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P Morand

Publications and source records attributed to P Morand.

At least 19 recordsLinked to original sources

[What's new in vaccines against herpes simplex infections?].

Herpes simplex viruses (HSV) can cause a variety of infections, including genital herpes. Despite effective antiviral therapy HSV infections remain a public health problem. Vaccines offer the possibility for controlling the spread and limiting HSV disease, two strategies for herpes vaccination: prophylactic immunization or therapeutic immunization. The article discusses the results of different studies, in particular, concerning recombinant vaccines, DISC vaccines and DNA vaccines.

Herpes Simplex↗

A prospective study of Epstein-Barr virus load in 85 hematopoietic stem cell transplants.

EBV viral load (EBV-VL) in PBMC was prospectively determined by semi-quantitative PCR in 85 stem cell transplants (40 genoidentical, 45 non-genoidentical) in order to characterize the kinetics of EBV-VL and to assess the ability of this measure to predict the development of EBV-induced lymphoproliferative disease (EBV-LPD). PCR was performed prior to and after transplantation. An EBV-VL >300 copies/microg DNA was chosen as the threshold for risk of developing an EBV-LPD. Two hundred and fifty-eight EBV-VL measures were evaluable. Five patients (5.9%) developed an EBV-LPD. All had an elevated EBV DNA peak level before EBV-LPD. Fifteen out of 80 recipients (18.7%) without EBV-LPD had EBV levels over 300 copies/microg DNA at least once during the follow-up. Overall, the manifestation of at least one EBV-VL over 300 copies/microg DNA during the entire follow-up demonstrated a sensitivity, specificity, positive and negative predictive value for the diagnosis of EBV-LPD of 100%, 81%, 25% and 100%, respectively. In patients without EBV-LPD, HLA incompatibility, grade > or = II acute GVHD and use of an unmanipulated graft were significantly associated with an EBV-VL >300 copies/microg DNA. This strategy appears sensitive for the diagnosis of EBV-LPD but its positive predictive value has to be improved in order to guide pre-emptive therapy.

Adolescent↗

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.

Adult↗

[Natural history of HSV1 and HSV2 infection. Asymptomatic viral excretion. Mother-infant transmission. Indirect transmission].

Recurrent asymptomatic viral shedding accounts for most of the oral, sexual and neonatal transmissions of herpes simplex infections (HSV). In immunocompetent individuals asymptomatic shedding, as determined by culture, occurs during 2-8p.100 of days, and more for persons with HIV infection or if measured by PCR. Antiviral therapy dramatically decrease but does not eliminate asymptomatic shedding. The main risk of HSV transmission to the neonate is during vaginal delivery from infected asymptomatic mothers who acquire HSV genital infection late in pregnancy. Because the survival of HSV out of the oral-genital secretions is weak, indirect and/or nosocomial transmisions of HSV are very rare and should be controlled by common-sense precautions. The prevention of the acquisition of genital or neonatal HSV infection is a challenge because it is based on the understanding and the control of asymptomatic shedding.

Female↗

Functional determinants of the Epstein-Barr virus protease.

Herpesvirus proteases are essential for the production of progeny virus. They cleave the assembly protein that fills the immature capsid in order to make place for the viral DNA. The recombinant protease of the human gamma-herpesvirus Epstein-Barr virus (EBV) was expressed in Escherichia coli and purified. Circular dichroism indicated that the protein was properly folded with a secondary structure content similar to that of other herpesvirus proteases. Gel filtration and sedimentation analysis indicated a fast monomer-dimer equilibrium of the protease with a K(d) of about 60 microM. This value was not influenced by glycerol but was lowered to 1.7 microM in the presence of 0.5 M sodium citrate. We also developed an HPLC-based enzymatic assay using a 20 amino acid residue synthetic peptide substrate derived from one of the viral target sequences for the protease. We found that conditions that stabilised the dimer also led to a higher enzymatic activity. Through sequential deletion of amino acid residues from either side of the cleavage site, the minimal peptide substrate for the protease was determined as P5-P2'. This minimal sequence is shorter than that for other herpesvirus proteases. The implications of our findings are discussed with reference to the viral life-cycle. These results are the first ever published on the EBV protease and represent a first step towards the development of protease inhibitors.

Amino Acid Sequence↗

Lack of seroconversion in a health care worker after polymerase chain reaction-documented acute hepatitis C resulting from a needlestick injury.

We present a case of documented acute hepatitis C that occurred in a health care worker who sustained a needlestick injury while caring for an individual who was infected with both hepatitis C virus (HCV) and human immunodeficiency virus (HIV). According to the findings of third-generation serological assays performed during a follow-up of >1 year, the health care worker, who was treated with interferon-alpha (during weeks 2-6) and ribavirin (during weeks 5-9), did not develop antibodies against HCV, in spite of documentation of an HCV-specific T cell response.

Adult↗

Change in transaminases in hepatitis C virus- and HIV-coinfected patients after highly active antiretroviral therapy: differences between complete and partial virologic responders?

Patients with HIV and hepatitis C virus (HCV) coinfection have more severe hepatitis-related disease than do patients with HCV infection alone. Highly active antiretroviral therapy (HAART) with protease inhibitor appears to restore pathogen-specific immune responses, especially in patients with persistent undetectable HIV viral load. To evaluate the potent impact of immune restoration induced by HAART on the course of HCV-related disease, HCV viremia and levels of transaminases were compared between two groups of patients: 10 HIV/HCV-coinfected patients with persistently undetectable HIV viremia (group A) and 12 HIV/HCV-coinfected patients with persistent detectable HIV viremia. No difference was detected in HCV viral load in either group. An increase in transaminases was found only in patients with persistent undetectable HIV viral load, which was correlated with the increase in CD8+ T cells. This may suggest that the restoration of CD8+ T cell cytotoxicity could lead to an enhancement of hepatitis C-related disease in HCV/HIV-coinfected patients receiving HAART.

Adult↗

[Malignant non-Hodgkins B lymphoma related to Epstein-Barr virus and chronic natural killer lymphocytosis in a immunocompromised patient].

INTRODUCTION: Immunocompromised patients are at high risk of Epstein-Barr virus (EBV)-related lymphoproliferative disorders. The lymphoproliferation affects B, T, and natural killer (NK) cells. EXEGESIS: We report the case of a woman suffering from systemic lupus erythematous. She developed an opportunistic pneumonia while immunodepressed during long-term corticotherapy aimed at curing her auto-immune disease. Chronic lymphocytosis was also diagnosed at this time. Several months later, non-Hodgkin's lymphoma was diagnosed. Genomic amplification of the Epstein-Barr virus in the patient's blood and positive EBV latent membrane protein 1 on the lymph nodes provided evidence for a strong correlation between EBV reactivation and lymphoma. CONCLUSION: Two distinct lymphoid diseases occurred during the immunosuppressive therapy for the auto-immune disease. PCR monitoring of Epstein-Barr virus allows for early screening of lymphoproliferative disorders in immunocompromised patients, leading to earlier and more efficient treatment.

Aged↗

Do pathogenic neisseriae need several ways to modify the host cell cytoskeleton?

Neisseria meningitidis and Neisseria gonorrhoeae are human pathogens which have to interact with mucosa and/or cellular barriers for their life cycle. Even though they both give rise to dramatically different diseases, most of the mechanisms mediating cellular interactions are common to N. meningitidis and N. gonorrhoeae. This suggests that bacterial cell interactions may be essential not only for pathogenesis but also for other aspects of the bacterial life cycle that are common to both N. meningitidis and N. gonorrhoeae. Opacity proteins and pili are two major components identified as transducing signals to host cells, thus leading to cytoskeleton modifications. This manuscript will review the recent developments concerning the mechanisms mediating cellular interactions of pathogenic Neisseria and will tentatively put them into the perspective of pathogenesis and bacterial life cycle.

Animals↗

Serologic and genetic characterization of HIV type 1 subtypes on Reunion Island.

The aim of this study was to determine the HIV subtypes present on Reunion Island, a French island located in the Indian Ocean, where the first case of AIDS was diagnosed in 1987. Paired sera and blood samples were collected between September 1996 and September 1997 from 53 HIV-1-positive patients. Subtyping was performed by serotyping with a previously described subtype-specific enzyme immunoassay (SSEIA) and by genotyping with the heteroduplex mobility assay (HMA). When samples gave uninterpretable results with either of the methods, or discordant results, the V3 env region was sequenced and genetic subtypes were determined by phylogenetic analysis. Genetic subtyping showed that 48 of 53 patients were infected with HIV-1 subtype B (90.5%). This high prevalence of subtype B on Reunion Island is probably due to the regular exchanges with metropolitan France. The other five patients were infected with subtype A (9.5%); they had been directly linked to African populations. Of the 48 subtype B samples, 44 (91.7%) were correctly subtyped by SSEIA and 43 (89.6%) by HMA. However, the SSEIA did not allow the subtyping of A strains in three of five patients. Thus, the SSEIA could be an alternative routine technique for screening subtype B versus nonsubtype B HIV-1 strains.

Amino Acid Sequence↗

[Dysthymic disorders].

Long lasting, low intensity depressive episodes have been diversely integrated according to the classifications types or the psychodynamic points of view. The concept of anxious persistent lasting depression, neurotic depressive states, neurotic depression ... have been unified into the dysthymic disorder category of the DSM classification. This concept unification have been a topic of dispute considering that dysthymic disorder was a restrictive, heterogeneous an extensively comorbid diagnosis. Nevertheless the definition of this category offers the opportunity to place the notions of temperament, personality, adjustment disorder. Including dysthymic disorders as a category inside of the mood disorders classification suggests the interest of using an antidepressive medication in presence of chronic depressive states not included in the major depressive disorder category.

Adjustment Disorders↗

Association between primary cytomegalovirus infection and severe hemolytic anemia in an immunocompetent adult.

Hemolysis is a rare complication of cytomegalovirus infection in the immunocompetent adult, and the mechanisms responsible for it remain obscure. Guidelines for treatment have yet to be established, and the effectiveness of antiviral therapy has not been proven. In this report, an unusual case of primary cytomegalovirus infection manifested by severe hemolysis in an immunocompetent adult is presented. Treatment with ganciclovir (5 mg/kg b.i.d.) for 10 days and prednisolone (2 mg/kg/day) for more than 3 months suggests that both virological and immunological mechanisms are probably responsible for the hemolysis.

Adult↗

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.

Disinfectants↗

[1977 mortality rate in HIV-infected patients presenting with hepatitis C cirrhosis. Results of the GERMIVC multicenter survey conducted in French departments of internal medicine or infectious disease].

PURPOSE: Hepatitis C (HCV) has a high prevalence (10-30%) among human immunodeficiency virus (HIV)-infected patients. However, little information is available regarding the impact of hepatitis C on survival. The objective of our study was to determine the incidence of hepatitis C-related deaths in HIV-HCV co-infected patients. METHODS: The study was a retrospective (1-year), multicenter cohort survey conducted in 63 departments of either internal medicine or infectious diseases in France. It included 26,497 HIV-infected patients, of whom 4,465 (16.8%) presented coinfection due to the hepatitis C virus. The following parameters were studied for the year 1997: total number of deaths, number of deaths related to either AIDS, cirrhosis, hepatocellular carcinoma, or other causes. RESULTS: Among the 26,497 patients, 543 deaths (incidence: 2%) were observed in 1997; 543 deaths were due to AIDS (incidence: 1.7%), 36 to cirrhosis and/or hepatocellular carcinoma (incidence: 0.13%), and 48 (incidence: 0.18%) to another cause. In the subgroup including 4,465 HIV-HCV-coinfected patients, 29 deaths (incidence: 0.64%) were due to either HCV-related cirrhosis or hepatocellular carcinoma. These results were compared with those of a previous similar survey conducted in 1995, before the era of highly active antiretroviral therapy. The only significant difference is the dramatic regression of deaths due to AIDS. CONCLUSION: The impact of hepatitis C virus on the mortality among HIV-infected patients whose follow-up took place in departments of either internal medicine or infectious diseases in France was very low in 1997. The expected increase in the life span in these patients could modify these results in the future, due to recent improvements in the HIV infection treatment.

Adult↗

Development of an Epstein-Barr virus type 2 (EBV-2)-associated hepatic B cell non-Hodgkin's lymphoma in an HIV-1-infected patient following a change in the EBV dominant type.

From the longitudinal study of a cohort of HIV-positive patients, we report the case of a patient who initially harbored the Epstein-Barr virus (EBV) type 1 and subsequently developed an EBV-2-associated non-Hodgkin's B lymphoma a few years after an EBV-2 reactivation, or an exogenous reactivation, in the blood. At the time of diagnosis of hepatic lymphoma, the blood and the throat harbored high levels of the EBV-1 dominant strain. Sequence analysis of EBNA-2 gene revealed that: (1) type 2 EBV detected during reactivation and then in hepatic tumor was very likely to be the same strain and was mostly identical to the EBV prototype AG876; (2) type 1 virus conserved the same mutations during all the follow-up. These results suggest that EBV-2 might be associated with lymphomatogenesis and that a transient reactivation could lead to the development of an EBV-associated disease.

Genotype↗

Interactions of pathogenic Neisseria with host cells. Is it possible to assemble the puzzle?

Neisseria meningitidis and Neisseria gonorrhoeae are human pathogens that have to interact with mucosa and/or cellular barriers for their life cycles to progress. Even though they both give rise to dramatically different diseases, the use of in vitro models has shown that most of the mechanisms mediating cellular interactions are common to N. meningitidis and N. gonorrhoeae. This suggests that bacterial cell interactions may be essential not only for pathogenesis but also for other aspects of the bacterial life cycle that are common to both N. meningitidis and N. gonorrhoeae. This manuscript will review the most recent developments concerning the mechanisms mediating cellular interaction of pathogenic Neisseria and will then try to put them into the perspective of pathogenesis and bacterial life cycle.

Animals↗