[Ocular manifestations of emerging arboviruses: Dengue fever, Chikungunya, Zika virus, West Nile virus, and yellow fever (French translation of the article)]. / Manifestations oculaires des arboviroses émergentes : dengue, chikungunya, infection à virus Zika, fièvre du Nil occidental et fièvre jaune.

Arboviruses are viral diseases transmitted by mosquitoes and tics bites. They are a major cause of morbidity and sometimes mortality. Their expansion is constant and due in part to climate change and globalization. Mostly found in tropical regions, arboviruses are sometimes the source of epidemics in Europe. Recently, the Chikungunya virus and the Zika virus were responsible for very large epidemics impacting populations that had never been in contact with those viruses. There are currently no effective antiviral treatments or vaccines. Ocular manifestations due to those infections are thus more frequent and increasingly better described. They are sometimes, as with Zika, complicated by a congenital ocular syndrome. The goal of this review is to describe the ophthalmological manifestations of Dengue fever, Chikungunya virus, Zika virus, West Nile virus, and yellow fever.

Ocular manifestations of emerging arboviruses: Dengue fever, Chikungunya, Zika virus, West Nile virus, and yellow fever.

Arboviruses are viral diseases transmitted by mosquitoes and tick bites. They are a major cause of morbidity and sometimes mortality. Their expansion is constant and due in part to climate change and globalization. Mostly found in tropical regions, arboviruses are sometimes the source of epidemics in Europe. Recently, the Chikungunya virus and the Zika virus were responsible for very large epidemics impacting populations that had never been in contact with those viruses. There are currently no effective antiviral treatments or vaccines. Ocular manifestations due to those infections are thus more frequent and increasingly better described. They are sometimes, as with Zika, complicated by a congenital ocular syndrome. The goal of this review is to describe the ophthalmological manifestations of Dengue fever, Chikungunya virus, Zika virus, West Nile virus, and yellow fever.

High prevalence of HPV infection in the remote villages of French Guiana: an epidemiological study.

Cervical cancer is the second most frequent cancer in women in French Guiana. Studies have shown that populations living in the remote areas of the interior have early sexual debut and that multiple sexual partnerships are common. The objective of the present study was thus to determine the prevalence of human papillomavirus (HPV) infection in these areas. A study was conducted in women aged 20-65 years with previous sexual activity. Women were included on a voluntary basis after using local media and leaders to inform them of the visit of the team. HPV infection was defined by the detection of HPV DNA using the Greiner Bio-One kit. In addition to HPV testing cytology was performed. The overall age-standardized prevalence rate was 35%. There was a U-shaped evolution of HPV prevalence by age with women aged >50 years at highest risk for HPV, followed by the 20-29 years group. Twenty-seven percent of women with a positive HPV test had normal cytology. Given the high incidence of cervical cancer in French Guiana and the high prevalence of HPV infections the present results re-emphasize the need for screening for cervical cancer in these remote areas. Vaccination against HPV, preferably with a nonavalent vaccine, also seems an important prevention measure. However, in this region where a large portion of the population has no health insurance, this still represents a challenge.

Prospective and descriptive study of adult dengue cases in an emergency department, in Martinique.

OBJECTIVE: Knowing about the clinical aspects of dengue in endemic zones is essential to implementation of appropriate case management protocols and public health interventions. PATIENTS AND METHODS: The authors made a 4-year prospective, observational study of dengue-infected patients admitted to the emergency department of the Fort-de-France University Hospital. RESULTS: Two hundred and sixty-three male and 297 female patients were included. The median age was 37 years (range: 14-91). The diagnosis was based on a positive RT-PCR (463 patients) or on the presence of specific IgM (97 patients). Two hundred and seventy-seven patients (49.5%) presented with dengue fever without complications. According to WHO criteria, 95 patients (17%) developed plasma leakage, including 39 patients (7%) diagnosed with DHF, and 10 (1.8%) diagnosed with DSS. Among the other patients without plasma leakage, 84 (15%) had isolated thrombocytopenia, 14 (2.5%) had internal bleeding, and 90 (16%) had unusual manifestations. Seven patients died (1.3%): fulminant hepatitis (two), myocarditis (one), encephalitis (one), acute respiratory failure (one), gangrenous cholecystitis (one), and post-traumatic intracranial hemorrhage (one). The other patients recovered. Seven patients were pregnant (1.3%) from 6 to 27 weeks of amenorrhea and carried their pregnancy to term without complications. CONCLUSION: With this experience, we were able to develop appropriate case management protocols for patients during dengue epidemics.

Role of Mycoplasma pneumoniae in pediatric encephalitis.

A retrospective study investigating all the infectious encephalitis cases hospitalized at the pediatric intensive care unit of Edouard Herriot University Hospital in Lyon, France, was carried out in order to estimate the prevalence of Mycoplasma pneumoniae in acute childhood encephalitis. From January 2001 to December 2005, the cases of 29 children were selected and reviewed. M. pneumoniae related encephalitis was considered as probable in five cases (17%) on the basis of positive serological tests or positive polymerase chain reaction (PCR) tests in throat or nasopharyngeal swab while the PCR tests performed from the cerebrospinal fluid were negative. This study suggests that M. pneumoniae may be a major cause of infectious encephalitis in children as well as enteroviruses or Epstein-Barr virus detected in five and three cases, respectively.

Monitoring of human cytomegalovirus infection in immunosuppressed patients using real-time PCR on whole blood.

BACKGROUND: Quantitative monitoring of human cytomegalovirus (HCMV) is currently used in the follow-up of immunosuppressed patients. OBJECTIVE: To investigate whether real-time PCR quantification (QPCR) of HCMV DNA could replace pp65 antigenemia. STUDY DESIGN: We compared HCMV QPCR on whole blood (WB) and on plasma with a pp65-antigenemia assay on 192 samples. Afterwards, we tested 1310 samples from 308 immunosuppressed patients both by antigenemia assay and QPCR on WB. RESULTS: The first study comparison showed that QPCR results on WB and plasma were significantly correlated with antigenemia. QPCR on WB was more sensitive than QPCR on plasma or antigenemia, detecting 31 and 49 additional positive samples, respectively. During the second comparison, QPCR on WB and antigenemia were again correlated (r=0.70; p<0.0001), but QPCR detected 244 additional positive samples. HCMV DNA was detected earlier than pp65 antigen (median difference: 14 days; range: 7-30). One, 5, 10, 50 and 100 pp65-positive cells/200,000 leukocytes corresponded to 439, 1531, 2623, 9150 and 15,671 HCMV DNA copies/mL of WB, respectively, but this equivalence differed according to the sub-group of patients considered. CONCLUSION: QPCR on WB is the most sensitive method for the monitoring of HCMV infection in immunosuppressed patients.

[Human herpesvirus 6 encephalitis after bone marrow transplantation]. / Un cas d'encéphalite à herpès virus humain de type 6 après transplantation de moelle osseuse.

Human herpesvirus 6 (HHV-6) encephalitis may induce neurological sequelae and death; the diagnosis is difficult because of an initially poor symptomatology and of the absence of specific biochemical, electric and radiological signs. We report on a 7-year-old boy with relapsed acute lymphoblastic leukaemia, who developed HHV-6 encephalitis after bone marrow transplantation; the patient recovered after treatment with ganciclovir.

[Drug hypersensitivity syndrome associated with a primary HHV6 infection]. / Syndrome d'hypersensibilité médicamenteuse associé à une primo-infection HHV6.

INTRODUCTION: Drug hypersensitivity syndrome is a severe life-threatening drug reaction. An association between this syndrome and HHV6 reactivation has been hypothesized. CASE-REPORT: A 45 year-old women was treated with sulfasalazine for polyarthralgia. One month after beginning the treatment, she developed a drug hypersensitivity syndrome with severe acute hepatic failure. HHV6 serology and serum PCR revealed a primary HHV6 infection. DISCUSSION: We report the second case of drug hypersensitivity syndrome associated with a primary HHV6 infection. An immunological disorder may explain such an association by increasing viral replication. Detection and titration of anti-HHV6 antibodies in each case of drug hypersensitivity syndrome should help to confirm this association and possibly modify treatment strategy.

[Human herpesvirus 6 encephalitis in trimethoprim-sulfamethoxazole-induced hypersensitivity syndrome]. / Association d'une encéphalite à herpès virus 6 et d'un syndrome d'hypersensibilité médicamenteuse au triméthoprime-sulfaméthoxazole.

INTRODUCTION: Human herpesvirus 6 (HHV-6), the causative agent of the common exanthem subitum, is a known cause of central nervous system infection in immunocompromised patients. It has been suggested that HHV-6 participate in the development of drug-induced hypersensitivity syndrome. CASE REPORT: We reported a case of HHV-6 encephalitis associated with hypersensitivity syndrome induced by trimethoprim-sulfamethoxazole in a 72-year-old HIV-negative woman. DISCUSSION: Our case confirmed that reactivation of HHV-6 infection may contribute to the development of the hypersensitivity syndrome.

[Nosocomial infections due to adenovirus in a paediatric unit]. / Infections nosocomiales à adénovirus dans un service de pédiatrie.

OBJECTIVE: We carried out a retrospective analysis of an outbreak of adenovirus (AdV) infections in a paediatric unit. The aim of the study was to analyse cases, determine the route of transmission and to evaluate the efficacy of the prevention measures. PATIENTS AND METHODS: The study was performed by recollection of AdV infection cases during a period of 1 year and the results were compared with the list of clinical cases recorded during the epidemic. The clinical files of children with a positive specimen were retrospectively analysed. During that period, five members of the medical staff showed clinical signs and symptoms of AdV infection. A throat swab was collected from a subset of the staff. RESULTS: Among nine patients with positive AdV detection, six were infected with an Adv type 2. Six were nosocomially-acquired, the other two were only probable nosocomial infections. The index case was a child presenting a febrile diarrhoea 48 h prior to being admitted to the hospital. Nosocomial transmission was associated with the prolonged shedding of the virus with faeces of the infected cases. The specimens collected from the staff remained negative. The outcome was favourable for all children. CONCLUSIONS: Prevention measures, implemented when the epidemic was characterised, allowed the control of the nosocomial outbreak.

Herpes simplex virus acute retinal necrosis during pregnancy.

PURPOSE: As pregnancy is liable to modify immune response, the authors explored the immune functions of a pregnant patient with acute retinal necrosis (ARN) to ascertain whether pregnancy may promote the onset of infection. METHODS: Polymerase chain reaction (PCR) was used for the detection of herpes simplex virus (HSV) DNA in ocular, uterus cervix, and cerebrospinal fluid samples. Peripheral blood mononuclear cells were cultured for 72 hours with mitogens and cellular proliferation was assessed using (methyl-3H) thymidine incorporation. Flow cytometry was performed for T, B, and NK cell count using CD2, CD3, CD4, CD8 (T cells), CD19, CD20 (B cells), and a combination of CD3-CD16 and CD56 monoclonal antibodies (NK cells). RESULTS: Unilateral ARN, with a confluent peripheral necrotizing retinitis extending throughout the entire retina, was diagnosed clinically. The herpetic infection (herpes simplex virus 1) was confirmed using PCR of aqueous humor specimen. The immunologic study performed during and after pregnancy showed that T and B lymphocytes were quantitatively normal and responses to concanavalin A, phytohemagglutinin, and pokeweed mitogens were weaker during pregnancy. CONCLUSIONS: A reduced response to mitogens, with postdelivery normalization, was noted in a pregnant woman with an ARN syndrome. Further studies are needed to explore the antigen-specific immune deviation in pregnant patients with ARN.

[Signification and limitations of virology diagnostic tools in herpes facialis, herpes genitalis, herpes gestationis and in neonates at risk]. / Signification et limites des moyens diagnostiques virologiques dans l'herpès oro-facial, l'herpès génital, l'herpès de la femme enceinte et chez le nouveau-né à risque.

INTRODUCTION: Cutaneomucous herpes is frequent in humans. Laboratory confirmation of clinical diagnosis is important, as there are atypical presentations in genital herpes. METHODS: The review of the French and English literature on virological diagnosis of herpes simplex, indexed in Medline (1990-2001), Embase and Cochran Library (1995-2001) was carried out. RESULTS: 172 publications were selected, and 125 of them were used for this work. The current methods to diagnose herpes in cutaneous lesions are detection of antigens by immunofluorescence or ELISA, culture and PCR. The sensitivity and accuracy of the diagnostic methods are directly linked to the quality of the sampling. Antigen detection is a rapid method, but lacks sensitivity. Culture (the gold standard) is sensitive but sometimes the detection of the virus requires several days. Most of the PCR procedures developed are individual non standardized "in house methods. However, the rapidity and sensitivity of this latter technic make it very useful. Serology allows determination of the immune status of the patients. The development of type specific serology had lead to numerous seroepidemiological studies demonstrating that genital herpes due to HSV2 has increased in most of the countries. CONCLUSION: Rapid and sensitive methods are available for the diagnosis of cutaneous herpes in virological laboratories. However, questions remain for the acceptance of PCR and type specific serology in routine diagnosis. These two technics still have to be standardised before being widely used.

Development of a real-time PCR procedure including an internal control for the measurement of HCMV viral load.

Human cytomegalovirus (HCMV) infections are frequent in immuno-compromised patients. The recent development of real-time PCR procedures that allow the rapid quantification of genome load will be helpful for accurate monitoring of these infections. Two extraction procedures were evaluated using 30 blood samples that were processed pure and diluted (1/10). Repeatability and reproducibility of the quantitative PCR procedure using an internal control for amplification were analysed, and its sensitivity compared to a qualitative PCR procedure using 50 HCMV culture positive blood samples. The real-time PCR and qualitative PCR procedures were positive in 46 and 48 of the samples tested, respectively. Discrepancies were observed for samples with a low viral load. The sensitivity of the real-time PCR procedure was evaluated at 500 HCMV DNA copies per ml of sera. The use of an internal control concomitantly processed during the HCMV quantification did not alter the sensitivity of the procedure, and was relevant for the detection of putative PCR inhibitors that may interfere with the amplification process. This procedure was used to measure genome load in two bone marrow transplant patients with HCMV disease, confirming that this new PCR procedure should be used widely for diagnosing and monitoring HCMV infections in transplant patients.

Diagnosis and surveillance of herpes simplex virus infection of the central nervous system.

Herpes simplex viruses (HSV) are responsible for neurological disorders that require rapid diagnostic methods and specific antiviral therapy. During 1997, 1431 cerebrospinal fluid samples (CSF) collected from 1339 patients with neurological disorder presentations were processed for HSV detection. Eleven patients were positive for HSV, seven presenting with encephalitis (6/7 due to HSV1) and 4 with aseptic meningitis (4/4 due to HSV2). The incidence of HSV encephalitis was 2.33 cases / 10(6) inhabitants/year. Among encephalitis (HSV encephalitis) cases, 1 patient died due to the late implementation of antiviral therapy, and sequelae were observed in 4 cases. No sequelae were observed in aseptic meningitis cases. Four HSV encephalitis cases were monitored by PCR detection in CSF. Despite acyclovir therapy, PCR remained positive in CSF up to 20 days in 2 cases. This result suggest that the antiviral treatment for HSV encephalitis should be monitored by PCR detection of HSV in CSF.

Screening for Chlamydia trachomatis and Ureaplasma urealyticum infection in semen from asymptomatic male partners of infertile couples prior to in vitro fertilization.

In a prospective study, the prevalence of infection with Chlamydia trachomatis and Ureaplasma urealyticum was evaluated in the semen of 92 asymptomatic male partners of infertile couples using polymerase chain reaction and culture, respectively. The results were compared with the detection of serologically specific antibodies. U. urealyticum and C. trachomatis were detected in 12 (13%) and 10 (10.8%) of the tested ejaculates, respectively. One mixed infection was detected. No correlation was found between detection of the pathogens in ejaculates and the presence of specific antibodies in serum. This study therefore confirms the limited diagnostic value of serological analysis to ascertain infection with C. trachomatis or U. urealyticum. The high frequency of detection of these pathogens among asymptomatic male partners of infertile couples emphasizes their potential role in the impairment of male fertility, and the need for sensitive and specific detection methods to prevent infection of the early embryo when using new reproductive techniques such as zona pellucida hatching or intracytoplasmic microinjection.

[Herpes simplex virus types 1 and 2 (HSV-1 and HSV-2)]. / Herpesvirus simplex de types 1 et 2 (HSV-1 et HSV-2).

Herpes simplex virus (HSV) infections are prevalent worldwide. HSV are characterized by their ability to establish and maintain latent infections that can be reactivated. Various clinical presentations of HSV infections are described. Mostly asymptomatic, these infections may become life-threatening when occurring in neonates or when infecting the central nervous system. Accurate diagnosis of HSV infections is important and PCR is the most sensitive technique for detecting HSV. Type-specific serologies could be particularly useful for seroprevalence rates. Aciclovir is an efficient drug for the treatment of herpes simplex virus infections and resistance to this drug has been reported mainly in immunocompromised patients during the course of aciclovir treatment. There is a variety of potential vaccines for prophylaxis of HSV infection, but no vaccine is now available.

[Recurrent Mollaret's meningitis of herpetic origin]. / Méningite multirécurrente de Mollaret d'origine herpétique.

BACKGROUND: Benign recurrent meningitis, or Mollaret's meningitis, is an uncommon disease whose viral origin was long unidentified. Since 1991, about twenty cases have been reported in patients with herpes infection. CASE REPORT: A female patient had experienced repeated episodes of spontaneous meningitis since 1983. The episodes resolved spontaneously and no etiology had been identified. A spinal tap was performed when the patient was again hospitalized a new episode of meningitis and PCR amplification of the herpes simplex virus type 2 (HSV 2) was positive. The patient was given long term acyclovir per os. A new spinal tap after resolution of the meningitis episode was PCR HSV2 negative. DISCUSSION: HSV2 infection is one of the known causes of Mollaret's meningitis. Long-term antiviral therapy appears to prevent recurrence as was observed in our patient.