Meningoradiculitis due to varicella zoster virus reactivation in a patient treated with ixekizumab.

INTRODUCTION: Ixekizumab is a recently developed biopharmaceutical used since 2016 in the US and Europe for the treatment of plaque psoriasis. Few adverse effects have been reported in the literature and ixekizumab is not known to increase the risk of viral reactivation. Herein we report the case of an immunocompetent female patient treated with ixekizumab who presented meningoradiculitis due to varicella zoster virus (VZV) reactivation. PATIENTS AND METHODS: A 51-year-old woman, treated with ixekizumab for psoriasis, consulted in March 2018 for left hemicrania headache associated with left facial paralysis, but without fever. Brain MRI scans revealed cerebral venous thrombosis of the superior sagittal sinus. Analysis of cerebrospinal fluid (CSF) revealed lymphocytic meningitis and positive VZV-PCR. PCR blood assay for VZV was negative. Blood concentrations of anti-VZV IgG antibody increased while Anti-VZV IgM antibodies remained negative. The final diagnosis was VZV meningoradiculitis complicated by cerebral thrombophlebitis. The absence of skin rash, the rapid increase in anti-VZV IgG antibodies, the absence of anti-VZV IgM antibodies, and the negative blood PCR assay suggested viral reactivation rather than primary infection. The patient received acyclovir and coumadin and her condition improved rapidly. After multidisciplinary discussion, ixekizumab was reintroduced together with valacyclovir prophylaxis. CONCLUSION: This case raises the question of the risk of viral reactivation during treatment with an IL-17 inhibitor and with biologics in general. Neurological and vascular complications of VZV may occur without skin lesions and their occurrence during ixekizumab therapy must be investigated by PCR testing of CSF for VZV DNA.

Predominance of G9P[8] rotavirus strains throughout France, 2014-2017.

OBJECTIVES: Group A rotavirus is a major cause of acute gastroenteritis in young children worldwide. A prospective surveillance network has been set up in France to investigate rotavirus infections and to detect the emergence of potentially epidemic strains. METHODS: From 2014 to 2017, rotavirus-positive stool samples were collected from 2394 children under 5 years old attending the paediatric emergency units of 13 large hospitals. Rotaviruses were genotyped by RT-PCR with regard to their outer capsid proteins VP4 and VP7. RESULTS: Genotyping of 2421 rotaviruses showed that after a marked increase in G9P[8] (32.1%) during the 2014-2015 season, G9P[8] became the predominant genotype during the 2015-2016 and 2016-2017 seasons with detection rates of 64.1% and 77.3%, respectively, whereas G1P[8] were detected at low rates of 16.8% and 6.6%, respectively. Phylogenetic analysis of the partial rotavirus VP7 and VP4 coding genes revealed that all of these G9P [8] strains belonged to the lineage III and the P [8]-3 lineage, respectively, and shared the same genetic background (G9-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1) as did most of previously detected G9P[8] strains and particularly the emerging G9P[8] strains from the 2004-2005 season in France. CONCLUSIONS: G9P[8] rotaviruses have become the predominant circulating genotype for the first time since their emergence a decade ago. In the absence of rotavirus immunization programmes in France, our data give an insight into the natural fluctuation of rotavirus genotypes in a non-vaccinated population and provide a base line for a better interpretation of data in European countries with routine rotavirus vaccination.

Clinical severity and molecular characteristics of circulating and emerging rotaviruses in young children attending hospital emergency departments in France.

Group A rotavirus (RVA) is the leading cause of acute gastroenteritis in young children worldwide. A prospective surveillance network has been set up to investigate the virological and clinical features of RVA infections and to detect the emergence of potentially epidemic strains in France. From 2009 to 2014, RVA-positive stool samples were collected from 4800 children <5 years old attending the paediatric emergency units of 16 large hospitals. Rotaviruses were then genotyped by RT-PCR with regard to their outer capsid proteins VP4 and VP7. Genotyping of 4708 RVA showed that G1P[8] strains (62.2%) were predominant. The incidence of G9P[8] (11.5%), G3P[8] (10.4%) and G2P[4] (6.6%) strains varied considerably, whereas G4P[8] (2.7%) strains were circulating mostly locally. Of note, G12P[8] (1.6%) strains emerged during the seasons 2011-12 and 2012-13 with 4.1% and 3.0% prevalence, respectively. Overall, 40 possible zoonotic reassortants, such as G6 (33.3%) and G8 (15.4%) strains, were detected, and were mostly associated with P[6] (67.5%). Analysis of clinical records of 624 hospitalized children and severity scores from 282 of them showed no difference in clinical manifestations or severity in relation to the genotype. The relative stability of RVA genotypes currently co-circulating and the large predominance of P[8] type strains may ensure vaccine effectiveness in France. The surveillance will continue to monitor the emergence of new reassortants that might not respond to current vaccines, all the more so as all genotypes can cause severe infections in infants.

A patient with fever, abdominal pain and bicytopenia: Trouble once again with these IgM antibodies!

We here report the case of a 30-year old man with a history of ulcerative colitis, who presented clinical and biological features compatible with a viral hepatitis. Initial serological results revealed the presence of IgM antibodies against many viruses, and the most likely diagnosis was viral hepatitis A. However, further investigations were performed and concluded to cytomegalovirus primary infection.

Persistent viral DNA detection in blood after primary herpes simplex 1 infection revealed by hepatitis with hemophagocytic syndrome.

We here report the case of a 52-year old man who presented hepatitis with hemophagocytic syndrome triggered by herpes simplex 1 (HSV-1) primary infection. A high-level viremia was observed, and HSV-1 DNA remained detectable in blood for a long time after patient's recovery.

Anti-viral therapy in haemodialysed HCV patients: efficacy, tolerance and treatment strategy.

BACKGROUND: In end-stage renal disease (ESRD) patients, hepatitis C virus (HCV) eradication improves patient and graft survival. AIM: To determine optimal use of erythropoietin (EPO) and ribavirin, to compare ribavirin concentrations with those of HCV patients having normal renal function and to evaluate sustained virological response (SVR) in a prospective observatory of ESRD candidates for renal transplantation. METHODS: Thirty-two naïve patients were treated with Peg-IFN-α2a and ribavirin. Two different schedules of ribavirin and EPO administration were used: starting ribavirin at 600mg per week and adapting EPO when haemoglobin (Hb) fell below 10g/dL (adaptive strategy) or starting ribavirin at 1000mg per week while increasing EPO from the start of treatment (preventive strategy). RESULTS: Patients treated with the adaptive strategy had lower median Hb levels (9.6 vs. 10.9g/dL, P=0.02) and more frequent median Hb levels below 10g/dL (58 vs. 5%, P=0.0007) despite lower median ribavirin doses (105 vs. 142mg/day, P<0.0001) than patients treated with the preventive strategy. There was a trend for more frequent transfusion in patients treated with the adaptive strategy than in patients treated with preventive strategy (50 vs. 20%, P=0.08). Compared to patients with normal renal function, ESRD patients had lower ribavirin concentrations during the first month (0.81 vs. 1.7mg/L, P=0.007) and similar concentrations thereafter. SVR was reached in 50%. CONCLUSIONS: Pegylated interferon (Peg-IFN) and an adapted schedule of ribavirin are effective in ESRD patients. Increasing EPO from the start of treatment provides better haematological tolerance. The optimal dosage of ribavirin remains unresolved, in light of frequent side effects.

A 2-log drop in viral load at 1 month is the best predictor of sustained response in HCV patients with normal ALT: a kinetic prospective study.

The most reliable predictor of a sustained virological response in patients with persistently normal ALT has not been identified. We analysed 17 patients with genotype 1 chronic HCV who underwent therapy with pegylated interferon alfa 2b and ribavirin for 48 weeks. Two patients discontinued therapy within 28 days because of side effects and the remaining 15 patients were analysed in detail. An analysis of on treatment virological response using area under the receiver operating characteristic analyses showed that a 2 log drop in HCV RNA at day 28 was the best predictor of a sustained virological response and a failure to reduce viral load by 2 logs correctly identified patients with a low (<15%) probability of achieving a sustained virological response. Introduction of this early discontinuation rule in patients with normal ALT would allow nearly half of the patients to discontinue futile therapy at an early stage.

[Role of N-linked glycans in the functions of hepatitis C virus envelope glycoproteins]. / Rôle des N-glycanes dans les fonctions des glycoprotéines d'enveloppe du virus de l'hépatite C.

Hepatitis C virus (HCV) is an enveloped virus and encodes two envelope glycoproteins, E1 and E2. E1 and E2 are transmembrane type I proteins with a N-terminal ectodomain and C-terminal anchor. During their synthesis, E1 and E2 ectodomains are targeted in the endoplasmic reticulum lumen where they are modified by N-linked glycosylation. After their synthesis, E1 and E2 assemble as a non-covalent heterodimer. The N-linked glycosylation is based on the recognition of specific asparagine residue in the context of the consensus sequence Asn-X-Ser/Thr. E1 contains potentially 4 or 5 N-linked glycosylation sites and E2 up to 11. Recent data indicated that some glycans of glycoproteins E1 and E2 play a major role in protein folding and heterodimer formation. Some N-linked glycans of E2 were involved in interactions with CD81, a putative cellular receptor for HCV. It appeared that N-linked glycans of E1 and E2 played an important role of in the viral entry.

[Simultaneous detection of IgM anti-Epstein-Barr virus and IgM anti-hepatitis A during an acute hepatitis]. / Détection simultanée d'IgM anti-Epstein-Barr virus et d'IgM anti-hépatite A lors d'une hépatite aiguë.

We report a case of a 15-year-old young man who was admitted for an acute hepatitis. Virological assessment showed both IgM anti-EBV and IgM anti-hepatitis A. IgG anti-EBNA and clinical history allowed to rule out the hypothesis of a recent EBV infection and confirmed the diagnosis of acute hepatitis A infection.

[Acute polyarthritis during a parvovirus B19 primary infection]. / Polyarthrite aiguë au cours d'une primo-infection à parvovirus B19.

Parvovirus B19 classically causes erythema infectiosum in children, febrile arthralgia or acute erythroblastopenia in adult. The clinical spectrum of adult primary infection is sometimes misleading. We report an observation of an acute rheumatoid-like arthritis following primary parvovirus B19 infection in a 42-year-old woman.

[Emergent viruses: SARS-associate coronavirus and H5N1 influenza virus]. / Virus respiratoires émergents : virus du Sras et virus influenza A/H5N1 hautement pathogène.

Two viral agents with RNA genome are responsible for emerging illnesses: influenza virus A/H5N1 and Severe Acute Respiratory Syndrome virus (SARS). For the diagnosis of SARS virus infection, an epidemiological investigation is necessary to know whether the patient has been exposed to a risk in a country where the SARS virus is circulating or whether the patient had worked in a laboratory handling SARS virus. The detection of SARS virus is possible in various clinical samples (including urine) by viral culture or RT-PCR. The handling of those samples and RNA extraction must be performed in a BSL3 laboratory. The SARS virus RT-PCR is poorly sensitive, therefore the test should be performed on samples collected consecutively for several days. In front of a suspicion of A/H5N1, similar procedures are recommended. An epidemiologic investigation is necessary to specify whether the patient stayed in a country where A/H5N1 virus was circulating. Clinical samples needed for a specific diagnosis are: nasopharyngeal, throat-swab or fecal samples, cerebrospinal fluid and blood. The presence of A/H5N1 virus is confirmed by viral isolation or RNA detection by RT-PCR. RNA extraction must be performed in a BSL3 laboratory. For diagnosis of A/H5N1 virus infection, RT-PCR test amplifies specifically a fragment of H5 gene (Hemagglutinin). In french laboratories of medical virology, procedures are ready to diagnose the first case of A/H5N1 virus infection and cases of reemerging SARS virus infection.

[Fatal evolution of a dilated cardiomyopathy during a primary Epstein-Barr virus infection]. / Myocardiopathie dilatée d'évolution fatale au cours d'une primo-infection par le virus Epstein-Barr.

We report the observation of a 2-year-old child who developed an acute heart failure during a primary EBV infection. The viral serological diagnosis showed CMV and EBV IgM positivity. The detection of EBV genome by PCR and the characteristic evolution of EBV serological response confirmed a primary EBV infection.

[Fatal fulminant Epstein-Barr virus hepatitis]. / Hépatite fulminante fatale à Epstein-Barr virus.

Infectious mononucleosis is a common and benign disease. Although hepatic cytolysis is common during infectious mononucleosis, fulminant hepatitis is rare. We report an observation of a fatal fulminant hepatitis complicating a primary EBV infection in a 15 year-old male.

[Various approaches of therapeutic vaccination for the treatment of HIV type 1 infection]. / Différentes approches de vaccination thérapeutique dans le traitement de l'infection par le VIH-1.

HIV-1 infection is a major pandemic situation. With the advent of highly active antiretroviral therapy (HAART), morbidity and mortality associated with HIV-1 infection have been dramatically reduced. However, HAART does not enable eradication of the virus. The efficacy of these new regimens is limited by problems over long-term use such as toxicity and resistance. Therapeutic vaccination is an alternative approach to HIV-1 infection. The main aim is to boost and reinforce virus-specific host immune responses. Several immunogens and schedules of immunization have been tested. In this review, various strategies designed for therapeutic vaccines for HIV-1 infection are presented.

[Mechanisms of imiquimod indirect antiviral activity]. / Mécanismes de l'activité antivirale indirecte de l'imiquimod.

The potential role of an immune response in HPV-related anogenital disorders had already been anticipated by clinicians. Indeed the lesions efflorescence and the relapsing HPV infection in HIV positive patients as well as the lack of recurrence in patients with spontaneous cure, provided relevant clues for a likely immune mechanism. At present time, the role of the immune system in the development of HPV-related anogenital disorders is well established : HPV induce a humoral and cell mediated immune response. This response is mainly exerted towards infected cells; it is also exerted at the systemic level, through antibodies synthesis, but this pathway remains a secondary one. Due to the limits of the present therapies (either purely destructive and characterized by the rate of recurrences, or antiviral, but difficult to use), it was necessary to find a new treatment type which enhances the local immune response, results in the disappearance of lesions and allows for a decrease in the risk of recurrences. The original mechanism of action of the first cell-mediated immune response modifier: imiquimod, for local use (Aldara 5 % cream) is an answer to this need. The first positive results observed in vitro and in animals were confirmed in patients with HPV anogenital warts in a double blind placebo-controlled study: imiquimod inhibits HPV replication and results in the condyloma regression. Its action is based on the combined activation of the natural local immunity, by stimulating interferon alpha; and of the acquired immunity, by stimulating a T-cell mediated immune response. Thus imiquimod appears to be an original antiviral compound, because it does not act directly on the virus itself.

[Renal hydatid cyst. Apropos of 22 cases]. / Le kyste hydatique rénal. A propos de 22 cas.

Renal hydatid cyst ranks third among all visceral localisations. It is most often latent due to the deep situation of the kidney. The authors report their experience with 22 cases of hydatid disease of the kidney, and place special emphasis on wedge resection of the cyst which is a simple and effective operation.

The cell adhesion molecule Cell-CAM 105 is an ecto-ATPase and a member of the immunoglobulin superfamily.

Cell-CAM 105 (C-CAM), a cell adhesion molecule in rat hepatocytes, was digested with trypsin, and peptides were isolated and sequenced by Edman degradation. The sequences of 4 peptides agreed with different regions of rat liver ecto-ATPase. Detailed biochemical analyses confirmed the identity between C-CAM and the ecto-ATPase. C-CAM/ecto-ATPase is a transmembrane protein having 4 immunoglobulin-like domains in the extracellular portion, demonstrating membership of the immunoglobulin superfamily. The ATPase activity suggests that ATP might influence cell adhesion, which would explain the inhibitory effect of exogenously added ATP on adhesion of several cell types.