Zika fever is an Aedes-borne disease caused by a flavivirus (Zika virus, ZIKV, genus Flavivirus). During the past years ZIKV spread in Polynesia, South-America and the Caribbean. Most ZIKV infections ...are asymptomatic or result in mild febrile disease with rash and conjunctivitis. Attention was recently drawn to non-vectored ZIKV transmission, including sexual, probable blood-borne and mother-to-fetus transmission, and to severe forms such as Guillain-Barré syndrome, acute neurological infections and fetal abnormalities (including microcephaly). Many aspects of Zika fever natural history remain unknown, e.g. the proportion of asymptomatic cases and the duration of viremia. Estimating the prevalence of Zika infections is difficult because a large proportion of infected individuals do not seek medical attention and seroprevalence studies are hampered by antigenic cross-reactivity with other flaviviruses, e.g. dengue virus. Here, we present a study of ZIKV infection in blooddonors from Martinique island (French West Indies, Caribbean region), with novel epidemiological, biological and clinical information that refine the picture of Zika fever in adults.
Au cours des dernières années, les arbovirus ont été responsables de nombreuses épidémies à travers le monde. Les départements français d’Amérique, en zone d’endémie pour la dengue, ont été affectés ...en peu de temps par 2 épidémies : en 2014 par le virus chikungunya et en 2016 par le virus zika, infections transmises par les moustiques du genre aèdes. Chacune de ces épidémies a duré environ 1 an et a conduit à la mise en œuvre de mesures de prévention du risque de transmission par les produits sanguins, incluant des mesures applicables à toutes les arboviroses (ex : ajournement des donneurs, quarantaine de 72 heures et renforcement de l’information postdon, détection par DGV, atténuation des pathogènes) et des mesures adaptées aux spécificités du virus zika : transfusion des femmes enceintes par des produits collectés en métropole et mesures d’ajournement (métropole et Réunion) pour risque d’origine sexuel. Au cours de ces 2 épidémies aux Antilles, les mesures mises en œuvre ont permis d’écarter de nombreux dons infectés par ces virus et de contribuer ainsi à la sécurité transfusionnelle. Aucun cas de contamination par des produits sanguins n’a été rapporté par le système d’hémovigilance. Cette expérience a permis de tirer de nombreux enseignements scientifiques et organisationnels. Des plans de continuité d’activité sont élaborés et actualisés chaque année pour que l’EFS ait une réactivité optimale face aux enjeux associés aux émergences virales.
Abstract We prospectively evaluated the Bio-Rad nonstructural 1 (NS1) enzyme-linked immunosorbent assay (ELISA) and lateral flow immunochromatographic assay (LFIA) in comparison to an in-place ...reverse transcription–polymerase chain reaction for dengue diagnosis. Among 537 consecutive samples from patients with acute febrile disease, 264 (49.2%) tested positive in reverse transcription–polymerase chain reaction (RT-PCR), 156 (29.1%) in NS1-antigen (Ag) ELISA, and 125 (23.3%) in NS1-Ag LFIA. Compared to the RT-PCR status, the specificity was 100% for the NS1-Ag ELISA and LFIA, but their respective sensitivities were 61.2% 95% confidence interval (CI), 55.2−67.2 and 49.4% (95% CI, 43.2−55.6), with nadirs of 37.9% and 24.1% on day 6 of illness. The NS1-Ag ELISA and LFIA were positive, respectively, for 48.0% and 40.7% of the secondary infections versus 85.0% and 66.7% of the primary infections. For patients <5 years old, NS1-Ag ELISA and LFIA reached respective sensitivities of 100% and 90.5%. Reports of results of dengue NS1-Ag assays should specify that negativity does not preclude DENV infection, and require further investigations in the case of severe disease.
Abacavir hypersensitivity Abel, Sylvie; Paturel, Laure; Cabié, André
The New England journal of medicine,
2008-Jun-05, Letnik:
358, Številka:
23
Journal Article
Abacavir Hypersensitivity Vandekerckhove, Linos; Blot, Stijn; Vogelaers, Dirk
New England journal of medicine/The New England journal of medicine,
06/2008, Letnik:
358, Številka:
23
Journal Article
Recenzirano
Odprti dostop
To the Editor:
The Prospective Randomized Evaluation of DNA Screening in a Clinical Trial (PREDICT-1) by Mallal et al. (Feb. 7 issue)
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showed that screening for HLA-B*5701 resulted in a significant ...reduction in the rate of hypersensitivity reactions (from 7.8% to 3.4%) among patients who were positive for the human immunodeficiency virus (HIV) and were receiving abacavir. However, because of methodologic limitations, this study will only modestly alter clinical practice. In the HLA-B*5701–negative group, all patients appeared to have a negative epicutaneous patch test (immunologic confirmation of a hypersensitivity reaction to abacavir). Notwithstanding the risks associated with rechallenge,
2
the investigators . . .
The HBV HBx regulatory protein is required for transcription from the covalently closed circular DNA (cccDNA) minichromosome and affects the epigenetic control of both viral and host cellular ...chromatin.
We explored, in relevant cellular models of HBV replication, the functional consequences of HBx interaction with DLEU2, a long non-coding RNA (lncRNA) expressed in the liver and increased in human hepatocellular carcinoma (HCC), in the regulation of host target genes and the HBV cccDNA.
We show that HBx binds the promoter region, enhances the transcription and induces the accumulation of DLEU2 in infected hepatocytes. We found that nuclear DLEU2 directly binds HBx and the histone methyltransferase enhancer of zeste homolog 2 (EZH2), the catalytic active subunit of the polycomb repressor complex 2 (PRC2) complex. Computational modelling and biochemical evidence suggest that HBx and EZH2 share two preferential binding sites in DLEU2 intron 1. HBx and DLEU2 co-recruitment on the cccDNA displaces EZH2 from the viral chromatin to boost transcription and viral replication. DLEU2-HBx association with target host promoters relieves EZH2 repression and leads to the transcriptional activation of a subset of EZH2/PRC2 target genes in HBV-infected cells and HBV-related HCCs.
Our results highlight the ability of HBx to bind RNA to impact on the epigenetic control of both viral cccDNA and host genes and provide a new key to understand the role of DLEU2 and EZH2 overexpression in HBV-related HCCs and HBx contribution to hepatocytes transformation.
A convenient, reproducible biomarker of hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) transcriptional activity is lacking. We measured circulating HBV RNA (cirB-RNA) in untreated ...and nucleos(t)ide analogues (NUC) treated chronic hepatitis B (CHB) patients to define its correlation with intrahepatic viral markers and HBV core-related antigen (HBcrAg).
Paired liver biopsy and serum samples were collected from 122 untreated and 30 NUC-treated CHB patients. We measured cirB-RNA, HBV DNA, hepatitis B surface antigen (HBsAg), HBcrAg and alanine aminotransferase levels. cirB-RNA was quantified using an investigational HBV RNA assay for use on the cobas 6800 system. The test detects a region spanning the HBV canonical polyadenylation site. cccDNA and 3.5 kb RNA in liver tissue were assessed by quantitative PCR and droplet digital PCR.
cirB-RNA was detectable in 100% of HBeAg(+) chronic hepatitis (CH), 57% and 14% of HBeAg(-) CH and chronic infection untreated patients and 47% of NUC-treated patients. cirB-RNA undetectability was associated with lower intrahepatic cccDNA transcriptional activity, as well as serum HBcrAg, but no significant differences in HBsAg, in both untreated and treated patients. In untreated HBeAg(-) patients, cirB-RNA correlated with intrahepatic 3.5 kb RNA and cccDNA transcriptional activity, serum HBV DNA and HBcrAg, but not with HBsAg or total cccDNA levels. Combined undetectability of both cirB-RNA and HBcrAg detection in untreated HBeAg(-) patients identified a subgroup with the lowest levels of intrahepatic transcriptionally active cccDNA.
Our results support the usefulness of quantification of circulating HBV RNA expressed from cccDNA as an indicator of intrahepatic active viral reservoir in both untreated and NUC-treated CHB patients.
NCT02602847.
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