HSV-2 Antibodies Research Articles

HSV encephalitis with normal initial CT scan - a case report with a review of the literature

Introduction. HSV-1 is the most common cause of viral encephalitis with a high mortality rate if left untreated and causes frequent diagnostic difficulties. It commonly involves the temporal, inferior frontal lobes and the limbic system. HSV can be differentiated by a combination of symptoms, laboratory tests and neuroimaging findings.Case report. A 29-year old female with HSV encephalitis, who, despite prevailing symptoms of altered mental status, had no abnormalities on initial CT head scan. Three MRI follow-up examinations revealed imaging findings with characteristic evolution. Despite CSF results being negative for HSV antibodies, the combination of symptoms, CSF analysis, and characteristic MRI findings were highly suggestive to diagnosing HSV encephalitis and to implement proper treatment.Discussion. In case of radiological changes in temporal lobe, the involvement of the Herpes simplex encephalitis (HSE) should always be considered. Although the laboratory tests happen to be inconclusive or even falsely negative, neuroimaging often helps to determine the diagnosis. Despite HSE being a severe neurological disorder, initial CT scans can be normal. MRI has become superior, especially at the early phase of the disease and is capable of determining the extensiveness of lesions.

Utility of HSV Serology for Chronic Corneal Pathology.

The purpose of this study is to determine the utility of obtaining herpes simplex virus (HSV) serology for patients presenting with chronic corneal pathology of unknown etiology for which HSV is a diagnostic consideration. A retrospective analysis was performed of all patients presenting to one cornea specialist (J.M.G.) between August 2011 and April 2018 with a chronic (>6 weeks) corneal condition for which HSV was suspected and serology was performed. Patient demographics, clinical presentation, treatment, final diagnosis, and follow-up duration were recorded. Fifty-four patients with a median age of 52 (range: 5-85) years were included in the study. Patients were classified by presenting clinical features as corneal ulcer (46.2%), stromal keratitis (24.1%), superficial keratitis (18.5%), or keratouveitis (11.1%). The seroprevalence of HSV-1 and HSV-2 antibodies were 42.6% and 18.5%, including 5 patients (9.3%) positive for both HSV-1 and HSV-2. Serology impacted management for all patients with negative titers (48.1%), defined as discontinuing antiviral medication, electing not to start antiviral medication, or continuing antiviral medication for a non-HSV etiology (e.g., varicella zoster keratitis). No patients with HSV serology were ultimately diagnosed with HSV keratitis. Median follow-up duration was 1.5 years (range 0.8-6.6 years). Although only useful when negative, our study confirms that serology may be useful for excluding HSV as a diagnostic consideration for patients presenting with chronic corneal pathology. The seroprevalence of HSV antibodies for our patient cohort was comparable with previous population-based studies.

2359 Acute Liver Failure in the Setting of HSV-Induced Hemophagocytic Lymphohistiocytosis

INTRODUCTION: Acute liver failure (ALF) is characterized by acute (< 26 weeks) liver injury, encephalopathy, and impaired synthetic function (INR ≥ 1.5) in a patient without a preexisting liver disease carries a poor prognosis1. Common etiologies of ALF include acetaminophen toxicity, sepsis, and toxin exposure2. Here, we present a rare case of ALF secondary to HSV-induced Hemophagocytic lymphohistiocytosis (HLH). CASE DESCRIPTION/METHODS: A 57-year old male with a history of hypertension presented with a week history of cough and fever. Review of systems also included fatigue, decreased appetite, and decreased interactiveness. Labs were remarkable for anemia, thrombocytopenia (plt 15,000), tranaminitis (AST/ALT 6943/1551), ferritinemia (>105,000 ng/mL) and hypofibrinogenemia (134 mg/dL). Workup for causes of ALF was unrevealing, including acetaminophen, viral hepatitis, Wilson Disease, and autoimmune hepatitis. Blood and urine cultures, respiratory viral PCR, Adenovirus PCR, HIV Ab/Ag, Lyme IgM/IgG, ANA and RF were negative. HSV and EBV antibodies were collected early in admission. A CT Chest was unremarkable and a CT abdomen showed diffuse hepatic hypo-attenuation. His course was complicated by hypothermia, hypotension, and unresponsiveness prompting intubation and admission into the ICU. He was started on broad spectrum antibiotics as well as high dose steroids. His clinical status continued to deteriorate after-which his family requested comfort care measures. Postmortem autopsy demonstrated hepatomegaly with HSV hemorrhagic and necrotic hepatitis resulting in confluent non-zonal hepatic necrosis, as well as splenomegaly. Postmortem his HSV IgM (type 1 and 2) was not detected. His serum EBV IgM and IgG elevated with PCR showing 2246 copies/mL. DISCUSSION: This was a case of ALF due to suspected HSV-induced HLH. In review of the literature, only one other case study has reported ALF in the setting of HSV-induced HLH3. The diagnosis of HLH clinically requires 5/8 criteria [Table 1]4. Our patient met five of eight criteria for HLH. Notably, both EBV and HSV have been strongly implicated as potential triggers for HLH5. Although primary liver disease and HLH can present in a similar fashion, HLH tends to incorporate more extensive organ involvement, cytopenias, extremely high ferritin, and neurologic findings. Our case a rare precipitating cause of ALF, highlighting the importance of considering HSV-induced HLH early in the course of newly diagnosed ALF given their rapid deterioration.

Rapid immunodiagnostics of multiple viral infections in an acoustic microstreaming device with serum and saliva samples.

There is a growing need to screen multiple infections simultaneously rather than diagnosis of one pathogen at a time in order to improve the quality of healthcare while saving initial screening time and reduce costs. This is the first demonstration of a five-step protein array assay for the multiplexed detection of HIV, HPV and HSV antibodies on an integrated microfluidic system. HIV, HPV and HSV reactive antibodies from both serum and saliva were rapidly detected by acoustic streaming-based mixing and pumping to enable an integrated, rapid and simple-to-use multiplexed assay device. We validated this device with 37 serum and saliva samples to verify reactivity of patient antibodies with HIV, HPV and HSV antigens. Our technology can be adapted with different protein microarrays to detect a variety of other infections, thus demonstrating a powerful platform to detect multiple putative protein biomarkers for rapid detection of infectious diseases. This integrated microfluidic protein array platform is the basis of a potent strategy to delay progression of primary infection, reduce the risk of co-infections and prevent onward transmission of infections by point-of-care detection of multiple pathogens in both serum and oral fluids.

Performance of ELISA and Western blot to detect antibodies against HSV-2 using dried blood spots

Background and aimsHerpes simplex virus type 2 (HSV-2) is a sexually transmitted agent and is detected worldwide. HSV-2 is the main cause of genital ulcers and is diagnosed mainly with serological tests. The objective of current study was to evaluate the use of DBS samples to detect HSV-2 antibodies using commercial ELISA and Western blot tests. Materials and methodsIgG-G2 ELISA (Human® Diagnostics, Germany) and Western blot IgG/IgM (EUROLINE-WB, Euroimmun® Germany) tests were modified to use DBS samples. Samples were processed by both methods to determine ELISA cutoff points using ROC curves. ELISA was performed with 100μl and the Western blot with 200μl of eluted DBS. A 1:5 dilution was used and the incubation times were increased for the Western blot. Results908 DBS samples were processed and the following cutoff points were determined: negative (0–3.79), undetermined (3.8–4.6) and positive (≥4.61), with sensitivity and specificity close to 95%. ConclusionModifications of the cutoff points of the ELISA test were obtained with technical adjustments done to detect HSV-2 antibodies by ELISA and Western blot using DBS samples.

Screening for cervical abnormalities associated with EBV, HPV and HSV-2 infections in South-West Nigeria: A tale between sex and non-sex workers

This study investigated socio-economic and clinical correlates of cervical abnormalities and some viral infections such as Human Papilloma virus (HPV), Epstein-Barr virus (EBV) and Herpes Simplex virus type 2 (HSV-2) among commercial sex workers (CSWs) and non-sex workers (NSWs) of reproductive age. It also estimated serum levels of SCCA1, p16 and Ki67 as potential non-invasive biomarkers of cervical abnormalities. This cross-sectional study included 203 consenting participants (NSWs = 98 and CSWs = 105) within the age-range of 20–49 years. Interview based risk factor questionnaire was administered, Pap smears were made from cervical scrapings and classified accordingly while serum levels of SCCA1, Ki67 and p16, EBV, HPV and HSV2 antibodies were determined by ELISA method. Multivariate and multiple logistic regression analysis were on generated data carried out and significance set at p < 0.05. Among NSWs, higher prevalence of cervicitis, atypical squamous cell of undetermined significance (ASCUS), low grade squamous cell intraepithelial lesion (LSIL) and high grade squamous cell intraepithelial lesion (HSIL) were 18.4%, 16.3%, 11.2% and 8.2%, respectively while the prevalence of the cervical abnormalities were 7.6%, 7.6%, 8.6% and 3.8%, respectively among CSWs (p = 0.04). Decreasing and increasing sero-prevalence of viral infections were observed from cervicitis, ASCUS, LSIL to HSIL among NSWs (77, 56, 54.5 and 50%) and CSWs (75, 87.5, 100 and 100%), respectively (p = 0.08). When only ASCUS, LSIL and HSIL were considered, statistics showed p16 sensitivity and specificity of 64.7% and 79.5%, respectively (Odd ratio {OR} 0.7118), SCCA1 sensitivity and specificity of 83.8% and 97%, respectively (OR 166.9) and ki67 sensitivity and specificity of 63.2% and 94.0%, respectively (OR 26.83). It revealed that serum levels of SCCA1, ki67 and p16 were sensitivity to the classes of Pap smear at p = 0.00; p = 0.00 and p = 0.01, respectively. This study suggests that while HPV infection could independently could promote the development of cervical abnormalities among CSWs, EBV infection and other factors may be potential factors among NSWs. It also suggests that serum levels of SCCA1, ki67 and p16 could be used as effective Pap smear complementary diagnostic biomarkers.

Seroprevalence, Type-Specific of Herpes Simplex Virus and Associated Risk Factors among Women of Child Bearing Age in Kogi State, Nigeria

Background: Viruses of the Herpes viridae family infect 90% of the Earth’s population. Humans are the hosts of at least nine unique herpes viruses. Aim: This study is aimed at evaluating the seroprevalence of type specific herpes simplex virus infection and the associated risk factors in a cross-section of asymptomatic healthy women of childbearing age in Kogi state, Nigeria. Methodology: A total of 330 females of child bearing age (15 - 49 years) participated in this study. They were recruited from various local government areas of three Senatorial districts of Kogi state. Blood samples were collected from participants and analyzed for HSV-1 and HSV-2 antibodies (IgG) quantitatively with ELISA kit. Results: The overall prevalence of HSV was 76.7%. Data further show that majority (96.4%) of the population studied had HSV-1, while 77% had HSV-2 infections. Results also showed that the young adults indicated prevalence of 95.7% for HSV-1 and 74.7% for HSV-2, while in the middle aged, the prevalence were 98.6% for HSV-1, and 84.9% for HSV-2. 99.2% of the married women were positive for HSV-1, while 86.9% were positive for HSV-2. 94.5% of the unmarried women were positive for HSV-1, while 70.5% were positive for HSV-2. The risk of HVS-1 or VS-2 infections was not associated with age, age of first sexual exposure and number sex partners before marriage. Married women were at greater risk for HSV-1 (p = 0.03) and HSV-2 (p ≤ 0.001) infections compared to the unmarried women. Conclusion: The prevalence of the HSV-1 and HSV-2 infections was high among asymptomatic healthy women of childbearing age in Kogi state, Nigeria. Efforts should be made to increase the awareness of HSV infection among the child bearing populace.

Performance of Commercial Enzyme-Linked Immunoassays for Diagnosis of Herpes Simplex Virus-1 and Herpes Simplex Virus-2 Infection in a Clinical Setting.

US Food and Drug Administration-approved enzyme-linked immunoassays (EIA) for determining type-specific herpes simplex virus (HSV) serostatus are widely used in clinical practice. We compared the performance of such assays with the University of Washington Western blot (UW WB) in patients who sought confirmation of their HSV serology result. We reviewed charts of all persons evaluated at the Westover Heights Clinic in Portland, Oregon, from July 2010 through September 2015, who had a HSV EIA, followed by UW WB. Of 864 persons, 47% were women. The median age was 36 years (range, 18-73 years). Using UW WB to define infection status, 286 (33%) persons were HSV-1 seropositive only, 104 (12%) were HSV-2 seropositive only, 134 (16%) were both HSV-1 and HSV-2 seropositive, 235 (27%) were HSV seronegative, and 105 (12%) had indeterminate results. Compared with the UW WB as the criterion standard, EIA was 70.2% sensitive and 91.6% specific for HSV-1, and 91.9% sensitive and 57.4% specific for HSV-2.Among 278 persons who were HSV-1 seropositive by EIA, 255 were confirmed by the UW WB (positive predictive value [PPV], 91.7%). Of the 360 persons that were HSV-1 seronegative by the EIA, 252 were seronegative by UW WB (negative predictive value [NPV], 70.0%). Among 381 persons with HSV-2 EIA seropositivity, 193 tested HSV-2 seropositive by the UW WB (PPV, 50.7%). Of the 270 persons HSV-2 seronegative by EIA, 17 were seropositive with the UW WB (NPV, 93.7%). Among 261 persons with an EIA HSV-2 index value = 1.1-2.9, 39.8% of results were confirmed by UW WB, compared with 78.6% of the 70 persons with an EIA index value of 3 or greater (P < 0.001). The risk of false-positive HSV-2 EIA results was higher in those with HSV-1 antibody (47.1% vs 37.1%, P = 0.036). US Food and Drug Administration-approved EIAs have poor PPV for HSV-2 and poor NPV for HSV-1 in clinical practice. More accurate rapid type-specific HSV antibody tests are needed.

Detection of cytomegalovirus, herpes virus simplex, and parvovirus b19 in spontaneous abortion placentas

Objective: This study aims to investigate the presence of Cytomegalovirus (CMV), herpes virus simplex (HSV), and parvovirus B19 (PVB19) in the placental tissue of patients who underwent abortions without an otherwise-defined aetiology.Study design: This cross-sectional study was conducted in a high-risk obstetric maternity facility at a University Hospital in Belo Horizonte, Brazil, from January 2013 to December 2015. We included placenta samples obtained from spontaneous abortions of unknown aetiology. Seventy placenta samples were identified and were classified according to histopathological characteristics. All samples were analysed using immunohistochemistry and polymerase chain reaction for CMV, PVB19, and HSV. The clinical variables were collected from the medical records of patients to verify the association of infection with villitis. The patients were divided into the following groups: I) with villitis (n = 28) and II) without villitis (n = 42).Methods: Immunohistochemistry used monoclonal anti-CMV antibody (NCL-CMVpp65, Leica Biosystems, Wetzlar, Germany), anti-PVB19 antibody (NCL-PARVO, Leica Biosystems, Wetzlar, Germany), and anti-HSV1/HSV2 antibodies (NCL-HSV-1 and HSV2, Leica Biosystems, Wetzlar, Germany). The data were analysed using the Statistical Package for Social Sciences (SPSS Inc, Chicago, IL) 19.0.Results: Viral agents were detected in five patients (7.14%) in the villitis group. Three patients were positive for CMV, one for PVB19, and one for HSV type 2. Foetal and maternal complications were significantly higher in the group with villitis compared with those in the group without villitis (p = .002).Conclusions: The prevalence of transplacental viral infections as a cause of spontaneous abortion should be considered high in the placenta with villitis. Thus, this study highlights the need for developing diagnostic tests to clarify the aetiology of abortion and foetal loss.

Expression and characterization of the soluble form of recombinant mature HSV-2 glycoprotein G for use in anti-HSV-2 IgG serodiagnostic immunoassay

Herpes simplex virus type-2 (HSV-2) specific glycoprotein G (gG-2) is widely used as the antigen of choice for serodiagnosis of HSV-2. In order to develop an ELISA for serodetection of HSV-2 IgG in patient sera, the soluble form of the mature gG-2 antigen (mgG-2), gG283-649, was expressed using a baculovirus expression system. gG283-649 contains the complete extracellular domain of mgG-2 including the C-terminal region, which despite homology to gG-1, does not cross-react with HSV-1 antibodies present in HSV-1 positive patient sera. gG283-649 had increased performance compared to a previously described gG-2 fragment and showed high sensitivity and specificity in a method comparison with HerpeSelect 1 & 2 Immunoblot IgG, a commercially available FDA-cleared assay for serodetection of HSV-1 and 2 antibodies. A total of 234 clinical samples consisting of 134 high risk samples, including 45 samples from pregnant subjects, and a panel of 100 mixed diagnosis samples, spanning the measurable range were tested in the method comparison. Clinical sensitivity and specificity were determined to be 94.2% and 100%, respectively. We conclude that this soluble form of mgG-2 is a novel antigen of choice for developing an ELISA for type-specific serodiagnosis of HSV-2.

HIV/Human herpesvirus co-infections: Impact on tryptophan-kynurenine pathway and immune reconstitution.

BackgroundCo-infections with human herpesvirus (HHV) have been associated with residual chronic inflammation in antiretroviral (ART)-treated human immunodeficiency virus (HIV)-infected individuals. However, the role of HHV in modulating the tryptophan-kynurenine pathway and clinical outcomes in HIV-infected individuals is poorly understood. Thus, we investigated the seroprevalence of four common HHVs among treated HIV-infected participants and their impact on kynurenine/tryptophan (K/T) ratio and long-term CD4 T-cell recovery in HIV/HHV co-infected participants.MethodIn this cross-sectional study, HIV-infected participants receiving suppressive ART for a minimum of 12 months were recruited from the University Malaya Medical Centre (UMMC), Malaysia. Stored plasma was analyzed for CMV, VZV, HSV-1 and HSV-2 IgG antibody levels, immune activation markers (interleukin-6, interferon-γ, neopterin and sCD14), kynurenine and tryptophan concentrations. The influence of the number of HHV co-infection and K/T ratio on CD4 T-cell recovery was assessed using multivariate Poisson regression.ResultsA total of 232 HIV-infected participants were recruited and all participants were seropositive for at least one HHV; 96.1% with CMV, 86.6% with VZV, 70.7% with HSV-1 and 53.9% with HSV-2. K/T ratio had a significant positive correlation with CMV (rho = 0.205, p = 0.002), VZV (rho = 0.173, p = 0.009) and a tendency with HSV-2 (rho = 0.120, p = 0.070), with CMV antibody titer demonstrating the strongest modulating effect on K/T ratio among the four HHVs assessed in SOM analysis. In multivariate analysis, higher K/T ratio (p = 0.03) and increasing number of HHV co-infections (p<0.001) were independently associated with poorer CD4 T-cell recovery following 12 months of ART initiation.ConclusionMultiple HHV co-infections are common among ART-treated HIV-infected participants in the developing country setting and associated with persistent immune activation and poorer CD4 T-cell recovery.

Invasive Obstetric Procedures and Cesarean Sections in Women With Known Herpes Simplex Virus Status During Pregnancy.

BackgroundNeonatal herpes is a potentially devastating infection that results from acquisition of herpes simplex virus (HSV) type 1 or 2 from the maternal genital tract at the time of vaginal delivery. Current guidelines recommend (1) cesarean delivery if maternal genital HSV lesions are present at the time of labor and (2) antiviral suppressive therapy for women with known genital herpes to decrease HSV shedding from the genital tract at the time of vaginal delivery. However, most neonatal infections occur in infants born to women without a history of genital HSV, making current prevention efforts ineffective for this group. Although routine serologic HSV testing of women during pregnancy could identify women at higher risk of intrapartum viral shedding, it is uncertain how this knowledge might impact intrapartum management, and a potential concern is a higher rate of cesarean sections among women known to be HSV-2 seropositive.MethodsTo assess the effects of prenatal HSV-2 antibody testing, history of genital herpes, and use of suppressive antiviral medication on the intrapartum management of women, we investigated the frequency of invasive obstetric procedures and cesarean deliveries. We conducted a retrospective cohort study of pregnant women delivering at the University of Washington Medical center in Seattle, Washington. We defined the exposure of interest as HSV-2 antibody positivity or known history of genital herpes noted in prenatal records. The primary outcome was intrapartum procedures including fetal scalp electrode, artificial rupture of membranes, intrauterine pressure catheter, or operative vaginal delivery (vacuum or forceps). The secondary outcome was incidence of cesarean birth. Univariate and multivariable logistic regressions were performed.ResultsFrom a total of 449 women included in the analysis, 97 (21.6%) were HSV-2 seropositive or had a history of genital herpes (HSV-2/GH). Herpes simplex virus-2/GH women not using suppressive antiviral therapy were less likely to undergo intrapartum procedures than women without HSV-2/GH (odds ratio [OR], 0.49; 95% confidence interval [CI], 0.25–0.95; P = .036), but this relationship was attenuated after adjustment for potential confounders (adjusted OR, 0.69; 95% CI, 0.34–1.41; P = .31). There was no difference in intrapartum procedures for women on suppressive therapy versus women without HSV-2/GH (OR, 1.17; 95% CI, 0.66–2.07; P = .60). Similar proportions of cesarean sections were performed within each group of women: 25% without history of HSV-2/GH, 30% on suppressive treatment, and 28.1% without suppressive treatment (global, P = .73).ConclusionsIn this single-site study, provider awareness of genital herpes infection either by HSV serotesting or history was associated with fewer invasive obstetric procedures shown to be associated with neonatal herpes, but it was not associated with an increased rate of cesarean birth.

Estimating seroprevalence of herpes simplex virus type 1 among different Middle East and North African male populations residing in Qatar.

HSV‐1 epidemiology in the Middle East and North Africa (MENA) remains poorly understood. Our study aimed to measure HSV‐1 antibody prevalence (seroprevalence) and its age‐distribution among select MENA populations residing in Qatar. Sera were collected from male blood donors attending Hamad Medical Corporation 2013‐2015. A total of 2,077 sera were tested for anti‐HSV‐1 antibodies using HerpeSelect® 1 ELISA IgG kits (Focus Diagnostics, Cypress, CA). Robust Poisson regression was conducted to estimate adjusted infection prevalence ratios. Country‐specific HSV‐1 seroprevalence was estimated for 10 national populations: 97.5% among Egyptians, 92.6% among Yemenis, 90.7% among Sudanese, 88.5% among Syrians, 86.5% among Jordanians, 82.3% among Qataris, 81.4% among Iranians, 81.4% among Lebanese, 80.5% among Palestinians, and 77.0% among Pakistanis. Age‐specific HSV‐1 seroprevalence was estimated for Egypt, the Fertile Crescent (Iraq, Jordan, Lebanon, Palestine, and Syria), and Qatar. Seroprevalence increased with age among Fertile Crescent and Qatari nationals. Seroprevalence increased from 70.0% among those aged ≤ 24 years up to 98.0% among those aged ≥55 years among Fertile Crescent nationals. Seroprevalence was consistently above 90% for all ages among Egyptians. HSV‐1 seroprevalence is high in MENA, though with some variation across countries. The seroprevalence appears to have declined among current young age cohorts compared to its levels a few decades ago.

Linear Multiepitope (Glyco)peptides for Type-Specific Serology of Herpes Simplex Virus (HSV) Infections.

Detection of type-specific antibodies is an important and essential part of accurate diagnosis, even in silent carriers of herpes simplex virus (HSV)-1 (oral) and HSV-2 (genital) infections. Serologic assays that identify HSV-1 and HSV-2 type-specific antibodies have been commercially available for more than a decade but often face problems related to cross-reactivity and similar issues. Attempts to identify type-specific peptide epitopes for use in serology for both HSV-1 and HSV-2 have been limited. We recently demonstrated epitope mapping of envelope glycoprotein G2 and identified a type-specific glycopeptide epitope that broadly recognized HSV-2 infected individuals. In the present work we have performed a comprehensive glycopeptide synthesis and microarray epitope mapping of 14 envelope proteins from HSV-1 and HSV-2, namely, gB, gC, gD, gE, gG, gH, and gI, using sera from HSV-1- and HSV-2-infected individuals and control sera. Several unique type-specific peptide epitopes with high sensitivity were identified and synthesized as one large linear multiepitope sequence using microwave-assisted solid-phase (glyco)peptide synthesis. Microarray validation with clinically defined HSV and Varicella Zoster (VZV) sera confirmed excellent cumulative specificities and sensitivities.

Positive correlation of anti-herpes simplex type I virus antibody levels with pemphigus vulgaris disease status and activity in a large patient cohort.

It is well accepted that pemphigus vulgaris (PV) is genetically linked to specific HLA class II subtypes. Environmental factors, including the role of herpes simplex virus (HSV1) in disease manifestation, have also been implicated, but in a limited number of patients and with inconsistent results. To clarify an association between HSV1 and PV in a large data set, including a stratification by dynamic and static clinical parameters, including disease activity, therapy status, HLA association, and gender. Serum HSV1 IgG levels from PV patients and healthy controls were measured by ELISA. Subjects were typed for HLA class II DRB1 and DQB1 alleles, and categorized as HLA-matched if homozygous or heterozygous for either one of the known PV-susceptibility alleles, DRB1*0402 and DQB1*0503. Our data indicate that PV patients carry significantly higher levels of anti-HSV1 antibodies than healthy controls, and that this effect was more pronounced in the active phase of disease when compared to remission. A mild positive association could also be observed for carriers of the PV-associated HLA alleles versus HLA-unmatched controls, as well as for female PV patients when compared to female control subjects. Our data suggest a role of HSV1 in the expression of PV and further show that HLA status and gender may influence HSV1 susceptibility and/or expression of anti-HSV1 antibodies. Additional research with larger datasets is required to determine whether HSV is causally linked to PV pathogenesis and conclusively link HLA status and gender to HSV1 antibody levels.

Recurrent herpes labialis and Herpes simplex virus-1 genitalis: what is the link?

Recently, Herpes simplex virus (HSV)-1 seroprevalence declined among adolescents, rendering young people lacking HSV-1 antibodies more susceptible to genital HSV-1 acquisition, if sexually exposed. The aim of the present study was to identify the possible risk factors for the development of HSV-1 related Herpes genitalis (HG). From January 2012 to December 2015, patients with HG attending three Sexually Transmitted Infections Units in Northern Italy were recruited. A genital swab on the lesions for the search of HSV-1/2 DNA through real time polymerase chain reaction (PCR) and a serum sample for HSV-1/2 specific serology were performed. Moreover, patients were asked whether they had personal history of herpes labialis (HL). Patients with PCR proved HSV-1 HG were included as cases; asymptomatic subjects attending STI Units for a blood check were recruited as controls and were checked for HSV-1/2 serology. The study included 141 cases and 70 controls. Specific HSV-1 antibodies were found in 34.7% of the cases and 67% of the controls. History of recurrent herpes labialis (RHL) was found in 4% of the cases and 31% of the controls. The occurrence of RHL in HSV-1 seropositive patients resulted lower in the case group compared to the control group. We can speculate about a protective role for RHL against the clinical appearance of HSV-1 HG. The clinical usefulness of our study involved especially the counselling in serodiscordant couples. The presence of HSV-1 antibodies in asymptomatic sexual partners does appear protective for HG manifestation only in presence of RHL history.

Carotid intima media thickness and blood biomarkers of atherosclerosis in patients after stroke or myocardial infarction.

AimTo test if circulating levels of markers of inflammation, endothelial function, and chronic infections, as well as association between these markers and carotid intima media thickness (CIMT), depend on the stage of atherosclerosis expressed as a history of a major vascular event.MethodsThe associations were analyzed separately in 75 healthy controls, 79 patients 3-6 months after the first-ever non-cardioembolic ischemic stroke (IS), and 37 patients 3-6 months after the first-ever myocardial infarction (MI). Data were collected prospectively in 2005. We measured high sensitivity C-reactive protein (hs-CRP), procalcitonin, E-selectin, intercellular adhesion molecule-1 (ICAM-1), serum level of immune complexes (IC), and identified antibodies against Herpes simplex virus type 1 (HSV), Cytomegalovirus, Chlamydia pneumonia, and Helicobacter pylori. Correlations with CIMT were determined using Pearson R and verified after adjustment for age, sex, hypertension, diabetes, and statin therapy.ResultsMedian ICAM-1 concentration was significantly lower in controls than in post-IS patients (188 μg/L vs 215 μg/L), and significantly lower in post-IS patients than in post-MI patients (215 μg/L vs 260 μg/L). Control patients also had significantly lower IC level (0.03 U/L) and HSV antibody index (6.0) compared to both post-IS (0.6 U/L, 9.6) and post-MI (0.4 U/L, 9.2) patients. CIMT was correlated with age (Pearson R = 0.38, P = 0.001) in the control group, immune complexes (R = 0.26, P = 0.023) in the post-IS group, and with hs-CRP (R = 0.40, P = 0.017) in the post-MI group. These correlations were confirmed using multiple regression analysis.ConclusionsOur study supports linear correlations between CIMT and IC and hs-CRP levels. However, these associations seem to depend on the type of vascular burden.

High seroprevalence of human herpesvirus 8 and herpes simplex virus 2 infections in men who have sex with men in Shanghai, China.

Men who have sex with men (MSM) are an important risk group for human immunodeficiency virus (HIV) and at high-risk of herpesvirus infection. However, limited information on epidemiologic patterns of HHV8 and HSV2 among MSM is available in mainland China. A cross-sectional study of 486 participants was performed in Shanghai, China from January 2013 to December 2014 to explore epidemiologic features of HHV8 and HSV2 among MSM. Serum samples were collected and tested for HHV8 by immunofluoresence assay and HSV2 antibodies by ELISA. Logistic regression analysis was conducted to determine the risk factors of HHV8 and HSV2 infections, respectively. The overall seroprevalence was 23.0% for HHV8 infection and 22.4% for HSV2 infection. HHV8 seropositivity was significantly associated with being a money boy (odds ratio (OR) = 1.64; 95%CI: 1.04-2.58), having a steady sex partner (OR = 0.52; 95%CI: 0.31-0.87), having ever had anal sex with men (OR = 2.05; 95%CI: 1.09-3.86), and being HSV2 positive (OR = 2.14; 95%CI: 1.22-3.76). HSV2 seropositivity was significantly associate with being positive for HIV (OR = 2.12; 95%CI: 1.01-4.42), syphilis (OR = 1.98; 95%CI: 1.12-3.52), HHV8 (OR = 2.17; 95%CI: 1.24-3.83), and was marginally associated with being a money boy (OR = 1. 61; 95%CI: 0.97-2.86), and having ever had unprotected casual sex (OR = 1. 72; 95%CI: 0.99-2.99). HHV8 and HSV2 infections are common in Chinese MSM. It is important to implement programs for preventing herpes virus infection among MSM, particularly high-risk groups such as money buys. And protected sexual intercourse should be propagated. J. Med. Virol. 89:887-894, 2017. © 2016 Wiley Periodicals, Inc.

High avidity HSV-1 antibodies correlate with absence of amnestic Mild Cognitive Impairment conversion to Alzheimer’s disease

Amnestic Mild Cognitive Impairment (aMCI) is an alteration in cognitive abilities that can progress to Alzheimer’s disease (AD), a condition in which herpes simplex type 1 (HSV-1) infection might play a pathogenetic role. Prognostic indexes capable of predicting aMCI conversion to AD are only partially understood. The objective of the present work is to verify whether HSV-1 immune responses is involved in conversion of aMCI to AD and correlate with grey matter brain morphometry. Two homogeneous groups of individuals who did or did not convert to AD over a 24-months period were selected after retrospective analysis of a cohort of patients with a diagnosis of aMCI. The selection of subjects was based on: a) clinical follow-up; b) neurocognitive evaluation at baseline and after 24months; c) availability of serum and DNA samples at baseline. 36 aMCI individuals, 21 of whom did (aMCI-converters) and 15 of whom did not (aMCI-non-converters) convert to AD, were included in the study. HSV-1 antibody (Ab) titers, avidity index and APOE genotyping were performed in all the enrolled individuals at baseline. Brain magnetic resonance imaging (MRI) by 1.5T scanner results at baseline were available as well in most (29/36) of these individuals. HSV-1-specific Ab titers were increased at baseline in aMCI-non-converters, and the avidity of these Ab was significantly higher in aMCI-non-converter compared to aMCI-converter (p=0.0018). Receiver operating characteristics analysis showed that HSV-1 avidity had a predictive value in distinguishing between aMCI-non-converters and aMCI-converters (p<0.0001). Notably, a positive correlation was detected as well between HSV-1 antibody titers and MRI-evaluated cortical volumes in the left hippocampus and amigdala (pcorr<0.05). In conclusion, stronger HSV-1-specific humoral responses associate with protection against AD conversion and better-preserved cortical volumes. These results reinforce the hypothesis for a role for HSV-1 in the pathogenesis of AD.

Genital herpes and encephalitis; a case history

A 19-year-old, previously healthy unmarried girl presented with sudden onset loss of consciousness preceded by genital ulcers, fever and headache. Examination revealed mild neck stiffness, 4/15 of GCS, and upper motor neuron signs in all four limbs. In addition, there were multiple, superficial and tender genital ulcers. Electro Encephalogram (EEG) showed evidence of encephalitis and subsequent serological tests revealed presence of HSV antibodies. Her condition improved remarkably following intravenous Aciclovir therapy. Presence of typical herpetic ulcers, positive type specific serology test for HSV, evidence of encephalitis in the EEG and good response to Aciclovir, favoured the possible diagnosis of Herpes Simplex Encephalitis (HSE). Sri Lanka Journal of Sexual Health and HIV Medicine Vol.1 2015: 29-32