Meningitis linfocítica recurrente por virus herpes simple tipo 2 / Recurrent lymphocytic meningitis by herpes simplex virus type 2

La meningitis linfocítica recurrente o meningitis de Mollaret es una entidad asociada a un gran número de etiologías infecciosas, autoinmunes, toxicológicas y neoplásicas. En la actualidad el virus herpes simple tipo 2 (HSV-2) es el agente más frecuentemente aislado. Afecta frecuentemente a mujeres de mediana edad y tiende a autolimitarse sin secuelas dentro de la primera semana de inicio de síntomas. El diagnóstico se basa en la detección de ácidos nucleicos virales en el líquido cefalorraquídeo. Al momento no se ha demostrado beneficio en el uso de tratamiento antiviral en la prevención de recurrencias.

Recurrent lymphocytic meningitis or Mollaret´s meningitis is a rare condition caused by a number of infectious, autoimmune, toxic and neoplastic diseases. Herpes simplex type 2 is the most commonly isolated agent. It usually compromises middle aged women, with a self-limited clinical presentation that resolves within a week leaving no sequelae. Its diagnosis is mainly based on nucleic acid detection on cerebrospinal fluid. Antiviral prophylaxis has not shown conclusive to avoid recurrences.

Detection of herpes simplex-1 and -2 and varicella zoster virus by quantitative real-time polymerase chain reaction in corneas from patients with bacterial keratitis / Detecção de vírus herpes simplex tipo 1 e 2 e varicella zoster por reação em cadeia de polimerase em tempo real em córneas de pacientes com ceratites bacterianas

ABSTRACT Objective: Bacterial keratitis occurs worldwide, and despite recent developments, it remains a potentially blinding condition. This study assesses the presence of herpes simplex virus (HSV-1 and -2) and varicella zoster virus (VZV) by quantitative real-time polymerase chain reaction (qPCR) in corneal scrapings from patients with bacterial keratitis. Methods: A total of 65 patients with clinical diagnoses of infectious corneal ulcers prospectively underwent clinical eye examinations. Corneal scrapings were investigated by Gram staining, Giemsa staining, culture, and qPCR (the study group). Risk factors and epidemiological data were recorded. The control group comprising 25 eyes with typical herpes dendritic keratitis was also analyzed by qPCR. Results: From the study group (n=65), nine patients (13.8%) had negative smears, cultures, and qPCR findings. Fifty-six (86.2%) patients had positive cultures: 51 for bacteria, 4 for fungi, and 1 for amoebae. Of the patients who had positive bacterial cultures, qPCR identified 10 patients who were also positive for virus: one for VZV and nine for HSV-1. Of the 25 patients in the control group, 21 tested positive for HSV-1 by qPCR analysis. Conclusions: Herpes may be present in patients with bacterial corneal ulcers, and qPCR may be useful in its detection.

RESUMO Objetivo: Ceratites bacterianas ocorrem mundialmente e apesar dos novos desenvolvimentos permanece como uma condição que pode levar à cegueira. Avaliar a presença de herpes simples (-1 e -2) e vírus varicella zoster (VZV) por reação em cadeia quantitativa de polimerase em tempo real (qPCR) em raspados corneanos de pacientes com ceratite bacteriana. Métodos: Sessenta e cinco pacientes com ceratite infecciosa foram submetidos a raspados corneanos estudados para gram, Giemsa, cultura e qPCR (grupo de estudo). Foram avaliados fatores de risco e epidemiológicos. O grupo controle foi composto por 25 casos de úlcera dendrítica típica por herpes analisados por qPCR. Resultados: Do grupo de estudo (n=65), nove pacientes (13,8%) apresentaram cultura, qPCR e raspado negativos. Cinquenta e seis (86,2%) pacientes apresentaram cultura positiva, 51 para bacteria, 4 para fungo e 1 para ameba. A qPCR identificou 10 pacientes do grupo de cultura positiva para bactéria que também foram positivos para vírus, um VZV e 9 para HSV-1. Dos 25 pacientes que compunham o grupo controle, 21 apresentaram qPCR positivo para HSV-1. Conclusão: Herpes pode estar presente em pacientes com úlceras de córnea bacterianas e a qPCR pode ser útil na sua detecção.

Prevalence & correlates of primary infertility among young women in Mysore, India.

Background & objectives: There are sparse data on the prevalence of primary infertility in India and almost none from Southern India. This study describes the correlates and prevalence of primary infertility among young women in Mysore, India. Methods: The baseline data were collected between November 2005 through March 2006, among 897 sexually active women, aged 15-30 yr, for a study investigating the relationship of bacterial vaginosis and acquisition of herpes simplex virus type-2 (HSV-2) infection. A secondary data analysis of the baseline data was undertaken. Primary infertility was defined as having been married for longer than two years, not using contraception and without a child. Logistic regression was used to examine factors associated with primary infertility. Results: The mean age of the women was 25.9 yr (range: 16-30 yr) and the prevalence of primary infertility was 12.6 per cent [95% Confidence Interval (CI): 10.5-15.0%]. The main factor associated with primary infertility was HSV-2 seropositivity (adjusted odds ratio: 3.41; CI: 1.86, 6.26). Interpretation & conclusions: The estimated prevalence of primary infertility among women in the study was within the range reported by the WHO and similar to other estimates from India. Further research is needed to examine the role of HSV-2 in primary infertility.

Incidence of herpes simplex virus type 2 in young reproductive age women in Mysore, India.

Context: There are sparse data on herpes simplex virus type 2 (HSV-2) infection in India. HSV-2 is one of the most common sexually transmitted infections and the primary cause of genital ulcer disease worldwide. Aim: The aim of this study is to describe the incidence of HSV-2 infection among young reproductive age women in Mysore, India. Setting and Design: Between October 2005 and April 2006, 898 women were enrolled into a prospective cohort study in Mysore, India, and followed quarterly for 6 months. Materials and Methods: An interviewer administered questionnaire was used to collect demographic and social risk factors, and physical examination was conducted for collection of biological specimens to screen for reproductive tract infections at each visit. Serologic testing was conducted for the presence of HSV-2 antibodies using HerpeSelect HSV-2 enzyme-linked immunosorbent assay. Statistical Analysis Used: Data were analyzed using R. Incidence density rates were calculated using Poisson distributions with person-time of follow-up as denominator. Person-time was calculated as time from enrollment until time of first positive HSV-2 test. Results: There were 107 women with HSV-2 antibodies leaving 700 women with negative results at enrollment. The analysis included 696 out of which, there were 36 HSV-2 seroconversions during the study period. The study cohort accumulated roughly 348 woman-years of follow-up, yielding an HSV-2 acquisition rate of 10.4 cases/100 woman-years. All detected infections were asymptomatic. Conclusions: HSV-2 incidence is moderate in this community sample of young reproductive age monogamous women. More research is needed to establish incidence estimates in different Indian settings.

Risk factors of herpes simplex virus type 2 among STD clinic attenders in Delhi, India.

The present study was conducted to determine the seroprevalence and risk factors associated with HSV-2 infection among sexually transmitted diseases (STD) clinic attenders of Delhi in India. Out of 128 patients included, 76 were males and 52 were females. Antibodies to HSV 1 and 2 and HIV infection were determined by ELISA. Syphilis seropositivity was determined by VDRL test and confirm by TPHA test. Ulcer scrapping were stained by Giemsa for Herpes progenitalis and Donovan bodies and Grams for Haemophilus decreyi infection. The HSV-2 and HSV-I seroprevalence was found to be 85.2% and 77.3% respectively. 87.3% of HSV-2 seropositive patients were asymptomic. 10.7% of patients had coinfection of HSV-2 and HIV. STDs like syphilis, chancroid, gonococcal and non-gonococcal urethritis were significantly associated in HSV-2 infection. Thus the study demonstrates high prevalence of HSV-2 infection in Delhi city. Significant association of HSV-2 infection with previous history of STD (p < 0.02) and multiple sexual partners in males was found (p < 0.002).

Disseminated herpes simplex infection with cystic fibrosis: a case report.

A 6 months old female infant presented with history of fever, cough and severe respiratory distress. There was past history of recurrent attacks of pneumonia. She succumbed to the illness after a hospital stay of 7 days. Postmortem revealed morphological evidence of cystic fibrosis along with herpes simplex infection of liver and adrenals. The co-existence of disseminated herpes simplex infection and cystic fibrosis is very rare.

Prevalence and incidence of, and risk factors for, HIV-1 infection among factory workers in Ethiopia, 1997-2001.

The study was conducted to determine the prevalence, incidence, and risk factors for HIV infection among factory workers at two sites in Ethiopia. During February 1997-December 2001, a structured questionnaire was used for obtaining information on sociodemographics, sexual behaviour, and reported sexually transmitted infections (STIs) from a cohort of 1679 individuals. Serum samples were screened for antibodies against HIV, Treponema pallidum haemaglutination (TPHA), and herpes simplex virus type 2 (HSV-2). The overall baseline prevalence of HIV was 9.4%-8.5% among males and 12.4% among females. For both the sexes, the factors independently associated with an increased risk of HIV infection were widowhood and having had antibodies against TPHA and HSV-2. The risk factors specific for males were being orthodox Christian, having had a higher lifetime number of sexual partners, and genital discharge in the past five years. The risk factors for females, included low income, one or more rape(s) over lifetime, and casual sex in the last year. The overall incidence of HIV infection was 0.4 per 100 person-years. The highest rate of incidence was observed among young women aged less than 30 years (1 per 100 person-years). The study confirmed that high-risk sexual behaviour and STIs play major roles in the spread of HIV infection in the Ethiopians of both the sexes, but the factors, such as rape and low economic status, make women more vulnerable than men.

High seroprevalence of HSV-1 and HSV-2 in STD clinic attendees and non-high risk controls: a case control study at a referral hospital in south India.

BACKGROUND: In Asia, HSV seroprevalence studies are sparse and they have recorded lower prevalence of HSV infection, especially HSV-2. AIMS: To ascertain the seroprevalence of HSV-1 and HSV-2 in patients attending a STD clinic in a referral hospital in south India and to compare it with a control group. METHODS: The study included 135 consecutive STD cases having history of ulcerative or non-ulcerative STD in the present or in the past 5 years and 135 age and sex-matched controls. Diagnostic serology was done for HSV-1 and HSV-2 using type specific IgG by indirect immunoassay using ELISA. The results were analyzed utilizing Chi- square test. RESULTS: Amongst 135 STD clinic cases, 106 cases were males and 29 cases were females with male to female ratio of 3.65:1. The mean age was 32.2 years (range 16-65 years). Among study group cases, 112 (82.9%) cases were co-infected with HSV-1 and HSV-2, 11 (8.1%) cases were seropositive for HSV-1 alone and 3 (2.2%) cases were seropositive for HSV-2 alone. In the control group, 112 (82.9%) cases were co-infected with HSV-1 and 2, 12 (9.6%) for HSV-1 alone and 1(0.8%) for HSV-2 alone. Correlation of HSV-1 and HSV-2 serology with various demographic and behavioral factors was statistically insignificant. CONCLUSIONS: Seroprevalence of HSV-1 and HSV-2 in STD clinic cases and control group is high, similar to that recorded in sub-Saharan Africa. Thus, serological studies for HSV-1 and HSV-2 cannot be taken as a marker of sexual behavior in our set of population.

Study on koilocytosis, X-chromatin and HSV-2 in cervical smears in Nepal.

A total of 1,106 cervical smears were studied during a one year period from Feb 1999 to Feb 2000. Majority of the lesions were Inflammatory smears constituting 91.0%, Cervical intraepithelial neoplasia [CIN] and Squamous cell carcinoma [SCC] cervix constituted 8.0% and 1.0% respectively. The percentage of different grades of CIN being CIN I 85.0%, CIN II 9.0% and CIN III 6.0%. Thirty cases were taken as a study group. The commonest age group for CIN was 31-40 years 80.0% and for carcinoma cervix above 50 years 63.0%. The most common risk factors were marriage before 20 years of age 80.0% and a low socio-economic status 70.0%. The common presenting feature in CIN was pain lower abdomen 88.0%, followed by whitish discharge per vagina 60.0%. Similarly in carcinoma cervix pain lower abdomen 80.0% followed by weight loss 60.0% were the common presenting symptoms. Koilocytic change was seen in 42.1% of the cases of CIN I. The incidence of X-chromatin positivity gradually decreased as the lesion advanced, the p-value between CIN I and CIN II [p=<0.02], CIN I and CIN III [0=0.00] and between CIN III and Carcinoma cervix [p=<0.004] being significant. An association with Herpes simplex virus-2 [HSV-2] was seen in 11.0% cases of CIN I, 33.0% cases of CIN IIl and 40.0% cases of carcinoma cervix with a gradual rising antibody titre of 1:2 in CIN I, 1:7 in CIN III and 1:7 to 1:9 in carcinoma cervix respectively.

Asymptomatic shedding of genital herpes simplex virus [HSV-2] during pregnancy and neonatal outcome

The objectives of this study were detection of the asymptomatic shedding of genital herpes simplex virus type 2 [HSV-2] in the cervical secretion among the pregnant women late in pregnancy, through viral isolation by tissue culture [TC] and correlating it to the other methods of diagnosis or HSV-2, and also correlating it to the neonatal outcome. This study was conducted on 90 pregnant women, during the 3rd trimester who were coming for antenatal care, with no history, and no clinical findings of genital herpes. Asymptomatic HSV-2 shedding was determined by TC and polymerase chain reaction [PCR] of the cervical secretion, and the serologic status was determined by detecting HSV-2 IgM antibody. All of them were followed till delivery. An oropharyngeal swab of the neonates was taken for viral isolation by TC, and cord blood sample for HSV-IgM antibody. We found that: the percent of positivity of HSV-2 isolation by TC increased by increasing age, parity and number of previous abortions. [2] Asymptomatic shedding was detected by TC in 44/90 [48.9%] of the cervical swabs, HSV-2 DNA was detected in 43/44 [97.7%] of the +ve cervical swab, while serum HSV-2 IgM antibody was detected in 16/89 [18%] serum samples, and these represented 16/44 [36.4%] and 16/43 [37.2%] of the women with HSV-2 +ve TC and HSV-2 DNA detected by PCR respectively. [3] Only 3/90 [3.3%] oropharyngeal swabs showed HSV-2 +ve TC, their mothers were also HSV-2 +ve TC, while HSV-2 DNA, and HSV-2 IgM antibody could not be detected. [4] There was a significant correlation between HSV-2 isolation by TC and the perinatal outcome e.g. intrauterine fetal death [IUFD] still birth [SB], Apgar score, neonatal weight and number of neonates transferred to the neonatal intensive care unit [NICU], [5] There was a highly significant correlation between HSV-2 isolation by TC and HSV-2 DNA detection by PCR; while measurement of HSV-2 IgM antibody is of limited value in relation to both of them. HSV-2 isolation by TC is accurate, sensitive technique of low cost but of long turnaround time for diagnosis of asymptomatic shedding of HSV-2 during pregnancy. HSV-2 DNA detection by PCR can replace TC as it is more rapid but more expensive, and the cost benefit should be evaluated. So, TC is recommended to be used for screening HSV-2 infection, while PCR used for rapid diagnosis when subsequent intervention is essential e.g. antiviral treatment We could not conclusively relate these neonatal outcome to the asymptomatically shedded HSV-2

Prevalence of herpes simplex virus infection in patients suspected of genital herpes; and virus typing by type specific fluorescent monoclonal antibodies.

During the period between April 1994 and February 1996, a total of 154 female patients who attended the Clinic of Female Sexually Transmitted Diseases, Siriraj Hospital with clinical symptoms suspected of genital herpes were investigated for herpes simplex virus (HSV) infection by the virus isolation method in Vero cell cultures. Swabs from external genital lesions and the cervix from each patient were collected separately and used as the clinical specimens for isolation of HSV. The virus isolates were identified by indirect immunofluorescence (IIF) staining of the infected cell cultures using polyclonal HSV-2 specific antiserum which was reactive to common HSV antigens for both types of viruses. Typing of HSV was performed by direct IF using monoclonal antibody specific to HSV-1 or HSV-2. HSV was isolated from 78.6 per cent (121 of 154) of the cases studied; and among the infected cases, there were 47.9 per cent (58 of 121) in whom the infection involved both external genital lesions and cervixes, and 50.4 per cent (61) in whom the infection was limited to external genital lesions only. There were 2 cases (1.7%) in whom HSV was isolated from cervixes but not external genital lesions. Seventy-five HSV isolates were further subjected to typing. The present study showed that HSV-1 was accounted for 18.7 per cent (14 isolates), while HSV-2 took the remaining part of 81.3 per cent (61 isolates). The data demonstrated an increase in the prevalence of HSV-1 in genital herpes in our people.

Progression of intravaginal infection by herpes simplex-2 in genetically athymic mice

The purpose of this paper was to study the pathogenesis of wild-type Herpes simplex-2 (HSV-2) primary intravaginal (IVAG) infection in genetically athymic (nude) mice. Nude (nu/nu) N: NIH(S) and Balb/c mice, as well as their euthymic counterparts were IVAG infected with 5 x 10(5) pfu of HSV-2. The progression of the infection was followed by HSV-2 immunolabeling using the peroxidase-antiperoxidase technique in tissue sections of the whole body, electron microscopy, and viremia titration at two different timepoints. 70 per cent of athymic NIH mice, 30 per cent of euthymic NIH mice, and 80 per cent of both athymic and euthymic Balb/c mice developed acute vulvovaginitis and died between 8-10 days post-infection (pi). Viremia was not detected in either athymic or euthymic mice. HSV-2 replicated in the vulvovaginal, vesical and perianal epithelia, then progressed towards the central nervous system mainly along autonomic nerves and ganglia. HSV-2 antigens were not detected in liver, spleen, kidney, skin, heart, lung or bone marrow. The conclusion is that the T-cell immune response seems to limit the IVAG infection of NIH mice at the inoculation site, but is not involved in preventing HSV-2 dissemination through the blood.

Diagnosis off human herpesvirus infections [epstein-barr virus and herps simplex viruses] by polymerase chain reaction test

Herpesviruses are important human pathogens which establish latent and asymptomatic infections in the majority of infected individuals. Commonly used antibody tests are frequently insufficient for diagnosing herpesvirus.associated diseases and should be supplemented with the direct detection of the virus or its components. The method of choice for this now is a polymerase chain reaction [PCR] test. In this study highly sensitive, nested PCR tests were developed for the detection and genotyping of Epstein-Barr virus [EBV] and for the detection of herpes simplex virus, type 1 and type 2 [HSV-1 and 2]. These tests were introduced in Kuwait for the first time and since have been offered for diagnosis of such HSV- and EBV-associated diseases as herpes encephalitis, post-transplantation and AIDS-related lymphomas, nasopharyngeal carcinoma and lymphoepithelioma-like cancers

Rapid diagnosis of asymptomatic recurrences of genital HSV during pregnancy

Samples were obtained from the endocervix and the major and minor labia of 154 full-term pregnant women with past history of suspected genital herpes. Cells obtained from the cervical and vulval swabs were stained with fluorescein isothiocynate [FITC]- labeled monoclonal antibody to HSV types 1 and 2 and examined at x250 with a fluorescence microscope. Two women [1.30%] had asymptomatic herpes virus shedding, one [0.65%] with simultaneous cervical and vulval shedding and the other [0.65%] with asymptomatic shedding from the external genitals only, the 2 viral isolates were identified and typed as HSV -2

Echovirus type 19 and herpes simplex type 2 infection in human placenta tissue explants

1. Light and electron microscopy have been used to characterize echovirus 19 and herpes simplex type 2 infection of human placenta tissue in vitro. Immunofluorescence, autoradiography and virus adsorption were used to determine virus replication in this system. 2. Placental tissue was permissive to echovirus 19. Trophoblast cells were lysed with liberation of mature virions. However, during the 48-h period of observation, few cells were damaged and the trophoblastic structure was maintained. 3. HSV-2 infection in placental tissue was aborted although trophoblastic cells allowed virus adsorption, penetration and uncoating. A characteristic cytopathic effect was observed in infected trophoblastic cells in spite of the abortive infection