Search Results (30)

Herpes simplex viruses (HSV-1 and HSV-2) are highly prevalent human pathogens that establish lifelong latency in sensory neurons, posing a persistent challenge to global public health. Their clinical manifestations range from mild, self-limiting orolabial lesions to severe, life-threatening conditions such as disseminated neonatal infections, focal encephalitis, and herpetic stromal keratitis, which can lead to irreversible corneal blindness. Beyond direct pathology, HSV-mediated genital ulcerative disease (GUD) significantly enhances mucosal susceptibility to HIV-1 and other sexually transmitted infections, amplifying co-infection risk and disease burden. Despite decades of clinical reliance on nucleoside analogues such as acyclovir, the therapeutic landscape has stagnated with rising antiviral resistance, toxicity associated with prolonged use, and the complete inability of current drugs to eliminate latency or prevent reactivation continue to undermine effective disease control. These persistent gaps underscore an urgent need for next-generation antivirals that operate through fundamentally new mechanisms. Marine ecosystems, the planet’s most chemically diverse environments, are providing an expanding repertoire of antiviral compounds with significant therapeutic promise. Recent discoveries reveal that marine-derived polysaccharides, sulfated glycans, peptides, alkaloids, and microbial metabolites exhibit remarkably potent and multi-targeted anti-HSV activities, disrupting viral attachment, fusion, replication, and egress, while also reshaping host antiviral immunity. Together, these agents showcase mechanisms and scaffolds entirely distinct from existing therapeutics. This review integrates emerging evidence on structural diversity, mechanistic breadth, and translational promise of marine natural products with anti-HSV activity. Collectively, these advances position marine-derived compounds as powerful, untapped scaffolds capable of reshaping the future of HSV therapeutics. Full article

Viral infections may vary from mild to severe, manifesting with a wide range of symptoms, including skin lesions, influenza-like symptoms, or meningitis/meningoencephalitis signs. Viruses that cause both skin lesions and meningitis comprise, e.g., Enteroviruses (EVs) and Herpes viruses (HV). EVs are responsible for approximately 90% of viral meningitis cases. They occur frequently among children under 3 years of age and are characterized by various types of rash. HV infections are responsible for up to 18% of viral meningitis, mostly among adults or older children. Most patients with viral meningitis recover entirely. However, the rates of serious complications and mortality may be as high as 74% and 10%, respectively, for particularly vulnerable neonatal or immunocompromised patients. Patients that present signs of encephalitis and/or are suspected to have HSV/VZV infection require immediate implementation of empiric acyclovir therapy before receiving the polymerase chain reaction (PCR) test results. The clinical picture of viral meningitis may differ depending on the virus, including the presence of both meningeal signs and skin lesions. Therefore, early identification of the etiological factor is necessary for early and proper treatment implementation. It is crucial to accurately differentiate between the causative agents, and this work focuses on answering the question of how skin lesions can assist in achieving a better and faster diagnosis. The aim of this review was to analyze the characteristics of skin lesions in the course of meningitis caused by various viral species. This can be helpful for physicians in the diagnostic process and subsequent treatment. Full article

In the first 90 days, most meningitis cases are viral. Newborns often show nonspecific symptoms, making early diagnosis difficult but crucial for effective treatment and good outcomes. Cerebro-spinal fluid (CSF) analysis is the gold standard for diagnosis, enabling targeted therapy. We report on a newborn with rare viral meningitis due to herpes simplex virus type 1 and enterovirus coinfection. This uncommon situation complicates diagnostic and therapeutic management. We share our experience and review the limited literature on such neonatal viral coinfections. Full article

Varicella-zoster virus is an α-herpes virus with a double-stranded DNA genome, which causes two main clinical pictures: varicella or chickenpox and herpes zoster. Chickenpox is the primary infection, predominantly affecting children, and it presents with fever and a cutaneous eruption consisting of a vesicular, pruritic, and painful rash. Herpes zoster is a viral infection that typically develops in adulthood as a result of the reactivation of the varicella-zoster virus. If acquired during pregnancy, chickenpox may be responsible for serious complications for the mother, the fetus, or the newborn. The most frequent complication of primary varicella-zoster virus infection in mothers is varicella pneumonia, while encephalitis and hepatitis are rare. The effects on the fetus due to chickenpox infection depend on the stage of pregnancy when the mother becomes infected. If the infection occurs during the first trimester, it does not increase the risk of miscarriage. However, if the infection occurs during the first or second trimester, it may cause fetal varicella syndrome or congenital varicella syndrome. During pregnancy, if the varicella-zoster virus reactivates, it usually does not cause harm to the fetus or lead to any birth defects. However, it may increase maternal morbidity due to herpes zoster and its complications. In the case of primary varicella-zoster virus infection in pregnant women, about 20% of newborns may get neonatal or infantile herpes zoster without any complications. However, it is recommended to start early treatment of herpes zoster in pregnant women as it is believed to accelerate the healing process of skin lesions and alleviate pain, reducing both its duration and severity. Through this narrative review, we discuss the approach to the optimal management of varicella-zoster virus infection during pregnancy. Full article

Viruses are the most common congenital infections in humans and an important cause of foetal malformations, neonatal morbidity, and mortality. The effects of these infections, which are transmitted in utero (transplacentally), during childbirth or in the puerperium depend on the timing of the infections. These vary from miscarriages (usually with infections in very early pregnancy), congenital malformations (when the infections occur during organogenesis) and morbidity (with infections occurring late in pregnancy, during childbirth or after delivery). The most common of these viruses are cytomegalovirus, hepatitis, herpes simplex type-2, parvovirus B19, rubella, varicella zoster and zika viruses. There are currently very few efficacious antiviral agents licensed for use in pregnancy. For most of these infections, therefore, prevention is mainly by vaccination (where there is a vaccine). The administration of immunoglobulins to those exposed to the virus to offer passive immunity or appropriate measures to avoid being infected would be options to minimise the infections and their consequences. In this review, we discuss some of the congenital and perinatal infections and their consequences on both the mother and fetus and their management focusing mainly on prevention. Full article

The risk of infection transmission from mother to fetus depends on the pathogen. TORCH agents cause some neuroinfections, including Toxoplasmosis, rubella, Cytomegalovirus, herpes simplex 1 and 2, and others (Varicella Zoster, Parvovirus B-19, Epstein–Barr virus, and Zika virus). The consequences can be stillbirth, prematurity, uterine growth restriction, and congenital malformations. The detection of DNA/RNA from CSF by molecular methods is a marker of the involvement of congenital infection in the central nervous system. This study aimed to identify the frequency of these pathogens in CSF samples from newborns (1 to 28 days old) at a tertiary hospital, using PCR, and determine the clinical consequences. Methods: This was a prospective descriptive study involving the molecular analysis of 151 CSF samples from neonates, collected for cytological and biochemical diagnosis from 2017 to 2021. After the results and consent from the participants’ caregivers were obtained, the leftover material was sent to the University’s Virology Laboratory and submitted for DNA/RNA extraction and Nested-PCR/RT-PCR. A review of the patients’ medical records and descriptive statistics was performed. This work was approved by the Ethics Committee (CAAE: 86760218.3.0000.5404). Results: A total of 151 CSF samples were obtained, 16 of which were positive (10.6% [95% CI%: 6.18–16.63%]). Two of these were PCR-positive for HSV-1 (1.3%), four for VZV (2.6%), one for CMV (0.67%), two for Toxoplasmosis (1.3%), four for Parvovirus B-19 (2.6%), and four for Zika (2.6%). The proportion of positive PCR results was higher in the group that presented with malformations (25.0% vs. 8.4%, p = 0.040). Conclusions: The pathogens identified by PCR were mostly Zika virus, VZV, and B-19, and these were mainly found in newborns with malformations. Full article

Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening syndrome characterized by an uncontrolled hyperinflammatory reaction. HLH is classified into primary (familial) and secondary (acquired). Secondary HLH is commonly triggered by infections, with viral infections being a leading cause. Its epidemiology and clinical features in cases associated with herpes simplex virus 1 and 2 remain underexplored. This study aimed to review all previously described cases of HSV-1 or -2-triggered HLH and provide information about this syndrome’s epidemiology, microbiology, clinical characteristics, treatment, and outcomes. Methods: A narrative review was performed based on a search in PubMed, the Cochrane Library, and Scopus. Studies published until 27 April 2024 providing relevant data for HLH due to HSV 1 and 2 in humans were included. Results: We identified 29 eligible studies reporting HLH due to HSV 1 and 2, involving 34 patients. Half of them were adults, and half were neonates. Fever and splenomegaly were the most common clinical findings. Most patients were diagnosed with HSV-1 (64.7%), with PCR being the primary diagnostic method. The median duration of in-hospital treatment was 21 days, with acyclovir and steroids being the mainstays of therapy. The overall mortality rate was 41.2%, and AST levels emerged as an independent predictor of mortality. Conclusions: Our findings underscore the need for heightened awareness surrounding HLH triggered by HSV 1 and 2 and the importance of prompt diagnosis and tailored treatment approaches. Full article

Maternal–fetal infectious pathology—notably the TORCH panel (Toxoplasma gondii, rubella, Cytomegalovirus, and herpes simplex viruses)—critically impacts maternal and neonatal health. This review collates data on the seroprevalence of IgG and IgM antibodies against TORCH agents in Romanian women, aiming to discern regional and population differences and identify risk factors. Twenty studies were included in the review, revealing variable seroprevalence rates across the country. Regions such as Moldavia and Banat showed higher anti-T. gondii IgG seroprevalence rates than Bihor, with notable declines in Banat. Rural, older, and multiparous women showed elevated T. gondii IgG rates. Anti-rubella vaccine introduction significantly reduced the prevalence of anti-rubella IgG antibodies, but recent vaccination coverage decreases raise concerns. CMV and HSV seroprevalence varied geographically, with rural areas generally showing higher CMV rates and HSV influenced by factors like education level and number of sexual partners. Concurrent seroprevalence of multiple TORCH components in some cases underscores potential common risk factors. This study highlights the importance of continuous monitoring and preventive measures such as vaccinations and awareness campaigns to mitigate the health impact on the pregnant population. Full article

Herpes simplex virus type 1 (HSV-1) infections are prevalent illnesses that can cause mucocutaneous ulcerative disease, keratitis, and genital herpes. In patients with compromised immune systems, the infection can lead to serious problems, such as encephalitis. Additionally, neonatal infections can cause brain problems and even death. Current first-line antiviral drugs are nucleoside analog inhibitors that target viral polymerase, and resistant strains have emerged. As a result, new drugs with distinct action modes are needed. Recent research indicates that cyclin-dependent kinases (CDKs) are prospective antiviral targets. Thus, CDK inhibitors may be effective antiviral agents against HSV-1 infection. In this study, we examined a panel of CDK inhibitors that target CDKs in the present study. BMS-265246 (BMS), a CDK 1/2 inhibitor, was found to effectively limit HSV-1 multiplication in Vero, HepG2, and Hela cells. A mechanism of action study suggested that BMS inhibits the early stages of viral replication when added early in the viral infection. The suppression of multiple steps in viral replication by BMS was revealed when HSV-1 infected cells were treated at different time periods in the viral life cycle. Our results suggest that BMS is a potent anti-HSV-1 agent and unique in that it may interfere with multiple steps in HSV-1 replication. Full article

Herpes simplex virus (HSV) is widespread in the population, causing oral or genital ulcers and, rarely, severe complications such as encephalitis, keratitis, and neonatal herpes. Current available anti-HSV drugs are acyclovir and its derivatives, although long-term therapy with these agents can lead to drug resistance. Thus, the discovery of novel antiherpetic compounds merits additional studies. In recent decades, much scientific effort has been invested in the discovery of new synthetic or natural compounds with promising antiviral properties. In our study, we tested the antiviral potential of a novel polyphenol-based nutraceutical formulation (named Taurisolo^®) consisting of a water polyphenol extract of grape pomace. The evaluation of the antiviral activity was carried out by using HSV-1 and HSV-2 in plaque assay experiments to understand the mechanism of action of the extract. Results were confirmed by real-time PCR, transmission electron microscope (TEM), and fluorescence microscope. Taurisolo^® was able to block the viral infection by acting on cells when added together with the virus and also when the virus was pretreated with the extract, demonstrating an inhibitory activity directed to the early phases of HSV-1 and HSV-2 infection. Altogether, these data evidence for the first time the potential use of Taurisolo^® as a topical formulation for both preventing and healing herpes lesions. Full article

Adolescents and young people are particularly vulnerable to contracting STIs, including HSV-2; furthermore, vaginal shedding of HSV-2 during pregnancy can cause vertical transmission and neonatal herpes. To evaluate the seroprevalence of HSV-2 and vaginal HSV-2 shedding in adolescent and young pregnant women, a cross-sectional study was carried out in 496 pregnant women—adolescents and young women. Venous blood and vaginal exudate samples were taken. The seroprevalence of HSV-2 was determined by ELISA and Western blot. Vaginal HSV-2 shedding was assessed by qPCR of the HSV-2 UL30 gene. The seroprevalence of HSV-2 in the study population was 8.5% (95% CI 6–11), of which 38.1% had vaginal HSV-2 shedding (95% CI 22–53). Young women presented a higher seroprevalence of HSV-2 (12.1%) than adolescents (4.3%), OR = 3.4, 95% CI 1.59–7.23. Frequent alcohol consumption was significantly associated with HSV-2 seroprevalence, OR = 2.9, 95% CI 1.27–6.99. Vaginal HSV-2 shedding is highest in the third trimester of pregnancy, but this difference is not significant. The seroprevalence of HSV-2 in adolescents and young women is similar to that previously reported in other studies. However, the proportion of women with vaginal shedding of HSV-2 is higher during the third trimester of pregnancy, increasing the risk of vertical transmission. Full article

(1) Background: One out of two pregnant women has a history of herpes infection. Initial infections have a high risk of neonatal transmission. Our objective was to analyse the professional practises of midwives regarding the management of herpes infections during pregnancy in France; (2) Methods: A national survey conducted via an online self-questionnaire, including clinical vignettes for which the midwives proposed a diagnosis, a drug treatment, a mode of birth, and a prognosis. These responses were used to evaluate the conformity of the responses to the guidelines, as well as the influence of certain criteria, such as mode of practise and experience; (3) Results: Of 728 responses, only 26.1% of the midwives reported being aware of the 2017 clinical practise guidelines. The midwives proposed taking the appropriate actions in 56.1% of the responses in the case of a recurrence, and in 95.1% of the responses in the case of a primary infection. For the specific, high-risk case of a nonprimary initial infection at 38 weeks of gestation, reporting knowledge of the recommendations improved the compliance of the proposed care by 40% (p = 0.02). However, 33.8% of the midwives underestimated the neonatal risk at term after a primary initial infection, and 43% underestimated the risk after a primary initial infection at term; (4) Conclusions: The majority of reported practises were compliant despite a low level of knowledge of the guidelines. The dissemination of guidelines may be important to improve information and adherence to appropriate therapeutic practise. Full article

TORCH pathogens are a group of globally prevalent infectious agents that may cross the placental barrier, causing severe negative sequalae in neonates, including fetal death and lifelong morbidity. TORCH infections are classically defined by Toxoplasma gondii, other infectious causes of concern (e.g., syphilis, Zika virus, malaria, human immunodeficiency virus), rubella virus, cytomegalovirus, and herpes simplex viruses. Neonatal disorders and congenital birth defects are the leading causes of neonatal mortality in Central America’s Northern Triangle, yet little is known about TORCH congenital syndrome in this region. This review synthesizes the little that is known regarding the most salient TORCH infections among pregnant women and neonates in Central America’s Northern Triangle and highlights gaps in the literature that warrant further research. Due to the limited publicly available information, this review includes both peer-reviewed published literature and university professional degree theses. Further large-scale studies should be conducted to clarify the public health impact these infections in this world region. Full article

Herpes viruses are widespread in the human population and can cause many different diseases. Genital herpes is common and can increase the risk of HIV infection and neonatal herpes. Acyclovir is the most used drug for herpes treatment; however, it presents some disadvantages due to its poor oral bioavailability. In this study, some ethylene vinyl acetate devices with different acyclovir amounts (0, 10, and 20 wt.%) were manufactured by fused filament fabrication in two different geometries, an intrauterine device, and an intravaginal ring. Thermal analyses suggested that the crystallinity of EVA decreased up to 8% for the sample loaded with 20 wt.% of acyclovir. DSC, SEM, and FTIR analyses confirmed that the drug was successfully incorporated into the EVA matrix. Moreover, the drug release tests suggested a burst release during the first 24 h followed by a slower release rate sustained up to 80 days. Biological assays showed the biocompatibility of the EVA/ACV device, as well as a 99% reduction in vitro replication of HSV-1. Finally, the EVA presented a suitable performance for 3D printing manufacturing that can contribute to developing personalized solutions for long-term herpes treatment. Full article

Intrauterine infections during pregnancy by herpes simplex virus (HSV) can cause significant neurodevelopmental deficits in the unborn/newborn, but clinical studies of pathogenesis are challenging, and while animal models can model some aspects of disease, in vitro studies of human neural cells provide a critical platform for more mechanistic studies. We utilized a reductionist approach to model neurodevelopmental outcomes of HSV-1 infection of neural rosettes, which represent the in vitro equivalent of differentiating neural tubes. Specifically, we employed early-stage brain organoids (ES-organoids) composed of human induced pluripotent stem cells (hiPSCs)-derived neural rosettes to investigate aspects of the potential neuropathological effects induced by the HSV-1 infections on neurodevelopment. To allow for the long-term differentiation of ES-organoids, viral infections were performed in the presence of the antiviral drug acyclovir (ACV). Despite the antiviral treatment, HSV-1 infection caused organizational changes in neural rosettes, loss of structural integrity of infected ES-organoids, and neuronal alterations. The inability of ACV to prevent neurodegeneration was associated with the generation of ACV-resistant mutants during the interaction of HSV-1 with differentiating neural precursor cells (NPCs). This study models the effects of HSV-1 infection on the neuronal differentiation of NPCs and suggests that this environment may allow for accelerated development of ACV-resistance. Full article