Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) are chronic, highly prevalent viral infections that cause significant morbidity around the world. HSV-2 is sexually transmitted and is the leading cause of genital ulcer disease (GUD). It also increases the risk of HIV acquisition, fueling the HIV epidemic. HSV-1 is typically acquired in childhood through nonsexual contact and contributes to oral and ocular disease, but it can also be sexually transmitted to cause GUD. Both HSV-1 and HSV-2 cause neonatal herpes and neurologic disease. Given the ubiquitous nature of HSV-1 and HSV-2 infections and the limited existing prevention and control measures, vaccination would be the most efficient strategy to reduce the global burden of morbidity related to HSV infection. Vaccine strategies include prophylactic vaccination, which would prevent infection among susceptible persons and would likely be given to adolescents, and therapeutic vaccinations, which would be given to people with symptomatic genital HSV-2 infection. This document discusses the vaccine value profile of both types of vaccines. This \'Vaccine Value Profile\' (VVP) for HSV is intended to provide a high-level, holistic assessment of the information and data that are currently available to inform the potential public health, economic and societal value of pipeline vaccines and vaccine-like products. This VVP was developed by subject matter experts from academia, non-profit organizations, government agencies and multi-lateral organizations. All contributors have extensive expertise on various elements of the HSV VVP and collectively aimed to identify current research and knowledge gaps. The VVP was developed using only existing and publicly available information.

We present a case of a primigravida in her 30s who had a caesarean delivery of dichorionic diamniotic twins at 33 weeks of gestation. Her postpartum course was complicated by a herpes simplex virus (HSV) infection of her nipple, found after her neonates were diagnosed with HSV encephalitis. She was evaluated at her 3-week postpartum visit and reported that her neonates were concurrently admitted to the neonatal intensive care unit with disseminated neonatal HSV-1. The patient and her partner were in a monogamous relationship with no known history of HSV. Physical examination demonstrated a vertical fissure on the face of her right nipple and a small cluster of vesicles on her left hand. PCR swabs of the lesions were positive for HSV-1 at both locations. The patient was started on oral valacyclovir 1000 mg two times per day, topical acyclovir ointment applied 4-6 times per day and mupirocin ointment applied 3 times per day to her breast with resolution of her breast lesions. She was able to continue expressing her breastmilk with the help of a pump and then resumed breastfeeding once her infection was cleared. Her infants recovered after prolonged parenteral antiviral therapy with age-appropriate development at follow-up.

BACKGROUND: In the conjugate vaccine era, viruses are the most common cause of meningitis. Here, we evaluated epidemiological trends in laboratory-confirmed viral meningitis across all age-groups over an 11-year period in England.
METHODS: In England, hospital laboratories routinely report laboratory-confirmed infections electronically to the UK Health Security Agency. Records of positive viral detections in cerebrospinal fluid during 2013-2023 were extracted. Incidence rates with confidence intervals were calculated using mid-year resident population estimates.
RESULTS: There were 22,114 laboratory-confirmed viral meningitis cases, including 15,299 cases during 2013-19 (pre COVID-19), with a gradual increase in incidence from 3.5/100,00 (95%CI: 3.3-3.6) to 3.9/100,000 (95%CI: 3.6-4.1). During 2020-21 when pandemic restrictions were in place, there were 2061 cases (1.8/100,000; 1.7-1.9), which increased to 4754 (4.2/100,000; 4.0-4.3) during 2022-23 (post pandemic restrictions). Infants aged <3 months accounted for 39.4% (8702/22,048) of all cases, with a stable incidence 2013-19 (504/100,000, 95%CI: 491-517), followed by a significant decline during 2020-21 (204/100,000; 188-221) and then an increase during 2022-23 (780/100,000; 749-812), with enteroviruses being the commonest cause (84.9%, 7387/8702; 424.74/100,000; 95%CI: 415.12-434.51), followed by parechoviruses (9.1%, 792/8702; 45.54/100,000; 95%CI: 42.42-48.82) and herpes simplex virus (4.4%, 380/8702; 21.85/100,000; 95%CI: 19.71-24.16). Pandemic restrictions were associated with significant declines in the incidence of enterovirus (77.7%) and parechoviruses (64% lower), with rebounds after societal restrictions were lifted.
CONCLUSIONS: Rates of viral meningitis have returned to pre-pandemic levels since societal restrictions were lifted. The highest incidence of viral meningitis remains in infants aged <3 months and most commonly due to enteroviral infection.

Herpes simplex virus (HSV) encephalitis, predominantly caused by HSV-1, presents with significant morbidity and mortality challenges. This research investigates the particular role of adjunctive corticosteroid therapy in fulminant HSV encephalitis through in-depth analyses of two contrasting cases. Corticosteroids show potential benefits to improve an exaggerated immune response and limit viral dissemination within the brain. Daily assessments and frequent neuroimaging, particularly using magnetic resonance imaging, aid in the management of fulminant cases. Although existing evidence relies on limited case series and retrospective comparisons, the results of the present study emphasize the necessity for large-scale controlled trials to establish definitive guidelines. The discretion of the treating neurologist governs the decision to implement corticosteroids, emphasizing the imperative need for continued research and evidence-based strategies for this challenging neurological condition.

This report summarizes incidence rates and trends of sexually transmitted infections (STIs) from 2015 through 2023 among active component service members of the U.S. Armed Forces. The data compiled for this report are derived from the medical surveillance of chlamydia, gonorrhea, and syphilis as nationally notifiable diseases. Case data for 2 additional STIs, human papilloma virus (HPV) and genital herpes simplex virus (HSV), are also presented. The crude total case rates of chlamydia and gonorrhea initially rose by an average of 6.7% and 9.8% per year, respectively, until 2019. From 2020 onwards, rates steadily declined. By 2023, chlamydia rates had dropped by approximately 39%, while gonorrhea rates had fallen by more than 40% for female, and 19% for male, service members. Initially syphilis increased, on average, 10% annually from 2015 to 2019, then declined in 2020, but resumed its upward trend through 2023, nearly doubling the 2015 rate in 2023. The total crude annual incidence rates of genital HPV and HSV exhibited downward trends in general over the surveillance period, decreasing by 30.7% and 24.7%, respectively. Age- and gender-adjusted case rates for chlamydia, gonorrhea, and syphilis remain elevated within the U.S. Armed Forces compared to the general U.S. population, which may be due to factors that include mandatory STI screening, more complete reporting, incomplete adjustment for age distribution, and inequitable comparisons between the military active duty and general U.S. populations. Social restrictions enacted during the COVID-19 pandemic may have contributed to declines in true case rates and screening coverage.

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UNASSIGNED: Herpes simplex virus encephalitis (HSVE) is associated with significant morbidity and mortality. Here, we present the occurrence of HSVE in a 36-year-old immunocompetent patient following craniotomy for a traumatic acute subdural hematoma (ASDH).
UNASSIGNED: Imaging after four days of progressive headache following a fall with head-strike demonstrated a 1 cm thick left holohemispheric ASDH with significant cerebral compression, edema, and 8 mm of left-to-right midline shift, and an emergent craniotomy and ASDH evacuation were performed, with additional treatment needed for reaccumulation. Postoperatively, the patient developed a worsening leukocytosis, became febrile, and was hypotensive requiring vasopressor support.
UNASSIGNED: Despite empiric antibiotics, the patient remained persistently febrile with significant leukocytosis. Repeat head CT showed a new left insular hypodensity and a subsequent viral encephalitis panel was positive for HSV-1. The patient was then started on intravenous acyclovir, with progressive neurological exam improvement. Of note, the patient was noted to have a positive serum HSV-1 IgG antibody titer, indicative of prior infection.
UNASSIGNED: Given the known systemic immunosuppression in brain injury and the high prevalence of HSV seropositivity, clinicians should consider the possibility of HSVE from HSV reactivation in TBI patients with persistent fever, leukocytosis, and/or neurological deficits without an obvious etiology.

UNASSIGNED: Oral herpes infections caused by herpes simplex virus type 1 (HSV-1) are one of the most common in the human population. Recently, they have been classified as an increasing problem in immunocompromised patients and those suffering from chronic inflammation of the oral mucosa and gums. Treatment mainly involves nucleoside analogues, such as acyclovir and its derivatives, which reduce virus replication and shedding. As drug-resistant strains of herpes emerge rapidly, there is a need for the development of novel anti-herpes agents. The aim of the study was to design an antiviral peptide, based on natural compounds, non-toxic to the host, and efficient against drug-resistant HSV-1. Here, we designed a lysine-rich derivative of amphibian temporin-1CEb conjugated to peptides penetrating the host cell membrane and examined their activity against HSV-1 infection of oral mucosa.
UNASSIGNED: We assessed the antiviral efficiency of the tested compound in simple 2D cell models (VeroE6 and TIGKs cells) and a 3D organotypic model of human gingiva (OTG) using titration assay, qPCR, and confocal imaging. To identify the molecular mechanism of antiviral activity, we applied the Azure A metachromatic test, and attachment assays techniques. Toxicity of the conjugates was examined using XTT and LDH assays.
UNASSIGNED: Our results showed that temporin-1CEb analogues significantly reduce viral replication in oral mucosa. The mechanism of peptide analogues is based on the interaction with heparan sulfate, leading to the reduce attachment of HSV-1 to the cell membrane. Moreover, temporin-1CEb conjugates effectively penetrate the gingival tissue being effective against acyclovir-resistant strains. Collectively, we showed that temporin-1CEb can be regarded as a novel, naturally derived antiviral compound for HSV-1 treatment.

Previous exposure to Epstein-Barr virus (EBV) is strongly associated with the development of multiple sclerosis (MS). By contrast, past cytomegalovirus (CMV) infection may have no association, or be negatively associated with MS. This study aimed to investigate the associations of herpesvirus infections with MS in an Italian population. Serum samples (n = 200) from Italian people with multiple sclerosis (PwMS) classified as the relapsing-and-remitting clinical phenotype and (n = 137) healthy controls (HCs) were obtained from the CRESM Biobank, Orbassano, Italy. Both PwMS and HCs samples were selected according to age group (20-39 years, and 40 or more years) and sex. EBV virus capsid antigen (VCA) IgG, EBV nucleic acid-1 antigen (EBNA-1) IgG, CMV IgG, herpes simplex virus (HSV) IgG, and varicella zoster virus (VZV) IgG testing was undertaken using commercial ELISAs. EBV VCA IgG and EBNA-1 IgG seroprevalences were 100% in PwMS and 93.4% and 92.4%, respectively, in HCs. EBV VCA IgG and EBNA-1 IgG levels were higher (p < 0.001) in PwMS compared with HCs. For PwMS, the EBNA-1 IgG levels decreased with age, particularly in females. The CMV IgG seroprevalence was 58.7% in PwMS and 62.9% in HCs. CMV IgG seroprevalence increased with age. The HSV IgG seroprevalence was 71.2% in PwMS and 70.8% in HCs. HSV IgG levels were lower (p = 0.0005) in PwMS compared with HCs. VZV IgG seroprevalence was 97.5% in PwMS and 98.5% in HCs. In the population studied, several herpesvirus infections markers may have been influenced by the age and sex of the groups studied. The lack of a negative association of MS with CMV infection, and the observation of lower levels of HSV IgG in PwMS compared with HCs are findings worthy of further investigation.

We report a 42-year-old female with confirmed recurrent genital herpes (HSV-2), which was well controlled on suppressive antiviral therapy with aciclovir 400 mg twice daily. The patient required bariatric surgery in order to manage what was deemed a dangerously high BMI. A Roux-en-Y procedure was performed which effectively reduced her weight; however, herpes suppression become ineffective post operatively, with serious herpes related complications, despite increasing the total dose of aciclovir and the frequency from twice daily to three times a day. Complete herpes control was restored by changing therapy to valaciclovir 500 mg twice daily. The Roux-en-Y procedure is the most common form of bariatric surgery. Consequences on the efficacy of different herpes antivirals can be predicted from what is known of their properties and sites of absorption. Similar problems with herpes virus suppression may be avoided by an anticipated change in therapy preoperatively.