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Aim . To carry out a comparative analysis of the cytotoxic and antiviral properties of synthesized tellurium derivatives in model cellular systems of infections caused by herpes simplex virus and cytomegalovirus. Material and Methods . 4 organo‐tellurium compounds were studied using primary and continuous cell cultures in various infection schemes. Results . For each biological model studied, different thresholds of cytotoxicity concentration (TCD50 acute CC50 and CD50 CC50) were identified. Tellurium derivatives with methoxyphenyl and ethoxyphenyl ethene exhibit virus‐neutralizing activity, preventing the penetration of herpes simplex virus virions into sensitive cells. HTI (SI selectivity index) for these compounds was 84 and 77, respectively. Conclusion . The manifestation of the cytotoxic effect of all tellurium‐containing organic compounds for transplanted cells lies in a lower concentration than for primary cells. The data obtained in the analysis of antiviral activity showed that the derivatives have therapeutic properties against HSV infection in cell culture.

BACKGROUND AND OBJECTIVESClinicians evaluating for herpes simplex virus (HSV) in febrile infants must balance detection with overtesting, and there is no universally accepted approach to risk stratification. We aimed to describe variation in diagnostic evaluation and empirical acyclovir treatment of infants aged 0 to 60 days presenting with fever and determine the association between testing and length of stay (LOS).METHODSIn this retrospective 44-hospital observational study, we used the Pediatric Health Information System database to identify infants aged ≤60 days evaluated for fever in emergency departments from January 2016 through December 2017. We described hospital-level variation in laboratory testing, including HSV, imaging and other diagnostic evaluations, acyclovir use, and LOS. We assessed the relationship between HSV testing and LOS using generalized linear mixed effects models adjusted for age and illness severity.RESULTSIn 24 535 encounters for fever, the median HSV testing frequency across hospitals was 35.6% (interquartile range [IQR]: 28.5%–53.5%) for infants aged 0 to 21 days and 12% (IQR: 8.6%–15.7%) for infants aged 22 to 60 days. Among HSV-tested patients, median acyclovir use across hospitals was 79.2% (IQR: 68.1%–89.7%) for those aged 0 to 21 days and 63.6% (IQR: 44.1%–73%) for those aged 22 to 60 days. The prevalence of additional testing varied substantially by hospital and age group. Risk-adjusted LOS for HSV-tested infants was significantly longer than risk-adjusted LOS for those not tested (2.6 vs 1.9 days, P < .001).CONCLUSIONSSubstantial variation exists in diagnostic evaluation and acyclovir use, and infants who received HSV testing had a longer LOS than infants who did not. This variability supports the need for further studies to help clinicians better risk-stratify febrile infants and to guide HSV testing and treatment decisions.

Neonatal herpes simplex virus (HSV) infection of the central nervous system (CNS) is an emergency that can have devastating structural consequences and clinical outcomes. As it presents non-specifically in neonates, it is difficult to rapidly diagnose without neuroimaging. Although once thought to cause widespread parenchymal destruction, neonatal CNS HSV infection may present with more focal parenchymal injury on neuroimaging, not involving the medial temporal lobes as in adults. We report a case of a three-week-old girl with herpes simplex virus type 2 (HSV-2) encephalitis with exclusive bilateral corticospinal and frontal opercular involvement, which remained undiagnosed and untreated until three months of age. Neuroimaging upon presentation to the emergency room demonstrates a highly suggestive pattern of severe neonatal CNS HSV-2 infection which followed the natural history on subsequent imaging, highlighting the importance of emergency neuroimaging as well as having a high index of suspicion for making the diagnosis.

Background/objective Herpes simplex virus (HSV) infection acquired in utero may present with non-vesicular dermatologic findings in affected newborns, which may pose a diagnostic dilemma. We aimed to describe and assess the range of non-vesiculobullous skin lesions that neonates with intrauterine HSV infection may manifest at birth. Methods We collected a multicenter case series and conducted a literature review of neonates with intrauterine HSV infection presenting with non-vesiculobullous cutaneous lesions. Results Twenty-two cases were reviewed, including six managed clinically by members of our team and 16 identified in the literature. Four (18%) were associated with twin pregnancies, and thirteen (59%) cases occurred in premature infants. Only four (18%) mothers had a documented history of HSV infection. Twelve (55%) cases resulted in poor outcomes, including long-term neurologic sequelae or death. Cutaneous manifestations included erosions, ulcerations, crusted papules or plaques, calcinosis cutis, excoriations, macules (erythematous, hypopigmented, or hyperpigmented), cutaneous atrophy, contractures, and bruising. About one-third of neonates developed new-onset vesicular lesions within a week of birth; in each of these cases, accurate diagnosis and therapy were delayed until appearance of vesicles. Conclusions The range of dermatologic findings associated with intrauterine HSV is extremely broad, and the various morphologies present at birth likely reflect different stages of the ongoing evolution of an HSV infection that began in utero. Clinicians should have a low threshold for HSV testing in premature neonates born with atypical cutaneous lesions, since early detection and treatment of HSV may reduce morbidity and mortality from systemic complications.

ObjectivesThe southeastern US is a domestic epicentre for incident HIV with high prevalence of herpes simplex virus (HSV) coinfection. We estimated the incidence rates (IR) of symptomatic herpetic anogenital ulcer disease (HAUD) and assessed its associations with demographic and clinical characteristics, specifically with immunological markers using median, nadir and trajectory CD4 counts.MethodsElectronic medical records (EMR) of over 7000 people living with HIV (PLWH) attending one of the leading HIV clinics in the southeastern US between 2006 and 2018 were reviewed and analysed. IR of HSV-related HAUD were estimated per 10 000 person years. Joinpoint regressions were performed to examine temporal changes in the trends of IR. All IR and trends were stratified by gender and race. Six CD4 trajectory groups were constructed using the group-based trajectory modelling. Multivariable logistic models were conducted to assess the associations of CD4 counts (nadir, median CD4 and newly defined CD4 trajectory), separately with HAUD.ResultsOf the 4484 PLWH eligible individuals (3429 men, 1031 women and 24 transgender), we observed 425 patients with HSV-related HAUD. The mean log10viral load was higher in HAUD than HAUD-free groups, whereas the median nadir CD4 count (cells/uL) was higher in the non-cases than the case groups (pConclusionsThere were significant differences between men and women with incident HAUD among PLWH. EMR-based studies can provide innovative trajectory models that can potentially be helpful in guiding screening and clinical care of HAUD among high-risk PLWH.

BackgroundDespite being variable and poorly characterized, the reported cutaneous manifestations of COVID-19 are of increasing concern.Aim of the StudyThis study aimed to assess the prevalence and possible association between COVID-19 and herpes simplex virus (HSV) infection.Patients and methodsA 9-item questionnaire was sent to 120 PCR-confirmed COVID-19 patients with a response rate of 66.67%. This cross-sectional observational study included 80 patients with mild to moderate COVID-19 infection who did not require hospitalization or steroid therapy.ResultsOne or more HSV infections were observed in 28 patients (35%) with COVID-19 infection, including 10 males (35.7%) and 18 females (64.29%). Of the 28 patients, fever was reported in 17 patients (75%) during COVID-19. Most of the respondents (78%) described a single HSV reactivation, 14.29% had 2 attacks, and 7.14% experienced 3 attacks. Compared to previous non-COVID-19 related HSV reactivation, the COVID-19 related attacks were more severe in 12 patients (42.85%), equally severe in 5 patients (17.85%) and less severe in 1 patient (3.57%). Interestingly, 10 patients (35.71%) developed an initial symptomatic HSV attack during COVID-19 infection.ConclusionsThis study demonstrated a possible association between COVID-19 infection and primary HSV infection and/or reactivation. The COVID-19 direct neuronal effect in addition to COVID-19 related psychological stress, fever and immunological dysregulation could play a potential role.

OBJECTIVES: The incidence of neonatal herpes simplex virus (nHSV) infections is monitored periodically in the Netherlands, yet management and outcome is unknown. Comprehensive national guidelines are lacking. We aim to describe management and outcome in the last decade to explore current diagnostic and therapeutic challenges. We aim to identify possible variability in management of patients with a suspected nHSV infection. METHODS: We conducted a retrospective case series of management and outcome of nHSV infections at 2 tertiary care center locations in the Netherlands. RESULTS: An nHSV infection was diagnosed in 1% (12 of 1348) of patients in whom polymerase chain reaction for HSV was performed. Of the patients with nHSV infection, 3 of 12 died, and 4 of 9 (44%) survivors suffered neurologic sequelae. Neurologic symptoms at presentation were seen in only 2 of 8 patients with nHSV encephalitis. A cerebral spinal fluid analysis was performed in 3 of 6 patients presenting with skin lesions. Only 3 of 6 patients with neurologic symptoms received suppressive therapy. nHSV infection was diagnosed in 8 of 189 (4%) patients who were empirically treated. CONCLUSIONS: Management of nHSV infection, particularly when presented with skin lesions, is inconsistent. Many infants without a HSV infection are exposed to antiviral medication. There is substantial interhospital variation in diagnostic and therapeutic management of a suspected infection. Comprehensive guidelines need to be developed to standardize management of suspected nHSV infection.

Herpes simplex virus (HSV) is a highly prevalent infection in the United States. One complication of HSV is HSV keratitis, an ocular HSV infection thought to be the leading cause of corneal blindness in the United States. Home care clinicians with knowledge of the signs and symptoms of HSV and HSV keratitis can aid in early detection and treatment of this potentially serious infection. This article discusses signs and symptoms of HSV keratitis, preventive measures, and treatment.

Background Neonatal herpes simplex virus infection (nHSV) leads to severe morbidity and mortality, but national incidence is uncertain. Florida regulations require that healthcare providers report cases, and clinical laboratories report test results when herpes simplex virus (HSV) is detected. We estimated nHSV incidence using laboratory-confirmed provider-reported cases and electronic laboratory reports (ELR) stored separately from provider-reported cases. Mortality was estimated using provider-reported cases, ELR, and vital statistics death records. Methods For 2011–2017, we reviewed: provider-reported cases (infants ≤ 60 days of age with HSV infection confirmed by culture or polymerase chain reaction [PCR]), ELR of HSV-positive culture or PCR results in the same age group, and death certificates containing International Classification of Disease, Tenth Revision, codes for herpes infection: P35.2, B00.0-B00.9, and A60.0-A60.9. Provider-reported cases were matched against ELR reports. Death certificates were matched with provider and ELR reports. Chapman’s capture-recapture method was used to estimate nHSV incidence and mortality. Mortality from all 3 sources was estimated using log-linear modeling. Results Providers reported 114 nHSV cases, and ELR identified 197 nHSV cases. Forty-six cases were common to both datasets, leaving 265 unique nHSV reports. Chapman’s estimate suggests 483 (95% confidence interval [CI], 383–634) nHSV cases occurred (31.5 infections per 100 000 live births). The nHSV deaths were reported by providers (n = 9), ELR (n = 18), and vital statistics (n = 31), totaling 34 unique reports. Log-linear modeling estimates 35.8 fatal cases occurred (95% CI, 34–40). Conclusions Chapman’s estimates using data collected over 7 years in Florida conclude nHSV infections occurred at a rate of 1 per 3000 live births.

International audience; Herpes simplex virus (HSV) infections remain an important cause of morbidity among immunocompromised patients, such as transplant recipients and human immunodeficiency virus [HIV]-infected individuals. Only few antiviral drugs are available to treat HSV infections: (val)acyclovir, foscarnet, and cidofovir. Prophylactic and curative antiviral treatments administered during prolonged periods among patients with altered T-cell immunity may lead to the emergence of HSV resistance to antivirals, contributing to a challenging therapeutic management of viral infection. The persistence of herpetic lesions after 10 days of well-conducted antiviral therapy is suggestive of viral resistance. Resistance to antivirals can be detected using genotypic methods (identifications of antiviral resistance-associated mutations by sequencing genes encoding viral proteins involved in the mechanism of action of antivirals) or phenotypic methods (measure of antiviral drug concentration inhibiting 50% of viral replication in cell culture). The prevalence of HSV resistance to acyclovir is below 1% in immunocompetent individuals, except those with herpetic keratitis for whom prevalence can reach 7%, and varies from 3.5% to 11% in immunocompromised patients. Adverse effects and the absence of eradication of viral latent infection constitute other limits to the use of antiviral drugs. New antiviral compounds undergoing clinical trials and novel potential viral targets seem very promising to enlarge the panel of efficient compounds to treat HSV infections.; Les infections par les virus herpes simplex (HSV) constituent une cause majeure de morbidité chez les patients immunodéprimés tels que les receveurs de greffe ou les individus infectés par le virus de l’immunodéficience humaine (HIV). Les molécules antivirales utilisées pour le traitement de ces infections sont actuellement peu nombreuses : (val)aciclovir, foscarnet et cidofovir. L’instauration de traitements antiviraux préventifs ou curatifs, souvent durant des périodes prolongées, chez des patients dont l’immunité cellulaire est altérée, peut conduire à l’émergence de résistance des HSV aux antiviraux, compliquant alors la prise en charge thérapeutique de l’infection virale. La persistance de lésions herpétiques après 10 jours de traitement antiviral bien conduit doit faire suspecter une résistance virologique. Il est possible de détecter cette résistance par des méthodes génotypiques (identification de mutations associées à la résistance aux antiviraux par séquençage des gènes codant les protéines virales directement impliquées dans le mécanisme d’action des antiviraux) ou par des méthodes phénotypiques (mesure de la concentration d’un antiviral inhibant 50 % de la multiplication virale en culture de cellules). La prévalence de la résistance des HSV à l’aciclovir est inférieure à 1 % chez les individus immunocompétents, hormis ceux souffrant de kératite herpétique pour qui elle est de l’ordre de 7 %, et elle varie de 2,5 % à 11 % chez les individus immunodéprimés. De plus, il existe d’autres limitations à l’utilisation de ces antiviraux, comme leurs effets indésirables ou l’impossibilité d’éradiquer les infections virales latentes. À ce jour, de nouveaux composés en cours d’essais cliniques et de nouvelles cibles virales potentielles semblent très prometteuses pour agrandir le panel de molécules efficaces pour traiter les infections dues aux HSV.

Neonatal herpes simplex virus (HSV) infection carries significant morbidity and mortality. In contrast to perinatal exposure, there are no clear guidelines for the management of postnatal HSV exposure. This review focuses on the risk of HSV infection following postnatal exposure and suggests an approach to management. While many infants are protected by transplacentally transferred maternal anti-HSV antibodies, infants of seronegative mothers with significant postnatal HSV exposure may be at risk of severe disease. Individual risk assessment, appropriate investigations, and empiric acyclovir treatment should be considered in postnatally exposed newborns, even if asymptomatic. In all cases, close clinical follow-up is indicated, as well as education of families on the symptoms of neonatal HSV disease. Finally, measures to reduce the risk of postnatal HSV infection should be considered, such as discouraging individuals, particularly those with a history of recurrent cold sores, from kissing newborns.

Herpes simplex virus (HSV) can cause severe infection in neonates leading to mortality and lifelong morbidity. Prophylactic approaches, such as maternal immunization, could prevent neonatal HSV (nHSV) infection by providing protective immunity and preventing perinatal transmission. We previously showed that maternal immunization with a replication-defective HSV vaccine candidate, dl5-29, leads to transfer of virus-specific antibodies into the neonatal circulation and protects against nHSV neurological sequela and mortality (C. D. Patel, I. M. Backes, S. A. Taylor, Y. Jiang, et al., Sci Transl Med, 11:eaau6039, 2019, https://doi.org/10.1126/scitranslmed.aau6039). In this study, we evaluated the efficacy of maternal immunization with an experimental trivalent (gC2, gD2, and gE2) subunit vaccine to protect against nHSV. Using a murine model of nHSV, we demonstrated that maternal immunization with the trivalent vaccine protected offspring against nHSV-disseminated disease and mortality. In addition, offspring of immunized dams were substantially protected from behavioral pathology following HSV infection. This study supports the idea that maternal immunization is a viable strategy for the prevention of neonatal infections. IMPORTANCE Herpes simplex virus is among the most serious infections of newborns. Current antiviral therapies can prevent mortality if infection is recognized early and treated promptly. Most children who survive nHSV develop lifelong neurological and behavioral deficits, despite aggressive antiviral treatment. We propose that maternal immunization could provide protection against HSV for both mother and baby. To this end, we used a trivalent glycoprotein vaccine candidate to demonstrate that offspring are protected from nHSV following maternal immunization. Significantly, this approach protected offspring from long-term behavioral morbidity. Our results emphasize the importance of providing protective immunity to neonates during this window of vulnerability.

Pseudoboehmite is a hydrated aluminium compound produced by sol-gel process and used in drug delivery systems. The graphene oxide is a material that allows for many possibilities application as modify agent in a ceramic structure. The global prevalence and incidence of herpes simplex virus infections (HSV-1 and HSV-2) have risen worldwide. A big problem is that most persons with genital HSV infection have not received a diagnosis. Other concerning situation is that the herpes infected patients are more susceptible to HIV infections. It is also observed that in women the HSV infection are more common than in men. Acyclovir is an efficient drug for the treatment of herpes viruses. However, the oral bioavailability of acyclovir is limited due to varying and incomplete absorption. In this work, pseudoboehmite was produced with incorporation of graphene oxide in the gel. The pseudoboehmite-graphene oxide was used in in vitro drug delivery system for acyclovir.

Rationale: Herpetic eczema (HE), being one of manifestations of generalized Herpes simplex virus (HSV) infection, presents mostly as a complication of atopic dermatitis (AD). This is a potentially life-threatening infection with mortality rates of up to 9%. Early diagnosis and timely beginning of antiviral treatment may help to avoid severe complications and mortality in children with HE. Aim: To evaluate factors predisposing to the development of HE in children with AD and to identify a high risk group. Materials and methods : One hundred and fifty (150) children with AD aged from 4 months to 18 years were recruited into this one-center prospective stratified observational study. The main group included 113 children with HE with underlying AD, while the comparison group comprised 37 children with AD exacerbations without HE. HSV infection was confirmed by determination of the viral DNA in blood by polymerase chain reaction. The severity of AD at study entry and during follow up was assessed with SCORAD scale. Results : All children with HE + AD (100%) had been in contact with individuals with clinical manifestations of HSV infection (35.1% in the comparison group, p < 0.001). The main predictors of HE in AD patients were as follows: age below 1 year (relative risk increase (RRI) 2.86, 95% confidence interval (CI) -7.91 / -0.68, p < 0.001), autumn and winter season (RRI 1.68, 95% CI -5.3 / -0.15, p = 0.018), moderate and severe AD (RRI 0.91, 95% CI -2.11 / -0.17, p < 0.002). Conclusion: A combination of 3 risk factors, such as age below 1 year, autumn and winter season, moderate and severe AD, puts a patient into a high risk of HE. Children from the risk group should be isolated from patients with manifest HSV infection.

Scientific and clinical data indicate that human herpes simplex virus 1 (HSV1) and, at a lesser extent, human herpes simplex virus 2 (HSV2) are factor(s) implicated in the development of erythema multiforme (EM). With a focus on oral EM, the present structured review of proteomic and epitope databases searched for the molecular basis that might link HSV1 and HSV2 infections to EM. It was found that a high number of peptides are shared between the two HSVs and human proteins related to the oral mucosa. Moreover, a great number of the shared peptides are also present in epitopes that have been experimentally validated as immunopositive in the human host. The results suggest the involvement of HSV infections in the induction of oral EM via a mechanism of autoimmune cross-reactivity and, in particular, highlight a potential major role for 180 kDa bullous pemphigoid antigen and HSV1 infection in the genesis of crossreactions potentially conducive to EM. Scientific and clinical data indicate that human herpes simplex virus 1 (HSV1) and, at a lesser extent, human herpes simplex virus 2 (HSV2) are factor(s) implicated in the development of erythema multiforme (EM). With a focus on oral EM, the present structured review of proteomic and epitope databases searched for the molecular basis that might link HSV1 and HSV2 infections to EM. It was found that a high number of peptides are shared between the two HSVs and human proteins related to the oral mucosa. Moreover, a great number of the shared peptides are also present in epitopes that have been experimentally validated as immunopositive in the human host. The results suggest the involvement of HSV infections in the induction of oral EM via a mechanism of autoimmune cross-reactivity and, in particular, highlight a potential major role for 180 kDa bullous pemphigoid antigen and HSV1 infection in the genesis of crossreactions potentially conducive to EM.

Herpes simplex virus type I (HSV-I) is a latent neuroinfection which can cause focal brain lesion. The role of HSV-infection in nerve regeneration has not been studied so far. The aim of the work was to study sciatic nerve regeneration in the presence of HSV-infection and the influence of an antiviral drug. BALB/c line mice were divided into five groups. Group 1 animals were infected with HSV-I. After resolution of neuroinfection manifestations the sciatic nerve of these animals was crushed. Group 2 mice were administered acyclovir following the same procedures. Groups 3-5 mice served as controls. Thirty days after the operation distal nerve stumps and m.gastrocnemius were studied morphologically and biochemically. Ultrastructural organization of the sciatic nerve in control animals remained intact. Morphometric parameters of the nerves from the experimental groups have not reach control values. However, in the group 1 diameter of nerve fibers was significantly smaller than in the group 2. Both nerve regeneration and m.gastrocnemius reinnervation were confirmed. The muscle hypotrophy was found in groups 1, 2, and 3 (the muscle fibers diameter decreased). Metabolic changes in the muscles of the infected animals (groups 1 and 2) were more pronounced than in control groups 3 and 4. The levels of TBA-active products, conjugated dienes, carbonyl and SH-groups were reduced in m.gastrocnemius of the experimental groups, however no significant difference associated with acyclovir administration was found. HSV-infection is not limited to the local neurodegenerative changes in the CNS but affects regeneration of the injured sciatic nerve. Anat Rec, 301:1734-1744, 2018. © 2018 Wiley Periodicals, Inc.

Herpes simplex virus (HSV) is among the most severely debilitating viruses that can infect the neonate, and is associated with significant mortality and morbidity. Neonatal HSV infection generally is acquired in the peripartum period, and can be devastating if not diagnosed appropriately. Studies conducted over several decades have advanced our knowledge of the benefit of antiviral therapy on neonatal HSV disease outcomes. As such, many neonates now are effectively treated and experience no or fewer long-term sequelae of this potentially devastating infection. Clinicians must be astute, because early diagnosis and early treatment are key to a better prognosis.

Herpes simplex virus (HSV) infection represents significant morbidity and mortality in the neonatal period. Although clear guidelines exist on the evaluation and management of the otherwise well-appearing febrile neonate pertaining to occult serious bacterial infections, there is no standardized approach regarding when to initiate testing and treatment for HSV infection. It is vital we establish a unified guideline based on available clinical research to aid in our decision to evaluate and initiate therapy for this disease.A PubMed search was performed using the keywords "neonate AND fever AND HSV" and "neonate AND fever AND acyclovir." The time period for the search was May 1982 to May 2016. Identified articles underwent further selection based on relevance to the clinical question. Selected articles then underwent detailed review and structured analysis.Our search identified 93 articles, of which 18 were found to be relevant to our clinical question. Recommendations were then made based on thorough review and analysis of the selected articles.Neonatal HSV infection carries significant morbidity and mortality if left untreated. High-quality clinical evidence on when to evaluate and treat for possible HSV infection is lacking. Based on available research, HSV infection in the febrile neonate should be strongly considered if age is 21 days, or if presenting with concerning clinical features. If testing is performed, empiric treatment with high-dose acyclovir should be initiated. Additional research is needed to further clarify which cases mandate evaluation and treatment for HSV, and to better define treatment protocols.

The absence of markers of inflammation in the cerebrospinal fluid (CSF) commonly predicts the absence of herpes simplex virus (HSV) central nervous system (CNS) infection. Consequently, multiple authors have proposed and validated criteria for deferring HSV PCR testing of CSF in immunocompetent hosts with normal CSF white blood cell and protein levels (≤5 cells/mm 3 and ≤50 mg/dl, respectively). Hosts are considered immunocompetent if they are ≥2 years old and have not had HIV or an organ transplant. Adoption of the criteria may erroneously exclude HSV-infected persons from a necessary diagnostic test or, alternatively, reduce the costs associated with HSV tests with minimal to no effect on patient care. Little is known about the cost-effectiveness of this approach. A decision analysis model was developed to evaluate the adoption of criteria for screening HSV tests of CSF. Estimates of input parameter values combined available literature with a multiyear multisite review at two of the largest health care systems in the United States. Adoption of criteria to screen for HSV test need proved cost-effective when less than 1 in 200 patients deferred from testing truly had an HSV CNS infection. Similar to prior studies, none of the deferred cases had HSV encephalitis ( n = 3120). Adoption of these criteria in the United States would save an estimated $127 million ($95 million to $158 million [±25%]) annually. The model calculations remained robust to variation in test cost, prevalence of HSV infection, and random variation to study assumptions. The adoption of criteria to screen HSV PCR tests in CSF represents a cost-effective approach.

Background Neonatal HSV infection is associated with substantial morbidity and mortality. Therefore, prompt identification and treatment of infected neonates is paramount. At Nationwide Children’s Hospital (NCH), Columbus, OH all neonates admitted in the first 2 weeks (up to 2010) and 4 weeks (since 2010) of age are evaluated for HSV infection in addition to routine bacterial and other viral infections. The frequency of co-infection with HSV and other potential pathogens is not fully known. Methods Retrospective review of the medical records of infants admitted to NCH with a diagnosis of neonatal HSV infection from 2001 to 2019. Patients less than 6 weeks of age were identified by review of the NCH Virology and Molecular Laboratory results for all positive HSV PCRs obtained from any body site as well as by discharge ICD-9 and ICD-10 codes for HSV infection. Medical records were reviewed for demographic, clinical, laboratory, outcome data, and maternal history of genital HSV lesions at or before delivery. Occurrence of positive bacterial and/or viral co-detection were identified. The data were managed using REDCap electronic data capture tools hosted at NCH. Results There were 93 infants with neonatal HSV infection (mean age, 9.5 days [IQR, 7-15]; 42%, HSV1; 53%, HSV-2). 32 infants had central nervous system infection (CNS) while 31 had Skin-Eye-Mouth (SEM) infection and 30 had Disseminated Disease. Mortality was 15% (n=14). Only 3 mothers had active genital HSV lesions at delivery. Of the 93 infants, 5 (5%) had bacterial (n=2) or viral (n=3) co-infections. All of the infants only had mucosal sites positive for HSV 1 (n=4) or 2 (n=1). Of the 2 infants with bacterial infection, 1 had bacteremia due to viridans streptococci while the other one had necrotizing enterocolitis and a positive blood culture for Clostridium butyricum. The 3 infants with viral co-detection also were full term and all had positive enterovovirus PCR tests (1, blood, throat; 1, blood and ceerebrospinal fluid (CSF); 1, CSF) Conclusion 5% of infants with neonatal HSV infection had bacterial or enteroviral co-infection. These findings have important implications in the management of neonates evaluated for possible sepsis. Disclosures Asuncion Mejias, MD, PhD, MsCS, Janssen (Grant/Research Support, Advisor or Review Panel member)Merck (Advisor or Review Panel member)Roche (Advisor or Review Panel member)

Herpes simplex viruses type 1 (HSV-1) and type 2 (HSV-2) are highly prevalent within the human population and are characterized by lifelong infections and sporadic recurrences due to latent neuron infection. Upon reactivations, HSVs may manifest either, symptomatically or asymptomatically and be shed onto others through mucosae body fluids. Although, HSVs can produce severe disease in humans, such as life-threatening encephalitis and blindness, the most common symptoms are skin and mucosal lesions in the oro-facial and the genital areas. Nucleoside analogs with antiviral activity can prevent severe HSV infection, yet they are not very effective for treating skin manifestations produced by these viruses, as they only reduce in a few days at most the duration of lesions. Additionally, HSV variants that are resistant to these antivirals may arise, especially in immunosuppressed individuals. Thus, new antivirals that can reduce the severity and duration of these cutaneous manifestations would certainly be welcome. Here, we review currently available anti-herpetic therapies, novel molecules being assessed in clinical trials and new botanical compounds reported in the last 20 years with antiviral activities against HSVs that might represent future treatments against these viruses.

Imiquimod is an imidazole derivative acting as an immunomodulator on the level of innate and adaptive immune system. Our objective was to evaluate the antiviral activity of generically reproduced imiquimod administered subcutaneously in mice and intravaginally in guinea pigs against herpes simplex virus (HSV), as well as to study the dynamics of serum interferon (IFN) synthesis under different dosing regimens.When administered subcutaneously at doses of 0.5, 1.0 and 10 mg/kg imiquimod increased IFN production in mice in a dose-dependent manner with maximum serum IFN concentrations occurring 4 hours after dosing. Imiquimod protected mice from intraperitoneal HSV infection at doses of 3.2 and 32 LD50.The utmost protection (100% survival) was observed when imiquimod was administered at a dose of 100 mg/kg daily for 5 days before infection. Topical application of imiquimod 5% cream exhibited significantly more rapid and complete virus elimination in guinea pigs intravaginally infected with HSV type 2 compared to control group.Imiquimod produced as a generic possesses the same immunomodulatory and antiviral properties as the originally synthesized substance.Производное имидазола - имихимод - относится к иммуномодуляторам, действующим на врожденную и адаптивную системы иммунитета. Целью исследований было изучение динамики синтеза сывороточного интерферона (ИФН) при разных режимах дозирования и оценка противовирусной активности воспроизведенного в России препарата имихимода в отношении вируса простого герпеса (ВПГ) при его подкожном применении мышам и интравагинальном - морским свинкам. Результаты. При подкожном введении имихимода мышам в дозах 0,5; 1 и 10 мг/кг наблюдали дозозависимое увеличение выработки ИФН, пик концентрации которых достигался через 4 ч после введения. Применение имихимода защищало лабораторных животных (мышей) от внутрибрюшинного заражения ВПГ в дозах 3,2 и 32 ЛД50. При этом максимальный защитный эффект (100% выживаемость) достигался при введении имихимода в дозе 100 мкг/кг ежедневно в течение 5 дней до заражения. Топическое применение имихимода в виде 5% крема по сравнению с контрольной группой сопровождалось достоверно более быстрой и полной элиминацией вируса при интравагинальном заражении морских свинок ВПГ 2-го типа. Заключение. Воспроизведенный аналог имихимода обладает иммуномодулирующими и противовирусными свойствами, выявленными у первоначально синтезированного химического соединения.

As a result of the data examination analysis of the blood serum of patients of the RPRC «Mother and Child» for IgM and IgG to herpes simplex virus (HSV) using immunological test systems, the possibility of determining the form of the disease on the basis of a qualitative determination of the concentration of antibodies of the IgM class and quantitative detection of antibodies was proved IgG class, as well as the possibility of determining the duration of HSV infection based on the quantitative determination of IgG antibodies to HSV and the distribution of immunoglobulin titers over concentration ranges, indicating a particular stage in the formation of the immune response

Background: Herpes Simplex (HSV) viruses are widely spread, highly contagious human pathogens. The statistics indicate that 50-90% of adults worldwide are seropositive for these viruses, mainly HSV-1 and HSV-2. The primary infection results in the appearance of watery blisters (cold sores) on the skin, lips, tongue, buccal mucosa or genitals. The ocular infection is the major cause of corneal blindness in the Western World. Once the HSV virus enters human body, it cannot be completely eradicated because HSV viruses are able to change into their latent form which can survive the treatment. The viron resides in trigeminal ganglia of the host, who becomes vulnerable to the reoccurrence of the disease during the whole lifespan. The neurotropic and neuro-invasive properties of HSV are responsible for neurodegenerative illnesses, such as Alzheimer's disease. Acyclovir and its analogues, being the inhibitors of the viral DNA replication, are the only approved medicines for HSV infection therapies. Objective: The current paper presents the up-to-date overview of the important pharmacological features of acyclovir, its analogues and their delivery systems including the mechanism of action, routes of administration, absorption and metabolism, as well as side effects of the therapy. Conclusion: Acyclovir remains the gold standard in the treatment of herpes virus infections, mainly due to the emerging of the new delivery systems improving considerably its bioavailability. The analogues of acyclovir, especially their esters, characterized by significantly higher bioavailability and safety, may gradually replace acyclovir in selected applications.

The study of herpetic infection is a topical problem. Although the peculiarities and consequences of acute HSV-I infection in the brain are quite well-studied, little is known about the damage to other organs which are not a source of latent HSV-I infection, the liver in particular. The current study is aimed at determining the ultrastructural changes in murine liver following HSV infection and stroke. Liver samples obtained from four groups of animals were studied: 1) intact mice; 2) mice with stroke; 3) mice infected with HSV-I; 4) mice aflicted with HSV-I and subsequently simulated stroke. The study showed the reproduction of the virus in hepatic endotheliocytes, although no virions were detected in the hepatocytes. Therefore, the described changes were considered the consequences of the infectious process. Pathological changes of hepatocytes consisted of deformation and fragmentation of the nuclei, as well as accumulation of osmiophilic granules, lysosomes and lamellary bodies. Latent HSV-I infection may reactivate in liver after the stroke, potentially causing the complications of the underlying disease.

Objective: Herpes simplex virus (HSV) encephalitis has an overall mortality rate of 11%–29% with treatment. Although rare, HSV encephalitis is frequently tested for and empirically treated, especially in the neonatal population. HSV infection can be diagnosed with polymerase chain reaction (PCR) testing, although this frequently requires sending samples to reference laboratories. The inherent delay in results may lead to prolonging empiric treatment and hospital stay, resulting in increased costs. This study investigates whether onsite HSV PCR testing decreases hospitalization duration, acyclovir treatment duration, and financial cost on an institution. Project design: This single-center project utilized the IHI model for improvement to evaluate third-party HSV PCR processing versus an implemented onsite PCR-based meningitis–encephalitis panel for HSV central nervous system evaluation. The primary outcome was hospital cost differential with secondary outcomes, including duration of acyclovir administration and time to result. Results: We identified 96 children age 0–18 from 2010 to 2016, 74 patients utilizing offsite third-party testing, and 22 patients utilizing onsite. We observed a per-patient cost savings of $428 ($618.43–$190.43, P = 0.029) upon the implementation of onsite testing. The mean duration of acyclovir therapy decreased from 3.7 to 0.26 days per patient (P < 0.001). Time to result decreased from 4.6 to 0.13 days (P < 0.001). Conclusions: Acquisition of real-time local HSV PCR capabilities significantly decreased time to result and empiric medication use while significantly reducing hospital costs in a military treatment facility.

Provide evidence of HPV, C. trachomatis, and HSV infection in the oral cavity from patients with different types of stomatological lesions. Oral swabs samples were collected from a total of 318 patients. The infectious agents were analyzed using the PCR technique. HPV genotyping and HSV type were studied using the RFLP method. Results: We studied 137 benign lesions (B), 96 potentially malignant disorders (PMD) and 85 oral squamous cell carcinomas (OSCC). The prevalence of HPV was 34%. The most frequently genotypes detected were 6 low risk and 16 high risk. The prevalence of C. trachomatis was 16% and HSV 3%. Co-infections were detected mostly in benign lesions as following: HPV-C. trachomatis in 4%, C. trachomatis- HSV in 1.8% and HPV-HSV in 0.3%. This report is the first contribution to the identification and genotype characterization of HPV in a scenario little studied in our area, and it also contributes to improving our understanding on sexually transmitted infectious agents and their associations with the oral cavity. Besides, we detect the presence of C. trachomatis and HSV and co-infection with HPV in the oral cavity, which they should be taken into account for diagnostic and treatment purposes. Fil: Mosmann, Jessica Paola. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; Argentina. Instituto Universitario de Ciencias Biomédicas de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Talavera, Angel Daniel. Universidad Nacional de Córdoba. Facultad de Odontología; Argentina Fil: Criscuolo, María Inés. Universidad Nacional de Córdoba. Facultad de Odontología; Argentina Fil: Venezuela, Raul Fernando. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; Argentina Fil: Kiguen, Ana Ximena. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; Argentina Fil: Panico, René Luis. Universidad Nacional de Córdoba. Facultad de Odontología; Argentina Fil: Ferreyra de Prato, Ruth. Universidad Nacional de Córdoba. Facultad de Odontología; Argentina Fil: Lopez de Blanc, Silvia Adriana. Universidad Nacional de Córdoba. Facultad de Odontología; Argentina Fil: Ré, Viviana Elizabeth. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Cuffini, Cecilia Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; Argentina

Background:Catastrophic antiphospholipid syndrome (CAPS) is a severe autoimmune condition, characterized by multiorgan failure due to thromboses and/or hemorrhage. Concurrent HSV/VZV infection is an exceedingly rare event, occurring mostly in immunocompromised patients. Herein, we report the first case of CAPS triggered by concurrent HSV/VZV infection, manifesting with zosteriform rash and haemorrhages at multiple sites.Objectives:To describe a case of CAPS provoked by concurrent HSV/VZV infection, manifesting with zosteriform rash and haemorrhages at multiple sites.Methods:A 36-year-old male, with a history of antiphospholipid syndrome (APS) presented with a 5-day history of epigastric pain, associated with fever, hematuria, rash and swelling in bilateral ears. Past medical history was remarkable for APS, based on 4 episodes of DVT/PE and triple positive antiphospholipid antibodies, on chronic well-maintained warfarin anticoagulation. On examination, a purpuric rash was evident on the right side of the neck as well as on both ears, consistent with a C3 dermatomal distribution (Figure 1). Laboratory studies revealed anemia, thrombocytopenia and acute kidney injury.Figure 1.Results:A full-body CT scan demonstrated the presence of multifocal lymphadenopathy, alveolar infiltrates suggestive of diffuse alveolar haemorrhage, and haemorrhage in both kidneys and the left adrenal gland; anticoagulation was held, despite the INR being within the patient’s baseline therapeutic levels. He was admitted with a working diagnosis of CAPS and possible zoster infection. Appropriate immunologic workup was requested. He was prescribed intravenous acyclovir, antibiotics, pulse dose of glucocorticoids, and IVIG. Bronchoscopy with bronchoalveolar lavage revealed the presence of haemosiderin-laden macrophages. The rash regressed, and the patients’ condition improved. He was discharged with glucocorticoid tapering regimen, hydroxychloroquine, aspirin and warfarin.Antibody titers were taken prior to IVIG administration at presentation, and at 4 weeks. High VZV IgG titers found at presentation regressed over four times on follow-up. Furthermore, at 4 weeks the patient had developed IgM antibodies against both VZV and HSV. These findings confirmed a concurrent infection.Conclusion:This is the first report of coexisting HSV/VZV infection associated with CAPS. A literature review identified a total of 28 patients with coexisting HSV/VZV infection, whereas only one case of CAPS triggered by HSV was identified1. This case illustrates that concurrent infection can occur in the absence of immunosuppressive therapy in patients with APS, serving as a trigger for hemorrhagic CAPS. Simultaneous treatment with antiviral against herpesviruses, glucocorticoids and IVIG may mitigate the inflammatory cascade associated with CAPS.References:[1]Catoggio C, Alvarez-Uría A, Fernandez PL, Cervera R, Espinosa G. Catastrophic antiphospholipid syndrome triggered by fulminant disseminated herpes simplex infection in a patient with systemic lupus erythematosus. Lupus. 2012 Oct;21(12):1359-61.Disclosure of Interests:None declared.

PURPOSE: To review the literature for outcome measures for oral viral infections in cancer patients. A secondary aim was to update the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) clinical practice guidelines for the management of oral viral infections in cancer patients.METHODS: Databases were searched for articles published in the English language, 1981-2013. Studies that met the eligibility criteria were reviewed systematically. The data about the outcome measures were classified according to the aim of the study: prevention, treatment, or non-interventional. The results of interventional studies were compared to the 2010 MASCC/ISOO publication.RESULTS: Multiple clinical and laboratory tests were used to measure oral viral infections, with great variability between studies. Most of the studies were about Herpes Simplex Virus (HSV). The outcome measure that was most commonly used was the presence of HSV infection diagnosed based on a combination of suggestive clinical presentation with a positive laboratory result. HSV culture was the most commonly reported laboratory outcome measure. Acyclovir and valacyclovir were consistently reported to be efficacious in the management of oral herpetic infections. No new data on the quality of life and economic aspects was found.CONCLUSIONS: Considering the variability in outcome measures reported to assess oral herpetic infections the researcher should select carefully the appropriate measures based on the objective of the study. Acyclovir and valacyclovir are effective in the management of oral herpetic infections in patients receiving treatment for cancer. Studies on newer anti-viral drugs may be useful to address the issue of anti-viral resistance.

Previous studies suggested that herpes simplex virus (HSV) PCR testing can be safely deferred in patients with normal cerebrospinal fluid (CSF) white blood cell (WBC) counts and protein levels as long as they are older than 2 years of age and are not immunocompromised, the so-called Reller criteria. In this multicenter study, we retrospectively assessed the validity of these screening criteria in our setting. A total of 4,404 CSF specimens submitted for HSV PCR testing to the respective microbiology laboratories at the participating hospitals between 2012 and 2018 were included. Six commercially available HSV PCR assays were used across the participating centers. Ninety-one of the 4,404 CSF specimens (2.1%) tested were positive for HSV DNA (75 samples for HSV-1 and 16 for HSV-2). Nine patients failed to meet the Reller criteria, of whom seven were deemed to truly have HSV encephalitis. Overall, no significant correlation between HSV PCR cycle threshold (CT) values and WBC counts or total protein levels was found. In addition, median HSV PCR CTs were comparable between patients who met the Reller criteria and those who did not (P = 0.531). In summary, we show that HSV DNA may be detected in CSF specimens with normal WBC and protein levels collected from immunocompetent individuals older than 2 years with HSV encephalitis. Nevertheless, the data also indicate that the number of cases detected could be lowered at least by half if CSF specimens with borderline WBC counts (4 cells/mm3) as well as children of any age are systematically tested.

Background: Neonatal herpes simplex virus (HSV) infection is rare but potentially devastating and can result in neonatal death or serious disability. National incidence was estimated at 1.65/100,000 live births in an earlier British Paediatric Surveillance Unit (BPSU) study of births 1986-1991. Methods: A second surveillance study of neonatal HSV was undertaken through the BPSU 2004-2006, with follow-up information collected on surviving children in early childhood. Results: Over the three-year period, 85 infants were reported with confirmed neonatal HSV, an estimated incidence of 3.58/100,000 live births (95% CI 2.86-4.42), about double that reported almost two decades earlier. Over 40% of infants were pre-term compared with 25% in the earlier period. Just over 70% had central nervous system (CNS) or disseminated infection, and among these 54% had no skin, eye or mouth lesions noted. Almost all received antivirals, but 22 (26%) neonates died, all with disseminated or CNS infection. All but six infections were typed, of which 57% involved HSV-2; the increased risk of adverse outcomes associated with HSV-2 in the earlier study was confirmed and strengthened, with twice as many deaths or long term disability in infants with HSV-2 than HSV-1. As before, a reported history or diagnosis of maternal HSV infection was rare prior to infant diagnosis. Likely timing of infant exposure to HSV could only be assigned in 43% of cases, of which just over half were probable postnatal transmissions. Conclusions: Neonatal HSV infection remains rare although incidence doubled in the British Isles between the late 1990s and the mid-2000s. These findings suggest that future research should explore the relationship between pre-term delivery and infant susceptibility, and also the role of postnatal acquisition of infection. Healthcare professionals and new parents must continue to be aware of this rare condition in order to enable prompt investigation and instigation of treatment.

Inclusion of interleukin-1β into complex therapy of severe forms of herpes recurrent, allows to remove very effectively immune disturbances and to prevent occurrence of new infection relapses. Prophylactic prescription of interleukin-1β during remission period of herpes recurrent also demonstrated advisability of the therapy. On the background of therapy with interleukin-1β, 12 patients had remission duration. So, in 10 patients prior to therapy with interleukin-1β, remission duration was 1.5 ‐ 2 months, and after the therapy in 9 of them it increased to 10 ‐ 11 months. In 5 female patients, remission duration was 2 ‐ 3 months, after the treatment using interleukin-1β remission lasted more than 12 months. 3 patients during 2-year follow-up had no relapses at all. Anti-recurrent effect of interleukin-1β is related with immunomodulatory properties of the preparation, consisting of increased content of ripe lymphocytes and active lymphocytes (CD25+), as well as increased values of spontaneous and induced LPS NBT-test.

Introduction. Kaposi varicelliform eruption (KVE) is a widespread cutaneous viral infection, most commonly herpes simplex virus, which affects patients with underlying dermatosis. When KVE occurs in a patient with a history of psoriasis, it is referred to as psoriasis herpeticum, a rare subtype of KVE with only a handful of cases reported in the literature. To the authors’ knowledge, we report for the first time a case of psoriasis herpeticum in pregnancy. Case Presentation. A 23-year-old woman in her third pregnancy presented at 26-week gestation with a 10-year history of psoriasis. Cutaneous examination revealed diffuse psoriatic plaques with scattered ~1 cm erosions. Punch biopsy of the skin revealed herpes simplex virus (HSV) infection within a psoriatic plaque, necessitating dermatological treatment. The patient experienced premature rupture of membranes at 37-week gestation. Pelvic exam showed no evidence of herpetic lesions. After labor augmentation, the patient delivered a healthy female infant with no evidence of HSV infection. Discussion. Psoriasis herpeticum is a rare and potentially devastating complication of an underlying dermatosis. With a paucity of data available to guide pregnancy-specific issues, the general management of this condition is controversial and requires a multidisciplinary care approach. Concerns for systemic infection in the mother and vertical transmission to the neonate are of critical importance.

Common to the types of surgery that are effective for the treatment of trigeminal neuralgia (TN) is reactivation of herpes simplex virus (HSV). It is likely that such HSV reactivation following surgery indicates altered trigeminal ganglion neuron function, which was caused by the surgery. It is not thought that HSV infection is related to the cause of TN or that HSV reactivation is important for surgical treatment efficacy. Rather, it is thought that HSV reactivation is a marker of altered trigeminal ganglion neuron function resulting from the TN surgery. It is suggested that HSV reactivation is a surrogate marker of ganglion neuron injury. The correlation between effective types of surgery and evidence that they alter ganglion neuron function suggests that altered trigeminal ganglion neuron function may be the basis of the surgical efficacy.