Infection à cytomégalovirus (intérêt de la charge virale en PCR temps réel chez l'immunodéprimé)

Le cytomégalovirus est une cause majeure de morbidité et mortalité chez les transplantés de moelle osseuse, d organe solide et chez les patients infectés par le VIH. L immunodépression sévère favorise la réactivation de l infection c est-à-dire la reprise de la réplication virale qui peut être sans conséquence clinique ou bien évoluer vers le stade de maladie. La mise en évidence de la réplication virale est déterminante dans la prise en charge du patient. Il est donc indispensable d avoir des outils virologiques performants. L antigénémie pp65 mise au point en 1988 a longtemps été considérée comme le Gold Standard jusqu au développement des techniques de PCR quantitative. L objectif de notre travail est de comparer les résultats d antigénémie et de charge virale en PCR temps réel au sein d une population d immunodéprimés, essentiellement des patients infectés par le VIH. Afin d évaluer la variabilité intertechnique, nous avons également comparé les performances de deux méthodes de PCR en temps réel, la PCR UL123 mise au point au laboratoire et la trousse commerciale PCR CMV R-gene®. Une bonne concordance et une bonne corrélation ont été retrouvées entre les trois méthodes. La charge virale en PCR temps réel est plus sensible que l antigénémie. En terme de faisabilité, la PCR est plus rapide, plus facile à mettre en oeuvre et plus reproductible que l antigénémie et de plus elle est réalisable chez des patients en aplasie sévère. Le manque de standardisation des techniques de PCR rend difficile la validation d un seuil de charge virale pour initier un traitement précoce. La création d un standard de référence résoudrait ces problèmes d interprétation.MONTPELLIER-BU Pharmacie (341722105) / SudocSudocFranceF

Le Norovirus (un problème émergent ?)

MONTPELLIER-BU Pharmacie (341722105) / SudocSudocFranceF

Severe Guillain-Barré syndrome associated with chronic active hepatitis C and mixed cryoglobulinemia: a case report

International audienceBackground: We describe a case of severe Guillain-Barre syndrome (GBS) associated with chronic active hepatitis C and mixed cryoglobulinemia (MC). To our knowledge, this association between GBS and hepatitis C virus (HCV) infection has been rarely reported.Case presentation: A 56-year-old man developed symmetrical muscle weakness in all extremities, areflexia and sensorial disorder followed by acute respiratory failure associated with chronic active hepatitis C, which was confirmed by the presence of anti-HCV antibodies in the serum and persistence of HCV RNA viral load for more than 6 months. Chronic hepatitis C was further complicated by type 3 MC. Electromyography showed peripheral nerve injury (mainly in axon). A severe acute motor sensory axonal neuropathy (AMSAN) was diagnosed. After treatment with intravenous immunoglobulin and plasma exchange followed by antiviral therapy by direct-acting antiviral agent, patient showed progressive recovery and was transferred 3 months after his first admission to a rehabilitation center.Conclusions: Our case reported a severe GBS associated with HCV infection and MC. EMG classified for the first time the subtype of GBS (severe AMSAN) correlated with severe clinical form. HCV infection should be screened in high-risk patients to prevent silent progression of the chronic hepatitis C and its potentially severe extra-hepatic manifestations

A review of a 13-month period of FilmArray Meningitis/Encephalitis panel implementation as a first-line diagnosis tool at a university hospital

International audienceEarly diagnosis and treatment of meningitis and encephalitis is essential for reducing both their morbidity and mortality. The FilmArray® Meningitis/Encephalitis (FA-M/E) panel is a recently available molecular tool allowing the simultaneous detection of 14 pathogens in about one hour. We evaluated its routine use over a 13-month period at Nîmes University Hospital, France. Cerebrospinal fluid (CSF) specimens were prospectively analyzed, independently of cell count; results were retrospectively analyzed and positive results compared to clinical and microbiological data. Among the 708 patients included (734 CSF samples), 89 (12.6%) had a positive FA-M/E panel, 71 (80%) for a viral pathogen and 18 (20%) for a bacterial pathogen. Enterovirus and HHV-6 were the main detected pathogens. Mean time-to-results was 1h46mn. Four non-clinically relevant results were detected (3 HHV-6 and 1 Haemophilus influenzae) on the basis of inconsistent clinical and/or biological data, and/or after visualization of melting curves. No CSF pleocytosis was observed in 11% of the patients with a positive FA-M/E panel. For the 18 patients with a positive FA-M/E panel for a bacterial pathogen, five (28%) had CSF samples showing a positive Gram stain allowing an early diagnosis of bacterial infection and 67% had CSF displaying a positive culture. Altogether the panel detected 5 cases of bacterial M/E (29%) not diagnosed by culture. Despite undeniable advantages, mainly ease of use, quick result availability, and an extremely low rate of invalid results, measures should be implemented to limit false-positive results due to contamination and a careful interpretation based on the overall data for each patient is required

Rhombencephalosynapsis and related anomalies: a neuropathological study of 40 fetal cases.

International audienceRhombencephalosynapsis is an uncommon cerebellar malformation defined by vermian agenesis with fusion of the hemispheres and of the dentate nuclei. Embryologic and genetic mechanisms are still unknown, and to date, no animal models are available. Ultrasound diagnosis is generally suspected after 22 weeks of gestation, and usually the abnormality is suggested by ventriculomegaly. Morphological analysis of 40 fetuses after medical termination of pregnancy allowed us to confirm that rhombencephalosynapsis was always associated with other brain abnormalities or malformations: Purkinje cell heterotopias, fusion of colliculi, forking and/or atresia of the aqueduct and of the third ventricle resulting in a fusion of the thalami, agenesis of the corpus callosum, lobar holoprosencephaly and neural tube defects. Pons and medulla were very infrequently abnormal. Furthermore, complete autopsy made it possible to separate either pure neurologic phenotypes, or associated with extraneural anomalies from syndromic forms: Gomez-Lopez-Hernandez syndrome (1 case) and VACTERL-H syndrome (6 cases). The number of our fetal cases strongly suggests that VACTERL-H association related with rhombencephalosynapsis emerges as a non-random association. Furthermore, recurrence and consanguinity were noted in two different families, which argue for a sporadic or inherited cause. From our results, it could be suggested that rhombencephalosynapsis may be due to defective genes regulating formation of the roof plate and the development of midline cerebellar primordium at the junction of the mesencephalon and of the first rhombomere

Surveillance of HIV-1 primary infections in France from 2014 to 2016: toward stable resistance, but higher diversity, clustering and virulence?

International audienc

New insights into the genetic etiology of Alzheimer’s disease and related dementias

Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

New insights into the genetic etiology of Alzheimer’s disease and related dementias

Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele