Genital Herpes Research Articles

Next-generation 3D printed multipurpose prevention intravaginal ring for prevention of HIV, HSV-2, and unintended pregnancy

Globally, nearly half of all pregnancies are unintended, ~1.3 million new human immunodeficiency virus (HIV) infections are reported every year, and more than 500 million people are estimated to have a genital herpes simplex virus (HSV-2) infection. Here we report the first 3D printed multipurpose prevention technology (MPT) intravaginal ring (IVR) for prevention of HIV, HSV-2, and unintended pregnancy. The IVRs were fabricated using state-of-the-art Continuous Liquid Interface Production (CLIP™) 3D printing technology using a biocompatible silicone-urethane based resin. Anti-HIV drug (Dapivirine, DPV), anti-herpes drug (Pritelivir, PTV) and a contraceptive drug (Levonorgestrel, LNG) were loaded in a macaque size IVR (25 mm outer diameter, OD; 6.0 mm cross-section, CS) allometrically scaled from the human size (54 mm OD; 7.6 mm CS) IVR analogue. All three active pharmaceutical ingredients (APIs) were loaded in the IVR using a single-step drug loading process driven by absorption. DPV, PTV, and LNG elicited zero-order release kinetics in vitro in simulated vaginal fluid (SVF) at pH 4 and pH 8 relevant to human and macaque vaginal pH respectively. CLIP 3D printed MPT IVRs remained stable after 6 months of storage at 4 °C with no change in physical, dimensional, or mechanical properties and no change in drug concentration and absence of drug degradation byproducts. The MPT IVRs elicited sustained release of all three APIs in macaques for 28 days with median plasma concentrations of 138 pg/mL (DPV), 18,700 pg/mL (PTV), and 335 pg/mL (LNG). Safety studies demonstrated that the MPT IVRs were safe and well tolerated in the macaques with no observed change or abnormalities in vaginal pH and no significant changes in any of the 22 mucosal cytokines and chemokines tested including pro-inflammatory (IL-1β, IL-6, IL-8, IFN-γ, TNF-α, IL-17, IL-18) and anti-inflammatory (IL-10, IL-12) cytokines while the MPT IVR was in place or after its removal. Additionally, MPT IVRs elicited no observed alterations in systemic CD4+ and CD8+ T cells during the entire study. Collectively, the proposed MPT IVR has potential to expand preventative choices for young women and girls against unintended pregnancy against two highly prevalent sexually transmitted infections (STIs).

HPV Vaccines

Human papillomavirus (HPV) is a double-stranded DNA virus and a source of infection that primarily affects the skin and mucous membranes. It can be transmitted through sexual contact and contaminated surfaces. There are over 200 genotypes of HPV, approximately 40 of which infect the anogenital region. High-risk HPV types, such as HPV-16 and HPV-18, can lead to the development of various cancers, particularly cervical cancer. Factors that increase the risk of transmission include having multiple sexual partners, early initiation of sexual activity, and having an uncircumcised male partner. Low socioeconomic status, poor nutrition, immunosuppression, and co-infections with HIV, genital herpes, or chlamydia can result in persistent and severe HPV infection. Three types of vaccines have been developed against HPV: bivalent, quadrivalent, and nonavalent vaccines. The bivalent vaccine provides protection against HPV-16 and HPV-18; the quadrivalent vaccine is effective against HPV-16, HPV-18, as well as HPV-6 and HPV-11. The nonavalent vaccine offers the broadest protection, covering nine different types of HPV. All vaccines are approved for males and females aged 9 and older. Vaccination before the onset of sexual activity significantly increases protection against cervical cancer.

Effects and Mechanisms of Lactobacillus Probiotics in Maintaining Women’s Vaginal Health: A Review

Probiotics are beneficial living microorganisms. They are useful to vaginal health when consumed in suitable doses. The dominant species included in probiotics are Lactobacillus. We can get these microbes naturally or commercially utilize them as functional food. Lactobacillus species form 70% of inhabitant bacteria in females compared to other warm-blooded animals. The prevalent Lactobacillus species are L. crispatus, L. gasseri, L. iners and L. jensenii. Because of the development of antibiotic resistance mechanisms, the beneficial relationship between humans and probiotics has been discussed for several years. Lactobacillus prevents the attachment of pathogens by using several mechanisms, for example, by increasing estrogen levels, production of lactic acid, lowering pH 4.0-4.5 to provide an acidic environment, release of hydrogen peroxide, bacteriocins and bacteriocins-like substances, adhesion and colonization properties. Lactobacillus prevent the entry and attachment of pathogenic bacteria, thus not only helping to control and manage different gynecological conditions like bacterial vaginosis, endometriosis, vulvovaginal candidiasis and genitourinary syndrome of menopause but also infections that can spread through sexual contacts such as gonorrhea, chlamydia, genital herpes, Human papillomavirus infections (HPV). Overall, the use of probiotics in improving vaginal health is beneficial, easy and cost-effective but the use of probiotics in HPV clearance is not quite beneficial. So, more work should be done on HPV preventive vaccines.

Seroprevalence of herpes simplex virus 2 infection among commercial sex workers in Colombo, Sri Lanka

Background: Herpes Simplex Virus Type 2 (HSV2) causes genital herpes, an incurable, lifelong sexually transmitted infection (STI). This study was conducted to describe the seroprevalence and associated factors of HSV2 infection in a cohort of Female Sex Workers (FSWs). Methods: A descriptive cross-sectional study was conducted on 136 FSWs who attended the central STD Clinic, in Colombo. They were assessed using an interviewer-administered questionnaire followed by serum sampling. Serum samples were tested for HSV2 IgG using an enzyme immunoassay specific for glycoprotein gG2 of HSV2. Results: HSV2 seroprevalence of FSW was 66.9% (91/136) of which only 14.3% (13/91) reported a history of genital infection. Age ≥35 years (OR 3.35, 95%CI 1.54-7.31, p=0.002), education ≥ grade 5 (OR 8.35, 95%CI 13.1- 64.7, p<0.001), lifetime sexual partners ≥ 200 (OR 5.33, 95% CI 2.3-12.36), p<0.001), duration of sex work ≥1 year (OR 4.5, 95% CI 2.09-9.65, p<0.001) and history of STI (OR 4.52, 95% CI 1.9-10.78, p<0.001) were statistically significant risk factors for high HSV2 prevalence. Consistent condom use by commercial partners in the last 3 months was not a significant protective factor in preventing HSV2 infection (OR 0.44, 95% CI 0.15-1.26, p = 0.12) in this cohort. Conclusions: The seroprevalence of HSV2 is high in this population and most of them did not report any genital infection. Multiple risk factors for higher prevalence were observed. Findings support the need for regular surveillance, monitoring of HSV-2 infection in high-risk populations, and expanding awareness of HSV-2 infection in the country.

Vaginal lactobacilli produce anti-inflammatory β-carboline compounds.

The optimal vaginal microbiome is a Lactobacillus-dominant community. Apart from Lactobacillus iners, the presence of Lactobacillus species is associated with reduced vaginal inflammation and reduced levels of pro-inflammatory cytokines. Loss of Lactobacillus-dominance is associated with inflammatory conditions, such as bacterial vaginosis (BV). We have identified that Lactobacillus crispatus, a key vaginal bacterial species, produces a family of β-carboline compounds with anti-inflammatory activity. These compounds suppress nuclear factor κB (NF-κB) and interferon (IFN) signaling downstream of multiple pattern recognition receptors in primary human cells and significantly dampen type I IFN receptor (IFNAR) activation in monocytes. Topical application of an anti-inflammatory β-carboline compound, perlolyrine, was sufficient to significantly reduce vaginal inflammation in a mouse model of genital herpes infection. These compounds are enriched in cervicovaginal lavage (CVL) of healthy people compared with people with BV. This study identifies a family of compounds by which vaginal lactobacilli mediate host immune homeostasis and highlights a potential therapeutic avenue for vaginal inflammation.

Herpes Simplex Virus Type 2 Blocks IFN-β Production through the Viral UL24 N-Terminal Domain-Mediated Inhibition of IRF-3 Phosphorylation.

Herpes simplex virus type 2 (HSV-2) is a sexually transmitted virus, the cause of genital herpes, and its infection can increase the risk of HIV-1 infection. After initial infection, HSV-2 can establish lifelong latency within the nervous system, which is likely associated with the virus-mediated immune evasion. In this study, we found that HSV-2 UL24 significantly inhibited the activation of the IFN-β promoter and the production of IFN-β at both mRNA and protein levels. Of importance, the inhibitory effect of HSV-2 on IFN-β production was significantly impaired in the context of HSV-2 infection when UL24 was knocked down. Additional studies revealed that, although the full-length HSV-2 UL24 affected cell cycle and viability to some extent, its N-terminal 1-202AA domain showed no obvious cytotoxicity while its C-terminal 201-281 AA domain had a minimal impact on cell viability. Further studies showed that the N-terminal 1-202 AA domain of HSV-2 UL24 (HSV-2 UL24-N) was the main functional region responsible for the inhibition of IFN-β production mediated by HSV-2 UL24. This domain significantly suppressed the activity of RIG-IN, MAVS, TBK-1, IKK-ε, or the IRF-3/5D-activated IFN-β promoter. Mechanistically, HSV-2 UL24-N suppressed IRF-3 phosphorylation, resulting in the inhibition of IFN-β production. The findings of this study highlight the significance of HSV-2 UL24 in inhibiting IFN-β production, revealing two potential roles of UL24 during HSV-2 infection: facilitating immune evasion and inducing cell cycle arrest.

Global, Regional, and National Trends Analysis in Incidence of Genital Herpes Among the Population Aged 15-49 Years - Worldwide, 1990-2021.

Genital herpes infection is a chronic condition that can cause recurrent symptoms, significantly affecting both quality of life and sexual relationships. However, there is currently no available data on the global trends and regional variations in the incidence of genital herpes among individuals of reproductive age. From 1990 to 2021, there was a 51.97% increase in global incident cases of genital herpes among individuals aged 15-49 years. The incidence rates also rose in low-middle socio-demographic index region, South Asia, Southern Sub-Saharan Africa, and Central Europe. Among these regions, countries in Southern Sub-Saharan Africa experienced the highest burden of genital herpes among individuals aged 15-49 years. Given the rise in global incident cases and incidence rates in some regions among individuals of reproductive age from 1990 to 2021, it is imperative to prioritize the implementation of preventive strategies and interventions for genital herpes infection. This includes a significant focus on the development of vaccines.

The application of photodynamic therapy in recurrent genital herpes

BackgroundFrequently recurrence of genital herpes imposes significant physical and psychological burdens on patients, while existing treatments are often ineffective in preventing recurrence. Previous studies have indicated that photodynamic therapy (PDT) showed promising outcomes in the treatment of labial herpes simplex virus (HSV) infections; however, its efficacy for genital herpes remained unclear. MethodThe study screened patients with genital herpes at Daping Hospital from July 2020 to May 2024. Patients were divided into two groups based on whether they received PDT treatment. Over a one-year follow-up period, patients' healing time and recurrence rates were compared between the two groups. The cumulative incidence of recurrence and restricted mean survival time (RMST) were used to assess outcomes. Propensity score matching (PSM) was employed to minimize bias. ResultA total of 41 patients enrolled in our study, with 8 (19.5%) received PDT. The non-PDT group exhibited a slower skin lesion healing time, averaging at 7.2 days compared to 5.4 days in the PDT group. A significant difference was observed in the cumulative incidence of recurrence between the PDT and non-PDT groups (37.5% versus 71.4%) after PSM. The RMST in the PDT group was 9.94 days, compared to 5.13 days in the non-PDT group before PSM, and 4.14 after PSM. ConclusionOur study demonstrated that the PDT effectively reduced lesion recovery time and delayed recurrences of genital herpes. We recommend considering PDT as a potential treatment option for patients with recurrent genital herpes.

Frequent Evaluation of Herpes Simplex Virus Type 2 in Women with Genital Herpes by Realtime PCR

Background: Herpes simplex type 2 is a common infection worldwide. This disease is common in both developed and developing countries. Early detection of infection is very important to reduce the risk of infection. Real-time reliable PCR is a very sensitive and specific method that can be used as the best marker in determining the therapeutic effect by identifying a viral genome in an individual. The prevalence of herpes simplex virus type 2 in women with genital herpes was evaluated by Real time PCR method. Methods: From January 1999 to March 2010, 45 samples of vaginal swabs and cervix of women with genital herpes were examined for HSV virus DNA detection using Real Time PCR. Results: The mean age of the patients was 35.9 + 5.9. The percentage of positive cases of herpes simplex virus type 2 in the studied women was 22.2% and the history of infection with hpv was 33.3% vs. 12.5%. = 0.094 which was significant. Conclusion: Clinical specimens of vaginal swabs from genital herpes caused by herpes simplex virus 2 can be quantitatively analyzed instead of nucleic acid extraction and amplification by PCR.

Single-cell RNA Sequencing Reveals the Diversity of the Immunological Landscape Response to Genital Herpes

Genital herpes (GH) is a common sexually transmitted disease, which is primarily caused by herpes simplex virus type 2 (HSV-2), and continues to be a global health concern. Although our understanding of the alterations in immune cell populations and immunomodulation in GH patients is still limited, it is evident that systemic intrinsic immunity, innate immunity, and adaptive immunity play crucial roles during HSV-2 infection and GH reactivation. To investigate the mechanisms underlying HSV-2 infection and recurrence, single-cell RNA sequencing (scRNA-seq) was performed on immune cells isolated from the peripheral blood of both healthy individuals and patients with recurrent GH. Furthermore, the systemic immune response in patients with recurrent GH showed activation of classical monocytes, CD4+ T cells, natural killer cells (NK cells), and plasmacytoid dendritic cells (pDCs), especially of genes associated with the Toll-like receptor signaling pathway and T cell activation. Circulating immune cells in GH patients show higher expression of genes associated with inflammation and antiviral responses both in the scRNA-Seq data set and in independent quantitative real-time polymerase chain reaction (qRT-PCR) analysis and ELISA experiments. This study demonstrated that localized genital herpes, resulting from HSV reactivation, may influence the functionality of circulating immune cells, suggesting a potential avenue for future research into the role of systemic immunity during HSV infection and recurrence.

An STI rarely comes alone-An overview of sexually transmitted infections

Sexually transmitted infections (STI) or sexually transmitted diseases (STD) can be caused by bacteria, viruses, fungi, protozoa and arthropods. The most frequent bacterial STIs include Chlamydia infections, syphilis and gonorrhea; viral STIs include herpes genitalis (herpes simplex virus 1 and 2), human papillomavirus (HPV) and human immunodeficiency virus (HIV). An empathetic medical history taking in cases of a clinical suspicion can provide important information for adequate diagnostics. When an STI is detected, a complete screening for other STIs should be carried out. The STIs result in awide variety of symptoms and it is often difficult to make a clear diagnosis to a certain pathogen based on the clinical symptoms. To avoid reinfections, it is recommended to also test recent sexual partners. For certain pathogens highly effective postexposure prophylaxis or preventive vaccinations are available.

Development and characterization of formulations based on combinatorial potential of antivirals against genital herpes.

Herpes simplex virus type 2 (HSV-2) treatment faces challenges due to antiviral resistance and systemic side effects of oral therapies. Local delivery of antiviral agents, such as tenofovir (TDF) and zinc acetate dihydrate (ZAD), may offer improved efficacy and reduced systemic toxicity. This study's objective is to develop and evaluate local unit dose formulations of TDF and ZAD combination for local treatment of HSV-2 infection and exploring their individual and combinatory effects in vitro. The study involved the development of immediate-release film and pessary formulations containing TDF and ZAD. These formulations were characterized for physicochemical properties and in vitro drug release profiles. Cytotoxicity and antiviral activity assays were conducted to evaluate the individual and combinatory effects of TDF and ZAD. Film formulations released over 90% of the drugs within 1h, and pessary formulations within 90min, ensuring effective local drug delivery. ZAD showed moderate antiviral activity while TDF exhibited significant antiviral activity at non-cytotoxic concentrations. The combination of TDF and ZAD demonstrated synergistic effects in co-infection treatments, reducing the concentration required for 50% inhibition of HSV-2. Developed film and pessary formulations offer consistent and predictable local drug delivery, enhancing antiviral efficacy while minimizing systemic side effects. The combination of TDF and ZAD showed potential synergy against HSV-2, particularly in co-infection treatments. Further preclinical studies on pharmacokinetics, safety, and efficacy are necessary to advance these formulations toward clinical application.

Evaluation of polymer combinations in vaginal mucoadhesive tablets for the extended release of acyclovir

Genital herpes, caused by herpes simplex virus type 2 (HSV-2), affects nearly 500 million people, mostly women. Since the main route of transmission is sexual contact, the development of an acyclovir extended-release vaginal microbicide would be a suitable tool for the prevention of virus transmission. In this work, we evaluated the potential of three polymers with different characteristics (chitosan, xanthan gum and ethyl cellulose) for obtaining acyclovir extended-release vaginal tablets. By combining the polymers, certain useful synergies were observed to modify their mucoadhesive capacity and control drug release. In the swelling studies, it observed that a polyelectrolyte complex with more moderate swelling and sustained gelation was formed between chitosan and xanthan gum exclusively in acidic medium (simulated vaginal fluid). This complex allowed prolonging the mucoadhesion of the tablets in ex vivo studies performed with vaginal mucosa, which would translate into better retention in the vagina after administration. In addition, the combination of chitosan and xanthan gum allowed obtaining a controlled release of acyclovir for 5 days, regardless of the pH of the medium, which would guarantee that drug release continues even in the presence of seminal fluid.

Joint British Association for Sexual Health and HIV and Royal College of Obstetricians and Gynaecologists national UK guideline for the management of herpes simplex virus (HSV) in pregnancy and the neonate (2024 update).

This updated national UK guideline offers recommendations on the management of genital herpes simplex virus (HSV) in mothers and pregnant people during pregnancy and within 4 weeks following birth. It includes recommendations for first episode and recurrent HSV, HSV in preterm pre-labour rupture of membranes and in co-infection with HSV and HIV. Recommendations around management of the neonate are made, on prevention of postnatal transmission, management of breastfeeding, and the management of clinically discordant couples. This guideline is aimed at healthcare professionals working in sexual health clinics, maternity units, and those working on postnatal wards and neonatal units in the UK. However, the principles of the recommendations should be adopted across all services, including community care.

Population-based risk factors and urogenital comorbidities associated with genital herpes: A nationwide study of 4 million women

ObjectivesTo explore the population-based risk factors for genital herpes in women and examine whether genital herpes occurs at higher rates in women diagnosed with cervical neoplasia and common urogenital infections. MethodsAn open cohort study consisting of 4,097,075 women ≥15 years of age in Sweden (2002-2018). The outcome was genital herpes diagnosis. The predictor variables were sociodemographic factors (age, educational level, family income, region of residence, and country of origin) and urogenital comorbidities (cervical carcinoma neoplasia, cystitis, vaginosis, and vulvovaginitis) and parity. National registers and primary health care data were used. Cox regression models were used to estimate hazard ratios with 95% confidence intervals. Interactions tests were conducted. ResultsA total of 15,727 women received a genital herpes diagnosis in inpatient and outpatient specialist care settings during the study period. Sociodemographic factors and parity were associated with genital herpes. than women without these comorbidities. ConclusionsGenital herpes occurs with higher rates in women of high family income, young age, Swedish origin, co-occurrence of urogenital comorbidities, and nulliparity. The findings can be used by clinicians when encountering women with these risk factors.

Disease Pattern among the Patients of Sexually Transmitted Infection : A Cross Sectional Study of 70 Cases

Background: Sexually Transmitted Infections (STIs) including Human Immunodeficiency Virus (HIV) continue to present major health problems in Bangladesh, leading to considerable morbidity, mortality and stigma. To determine the diseases pattern among the patients of sexually transmitted infection attending at the Department of Dermatology and Venereology, Bangabandhu Memorial Hospital of Chattogram, this study was performed. Materials and methods : This cross sectional study was carried in the Department of Dermatology & Venereology, Bangabandhu Memorial Hospital, Chattogram during the period August to November 2023. A total of 70 cases were enrolled in this study. Among them, 58 patients were male and 12 patients were female. Results: Genital ulcer (28.57%) was the most common clinical presentation among the attendees. Primary syphilis was the most common (18.57%) STI detected among the participants followed by herpes genitalis (17.14%). The most common mixed infection was primary syphilis with chancroid (33.34%) followed by herpes genitalis with primary syphilis (25%). Conclusion: Ulcerative STIs singly or in combination are more frequent than the non-ulcerative STIs. IAHS Medical Journal Volume 06(2), December 2023; 5-8

Recent Advances in the Study of Alphaherpesvirus Latency and Reactivation: Novel Guidance for the Design of Herpesvirus Live Vector Vaccines.

Alphaherpesviruses, including herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), and varicella-zoster virus (VZV), infect a diverse array of hosts, spanning both humans and animals. Alphaherpesviruses have developed a well-adapted relationship with their hosts through long-term evolution. Some alphaherpesviruses exhibit a typical neurotropic characteristic, which has garnered widespread attention and in-depth research. Virus latency involves the retention of viral genomes without producing infectious viruses. However, under stress, this can be reversed, resulting in lytic infection. Such reactivation events can lead to recurrent infections, manifesting as diseases like herpes labialis, genital herpes, and herpes zoster. Reactivation is a complex process influenced by both viral and host factors, and identifying how latency and reactivation work is vital to developing new antiviral therapies. Recent research highlights a complex interaction among the virus, neurons, and the immune system in regulating alphaherpesvirus latency and reactivation. Neurotropic alphaherpesviruses can breach host barriers to infect neurons, proliferate extensively within their cell bodies, and establish latent infections or spread further. Whether infecting neurons or spreading further, the virus undergoes transmission along axons or dendrites, making this process an indispensable part of the viral life cycle and a critical factor influencing the virus's invasion of the nervous system. Research on the transmission process of neurotropic alphaherpesviruses within neurons can not only deepen our understanding of the virus but can also facilitate the targeted development of corresponding vaccines. This review concentrates on the relationship between the transmission, latency, and activation of alphaherpesviruses within neurons, summarizes recent advancements in the field, and discusses how these findings can inform the design of live virus vaccines for alphaherpesviruses.

A nonhuman primate model for genital herpes simplex virus 2 infection that results in vaginal vesicular lesions, virus shedding, and seroconversion.

The most commonly used animal models for evaluating the efficacy of HSV-2 candidate vaccines are mice and guinea pigs. While numerous HSV-2 vaccine candidates have been tested in these animals and were effective in reducing disease and mortality, these results did not predict the effectiveness of the vaccines in human trials. Infection of rhesus macaques rarely results in lesions or HSV-2 specific antibody responses. In seeking an animal model that better recapitulates human disease and that might be more predictive of the efficacy of prophylactic vaccines than mice and guinea pigs, we evaluated Cebus apella (C. apella), a New World primate, in an HSV-2 genital infection model. Infectious HSV-2 was cultured from vaginal swabs from all 4 animals for 9-14 days after intravaginal inoculation of HSV-2 seronegative monkeys. Two of 4 monkeys had vesicular lesions in the vagina or vulva. No neurological symptoms were noted. Recurrent lesions and HSV-2 DNA shedding after acute disease resolved was infrequent. UV irradiation of the genital area did not induce recurrent genital lesions or virus shedding. All 4 monkeys developed HSV-2 neutralizing antibodies as well as virus-specific CD4 and CD8 T cell responses. Reinfection of animals 15 to 19 months after primary infection did not result in lesions; animals had reduced virus shedding and a shorter duration of shedding compared with that during primary infection, suggesting that primary infection induced protective immunity. Primary fibroblasts from C. apella monkeys supported the growth of HSV-2 in vitro; in contrast, HSV-2 did not replicate above the titer of the input inoculum in fibroblasts from rhesus macaques. These observations suggest that the C. apella monkey has potential to serve as a model for evaluating the efficacy of prophylactic vaccines, antivirals, or monoclonal antibodies to HSV-2.

Reflections on Progress in Genital Herpes Therapy and Prevention 1997 to 2024.

Reflections on Progress in Genital Herpes Therapy and Prevention 1997 to 2024.

52384 Genital ulcers in hospitalized patients: How often is genital herpes the culprit?

52384 Genital ulcers in hospitalized patients: How often is genital herpes the culprit?