Epidemiology of orofacial herpes simplex virus infections in the general population in France: results of the HERPIMAX study.

BACKGROUND: Prevalence of clinically manifest orofacial herpes in the general population is poorly characterized. Objectives To establish the lifetime prevalence of clinically manifest orofacial herpes and its relationship with herpes simplex virus (HSV) serotype in the French general population. PATIENTS/METHODS: Subjects (N = 2796) were serotyped for HSV1 and HSV2 and provided data on herpetic symptoms by questionnaire. Subjects reporting at least one episode of orobuccal ulcerative mucosal lesions were classified as clinically manifest orofacial herpes. RESULTS: Lifetime prevalence of clinically manifest orofacial herpes was 38.3% (42.1% in women, 32.4% in men). Prevalence in subjects seropositive for HSV1 was 50.3%. This prevalence rate was independent of HSV2 serotype. Prevalence in subjects infected with HSV2 alone was similar to that in subjects seronegative for HSV. LIMITATIONS: Lack of case ascertainment limits precision of the data. CONCLUSIONS: Clinically manifest orofacial herpes was reported in one third of the sample, principally associated with HSV1 infection. HSV2 infection did not produce orofacial lesions nor influence clinical manifestations of HSV1 infection.

Surveillance network for herpes simplex virus resistance to antiviral drugs: 3-year follow-up.

Herpes simplex virus (HSV) infections are very common in the general population and among immunocompromised patients. Acyclovir (ACV) is an effective treatment which is widely used. We deemed it essential to conduct a wide and coordinated survey of the emergence of ACV-resistant HSV strains. We have formed a network of 15 virology laboratories which have isolated and identified, between May 1999 and April 2002, HSV type 1 (HSV-1) and HSV-2 strains among hospitalized subjects. The sensitivity of each isolate to ACV was evaluated by a colorimetric test (C. Danve, F. Morfin, D. Thouvenot, and M. Aymard, J. Virol. Methods 105:207-217, 2002). During this study, 3900 isolated strains among 3357 patients were collected; 55% of the patients were immunocompetent. Only six immunocompetent patients excreted ACV-resistant HSV strains (0.32%), including one female patient not treated with ACV who was infected primary by an ACV-resistant strain. Among the 54 immunocompromised patients from whom ACV-resistant HSV strains were isolated (3.5%), the bone marrow transplantation patients showed the highest prevalence of resistance (10.9%), whereas among patients infected by human immunodeficiency virus, the prevalence was 4.2%. In 38% of the cases, the patients who excreted the ACV-resistant strains were treated with foscarnet (PFA), and 61% of them developed resistance to PFA. The collection of a large number of isolates enabled an evaluation of the prevalence of resistance of HSV strains to antiviral drugs to be made. This prevalence has remained stable over the last 10 years, as much among immunocompetent patients as among immunocompromised patients.

[Clinical management of genital herpes: what can be done in pregnancy?]. / Prise en charge pratique de l'herpès génital: que faire en cas de grossesse?

Neonatal herpes infection is the major complication of genital herpes even if it occurs in less than 1/10,000 births. A great number of recent studies illustrates the natural history of genital herpes. The importance of viral transmission by asymptomatic shedding is now well established. The widespread use of viral diagnosis strategies is the prerequisite to efficient genital herpes prevention in order to eradicate viral mother-to-child transmission. This starts with the detection of at-risk situations such as primary infection in late pregnancy. Once the at-risk situation is known there should be concern about the adaptation of treatment strategies including antiviral therapy. The following work proposes different strategies facing each at-risk situation in order to discuss the efficiency of new diagnostic and treatment tools.

[Therapeutic strategies for genital herpes]. / Stratégies thérapeutiques face à l'herpès génital.

Genital herpes, usually a benign infection, has nevertheless an important psychological impact by its recurrent character. The clinical management needs first well done patient counseling, and second, the biological documentation of the virus excretion. When this is achieved, different treatment strategies may be proposed targeting mainly acute crisis. There is, however, a strong trend towards the prevention of recurrences using suppressive antiviral treatment or modulating the immune system (vaccines, immunomodulators). Indeed, there is a hope that these new approaches may lead to the reduction of disease transmission by diminishing the viral shedding.

[Genital herpes: practical impact of the 2001 consensus conference?]. / Herpès génital: que faut-il retenir de la conférence de consensus 2001?

Genital herpes, usually a benign infection, has nevertheless an important psychological impact by its recurrent character. The clinical management needs first a well done patient counseling, and second, the biological documentation of the virus excretion. When this is achieved, different treatment strategies may be proposed aiming mainly acute crisis. There is, however, a strong trend towards the prevention of recurrences using suppressive antiviral treatment or modulating the immune system (vaccines, immunomodulators). Indeed, there is a hope that these new approaches may lead to the reduction of disease transmission by diminishing the viral shedding.

Seroprevalence of HSV-1 and HSV-2 infection in the general French population.

BACKGROUND: In spite of the large prevalence and growing incidence of herpes simplex infection (HSV-1 and HSV-2), relatively few large serological surveys are available worldwide and it is still difficult compare frequencies of HSV contaminations in various countries. We present the results of HERPIMAX, the first epidemiological inquiry on HSV prevalence in the general French population. METHODS: Of a cohort of 12,735 presumed healthy adult volunteers included in the prospective study SU.VI.MAX, designed to assess the relation between nutritional supplementations and degenerative diseases, HERPIMAX randomly selected 4412 subjects (females 66.5%, males 33.5%). All serum samples were assessed for HSV-1 and HSV-2 IgG antibodies with a HSV type specific, enzyme immunosorbent assay (EIA). Equivocal result were retested with another HSV type specific immunoblot assay combined with a type common HSV IgG EIA in order to give a definitive interpretation. RESULTS: The mean seroprevalence was 67% for HSV-1 and 17.2% for HSV-2. For HSV-2 the seroprevalence was higher in females (17.9%) compared with males (13.7%) (p<0.001). For both HSV types, there was no significant difference in prevalence as regards age distribution in males and females, whereas prevalence increased significantly with age in females for HSV-1. Univariate analysis showed a significant association between HSV-1 prevalence and education level in males and females (p<0.001) and between HSV-2 prevalence and marital status in both sexes (p<0.001). There were geographical disparities, with a higher HSV-2 prevalence in the south of France as well as in Paris. CONCLUSION: These results confirm a high prevalence of HSV infection in France. They are also in agreement with previous results of other survey carried out in other developed countries as regards higher prevalence of HSV-2 infection in women, the stability of seroprevalence for both HSV types after 35 years of age in females and 45 years of age in males.

Effectiveness of a manual disinfection procedure in eliminating hepatitis C virus from experimentally contaminated endoscopes.

BACKGROUND: Transmission of hepatitis C virus (HCV) through endoscopy has been reported, but the implications as a public health concern remain controversial. This study investigated the degree to which a thorough manual cleaning-washing-disinfection procedure can decontaminate all channels of a flexible submersible endoscope experimentally contaminated with HCV. METHODS: To assess the accuracy of the method currently in use, the initial investigation focused on sampling effectiveness. Nine endoscopes were contaminated with high-titer HCV-positive plasma and flushed with 150 mL of sampling solution (distilled water) before disinfection. To assess the effectiveness of the disinfection procedure, the following sequence was performed on another 10 endoscopes: inoculation, disinfection, and sampling. After concentration residual viruses were detected by means of RNA amplification with commercial assays. RESULTS: The study showed that sampling alone can reduce viral titer to one-fourth its original value. Within the limits of this method, HCV RNA was never detected by means of polymerase chain reaction after disinfection, whereas all internal amplification controls were positive. This reduction to less than 1/100,000 of original titer exceeds the criterion expected for the virucidal activity of disinfectants. CONCLUSIONS: The results of this in vitro experiment provided evidence that patient-to-patient endoscopic transmission HCV can be reduced, if not eliminated, with the current mechanical cleaning-washing-disinfection procedure.

Zidovudine resensitization and dual HIV-1 resistance to zidovudine and lamivudine in the delta lamivudine roll-over study.

OBJECTIVE: To study zidovudine resensitization and dual resistance to zidovudine/lamivudine in HIV-1 isolates from nucleoside reverse transcriptase (RT) inhibitor-experienced patients during selective pressure exerted by zidovudine/lamivudine combination therapy. DESIGN AND METHODS: HIV-1 isolates from 29 patients receiving zidovudine/lamivudine combination therapy in the Delta roll-over study were analysed at entry and during a 1 year follow-up period for phenotypic susceptibility to zidovudine and lamivudine in the ANRS PBMC assay. The RT gene from codon 20 to 230 and at codon 333 was analysed by nucleotide sequencing of the corresponding isolates. RESULTS: HIV-1 isolates from 23 of the 29 patients were phenotypically resistant to zidovudine at baseline; 61% of these patients showed significant zidovudine resensitization during follow-up. The zidovudine IC50 value correlated positively with log10 plasma HIV-1 RNA (P = 0.02) and negatively with the CD4 cell count (P = 0.004). Zidovudine resensitization (related to acquisition of the M184V mutation) was transient, with evolution towards dual resistance to zidovudine and lamivudine in 20 of the 29 patients. The phenotype of certain dually resistant isolates coincided with the emergence of multiple mutations in the 5' part of the RT gene. CONCLUSIONS: M184V-mediated zidovudine resensitization of HIV-1 is transient in most patients who are given zidovudine/lamivudine combination therapy when zidovudine resistance has already emerged. The subsequent evolution towards dual phenotypic resistance to zidovudine/lamivudine corresponds to complex genotypic profiles.

Human herpesvirus 8 and Epstein Barr-virus in a cutaneous B-cell lymphoma and a malignant cell line established from the blood of an AIDS patient.

Human Herpesvirus 8 (HHV-8) has been consistently associated with Primary Effusion Lymphoma (PEL or body-cavity-based lymphoma) but not with other lymphomas. This paper reports on an AIDS patient without obvious malignant effusion in body cavities but with a cutaneous lymphoma where HHV-8 and Epstein-Barr virus (EBV) were detected by PCR and electron microscopy. Both viruses were also detected in all the cells of a malignant cell line (BBG1) established from the patient's peripheral blood mononuclear cells. As in PEL and PEL-derived cell lines, both the tumor and the lines lacked B-antigen expression in immunological studies but were of the same B origin as shown by clonal immunoglobulin gene rearrangements. In contrast to other co-infected cell lines, BBG1 and subclones spontaneously expressed the HHV-8 lytic antigens p40, p27, p60 and the EBV transforming latent antigen EBNA2. These data suggest that the clinical and biological features of HHV-8-and EBV-associated lymphomas could be wider than has been described to date in PEL particularly with the in vivo presence of circulating malignant dually-infected cells engaged in a spontaneous HHV-8 lytic infection.

[Virus resistance in a hospital environment: overview of the virucide activity of disinfectants used in liquid form]. / Résistance des virus dans l'environnement hospitalier: le point sur l'activité virucide des désinfectants utilisés à l'état liquide.

Human pathogenic viruses can be detected in the hospital environment, on contaminated surfaces or medical instruments. Their transmission to patients or staff has already been reported. Lipophilic viruses (HIV, HBV, HCV,...) are susceptible to many liquid chemicals, but they can survive during short time on inadequately disinfected surfaces. Hydrophilic viruses, without envelope, are more resistant, but generally not associated with severe illnesses. Viruses survival in environment depends on many factors and is always improved with viral aggregation and low temperature, whereas organic matters and relative humidity effects are contrasted. The mechanism of virucide disinfectants is not yet well established, and their targets are not known with precision. Different disinfection procedures (disinfectant concentration, contact time, temperature, pH) can provide a similar virucidal activity on a given virus. The virucidal activity of a disinfectant is evaluated with a cell culture assay in Afnor guidelines. But, there are three major problems with this method, concerning need of high viruses titers, residual disinfectant cytotoxicity on cell culture, and non cultivable viruses. Non standardized tests are also described in papers, but their results can generally not be compared. Molecular biology improvements may lead to reproducible and sensitive tests. At present, no general disinfection procedure effective for most of the viruses, without risks for staff or materials, and with an acceptable economic cost can be recommended.

Cytomegalovirus seroprevalence in French pregnant women: parity and place of birth as major predictive factors.

In this study we present data on cytomegalovirus (CMV) seroprevalence in pregnant women in France. One thousand and eighteen women were enrolled in a prospective study carried out in Grenoble. The overall rate of seropositivity, using a specific IgG ELISA test, was 51.5 % (95 % CI: 48.5-54.5). Among a homogeneous population of 873 women born in France with high or middle socioeconomic status, CMV seropositivity increased with age and parity. The seroprevalence according to age was found to depend on parity. It increased with age in women with no children or with only one; it was higher but no more age-dependent in women with two children or more. In addition, CMV seroprevalence was significantly higher in women born in southern France (51.6%) than in those born in northern France (37.4%), these findings being consistent with the existence, within France, of a gradient in seroprevalence rate, increasing from the North to the South. A logistic regression analysis reveals the place of birth in France as a major predictive factor of CMV antibody status (OR: 3.5) followed by age (OR: 2) and parity (OR: 1.7). In this study, we show an independent effect of parity on CMV seroprevalence, arguing for the importance of child-to-mother transmission; nevertheless, the latitude of the place of birth, even within a size-limited country such as France, appears to be a major predictive factor of CMV seroprevalence.

Transient infection of astrocytes with HIV-1 primary isolates derived from patients with and without AIDS dementia complex.

We have studied the replication capacity of primary HIV-1 isolates obtained from four AIDS patients in astrocytes. Two patients (P1 and P2) had neurological manifestations without AIDS Dementia Complex (ADC). The other two patients (P3 and P4) had ADC. Two astrocytoma cell lines and normal fetal astrocytes were inoculated with each of these four viral isolates. Viral DNA and mRNA synthesis and also protein accumulation were followed at various times after infection. We found that tumoral as well as fetal astrocytes were susceptible to HIV-1 infection. Three of four viral isolates (P2, P3, P4) were able to infect astrocytes. Both ADC viral isolates (P3, P4) infected astrocytes with identical transcriptional patterns: rev, nef and unspliced mRNAs were expressed for 2 days after infection. The non-ADC patient (P2) with the isolate leading to viral replication in astrocytes had an HIV-1 associated multifocal demyelinating neuropathy. In this case, only nef and unspliced mRNAs were detected a few days after virus inoculation. In all cases, infection of astrocytes was transient and the level of unspliced mRNAs in infected astrocytes was lower than in chronically HIV-1 infected T cells. More extensive work would allow a better understanding of the role of astrocytes in ADC.