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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.


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.


PubMed | Pitie Salpetriere Hospital, Leeds Teaching Hospitals NHS Trust, Creighton University, Innsbruck Medical University and 17 more.
Type: Journal Article | Journal: Journal of clinical immunology | Year: 2016

Spondyloenchondrodysplasia is a rare immuno-osseous dysplasia caused by biallelic mutations in ACP5. We aimed to provide a survey of the skeletal, neurological and immune manifestations of this disease in a cohort of molecularly confirmed cases.We compiled clinical, genetic and serological data from a total of 26 patients from 18 pedigrees, all with biallelic ACP5 mutations.We observed a variability in skeletal, neurological and immune phenotypes, which was sometimes marked even between affected siblings. In total, 22 of 26 patients manifested autoimmune disease, most frequently autoimmune thrombocytopenia and systemic lupus erythematosus. Four patients were considered to demonstrate no clinical autoimmune disease, although two were positive for autoantibodies. In the majority of patients tested we detected upregulated expression of interferon-stimulated genes (ISGs), in keeping with the autoimmune phenotype and the likely immune-regulatory function of the deficient protein tartrate resistant acid phosphatase (TRAP). Two mutation positive patients did not demonstrate an upregulation of ISGs, including one patient with significant autoimmune disease controlled by immunosuppressive therapy.Our data expand the known phenotype of SPENCD. We propose that the OMIM differentiation between spondyloenchondrodysplasia and spondyloenchondrodysplasia with immune dysregulation is no longer appropriate, since the molecular evidence that we provide suggests that these phenotypes represent a continuum of the same disorder. In addition, the absence of an interferon signature following immunomodulatory treatments in a patient with significant autoimmune disease may indicate a therapeutic response important for the immune manifestations of spondyloenchondrodysplasia.


Deroux A.,Service de medecine interne | Brion J.P.,Service de maladies infectieuses | Hyerle L.,Service de maladies infectieuses | Belbezier A.,Service de medecine interne | And 5 more authors.
Journal of Clinical Virology | Year: 2014

Hepatitis E (HEV) is an emerging disease in our developed countries, but is not routinely tested for in case of liver cytolysis. However, a growing number of extra-hepatic manifestations of HEV infection associated with acute hepatitis are reported. In this article, we discuss two cases of HEV with neurological symptoms, one with encephalitis, and the other with Parsonage Turner syndrome. All these disorders appeared concomitantly with liver cytolysis and disappeared quickly, following the viral kinetics. Only twenty cases of neurological manifestation of HEV have been described before. The use of HEV serology in patients with concurrent liver cytolysis and neurological symptoms has to be improved. © 2014 Elsevier B.V.


Ittah M.,University Paris - Sud | Miceli-Richard C.,University Paris - Sud | Lebon P.,Service de Virologie | Pallier C.,Service de Virologie | And 2 more authors.
Journal of Innate Immunity | Year: 2011

B cell-activating factor of the TNF family (BAFF) plays a key role in promoting B lymphocyte activation and survival. We previously showed in primary Sjögren's syndrome that salivary gland epithelial cells (SGECs), the resident targeted cells of autoimmunity in this disease, can produce BAFF after infection with a double-stranded RNA (dsRNA) virus by a protein kinase RNA (PKR)-dependent mechanism. This study aimed to assess the effect of different viruses on various cell types - SGECs but also dendritic cells (DCs) and monocytes - in the induction of BAFF. BAFF induction was observed after Sendai virus infection of monocytes and SGECs, as well as poly(I:C) stimulation of DCs. However, PKR inhibition by 2-aminopurine failed to reduce BAFF expression in these infected or stimulated cells. Conversely, in Sendai virus-infected monocytes, blocking type 1 interferon (IFN) receptor by anti-IFNAR1 antibody strongly inhibited BAFF expression. These results provide additional data suggesting that both dsRNA virus stimulation of DCs and single-stranded RNA virus infection of SGECs or monocytes can induce BAFF expression, but through a PKR-independent mechanism for these 3 cell types and a type 1 IFN-dependent mechanism in monocytes and SGECs. Thus, BAFF induction by viral infection is a general phenomenon, but the types of viruses and mechanisms of the induction depend on the cell type. Copyright © 2010 S. Karger AG.


Besnard M.,Center Hospitalier Of Polynesie Francaise Chpf | Eyrolle-Guignot D.,Service d'obstetrique | 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.


Rosain J.,Service de Virologie | Froissart A.,Service de Medecine Interne | Estrangin E.,Laboratoire Of Microbiologie | Rozenberg F.,Service de Virologie
Journal of Clinical Virology | Year: 2015

Whereas herpes simplex virus type 1 (HSV-1) is a recognized cause of acute oropharyngeal infection in young adults, HSV-2 infections are mostly associated with genital symptoms. We report a case of acute and prolonged febrile ulcerative pharyngotonsillitis with inflammatory syndrome which persisted despite antibiotic therapy for 8 days and required hospitalization in an 18-year old immune competent and sexually active female patient. HSV-2 was evidenced in tonsillar samples and blood by real time PCR, and HSV type-specific serology showed HSV-2 primary infection. Despite delayed diagnosis, acyclovir treatment led to rapid clinical improvement. This case highlights HSV-2 as an unusual cause of pharyngotonsillitis that should be reminded in sexually active patients. © 2014 Elsevier B.V.


PubMed | Angers University Hospital Center, Center Hospitalier Of Rodez, Service de virologie and British Petroleum
Type: Journal Article | Journal: Medecine et sante tropicales | Year: 2016

Experience of four years of control of the transmission of hepatitis B in a rural area in Far North Cameroon is presented: (i) prevention of mother to child transmission, (ii) HBsAg screening before blood transfusion, (iii) detection of HIV/HBV co-infections, (iv) protection of healthcare workers. The prevalence of HBsAg is very high in the four populations studied: 18.2% of pregnant women, 16.9% of candidate for blood donation, 14.4% of people living with HIV and 18% of healthcare workers. Despite limited resources, effective actions are possible. Prevention of mother to child transmission of HBV with vaccination at birth has been set up, with bottlenecks - similar to those observed in HIV - but decreasing over the study. The screening of all potential blood donors has been reached over the years for HIV, HBsAg and HCV, which has led to the eviction of one out of five potential blood donors. Screening of healthcare workers reminded us that adult protection is based on a very early vaccination and not when hiring, even if it is possible to diagnose rare adults eligible for vaccination by research of anti-HBc antibody. A program of hepatitis B control, essential in Africa, appears feasible in rural areas in a framework of an overall improvement in care delivery.


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.


PubMed | Service de Virologie, Hopitaux Universitaires Pitie Salpetriere and Service dHematologie et Therapie Cellulaire
Type: Journal Article | Journal: Transplant infectious disease : an official journal of the Transplantation Society | Year: 2016

Hemorrhagic cystitis (HC) is a common complication after hematopoietic allogeneic stem cell transplantation (HSCT) associated with intensity of the conditioning regimen, cyclophosphamide (Cy) therapy, and BK polyomavirus (BKPyV) infection.We analyzed 33 consecutive haploidentical (haplo) HSCT recipients transplanted for hematologic diseases. Eleven patients had a previous transplant. Median follow-up was 11 months. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine + mycophenolate mofetil and post-HSCT Cy.Thirty-two of 33 patients achieved neutrophil recovery. Cumulative incidence (CI) of platelet recovery was 65%. CI grade II-IV acute GVHD was 44%. Twenty patients developed HC in a median time of 38 days. CI of HC at day 180 was 62%. BKPyV was positive in blood and urine of 91% of patients at HC onset. HC resolved in 18/20 patients. Factors associated with HC were previous transplant (P = 0.01) and occurrence of cytomegalovirus reactivation before HC (P = 0.05). Grade II-IV acute GVHD was not associated with HC (P = 0.62). CI of day 180 viral infections was 73%. Two-year overall survival (OS) was 50%; HC did not impact OS (P = 0.29).The incidence of HC after haplo with post-HSCT Cy is high and is associated with morbidity, especially in high-risk patients such as those with a previous transplant history and with impaired immune reconstitution.

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