Herpes Simplex Virus Antibodies Research Articles

Human Antibodies against Herpes Simplex Virus 2 Glycoprotein G Do Not Neutralize but Mediate Antibody-Dependent Cellular Cytotoxicity.

Herpes simplex virus 2 (HSV-2) is a sexually transmitted infection affecting 491 million individuals globally. Consequently, there is a great need for both prophylactic and therapeutic vaccines. Unfortunately, several vaccine clinical trials, primarily employing the glycoprotein D of HSV-2 (gD-2), have failed. The immune protection conferred by human anti-HSV-2 antibodies in genital infection and disease remains elusive. It is well-known that gD-2 elicits cross-reactive neutralizing antibodies, i.e., anti-gD-2 antibodies recognize gD in HSV-1 (gD-1). In contrast, anti-glycoprotein G in HSV-2 (mgG-2) antibodies are exclusively type-specific for HSV-2. In this study, truncated versions of gD-2 and mgG-2 were recombinantly produced in mammalian cells and used for the purification of anti-gD-2 and anti-mgG-2 antibodies from the serum of five HSV-2-infected subjects, creating a pool of purified antibodies. These antibody pools were utilized as standards together with purified mgG-2 and gD-2 antigens in ELISA to quantitatively estimate and compare the levels of cross-reactive anti-gD-1 and anti-gD-2 antibodies, as well as anti-mgG-2 antibodies in sera from HSV-1+2-, HSV-2-, and HSV-1-infected subjects. The median concentration of anti-mgG-2 antibodies was five times lower in HSV-1+2-infected subjects as compared with cross-reactive anti-gD-1 and anti-gD-2 antibodies, and three times lower in HSV-2 infected subjects as compared with anti-gD-2 antibodies. The pool of purified anti-gD-2 antibodies presented neutralization activity at low concentrations, while the pool of purified anti-mgG-2 antibodies did not. Instead, these anti-mgG-2 antibodies mediated antibody-dependent cellular cytotoxicity (ADCC) by human granulocytes, monocytes, and NK-cells, but displayed no complement-dependent cytotoxicity. These findings indicate that antibodies to mgG-2 in HSV-2-infected subjects are present at low concentrations but mediate the killing of infected cells via ADCC rather than by neutralizing free viral particles. We, and others, speculate that Fc-receptor mediated antibody functions such as ADCC following HSV-2 vaccination may serve as a better marker of protection correlate instead of neutralizing activity. In an mgG-2 therapeutic vaccine, our findings of low levels of anti-mgG-2 antibodies in HSV-2-infected subjects may suggest an opportunity to enhance the immune responses against mgG-2. In a prophylactic HSV-2 mgG-2 vaccine, a possible interference in cross-reactive immune responses in already infected HSV-1 subjects can be circumvented.

Performance characteristics of highly automated HSV-1 and HSV-2 IgG testing.

Herpes simplex virus (HSV) infections are one of the most common and stigmatized infections of humankind, affecting more than 4 billion people around the world and more than 100 million Americans. Yet, most people do not know their infection status, and antibody testing is not recommended, partly due to poor test performance. Here, we compared the test performance of the Roche Elecsys HSV-1 IgG and HSV-2 IgG, DiaSorin LIAISON HSV-1/2 IgG, and Bio-Rad BioPlex 2200 HSV-1 and HSV-2 IgG assays with the gold-standard HSV western blot in 1,994 persons, including 1,017 persons with PCR or culture-confirmed HSV-1 and/or HSV-2 infection. Across all samples, the Bio-Rad and Roche assays had similar performance metrics with low sensitivity (<85%) but high specificity (>97%) for detecting HSV-1 IgG and both high sensitivity (>97%) and high specificity (>98%) for detecting HSV-2 IgG. The DiaSorin assay had a higher sensitivity (92.1%) but much lower specificity (88.7%) for detecting HSV-1 IgG and comparatively poor sensitivity (94.5%) and specificity (94.2%) for detecting HSV-2 IgG. The DiaSorin assay performed poorly at low-positive index values with 60.9% of DiaSorin HSV-1 results and 20.8% of DiaSorin HSV-2 results with positive index values <3.0 yielding false positive results. Based on an estimated HSV-2 seroprevalence of 12% in the United States, positive predictive values for HSV-2 IgG were 96.1% for Roche, 87.4% for Bio-Rad, and 69.0% for DiaSorin, meaning nearly one of every three positive DiaSorin HSV-2 IgG results would be falsely positive. Further development in HSV antibody diagnostics is needed to provide appropriate patient care.IMPORTANCESerological screening for HSV infections is currently not recommended in part due to the poor performance metrics of widely used commercial HSV-1 and HSV-2 IgG assays. Here, we compare three Food and Drug Administration (FDA)-cleared automated HSV-1 and HSV-2 IgG assays to the gold-standard western blot across nearly 2,000 samples. We find that not all commercially available HSV assays are created equal, with comparably low sensitivities for HSV-1 IgG across platforms and high false positivity rates for DiaSorin on HSV-2 IgG. This study is the first large-scale comparison of performance metrics for the Bio-Rad and Roche assays in over 10 years. Our study confirms that there remains room for improvement in HSV serological diagnostic testing-especially in regard to low sensitivities for HSV-1 IgG detection-and highlights that some previously less-studied assays may have better performance metrics than previously considered typical of commercially available HSV-2 IgG assays.

Serious neurological adverse events in immunocompetent children and adolescents caused by viral reactivation in the years following varicella vaccination.

Serious adverse events following vaccination include medical complications that require hospitalisation. The live varicella vaccine that was approved by the Food and Drug Administration in the United States in 1995 has an excellent safety record. Since the vaccine is a live virus, adverse events are more common in immunocompromised children who are vaccinated inadvertently. This review includes only serious adverse events in children considered to be immunocompetent. The serious adverse event called varicella vaccine meningitis was first reported in a hospitalised immunocompetent child in 2008. When we carried out a literature search, we found 15 cases of immunocompetent children and adolescents with varicella vaccine meningitis; the median age was 11years. Eight of the children had received two varicella vaccinations. Most of the children also had a concomitant herpes zoster rash, although three did not. The children lived in the United States, Greece, Germany, Switzerland, and Japan. During our literature search, we found five additional cases of serious neurological events in immunocompetent children; these included 4 cases of progressive herpes zoster and one case of acute retinitis. Pulses of enteral corticosteroids as well as a lack of herpes simplex virus antibody may be risk factors for reactivation in immunocompetent children. All 20 children with adverse events were treated with acyclovir and recovered; 19 were hospitalised and one child was managed as an outpatient. Even though the number of neurological adverse events remains exceedingly low following varicella vaccination, we recommend documentation of those caused by the vaccine virus.

Herpes Simplex Virus Infection and in vivo Alzheimer’s Disease Pathologies

AbstractBackgroundInterest in the role of Herpes Simplex Virus (HSV) infection in the pathogenesis of Alzheimer’s disease (AD) has increased in recent years. However, previous studies yielded inconsistent findings and no studies have yet investigated the relationship between HSV infection and in vivo AD pathologies such as beta‐amyloid (Aβ) and tau deposition in brain. We examined whether the level of serum anti‐HSV immunoglobulin G (IgG) antibodies (HSV‐IgG), an index of past infection of HSV, is associated with in vivo Aβ and tau deposition in nondemented individuals. We also investigated the modulating effect of HSV‐IgG titer on the relationship between Aβ and tau deposition.MethodA total of 426 nondemented older individuals (55‐90 years old) were recruited from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE) cohort. All participants underwent comprehensive clinical assessment, [11C]‐Pittsburgh Compound B positron emission tomography (PET), and blood sampling for measurement of serum HSV antibodies. A subset of participants (N = 129) underwent [18F] AV‐1451 PET. Individuals whose HSV‐IgG titer was lower than 25 percentile of the whole group was classified as the HSVlow group, while those with HSV‐IgG titer higher than 25 percentile were classified as the HSVhigh group.ResultThere was no significant difference in age, sex, clinical diagnosis (cognitive normal vs. mild cognitive impairment), and apolipoprotein E e4 positivity (APOE4) between the HSVlow (N = 106) and HSVhigh (N = 320) groups. In terms of AD biomarkers, neither global Aβ nor tau deposition was different between the HSVhigh and HSVlow groups, even after controlling the effect of age, sex, and APOE4. However, there was a significant HSV group x Aβ deposition interaction effect on tau deposition (p = 0.037), suggesting the level of HSV‐IgG modulates the relationship between Aβ and tau deposition. Subsequent subgroup analyses showed a significant positive association between Aβ and tau deposition only in the HSVhigh group (p &lt; 0.001), but not in the HSVlow group.ConclusionOur finding suggests that past HSV infection may aggravate the influence of Aβ on tau deposition. In regard of AD prevention, the result also supports that more attention needed to be paid to controlling HSV infection.

Does genital herpes symptom history predict herpes simplex virus type 2 antibody positivity?

Sexually transmitted infections (STIs) associated with genital ulcer disease due to herpes simplex virus-2 (HSV-2) are a prominent cause of morbidity and mortality. Serologic screening for HSV-2 is recommended only for individuals with genital herpes symptom history. However, no validated symptom screening tool currently exists. Currently asymptomatic adults presenting for routine care at STI clinics in Lima, Peru completed a survey of prior genital herpes symptoms and received HSV-2 serological testing with the Euroimmun Anti-HSV-2 (gG2) ELISA IgG (Lubeck, Germany). A sub-sample of indeterminate results were sent for Western blot confirmatory testing. We assessed associations between past symptoms and anti-HSV-2 positivity and corrected the HSV-2 prevalence by re-classifying indeterminates per Western Blot results. We enrolled 131 participants between July and October 2022. HSV-2 antibody test results found 21.4% positive, 41.2% indeterminate, and 37.4% negative. Excluding indeterminate results, 36.4% were positive. Of participants with no prior symptoms 31.2% tested positive, compared to 35.7% with one prior symptom, 50.0% with 2, and 50.0% with 3+ prior symptoms. Among the sub-sample of indeterminates, 92.6% were confirmed positive by Western Blot, bringing the total estimated proportion of participants with HSV-2 antibodies to 59.5%. Either based on the original classification of HSV-2 antibody status or after incorporation of confirmatory testing results, there was no significant association between symptom history and HSV-2 antibody positivity. With currently available tests, recommendations to screen individuals based on genital herpes symptom history may not be useful. More discriminatory symptom screening tools or HSV-2 antibody tests with better performance are needed.

Prior Herpes Simplex Virus Infection and the Risk of Herpes Zoster.

The incidence of herpes zoster (HZ) has increased in the United States concurrent with decrease in herpes simplex virus (HSV) prevalence. We hypothesized that lack of HSV-elicited cross-reactive immunity to varicella-zoster virus (VZV) results in an increased risk of HZ. Using specimens from the placebo arm of the Shingles Prevention Study, we investigated whether persons who develop HZ are less likely to have prior HSV infection than persons who do not develop HZ, and whether HZ is less severe in persons with HSV than in HSV seronegative persons. We conducted a nested case-control (1:2) study comparing the seroprevalence of HSV-1 and HSV-2 in cases (persons with polymerase chain reaction-confirmed HZ) to age-, sex-, and health-matched controls (persons without HZ). Sera from 639 study participants (213 cases and 426 controls) yielded definitive HSV antibody results and were analyzed. Overall, HSV seropositivity rate was 75%. HSV seronegativity was significantly higher in HZ cases than controls (30.5% vs 22.3%; P = .024), with a 55% higher risk of HZ in HSV seronegative than HSV seropositive participants. HSV seropositivity was associated with more severe HZ (P = .021). Our study demonstrated that prior infection with HSV partly protects against HZ.

P31: Antigenic target, antibody subclass, function and glycans and SARS‐CoV‐2 coinfection impact the placental transfer of herpes simplex virus antibodies

P31: Antigenic target, antibody subclass, function and glycans and SARS‐CoV‐2 coinfection impact the placental transfer of herpes simplex virus antibodies

210 Antibody function, antigenic target and glycans determine the transfer of herpes simplex virus (HSV) antibodies (Abs) from mothers to newborns and transfer is altered by SARS-CoV-2

OBJECTIVES/GOALS: Murine and clinical data suggest that antibody-dependent cellular cytotoxicity (ADCC) is associated with greater protection against disseminated neonatal HSV disease. To quantify the relative transfer of Abs with different functions and targets, we conducted a prospective study of mother-infant term and preterm dyads pre and during COVID-19 METHODS/STUDY POPULATION: Total and HSV lysate, glycoprotein D (gD) and glycoprotein B (gB)-specific IgG, IgG1 and IgG3 as well as HSV neutralizing Abs (nAbs) and ADCC were quantified in paired 3rd-trimester pregnant women and their newborns (cord) blood. Transfer ratios (TR) were defined as cord:maternal Ab levels. IgG1 and IgG3 subclass and gD or gB-specific Abs were isolated by column purification and glycan profiles were assessed by mass spectrometry. The study population included 21 term and 15 preterm dyads who were HSV-1 (+/- HSV-2) seropositive enrolled between 2018-2019 (pre-COVID) and 25 additional HSV-1 (+/- HSV-2) seropositive term dyads whose mothers were SARS-CoV-2 PCR and COVID Ab+ at delivery; 14 were asymptomatic and 11 had mild-moderate COVID disease. None of the mothers had active genital HSV lesions during delivery RESULTS/ANTICIPATED RESULTS: Anti-HSV IgG, IgG1 and IgG3 TR were higher in term vs. preterm dyads (p&lt;0.05). The nAb TR was 2.4 in term vs. 0.8 in preterm (p&lt;0.001) but the ADCC TR was &lt; 1.0 for both. To determine if the latter reflected antigenic target, subclass or glycans, we enriched for gD and gB specific and IgG1 and IgG3 Abs. The gD Abs were IgG1 and had only neutralizing activity. In contrast, gB Abs were polyfunctional and included IgG1 and IgG3 but only the IgG1 Abs had ADCC activity. The gD Abs were enriched for glycans associated with an affinity for the neonatal Fc receptor (FcRn); gB Abs expressed glycans associated with both FcRn and FcγRIIIa binding. There was no significant difference in total HSV-specific IgG TR in pre-COVID vs post-COVID dyads but the nAb TR was lower (p=0.018) and ADCC TR higher (p&lt;0.001) in the COVID compared to pre-COVID cohort DISCUSSION/SIGNIFICANCE: HSV ADCC Abs, which may provide greater protection than nAbs against neonatal disease, transfer poorly particularly to preterm newborns. However, in the setting of SARS-CoV-2, the TR of HSV ADCC is significantly higher. This may reflect alterations in the placental architecture and/or glycan composition which is currently being investigated.

B cells join T cell clusters in the host response to recurrent herpes simplex virus 2 infection.

Recurrent genital herpes lesions are infiltrated by various leukocytes, yet the role of B cell subsets in this process is unknown. In this issue of the JCI, Ford et al. describe the presence and antibody-secreting role of local B cell populations in herpes simplex virus 2 (HSV-2) recurrent lesions. The authors analyzed a comprehensive array of sequential skin biopsy specimens from HSV-2-infected patients over time and at various stages of infection. Using immunofluorescence and in situ hybridization, the authors show the presence of rare IgD+ naive B cells and IgG-expressing antibody-secreting cells (ASCs) in recurrent HSV-2 lesions embedded in CD4+ T cell-rich dermal immune infiltrates, levels of which transiently increase during lesion reactivation and healing. Notably, local increases in HSV-2-specific antibodies in recurrent lesions were detected, whereas serum HSV-2 antibody levels remained stable. Future research is needed to understand the precise role of these tissue-visiting B cells in disease resolution.

S2692 Fulminant Hepatic Failure Caused by Primary Herpes Simplex Virus Infection

INTRODUCTION: Herpes simplex virus (HSV) types 1 and 2 are common lifelong infections. Disseminated HSV is a rare but fatal complication of HSV infection, traditionally affecting immunocompromised individuals. Here we present a case of an immunocompetent 72-year old male with primary disseminated HSV-2 whose clinical picture rapidly progressed from abdominal pain to fulminant hepatic failure and death. CASE DESCRIPTION/METHODS: A 72-year-old Caucasian man presented to the ER for abdominal pain and sore throat. His only chronic medical conditions were BPH and hypertension. On presentation he was febrile (38.9oC) and tachycardic (117). Physical exam was remarkable for pharyngeal erythema with white ulcerative lesions and diffuse abdominal tenderness. Laboratory evaluation revealed an elevated WBC count (14.6), transaminitis (AST 336 U/L, ALT 486 U/L, ALP 153 U/L), and normal total bilirubin. CT abdomen revealed hepatomegaly, and the patient was admitted for treatment of sepsis. Blood serological studies at time of admission were negative for Hepatitis A/B/C, HSV 1/2, CMV, and EBV (immunoglobulin (Ig)M). He continued to be febrile despite broad spectrum antibiotics and LFTs trended up into the 1,000s so a liver biopsy was performed on day 8. On day 9, he developed a few small blisters on his right thigh and abdomen. These were biopsied and the patient was placed on empiric acyclovir with new studies ordered. On day 14 biopsy results from both the leg and liver showed disseminated HSV. Repeat serologies then confirmed disseminated HSV with high titers for HSV-2 IgM. Despite 2 weeks of IV acyclovir the patient declined rapidly, was transferred to hospice on day 21, and died shortly after. DISCUSSION: The diagnosis of disseminated HSV is typically made via serological studies demonstrating high titers of IgM HSV antibodies. However, this method of diagnosis is flawed in that it misses early primary infections, as was the case in our patient. Based on literature review by Levitsky et al. early empiric treatment of HSV hepatitis with acyclovir leads to a significant decrease in mortality. Because HSV hepatitis is difficult to diagnose, treatment is often delayed and the infection progresses to acute liver failure in 74% of cases, with a 90% mortality rate. This case highlights two key barriers to achieving better outcomes in HSV hepatitis management: lack of sensitive screening tests and lack of standard guidelines on the use of empiric antivirals in cases of fulminant hepatic failure of unclear etiology.Figure 1.: Liver immunohistochemical staining for HSV-2.Figure 2.: Skin lesions right lower extremity.

Clinico-Pathological Profiles and Outcomes of Acute Viral Encephalitis in Children

Background: Encephalitis is an acute inflammatory process that affects brain tissue and is almost always accompanied by inflammation of the adjacent meninges. The disease is most commonly caused by viral infection.&#x0D; Objective: The purpose of the present study was to determine the clinical and cerebrospinal fluid profile of childhood encephalitis and to document Herpes simplex antibody status in cerebrospinal fluid.&#x0D; Methodology: This descriptive analytical study was conducted in Department of Paediatrics of Shaheed Suhrawardy Medical College Hospital and Dhaka Medical College Hospital from May 2011 to October 2011. A total of 30 children of encephalitis were included in this study. Cerebrospinal fluid (CSF) routine and Herpes Simplex virus (HSV) antibody in CSF were done to all patient.&#x0D; Result: Fever and convulsion was found in 29(96.7%) and 28(93.3%) cases respectively in studied patients. Altered level of consciousness was present in 29(96.7%) cases. Fever, convulsion and altered level of consciousness was statistically significant (p&lt;0.05). Glasgow coma scale (GCS) between 4 to 8 was found in 27 (90%) cases. Signs of meningeal irritation and cranial nerve palsies was found in 9 (30%) and 4 (13.3%) cases respectively. Exaggerated deep reflex was found in 23 (76.6%) cases whereas diminished deep reflex was found in 7 (23.3 %) cases. In cytological study of CSF, lymphocyte was found in 28 (93.3%) patients. Raised protein was found in 16(53.3%) and normal in 14 (46.7%) cases. Among the 30 studied cases 9(30%) cases were IgG positive for HSV, 21 (70.0%) were IgG negative and none were IgM positive.&#x0D; Conclusion: Fever, convulsion, altered sensorium and low GCS were common clinical profile in children. Normal colour, increase lymphocyte count, normal sugar level were significant findings in CSF study.&#x0D; Bangladesh Journal of Infectious Diseases 2020;7(1):8-11

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.

Characterization of polyclonal antibodies to Herpes Simplex Virus types 1 and 2

ABSTRACTInfections with herpes simplex virus (HSV) types 1 and 2 have been linked to oral, facial, genital lesions, as well as some visceral organ changes in patients under immunosuppressed conditions. Immunohistochemistry (IHC) with HSV antibodies is used for identification of the viruses in tissue samples. In this study, two polyclonal antibodies, prepared separately with HSV-1 and HSV-2 immunogens, were characterized in comparison to a monoclonal antibody to HSV-1 (10A3). The polyclonal anti-HSV-1 and monoclonal antibody 10A3 were shown to be reactive to viral proteins of both HSV-1 and HSV-2 on Western blots, while the polyclonal anti-HSV-2 was reactive to HSV-2 proteins, but not to those of HSV-1. Cross-reactivity was not observed to proteins of six other frequently encountered herpes viruses. IHC characterization was performed on 29 cases of HSV-infected tissue samples, 61 samples infected with other herpes viruses and 35 samples without known infection. By IHC, the polyclonal anti-HSV-1 and a monoclonal antibody 10A3 exhibited a signal, mainly in a nuclear pattern, in all of the HSV-infected samples and not in other tissue types. A positive signal, mainly in the cytoplasm, was identified with the polyclonal anti-HSV-2 in 21 of the 29 HSV-infected samples. Genotyping analysis was successful in 14 of the HSV-infected samples, with IHC HSV-2 positivity correlative to the HSV-2 genotype. The results demonstrate that these antibodies are useful tools for identification of HSV-1 and HSV-2, and their combinatorial application may help to distinguish between these two types of infection.

Herpes Simplex Virus, APOEɛ4, and Cognitive Decline in Old Age: Results from the Betula Cohort Study.

Herpes simplex virus (HSV) has been suggested to play a role in Alzheimer's disease (AD) development. The aim of the present study was to investigate the early AD-related symptom episodic memory decline in relation to HSV and carriage of allele 4 of the apolipoprotein E gene (APOEɛ4) in a large population-based cohort with a long follow-up time. The study included 3,413 persons, with longitudinal data available for 1,293 persons with a mean follow-up time of 11.6 years. The associations between HSV carriage, APOEɛ4 carriage, and episodic memory was investigated at baseline, as well as in longitudinal analyses where individuals with and without HSV antibodies (HSV1/2 non-specific) were matched and episodic memory decline compared. Cross-sectional analyses revealed an age-dependent association of HSV carriage with lower episodic memory function, particularly among APOEɛ4 carriers (p = 0.008). Longitudinal analyses showed an increased risk of episodic memory decline in HSV carriers (≥65 years: p < 0.001, all ages: non-significant), and a significant interaction between HSV and APOEɛ4 for episodic memory decline (p < 0.001). In this large population-based cohort study, both cross-sectional and longitudinal results support an association between HSV carriage and declining episodic memory function, especially among APOEɛ4 carriers. The results strengthen the hypothesis that HSV is associated with AD development.

Delayed facial nerve palsy after vestibular schwannoma surgery

Background: Facial nerve dysfunction may occur immediately after vestibular schwanoma surgery. Electromyographyc monitoring of motor cranial nerves during cerebellopontine angle surgery has become an essential tool. Although delayed onset of facial nerve dysfunction hours to months following vestibular schwanoma surgery are rare. Case description: We describe the case of a 70-years-old male who was admitted with a left side tinnitus and hearing loss of the last 3 years. Magnetic resonance imaging (MRI) T1-weighted demonstrated an isointensity lesion, 30mm in diameter, at the left cerebello-pontine angle with a small portion in the internal auditory canal. The patient was surgically treated by means of a standart suboccipital retrosigmoid approach. The facial nerve was monitored by continuously during surgery. Surgical removal was macroscopically complete. The facial nerve was well-preserved during surgery and showed at the end of the procedure normal electromyographic activity. The patient did well postoperatively and was discharged at the 4th postoperative day and facial function was normal (House-Brackmann grade I). On the 10th postoperative day he notices difficult closing his left eye that progressed to complete facial nerve palsy (House-Brackmann grade III). Steroid therapy was performed for five days associated with physical therapy. One month later his facial nerve function had completely recovered. After six months, the patient remains asymptomatic and neurologically intact. MRI obtained at the 16th postoperative day showed intense enhancement of the intracranial facial nerve segment and also demonstrated no residual tumor. Immunological study at the time of onset showed herpes simplex virus antibody titer normal as well as those for herpes zoster virus. Conclusions: Delayed facial nerve palsy remains an under reported and consequently not very known phenomenon in the neurosurgical practice and literature. Because of the 2009favorable rate of recovery, patients should be reassured in the interim and should not undergo any corrective surgical procedures to improve facial nerve function. Delayed facial nerve palsy is uncommon after vestibular schwannoma surgery. Excellent recovery of facial nerve function to the original postoperative status nearly always occurs in those circumstances.

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.

Decreased HHV-6 IgG in Alzheimer's Disease.

Human herpesviruses have previously been implicated in the pathogenesis of Alzheimer’s disease (AD) but whether they are causal, facilitating, or confounding factors is yet to be established. A total of 50 AD subjects and 52 non-demented (ND) controls were analyzed in a multiplex assay for IgG reactivity toward herpes simplex virus (HSV), varicella zoster virus (VZV), cytomegalovirus (CMV), and human herpesvirus 6 (HHV-6). The HHV-6 IgG reactivity was significantly lower in AD subjects compared to ND controls, whereas there were no differences in HSV, VZV, or CMV antibody levels between the groups. Analysis of peripheral blood mononuclear cells with a subtype-specific HHV-6 PCR revealed no signs of reactivation, as AD and ND subjects presented with comparable HHV-6 DNA levels in PBMCs, and all positive samples were of subtype B. Whether HHV-6 is a factor in AD remains to be elucidated in future studies.

Genital Ulcers in Women with HIV Proposed Revision on Management Algoritm

More than 100,000 people has been infected by HIV (Human Immunodeficiency Virus) in Indonesia. Mucocutaneous disorders occur in most patients with HIV during the course of the disease, it is caused by acquired immunodeficiency or the effects of the HIV therapy. One of the most important clinical manifestations is genital ulcers. A specific attention is needed to identify the clinical manifestations of genital ulcers in HIV patients to find the etiology so that the treatment of the case can be more appropriate. There are 4 cases of genital ulcers in women with AIDS (Acquired Immune Deficiency Syndrome). Both VDRL test (Venereal Disease Reseach Laboratory) and TPHA (Trepenoma pallidum Haemagglutination) test gave negative results. Two cases has successful therapy with acyclovir 400 mg three times for 2 weeks. Test results for herpes simplex antibodies is 2 positive. The incidence of genital ulcers, especially in the chronic form, increases along with the incidence of the growing AIDS epidemic. A prospective study in Paris shows that the most common cause of genital ulcers in patients with AIDS is syphilis. All of these four cases have negative results of VDRL and TPHA, so it is necessary to consider another diagnosis as the cause of genital ulcers in immunocompromised patients that often give atypical clinical symptoms. The accuracy of the diagnosis is necessary to provide adequate treatment, especially in immunocompromised patient.

Non-specific immunological effects of selected routine childhood immunisations: systematic review

Objective To identify and characterise non-specific immunological effects after routine childhood vaccines against BCG, measles, diphtheria, pertussis, and tetanus.Design Systematic review of randomised controlled trials, cohort studies, and case-control studies.Data...

Herpes simplex virus type 1 and type 2 in the Netherlands: seroprevalence, risk factors and changes during a 12-year period.

BackgroundGenital herpes results in considerable morbidity, including risk of neonatal herpes, and is increasingly being caused by Herpes Simplex Virus (HSV) type 1. Possibly children are less often HSV-1 infected, leaving them susceptible until sexual debut. We assessed changes in the Dutch HSV-1 and HSV-2 seroprevalence over time and determinants associated with HSV seropositivity.MethodsWe used data from two population-based seroepidemiological studies conducted in 1995–6 and 2006–7 with a similar study design. Serum samples of 6 months to 44-year-old participants were tested for type-specific HSV antibodies using HerpesSelect® with a cut-off level of >1.10 for seropositivity. Age and sex-specific HSV-1 and HSV-2 seroprevalence was weighted for the Dutch population. Logistic regression was performed to investigate determinants associated with HSV seropositivity.ResultsOverall, weighted HSV-1 seroprevalence was significantly lower in 2006–7 [42.7 % 95 % confidence interval (CI) 39.9-45.4] than in 1995–6 (47.7 % 95 % CI 44.8-50.7), especially among 10- to 14-year-olds. Overall, weighted HSV-2 seroprevalence remained stable: 6.8 % in 1995–6 and 6.0 % in 2006–7. Adults who ever had sexual intercourse were more often seropositive for HSV-1 [adjusted Odds Ratio (aOR) 1.69 95 % CI 1.33-2.16] and HSV-2 (aOR 2.35 95 % CI 1.23-4.52). Age at sexual debut was the only sexual risk determinant associated with HSV-1 seropositivity.ConclusionsBecause of the lower HSV-1 seroprevalence in 2006–7 compared to 1995–6, more adults are susceptible to genital HSV-1, including women of reproductive age. Given the higher risk of neonatal herpes when HSV is acquired during pregnancy, prevention and control measures during pregnancy also targeting HSV-1, are important.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-1707-8) contains supplementary material, which is available to authorized users.