Impact of heavy metals exposure on herpes simplex virus type I infection: A population-based cross-sectional study.

This study aims to investigate the significant relationship between serum heavy metals (lead [Pb], cadmium [Cd], mercury [Hg]) and the risk of herpes simplex virus type 1 (HSV-1) infection. Data were derived from the National Health and Nutrition Examination Survey (NHANES) conducted in the United States from 2007 to 2016. This nationally representative survey, conducted by the National Center for Health Statistics, assessed the health status of participants through interviews, physical examinations, and laboratory tests. After excluding participants lacking serum Pb, Cd, and Hg data, as well as those missing HSV-1 testing data and pregnant women, the analysis included 13 772 participants, among whom 3363 were adolescents. A survey-weighted multivariate logistic regression model was used to evaluate the association between heavy metal exposure and the risk of HSV-1 infection, and to explore the dose-response relationship between them. In adults and adolescents, serum concentrations of Pb and Cd were higher in those infected with HSV-1 than in those not infected. However, an increase in serum Hg concentration was observed only in infected adolescents. After adjusting for potential confounders, elevated serum Pb and Cd concentrations in adults were associated with an increased risk of HSV-1 infection. Higher serum Pb and Cd concentrations were associated with an increased risk of HSV-2 infection, irrespective of HSV-1 infection status. In adults, serum concentrations of Pb and Hg showed an approximately linear relationship with HSV-1 infection risk (p for nonlinearity > 0.05), whereas the dose-response relationship between serum Cd concentration and HSV-1 infection was nonlinear (p for nonlinearity = 0.004). In adolescents, serum concentrations of heavy metals (Pb, Cd, Hg) showed an approximately linear relationship with HSV-1 infection (p for nonlinearity > 0.05). Furthermore, the study examined the relationship between serum heavy metal levels and the risk of HSV-1 infection across different genders, races, income levels, weight statuses, and immune statuses. In conclusion, there is a significant association between serum heavy metal concentrations and HSV-1 infection, which warrants further investigation into the causal relationship between them.

Seroprevalence of human alphaherpesvirus 1 and 2 among pregnant women infected or uninfected with Zika virus from Rio de Janeiro, Brazil.

Pregnant women are an important group to be monitored for infection due to the risk of transmitting infections to their babies. Both herpes simples virus (HSV) and Zika virus (ZIKV) are neurotropic viruses that can be transmitted congenitally. In this study, the prevalence and risk factors of HSV among Zika-positive and -negative pregnant women from Rio de Janeiro, Brazil, were evaluated and compared. About 167 serum samples included in our study were from pregnant women with ZIKV infection symptoms, who were attended to in different hospitals in Rio de Janeiro between November 2015 to February 2016. Blood samples collected from 167 pregnant women were used for this study. The presence of HSV antibodies and viremia were evaluated by commercial ELISA and quantitative real-time polymerase chain reaction analyses, respectively. The data obtained from medical records were statistically analyzed. The HSV-1 and HSV-2 prevalence among pregnant women was 80.2% and 12.5% for Zika-positive women and 84.5% and 5.6% for Zika-negative women, respectively. None of the pregnant women exhibited HSV viremia. Age, trimester of gestation, and skin color were associated with HSV-1 and HSV-2 prevalence among the groups studied. HSV-2 was more prevalent in Zika-positive pregnant women than in Zika-negative pregnant women, and this simultaneous infection should be better investigated in future studies.

Seroprevalence of herpes simplex virus type 1 among people living with HIV in Mbeya, Tanzania.

BACKGROUND: Despite the significant decline in the prevalence of HIV in Tanzania, the prevalence rates in Mbeya, Iringa, and Njombe regions are higher than the national average and have remained stable for years. The current stable HIV prevalence may be driven by factors such as a high incidence of sexually transmitted infections (STIs) and high-risk behaviours. In sub-Saharan Africa, it has previously been observed that up to 50% of HIV cases were attributed to herpes simplex type 2 (HSV-2) among low-risk populations. Because the proportion of sexually transmitted HSV-1 is rising, it is essential to study the interaction between HSV-1 and HIV infections. METHODS: We conducted a study in Mbeya region using the archived blood sera of participants from the recently completed EU-funded EMINI project. A specially designed questionnaire was used to obtain the social and demographic characteristics of the study participants in the database. We tested archived participants' sera for herpes simplex virus type 1 using Virotech HSV-1 (gG1) IgG ELISA (Enzygnost, Behring, Germany). Univariate and multivariate Poisson regression models were used to identify factors associated with HSV-1. RESULTS: A total of 640 adults were randomly recruited after stratification by HIV status (318 were HIV positive), age, and sex. The overall seroprevalence of HSV-1 in the study population was 92.1%. The extrapolated seroprevalence estimate of herpes simplex virus type 1 in the general population was 95.0% (96.0% in males versus 94.0% in females). Males and females were equally affected by HSV-1. HSV-1 was less prevalent in HIV-positive individuals than in HIV-negative individuals. CONCLUSION: People living with HIV were less likely to be HSV-1 seropositive. Further prospective studies are necessary to conclude a causal association.

Seasonal influence on TORCH infection and analysis of multi-positive samples with indirect immunofluorescence assay.

BACKGROUND: TORCH including the pathogens of Toxoplasma gondii (TOX), rubella virus (RV), cytomegalovirus (CMV), and herpes simplex virus (HSV) causes intrauterine infections and poses a worldwide threat to women especially in pregnancy. In this study, we described the seasonal difference in TORCH infection and analyzed the anti-TORCH IgM multipositive serum samples by the indirect immunofluorescence assays (IFA). METHODS: To observe the seasonal influence of the anti-TORCH IgG and IgM antibodies, a retrospective study was conducted with 10 669 women (20-40 y old) before pregnancy from August 2016 to July 2017. Totally 199 ELISA anti-TORCH IgM multipositive serum samples were further tested by IFAs for false-positive analysis. RESULTS: The prevalence of positive HSV1-IgM, RV-IgM, HSV2-IgM, CMV-IgM, and TOX-IgM in the present population was 6.30%, 2.55%, 1.94%, 1.24%, and 0.67%, respectively. Additionally, the prevalence of positive RV-IgM, CMV-IgM, and HSV1-IgM was statistically different among four seasons, with the highest positive rates of RV-IgM (4.12%) in autumn, CMV-IgM (1.75%) in summer, and HSV1-IgM (7.53%) in winter. The confirmatory IFAs showed that the positive rates of RUV-IgM, CMV-IgM, and HSV2-IgM were significantly different from those in ELISA screening experiments. Interestingly, only 32.7% (65/199) of the TORCH IgM multipositive results were consistent with those by the IFA, indicating that cross-reaction caused false positives were common in ELISA IgM antibody screening. CONCLUSION: The TORCH infection displayed different prevalence among four seasons in our 12-month retrospective study. The IgM multipositives by ELISA screening may need further confirmation analysis due to its relatively high cross-reaction rate.

Critically Severe Case of Neonatal Herpes with High Viral Load and Hemophagocytic Syndrome.

Neonatal disseminated herpes simplex virus (HSV) infection is a severe disease with high mortality and morbidity; yet, the pathophysiology remains unclear. Here, we report a male infant with disseminated HSV type 1 (HSV-1) infection, complicated by hemophagocytic lymphohistiocytosis (HLH) and multiple organ failure. The infant, born at 39 weeks of gestation by normal delivery, developed fever (38.5˚C) with the high serum C-reactive protein levels on the 1st day of life, and exhibited tachypnea on the 3rd day. On the 5th day of life, the patient received mechanical ventilation and was transferred to our neonatal ICU. Real-time PCR for HSV-1 DNA revealed an extremely high serum concentration (1.0 × 109 copies/µL), and he was diagnosed with HSV-1 infection. Acyclovir (ACV) and corticosteroid pulse therapies with methylprednisolone were started. Continuous hemodiafiltration (CHDF) using cytokine-absorbing hemofilters was also initiated because of renal failure. These therapies, however, failed to control the disease, and the patient died on the 41st day of life. The dose of ACV on CHDF might not be adequate, although we could not measure the serum ACV concentrations. After the patient's death, we measured his serum cytokine concentrations taken four times during the clinical course. Serum concentrations of interleukin (IL)-6, IL-10, IL-1ß, and interferon (IFN)-γ were elevated at the time of admission and were remarkably decreased by 10 days after treatment. In particular, the concentrations of IL-1ß and IFN-γ were lower than the measurable ranges. It is therefore important to measure serum cytokine concentrations in real time to prevent excessive immune suppression.

Accuracy of Herpes Simplex Virus Polymerase Chain Reaction Testing of the Blood for Central Nervous System Herpes Simplex Virus Infections in Infants.

There were 1038 infants with herpes simplex virus polymerase chain reaction testing performed of blood and cerebrospinal fluid specimens. There were 21 (2.0%) with a positive cerebrospinal fluid PCR, of whom 16 also had a positive blood PCR (sensitivity 76%; 95% CI, 53%-92%). Blood PCR cannot exclude herpes simplex virus central nervous system infection.

Infection status of human parvovirus B19, cytomegalovirus and herpes simplex Virus-1/2 in women with first-trimester spontaneous abortions in Chongqing, China.

BACKGROUND: Infection with Parvovirus B19 (B19V), Cytomegalovirus (CMV) and Herpes Simplex Virus-1/2 (HSV-1/2) may cause fetal loses including spontaneous abortion, intrauterine fetal death and non-immune hydrops fetalis. Few comprehensive studies have investigated first-trimester spontaneous abortions caused by virus infections in Chongqing, China. Our study intends to investigate the infection of B19V, CMV and HSV-1/2 in first-trimester spontaneous abortions and the corresponding immune response. METHODS: 100 abortion patients aged from 17 to 47 years were included in our study. The plasma samples (100) were analyzed qualitatively for specific IgG/IgM for B19V, CMV and HSV-1/2 (Virion\Serion, Germany) according to the manufacturer's recommendations. B19V, CMV and HSV-1/2 DNA were quantification by Real-Time PCR. RESULTS: No specimens were positive for B19V, CMV, and HSV-1/2 DNA. By serology, 30.0%, 95.0%, 92.0% of patients were positive for B19V, CMV and HSV-1/2 IgG respectively, while 2% and 1% for B19V and HSV-1/2 IgM. CONCLUSION: The low rate of virus DNA and a high proportion of CMV and HSV-1/2 IgG for most major of abortion patients in this study suggest that B19V, CMV and HSV-1/2 may not be the common factor leading to the spontaneous abortion of early pregnancy.

Reaction of complement factors and proteasomes in experimental encephalitis.

Herpes simplex virus type 1 (HSV-1) encephalitis causes a deleterious inflammation and elevated intracranial pressure. As a step towards examining the origin of the inflammation, we here report the response of circulating proteasomes and complement factors in blood and cerebrospinal fluid (CSF) in rats infected with HSV-1. Infection was via the nasal route, with 1.1 × 104 plaque-forming units of HSV-1 strain 2762 given in one or both nostrils. A sandwich enzyme-linked immunosorbent assay was used to study the level of 26S proteasomes and their complex formation with complement factors 3 and 4. HSV-1 infection in the rat causes a complex formation between complement factors and proteasomes, which we designate compleasomes. In the first experiment, with HSV-1 given in both nostrils, compleasomes containing complement factors 3 and 4 increased significantly in both blood plasma and CSF. The concentration of proteasomes in plasma was similar in controls and infected rats (320 ± 163 vs. 333 ± 125 ng/ml). In the second experiment, with HSV-1 given in one nostril, CSF levels were 1 ± 1 ng/ml in controls and 56 ± 22 ng/ml in the HSV-1 group, whereas the total protein concentration in CSF remained the same in the two groups. The compleasome response was limited to CSF, with a highly significant difference between infected rats and controls (n = 11, p < 0.001). It was possible to mimic the reaction between proteasomes and complements 3 and 4 in vitro in the presence of ATP.

Herpes simplex virus 1 and cytomegalovirus are associated with pemphigus vulgaris but not with pemphigus foliaceus disease.

Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are blistering autoimmune diseases that depend on interaction between genetic and environmental factors. Viral infections, like herpes simplex viruses 1 and 2 (HSV1/2), cytomegalovirus (CMV), Epstein-Barr virus and dengue virus, could trigger or exacerbate pemphigus. IgM and IgG antibodies against these viruses in serum from PV and PF, their relatives and controls were determined. HSV1/2 expression was evaluated by direct immunofluorescence (DIF) and qPCR in affected or not oral mucosa from PV patients compared with uninjured PF mucosa. IgG anti-HSV1 was higher in the PV group compared with all groups. IgG anti-CMV resulted higher in PV group compared with PF patients and PV relatives. HSV1 was confirmed by DIF and qPCR on oral samples from patients with PV. Lack of HSV1 expression in the oral mucosa of patients with PF corroborate that immunosuppressive therapy cannot be the main cause for HSV1 replication in PV disease.

Impact of an Institutional Guideline on the Care of Neonates at Risk for Herpes Simplex Virus in the Emergency Department.

BACKGROUND AND OBJECTIVES: Herpes simplex virus (HSV) is rare in neonates but carries significant morbidity and mortality in that group. Emergency department (ED) clinicians have little guidance to decide when to test for HSV and give acyclovir. We created an institutional guideline to provide guidance in patients younger than 6 weeks. Our objective was to evaluate whether guideline implementation affected the ED's decision to test for HSV, and ED use of HSV polymerase chain reactions (PCRs) and acyclovir. METHODS: We reviewed charts for patients 1 year before implementation and 1 year after implementation of our guideline. Inclusion criteria were younger than 60 days, admitted through the ED, symptom onset younger than 6 weeks, and any one of the following criteria: (1) ED blood culture obtained, (2) ED or inpatient HSV PCR obtained, and (3) ED or inpatient acyclovir treatment. Premature patients and transfer patients were excluded. We compared whether the decision to initiate HSV testing, ED use of HSV PCRs, serum alanine aminotransferase, and acyclovir use changed post-guideline implementation. RESULTS: We reviewed 173 charts pre-implementation and 129 post-implementation. We found a significant decrease in ED testing for HSV among patients who did not meet guideline criteria (P < 0.01). We saw an improvement in the use of alanine aminotransferase among patients who met criteria for testing (P = 0.02), but no change in the use of HSV PCRs or acyclovir use among tested patients. CONCLUSIONS: Guideline implementation reduced HSV evaluations in low-risk patients, but did not improve test utilization or acyclovir administration among those tested. Additional work is needed to improve guideline utilization.

Evaluation of an Automated Chemiluminescent Immunoassay in Typing Detection of IgG Antibodies Against Herpes Simplex Virus.

BACKGROUD: Herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) are common infectious agents worldwide and the primary infection of HSV remains a major problem in the pregnant women in China nowadays. At present, typing detection of HSV is mainly based on ELISA in China. METHODS: In this study, we evaluated the performance of a newly introduced chemiluminescent immunoassay assay (CLIA) for the determination of serum HSV-1 and HSV-2 immunoglobulin G (IgG) antibodies. RESULTS: The functional sensitivity of detecting HSV-1 and HSV-2 IgG were 0.7 Index and 0.6 Index, respectively. The repeatability and the total imprecision coefficient of variations were both below 10%, and the recoveries of these assays ranged from 90% to 110%. High concentration of hemoglobin, lipids, and bilirubin in samples did not affect the results. The infective rates of HSV-1 and HSV-2 were 919 (87.5%) and 169 (16.1%), respectively. HSV-1 seroprevalence was significantly higher than that of HSV-2 (P < 0.001). CONCLUSION: CLIA is an excellent method for HSV-1 and HSV-2 IgG measurement and can be used as a routine screening test. The infective rate of HSV was pretty high among women before pregnancy or in the period of pregnancy in Beijing.

Seroprevalence of CMV, HSV-2 and HBV among HIV-Infected Malawian Children: A Cross-sectional Survey.

BACKGROUND: Little is known about viral co-infections in African human immunodeficiency virus (HIV)-infected children. We examined the prevalence of seromarkers for cytomegalovirus (CMV), herpes simplex virus type 2 (HSV-2) and hepatitis B virus (HBV) infections among HIV-infected, antiretroviral treatment (ART)-naïve children in Lilongwe, Malawi. METHODS: Ninety-one serum samples were tested for IgG and IgM antibodies to CMV, and IgG antibodies to HSV-2 and hepatitis B surface antigen (HBsAg). Baseline demographic, clinical and laboratory data were abstracted from electronic records. RESULTS: CMV IgG was the most common positive result in all age groups (in 73% of children <1 year, and 100% in all other groups). Three patients were CMV IgM positive (3.3%), suggesting acute infection. HSV-2 IgG was positive in four patients (4.4%), and HBsAg in two (2.2%). CONCLUSIONS: CMV infection occurred early in life, and few children had specific signs of CMV infection at the time of ART initiation. Unrecognized HBV infection represents opportunities for testing and treatment of HIV/HBV co-infected children.

Herpes Simplex Virus DNAemia Preceding Neonatal Disease.

Polymerase chain reaction testing of blood for herpes simplex virus (HSV) is recommended for newborns delivered to mothers with active genital HSV lesions at delivery. We report an infant who had a positive blood HSV polymerase chain reaction test before the onset of clinical signs of HSV disease.

Plasma and cerebrospinal fluid herpes simplex virus levels at diagnosis and outcome of neonatal infection.

OBJECTIVE: To evaluate the utility of quantitative herpes simplex virus (HSV) polymerase chain reaction (PCR) levels for prognosis and management of neonatal HSV disease. STUDY DESIGN: Clinical and virologic data were abstracted by medical record review from neonatal HSV cases treated at Seattle Children's Hospital between 1993 and 2012. HSV PCR results from plasma (n = 47), cerebrospinal fluid (n = 56), or both (n = 40) at the time of diagnosis were available from 63 infants; 26 with skin-eye-mouth (SEM), 18 with central nervous system (CNS), and 19 with disseminated (DIS) disease. RESULTS: Plasma HSV PCR was positive in 78% of the infants with SEM, 64% with CNS and 100% with DIS disease. Mean plasma viral level was 2.8 log10 copies/mL in SEM, 2.2 log10 copies/mL in CNS, and 7.2 log10 copies/mL in DIS infants. The HSV levels were higher among infants who died compared with surviving infants, 8.1 log10 copies/mL (range 7.7-8.6) vs 3.8 log10 copies/mL (range 0.0-8.6), P = .001, however, level of HSV DNA in the cerebrospinal fluid or in plasma did not correlate with neurologic outcome. Dynamics of HSV clearance from plasma during high-dose acyclovir treatment showed single-phase exponential decay with a median viral half-life of 1.26 days (range: 0.8-1.51). CONCLUSIONS: Plasma HSV levels correlate with clinical presentation of neonatal HSV disease and mortality, but not neurologic outcome.

Seroprevalence of Herpes Simplex Virus Type 1 and Type 2 and Coinfection With HIV and Syphilis: The First National Seroprevalence Survey in Saudi Arabia.

BACKGROUND: Herpes simplex virus (HSV) infection is one of the most common viral infections worldwide. Genital herpes is associated with other sexually transmitted infections (STIs) including HIV. Data on prevalence of HSV infections and other STIs in the Kingdom of Saudi Arabia are limited. METHODS: We conducted the first national seroprevalence survey to determine the prevalence and epidemiology of HSV infection among adult Saudis and coinfection with other STIs. Serology was used to detect HSV-1, HSV-2, HIV, and syphilis infections among 4985 participants recruited from across the Kingdom. RESULTS: The overall prevalence of HSV-1 and HSV-2 in the enrolled population was 88.8% and 1.26%, respectively. Although not significant for HSV-2, HSV infection was more prevalent among females, those working, and those who were married (married, divorced, or widowed), especially those married at a younger age. Prevalence of both viruses was statistically significantly higher among those with low education and increased with age. Prevalence of Treponema pallidum antibodies and HIV in the sampled population was very low (0.55% and 0.06%, respectively), as was their prevalence among HSV-2-positive participants (1.6% for both). The correlation between HSV-2 infection and other STIs was significant for HIV (P < 0.0001) but not for T. pallidum antibodies (P = 0.25). CONCLUSIONS: Herpes simplex virus type 1 infection is highly prevalent in Saudi Arabia and mostly acquired before adulthood. Herpes simplex virus type 2 prevalence is very low, acquired in adulthood, and increased with age. Monitoring the prevalence of HSV infection can help inform targeted strategies to prevent new infections, neonatal transmission, and the spread of other STIs in the Kingdom.

Unpacking the 'black box' of total pathogen burden: is number or type of pathogens most predictive of all-cause mortality in the United States?

A 'black box' paradigm has prevailed in which researchers have focused on the association between the total number of pathogens for which individuals are seropositive (i.e. total pathogen burden) and various chronic diseases, while largely ignoring the role that seropositivity for specific combinations of pathogens may play in the aetiology of such outcomes and consequently mortality. We examined the association between total pathogen burden as well as specific pathogen combinations and all-cause mortality in the United States. Data were from individuals aged ⩾25 years tested for cytomegalovirus (CMV), herpes simplex virus (HSV)-1, HSV-2 and Helicobacter pylori, with mortality follow-up to 31 December 2006 in the National Health and Nutrition Examination Survey (NHANES) III (N = 6522). We did not observe a statistically significant graded relationship between total pathogen burden level and all-cause mortality. Furthermore, compared to those seronegative for all four pathogens, the greatest statistically significant rate of all-cause mortality was for those CMV+/HSV-2+ (hazard ratio 1·95, 95% confidence interval 1·13-3·35) adjusting for age, gender, race/ethnicity, education level, body mass index (kg/m2) and smoking status. Interventions targeting prevention or treatment of particular pathogens may be more effective for reducing mortality than those focused solely on reducing overall pathogen burden.

Development of a time-resolved fluorescence immunoassay for herpes simplex virus type 1 and type 2 IgG antibodies.

Enzyme-linked immunosorbent assays (ELISA) specific for anti-HSV glycoprotein G (gG) are most commonly used in the clinical diagnosis of HSV infection. But most of them are qualitative and with narrow detection ranges. A novel time-resolved fluoroimmunoassay (TRFIA) methodology was developed for the quantitative determination of HSV IgG in human serum. The assay was based on an indirect immunoassay format, and performed in 96-well microtiter plates. HSV-1 and HSV-2 were used as the coating antigens. Eu(3+)-labeled goat anti-(human IgG) polyclonal antibodies were used as tracers. The fluorescence intensity of each well was measured and serum HSV IgG levels quantified against a calibration curve. The detection range of the novel TRFIA was between 5 and 500 AU/mL. Assay sensitivity was 0.568 AU/mL. The intra- and inter-assay coefficients of variation were 0.59-3.63% and 3.65-6.81%, respectively. Analytical recovery, dilution tests and serum panel tests were performed using TRFIA and the results proved satisfactory. There were no statistically significant differences in sensitivity and specificity between the TRFIA and commercial ELISAs. An effective, sensitive and accurate quantitative HSV type 1 and type 2 IgG TRFIA was successfully developed and provided diagnostic value in clinical use.

Serum HSV-1 and -2 IgM in pregnant women in Port Harcourt, Nigeria.

The present study was undertaken for the purpose of finding IgM antibodies against HSV-1 and 2 infections among pregnant women and also to evaluate correlation of Serum HSV-1 and 2 IgM in these pregnant women. A total of 180 pregnant women attending antenatal clinic at Braithwaite Memorial Specialist Hospital (BMSH) in Port Harcourt, Nigeria were consecutively recruited, after they had given consents to participate in the study. Serum of each sample was assayed for HSV-1&2 IgM antibody using a commercial ELISA. Five (2.8%) of the pregnant women were positive for IgM antibody against HSV-1&2. Marital status mainly correlated (χ(2) = 221.5, P < 0.05) with HSV-2 infection and HSV-1/HSV-2 co-infection. Age, educational level, occupation, and gestation were not consistently associated (P>0.05) with HSV-1/HSV-2 infection and co-infection. We also observed a high overall anti-HSV-1&2 IgM seronegativity of 97.2% among these pregnant women. Group-specific seronegativity was also high ranging from 93.3-100%. Although the age-groups significantly differed, none of their variables showed statistical association with the seronegativity. This represents the first analysis of HSV IgM antibody reported in Port Harcourt, Nigeria and has important public health implications, particularly for pregnant women. Consideration of this information would benefit physicians providing primary gynecological and obstetric care to this population of women.

Herpes simplex infection and the risk of Alzheimer's disease: A nested case-control study.

BACKGROUND: Herpes simplex virus (HSV) is thought to play an etiological role in the development of Alzheimer's disease (AD). METHODS: Plasma samples from 360 AD cases (75.3% women, mean age 61.2 years) and 360 age- and sex-matched dementia-free controls, taken on average 9.6 years before AD diagnosis, were analyzed for anti-HSV antibodies (immunoglobulin G, IgG, and immunoglobulin M, IgM) by enzyme-linked immunosorbent assays. RESULTS: In the complete sample group, the presence of anti-HSV IgG and IgM antibodies did not increase the risk of AD significantly (odds ratio (OR) 1.636, P = .069 and OR 1.368, P = .299, respectively). In cases with 6.6 years or more between plasma sampling and AD diagnosis (n = 270), there was a significant association between presence of anti-HSV IgG antibodies and AD (OR 2.250, P = .019). CONCLUSION: Among persons with a follow-up time of 6.6 years or more, HSV infection was significantly associated with AD.

[Immune signs of activation of the herpes simplex virus in women with physiological pregnancy].

Reactivation of the herpes simplex virus (HSV) is frequently observed in women during pregnancy. However, the concomitant changes in the immune system are still insufficiently understood. The goal of this work was to present a comparative analysis intended to identify specific antiviral IgM antibodies and IgG to determine their titles, concentration, and avidity in paired sera of 49 HSV-positive pregnant women without complicated obstetric-gynecological history. The serology results were compared with the quantitative determination in the serum IFNγ, as well as with the level of spontaneous and induced cytokine production by blood lymphocytes. For this purpose, 5.0 ml of blood from a vein was collected in pregnant women (9-11 weeks of gestation). The procedure was repeated in 4 weeks. The nonspecific induction of the IFNγ was performed using phytohemagglutinin (PanEco, Russia). Given the concentration of the immune markers in the samples, such values were evaluated by ELISA using certified commercial kits available from Vector-Best Ltd. (Russia) and Diagnostic System Scientific Manufacturing Association (Russia). IgM antibodies in paired sera had not been detected in any of the 49 women. High-avidity IgG antibodies were detected in all women in the titer 1:50-1:100, but in the second sample of sera from 32 women (study group) antibody titers were found to be as high as 1:600-1:800. The women with no growth of the serum antibodies were included in the control group (n = 17). Comparative analysis of the amount of IFNγ in sera showed that the content of the cytokine in the first blood sample and the level of the spontaneous production in women of the study group were statistically significantly higher than in the control group (4.2 vs. 2.7, p = 0.05; 7.5 vs. 2.0, p = 0.03, respectively). In the blood samples taken after 4 weeks the serum concentration of IFNγ (2.6 vs. 4.2, p = 0.049), and its spontaneous product (4.5 vs. 7.5, p = 0.046) were considerably lower than in the first blood samples. These results demonstrate that the reactivation of the HSV infection occurs in women with normal pregnancy and the lack of complicated obstetric and gynecological history. Increasing the concentration of IFNγ serum levels and spontaneous cytokine production is the earliest sign of acute infection in the women during pregnancy. These changes precede the increase in the IgG antibodies and assume normal values when the level of indirect marker of HSV rises. The lack of the IgM antibodies to the virus is not a strict criterion of inactive infection.