The lack of association between herpes simplex virus 1 or Toxoplasma gondii infection and cognitive decline in the general population: An 11-year follow-up study.

BACKGROUND: Inflammation has been suggested to be one, possibly treatable, cause of cognitive decline and dementia. The purpose of the present article was to investigate whether the herpes simplex virus 1 (HSV-1) or Toxoplasma gondii (T. gondii) infections are related to cognitive decline or dementia. METHOD: The Health 2000 survey, conducted 2000-2001, is a population-representative sample of people over 30 years old that involved 7112 participants. The sample was followed up in the year 2011, in the Health 2011 study. At both time points, cognitive performance was assessed with two tests from the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) assessing verbal fluency and verbal learning. In addition, the abbreviated Mini-Mental State Examination was administered to people aged over 55. In addition, tests assessing reaction and movement time were performed at baseline. Dementia diagnoses from nationwide health care registers were followed up until the end of year 2013. The presence of HSV-1 and T. gondii immunoglobulin G (IgG) was determined by solid-phase immunoassay at baseline. RESULTS: HSV-1 or T. gondii seropositivity, or IgG antibody levels, were not associated with cognitive decline when investigated as infection × time interactions. In addition, the infections were not associated with the risk of dementia. CONCLUSIONS: In a large sample of participants that is representative of the whole country and with a long follow-up, the results suggest that latent HSV-1 or T. gondii infections are not related to either decline in cognitive performance or dementia risk.

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.

Viral Hypothesis and Antiviral Treatment in Alzheimer's Disease.

PURPOSE OF REVIEW: Viruses, particularly herpes simplex virus (HSV), may be a cause of Alzheimer's disease (AD). The evidence supporting the viral hypothesis suggests that antiviral treatment trials, which have not been conducted, are warranted. RECENT FINDINGS: HSV1 (oral herpes) and HSV2 (genital herpes) can trigger amyloid aggregation, and their DNA is common in amyloid plaques. HSV1 reactivation is associated with tau hyperphosphorylation and possibly tau propagation. Anti-HSV drugs reduce Aß and p-tau accumulation in infected mouse brains. Clinically, after the initial oral infection, herpes simplex virus-1 (HSV1) becomes latent in the trigeminal ganglion and recurrent reactivation may produce neuronal damage and AD pathology. Clinical studies show cognitive impairment in HSV seropositive patients, and antiviral drugs show strong efficacy against HSV. An antiviral treatment trial in AD is clearly warranted. A phase II treatment trial with valacyclovir, an anti-HSV drug, recently began with evaluation of clinical and biomarker outcomes.

Seropositivity of neurotropic infectious agents in first-episode schizophrenia patients and the relationship with positive and negative symptoms.

BACKGROUND: According to the neurodevelopmental model, schizophrenia is a disorder that occurs as a result of different etiologic factors during brain development, including viral infections. However, it is unclear whether these infections are related to the disease or whether they affect the symptom pattern. We investigated the presence of four herpes viruses (EBV, CMV, HSV-1 and HSV-2) in first-episode schizophrenia patients and compared seropositive with seronegative patients and healthy volunteers to reveal the etiological role of viral agents on schizophrenia symptoms. SUBJECTS AND METHODS: Ninety-two first-episode patients who met the DSM-IV diagnostic criteria for schizophreniform disorder were included the study, along with 88 healthy volunteers. The presence of the four herpes viruses was investigated with serological methods (ELISA) in both groups. Positive and negative symptoms were evaluated with Scale for the Assessment of Negative Symptoms (SANS) and the Scale for the Assessment of Positive Symptoms (SAPS). RESULTS: There was no difference between the patient and control groups in terms of seropositivity of the four viruses. We found that SANS scores of HSV-1 and CMV seropositive schizophrenia patients were significantly higher than the scores of patients with seronegative schizophrenia. No difference was found in SAPS scores. CONCLUSIONS: The results suggest a role of HSV and CMV infections in negative symptoms. This supports the hypothesis that viruses do not directly give rise to schizophrenia, but patients who were previously been infected with these viral agents may be prone to schizophrenia, and some of the symptom patterns may be related to different agents.

Psychological distress, emotional stability, and emotion regulation moderate dynamics of herpes simplex virus type 2 recurrence.

BACKGROUND: Herpes simplex virus type 2 (HSV-2) genital lesion recurrence is modulated by psychological factors, but no such link with viral shedding (and thus asymptomatic transmission) has been observed in humans. PURPOSE: The moderating effects of average psychological distress, emotional stability, and emotion regulation on HSV-2 recurrence were tested. METHODS: Nineteen HSV-2 seropositive women were followed over 22 weeks. Daily measures of HSV-2 recurrence and psychological distress were collected. HSV-2 lesions and viral shedding were modeled as linear oscillator systems, with psychological distress moderating the periodicity of each process. RESULTS: High levels of distress, more labile moods, and less ability to regulate emotional states were associated with fewer days elapsed between the onset of lesion episodes. Viral shedding showed the same pattern. CONCLUSIONS: Results are consistent with research indicating that psychological distress suppresses immune system functioning, and provide new evidence that genital HSV-2 viral shedding is related to, and regulated by, psychological distress.

Persistent viral pathogens and cognitive impairment across the life course in the third national health and nutrition examination survey.

BACKGROUND: Herpesviruses have been linked to cognitive impairment in older individuals but little is known about the association in the general US population. METHODS: We determined whether cytomegalovirus (CMV) and herpes simplex virus 1 (HSV-1) seropositivity were associated with cognitive impairment among children (aged 6-16 years) and adults aged 20-59 or ≥60 years, using data from the National Health and Nutrition Examination Survey (NHANES) III. Linear and logistic regression models were used to examine the associations between pathogen seropositivity and cognitive impairment. RESULTS: Among children, HSV-1 seropositivity was associated with lower reading and spatial reasoning test scores (ß, -0.69; 95% confidence interval [CI], -1.18 to -.21 and ß, -0.82; 95% CI, -1.29 to -.36, respectively). Among middle-aged adults, HSV-1 and CMV seropositivity were associated with impaired coding speed (odds ratio [OR], 1.54; 95% CI, 1.13-2.11, and OR, 1.41; 95% CI, 1.09-1.82, respectively). CMV seropositivity was also associated with impaired learning and recall (OR, 1.43; 95% CI, 1.14-1.80). Among older adults, HSV-1 seropositivity was associated with immediate memory impairment (OR, 3.26; 95% CI, 1.68-6.32). CONCLUSIONS: Future studies examining the biological pathways by which herpesviruses influence cognitive impairment across the life course are warranted.

Diagnostic classification, viral sexually transmitted infections and discourses of femininity: limits of normalisation to erase stigma.

Clinicians in the field of women's sexual health typically classify the two most common viral sexually transmitted infections (STIs), the human papilloma virus and the herpes simplex virus, as relatively innocuous infections. Teaching interventions include 'normalising' adult sexual activity and the epidemiological ordinariness of infection. Normalising is intended to disarm the potential stigma of the diagnosis. In this study, in-depth email interviews were conducted with 26 women with a viral STI diagnosis and 12 sexual health clinicians. Data were analysed thematically using a feminist, poststructuralist approach. Normalising is contextualised as an example of the workings of western philosophical thought whereby dualistic classifications privilege certain terms and subordinate other terms. In this instance, the relative medical normalcy of viral STIs is given primacy compared to the social abnormality experienced by women. Although these viral STIs infect women and men, this research concentrates on women's learning about viral STIs. For women, beliefs about femininity, sexuality, health, morality and responsibility influence effects of a viral STI diagnosis. These discourses are clinically significant because beliefs that specifically link to ideas about how to be a woman are overlooked when clinicians devise educational interventions.

The association of depression, risky sexual behaviours and herpes simplex virus type 2 in adults in NHANES, 2005-2008.

OBJECTIVES: Depression has been linked to risky sexual behaviours in adolescents, but there is little research among adults. The goal of this analysis was to examine the associations between current depression and self-reported risky sexual behaviours in a nationally representative sample of US adults aged 20-59 years. The authors also examined the association between depression and infection with herpes simplex virus type 2 (HSV-2), a biological marker of risky sexual behaviours. METHODS: The authors used data from the 2005-2008 National Health and Nutrition Examination Surveys. Current depression was measured by the Patient Health Questionnaire-9. Antibodies to HSV-2 were tested using the enzymatic immunodot assay. The authors used logistic regression to examine the associations controlling for socio-demographic variables. RESULTS: Among 5273 adults aged 20-59 years, 7% had depression, 36% reported 10 or more lifetime sex partners, 15% had two or more past-year sex partners and 13% had first sex before 15 years of age. Persons with each of the risky sexual behaviours were more likely to have depression than those without. In stratified analyses, risky sexual behaviours were associated with depression in women but not in men. Among 3940 adults aged 20-49 years, 19% had HSV-2 infection. Persons with HSV-2 infection were more likely to have depression (OR 2.1, 95% CI 1.5 to 2.9). CONCLUSIONS: Risky sexual behaviour is related to current depression in adult women. Healthcare providers should be aware of this association and its potential implications in order to deliver better care for patients with depression or sexually transmitted infections.

HSV serologic testing for pregnant women: willingness to be tested and factors affecting testing.

OBJECTIVE: This prospective study was undertaken to evaluate pregnant women's willingness to undergo HSV type-specific serologic testing and factors affecting willingness in an obstetrics/gynecology ambulatory unit. METHODS: At prenatal Visit 1, pregnant women (n = 303) with no history of HSV-2 were tested for HSV-1/HSV-2 before and after they received counseling on genital and neonatal herpes. RESULTS: In both the Unwilling Subgroup and the group that changed from being willing to being unwilling, the most common reasons for choosing not to be tested were not being at risk for genital herpes, being tested is too personal, and concern about what will be done with the results. Of the 134 participants in the Willing/Tested Subgroup, 27 (20%) were HSV-2 seropositive and 81 (60%) were HSV-1 seropositive. Conclusions. These results support the feasibility of HSV serologic testing and counseling in pregnant women.

Psychosocial impact of a positive HSV-2 diagnosis on adults with unrecognized HSV-2 infection.

OBJECTIVE: To evaluate the current research on the psychosocial impact of a positive herpes simplex virus type 2 (HSV-2) diagnosis on asymptomatic adults. DESIGN AND SAMPLE: A structured review of PubMed, CINAHL, and MEDLINE resulted in 8 articles published between 2000 and 2008. MEASURES: Articles were included if they investigated psychosocial reactions to HSV serological testing, including asymptomatic individuals, and used measurement instruments with adequate psychometric properties. RESULTS: The studies included participants of various backgrounds, including individuals with a new HSV-2 diagnosis concurrently receiving human immunodeficiency virus treatment, students within a university setting, and an HMO population. Current research indicates that a diagnosis of HSV-2 does not result in persistent psychosocial morbidity. However, studies that assessed for more nuanced reactions noted an impact on quality of life related to herpes. CONCLUSIONS: Further research is needed to confirm these findings among varied populations, to explore quality of life following HSV screening, and to identify the characteristics that may make particular individuals more susceptible to adverse psychological consequences.

Recovery of immune control over herpes simplex virus type 1 in female victims of intimate partner violence.

OBJECTIVES: To assess the course of immune control over Herpes simplex virus type 1 (HSV-1) through three salivary measures: neutralization of HSV-1, levels of specific antibody against HSV-1 (HSV-1-sIgA) and total immunoglobulin A (total sIgA), and to determine the factors that contribute to its recovery or deterioration. Several studies have demonstrated that intimate partner violence (IPV) affects immune responses in women, but none have investigated the impact longitudinally over time. METHODS: Women (n = 60), who participated in our previous cross-sectional study (T-1) and who had been either physically/psychologically (n = 22) or psychologically abused (n = 14) by their partners, were evaluated 3 years later (T-2). A control group of women (n = 24) was included for comparison. Saliva samples were collected twice a day (8 AM-9 AM, and 8 PM-9 PM) on 2 days spaced 2 weeks apart. Information about psychological and lifestyle variables was obtained by structured interviews. RESULTS: Physically/psychologically abused women had a significant improvement in both the capacity to neutralize HSV-1 and HSV-sIgA levels, and at T-2 the capacity of their saliva to inhibit virus was no longer different from the other two groups. Regression analysis indicated that the cessation of physical IPV was the main predictor of this recovery. CONCLUSIONS: This study shows that recovery of immune control over HSV-1 is possible in women who had been exposed to physical/psychological IPV despite an initially low antiviral capacity. Other longitudinal studies are needed to determine which factors best predict the restoration of physical and emotional well-being in order to design more effective intervention programs.

HSV-2 seroincidence among Mexican college students: the delay of sexual debut is not enough to avoid risky sexual behaviours and virus transmission.

OBJECTIVES: Early sexual debut is a behaviour that has been associated with acquiring sexually transmitted infections. Higher schooling may delay sexual debut, thus the university population is categorised with low-risk sexual behaviours. The rate ratio of herpes simplex virus type 2 (HSV-2) seroincidence according to demographic characteristics and sexual behaviour was estimated for a cohort of university students. METHODS: A dynamic cohort of university students was followed at the Autonomous University of Morelos, in central Mexico, during the years 2001-5. After obtaining informed consent, information was gathered annually regarding demographic characteristics and sexual behaviour and blood samples were obtained to determine HSV-2 antibodies. Seroincidence was estimated and the incidence rate ratio was evaluated using the Poisson regression model. RESULTS: A total of 404 students participated, with 669.2 person-years of follow-up. An incidence of 4.2 cases per 100 person-years was estimated. The variables delayed sexual debut (≥18 years) and multiple sexual partners (two or more sexual partners during the past year) had a rate ratio of 4.1 (95% CI 1.2 to 14.3) and 2.5 (95% CI 1.1 to 5.6), respectively. Incidence for students with delayed sexual debut and multiple partners is estimated to be 10.3 cases per 100 person-years. CONCLUSIONS: Delayed sexual debut was a risk factor for acquiring HSV-2, due to a subgroup with sexual debut at 18 years of age or older that had multiple sexual partners; therefore, in the university population that tends to delay sexual debut, it is necessary to implement prevention programmes to promote the decrease of other risky sexual behaviours, as well as the promotion of the consistent use of condoms.

Repeated social stress enhances the innate immune response to a primary HSV-1 infection in the cornea and trigeminal ganglia of Balb/c mice.

Three to 5 days after a primary HSV-1 infection, macrophages infiltrate into the trigeminal ganglia (TG) and produce anti-viral cytokines to reduce viral replication. Previous research demonstrated that social disruption stress (SDR) enhances the trafficking of monocytes/macrophages from the bone marrow to the spleen and increases pro-inflammatory cytokine production in vitro and in vivo. The impact of SDR on the trafficking of these cells to loci of herpes simplex virus type 1 (HSV-1) infection and subsequent function has not been examined. The following studies were designed to determine whether SDR would enhance the innate immune response during a primary HSV-1 infection by increasing the number of macrophages in the cornea and TG, thus increasing anti-viral cytokine production and reducing viral replication. BALB/c mice were exposed to six cycles of SDR prior to ocular infection with HSV-1 McKrae virus. Flow cytometric analysis of cells from the TG revealed an increase in the percentage of CD11b+ macrophages in SDR mice compared to controls. Immune cell infiltration into the cornea, however, could not be determined due to low cell numbers. Although gene expression of IFN-beta was decreased, SDR increased gene expression of IFN-alpha, and TNF-alpha, in the cornea and TG. Examination of viral proteins showed decreased expression of infected cell protein 0 (ICP0), glycoprotein B (gB), glycoprotein H (gH) and latency-associated transcript (LAT) in the TG, however, expression of ICP0 and gB were elevated in the cornea of SDR mice. These results indicate that the innate immune response to HSV-1 was altered and enhanced by the experience of repeated social defeat.

The association between exposure to herpes simplex virus type 1 (HSV-1) and cognitive functioning in schizophrenia: A meta-analysis.

Cognitive deficits are characteristic of schizophrenia but their etiology is not understood. Previous studies show an association between viral exposures and cognitive impairment. This meta-analysis was undertaken to determine the relationship of herpes simplex virus type 1 (HSV-1) exposure and cognitive functioning in schizophrenia. A systematic search was performed for studies comparing the cognitive functioning of HSV-1 seropositive vs. seronegative persons with schizophrenia. The primary outcome was the standardized mean difference (SMD) in composite cognitive score using Hedges' g. Secondary outcomes were SMDs in 9cognitive domains. Study heterogeneity was estimated using the I2 index and formal tests of heterogeneity using Cochran's Q. In a sample of 3516 individuals from 9 studies the SMD was negative for the composite score and all 9 domains indicating a significant deficit for seropositive individuals in 8 domains. The SMDs ranged from -0.11 (Working Memory) to -0.36 (Visual Spatial). Cochran's Q test indicated heterogeneity for one domain. The I2 index of heterogeneity was in the low -moderate range for all but one domain. Exposure to HSV-1 is associated with decreased cognitive functioning in schizophrenia. An increased understanding of HSV-1 exposure might lead to improved methods for the prevention and treatment of cognitive deficits in schizophrenia.

Does psychosocial stress predict symptomatic herpes simplex virus recurrence? A meta-analytic investigation on prospective studies.

Previous psychological studies have paid extensive attention to the association between psychosocial stress and symptomatic herpes simplex virus (HSV) recurrence, but subsequent research has been conducted and conflicting findings have been published. We aimed to quantify the longitudinal association between psychosocial stress and recurrent HSV in the contemporary literature. We searched Medline; PsycINFO; Web of Science; PubMed up to March 2009, and included prospective studies that investigated associations between psychosocial stress and symptomatic HSV recurrence. Two reviewers independently extracted data on study characteristics, quality, and estimates of associations. The overall meta-analysis examining 11 articles (17 psychosocial and disease related relationships) exhibited a robust positive association between psychosocial stress and symptomatic HSV recurrence (correlation coefficient as combined effect size 0.083, 95% confidence interval 0.025-0.141, p=0.005). This finding was supported by more conservative analysis of aggregate effects and by sensitivity analysis of the methodologically strong studies. There were indications of publication bias in some analyses. Intriguingly, sensitivity analyses demonstrated that psychological distress was more strongly associated with symptomatic HSV recurrence than stress stimuli per se, and that psychosocial stress tended to be more strongly associated with oral than genital herpes recurrence. In conclusion, the current review reveals a robust relationship between psychosocial stress and symptomatic HSV recurrence, justifying further research in this field, especially clinical trials evaluating the efficacy of stress reduction interventions on HSV recurrence.

Is education the link between orphanhood and HIV/HSV-2 risk among female adolescents in urban Zimbabwe?

As the population of orphans grows in AIDS-affected settings, recent studies describe a heightened risk of HIV and sexual risk behaviours among adolescent orphans compared to their non-orphaned peers. This study explores the role of education in explaining the excess sexual risk previously documented among unmarried female orphans in urban Zimbabwe. School attendance and attainment were assessed by type of orphanhood, and for their association with markers of sexual risk (HIV and/or HSV-2 infection) among 743 participants drawn from a random sample of 15-19-year-old girls identified in a cross-sectional survey in Highfield, Harare, in 2004. Multivariable logistic regression was used to assess the role of educational status in explaining the higher prevalence of adverse sexual outcomes among unmarried orphans compared to non-orphans, adjusting for possible confounders. Double orphans had significantly lower educational attendance and attainment than non-orphans. Maternal orphans had higher odds of school drop-out, although this association disappeared when adjusted for recent mobility. Educational status was strongly associated with HIV/HSV-2 risk, but explained only a small part of double orphans' sexual risk and did not explain the HIV/HSV-2 risk of maternal and paternal orphans. High overall levels of secondary school participation and school fee assistance provided to vulnerable families may have reduced the schooling disparities between orphans and non-orphans in Highfield. However, further efforts are needed to rectify the schooling inequities that persist, while additional research is needed to identify other socio-economic and emotional factors driving orphans' sexual risk so that prevention and support programmes can meet the needs of this growing population.