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Le Touquet – Paris-Plage, France

Herpes simplex encephalitis (HSE) is a rare but severe complication of frequent and mostly benign infection with herpes simplex virus (HSV). Although rapid and sensitive diagnosis tools and active antiviral drugs are available, HSE morbidity/mortality levels remain unsatisfactory. Molecular and cellular determinants of HSE are incompletely understood. The rarity and severity of the disease have suggested an increased susceptibility of some subjects to HSV infection. Numerous experimental studies have investigated the respective role of host and viral factors in HSE. The results of these studies have illustrated the major role of the innate immune response, in particular interferons (IFNs), in limiting access of the virus into and/or virus replication in the central nervous system (CNS). In a few children with HSE, specific defects of the immune innate response have been identified, which impair the IFN-α/β and IFN-λ production of fibroblasts and/or neurons infected with HSV and render these cells more permissive to infection. The mutations affect proteins involved in the IFN pathway induced by stimulation of the TLR3 receptor. The patients' susceptibility to infection is restricted to HSV CNS invasion, underlining the major role of TLR3 in CNS protection against viral infection. The incomplete clinical penetrance of these molecular defects suggests that other factors (age, infectious dose) are involved in HSE. Whether pathogenesis of adult HSE is similar has not been investigated. © 2013 Elsevier Masson SAS.

Besnard M.,Center Hospitalier Of Polynesie Francaise Chpf | Eyrolle-Guignot D.,Service dObstetrique | Guillemette-Artur P.,Service de radiologie | Lastere S.,Laboratoire Of Biologie Medicale | And 9 more authors.
Eurosurveillance | Year: 2016

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. © 2016, European Centre for Disease Prevention and Control (ECDC). All Rights Reserved.

Cadranel J.,University Pierre and Marie Curie | Guihot A.,University Pierre and Marie Curie | Guihot A.,French Institute of Health and Medical Research | Marcelin A.G.,Service de Virologie | And 4 more authors.
European Respiratory Journal | Year: 2013

Human herpesvirus (HHV)-8 is an oncogenic gamma herpesvirus that was first described in 1994 in Kaposi sarcoma lesions. HHV-8 is involved in the pathophysiological features of multicentric Castleman's disease (MCD) and primary effusion lymphoma (PEL), both rare B-cell lymphoproliferative diseases. HHV-8-related tumours occur almost exclusively in immunocompromised patients, mostly those with HIV infection. Combined antiretroviral therapies have reduced the incidence of Kaposi sarcoma but not MCD and PEL. HHV-8-related diseases frequently exhibit pulmonary involvement, which may indicate the disease. Kaposi sarcoma in the lung is often asymptomatic but may require specific therapy. It mostly shows cutaneous or mucosal involvement. Patients with typical MCD present fever and lymphadenopathy associated with interstitial lung disease without opportunistic infection. Specific treatment may be urgent. PEL provokes a febrile, lymphocytic-exudative pleural effusion, without a pleural mass on computed tomography scan. Rapid diagnosis prevents unnecessary examinations and leads to specific, rapid treatment. Therapy is complex, combining antiretroviral therapy and chemotherapy. Copyright ©ERS 2013.

Laverdure N.,Service dHepato gastroenterologie et nutrition pediatrique | Scholtes-Brunel C.,Service de Virologie | Rivet C.,Service dHepato gastroenterologie et nutrition pediatrique | Heissat S.,Service dHepato gastroenterologie et nutrition pediatrique | And 5 more authors.
Journal of Clinical Virology | Year: 2015

Background: Hepatitis E is an emerging disease in developed countries and is usually asymptomatic, particularly in children. Chronic infection is possible in immunocompromised individuals. In the context of a liver transplant, it can simulate a rejection. In this case, antiviral therapy may be considered, thus highlighting the need to diagnose hepatitis E virus (HEV) infection in this population. Objectives: Given the lack of data in France, we have studied the the prevalence of antibodies to HEV in the paediatric liver transplant population. Study design: This was a retrospective study, carried out in Lyon between 1st January 2010 and 31 May 2013. HEV serology (anti-HEV IgM &IgG) and HEV PCR were studied in 96 children who had undergone liver transplants (84 isolated liver and 12 combined liver and kidney transplants). Results: Eight patients (8.3%; 62.5% girls; mean age:12.3 years) were HEV seropositive. The mean period since their transplantation was 10 years (range:2-21.8 years). Biliary atresia was the principal indication for transplantation. Seven of these eight children had received liver transplants. There were no differences between the epidemiological and clinical data concerning these patients and the remainder of the study population, particularly with respect to immunosuppression(7/8 tacrolimus; 50% dual immunosuppression). No cases of chronic hepatitis E were found, but 1/8 had chronic cytolysis(EBV&adenovirus infection). In all the patients tested(4/8), seroconversion had occurred after the transplant. There was no significant differences between the age groups in this study. Conclusions: This study showed that in France, the prevalence of antibodies to HEV in paediatric liver and combined liver and kidney transplant patients is 8.3%, as has been found by other European authors. © 2015 Elsevier B.V.

Thibault V.,Service de Virologie | Bara J.-L.,SAFE , LLC | Nefau T.,University Paris - Sud | Duplessy-Garson C.,SAFE , LLC
Journal of Infectious Diseases | Year: 2011

Prevention programs for intravenous drug users have proven their efficacy in decreasing human immunodeficiency virus transmission but have limited effect on hepatitis C virus (HCV) contamination. A study was conducted to document the presence of HCV genome (HCV RNA) in 620 items of used injecting paraphernalia collected from representative sites. Using sensitive molecular techniques, HCV RNA was not detected on used filters or water vials and was seldom detected on cups (9%). However, HCV RNA was frequently found on syringe pools (38%) and on swabs (82%) at high titers. Our investigation, which was conducted in real injecting settings, highlights swabs as a potential source for HCV transmission. © 2011 The Author.

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