatment with IFN-α2b or IFN-λ1 rescues this phenotype. AD TLR3 deficiency may thus underlie IAV-ARDS by impairing TLR3-dependent, type I and/or III IFN-mediated, PEC-intrinsic immunity. Its clinical penetrance is incomplete for both IAV-ARDS and HSE, consistent with their typically sporadic nature.

6.
Invest Ophthalmol Vis Sci ; 60(7): 2399-2405, 2019 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-31157832

RESUMO

Purpose: To investigate the clinical and virologic-associated and predictive factors of intraocular pressure (IOP) evolution over time and its severity in Fuchs' heterochromic iridocyclitis (FHC). Methods: Consecutive patients with both clinical FHC and intraocular synthesis of rubella virus (RV)-specific antibodies were included in this study. Specific ocular production of RV antibodies was confirmed using the quotient of serum/aqueous humor ratio of RV IgGs (Crv) and control antiviral IgGs (Cctl), using quantitative serology methods. Epidemiologic, clinical, biological, and virologic data at referral were collected and correlated with IOP values over time, occurrence, and severity of glaucoma. Results: Sixty-eight eyes of 68 patients were included. Mean age at diagnosis was 40.7 ± 11.1 years. Mean follow-up was 4.3 ± 4.3 years. Mean baseline Crv and Cctl values were 12.34 ± 14.67 and 216.70 ± 98.4, respectively. Mean baseline IOP was 17.2 ± 7.2 mm Hg (range, 9-40) and 15.6 ± 5.6 (range, 3-30) 5 years after referral. The predictive factors for pejorative IOP evolution over time and glaucoma severity were male sex (P = 0.03) and decreased Crv (P = 0.04) and presence of iris nodules (P < 0.001) and decreased Cctl (P = 0.02), respectively. Diagnostic delay was associated with increased likelihood of undergoing glaucoma surgery (P = 0.02). Conclusions: Time to diagnosis, male sex, presence of iris nodules at baseline, and decreased Crv and Cctl ratios were associated with increased likelihood of pejorative IOP evolution over time. Given the aggressiveness of glaucoma in FHC, these results provide interesting insight into what category of patients should need the closest screening.

7.
Emerg Infect Dis ; 25(6): 1204-1208, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31107209

RESUMO

In 2016, an upsurge of neurologic disease associated with infection with multirecombinant enterovirus A71 subgenogroup C1 lineage viruses was reported in France. These viruses emerged in the 2000s; 1 recombinant is widespread. This virus lineage has the potential to be associated with a long-term risk for severe disease among children.

8.
J Clin Immunol ; 39(1): 55-64, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30552536

RESUMO

PURPOSE: Progressive multifocal leukoencephalopathy (PML) is a rare but severe demyelinating disease caused by the polyomavirus JC (JCV) in immunocompromised patients. We report a series of patients with primary immune deficiencies (PIDs) who developed PML. METHODS: Retrospective observational study including PID patients with PML. Clinical, immunological, imaging features, and outcome are provided for each patient. RESULTS: Eleven unrelated patients with PIDs developed PML. PIDs were characterized by a wide range of syndromic or genetically defined defects, mostly with combined B and T cell impairment. Genetic diagnosis was made in 7 patients. Before the development of PML, 10 patients had recurrent infections, 7 had autoimmune and/or inflammatory manifestations, and 3 had a history of malignancies. Immunologic investigations showed CD4+ lymphopenia (median 265, range 50-344) in all cases. Six patients received immunosuppressive therapy in the year before PML onset, including prolonged steroid therapy in 3 cases, rituximab in 5 cases, anti-TNF-α therapy, and azathioprine in 1 case each. Despite various treatments, all but 1 patient died after a median of 8 months following PML diagnosis. CONCLUSION: PML is a rare but fatal complication of PIDs. Many cases are secondary to immunosuppressive therapy warranting careful evaluation before initiation subsequent immunosuppression during PIDs.


Assuntos
Síndromes de Imunodeficiência/complicações , Síndromes de Imunodeficiência/imunologia , Leucoencefalopatia Multifocal Progressiva/etiologia , Leucoencefalopatia Multifocal Progressiva/imunologia , Adolescente , Adulto , Azatioprina/uso terapêutico , Linfócitos B/imunologia , Feminino , Humanos , Imunoterapia/métodos , Vírus JC/imunologia , Leucoencefalopatia Multifocal Progressiva/terapia , Linfopenia/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Rituximab/uso terapêutico , Linfócitos T/imunologia , Fator de Necrose Tumoral alfa/imunologia , Adulto Jovem
9.
Arthritis Rheumatol ; 2018 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-30507062

RESUMO

OBJECTIVES: No simple or standardized assay is available to quantify interferon-α (IFNα) in routine clinical practice. Single-molecule-array (Simoa) digital enzyme-linked immunosorbent assay (ELISA) technology enables direct IFNα quantification at fg/mL concentrations. This study was undertaken to assess IFNα digital ELISA diagnostic performances to monitor systemic lupus erythematosus (SLE) activity. METHODS: IFNα concentrations in serum samples from 150 consecutive SLE patients in a cross-sectional study were determined with digital ELISA and a functional biological activity assay (bioassay). According to their SELENA-SLEDAI flare composite, patients were divided into groups with inactive (SLEDAI <4 or clinical SLEDAI =0) or active SLE (SLEDAI ≥4 or clinical SLEDAI >0), and into groups with no flare or mild/moderate flare or severe flare. RESULTS: Based on healthy blood donors, the abnormal serum-IFNα level threshold value was 136 fg/mL. Next, using receiver operating characteristics curves for an SLE-patient series, widely heterogeneous for disease activity and organ involvement, the threshold IFNα value associated with active disease was determined to be 266 fg/mL. The digital ELISA-assessed serum-IFNα level was a better biomarker of disease activity than the Farr test: its specificity, likelihood ratio for positive results and positive-predictive value better discerned active SLE or flare from inactive patients. The digital ELISA was more sensitive than the bioassay to detect low-abnormal serum-IFNα concentrations and patients with low disease activity. CONCLUSION: Direct serum-IFNα determination with a highly sensitive assay might improve monitoring of clinical SLE activity and selection of the best candidates for anti-IFNα treatment. This article is protected by copyright. All rights reserved.

11.
Lancet Infect Dis ; 18(12): 1385-1396, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30389482

RESUMO

BACKGROUND: Enteroviruses are the most frequent cause of acute meningitis and are seen increasingly in sepsis-like disease and fever without source in the paediatric population. Detection of enterovirus in cerebrospinal fluid (CSF) specimens by PCR is the gold standard diagnostic test. Our aim was to assess a method of detecting enterovirus in blood specimens by PCR. METHODS: We did a prospective, multicentre, observational study at 35 French paediatric and emergency departments in 16 hospitals. We recruited newborn babies (aged ≤28 days) and infants (aged >28 days to ≤2 years) with fever without source, sepsis-like disease, or suspected meningitis, and children (aged >2 years to ≤16 years) with suspected meningitis, who were admitted to a participating hospital. We used a standardised form to obtain demographic, clinical, and laboratory data, which were anonymised. Enterovirus PCR testing was done in blood and CSF specimens. FINDINGS: Between June 1, 2015, and Oct 31, 2015, and between June 1, 2016, and Oct 31, 2016, we enrolled 822 patients, of whom 672 had enterovirus PCR testing done in blood and CSF specimens. Enterovirus was detected in 317 (47%) patients in either blood or CSF, or both (71 newborn babies, 83 infants, and 163 children). Detection of enterovirus was more frequent in blood samples than in CSF specimens of newborn babies (70 [99%] of 71 vs 62 [87%] of 71; p=0·011) and infants (76 [92%] of 83 vs 62 [75%] of 83; p=0·008), and was less frequent in blood samples than in CSF specimens of children (90 [55%] of 163 vs 148 [91%] of 163; p<0·0001). Detection of enterovirus was more frequent in blood samples than in CSF specimens of infants aged 2 years or younger with fever without source (55 [100%] of 55 vs 41 [75%] of 55; p=0·0002) or with sepsis-like disease (16 [100%] of 16 vs nine [56%] of 16; p=0·008). Detection of enterovirus was less frequent in blood than in CSF of patients with suspected meningitis (165 [67%] of 246 vs 222 [90%] of 246; p<0·0001). INTERPRETATION: Testing for enterovirus in blood by PCR should be an integral part of clinical practice guidelines for infants aged 2 years or younger. This testing could decrease the length of hospital stay and reduce exposure to antibiotics for low-risk patients admitted to the emergency department with febrile illness. FUNDING: University Hospital Clermont-Ferrand.

12.
Fetal Diagn Ther ; : 1-11, 2018 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-30032153

RESUMO

BACKGROUND: Infection with parvovirus B19 (B19V) during pregnancy may cause severe fetal anemia, hydrops, and fe tal death. Furthermore, neurodevelopmental impairment among survivors may occur despite appropriate prenatal management, including intrauterine transfusion (IUT). OBJECTIVES: Our primary objective was to describe cerebral lesions on MRI in fetuses with severe anemia requiring IUT for B19V infection. Our secondary objective was to search for clinical and biological characteristics associated with the occurrence of such lesions. STUDY DESIGN: We performed a retrospective review of data on fetuses infected with B19V and requiring at least one IUT between 2005 and 2016. Fetuses with abnormal cerebral MRI results in the 3rd trimester were compared to those with normal MRI results. RESULTS: Of 34 transfused fetuses, 26 children were born at full term. Five intrauterine fetal deaths, 1 neonatal death, and 2 terminations of pregnancy occurred. Cerebral anomalies were observed in 7/27 fetuses on MRI, including cerebellar hemorrhage or a small cerebellum. Only viral load in fetal blood appeared to be associated with brain lesions (11.5 log10 copies/mL [10.5-12.5] in case of abnormal MRI results vs. 9.5 log10 copies/mL [7.8-10.0]; p = 0.05). CONCLUSIONS: Among the fetuses transfused for B19V infection, 26% presented with prenatal abnormal cerebral imaging results. In our study, viral load in fetal blood appeared to be the only factor associated with fetal brain lesions.

13.
Am J Ophthalmol ; 194: 134-142, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30055154

RESUMO

PURPOSE: To report the characteristics of cytomegalovirus anterior uveitis (CMV AU) and the comparative response to 2 types of antiviral induction treatments. DESIGN: Retrospective, consecutive case series. METHODS: Consecutive immunocompetent patients with polymerase chain reaction-positive CMV AU were included. For each patient, best-corrected visual acuity (BCVA), intraocular pressure (IOP), clinical characteristics at baseline and latest visit, and number of relapses were recorded. All patients received an induction dose of intravenous (IV) ganciclovir or oral valganciclovir and a maintenance dose of oral valganciclovir. RESULTS: Thirty-six eyes of 35 patients were included. Mean age at diagnosis was 55.5 years. Mean follow-up was 4.13 years. Posner-Schlossman and chronic nonspecific AU were observed in 69.4% and 30.6% of cases, respectively. We did not observe any case of Fuchs uveitis or endotheliitis. At baseline, mean BCVA was 20/25 and mean IOP was 29.19 mm Hg. Keratic precipitates and iris atrophy were seen in 91.4% and 25.7% of cases. Induction therapy consisted of oral valganciclovir and IV ganciclovir in 40% and 60% of cases. A total of 94.2% of patients responded to the first line of therapy. Recurrence was reported in 73.5% of cases. Glaucoma surgery was necessary in 25.7% of cases. Early initiation of antiviral therapy (≤700 days) seemed to decrease the recourse to glaucoma surgery. Both IV and oral induction treatments seemed similar in terms of BCVA changes and occurrence of relapses. CONCLUSIONS: Characteristics of CMV AU seem to show specificities in this French cohort. Early initiation of antiviral therapy seems to reduce the severity of glaucoma.

14.
PLoS One ; 13(6): e0199171, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29944671

RESUMO

JC virus (JCV), a ubiquitous human polyomavirus, can cause fatal progressive multifocal leukoencephalopathy (PML) in immune compromised patients. The viral genome is composed of two conserved coding regions separated by a highly variable non-coding control region (NCCR). We analyzed the NCCR sequence from 10 PML JCV strains and found new mutations. Remarkably, the NCCR f section was mutated in most cases. We therefore explored the importance of this section in JCV expression in renal (HEK293H) and glioblastoma (U-87MG) cell lines, by adapting the emerging technology of DNA minicircles. Using bidirectional fluorescent reporters, we revealed that impaired NCCR-driven late expression in glioblastoma cells was restored by a short deletion overlapping e and f sections. This study evidenced a relevant link between JCV NCCR polymorphism and cell-type dependent expression. The use of DNA minicircles opens new insights for monitoring the impact of NCCR variation.

15.
Brain ; 141(6): 1609-1621, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29741608

RESUMO

Dermatomyositis is an acquired auto-immune disease characterized by skin lesions and muscle-specific pathological features such as perifascicular muscle fibre atrophy and vasculopathy. Dermatomyositis patients display an upregulation of type I interferon-inducible genes in muscle fibres, endothelial cells, skin and peripheral blood. However, the effect of type I interferon on muscle tissue has not yet been determined. Our aim was to study the pathogenicity of type I interferon in vitro and to evaluate the efficacy of the type I interferon pathway blockade for therapeutic purposes. The activation of type I interferon in differentiating myoblasts abolished myotube formation with reduced myogenin expression while in differentiated myotubes, we observed a reduction in surface area and an upregulation of atrophy-associated genes. In vitro endothelial cells exposure to type I interferon disrupted vascular network organization. All the pathogenic effects observed in vitro were abolished by ruxolitinib. Finally, four refractory dermatomyositis patients were treated with ruxolitinib and improvement ensued in skin lesions, muscle weakness and a reduced serum type I interferon levels and interferon-inducbile genes scores. We propose JAK inhibition as a mechanism-based treatment for dermatomyositis, a finding that is relevant for the design of future clinical trials targeting dermatomyositis.

16.
Ocul Immunol Inflamm ; 26(1): 94-103, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28628343

RESUMO

INTRODUCTION: Chronic uveitis treated with immunosuppressive agents may have unfavorable outcomes due to delays in diagnosis. The aim of this study was to review initial data from clinical and ocular assessments and patient outcomes following specific treatments for atypical herpes virus ocular infections. METHODS: The records of four consecutive patients with recurrent uveitis for at least five years treated in our department between 2001 and 2016 were retrospectively reviewed. They had atrophic retinal lesions resulting in an unfavorable outcome with lesion progression and vision loss under immunosuppressive treatment. Varicella zoster virus (1 case) and herpes simplex virus type 2 (3 cases) were detected in ocular samples. RESULTS: Uveitis was granulomatous and bilateral (3 cases) or unilateral (1 case). Immunosuppressive treatments worsened the clinical situation whereas antiherpetic treatments improved the control of intraocular inflammation. CONCLUSION: This description should be added to the broad repertoire of clinical polymorphisms associated with herpes virus infections. Recognizing these cases should be useful due to their sensitivity to antiherpetic treatments.


Assuntos
Infecções Oculares Virais/diagnóstico , Herpes Simples/diagnóstico , Herpes Zoster Oftálmico/diagnóstico , Herpesvirus Humano 2/isolamento & purificação , Herpesvirus Humano 3/isolamento & purificação , Retinite/diagnóstico , Adulto , Anticorpos Antivirais/sangue , Antivirais/uso terapêutico , Humor Aquoso/virologia , Doença Crônica , DNA Viral/genética , Infecções Oculares Virais/tratamento farmacológico , Infecções Oculares Virais/virologia , Feminino , Seguimentos , Herpes Simples/tratamento farmacológico , Herpes Simples/virologia , Herpes Zoster Oftálmico/tratamento farmacológico , Herpes Zoster Oftálmico/virologia , Herpesvirus Humano 2/genética , Herpesvirus Humano 2/imunologia , Herpesvirus Humano 3/genética , Herpesvirus Humano 3/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Retinite/tratamento farmacológico , Retinite/virologia , Estudos Retrospectivos , Resultado do Tratamento
17.
J Exp Med ; 214(5): 1547-1555, 2017 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-28420733

RESUMO

Type I interferons (IFNs) are essential mediators of antiviral responses. These cytokines have been implicated in the pathogenesis of autoimmunity, most notably systemic lupus erythematosus (SLE), diabetes mellitus, and dermatomyositis, as well as monogenic type I interferonopathies. Despite a fundamental role in health and disease, the direct quantification of type I IFNs has been challenging. Using single-molecule array (Simoa) digital ELISA technology, we recorded attomolar concentrations of IFNα in healthy donors, viral infection, and complex and monogenic interferonopathies. IFNα protein correlated well with functional activity and IFN-stimulated gene expression. High circulating IFNα levels were associated with increased clinical severity in SLE patients, and a study of the cellular source of IFNα protein indicated disease-specific mechanisms. Measurement of IFNα attomolar concentrations by digital ELISA will enhance our understanding of IFN biology and potentially improve the diagnosis and stratification of pathologies associated with IFN dysregulation.


Assuntos
Ensaio de Imunoadsorção Enzimática/métodos , Interferon-alfa/sangue , Humanos , Fatores Reguladores de Interferon/sangue , Fatores Reguladores de Interferon/líquido cefalorraquidiano , Interferon-alfa/líquido cefalorraquidiano , Lúpus Eritematoso Sistêmico/sangue , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Linfócitos T/metabolismo , Estomatite Vesicular/imunologia
18.
Euro Surveill ; 21(13)2016.
Artigo em Inglês | MEDLINE | ID: mdl-27063794

RESUMO

We detected an unusual increase in congenital cerebral malformations and dysfunction in fetuses and newborns in French Polynesia, following an epidemic of Zika virus (ZIKV), from October 2013 to March 2014. A retrospective review identified 19 cases, including eight with major brain lesions and severe microcephaly, six with severe cerebral lesions without microcephaly and five with brainstem dysfunction without visible malformations. Imaging revealed profound neurological lesions (septal and callosal disruption, ventriculomegaly, abnormal neuronal migration, cerebellar hypoplasia, occipital pseudocysts, brain calcifications). Amniotic fluid was drawn from seven cases at gestation weeks 20 to 29. ZIKV RNA was detected by RT-PCR and infectious ZIKV isolates were obtained in four of five microcephalic, but not in two non-microcephalic cases with severe brain lesions. Medical termination of pregnancy was performed in eleven cases; two cases with brainstem dysfunction died in the first months of life; six cases are alive, with severe neurological impairment. The results show that four of seven tested fetuses with major neurological injuries were infected with ZIKV in utero. For other non-microcephalic, congenital abnormalities we were not able to prove or exclude ZIKV infection retrospectively. The unusual occurrence of brain malformations or dysfunction without microcephaly following a ZIKV outbreak needs further studies.


Assuntos
Líquido Amniótico/virologia , Encéfalo/patologia , Feto/anormalidades , Microcefalia/diagnóstico , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/epidemiologia , Zika virus/isolamento & purificação , Adulto , Encéfalo/diagnóstico por imagem , Epidemias , Feminino , Feto/fisiopatologia , Humanos , Recém-Nascido , Imagem por Ressonância Magnética , Microcefalia/complicações , Polinésia/epidemiologia , Gravidez , Complicações Infecciosas na Gravidez/virologia , RNA Viral/genética , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Tomografia Computadorizada por Raios X , Infecção por Zika virus/complicações , Infecção por Zika virus/virologia
19.
J Clin Virol ; 74: 37-42, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26655266

RESUMO

BACKGROUND: The monitoring and genotyping of Enterovirus (EV) infections can help to associate particular or severe clinical manifestations with specific EV types and to identify the aetiology of infectious outbreaks. OBJECTIVES: To describe the epidemiological features of EV infections diagnosed during the year 2013 in the Greater Paris area (Ile de France). STUDY DESIGN: During 2013, 2497 samples taken from 470 patients in 33 hospitals of Ile-de France were tested for EV genome by RT-PCR. EV genotyping was performed by the National Reference Centre (NRC) laboratories. EV infections were retrospectively reviewed by retrieving clinical and genotyping data from the NRC database. RESULTS: Of the 2497 samples, 490 (19.6%) was positive for EV genome detection. These EV infections represented 88.7% and 24.1%, respectively, of all reported regional and national infections. Twenty-seven different genotypes were identified. Echovirus 30 (E-30) accounted for 54.1% of all characterized strains and caused a large outbreak. Four severe neonatal infections were reported, of which two were caused by EV-A71. Respiratory infections involving EV-D68 were observed in two adults. One fatal case of Coxsackievirus A2-associated myocarditis was reported. CONCLUSION: Monitoring EV infections in combination with EV genotyping via the French EV network characterized the epidemiology of EV infections in the Ile de France region in 2013 and documented severe EV infections associated with EV-A71 or CV-A2.


Assuntos
Infecções por Enterovirus/epidemiologia , Enterovirus/classificação , Enterovirus/isolamento & purificação , Genótipo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Enterovirus/genética , Feminino , Hospitais , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Paris/epidemiologia , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adulto Jovem
20.
Fetal Diagn Ther ; 39(1): 4-12, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-25997482

RESUMO

INTRODUCTION: Guidelines for the management of cytomegalovirus (CMV) infection of the fetus are rare. Our main objective was to evaluate how health care practitioners in France manage cases of CMV seroconversion during pregnancy. MATERIAL AND METHODS: A questionnaire was e-mailed to health care practitioners potentially concerned by CMV seroconversion during pregnancy. They were asked if they would recommend amniocentesis, fetal cerebral MRI examination and fetal blood analysis (FBA), depending on the ultrasound results. They then had to indicate whether they would accept termination of pregnancy (TOP), depending on the results of these examinations. RESULTS: A total of 380 health care practitioners responded, mainly obstetricians (73.9%) and midwives (20.2%). Overall, 57% of respondents recommended amniocentesis in the case of CMV seroconversion during the first trimester of pregnancy, ultrasound findings being normal. In cases of positive amniocentesis and a major ultrasound abnormality, 84.5% of respondents would perform cerebral MRI, and 44.4% would perform FBA. In this case, the rate of acceptance of TOP was not significantly different whether the examinations were normal (337/372, 90.6%) or not performed (339/374, 93.3%; p = 0.17). DISCUSSION: Amniocentesis is too infrequently used and should be encouraged. The results of MRI and FBA are often not taken into account in the final decision concerning TOP. Guidelines are needed to clarify the management of CMV seroconversion during pregnancy.


Assuntos
Infecções por Citomegalovirus/terapia , Obstetrícia/estatística & dados numéricos , Complicações Infecciosas na Gravidez/terapia , Feminino , França , Humanos , Obstetrícia/normas , Gravidez , Soroconversão , Inquéritos e Questionários
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