[One episode of meningoencephalitis, three diagnoses]. / Méningo-encéphalite herpétique, aciclovir et maladie VIH, une histoire en 3 actes.

Meningo-encephalitis is a set of threatening diseases. The treatment needs to be started quickly for pathogens such as herpes simplex virus type 1 or Listeria monocytogenes. Apart from these classical etiologies, many other diseases may induce meningo-encephalitis. We report the case of a patient, infected with HIV, who presented a history of meningo-encephalitis due to herpes simplex type 1. Three weeks later, he presented an encephalopathy due to aciclovir and then we discovered a chronic meningitis in relation with his HIV infection.

[Herpesviruses serologic survey of corneal allograft recipients]. / Surveillance sérologique pour les Herpesvirus chez les receveurs de cornée.

AIMS: Herpesviruses are ubiquitous viruses, providing circulating antibodies in a wide range of patients. Donor-to-host transmission of Herpes simplex virus via corneal graft has been proven, leading to primary graft failure. However, the serological survey of the corneal recipient for Herpesviruses has not yet been investigated. METHODS: Circulating antibodies to HSV, VZV, CMV, and EBV were tested in 117 corneal recipients prior to surgery as well as 8 days and 3 months following surgery. Twenty-two patients had a history of corneal herpes. All patients were treated with local steroids, and no patient received systemic immunosuppressive therapy. RESULTS: No seroconversion was encountered, in particular, no CMV--patient was found CMV+ after grafting. The mean concentration of antibodies significantly decreased after grafting in a few patients. A serological profile of EBV reactivation was detected after surgery in four patients at day 8 and three more patients at 3 months. CONCLUSIONS: This study shows no significant seroconversion after grafting. However, it shows a postoperative decrease in antibody levels as well as a serological profile of EBV reactivation, possibly related to local steroids or graft immune processes.

Human tumor suppressor p53 and DNA viruses.

Human tumor suppressor protein p53 plays a major role in the cell cycle, orchestrating a number of important genes involved in cell-cycle control and apoptosis, and seems to be one of the most important molecules protecting cells from malignant transformation. Mutations in the p53 gene are observed in about 50% of primary tumors, inducing defective p53 protein no longer capable of binding DNA and of activating transcription. Certain DNA viruses are thought to act in a similar way and may also contribute to the progression of invasive cancer in infected tissue. One of the most effective strategies employed by these viruses is the inhibition of p53 protein by interaction with viral oncoproteins, implying a direct but also an indirect role of these viruses in the impairment of p53 structure and function. This article provides a summary of current knowledge concerning p53 tumor suppressor protein and reviews the different mechanisms adopted by different DNA viruses in undermining p53 function.

[Antiviral therapy adjustment in corneal recipients using antibody testing in the aqueous humor]. / Ajustement du traitement antiviral après greffe de cornée par mesure de la production d'anticorps dans l'humeur aqueuse.

INTRODUCTION: In corneal recipients with herpes infection, acyclovir given for 1 year postoperatively prevents viral reactivation and improves graft outcome. The indication for prophylactic antiviral therapy relies on the preoperative diagnosis of herpes. However, many patients present with corneal scars featuring sequelae of herpes without a proven history of herpes. Here we report the results of a prospective study of anti-herpes simplex virus (anti-HSV) and varicella zoster virus (VZV) antibody testing in the aqueous humor at the time of corneal transplantation to refine the indication of the antiviral treatment. MATERIAL AND METHODS: The study involved 33 keratitis corneal graft recipients, 21 of whom had documented herpes keratitis. A control group was made with 11 cataract patients. An anterior chamber puncture was performed just before surgery. The micro-ELISA test was done on both aqueous humor and serum, and local anti-HSV or VZV antibody synthesis was acknowledged if the ratio of antibody concentrations was above 4. RESULTS: Local antibody synthesis to HSV was detected in 22 cases, to VZV in 9 cases, to both HSV and VZV in 6 cases, and no synthesis in 8 cases. The sensitivity of the test was 65% in patients with a documented history of herpes (14 cases out of 21). Among non-herpetic patients, the test was positive in 9 patients, who thus benefited from postoperative antiviral therapy. No viral reactivation was encountered after a minimum follow-up of 1 year. CONCLUSIONS: Antibody testing in the aqueous humor at the time of keratoplasty is a convenient, inexpensive diagnostic tool in corneal recipients. It provides useful information before prescribing a long and expensive postoperative antiviral therapy.

Drug-induced hypersensitivity syndrome associated with Epstein-Barr virus infection.

Association of drug-induced hypersensitivity syndrome with viral infection is debated. Human herpesvirus 6 (HHV-6) reactivation has been the most frequently reported infection associated with this syndrome. However, a case of cytomegalovirus (CMV) infection was recently described associated with anticonvulsant-induced hypersensitivity syndrome. We report a case of severe allopurinol-induced hypersensitivity syndrome with pancreatitis associated with Epstein-Barr virus (EBV) infection. Active EBV infection was demonstrated in two consecutive serum samples by the presence of anti-EBV early antigen (EA) IgM antibodies and an increase in anti-EBV EA IgG antibodies, whereas no anti-EBV nuclear antigen IgG antibodies were detected. EBV DNA was detected by polymerase chain reaction (PCR) in peripheral blood mononuclear cells. Reactivation of HHV-6 was suggested only by the presence of anti-HHV-6 IgM antibodies, but HHV-6 DNA was not detected by PCR in the serum. Other viral investigations showed previous infection (CMV, rubella, measles, parvovirus B19), immunization after vaccination (hepatitis B virus), or absence of previous infection (hepatitis C virus, human immunodeficiency virus). We suggest that EBV infection may participate in some cases, as do the other herpesviruses HHV-6 or CMV, in the development of drug-induced hypersensitivity syndrome.

[Hepatitis viruses: mother to child transmission]. / Virus des hépatites : transmission mère-enfant.

The infection by the hepatitis viruses, when appearing during the pregnancy, could result in damages for the infant. However, risks differ according to the implicated virus. Hepatitis B virus infection, for which prevalence varies according to areas, is injurious when the mother is chronic HBsAg carrier. Risk consists of neonate's contamination during the labour, and if contaminated, the neonate becomes a chronic carrier himself in 80 to 90% of cases. When the mother is positive for viral DNA in her serum, transmission rate is estimated at 90%. In the opposite, if the mother is negative for viral DNA in the serum, transmission rate is about 10 to 30%. HBsAg screening is obligatory in France during the sixth month of pregnancy: in case of positivity, serovaccination of the neonate is systematically carried out. Protection rate is 100% if the mother had a low viral load (<150 pg/ml) at the end of pregnancy, and weaker (about 70%) if the mother had a higher level of viral DNA. Transmission risk of hepatitis C virus (HCV) is much lesser, since it is about 5% for a woman who is positive for viral RNA at the end of her pregnancy, and at least 10% if the woman is moreover positive for the HIV. Risk is more important if the woman had an important plasmatic viral load (> 10(5) copies/ml) and if the duration between membrane rupture and delivery is long. Vaginal delivery and breast-feeding are not advised. Neonates from mothers who replicate the HCV at the end of pregnancy are serologically evaluated until 12-15 months of age, in order to determine their possible contamination.Delta virus transmission from mother to infant is exceptional and could be avoided by the HBV serovaccination of the new-born.Intra-utero transmission of hepatitis A virus is very rare, but perinatal transmission could occur. Materno-fetal transmission of hepatitis E virus has been reported, but the virus is essentially dangerous for the mother, resulting in a mortality rate of 15 to 25% if the acute infection occurs during the third trimester of the pregnancy.

Real-time PCR for quantification of human herpesvirus 6 DNA from lymph nodes and saliva.

A real-time quantitative PCR assay has been developed to measure human herpesvirus 6 (HHV-6) DNA in biological specimens. The assay sensitivity was 10 copies of DNA per well, with a linear dynamic range of 10 to 10(7) copies of HHV-6 DNA. Intra- and interassay variations were, respectively, 0.88 and 0.8% for samples containing 10(2) DNA copies, 0.99 and 0.96% for samples containing 10(4) copies, and 0.76 and 0.9% for samples containing 10(6) copies. Among 34 saliva samples from healthy subjects, 26 were found to contain HHV-6 DNA (76.5%; median, 23,870 copies/ml), and following a single freeze-thaw cycle, 25 of the same samples were found to be positive for HHV-6 DNA, although at a statistically significantly lower concentration (median, 3,497 copies/ml). The assay enabled detection of HHV-6 DNA in lymph node biopsies from patients with Hodgkin's disease (HD) (13 of 37 patients [35.1%]), B-cell neoplasms (8 of 36 patients [22.2%]), and T- or NK-cell neoplasms (3 of 13 patients [23.1%]), with concentrations ranging from 100 to 864,640 HHV-6 copies per microg of DNA (HHV-6B being found in every case except two). All HD patients infected with HHV-6 presented clinically with the nodular sclerosis subtype of HD. The real-time quantitative PCR assay developed here was simple to perform and was sensitive over a wide range of HHV-6 concentrations. It therefore appears to be of potential value in clinical investigation or diagnosis of HHV-6 infection.

Reactivation of human herpesvirus type 6 in multiple organ failure syndrome.

Human herpesvirus type 6 (HHV-6) and cytomegalovirus (CMV) are known to interact with the production of cytokines. In this study, we sought to determine the incidence of HHV-6 and CMV reactivation during multiple organ failure syndrome (MOFS) and to evaluate the potential effects of viral replication on both the morbidity and mortality associated with MOFS. Viral reactivation was assessed by use of specific polymerase chain reaction (PCR) analysis of the serum samples obtained from 48 consecutive patients with MOFS (the MOFS group) and from 48 sex- and age-matched patients with <2 organ failures (the control group). In addition, HHV-6 replication was assessed in 106 blood donors (the normal group). The incidence of HHV-6 replication was higher in the MOFS group than in the control and normal groups (26 [54%] of 48 vs. 7 [15%] of 48 and 5 [5%] of 106, respectively; P<.0001), with apparently no influence on morbidity and mortality rates. In contrast, reactivation of CMV was found in a single patient. Further studies are needed to evaluate the pathogenesis of HHV-6 replication in critically ill patients.

Evaluation of BC-3 and BCP-1 cell lines in immunofluorescence assay to detect HHV-8 antibodies in Kaposi's sarcoma, multiple myeloma and other groups.

BACKGROUND: We describe a comparative study of an immunofluorescence assay using inducible BC-3 and BCP-1 cell lines as sources of HHV-8 antigens. STUDY DESIGN: Detection of both antibodies to proteins expressed in lytic cycle and during latency in sera from HIV-infected patients with KS, HIV-positive patients without KS, normal blood donors, HIV-negative pregnant women and HIV-negative patients with multiple myeloma. Where possible, detection of antibody was associated with nested PCR detection of HHV-8 in peripheral mononuclear cell (PBMC) samples collected from AIDS-KS patients. RESULTS: Immunofluorescence was more intense with the BC-3 cell line than with BCP-1, thus facilitating examination under the microscope. HHV-8 antibodies were detected among 82.75% of AIDS-KS patients, in 27.3% of HIV-infected homosexual men, 2% of blood donors and in 2% of pregnant women. No HHV-8 antibodies were detected in serum samples from HIV-negative patients presenting multiple myeloma. HHV-8 DNA sequences were detected and confirmed by southern blot hybridization in five out of 17 (29.4%) PBMC samples from AIDS-KS patients. Titre of antibodies to proteins expressed in lytic cycle was much higher than the titre of antibodies to proteins expressed during latency. CONCLUSIONS: Both immunofluorescence assays were found useful and HHV-8 seroprevalence rates reported in previous studies were confirmed. In addition, results obtained using these assays tend to provide evidence for a lack of epidemiological association between HHV-8 infection and development of multiple myeloma.

[Human herpesviruses 6 and 7 (HHV-6 and HHV-7)]. / Herpesvirus humains 6 et 7 (HHV-6 et HHV-7).

Human herpesviruses 6 (HHV-6) and 7 (HHV-7) are world wide T lymphotropic viruses recently discovered. Their transmission is essentially by salivary route. Primary infections which occurred early in infancy, respectively during the first year of life for HHV-6 and in the second or third year for HHV-7, are followed by latency for life. HHV-7 is not actually associated with a disease. HHV-6 primary infection is often asymptomatic, if not it can induce exanthem subitum. HHV-6 reactivation can be symptomatic in immunodeficient subjects. The role of HHV-6 in the arising of lymphoproliferative or auto-immune diseases, discussed for a long time, is still to elucidate. HHV-6 infection is diagnosed by serodiagnosis in case of primary infection, but in the great number of cases, it would be realized by polymerases chain reaction.

[Virus and gastrointestinal infections]. / Virus et infections gastro-intestinales.

Numerous viruses found in the gut are not associated with primary infection or disease of the gastrointestinal tract. Other groups or viruses are not classically associated with infection of the gut but can infect the gastrointestinal tract in immunocompromised individuals (herpes simplex virus, cytomegalovirus, papillomavirus ....). The viruses associated with gastroenteritis represent a large number of taxonomic group. Because these viruses have in general been difficult to cultivate, most members of this group were firstly detected by electron microscopic examination (adenovirus, astrovirus, calicivirus, coronavirus, rotavirus ....). The most widely used diagnostic techniques for adenovirus (40/41), rotavirus and astrovirus detection in faecal samples include immunoassays such as Elisa and latex agglutination. Nucleic acid hybridization techniques have generally not proven to be substantially sensitive and the more sensitive techniques recently developed use the polymerase chain reaction (adenovirus) or the reverse transcription/polymerase chain reaction (astrovirus, calicivirus, coronavirus, rotavirus). Special efforts have been made in the search for efficient procedures to extract viral nucleic acids, and to establish the optimal conditions for the amplification and identification of PCR products but the candidate viruses were very different, consensus procedures were not determined, and amplification kits were not actually commercialized.

[Primary cytomegalovirus infection and pregnant women: epidemiological study on 1100 women at Limoges]. / Primo-infection à cytomégalovirus et femmes enceintes: étude épidémiologique portant sur 1100 femmes à Limoges.

During 13 months, 1101 women attending for antenatal care at Limoges University Hospital were prospectively studied to determine the prevalence of Cytomegalovirus (CMV) antibodies: 47.9% of these women were CMV seropositive. Ethnic group was strongly associated with CMV status: 42.6% of metropolitan and 94.5% of immigrant women were seropositive. Seropositivity was associated with increasing parity and older age. The risk of a susceptible woman to acquire CMV infection during pregnancy is 0.7%. Among the 4 seroconversions, 3 children were infected, with developmentally and neurologically normal status in one case, moderate ear damage in an other case and a disseminated infection in the third case requiring a provoked abortion.

Evaluation of rapid culture centrifugation method for adenovirus detection in stools.

Routine laboratory testing for adenovirus (Adv) requires a procedure that is rapid and reliable, especially for samples from children and immunosuppressed patients, when diarrhea may signal the onset of severe gastrointestinal disorders. An improved culture technique for Adv isolation, using centrifugation step of 24-well plates and needing only 48 h incubation, was evaluated for 382 stool samples. This technique was compared with conventional tube cell culture and a commercial enzyme-linked immunosorbent assay (ELISA) kit. Adv was isolated in 36 samples (9.4%) by rapid culture, in 32 (8.4%) by conventional culture, and in 42 samples (11%) using genus-specific ELISA. A total of 30 isolates were found to be Adv positive in both rapid and conventional cultures, and half of the Adv-positive rapid culture isolates were identified as serotypes 40/41 using a type-specific ELISA. The improved culture method considerably reduces incubation time and also offers a slightly enhanced sensitivity to Adv serotypes. Combined with appropriate cell lines adapted to the isolation of enteric adenoviruses, it therefore constitutes a valuable laboratory test particularly useful in the diagnosis of gastroenteritis.

[New hepatitis viruses "E, GB, etc."]. / Les nouveaux virus des hépatites <>.

Some cases of hepatitis were non A, non B, non C, non D. Hepatitis E virus (Calicivirus) transmission is fecal-oral similar to that of the hepatitis A virus. Viral hepatitis E is endemic and frequently epidemic in many developing countries, but exceptionally observed in France. A high mortality rate was observed in pregnant women. Recently, ELISA assays for IgM anti-HCV are available. Many hepatitis cases (acute and chronic) are not caused by known viruses (non A-non E). Four Flavivirus like have recently been cloned from infectious tamarin serum, derived from human viral hepatitis. Three viruses GB Virus A (GBV-A), GB Virus B (GBV-B) and GB Virus C (GBV-C) were identified. The GB viruses and HG Virus are not genotypes of hepatitis C Virus (HCV) and perhaps that GBV-A/GBV-C and HGV are closely related. GBV-A could be an indigenous tamarin virus. The new hepatitis (non A-non E) viruses were associated with blood transmission and with chronic diseases. The development of specific diagnostic reagents using polymerase chain reaction (PCR) and ELISA assays are essential to answer many questions on the epidemiology (and the incidence of post-transfusion hepatitis), and the pathogenesis of GBV and HGV viruses.

Large-scale study suggests no direct link between human herpesvirus-6 and primary Sjögren's syndrome.

The aim of this study was to evaluate the role of human herpesvirus-6 (HHV-6) in the development of primary Sjögren's syndrome (PSS). Serum HHV-6 antibody levels, as measured by immunofluorescence assay (IFA) and the prevalence of HHV-6 DNA in peripheral blood mononuclear cells (PBMCs) determined by polymerase chain reaction (PCR), were studied in 49 PSS patients and 50 control subjects, all in-patients in the University Hospital Internal Medicine ward, Limoges, France. In addition, portions of labial salivary gland were obtained from 34 patients and 15 controls, the presence of viral DNA being detected by the same PCR technique. The results were then compared with clinical observations of systemic disease manifestations in patients and a histological study of salivary gland involvement. No significant difference in HHV-6 seroprevalence was found between control subjects (50.0%) and patients (63.3%) nor was there any statistically significant difference between patient and control groups for total viral DNA in PBMCs (22.4%, 12.0%) and salivary glands (8.8%, 6.6%). Analysis of clinical and histological data revealed no detectable correlation between disease severity and viral involvement. Tests for HHV-6A and HHV-6B proved positive in patient and control groups, HHV-6B being the most frequently encountered type in both groups. In conclusion, the results of this large-scale trial does not confirm the suspected direct role of HHV-6 in the etiology of PSS.

[Adenoviruses from stool samples in hospital units. Comparison with main pathogens in gastroenteritis (rotavirus, Campylobacter, Salmonella)]. / Les adénovirus dans les prélèvements de selles en milieu hospitalier. Comparison avec les principaux agents des gastroentérites (rotavirus, Campylobacter, Salmonella).

During a six-years period (1988-1993), a total of 14,644 stool samples from in-patients of Limoges University Hospital were examined for the presence of principal enteric pathogens, such as adenovirus, rotavirus, Campylobacter, Salmonella, Shigella and others. Stools were processed for identification of bacteria by standard methods and viruses were detected in fecal specimens using antigen detection methods: ELISA (Enzyme Linked Immunosorbent Assay) and latex agglutination test. The decreasing rates of presence of enteric agents were respectively 6% for rotavirus, 3.2% for Salmonella, 2% for adenovirus, 1.6% for Campylobacter and 0.2% for Shigella, but according to the lack of sensibility of latex agglutination test, adenovirus prevalence was probably underestimated. Concerning the distribution of enteric pathogens throughout the year, our data demonstrate that rotavirus were rather shed during the months from January to April, adenovirus between April and August, Campylobacter during summer and Salmonella from July to October. The two thirds of Campylobacter and rotavirus infections and the half of adenovirus and Salmonella infections were identified during the ten first years of life. The highest prevalence occurs before 5 years old, during the 2nd year of life for adenovirus (4.4%) and rotavirus (22.3%) and during the 3rd year of life for Campylobacter (6.84%) and Salmonella (8.6%).