Sophie Minjolle

Increasing Incidence of Severe Epstein-Barr Virus-Related Infectious Mononucleosis: Surveillance Study

ABSTRACT Older patients are more susceptible to severe Epstein-Barr virus (EBV)-related infectious mononucleosis (IM). This condition may increase in industrialized countries where primary EBV infection occurs later in life. Between 1990 and 2004, 38 patients were admitted to our department with EBV-related IM. Two patients died. The annual incidence increased significantly (r = 0.623; P = 0.013).

Detection of herpesvirus genomes by polymerase chain reaction in cerebrospinal fluid and clinical findings

BACKGROUND The viruses of the Herpesviridae family, in particular herpes simplex virus types 1 (HSV-1) and 2 (HSV-2), cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella zoster virus (VZV), and human herpesvirus 6 (HHV-6), are responsible for numerous infections of the central nervous system (CNS). These infections manifest as diverse clinical signs, many of which are not specific. The diagnosis of these infections is necessary to make it possible to adapt treatment appropriately, as treatment is specific for the particular virus concerned. OBJECTIVES To apply a polymerase chain reaction (PCR) technique for the diagnosis in a single reaction of the six herpesviruses most frequently detected in the cerebrospinal fluid (CSF) and to analyse clinical events in patients presenting positive results in PCR for herpesviruses. STUDY DESIGN We studied 141 patients, from whom 180 CSF samples were collected. The clinical files of the patients were consulted retrospectively, and a list of clinical signs was recorded. After testing by targeted PCR, at the clinicians demand, we tested these samples by herpes consensus PCR, which detects six herpesviruses (HSV-1, HSV-2, CMV, EBV, VZV, HHV-6), in a single PCR. RESULTS Targeted PCR tests identified 25 CSF samples (13.9%), corresponding to 18 patients (12%), as positive. The herpes consensus PCR test detected 49 samples (27.2%) as positive, resulting in the identification of 54 individual viruses (four samples displayed co-infection) from 39 patients (27%). 130 CSF samples, from 101 patients, tested negative by both techniques. 23 HIV-positive patients (30.6%), three HIV-negative immunocompromised patients (27%), and 14 immunocompetent patients (25%) were CSF PCR-positive. In HIV-positive patients, CMV was the virus most frequently identified (13%), followed by EBV (10.6%), VZV (5.3%) and finally HSV-1 and HSV-2 (both 1.3%). We did not detect HHV-6 in any of these samples. We detected only HSV-2, EBV and VZV in the 11 HIV-negative immunocompromised patients. CSF samples of immunocompetent patients contained mostly VZV (9%) and HSV-1 (7.3%). CONCLUSIONS The herpes consensus PCR for a given virus was more sensitive than the standard, targeted PCR used in our laboratory. The clinical signs presented by patients infected with HSV-1, HSV-2 and CMV were similar to those reported in previous studies. For VZV, we report the possibility of mild, transient cerebral viral reactivation. Our data on the detection of EBV by PCR suggest that the PCR test is of predictive value for cerebral lymphoma in immunocompromised patients. The possible role of HHV-6 in a subacute neurological disorder merits further investigation.

Incidence of Yellow Fever Vaccine-Associated Neurotropic Disease

Although the yellow fever 17D strain live-attenuated vaccine has been widely used over the past seven decades with a long history of safe records, recent reports of serious, sometimes fatal, adverse events, raised concerns about its tolerance. We extracted all cases of serious neurologic adverse events that occurred within 30 days of yellow fever vaccination in our institution during 2000-2008. Four cases (meningitis, n = 2 and meningo-encephalitis, n = 2) were identified. The male:female ratio was 3:1, and ages ranged from 21 to 55 years. Cerebrospinal fluid examination showed pleocytosis (10-82 cells/mm(3), 64-84% lymphocytes), with slightly elevated protein levels (0.4-0.68 g/L). All symptoms resolved in three patients, but attention disorder and cerebellar syndrome persisted in one patient (at six months follow-up). The incidence of yellow fever vaccine-associated serious neurologic events was estimated to be 9.9/100,000 vaccine doses (95% confidence interval = 2.7-25.4/100,000) in this study, which was 10 times higher than previous estimates that did not include acute meningitis.

Benefits of Management Strategy Adjustments During an Outbreak of Enterovirus Meningitis in Adults

Enteroviruses (EVs) are the most common identifiable cause of the aseptic meningitis syndrome. Widespread seasonal outbreaks of EV meningitis result in a high financial cost to the community, in part because of the difficulty of discriminating between viral and bacterial meningitis. During a nationwide outbreak of EV meningitis due to echovirus 30 in France we tested the hypothesis that a management strategy including early testing of cerebrospinal fluid (CSF) by means of EV PCR in all adult patients with acute aseptic meningitis on admission might reduce the duration of hospitalization and thus the expenditure on health resources. We compared the characteristics of adult patients with acute aseptic meningitis seen in our institution before (n = 21) and after (n = 27) implementation of this strategy. The strategy was cost-effective in that it significantly reduced (i) the mean duration of hospital stay (from 103 to 80 h; p = 0.04); and (ii) the mean duration of antibacterial treatment (from 115 to 69 h; p = 0.02). Systematic testing of CSF in adult patients with aseptic meningitis by means of EV PCR may be cost-effective during an outbreak of EV meningitis.

Detection of HHV-6 in over a thousand samples: new types of infection revealed by an analysis of positive results.

BACKGROUND Clinical manifestations of human herpesvirus-6 (HHV-6) have not been clearly defined, and the role of HHV-6 in human disease remains to be fully elucidated. OBJECTIVE To determine the frequency of HHV-6 infections at Rennes Teaching Hospital and to describe all possible symptoms of such infections. STUDY DESIGN We systematically analyzed in a retrospective study all the samples between May 2003 and December 2004 from patients with HHV-6 by polymerase chain reaction (PCR). Clinical records of patients with positive HHV-6 PCR were recorded. Diagnosis of HHV-6 infection was accepted if all other possible diagnoses had been eliminated. RESULTS Over the study period, 1591 PCRs were performed from various tissues, including blood, cerebrospinal fluid, ascitis and tissue biopsies. Forty-three samples from 25 patients tested positive (3%). We describe three groups of clinical manifestations of HHV-6 infection. The first group consisted of neurological complications (32% of patients), including convulsions, encephalitis and chronic psychiatric disorders in immunocompetent patients. The second group consisted of clinical problems relating to gastrointestinal tract, which was found in 9 of our patients (36%). All of these patients were immunocompromised. Four of them presented colitis, and one of them died one month after liver transplantation because of this colitis. The last group of clinical symptoms was associated with maternal-fetal infection leading to abortion following HHV-6 seroconversion during pregnancy. CONCLUSION Three clinical types of HHV-6 infections are described: neurological manifestations including encephalitis in non-immunocompromised patients, digestive problems in immunosuppressed patients and severe maternal-fetal infection.

New PCR Test That Recognizes All Human Prototypes of Enterovirus: Application for Clinical Diagnosis

ABSTRACT We describe a new PCR test (Penter RT-PCR) that recognizes all 64 prototypes of enterovirus. Sixty clinical samples were analyzed in parallel with this Penter RT-PCR and previously described PCR tests: 34 and 32 samples tested positive, respectively. This assay is suitable for use in clinical diagnosis, and its ability to amplify all known serotypes makes it more useful than other consensus PCR tests.

HLA-G Expression in Guillain-Barré Syndrome Is Associated with Primary Infection with Cytomegalovirus

GUILLAIN-BARRE SYNDROME (GBS) is an acute peripheral neuropathy characterized by a symmetric, usually ascending paralysis due to an acute inflammatory demyelination. GBS is considered the prototype of postinfectious illness with immunopathologic features that include an inadequate immune response against persistent foreign epitopes which cross-react with self-epitopes of peripheral nerves. Regarding this hypothesis, progressive understanding of the immunopathological phenomena leading to the persistence of infective agents in host may provide a rationale for targeting immunotherapy in GBS. In the field of immune tolerance, recent studies have focused on the role of the Human Leukocyte Antigen–G (HLA-G) molecules, which belong to the non-classical HLA class Ib molecules. HLA-G proteins differ from classical HLA-Ia molecules by their low polymorphism, their restricted tissue distribution in tumors (1), and pulmonary (5) or muscle inflammation (6). Furthermore, they exert immunotolerant functions in feto-maternal tolerance, heart-graft acceptance, and tumor immunoevasion (1). Lastly, in a previous report, we evidenced HLA-G expression on monocyte-macrophages during human cytomegalovirus (HCMV) reactivation. We proposed this phenomenon as a new mechanism that could help HCMV eluding host defences and persisting in human body (4). Consequently, and because CMV infection is the most common viral disease causing GBS (2), we examined HLA-G expression on peripheral monocytes in a patient with a GBS induced by HCMV primary infection. A 41-year-old man presented with a bilateral ascending paresthesias and a progressive weakness in lower limbs. On admission, he was afebrile, presented with areflexia of the lower limbs, and had progressively developed a flaccid ascending tetraparesis. GBS was confirmed by elevated CSF protein concentration (0.6g/L) without cellular response and an absence of spinal cord compression on CT scan. Electrophysiological studies showed slow motor conduction, increased distal latencies, an abolition of F waves, and a normal sensory parameters. Acute HCMV infection was proved by high anti-CMV IgM and IgG antibodies, and positive blood PCR (3). Primary infection was demonstrated by an urea denaturation test showing predominance of low-avidity IgG produced early in infection. Tests for other viruses (HSV, HIV, HAV, HBV, and HCV) remained negative. Despite treatment by immunoglobulins and ganciclovir, the patient developed respiratory failure and required mechanical ventilation for 2 months. Recovery was slow, and he was discharged 3 months after admission. We evidenced HLA-G expression on some of the patient’s blood monocytes by allogeneic stimulation. Briefly, monocytes were isolated at the onset of the disease by Ficoll density gradient centrifugation and

Use of human papillomavirus genotyping and biomarkers for targeted screening of anal dysplasia in human immunodeficiency virus-infected patients

BACKGROUND Screening for anal dysplasia in human immunodeficiency virus (HIV)-infected patients is not standardized. High-resolution imaging is not adequate for mass screening, and anal cytology requires expertise. New biomarkers, selected because of their use in cervical cancer mass screening, have been originally tested for targeted and easy-to-perform screening. METHODS 120 HIV-infected individuals (males 96.4%, mean age 47±11 years) were referred for clinical examination, anoscopy, and cytological studies on anal swab. Dysplasia grading, Human Papilloma Virus genotyping, E6/E7mRNA detection and p16(INK4A)/Ki-67 immunostaining were performed. High-grade lesions were histologically confirmed by anal biopsies after high-resolution anoscopy. RESULTS Among the 120 anal swabs analyzed, 36 (30%) had low grade and 6 (5%) had high-grade lesions. Virus genotype was identified in 88 patients (73.3%), and 77 (64.2%) were positive for high-risk genotype(s). High-risk genotype was associated to low-grade or high-grade lesions with a sensitivity of 0.93 and a specificity of 0.51. For E6/E7mRNA, sensitivity and specificity for low-grade and high-grade lesions were, respectively, 0.88 and 0.78. Combination of genotyping, E6/E7mRNA and p16(INK4A)/Ki-67 appropriately ruled out dysplasia in 55% of patients. CONCLUSIONS Three routine biomarkers may avoid unnecessary invasive procedures with the perspective of an improvement of patient compliance. A decision making algorithm, based on the combination of these three biomarkers, is proposed.

Astrovirus and digestive disorders in neonatal units.

Aim:  To describe clinical signs associated with Human Astrovirus (HAstV) in stools in neonatal units.