Herpesvirus encephalitis diagnosed by polymerase chain reaction at the National Institute of Neurology of Mexico.

The frequency of central nervous system infections due to herpesvirus have been studied in various populations; however, studies in Mexican mestizo patients are scant. This paper documents the frequency of herpesvirus encephalitis in Mexican mestizo patients from the National Institute of Neurology and Neurosurgery (NINN) of Mexico. To study the frequency of herpetic viral encephalitis at the NINN in the period from 2004 to 2009. We reviewed clinical records from patients with clinically suspected encephalitis; polymerase chain reaction assays were done for detection of herpesviruses in cerebrospinal fluid (CSF) samples. The total number of patients studied was 502; in 59 (12%), the diagnosis of herpetic encephalitis was confirmed by PCR-based testing of CSF. Of them, 21 (36%) were positive for herpes simplex virus type 1, 15 (25%) for Epstein-Barr virus, 10 (17%) for varicella zoster virus, 8 (14%) for cytomegalovirus, 3 (5%) for human herpesvirus 6, and 2 (3%) for herpes simplex virus 2. Our results show a varied frequency of viral encephalitis in mestizo patients due to herpesviruses in a tertiary neurological center and point out the importance of modern molecular technology to reach the etiological diagnosis in cases of encephalitis.

Herpes simplex virus type 2 meningitis as a manifestation of Good's syndrome.

Good's syndrome is a primary immunodeficiency phenocopy characterized for thymoma and immunodeficiency. The most frequent clinical presentation is recurrent or opportunistic infections, hematological alterations, and chronic diarrhea. We treated a 66-year-old man who consulted for 5 days of headache and diplopia with right sixth cranial nerve palsy at examination. Patient reported chronic diarrhea and prolonged febrile syndrome accompanied by weight loss of 23 kg in the last year. Exhaustive evaluation revealed Herpes simplex virus (HSV) type 2 meningitis, eosinophilic colitis, and type A thymoma. Severe antibody deficiency (hypogammaglobulinemia) associated with thymoma confirmed the diagnosis of Good's syndrome.

Meningite recorrente de Mollaret: uma revisão / Mollaret's recurrent meningitis: an overview

A meningite recorrente linfocítica benigna ou meningite de Mollaret, inicialmente descrita pelo neurologista francês Pierre Mollaret em 1944, é uma condição relativamente rara, benigna mas incapacitante durante os seus períodos de agudização. Trata-se de quadro inflamatório meníngeo recorrente devido a reativação de infecção pelo herpes simples vírus, particularmente o herpesvirus do tipo 2 (HSV-2). Pode ser reconhecida a partir do seu quadro clínico de meningismo agudo, perfil liquórico linfocítico e identificação do genoma viral por PCR no líquor. Aciclovir e seus derivados podem ser utilizado no seu tratamento ou na sua profilaxia. Sua identificação é importante no sentido de se excluir outras causas de quadros meníngeos recorrentes.

Benign recurrent lymphocytic meningitis or Mollaret's meningitis (MM) was frst described by the French neurologist Pierre Mollaret in 1944. MM is a relatively rare, benign but disabling condition. MM is a recurrent meningeal inflammatory illness due to reactivation of herpes simplex virus infection, particularly herpesvirus type 2 (HSV-2). It can be recognized from its clinical picture of acute meningism, lymphocytic CSF profle and by the identifcation of the viral genome in the CSF by PCR. Acyclovir and its derivatives may be used for its treatment or prophylaxis. The identifcation of MM is important in order to exclude other causes of recurrent meningeal conditions.

Herpes Simplex Virus Evasion of Early Host Antiviral Responses.

Herpes simplex viruses type 1 (HSV-1) and type 2 (HSV-2) have co-evolved with humans for thousands of years and are present at a high prevalence in the population worldwide. HSV infections are responsible for several illnesses including skin and mucosal lesions, blindness and even life-threatening encephalitis in both, immunocompetent and immunocompromised individuals of all ages. Therefore, diseases caused by HSVs represent significant public health burdens. Similar to other herpesviruses, HSV-1 and HSV-2 produce lifelong infections in the host by establishing latency in neurons and sporadically reactivating from these cells, eliciting recurrences that are accompanied by viral shedding in both, symptomatic and asymptomatic individuals. The ability of HSVs to persist and recur in otherwise healthy individuals is likely given by the numerous virulence factors that these viruses have evolved to evade host antiviral responses. Here, we review and discuss molecular mechanisms used by HSVs to evade early innate antiviral responses, which are the first lines of defense against these viruses. A comprehensive understanding of how HSVs evade host early antiviral responses could contribute to the development of novel therapies and vaccines to counteract these viruses.

Behavioral, Psychological, Gender, and Health Service Correlates to Herpes Simplex Virus Type 2 Infection among Young Adult Mexican-American Women Living in a Disadvantaged Community.

Herpes simplex virus type 2 (HSV-2) is among the most prevalent sexually transmitted infections in the United States. Despite this, there has been limited research on the correlates to HSV-2 among disadvantaged and marginalized women, particularly among Latinas. Data for the present analysis include 125 young adult Mexican-American women enrolled in a longitudinal study in a disadvantaged urban community in San Antonio, Texas. The current rate of tested HSV-2 infection is 56.8%. Our findings suggest strong comorbidity of genital herpes with injecting heroin use, Hepatitis C, sexual violence, incarceration, and mental illness. Contributing to this population's nexus of risk are the low rates of health service utilization among those infected with HSV-2. Integration between behavioral health and primary care, including access to preventative services, are essential for improving the health of Latinas living in disadvantaged neighborhoods.

Seroprevalence of Herpes Simplex Virus type-2 (HSV-2) among pregnant women who participated in a national HIV surveillance activity in Haiti.

BACKGROUND: Herpes simplex virus type 2 (HSV-2), one the most common causes of genital ulcers, appears to increase both the risk of HIV acquisition and HIV transmission. HSV-2/HIV co-infection among pregnant women may increase the risk of perinatal transmission of HIV. This study describes rates of HSV-2 among pregnant women in Haiti and HSV-2 test performance in this population. METHODS: Unlinked residual serum specimens from the 2012 National HIV and Syphilis Sentinel Surveillance Survey among pregnant women in Haiti were tested using two commercial kits (Focus HerpeSelect, Kalon) for HSV-2 antibodies. We evaluated rates of HSV-2 seropositivity and HSV-2/HIV co-infection, associations between HSV-2 and demographic characteristics using multivariable Cox proportional hazards modeling, and HSV-2 test performance in this population. RESULTS: Serum samples from 1000 pregnant women (all 164 HIV positive and 836 random HIV negative) were selected. The overall weighted prevalence of HSV-2 was 31.4% (95% CI: 27.7-35.4) and the prevalence of HIV-positivity among HSV-2 positive pregnant women was five times higher than the prevalence among HSV-2 negative women (4.8% [95% CI: 3.9-6.0] vs. 0.9% [95% CI: 0.6-1.3], respectively). Factors significantly associated with HSV-2 positivity were HIV-positivity (PR: 2.27 [95% CI: 1.94-2.65]) and older age (PRs: 1.41 [95% CI: 1.05-1.91] for 20-24 years, 1.71 [95% CI:1.13-2.60] for 30-34 years, and 1.55 [95% CI: 1.10-2.19] for 35 years or greater]), while rural residence was negatively associated with HSV-2 positivity (PR 0.83 [95% CI: 0.69-1.00]), after controlling for other covariables. For this study a conservative Focus index cutoff of 3.5 was used, but among samples with a Focus index value ≥2.5, 98.4% had positive Kalon tests. CONCLUSION: The prevalence of HSV-2 is relatively high among pregnant women in Haiti. Public health interventions to increase access to HSV-2 screening in antenatal services are warranted.

Herpesvirus: an underestimated virus.

Herpes simplex virus (HSV) infections are common and widespread; nevertheless, their outcome can be of unpredictable prognosis in neonates and in immunosuppressed patients. Anti-HSV therapy is effective, but the emergence of drug-resistant strains or the drug toxicity that hamper the treatment is of great concern. Vaccine has not yet shown relevant benefit; therefore, palliative prophylactic measures have been adopted to prevent diseases. This short review proposes to present concisely the history of HSV, its taxonomy, physical structure, and replication and to explore the pathogenesis of the infection, clinical manifestations, laboratory diagnosis, treatment, prophylaxis and epidemiology of the diseases.

Diphenyl Diselenide Reduces Oxidative Stress and Toxicity Caused by HSV-2 Infection in Mice.

Herpes simplex viruses can cause uncommon systemic complications as acute liver failure (ALT) or urinary tract dysfunctions. Diphenyl diselenide, (PhSe)2 , a classical studied organic selenium compound, has a novel antiviral action against HSV-2 infection and well-known antioxidant and anti-inflammatory properties. This study aimed to investigate if (PhSe)2 reduces oxidative stress and systemic toxicity caused by HSV-2 infection in mice. Adult BALB/c mice were pre-treated with (PhSe)2 (5 mg kg-1 /day, intragastric, i.g.) during 5 days; at day 6 mice were infected with HSV-2 (10 µl-105 PFU/mL-1 ) and post-treated with (PhSe)2 for more 5 days. At day 11, they were killed and samples of liver and kidney were obtained to determine: reactive species (RS); malondialdehyde (MDA), and non-protein thiols (NPSH) levels; the activities of antioxidant enzymes, superoxide dismutase (SOD), and catalase (CAT). The activities of adenosine deaminase (ADA), Na+ /K+ -ATPase (liver and kidney); alanine aminotransferase (ALT), aspartate aminotransferase (AST), and the levels of urea (plasma) were determined as markers of hepatic and renal toxicity. The results revealed that (PhSe)2 treatment was effective against the increase of renal and hepatic oxidative stress in infected mice and also normalized hepatic and renal ADA activity. It recovered the activity of Na+ /K+ - and was not effective against the increase in urea levels in infected mice. Different from (PhSe)2 , acyclovir (positive control), caused an increase in ADA activity and a decrease in hepatic CAT activity. Considering the interest of alternative therapies to treat HSV-2 infections and secondary complications, (PhSe)2 become a notable candidate. J. Cell. Biochem. 118: 1028-1037, 2017. © 2016 Wiley Periodicals, Inc.

Incidence of Alpha-Herpes virus induced ocular disease in Suriname.

Herpes simplex virus (HSV) infection of the corneal stroma is the most prominent cause of scar formation impairing visual acuity and HSV keratitis is the leading cause of corneal opacity throughout the world. Suriname lacked test systems for microbial causes of ocular disease, therefore a polymerase chain reaction-based Herpes virus assay was introduced, enabling prompt recognition, and timely treatment, preventing progressive eye damage. The incidence and epidemiology of Herpes simplex virus type 1 (HSV-1), type 2 (HSV-2), and varicella zoster virus (VZV) in ocular disease in Suriname was assessed. In a cross-sectional prospective study, ocular swabs were collected from 91 patients with a presumptive α-Herpes virus ocular infection attending the Academic Hospital between November 2008 and August 2010 and were tested by a PCR-based α-Herpes virus assay. Alpha-Herpes virus ophthalmic infections were caused predominantly by HSV-1 with a prevalence of 31%. The prevalences of VZV, HSV-2, and a mixed HSV-1/HSV-2 infection were 4%, 3%, and 2%, respectively. The first reported annual incidence of herpetic induced ocular disease in Suriname was estimated at 11.4 per 100,000 person-years (95% CI, 4.8-18.1). No clear age, ethnic or gender dependent difference in incidence was observed. The information obtained on α-Herpes virus positive ocular infections and the distribution of subtypes provided the first insight in the South American situation of α-Herpes virus induced ocular disease.

In vitro antiherpes effects of a C-glycosylflavonoid-enriched fraction of Cecropia glaziovii Sneth.

AIMS: To investigate the in vitro antiherpes effects of the crude aqueous extract obtained from Cecropia glaziovii leaves and their related fractions, the n-butanol fraction (n-BuOH) and the C-glycosylflavonoid-enriched fraction (MeOH(AMB)), and to determine the viral multiplication step(s) upon which this C-glycosylflavonoid-enriched fraction acts. METHODS AND RESULTS: The antiviral activity was evaluated against human herpes virus types 1 and 2 (HHV-1, HHV-2) by plaque reduction assay. The mode of action of the most active fraction was investigated by a set of assays, and the results demonstrated that MeOH(AMB) fraction exerts anti-herpes action by the reduction of viral infectivity (only against HHV-2); by the inhibition of virus entry into cells; by the inhibition of cell-to-cell virus spread as well as by the impaired levels of envelope proteins of HHV-1. The high-performance liquid chromatography (HPLC)-photo-diode array (PDA) analysis showed that the C-glycosylflavonoids are the major constituents of this fraction. CONCLUSIONS: These data showed that the MeOH(AMB) fraction has an antiviral activity against HHV types 1 and 2. The C-glycosylflavonoids are the major constituents of this fraction, which suggests that they could be one of the compounds responsible for the detected anti-herpes activity. SIGNIFICANCE AND IMPACT OF THE STUDY: The MeOH(AMB) fraction can be regarded as a phytopharmaceutical candidate for the treatment of herpetic infections.

[Association between HSV-2 infection and serum anti-rat brain antibodies in patients with autism]. / Infecciones por HSV-2 y su relación con anticuerpos antiencéfalo de rata en suero de pacientes con autismo.

Some cases of autism could be linked to viral infections able to induce autoimmune mechanisms directed against the encephalon. Neurothophic virus infections in animals are associated with clinical signs that are similar to those observed in neurodevelopment disorders. Thus, in this study, we determined the co-existence of antibodies against nerve tissue and viruses with neurothophic competence (HSV-1/2, Epstein-Barr-EBV, cytomegalovirus, measles and rubella) in serum of forty autistic children and forty healthy children. The presence of antibodies against nerve tissue was detected in slices of rat encephalic tissue by indirect immunofluorescence. The levels of anti-viral IgG and IgM antibodies were measured by indirect ELISA. The proportion of autistics with anti-encephalon IgG antibodies (77% anti-amygdala, 70% anti-caudate nucleus, 47.5% anti-cerebellum y anti-brain stem, 45% anti-hippocampus, 40% anti-corpus callosum and 17,5% anti-cortex) was significantly greater than that of controls (10% anti- amygdala y 5% anti- cerebellum) and was directly related to the severity of the autism. The proportion of children with positive levels (greater than 1.1.mg/dL) for anti-HSV IgM antibodies (indicative of acute infection) was significantly greater in autistics (65%) than in healthy children (17.5%). Ninety six percent of the autistics with anti-HSV antibodies also had anti-encephalon antibodies, percentage that was significantly greater than that of autistics negative to the anti-HSV-antibody (43%). In contrast, there were no significant differences for IgG and IgM antibodies for EBV, cytomegalovirus, measles and rubella. This suggests that autoimmunity against encephalic structures elicited by HSV infections could be involved in autism.

Epidemiology of herpes simplex virus type 2 infection in the developing world.

Herpes simplex virus type 2 (HSV-2) is a common infection in many countries, with prevalence in some regions, such as sub-Saharan Africa, higher than in the USA. Prevalence in adult general populations in sub-Saharan Africa ranges from 30% to 80% in women, and from 10% to 50% in men. Most data from Central and South America are from women, in whom HSV-2 prevalence ranges from about 20% to 40%. Prevalence in the general population in developing Asian countries appears to be lower (10-30%). In common with the developed world, HSV-2 seropositivity is uniformly higher in women than in men and increases with age. In general, HSV-2 seroprevalence is high in populations whose behaviour leads to a high risk of acquiring other sexually transmitted infections (STIs), such as STI clinic attendees and sex workers (SWs), with some African studies reporting greater than 80% HSV seropositivity in SWs. New infections are most common among young adults, a fact that should be considered when proposing and implementing measures to reduce HSV, and possibly HIV, transmission. Currently, comparison between studies is hampered by the lack of a validated type-specific serological assay that has a similar performance across a range of populations. HSV-2 is a major cause of genital ulcer disease (GUD) in the developing world. Genital herpes is a cause of morbidity and increases the risk of HIV acquisition, due to disruption of mucosal membranes. Where possible, the aetiology of GUD should be evaluated using polymerase chain reaction (PCR), while recognizing that co-pathogens can exist in a lesion. GUD management should incorporate HIV testing and antiherpetic treatment.

Nitric oxide and HSV vaginal infection in BALB/c mice.

Here we study the role of nitric oxide in the vaginal infection of Balb/c mice with herpes simplex virus type 2. Inducible nitric oxide synthase (iNOS) mRNA was detected by RT-PCR in vaginal tissue and inguinal lymph nodes early postinfection. iNOS was also found to be activated in cells recovered from vaginal washings of infected animals. Animals treated with aminoguanidine (AG), an iNOS inhibitor, showed a dose-dependent increase in vaginal pathology after viral infection compared to controls. Viral titers in vaginal washings and vaginas were higher in AG-treated mice. Treated animals presented higher PMN counts in vaginal washings compared to controls. Histopathology studies revealed a profound inflammatory exudate in vaginal tissue of treated animals. Finally, RT-PCR analysis showed increased expression of the chemokines MIP-2 and RANTES in vaginal tissue and inguinal lymph nodes of these animals.

Antiviral activity of enterocin CRL35 against herpesviruses.

Enterocin CRL35 is an antibacterial polypeptide of 3.5 x 10(3) Da produced by Enterococcus faecium CRL35. A series of experiments are described that show the enterocin also had antiviral activity against thymidine-kinase positive (tk+) and deficient (tk-) strains of herpes simplex (HSV) type 1 and 2 in Vero and BHK-21 cells. This activity was observed at 100 microg/ml, 15-fold lower than the cytotoxic concentration. In both cell lines there was a 2 log inhibition of infectivity. The compound inhibited viral multiplication in a dose-dependent manner and had no virucidal effect. Enterocin CRL35 also inhibited the virion-associated host shutoff in infected Vero cells showing that intracellular viral multiplication was affected.

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 time points. 70% of athymic NIH mice, 30% of euthymic NIH mice, and 80% 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.

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.

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. (AU)

Encefalitis neonatal por virus herpes tipo 2 en un paciente sin alteraciones en líquido cefalorraquídeo: informe de un caso y revisión de la literatura / Neonatal encephalitis for herpes virus type 2 in patient without alterations in cerebrospinal fluid: report of a case and review of the literature

Se presenta el caso de una paciente femenina de 25 días de edad que desarrolló un cuadro de encefalitis por herpes tipo 2. Esta niña tuvo el antecedente de que su madre presentó lesiones genitales causadas por virus herpes desde las 30 semanas de edad gestacional; el diagnóstico en la madre fue corroborado mediante serología positiva para este virus. A los 20 días de edad presenta fiebre, deterioro del sensorio y cuadro convulsivo. El análisis del líquido cefalorraquídeo fue normal, pero la serología (IgG) para herpes simple en este fluido fue determinante en el diagnóstico de encefalitis. Se realizó una revisión de estudios publicados al respecto, confirmando lo infrecuente de esta patología cuando la enfermedad es adquirida de una madre con infección recurrente por este agent viral en el período neonatal. Se discuten los aspectos epidemiológicos y clínicos de la enfermedad, haciendo énfasis en la transmisión perinatal y en la importancia de la historia clínica materna para la prevención de casos neonatales

Cervical cancer and herpes simplex virus type 2: case-control studies in Spain and Colombia, with special reference to immunoglobulin-G sub-classes.

Two case-control studies, including 449 histologically confirmed cases of cervical intra-epithelial neoplasia (CIN) III and 425 controls, and 2 studies on invasive cervical cancer, involving 316 histologically confirmed cases and 330 population controls, were conducted in Colombia and Spain to assess the role of herpes simplex virus type 2 (HSV-2) in cervical neoplasia. Antibodies to this virus were also measured in the sera of 931 husbands of cases and controls. A serological assay using type-specific antigens, glycoprotein C for type I (gC-I) and glycoprotein G for type 2 (gG-2) was employed. Immunoglobulin-G (IgG) sub-classes, IgG1 and IgG3, were measured in women positive for HSV-2 antibodies. No increase in risk of CIN III or invasive cancer was found in women whose sera or whose husbands' sera were positive to HSV-2. However, compared with women negative to HSV-2, the risk of CIN III progressively increased with increasing levels of IgG1. The trend was statistically significant in Colombia. There was also a statistically significant increasing trend in risk of invasive cancer with levels of IgG1 in Spain. The levels of IgG3 and its ratio to IgG1, which may indicate recurrent infections, were not associated with the risk of either type of cancer. When the association with IgG1 was analyzed by human papillomavirus (HPV) DNA status, as determined by polymerase chain reaction, the trend was clearer in women whose HPV status was not determined or in those with negative HPV DNA. These results suggest that the role of HSV-2 is merely marginal and do not support the hypothesis that recurrent HSV-2 infections are of importance for cervical neoplasia.