[Herpes serology for genital herpes]. / Quelle place pour la sérologie herpétique dans l'herpès genital?

The epidemiology of genital herpes is changing. The seroprevalence of HSV-2 infections is increasing, while HSV-1 is an increasingly common cause of herpetic ulcerations. The reference examination provides direct diagnosis after viral isolation in a cell culture or genome amplification. Herpes serology is indicated principally if direct examination is negative and in the absence of lesions. Non-type-specific serology detects antibodies common to HSV-1 and HSV-2. Its specificity and sensitivity are excellent, and it is approved as a reimbursable laboratory procedure. It cannot specify the viral type involved. Type-specific serology can distinguish between anti-HSV-1 and anti-HSV-2 antibodies. Currently available kits have a sensitivity and specificity, depending on the population studied, of 90 to 100%. It is not approved as a reimbursable laboratory procedure. HSV-1-specific serology cannot diagnose old HSV-1 genital infections, but seropositivity for HSV-2 generally suffices to diagnose HSV-2 genital herpes. The indication for type-specific serology must be discussed according to clinical context. The value of non-type-specific serology is limited.

Human parainfluenza virus type 4 infections: a report of 20 cases from 1998 to 2002.

BACKGROUND: Human Parainfluenza Viruses (HPIV) type 4 are responsible for respiratory infections. Unlike HPIV types 1-3, they are associated with mild infections and appear to be infrequent. Thus, they often go undetected. STUDY DESIGN: From 1998 to 2002, in 20 respiratory samples of hospitalised patient, we isolated viruses presenting a large syncytial cytopathic effect when inoculated on LLC-MK2 cells. Most of the patients (16/20) were young infants and all of them presented with respiratory infections. RESULTS: We detected 18 cases during autumn and winter, 1 case during spring and 1 during summer. We could not identify these viruses using the panel of routine assays. Samples were then analysed by specific HPIV 4 RT-PCR and IF assays. All the samples were scored positive with both methods. CONCLUSION: We conclude that HPIV 4 infections are probably underestimated. Their role in viral respiratory infections should be carefully investigated using techniques adapted to their detection and culture.

A retrospective, case-control study of acyclovir resistance in herpes simplex virus.

BACKGROUND: Occasional cases of acyclovir resistance have been documented in the treatment of herpes simplex virus (HSV) infection. Thirty-eight subjects with acyclovir-resistant infections were identified in an epidemiological surveillance program involving 1811 HSV-infected subjects in France. METHODS: Twenty-three index cases from whom acyclovir-resistant HSV strains had been isolated were compared with 46 control subjects matched for immunological status. Sociodemographic characteristics, features of the acyclovir-resistant HSV episode, history of HSV infection, treatment, outcome, and immunological history were recorded. RESULTS: Twenty-two index case patients presented with immunodepression. Sixty-five percent reported clinically manifest recurrences, compared with 33% of matched control subjects. Significantly more index case patients had used antiviral drugs, and they had used them more often than had control subjects. However, 26.1% of index case patients reported no antiviral exposure in the previous 2 years. Two-thirds of the strains recovered from the index case patients were isolated because of suspicion of clinical resistance to acyclovir. CONCLUSIONS: Clinical treatment resistance is associated with acyclovir-resistant HSV strains, but acyclovir-resistant strains were also isolated from treatment-naive subjects.

HSV excretion after bone marrow transplantation: a 4-year survey.

BACKGROUND: Herpes simplex virus (HSV) oral excretions are common after bone marrow transplantation (BMT). OBJECTIVE: We report a 4-year systematic survey of HSV excretions in an adult population who underwent BMT (289 transplantations). STUDY DESIGN: Patients received either intravenous ACV treatment when mucositis occurred or systematic intravenous ACV prophylaxis from initiation of the BMT conditioning until the end of aplasia. All patients were followed up for HSV excretions. RESULTS: Twenty-eight patients (9.7%) excreted HSV. The occurrence of HSV excretions was similar in both allogeneic and autologous transplant patients. The incidence was significantly lower when ACV was systematically used after transplantation (2.5%) compared to when ACV was implemented for mucositis (12%). ACV-resistant HSV was detected in three patients who received allogeneic transplantation, representing 27% of allogeneic recipients excreting HSV. CONCLUSION: HSV infection prophylaxis with high dose of intravenous ACV resulted in a decreased incidence of HSV excretion. Nevertheless, the risk of emergence of ACV resistance, especially among allogeneic transplant patients, appears to be identical whatever the route and dose of ACV prophylaxis.

Cytomegalovirus and adenovirus infections and diseases among 75 paediatric unrelated allogeneic bone marrow transplant recipients.

Viral infections remain a major complication of allogeneic bone marrow transplantation. A population of children who underwent unrelated allogeneic bone marrow transplantation in a single centre has been followed-up for viral infections and diseases. We describe the detection of cytomegalovirus (CMV) and adenovirus among 75 children transplanted between 1989 and 2000. CMV was detected among 22 patients (29%) and adenovirus among 19 patients (25%); they were associated with clinical diseases in 10 and 8 patients, respectively. Four patients had adenovirus and CMV coinfection. The obvious risk factor for CMV infection is seropositivity of the recipient prior to transplantation. Adenovirus is detected significantly more frequently when conditioning regimen includes anti-thymocyte or anti-lymphocyte globulin. Diseases associated with adenovirus have been correlated with a significantly higher mortality rate, stressing the need for the implementation of a systematic virological survey for this virus and for the evaluation of therapeutic protocols including new molecules.

Burden of influenza in children: preliminary data from a pilot survey network on community diseases.

BACKGROUND: The burden of influenza and its clinical presentation are both poorly documented in French children. METHODS: To measure the prevalence of acute respiratory infections over two winters (2000 to 2001 and 2001 to 2002), we performed a prospective community survey of 0- to 15-year-olds (n = 11 500 and 40 000, respectively) through a network [Grippe et Infections Respiratoires Aiguës Pédiatriques (GIRAP)] of general practitioners and pediatricians. Influenza viruses were detected by antigen detection and culture from nasopharyngeal swabs. Data on the clinical presentation of children infected with influenza A/H1N1, A/H3N2 or B viruses were derived from standardized forms. RESULTS: The prevalences of symptomatic acute respiratory infections were 28% and 27% for 2000 to 2001 and 2001 to 2002, respectively. In the winter of 2000 to 2001, a mild outbreak of influenza A/H1N1 affected 5.4% of the study population. The attack rates of influenza A/H1N1 were highest in children 5 to 15 years of age. In the winter of 2001 to 2002, influenza activity remained at a subepidemic level (5.9%; A/H3N2, 60%; B, 40%). The incidence of influenza A/H3N2 infections was highest in 2- to 4-year-old children, whereas influenza B strains were most frequently detected in children 4 to 10 years of age. CONCLUSIONS: Despite subepidemic levels of influenza, the GIRAP network was able to detect influenza A or B viruses in 35 to 60% of the samples during the peak of influenza epidemic. The frequency of influenza virus excretion in children with mild clinical symptoms indicates that children are an important reservoir and source of transmission of this virus.

Temporal surveillance of the humoral immunity against influenza vaccine in the elderly over 9 consecutive years.

BACKGROUND: The effect of age on declining immunity is well established, but its influence on humoral responses to influenza vaccines is still debated. OBJECTIVE: To compare prospectively the immunogenicity of an influenza vaccine in elderly and healthy control subjects and to search for correlations between this specific humoral protection and clinical and virological parameters. METHODS: A prospective study of the humoral response to influenza vaccine was conducted over 9 consecutive years in the long-term care units of the Saint-Etienne University Hospital, France. Antibodies directed against the vaccinal strains in an inactivated trivalent vaccine were tested by radial haemolysis before and 1 month after 477 and 242 cumulative annual vaccinations in elderly people and in healthy controls, respectively. During the last 6 years of the study, clinical samples from patients with fever > or =38 degrees C were tested systematically for the diagnosis of an influenza infection. RESULTS: A significant rise in anti-A/H3N2 antibody titres was observed in 49.3% of the elderly subjects and in 48.3% of the controls (not significant). The rises for the A/H1N1 and B strains were 31.4 and 39.2% (p < 0.001) and 30.6 and 40.5 (p < 0.001), respectively. When control subjects under 31 years old were excluded, no significant difference was recorded for any strain. Only 3.9% of the vaccinated elderly experienced any clinical influenza infection as defined by fever >/=38 degrees C and virological proof. CONCLUSIONS: The humoral response to influenza immunization is not impaired in the elderly compared with middle-aged controls, and the incidence of febrile episodes due to influenza is low in this vaccinated elderly population. These findings provide further evidence supporting the recommendation for annual influenza vaccination in the elderly.

Sequencing of 'untypable' enteroviruses reveals two new types, EV-77 and EV-78, within human enterovirus type B and substitutions in the BC loop of the VP1 protein for known types.

The N-terminal part of VP1 was sequenced for 43 enterovirus isolates that could not initially be neutralized with LBM pools or in-house antisera. Most isolates were found to belong to human enterovirus type A (HEV-A) and HEV-B (18 isolates of each). All HEV-A isolates could be typed by sequencing, with CV (coxsackievirus)-A16 and EV (enterovirus)-71 being dominant (nine and seven isolates, respectively). These types thus seem to have diverged more from their prototypes than the other types. Among the HEV-B isolates, E-18 dominated with five isolates that became typable after filtration. The virus type obtained by molecular typing was verified for 28 of the other patient isolates by neutralization using high-titre monovalent antisera or LBM pools. Twenty-two of the other 30 'untypable' isolates had substitutions in the VP1 protein within or close to the BC loop. Two closely related HEV-B isolates diverged by 19.4 % from E-15, the most similar prototype. Two non-neutralizable HEV-C isolates split off from the CV-A13/CV-A18 branch, from which they diverged by 15.7-18.2 %. Three of the six non-neutralizable isolates, W553-130/99, W543-122/99 and W137-126/99, diverged by >24.2 % from the most similar prototype in the compared region. The complete VP1 was therefore sequenced and found to diverge by >29 % from all prototypes and by >28 % from each other. Strains similar to W553-130/99 that have been identified in the USA are tentatively designated EV-74. The two other isolates fulfil the molecular criterion for being new types. Since strains designated EV-75 and EV-76 have been identified in the USA, we have proposed the tentative designations EV-77 and EV-78 for these two new members of HEV-B.

Encephalomyelitis due to human parechovirus type 1.

OBJECTIVES: The implication of a viral agent in encephalomyelitis has been reported for several years. In the present study we wanted to demonstrate the presence of human parechovirus type 1 (HPEV1) in a patient diagnosed with encephalomyelitis. STUDY DESIGN: Clinical samples (throat and rectal swabs, acute and convalescent sera, cerebrospinal fluid) were collected from a 10-month-old boy diagnosed with encephalomyelitis. The appropriated samples were tested for cytomegalovirus, varicella zona virus, mumps virus and enteroviruses with specific culture, and serological and molecular biological techniques. RESULTS: HPEV1 was isolated from the throat and its genome was additional detectable in the cerebrospinal fluid, throat swab and acute serum. The samples were negative for all other tested viruses. CONCLUSION: To our knowledge, this is the first reported case of HPEV1 infection related to encephalomyelitis. This emphasis that human parechoviruses can be responsible for severe central nervous system infections in children.

[Current epidemiology of herpes]. / Epidémiologie actuelle de l'herpès.

The epidemiology of herpes simplex virus (HSV) infections describes: the clinical picture varying from subclinical to severe in various age groups, latency and recurrent infections, the transmission through direct contact related to the localisation of the lesions (ano-uro-genital for HSV2, oro-labial for HSV1), the world wide human reservoir, the lack of seasonal peak of incidence and the exceptional limited outbreaks. Serological and virological tests used for evaluating the frequency of acquired infections and the prevalence of various clinical and epidemiological aspects of herpetic infections have greatly changed in the last decade: (a) specific serological tests differentiate anti HSV1 and anti HSV2 antibody, allow the precise measurement of HVS1 and HSV2 infections prevalence and demonstrate the increasing frequency of Herpes Simplex genital infections in the last decades, in most of the countries (but Japan), (b) the development of direct diagnostic tests: virus growth in cells cultures, antigens detection by immuno-fluorescence and ELISA tests, genome amplification and detection by PCR and hybridization pointed but that: (1) the asymptomatic genital HSV excretion represents a frequent risk for neonatal contamination, (2) genital HSV1 noticeably increased in frequency, its epidemiological consequences are not yet evaluated, (3) a severely compromised immune status favours the frequency, the severity and chronicity of HSV infections, and the selection of antiviral resistant strains. The large use of acyclovir and derivatives in treatment and prophylaxis of HSV infections deeply modified the evolution, prognosis and management of HSV infections, but stressed the need for a survey of acyclovir resistant strains in immuno-competent and immuno-compromised patients.

[Herpes as viewed by the French: result of a survey conducted on 10,000 persons]. / L'herpès vu par les Français: résultat d'une enquête portant sur 10,000 personnes.

Herpes is a viral infection which increases, specifically genital herpes. The aim of this survey was to assess the perception of herpes in the general population and in patients with herpes in France using a self-administered questionnaire. A total of 10,000 persons answered the questionnaire among which 128 patients presented herpes. This study showed that only 5% of the French population knew that herpes was a viral infection, and 7% a sexually transmitted disease. Among patients with genital herpes only 34% indicated a sexual relationship and a mode of contamination. The interference with sexual and social life is important. Development of information and communication on herpes appears crucial.

A screening dye-uptake assay to evaluate in vitro susceptibility of herpes simplex virus isolates to acyclovir.

The widespread use of acyclovir (ACV) could increase the prevalence of herpes simplex virus (HSV) ACV-resistant isolates, and a screening assay are thus important for routine surveillance of the ACV susceptibility of HSV. A screening dye-uptake assay was developed, based on the conventional dye-uptake assay [J. Biol. Stand. 14 (1986) 201]. The susceptibility of HSV was measured by testing two virus dilutions (10(-1) and 10(-2)) against two ACV concentrations (5 and 10 microM) on Vero cells and expressed as a reduced percentage of viral replication. The reproducibility was evaluated with HSV1 and HSV2 ACV-sensitive and ACV-resistant reference strains introduced as controls in successive series. The dye-uptake by Vero cells, the growth capacity of the HSV strains and the reduction of the viral replication in the presence of acyclovir varied by less than 14, 20 and 30%, respectively. This assay allowed the detection of a heterogenous population containing as few as 20% of ACV-resistant strain. The screening test was applied to 500 HSV isolates in a prospective study, and over 95% of the HSV isolates tested were characterised using a single test. This test appeared to be half the cost and much easier to carry out than the conventional dye-uptake assay, and consequently is well suited for large scale surveillance.

Quantification of neuramidase (NA) protein content.

An ELISA-immunocapture assay was developed for quantification of influenza neuraminidases (N2 and B), with a sensitivity about 10 ng neuramidase(NA)/ml. This sensitive and specific assay was applied to several trivalent vaccine preparations (1997/1998 and 1998/1999). It was shown capable to detect 3.5-6.9 microg NA/ml according to the influenza strain and the vaccine origin.