Chronic hepatitis delta cirrhosis cured by adapting PEG-IFNα-2a + tenofovir disoproxil fumarate treatment duration until HBsAg loss.

As the loss of HBsAg during treatment of chronic hepatitis delta (CHD) is mandatory for definitive clearance and durable response, the optimal target of therapy should be complete response (CR), defined as loss of HDV RNA and HBsAg, plus development of anti-HBs. The optimal treatment duration of CHD is not well established. We present 2 cases of patients with CHD cirrhosis who were treated with prolonged Peg-IFNα-2a + tenofovir disoproxil fumarate until HBsAg loss, and who achieved CR after 46 and 55 months of treatment respectively. A personalized approach and prolonged treatment duration determined by HBsAg loss may increase the likelihood of CR in CHD.

Acute Coxsackievirus B3-induced meningo-cerebellitis in an immunocompetent adult patient.

We report an acute Coxsackievirus B3 (CVB3)-induced meningo-cerebellitis in an immunocompetent adult patient. CVB3 has a global distribution and is the most common Enteroviruses cause of myocarditis and sudden cardiac death. To our knowledge, CVB3 is exceedingly rare as causes of meningo-encephalitis in immunocompetent adults, whereas some cases have been reported in neonates due to perinatal acquired infections or in immunocompromised patients.

Primary resistance to antiretroviral drugs of HIV strains in Chad: a retrospective investigation by analysis of frozen dried blood spot samples.

No data concerning antiretroviral drug's (ARV) primary resistance mutation rates in Chad are available. We retrospectively analysed frozen-stored dried blood spot samples that were collected from 48 Chadian human immunodeficiency virus (HIV)-1 seropositive patients naïve of ARV. HIV-1 protease and reverse transcriptase genes were successfully sequenced for 24 (60.0%) of the 40 patients displaying a viral load > 1000 copies/ml. Seven (29.2%) displayed mutations conferring resistance against one or more classes of ARV. We evidenced high levels of primary ARV resistance mutations in Chad, but lower than those observed in patients with failure to first-line ARV.

Major 5'terminally deleted enterovirus populations modulate type I IFN response in acute myocarditis patients and in human cultured cardiomyocytes.

Major 5'terminally deleted (5'TD) group-B enterovirus (EV-B) populations were identified in heart biopsies of patients with fulminant myocarditis or dilated cardiomyopathy suggesting that these 5'TD forms are key drivers of host-cell interaction in EV cardiac infections. To date, early emergence of EV-B 5'TD forms and its impact on type 1 IFN response during acute myocarditis remains unknown. Using quantitative RACE-PCR assay, we identified major EV-B 5'TD RNA populations in plasma or heart samples of acute myocarditis cases. Deletions identified within the 5' non-coding region of EV-B populations only affected secondary-structural elements of genomic RNA domain I and were distinguished in two major groups based on the extent of RNA structural deletions. Proportions of these two respective EV-B 5'TD population groups were positively or negatively correlated with IFN-ß levels in plasma samples of myocarditis patients. Transfection of synthetic CVB3/28 RNAs harboring various 5'terminal full-length or deleted sequences into human cultured cardiomyocytes demonstrated that viral genomic RNA domain I possessed essential immunomodulatory secondary-structural elements responsible for IFN-ß pathway induction. Overall, our results highlight the early emergence of major EVB-TD populations which deletions affecting secondary-structures of RNA domain I can modulate innate immune sensing mechanisms in cardiomyocytes of patients with acute myocarditis.

Cerebral venous thrombosis: a rare complication of herpes simplex encephalitis.

We report a case of classic HSE with early neurological relapse 7 days after onset of acyclovir treatment secondary to cerebral venous thrombosis (CVT). The development of CVT after meningoencephalitis has been described with neurotropic viruses such as HSV, HIV, or enteroviruses and also bacterial or fungal agents. CVT is probably the consequence of the inflammation secondary to these infections. A diagnosis of CVT, although rarely described, should be systematically suspected in patients with HSE who present no or only moderate improvement, or early relapse of symptoms despite adapted acyclovir treatment.

Post-mortem microbiology in sudden death: sampling protocols proposed in different clinical settings.

BACKGROUND: Autopsies, including minimally invasive autopsies, are a powerful tool for determination of the cause of death. When a patient dies from an infection, microbiology is crucial to identify the causative organism. Post-mortem microbiology (PMM) aims to detect unexpected infections causing sudden deaths; confirm clinically suspected but unproven infection; evaluate the efficacy of antimicrobial therapy; identify emergent pathogens; and recognize medical errors. Additionally, the analysis of the thanatomicrobiome may help to estimate the post-mortem interval. AIMS: The aim was to provide advice in the collection of PMM samples and to propose sampling guidelines for microbiologists advising autopsy pathologists facing different sudden death scenarios. SOURCES: A multidisciplinary team with experts in various fields of microbiology and autopsies on behalf of the ESGFOR (ESCMID - European Society of Clinical Microbiology and Infectious Diseases - study group of forensic and post-mortem microbiology and in collaboration with the European Society of Pathology) developed this narrative review based on a literature search using MedLine and Scopus electronic databases supplemented with their own expertise. CONTENT: These guidelines address measures to prevent sample contamination in autopsy microbiology; general PMM sampling technique; protocols for PMM sampling in different scenarios and using minimally invasive autopsy; and potential use of the evolving post-mortem microbiome to estimate the post-mortem interval. IMPLICATIONS: Adequate sampling is paramount to identify the causative organism. Meaningful interpretation of PMM results requires careful evaluation in the context of clinical history, macroscopic and histological findings. Networking and closer collaboration among microbiologists and autopsy pathologists is vital to maximize the yield of PMM.

Epsilon wave on an electronic loop in a case of arrhythmogenic right ventricular dysplasia with myocarditis: an updated definition of the Epsilon wave.

A young man presented with a history of myocarditis with palpitations and dizziness. He had implantation of a loop recorder that showed repetitive short episodes of VT. In addition, there were fragmented potentials immediately following the large and sharp electrograms (EGMs) before as well as after episodes of VT suggesting an Epsilon wave. This signal can be observed in multiple cardiac conditions including coronary artery disease. It was originally recorded on the epicardium as well as on the endocardium. However, in ARVD it can be defined as an electric signal observed after the end of the QRS complex in the right as opposed to the left precordial leads (difference ≥ 25 ms). It can also be an aid to the diagnosis of patients with ARVD who have other signs or symptoms suggesting ARVD including episodes of myocarditis. This potential consists of a slurring at the end of the QRS complex or an independent potential after the return to the isoelectric line. It can be better observed by increasing amplification of the ECG tracing as well as double speed using the Fontaine lead system. Epsilon wave too small to be recorded on the standard ECG can be extracted by Signal Averaging ECG SAECG).

[Diagnostic and therapeutic contribution of microbiological analysis in severe microbial keratitis at Reims University Hospital between 2012 and 2014]. / Apport diagnostique et thérapeutique des prélèvements microbiologiques des abcès de cornées avec critères de gravité au CHU de Reims entre 2012 et 2014.

PURPOSE: To investigate the contribution of microbial analysis in the diagnosis and management of severe microbial keratitis. MATERIAL AND METHOD: This is a monocentric retrospective study at the University Hospital of Reims from January 2012 to December 2014. Corneal scrapings with infectious keratitis were subjected to routine bacterial and fungal culture. PCR was also performed to detect various viral DNA (VZV, CMV, EBV, HSV 1 & 2, adenovirus) and Acanthamoeba sp. DNA. All contact lens cases were analyzed if available. RESULTS: One hundred and six patients were hospitalized, including 30 contact lens wearers (28.3%). Sixty-four bacterial cultures were positive (68%). Twenty-five different bacterial species were identified with a majority of gram-positive bacteria (67.92%). Among contact lens wearers, the initial VA was better than non-wearers (P=0.0004) and 37% of bacteria identified (a plurality) were gram positive. Of 11 contact lens case analyzed, in only one case (3.3%) did the result correlate with the corneal culture. Only 9 samples from the 323 viral DNA extractions and real time PCR were positive (2.8%); 7 were HSV1. No prior antiviral therapy had been started. Fungal culture was positive in 2 of the 97 corneal samples taken and 63.6% of the contact lens cases (7/11 cases). Only one of the 40 Acanthamoeba sp. PCR's was positive. CONCLUSION: The systematic performance of microbiological investigations is a good diagnostic approach given the polymorphism of clinical presentations of corneal ulcers, which can sometimes be extremely misleading. Culture of contact lens cases appears ineffective for the detection and determination of the causative microorganism. The high incidence of Staphylococcus in bacterial keratitis and the prevalence of infections with gram-positive bacteria in contact lens wearers were noted.

The microarray technology: facts and controversies.

Molecular diagnostic techniques for viral testing have undergone rapid development in recent years. They are becoming more widely used than the classical virological assays in the majority of clinical virology laboratories, and now represent a new method for the diagnosis of human viral infections. Recently, new techniques based on multiplex RT-PCR amplification followed by microarray analysis have been developed and evaluated. On the basis of amplification of viral genome-specific fragments by multiplex RT-PCR and their subsequent detection via hybridization with microorganism-specific binding probes on solid surfaces, they allow simultaneous detection and identification of multiple viruses in a single clinical sample. The management of viral central nervous system and respiratory tract infections currently represents the two main applications of the microarrays in routine virological practice. Microarrays have shown reliable results in comparison with those of referenced (RT)-PCR assays, and appear to be of major interest for the detection of a broad range of respiratory and neurotropic viruses, assessment of the pathogenicity of newly discovered or neglected viruses, and identification of multiple viral infections in clinical samples. Despite several limitations observed during the different studies performed, this new technology might improve the clinical management of patients by enlarging the range of the viruses detected, in particular in cases of severe infections leading to patient hospitalization in the intensive-care unit. They might also help in the prevention of nosocomial transmission in hospital departments by contributing to the development of new epidemiological surveillance systems for viral infections.

JC human polyomavirus is associated to chromosomal instability in peripheral blood lymphocytes of Hodgkin's lymphoma patients and poor clinical outcome.

BACKGROUND: B cells are potential sites for latency and reactivation of the human neurotropic JC polyomavirus (JCV). We investigated JCV and Epstein-Barr virus (EBV) status in peripheral blood lymphocytes (PBL) from 74 Hodgkin's lymphoma (HL) and 91 B-cell non-Hodgkin's lymphoma (B-NHL) patients. PATIENTS AND METHODS: JCV and EBV DNA were assessed by PCR, and FISH technique was used to localize viral infection and to estimate chromosomal instability (rogue cells, 'chromosomal aberrations') throughout evolution. The influence of viral infection and chromosomal instability on freedom from progression (FFP) was investigated in HL patients. RESULTS: PCR product sequencing of PBL identified JCV in 42 (57%) circulating lymphocytes of HL patients. FISH analysis revealed that the presence of cells with a high JCV genome copy number--associated to the presence of rogue cells and 'higher frequency of chromosomal aberrations'--increased from 15% before treatment to 52% (P < 10(-5)) after. The co-activation of JCV and EBV was independent of known prognostic parameters and associated with a shorter FFP (JCV and EBV co-activation P < 0.001, rogue cells P < 0.002). CONCLUSION: In HL, JCV activation and chromosomal instability have been identified in PBL and associated with a poorer prognosis, especially in EBV+.

Immunogenicity and booster efficacy of pre-exposure rabies vaccination.

A multivariate analysis was used to identify factors influencing the immunogenicity of rabies vaccine and to assess the efficacy of booster injections in a cohort of 407 people monitored prospectively for 10 years after primary vaccination. Rabies vaccine (HDCV or PVRV) was injected by intramuscular route either on days 0 and 28 or on days 0, 7 and 28. All the participants received a booster injection on day 365. At the end of follow-up (year 10), 163 subjects had titers >0.5IU/ml (group A) and 59 subjects had titers <0.5IU/ml (group B: poor responders). The number of injections had a significant influence (P<0.001) on the magnitude of the serological response to rabies vaccine, but the type of vaccine and the potency of the batches did not (P=0.07 and P=0.06, respectively). The difference between GMTs on day 365 and day 379 was significantly lower in group B than in group A (13 and 50.70IU/ml, respectively; P<0.001). In conclusion, our study confirms that the rabies pre-exposure vaccination protocol of three intramuscular injections significantly decreases the proportion of poor responders at 10 years. Moreover, our findings indicate that a routine booster injection at 1 year could significantly increase the levels and duration of antibody titers.

Nephropathia epidemica and leptospirosis in Champagne-Ardenne, France: comparison of clinical, biological and epidemiological profiles.

In the present retrospective study, we described a series of 45 non-icteric leptospirosis and 44 nephropathia epidemica (NE) patients diagnosed in the northeast of France from 1995 to 2005 and compared their clinical picture and laboratory parameters, as well as some epidemiological data. Loin pain (P < 0.001), abdominal pains (P = 0.007), rise of blood pressure (P < 0.001) and pharyngitis (P = 0.01) were more frequently found in NE patients. Aspartate aminotransferase (ASAT) (P = 0,006), creatine phosphokinase (CPK) (P < 0.0001) and C-reactive protein (CRP) (P < 0.0001) were higher in leptospirosis, whereas creatinine (P = 0.009) was higher in NE. Leptospirosis mainly concerns occupational hazards, e.g. farmers, and leisure activities like swimming, and NE concerns professional foresters or leisure activities in the forest and the cleaning of attics. During hospitalisation, patients receiving antibiotics were more frequent among leptospirosis than among NE patients (80% versus 59%, P = 0.06). Among the various common clinical signs, only acute myopia appeared to be a pathognomonic but inconsistently observed clinical sign, which was only observed in 47% of NE cases.

Fatal Epstein-Barr virus primo infection in a 25-year-old man treated with azathioprine for Crohn's disease.

We report a case of Epstein-Barr virus (EBV) primo infection with the development of successive infectious mononucleosis, hemophagocytic lymphohistiocytosis, and B-cell lymphoproliferative disorder in a patient treated with azathioprine for Crohn's disease. This case report suggests that specific EBV-related clinical and virological management should be considered when treating a patient with inflammatory bowel disease with azathioprine.

[Epidemiological and clinical study of Mycoplasma pneumoniae respiratory infections in children hospitalized in a pediatric ward between 1999 and 2005 at the Reims University Hospital]. / Etude épidémiologique et clinique des infections respiratoires àMycoplasma pneumoniae chez les enfants hospitalisés en pédiatrie entre 1999 et 2005 au CHU de Reims.

OBJECT: To determine the frequency, clinical features, and morbidity of Mycoplasma pneumoniae infections. METHOD: Retrospective study of 76 consecutive children under 16 years of age hospitalized at the Reims University Hospital from 1999 to 2005 with M. pneumoniae pneumonia. The infection was defined by the presence of M antibodies and/or an increase in G antibodies (quantitative Elisa test). RESULTS: M. pneumoniae was the cause of 16% (76/464) of hospitalized pneumonia cases. A significantly increased frequency was observed in 2004 (34%; 19/56) and 2005 (26%; 22/84) versus 11% from 1999 to 2003, p<5.10(-4). The mean age of the patients was 6 years and 8 months, with a peak at 3 years (14/76; 18% of patients). The most frequent clinical feature was cough (80%; 56/70). The chest X-ray showed typical radiological features such as peribronchial and perivascular interstitial infiltrates in only 23% (16/69). Respiratory and extrarespiratory complications were seen in 17 and 12 children, respectively. Only 1 child suffered from respiratory sequelae. CONCLUSION: M. pneumoniae pneumonia is frequent in children over 2 years of age. The diagnosis is sometimes difficult to initially assert because there are no specific features. Respiratory and extrarespiratory complications remain possible. Respiratory sequelae can still exist even if most cases evolve favorably under treatment by macrolides.

Dual infections by influenza A/H3N2 and B viruses and by influenza A/H3N2 and A/H1N1 viruses during winter 2007, Corsica Island, France.

BACKGROUND: The investigation of dual influenza infection human cases is of major interest specifically for the control of new emerging influenza strains. OBJECTIVES: Using RT-PCR assays, we retrospectively assessed the prevalence of dual influenza virus infections that occurred in patients during the 2006-2007 winter season in Corsica Island (France). STUDY DESIGN: One hundred and thirty-four nasal swabbing samples taken from patients suffering from influenza-like illness between February and March 2007 were analysed using a rapid influenza antigen detection test, cell culture and RT-PCR assays. RESULTS AND CONCLUSION: Influenza viruses were detected in 93 (69.4%) of 134 patients with influenza-like illness using the combination of classical and molecular assays. Dual respiratory infections by influenza viruses were detected in 3 (3.2%) of the 93 influenza positive patients, including two cases of infection by influenza A/H3N2 and B viruses and one case of dual infection by influenza A/H3N2 and A/H1N1 viruses. In the present report, human co-infection cases by two influenza viruses appeared as a rare event in symptomatic patients. However, the virological and epidemiological mechanisms that determine the occurrence of dual influenza infections remain to be fully investigated in further prospective multicentric studies.

[Enteroviruses receptors and cell entry]. / Récepteurs et voies d'entrée des entérovirus dans la cellule cible.

Human enteroviruses, which belong to the family of Picornaviridae, are common infectious viral agents transmitted by fecal-oral or airway routes. These positive RNA viruses possess a high genetic diversity and variability. They can evolve through genetic mutations or recombination mechanisms that are associated to the emergence of new potential epidemic serotypes. Human enteroviruses use different cellular receptors: receptors and co-receptors that are directly related to the tropism and the epidemiologic characteristics of some enterovirus serotypes. The receptors onto the cell-surface settle within a capsid depression, called canyon, initiating the process of viral uncoating. For some enteroviruses, a co-receptor molecule allows the crossing of cell topological barriers that is required to initiate the target cell infection. After the attachment phase, enteroviruses use the endocellar signaling pathways to support and optimize their entry into target-cells via endocytic pathways. The clathrin coated pits and the caveolae are both major ways of enterovirus entry in the cell even if "new" endocytic pathways regulated by enzymes of theADP ribosylation factors family and of the Rho family small GTPases have been recently described. The viral genetic diversity allows the human enteroviruses to simultaneously or alternatively use several distinct endocytic pathways in accordance to the infected cell lines, and allows a rapid and efficient adaptation to cellular microenvironments and to multiple immune selection pressures developed during the pathophysiological course of human infection. In conclusion, entry mechanisms used by human enteroviruses to infect target cells are various but they are closely dependent on the cellular functions that will be driven towards viral benefits. In the present time, the attachment and entry phases of the human enteroviruses into the target cell represent major viral events that may be targeted for the development of further new antiviral strategies.

[A case of influenza A community-acquired pneumonia in an elderly subject hospitalised in intensive care unit]. / A propos d'un cas de pneumopathie communautaire grippale chez un sujet âgé en réanimation.

Influenza pneumonia and influenza-associated severe exacerbation of pre-existing heart and lung disease are responsible for major complications that may require intensive care unit admission. Here, we report the case of a diabetic 70 year-old man hospitalised in the intensive care unit (ICU) of the University Medical Center of Reims (France) for a severe bilateral and alveolar pneumonia requiring mechanical ventilation. This patient had received a classical antibiotic treatment by amoxycillin (3 g/24 hours per os); 48 hours later, he was admitted in ICU for a respiratory failure that evolved rapidly towards an acute respiratory distress syndrome. Because of the context of a winter influenza outbreak, a nasal swabbing sample was tested for the presence of Influenzavirus nucleocapsid-antigens (Immunochromatographic test; BinaxNow Flu A & B, Binax, Portland, USA). This rapid assay revealed the presence of an Influenzavirus A respiratory infection five days after the beginning of the respiratory syndrome. This rapid viral diagnosis will be further confirmed in post mortem by the positive Influenza strain isolation onto lung tissues by classical cell culture techniques (Influenzavirus A strain, H3N2). Influenza pneumonia is a significant cause of morbidity and mortality, especially during influenza epidemics. The use of commercially available rapid diagnostic tests for influenza associated pneumonia, allows the potential use of new specific anti-neuraminidase drugs, which can be efficient during the 30 hours after the beginning of the clinical influenza syndrome.

[A fatal case of Herpes simplex virus meningoencephalitis in an immunocompetent adult]. / Un cas mortel de méningoencéphalite à Herpes simplex virus chez un adulte immunocompétent.

Management of herpes simplex virus encephalitis (HSE) has been considerably improved by the development of rapid polymerase chain reaction (PCR) assays and by the use of intravenous acyclovir. However, an absence of early antiviral treatment has been associated to a poor outcome in patients with HSE. In the present report, we described the case of a 53 years-old adult immunompetent patient who was admitted to the emergency department of university medical center of Reims (France). At the time of hospitalisation, he was suffering from a febrile encephalitis syndrome evolving for more than 24 hours. A cerebrospinal fluid (CSF) puncture was performed demonstrating the presence of a lymphocytic meningitidis (42 leukocytes/mm3 which 90% of mononuclear cells; CSF protein = 1650 mg/L) associated with high levels of interferon alpha (75 UI/mL). Specific herpesvirus PCR and hybridisation assays (Herpes Consensus Hybridowell, Argene, France) were positive for the detection of HSV-1 genome on this CSF sample. Despite the intravenous acyclovir treatment (15 mg/kg/8 hours) delivered at the time of hospitalisation, this immunocompetent adult patient will dead 15 days later by a cardiorespiratory failure that was related to extensive HSE lesions. The time delay between the beginning of the clinical syndrome and the instauration of intravenous acyclovir treatment (more than 24 hours) was the only point susceptible to explain the presence of extensive CNS lesions in this patient. Specific Herpesvirus PCR detection assays are powerful tools that are actually used to establish a rapid etiological diagnosis of viral meningo-encephalitis. However, in patients demonstrating clinical signs of encephalitis associated with an aseptic CSF, it remains essential to urgently initiate a presumptive intravenous acyclovir treatment (10-15 mg/kg/8 hours). Actually, this medical practice is the only one susceptible to reduce the morbi-mortality rates linked to HSE.