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BackgroundIFNL4 genetic variants that are strongly associated with clearance of hepatitis C virus have been linked to risk of certain opportunistic infections (OIs) and cancers, including Kaposi sarcoma, cytomegalovirus infection, and herpes simplex virus infection. As the interferon (IFN) λ family plays a role in response to viral, bacterial, and fungal infections, IFNL4 genotype might affect risk for a wide range of OIs/cancers.MethodsWe examined associations between genotype for the functional IFNL4 rs368234815 polymorphism and incidence of 16 OIs/cancers among 2310 men with human immunodeficiency virus (2038 white; 272 black) enrolled in the Multicenter AIDS Cohort Study during 1984-1990. Our primary analyses used Cox proportional hazards models adjusted for self-reported racial ancestry to estimate hazard ratios with 95% confidence intervals, comparing participants with the genotypes that generate IFN-λ4 and those with the genotype that abrogates IFN-λ4. We censored follow-up at the introduction of highly effective antiretroviral therapies.ResultsWe found no statistically significant association between IFNL4 genotype and the incidence of Kaposi sarcoma (hazard ratio, 0.92 [95% confidence interval, .76-1.11]), cytomegalovirus infection (0.94 [.71-1.24]), herpes simplex virus infection (1.37 [.68-2.93]), or any other OI/cancer. We observed consistent results using additive genetic models and after controlling for CD4 cell count through time-dependent adjustment or restriction to participants with a low CD4 cell count.ConclusionsThe absence of associations between IFNL4 genotype and these OIs/cancers provides evidence that this gene does not affect the risk of disease from opportunistic pathogens.

Background: Tildrakizumab, the IL-23 inhibitor, is used to treat plaque psoriasis and psoriatic arthritis. Many studies have reported adverse drug reactions (ADRs) associated with Tildrakizumab. Objective: The aim of this study was to describe ADRs associated with Tildrakizumab monotherapy by mining data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: The signals of Tildrakizumab-associated ADRs were quantified using disproportionality analyses such as the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multiitem gamma Poisson shrinker (MGPS) algorithms. Results: A total of 10,530,937 reports of ADRs were collected from the FAERS database, of which 1,177 reports were identified with tildrakizumab as the "primary suspect (PS)". Tildrakizumab-induced ADRs occurred against 27 system organ classes (SOCs). A total of 32 significant disproportionality Preferred Terms (PTs) conformed to the algorithms. Unexpected significant ADRs such as coronavirus infection, herpes simplex, diverticulitis, atrial fibrillation and aortic valve incompetence were also possible. The median time to onset of Tildrakizumabassociated ADRs was 194 days (interquartile range [IQR] 84-329 days), with the majority occurring, within the first 1 and 3 months after initiation of Tildrakizumab. Conclusion: This study identified a potential signal for new ADRs with Tildrakizumab, which might provide important support for clinical monitoring and risk prediction. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Neutrophils are critical immune cells in severe coronavirus disease 2019 (COVID-19). S100 calcium-binding protein A12 (S100A12) is highly expressed in neutrophils during acute inflammation. The aim of this study was to evaluate serum S100A12 levels as a diagnostic and prognostic tool in COVID-19. Serum samples of patients with moderate and severe COVID-19 were collected during 2020 to 2024. Enzyme-linked immunosorbent assay was used to measure serum S100A12 levels in 63 patients with moderate COVID-19, 60 patients with severe disease and 33 healthy controls. Serum S100A12 levels were elevated in moderate COVID-19 compared to controls and were even higher in severe cases. In moderate disease, serum S100A12 levels positively correlated with immune cell counts. While C-reactive protein and procalcitonin are established inflammation markers, they did not correlate with serum S100A12 levels in either patient cohort. Patients with severe COVID-19 and vancomycin-resistant enterococcus (VRE) infection had increased S100A12 levels. Elevated S100A12 levels were also observed in patients with herpes simplex reactivation. Fungal superinfections did not alter S100A12 levels. These data show that serum S100A12 increases in moderate and severe COVID-19 and is further elevated by VRE bloodstream infection and herpes simplex reactivation. Therefore, S100A12 may serve as a novel biomarker for severe COVID-19 and an early diagnostic indicator for bacterial and viral infections. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To assess the management and outcomes of afebrile infants who received a pediatric dermatology consultation for pustules and/or vesicles. METHODS: Medical records were reviewed for all infants 60 days of age or younger who received a pediatric dermatology consult across 6 academic institutions between September 1, 2013 and August 31, 2019 to identify those infants with pustules and/or vesicles. RESULTS: Of the 879 consults, 183 afebrile infants presented with pustules and/or vesicles. No cerebrospinal fluid cultures or blood cultures were positive for bacteria. No concordant positive urine cultures were identified in infants with cutaneous infection. Nine infants were diagnosed with herpes simplex virus (HSV). Five preterm infants were diagnosed with angioinvasive fungal infections. CONCLUSIONS: No serious bacterial infections attributable to a skin source were identified, yet 53% of these infants received parenteral antibiotics. HSV was diagnosed in 7% of this cohort, 77.8% (7/9) of whom were term infants and 22.2% (2 of 9) of whom were preterm. Angioinvasive fungal infection was diagnosed in 3%, all of whom (100%, 5 of 5) were extremely preterm at <28 weeks gestational age. These findings suggest that in full-term afebrile infants #60 days, the likelihood of a life-threatening etiology of isolated pustules or vesicles is low once HSV infection is excluded. In preterm infants with pustules and/or vesicles, a high index of suspicion must be maintained, and broad infectious evaluation is recommended. HSV testing is recommended for all infants with vesicles, grouped pustules and/or punched-out erosions. [ABSTRACT FROM AUTHOR]

Background and Aim: Inner ear infection with some viruses may be one of the possible causes of Sensorineural Hearing Loss (SNHL). This study aims to determine the frequency of Herpes Simplex Virus 1 and 2 (HSV-1, HSV-2) and Cytomegalovirus (CMV) in perilymph and peripheral blood samples of cochlear-implanted children. Methods: In this cross-sectional study, 30 children with severe-to-profound SNHL (aged 1.1–5 years) underwent cochlear implantation surgery. During surgery, their perilymph and peripheral blood samples were collected. The samples were analyzed separately for the presence of herpes HSV-1, HSV-2, and CMV by real-time Polymerase Chain Reaction (PCR) method. The load of IgG and IgM antibodies against these viruses was determined using the Enzyme-Linked Immunosorbent Assay (ELISA) method. Results: The frequency of CMV in perilymph samples was 16.7% (5 patients) and in peripheral blood samples was 3.3% (1 patient). The IgG antibody against CMV and HSV1 was positive in 80% and 46.7% of the patients, respectively. The IgM antibody against CMV was positive in 10%. The mean IgM serum antibody load against HSV-1, HSV-2, and CMV was 2.70, 1.70, and 5.47, respectively, and the mean IgG antibody load against these viruses was 56.07, 2.50, and 23.67, respectively. Conclusion: The IgG test is positive in cochlear-implanted children with CMV in their perilymph samples, and the CMV genome is not present in their peripheral blood. This may indicate the previous presence of this virus in the ear and its role in hearing loss. [ABSTRACT FROM AUTHOR]

Background: Abrocitinib, an oral, once-daily, Janus kinase 1-selective inhibitor, is efficacious in moderate-to-severe atopic dermatitis with a manageable long-term safety profile. Objective: We aimed to provide updated integrated long-term safety results for abrocitinib from available data accrued up to a maximum of almost 4 years in patients with moderate-to-severe atopic dermatitis from the JADE clinical development program. Methods: Analysis included 3802 patients (exposure: 5213.9 patient-years) from the phase II monotherapy study (NCT02780167) and the phase III studies JADE MONO-1 (NCT03349060), JADE MONO-2 (NCT03575871), JADE TEEN (NCT03796676), JADE COMPARE (NCT03720470), JADE DARE (NCT04345367; 200 mg only), JADE REGIMEN (NCT03627767), and JADE EXTEND (NCT03422822; data cutoff 25 September, 2021). Data from patients receiving one or more doses of abrocitinib 200 mg or 100 mg were pooled in a consistent-dose cohort (patients were allocated to receive the same abrocitinib dose throughout exposure in the qualifying parent study and/or long-term study) or a variable-dose cohort (patients received open-label abrocitinib 200 mg; responders were randomized to abrocitinib 200 mg, 100 mg, or placebo, and could then receive abrocitinib 200 mg plus topical corticosteroids as rescue therapy). Incidence rates of adverse events of special interest were assessed. Cox regression analysis of risk factors for herpes zoster and serious infections was performed. Results: Overall, this safety analysis of long-term data up to a maximum of ~ 4 years of abrocitinib exposure does not indicate any changes from the previously reported risk profile. The most frequent serious infections (per Medical Dictionary for Regulatory Activities preferred term) with consistent-dose abrocitinib 200 mg and 100 mg were herpes zoster (0.5% and 0.2%), pneumonia (0.2% with either dose), and herpes simplex (0.1% with either dose). Risk factors for herpes zoster were a history of herpes zoster, abrocitinib 200-mg dose, age ≥ 65 years, absolute lymphocyte count < 1 × 103/mm3 before the event, and residing in Asia. For serious infections, > 100 kg body weight was a risk factor. Incidence rate/100 patient-years (95% confidence interval) with the consistent abrocitinib 200-mg and 100-mg dose combined was higher in older (aged ≥ 65 years) patients versus younger (aged 18 to < 65 years) patients for serious adverse events (17.6 [11.7‒25.4] vs 6.7 [5.8‒7.8]), malignancy excluding non-melanoma skin cancer (2.4 [0.6‒6.0] vs 0.1 [0.0‒0.4]), non-melanoma skin cancer (2.4 [0.6‒6.1] vs 0.2 [0.1‒0.4]), lymphopenia (3.5 [1.3‒7.6] vs 0.1 [0.0‒0.3]), and venous thromboembolism (1.7 [0.4‒5.1] vs 0.1 [0.0‒0.3]). Incident rate/100 patient-years (95% confidence interval) of non-melanoma skin cancer with the consistent abrocitinib 200-mg and 100-mg dose combined was higher in current/former smokers (0.9 [0.4‒1.6]) vs never-smokers (0.0 [0.0‒0.1]). Conclusions: This safety update showed a consistent profile for abrocitinib with no new safety signals and continues to support that abrocitinib has a manageable long-term safety profile in patients with moderate-to-severe atopic dermatitis. Risk of specific adverse events was higher in certain patient populations, especially those aged ≥ 65 years. [Video abstract available.] Clinical Trial Registration: NCT02780167; study start date: April, 2016; primary completion date: March, 2017; study completion date: April, 2017. NCT03349060; study start date: 7 December, 2017; study completion date: 26 March, 2019. NCT03575871; study start date: 29 June, 2018; study completion date: 13 August, 2019. NCT03720470; study start date: 29 October, 2018; primary completion date: 27 December, 2019; study completion date: 6 March, 2020. NCT03796676; study start date: 18 February, 2019; study completion date: 8 April, 2020. NCT03627767; study start date: 11 June, 2018; primary completion date: 2 September, 2020; study completion date: 7 October, 2020. NCT04345367; study start date: 11 June, 2020; primary completion date: 16 December, 2020; study completion date: 13 July, 2021. NCT03422822; study start date: 8 March, 2018; study completion date: ongoing (estimated completion date: 31 January, 2026). Plain Language Summary: Abrocitinib is an approved treatment for people with moderate or severe atopic dermatitis, also known as AD or atopic eczema. Abrocitinib is a tablet that is taken by mouth once a day. This safety analysis looked at the side effects of treatment in a large group of adults and adolescents with moderate or severe AD who took abrocitinib up to a maximum of almost 4 years. This analysis also looked at which people were more likely to have certain side effects after taking abrocitinib. The results from this analysis were similar to those of previous safety analyses with abrocitinib, with no new side effects. Infections such as shingles, pneumonia, or herpes simplex can occur during treatment with abrocitinib. Shingles was more likely to occur in people who previously had shingles before taking abrocitinib, or who took the higher dose of abrocitinib (200 mg), or were 65 years of age or older, or had certain blood test results, or lived in Asia. People who are 65 years of age or older and took abrocitinib were more likely to develop some types of cancer, have certain abnormal blood test results, or develop blood clots in the veins than people with AD who were younger and took abrocitinib. Current or former smokers with AD who took abrocitinib were more likely to develop skin cancer (but not melanoma) than people with AD who took abrocitinib but have never smoked. This analysis further shows that abrocitinib had manageable safety in patients with moderate-to-severe AD. Dex5AhfAxs29XQspjFnxYi Video abstract: Integrated safety update of abrocitinib in 3802 patients with moderate-to-severe atopic dermatitis: data from more than 5200 patient-years with up to 4 years of exposure (MP4 63720 KB) [ABSTRACT FROM AUTHOR]

The article focuses on investigating the correlation between autoimmune diseases, immunosuppressive medications, and the onset of herpes simplex virus encephalitis (HSVE), highlighting associations found in a large U.S. Medicaid database study.

Atopic conditions are known to be associated with viral and bacterial infections. The purpose of this study was to determine the relationship between the effects of atopic conditions on the severity and recurrence of ocular infections including herpes simplex virus (HSV). This study was performed on 474 consecutive patients with infectious keratitis caused by bacteria, fungus, acanthamoeba, HSV, or varicella-zoster virus. The relationships between the atopic condition and specific infectious pathogens and HSV were determined using real-time PCR. Our findings showed that atopic dermatitis (AD) was significantly associated with the incidence of HSV keratitis (odds ratio (OR), 10.2; P = 0.000). Other associations with AD were observed only with bacteria in an adverse manner. HSV proliferation in the lesions of patients with HSV keratitis whose AD was associated with non-infectious atopic blepharitis were significantly greater by 145-folds (P = 0.000). The presence of asthma or allergic rhinitis also increased the HSV DNA copy numbers. A recurrence of HSV keratitis was observed in 70 patients (43.2 %), and mean time to recurrence was 1647 days. Cox proportional hazard model indicated that the epithelial type of HSV recurrence but not the stromal type was associated with atopic conditions especially with AD. The factors significantly associated with a recurrence was AD associated with non-infectious atopic blepharitis (HR: 6.11, P = 0.000) and asthma (HR: 3.03, P = 0.025). Atopic conditions, especially AD with atopic blepharitis, are significantly associated with the development, increased proliferation, and shorter time to a recurrence on HSV keratitis. [ABSTRACT FROM AUTHOR]

This article provides information on fetal growth restriction (FGR), a condition where a fetus does not reach its full growth potential due to a pathological factor. It discusses the classification of FGR based on gestational age at diagnosis and explores the causes and outcomes of pre- and periviable FGR. The article emphasizes the importance of genetic counseling and testing in cases of FGR and provides information on the prevalence of genetic anomalies, structural defects, and congenital infections in these cases. It also discusses the incidence and outcome of placental insufficiency as a cause of FGR. The article highlights the varying frequency of hypertensive disorders of pregnancy (HDP) in pre- and periviable FGR and their impact on maternal and fetal/neonatal health. It concludes by discussing the management of pre- and periviable FGR, including the consideration of termination of pregnancy in certain cases and the determination of the mode of delivery for fetuses alive at birth. [Extracted from the article]

Herpesvirus assembly requires the cytoplasmic association of large macromolecular and membrane structures that derive from both the nucleus and cytoplasmic membrane systems. Results from the study of human cytomegalovirus (HCMV) in cells where it organizes a perinuclear cytoplasmic virus assembly compartment (cVAC) show a clear requirement for the minus-end-directed microtubule motor, dynein, for virus assembly. In contrast, the assembly of herpes simplex virus -1 (HSV-1) in epithelial cells where it forms multiple dispersed, peripheral assembly sites is only mildly inhibited by the microtubule-depolymerizing agent, nocodazole. Here, we make use of a neuronal cell line system in which HSV-1 forms a single cVAC and show that dynein and its co-factor dynactin localize to the cVAC, and dynactin is associated with membranes that contain the virion tegument protein pUL11. We also show that the virus membraneassociated structural proteins pUL51 and the viral envelope glycoprotein gE arrive at the cVAC by different routes. Specifically, gE arrives at the cVAC after retrieval from the plasma membrane, suggesting the need for an intact retrograde transport system. Finally, we demonstrate that inhibition of dynactin function profoundly inhibits cVAC formation and virus production during the cytoplasmic assembly phase of infection. IMPORTANCE Many viruses reorganize cytoplasmic membrane systems and macromolecular transport systems to promote the production of progeny virions. Clarifying the mechanisms by which they accomplish this may reveal novel therapeutic strategies and illustrate mechanisms that are critical for normal cellular organization. Here, we explore the mechanism by which HSV-1 moves macromolecular and membrane cargo to generate a virus assembly compartment in the infected cell. We find that the virus makes use of a well-characterized, microtubule-based transport system that is stabilized against drugs that disrupt microtubules. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are membrane-bound vesicles secreted by all cell types that play a central role in cell-to-cell communication. Since these vesicles serve as vehicles of cellular content (nucleic acids, proteins and lipids) with the potential to cross biological barriers, they represent a novel attractive window into an otherwise inaccessible organ, such as the brain. The composition of EVs is cell-type specific and mirrors the physiological condition of the cell-of-origin. Consequently, during viral infection, EVs undergo significant changes in their content and morphology, thereby reflecting alterations in the cellular state. Here, we briefly summarize the potential of brain-derived EVs as a lens into viral infection in the central nervous system, thereby: 1) uncovering underlying pathophysiological processes at play and 2) serving as liquid biopsies of the brain, representing a non-invasive source of biomarkers for monitoring disease activity. Although translating the potential of EVs from research to diagnosis poses complexities, characterizing brain-derived EVs in the context of viral infections holds promise to enhance diagnostic and therapeutic strategies, offering new avenues for managing infectious neurological diseases. [ABSTRACT FROM AUTHOR]

Background: Acyclovir is an anti-viral medication given to treat herpes simplex and herpes zoster infection. In some severe conditions such as herpes encephalitis, acyclovir is administered intravenously. However, high acyclovir doses may cause acute kidney injury and low acyclovir dose may predispose the patient to inadequate exposure to acyclovir which could be fatal in some conditions. In such cases, the acyclovir plasma concentrations will potentially guide the diagnosis and management of the kidney injury. In this study, we provide a simple and time-efficient method for analyzing acyclovir in human plasma using high-performance liquid chromatography (HPLC). Results: The process starts with a single protein precipitation step by adding acetonitrile to deproteinize 300 µL of plasma. The chromatographic separation conditions consist of a mobile phase of water: methanol (97:3, v/v), a flow rate of 1 mL/min, a run time of 17 min, and a detection wavelength of 254 nm. The calibration curve was linear over the range of (0.70–60 mg/L) (r2 ˃ 0.99). The retention times of acyclovir and the internal standard were around 15 and 12 min, respectively. The intra-day and inter-day analysis of acyclovir in plasma using this method exhibited accuracy and precision of less than 7%, which lies within the acceptable range. Different greenness assessment tools confirmed that the proposed method is eco-friendly. Conclusion: The proposed method of analysis of acyclovir in the plasma using HPLC is simple, green and accurate method. This method could be applied in clinical settings where monitoring acyclovir concentrations is essential as it has wide range of the concentrations that could be detected. [ABSTRACT FROM AUTHOR]

Background: Herpes simplex encephalitis (HSE) is an important central nervous infection with severe neurological sequelae. The aim of this study was to describe clinical characteristic and outcomes of patients with HSE in Vietnam. Methods: This was a retrospective study of 66 patients with herpes simplex encephalitis who admitted to the National Hospital for Tropical Diseases, Hanoi, Vietnam from 2018 to 2021. The detection of herpes simplex virus (HSV) in cerebrospinal fluid was made by the real-time PCR assay. We reported the clinical manifestation on admission and evaluated clinical outcomes at the hospital discharge by modified Rankin Scale (mRS). Multivariate logistic regression analysis was used to analyze the independent risk factors of severe outcomes. Results: Of the 66 patients with laboratory confirmed HSE, the median age was 53 years (IQR 38–60) and 44 patients (69.7%) were male. The most common manifestations included fever (100%), followed by the consciousness disorder (95.5%). Other neurological manifestation were seizures (36.4%), memory disorders (31.8%), language disorders (19.7%) and behavioral disorders (13.6%). Conventional magnetic resonance imaging (MRI) showed 93.8% patients with temporal lobe lesions, followed by abnormalities in insula (50%), frontal lobe (34.4%) and 48.4% of patients had bilateral lesions. At discharge, 19 patients (28.8%) completely recovered, 15 patients (22.7%) had mild sequelae, 28 patients (42.4%) had moderate to severe sequelae. Severe neurological sequelae were memory disorders (55.8%), movement disorders (53.5%), language disorders (30.2%). Multivariate logistic regression analysis showed that Glasgow score decrement at admission, seizures, and time duration from onset of symptoms to the start of Acyclovir treatment > 4 days were independent factors associated with severe outcomes in HSE patients. Conclusion: Glasgow score decrement, seizures and delay treatment with Acyclovir were associated with the poor outcome of patients with HSE. [ABSTRACT FROM AUTHOR]

Ophthalmia neonatorum (ON) is a form of conjunctivitis occurring within the 1st month of life, primarily attributable to bacterial pathogens. The predominant etiological agents include Chlamydia trachomatis and Neisseria gonorrhoeae. Viral pathogens such as herpes simplex, adenovirus, and enterovirus may also incite ON. Hospital-acquired conjunctivitis (HAC) rarely affects healthy infants who have received prophylactic treatment against ON. Herein, we report a case of ON in a healthy female newborn female caused by Klebsiella pneumoniae. Following the infant's and her parents' treatment, the patient's condition improved, leading to discharge. Strict adherence to infection control protocols, including meticulous hand hygiene practices, is crucial for attenuating this issue and averting the serious complications associated with HAC. [ABSTRACT FROM AUTHOR]

Currently, four vaccines for COVID-19 have been licensed by the European Medicines Agency: two viral vector-based vaccines and two mRNA-based vaccines. Since their approval, several cutaneous reactions related to vaccination have been reported in the literature. Among these, viral reactivations are one of the most frequent. The aim of this article was to investigate the current literature regarding viral reactivations following COVID-19 vaccination, focusing attention on pityriasis rosea (PR), herpes zoster and herpes simplex. A comprehensive literature search using various databases was performed and we included metanalyses, reviews, letters to the editor, real-life studies, case series and reports. A total of 48 articles involving 2067 patients were selected. Of these, 32, 6 and 17 articles reported varicella zoster virus (VZV) reactivation (1758 patients), herpes simplex virus (HSV) (238 patients) onset and PR (71 patients), respectively (some articles discussed more than one of these three reactivations). Possible pathogenetic mechanisms underlying viral reactivation are still not understood. Also, the possible correlations between vaccination and viral reactivation should be clarified. Certainly, vaccination should not be discouraged. [ABSTRACT FROM AUTHOR]

Aciclovir is considered the first‐line treatment against Herpes simplex virus (HSV) infections in new‐borns and infants. As renal excretion is the major route of elimination, in renally‐impaired patients, aciclovir doses are adjusted according to the degree of impairment. However, limited attention has been given to the implications of immature renal function or dysfunction due to the viral disease itself. The aim of this investigation was to characterize the pharmacokinetics of aciclovir taking into account maturation and disease processes in the neonatal population. Pharmacokinetic data obtained from 2 previously published clinical trials (n = 28) were analyzed using a nonlinear mixed effects modeling approach. Post‐menstrual age (PMA) and creatinine clearance (CLCR) were assessed as descriptors of maturation and renal function. Simulation scenarios were also implemented to illustrate the use of pharmacokinetic data to extrapolate efficacy from adults. Aciclovir pharmacokinetics was described by a one‐compartment model with first‐order elimination. Body weight and diagnosis (systemic infection) were statistically significant covariates on the volume of distribution, whereas body weight, CLCR and PMA had a significant effect on clearance. Median clearance varied from 0.2 to 1.0 L/h in subjects with PMA <34 or ≥34 weeks, respectively. Population estimate for volume of distribution was 1.93 L with systemic infection increasing this value by almost 3‐fold (2.67 times higher). A suitable model parameterization was identified, which discriminates the effects of developmental growth, maturation, and organ function. Exposure to aciclovir was found to increase with decreasing PMA and renal function (CLCR), suggesting different dosing requirement for pre‐term neonates. [ABSTRACT FROM AUTHOR]

Adolescents and young adults (AYAs) living with HIV have high rates of co-sexually transmitted infections (STIs). During the coronavirus disease (COVID) pandemic, STI prevention strategies, including access to testing/treatment facilities, availability of health care workers, and condom availability, may have decreased. This study aimed to determine if differences in STI incidence for first infection and reinfection existed between the pre-COVID and COVID eras in a cohort of AYAs living with HIV in Atlanta, GA. Retrospective chart review was conducted for all patients between ages 13 and 24 at the Grady Ponce Clinic. Two eras were identified: a pre-COVID era (January 1, 2009–December31, 2019) and a COVID era (January 1, 2020–June 30, 2021). STIs recorded included gonorrhea, chlamydia, human papillomavirus, syphilis, trichomonas, herpes simplex virus, lymphogranuloma venereum, hepatitis C, bacterial vaginosis, and chancroid. First and recurrent incidence rates for any STIs were reported. Our sample included 766 sexually active AYAs with HIV. A total of 721 patients were included in the pre-COVID era and 583 (80.9%) had at least one STI. A total of 337 patients were included in the COVID era, and 158 had at least one STI (46.9%). The overall first STI incidence rate increased from 42.47 to 58.67 per 100 person-years (PY) and the recurrent STI incidence rate increased from 121.50 to 169.85 per 100 PY from the pre-COVID to the COVID era (p < 0.001). Our study demonstrated significantly higher incidence rates of first and recurrent STIs in AYAs living with HIV in the COVID era. We urge continuation of existing STI prevention programs to avoid secondary clinical and economic adverse effects of increased infections. [ABSTRACT FROM AUTHOR]

Herpes stromal keratitis (HSK) is an immune-mediated corneal inflammation that occurs after a herpes simplex virus infection. This paper aims to systematically identify and compare interventions for treating HSK and their patient outcomes. This systematic review followed the PRISMA methodology. Online databases were searched to obtain all relevant papers. Two independent reviewers screened through 168 records. Seven papers were included and used for data extraction. A qualitative analysis was conducted. HSK patients receiving prednisolone phosphate and acyclovir showed a higher treatment success rate and significantly longer time to failure compared to patients receiving only acyclovir (P <.001). No difference in resolution time was found between oral and topical acyclovir. Between groups receiving dexamethasone and flurbiprofen, resolution occurred in 93% and 67% of patients, and BCVA (LogMAR) improved from 1.0 to 0.30 and 0.48, respectively. BCVA improved in both cyclosporine-A (P <.001) and its control (prednisolone) groups (P =.002). A tacrolimus treatment group showed greater improvement in BCVA compared to its control (prednisolone) group (P <.001). Corticosteroids and antivirals managed HSK most effectively only when used concurrently. Oral acyclovir showed similar effectiveness to its ointment counterpart, a preferable alternative for easier administration. Corticosteroid use could induce greater therapeutic benefits when tapered in concentration and frequency and administrated for at least 10 weeks. Anti-inflammatory drugs including flurbiprofen, cyclosporine-A, and tacrolimus could be safe and effective for treating HSK. Future long-term follow-up and RCTs could provide insights on the therapeutic benefits of these potential alternatives. [ABSTRACT FROM AUTHOR]

This study examines the clinical features and risk factors associated with early mortality in patients with cartilage-hair hypoplasia (CHH), a rare genetic disorder. The study compares data from three international registries and finds that uncontrolled Epstein-Barr virus (EBV) infection is the only factor significantly correlated with early mortality. The study also notes that allogeneic hematopoietic stem cell transplantation (HSCT) was more common in the USIDNET registry, and that the median age at latest follow-up was shortest in the USIDNET cohort. The study concludes that screening for EBV infection and early management of uncontrolled EBV proliferation should be considered in CHH patients. [Extracted from the article]

Herpes simplex virus type 1 (HSV-1) infection of the eyes results in herpes simplex keratitis (HSK), which has led to vision loss and even blindness in patients. However, the rate of drug resistance in HSV is on the rise; therefore, new antiviral agents with sufficient safety profiles must be developed. At present, we assessed the anti-HSV-1 activity of 502 natural compounds and their ability to reduce the HSV-1-induced cytopathic effect. We chose harmol for further studies because it exhibited the highest antiviral activity. We found that harmol inhibited both HSV-1 F and HSV-1/153 (a clinical drug-resistant strain) replication, with an EC50 of 9.34 µM and 5.84 µM, respectively. Moreover, harmol reduced HSV-1 replication in corneal tissues and viral progeny production in tears, and also alleviated early corneal surface lesions related to HSK. For example, harmol treatment preserved corneal thickness and nerve density in HSK mice. Interestingly, harmol also showed a promising antiviral effect on HSV-1/153 induced HSK in mouse model. Furthermore, harmol combined with acyclovir (ACV) treatment showed a greater antiviral effect than either one alone in vitro. Therefore, harmol may be a promising therapeutic agent for managing HSK. [ABSTRACT FROM AUTHOR]

Herpes simplex virus (HSV) is a causative agent of fever blister, genital herpes, and neonatal herpes. Nowadays, edible algae are recognized as health food due to high nutrition content and their many active compounds that are beneficial to health. The purpose of this study is to investigate the inhibitory effects of algal polysaccharide extract from Cladophora spp. against herpes simplex virus type 1 and type 2 on Vero cells. In this study, the structure of polysaccharide extract is presented as S=O and C–O–S of the sulfate group, as identified by the FT-IR technique. The toxicity of algal polysaccharide extract on Vero cells was determined by MTT assay. The algal extract showed low toxicity on the cells, with 50% cytotoxic concentration (CC50) value greater than 5000 µg mL−1. The inhibition of HSV infection by the algal extract was then evaluated on Vero cells using plaque reduction assay. The 50% effective concentration (EC50) values of algal extract exhibited antiviral activity against HSV-1 upon treatment before, during, and after viral adsorption with and without removal of the extract were 70.31, 15.17, > 5000 and 9.78 µg mL−1, respectively. Additionally, the EC50 values of algal extract against HSV-2 upon treatment before, during and after viral adsorption with, and without removal of the extract were 5.85, 2.57, > 5000 and 26.96 µg mL−1, respectively. Moreover, the algal extract demonstrated direct inactivation of HSV-1 and HSV-2 virions as well as inhibitory effect against HSV replication. Accordingly, algal polysaccharide extract containing sulfated polysaccharides showed strong activity against HSV. Therefore, it is proved to be useful to apply Cladophora spp. polysaccharide extract as an anti-HSV agent. [ABSTRACT FROM AUTHOR]

Encephalitis is a rare and potentially fatal manifestation of herpes simplex type 1 infection. Following genome-wide genetic analyses, we identified a previously uncharacterized and very rare heterozygous variant in the E3 ubiquitin ligase WWP2, in a 14-month-old girl with herpes simplex encephalitis. The p.R841H variant (NM_007014.4:c.2522G > A) impaired TLR3 mediated signaling in inducible pluripotent stem cells-derived neural precursor cells and neurons; cells bearing this mutation were also more susceptible to HSV-1 infection compared to control cells. The p.R841H variant increased TRIF ubiquitination in vitro. Antiviral immunity was rescued following the correction of p.R841H by CRISPR-Cas9 technology. Moreover, the introduction of p.R841H in wild type cells reduced such immunity, suggesting that this mutation is linked to the observed phenotypes. Encephalitis is a rare and severe complication of Herpes Simplex type 1 infection. Here, Bibert et al describe a genetic variant in a 2-year-old affected child that impairs interferon production in neuronal cells and enhances viral replication. [ABSTRACT FROM AUTHOR]

Background: Autoimmune diseases have always been one of the difficult diseases of clinical concern. Because of the diversity and complexity of its causative factors, unclear occurrence and development process and difficult treatment, it has become a key disease for researchers to study. And the disease explored in this paper, anti-NMDA encephalitis, belongs to a common type of autoimmune encephalitis. However, the quality of articles and research hotspots in this field are not yet known. Therefore, in this field, we completed a bibliometric and visualization analysis from 2005 to 2023 in order to understand the research hotspots and directions of development in this field. Materials and methods: We searched the SCI-expanded databases using Web of Science's core databases on January 22, 2024 and used tools such as VOS viewer, Cite Space, and R software to visualize and analyze the authors, countries, journals, institutions, and keywords of the articles. Results: A total of 1,161 literatures were retrieved and analyzed in this study. China was the country with the most total publications, and USA and Spain were the most influential countries in the field of anti-NMDA encephalitis. University of Pennsylvania from USA was the institution with the highest number of publications. While Dalmau Josep is the most prolific, influential and contributing author who published one of the most cited articles in Lancet Neurology, which laid the foundation for anti-NMDA encephalitis research, the top three appearances of keyword analysis were: "antibodies", "diagnosis", and "autoimmune encephalitis." Conclusion: Bibliometric analysis shows that the number of studies on anti-NMDA encephalitis is generally increasing year by year, and it is a hot disease pursued by researchers. USA and Spain are leading in the field of anti-NMDA encephalitis, while China should continue to improve the quality of its own research. The suspected causes of anti-NMDA encephalitis other than ovarian teratoma and herpes simplex, the specific clinical manifestations that are not masked by psychiatric symptoms, the diagnostic modalities that are faster and more accurate than antibody tests, and the improvement of treatment modalities by evaluating prognosis of various types of patients are the hotspots for future research. [ABSTRACT FROM AUTHOR]

Polymicrobial infections are the leading causes of complications incurred from injuries that burn patients develop. Such patients admitted to the hospital have a high risk of developing hospital-acquired infections, with longer patient stays leading to increased chances of acquiring such drug-resistant infections. Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Proteus mirabilis are the most common multidrug-resistant (MDR) Gram-negative bacteria identified in burn wound infections (BWIs). BWIs caused by viruses, like herpes simplex and varicella zoster, and fungi-like Candida species appear to occur occasionally. However, the preponderance of infection by opportunistic pathogens is very high in burn patients. Variations in the causative agents of BWIs are due to differences in geographic location and infection control measures. Overall, burn injuries are characterized by elevated serum cytokine levels, systemic immune response, and immunosuppression. Hence, early detection and treatment can accelerate the wound-healing process and reduce the risk of further infections at the site of injury. A multidisciplinary collaboration between burn surgeons and infectious disease specialists is also needed to properly monitor antibiotic resistance in BWI pathogens, help check the super-spread of MDR pathogens, and improve treatment outcomes as a result. Key Words: burn wound infections; biofilm; epidermis; hospital; opportunistic infection [ABSTRACT FROM AUTHOR]

To benchmark the epidemiologic features of pediatric ocular surface inflammatory diseases (POSID). Retrospective cohort study. Patients 18 years of age or younger with a medical claim for a diagnosis of POSID in the Optum Labs Data Warehouse between 2007 and 2020. Patients with claims of blepharokeratoconjunctivitis (BKC), herpes simplex keratoconjunctivitis (HSK), or vernal keratoconjunctivitis (VKC) were included. Those with less than 6 months of follow-up before the initial diagnosis of POSID were excluded. Odds ratios (ORs) were derived from multivariable logistic regression analyses evaluating the associations between epidemiologic variables and POSID development. The primary outcome was the estimated prevalence of POSID. Prevalence of POSID subtypes and changes in prevalence over time were also evaluated. Two thousand one hundred sixty-eight patients with POSID were identified from 2018 through 2019, yielding an estimated prevalence of 3.32 per 10 000. The prevalence of POSID was higher among children between 5 and 10 years of age, male children, those of Asian descent, and those living in the Northeast and the West census regions of the United States. The prevalence (per 10 000) of BKC, HSK, and VKC in the same period were 0.59 (95% confidence interval [CI], 0.53–0.65), 0.74 (95% CI, 0.68–0.81), and 1.99 (95% CI, 1.88–2.10), respectively, and significant differences were found in terms of age, sex, racial, ethnic, and regional distributions among the diagnoses. Between 2008 through 2009 and 2018 through 2019, a significant increase in POSID was noted among Asians (from 6.26 [95% CI, 5.28–7.36] to 11.80 [95% CI, 10.40–13.34]) driven by changes in VKC. Multivariable analysis demonstrated that age older than 5 years (OR, 2.57–3.75; 95% CI, 2.17–4.34), male sex (OR, 1.38; 95% CI, 1.26–1.50), Asian descent (OR, 3.12; 95% CI, 2.70–3.60), and Black or African American descent (OR, 1.26; 95% CI, 1.02–1.55) were associated with POSID development. This study provides an estimated prevalence of POSID and its 3 common subtypes in the United States, with important epidemiologic differences among them. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. [ABSTRACT FROM AUTHOR]

Acquiring resistance against antiviral drugs is a significant problem in antimicrobial therapy. In order to identify novel antiviral compounds, the antiviral activity of eight plants indigenous to the southern region of Hungary against herpes simplex virus-2 (HSV-2) was investigated. The plant extracts and the plant compound carnosic acid were tested for their effectiveness on both the extracellular and intracellular forms of HSV-2 on Vero and HeLa cells. HSV-2 replication was measured by a direct quantitative PCR (qPCR). Among the tested plant extracts, Salvia rosmarinus (S. rosmarinus) exhibited a 90.46% reduction in HSV-2 replication at the 0.47 μg/mL concentration. Carnosic acid, a major antimicrobial compound found in rosemary, also demonstrated a significant dose-dependent inhibition of both extracellular and intracellular forms of HSV-2. The 90% inhibitory concentration (IC90) of carnosic acid was between 25 and 6.25 μg/mL. Proteomics and high-resolution respirometry showed that carnosic acid suppressed key ATP synthesis pathways such as glycolysis, citrate cycle, and oxidative phosphorylation. Inhibition of oxidative phosphorylation also suppressed HSV-2 replication up to 39.94-fold. These results indicate that the antiviral action of carnosic acid includes the inhibition of ATP generation by suppressing key energy production pathways. Carnosic acid holds promise as a potential novel antiviral agent against HSV-2. [ABSTRACT FROM AUTHOR]

Background: The manifestations of bullous pemphigoid (BP) and herpes simplex virus (HSV) infection are similar in oral mucosa, and the laboratory detection of HSV has some limitations, making it difficult to identify the HSV infection in oral lesions of BP. In addition, the treatments for BP and HSV infection have contradictory aspects. Thus, it is important to identify the HSV infection in BP patients in time. Objective: To identify the prevalence and clinical markers of HSV infection in oral lesions of BP. Methods: This prospective cross-sectional descriptive analytical study was conducted on 42 BP patients with oral lesions. A total of 32 BP patients without oral lesions and 41 healthy individuals were enrolled as control groups. Polymerase chain reaction was used to detect HSV. Clinical and laboratory characteristics of patients with HSV infection were compared with those without infection. Results: A total of 19 (45.2%) BP patients with oral lesions, none (0.0%) BP patients without oral lesions, and four (9.8%) healthy individuals were positive for HSV on oral mucosa. Among BP patients with oral lesions, the inconsistent activity between oral and skin lesions (p=0.001), absence of blister/blood blister in oral lesions (p=0.020), and pain for oral lesions (p=0.014) were more often seen in HSV-positive than HSV-negative BP patients; the dosage of glucocorticoid (p=0.023) and the accumulated glucocorticoid dosage in the last 2 weeks (2- week AGC dosage) (p=0.018) were higher in HSV-positive BP patients. Combining the above five variables as test variable, the AUC was 0.898 (p<0.001) with HSV infection as state variable in ROC analysis. The absence of blister/blood blister in oral lesions (p=0.030) and pain for oral lesions (p=0.038) were found to be independent predictors of HSV infection in multivariable analysis. A total of 14 (73.7%) HSV-positive BP patients were treated with 2- week famciclovir and the oral mucosa BPDAI scores significantly decreased (p<0.001). Conclusion: HSV infection is common in BP oral lesions. The inconsistent activity between oral and skin lesions, absence of blister in oral lesions, pain for oral lesions, higher currently used glucocorticoid dosage, and higher 2-week AGC dosage in BP patients should alert physicians to HSV infection in oral lesions and treat them with 2-week famciclovir in time. [ABSTRACT FROM AUTHOR]

Herpes simplex encephalitis (HSE) is a common viral encephalitis that can be fatal if not adequately treated. Fever, cerebrospinal fluid (CSF) pleocytosis, and typical neuroimaging findings are commonly observed in HSE cases. We encountered a patient with HSE who did not exhibit these classic clinical features. A 63-year-old male presented with his first-ever seizure. Fever did not develop until the fourth day of admission, and neither neuroimaging nor CSF analysis revealed abnormalities. Under suspicion of autoimmune encephalitis, methylprednisolone was administered. Subsequently, when the patient developed fever, a follow-up neuroimaging study was performed and revealed abnormalities consistent with HSE. The patient was promptly treated with acyclovir, which led to a full recovery. Diagnosing HSE in patients who present without fever or CSF pleocytosis and with typical neuroimaging findings poses a challenge. Therefore, prior to initiating immunosuppressive treatment, it is crucial to closely observe patients and to conduct follow-up tests, including neuroimaging and CSF analysis.

Abstract Background Human herpesviruses are widespread among the human population. The infections often occur unnoticed, but severe disease as well as long-term sequelae are part of the symptom spectrum. The prevalence varies among subpopulations and with time. The aim of this study was to describe the seroprevalence of Immunoglobulin G against Herpes simplex 1, Herpes simplex 2, Epstein-Barr virus and Cytomegalovirus in the adult Swedish population over a time period of several decades. Methods Serum samples (n = 892) from biobanks, originating from 30-year-old women, 50-year-old men and 50-year-old women sampled between 1975 and 2018, were analyzed for presence of anti-herpesvirus antibodies. Linear regression analysis was used to test for a correlation between birth year and seroprevalence. Multiple linear regression analysis was used to differentiate between other factors such as age and gender. Results Birth year correlated negatively with the prevalence of immunoglobulin G against Herpes simplex 1 and Epstein-Barr virus (p = 0.004 and 0.033), and positively with Immunoglobulin G against Cytomegalovirus (p = 0.039). When participant categories were analyzed separately, birth year correlated negatively with the prevalence of Immunoglobulin G against Herpes simplex 1 and Herpes simplex 2 (p = 0.032 and 0.028) in 30-year-old women, and with the prevalence of Immunoglobulin G against Cytomegalovirus in 50-year-old men (p = 0.011). Conclusions The prevalence of Immunoglobulin G against Herpes simplex 1, Herpes simplex 2 and Epstein-Barr virus decreases in later birth cohorts. This indicates a trend of declining risk of getting infected with these viruses as a child and adolescent.

This article discusses a case of folliculotropic mycosis fungoides (FMF), a type of cutaneous lymphoma, that was successfully treated with the oral selective JAK1 inhibitor abrocitinib. The patient, a 46-year-old Chinese male, had previously tried interferon and phototherapy with minimal improvement. After adding abrocitinib to the treatment plan, there was significant improvement in the skin lesions and reduction in pruritus. The study suggests that selective JAK1 inhibitors may be a promising adjunct therapy for refractory FMF. [Extracted from the article]

This article presents a case study of a 32-month-old girl who developed blistering dermatitis on her buttocks after using a senna laxative. The diagnosis was senna laxative-induced dermatitis, which is a rare complication in infants. The article discusses the use of senna as a common treatment for childhood constipation and highlights the importance of recognizing the clinical features of senna-induced diaper dermatitis. It also provides recommendations for managing and preventing this condition, such as discontinuing the laxative, using barrier cream, and prompt diaper changes. The article emphasizes the need for healthcare providers to inquire about over-the-counter medications, as they may be underreported by parents. [Extracted from the article]

Encephalitis due to herpes simplex virus 1 (HSV1) has been described as a potential trigger for the development of anti-N-methyl-D-aspartate receptor (NMDAR) autoimmune encephalitis within few days to months. Here, we report one such case of anti-NMDAR encephalitis which was triggered by preceding HSV encephalitis. The patient had a history of headache and fever of 1–2-week duration, and cerebrospinal fluid and magnetic resonance imaging picture suggestive of HSV encephalitis. After 2 weeks of completion of 14-day course of acyclovir, he had symptoms of altered behavior, headache, and vomiting. The possibility of anti-N-methyl-D-aspartate (NMDA) encephalitis occurring after HSV encephalitis was considered. Serum for anti-NMDA antibody came positive, and he improved with treatment. A high index of suspicion and awareness of such a possibility can help in making the diagnosis and initiate early therapy. [ABSTRACT FROM AUTHOR]

This article discusses the emergence of doxycycline-induced fixed drug eruption (FDE), a common adverse reaction characterized by red patches on the skin or mucosa. FDE is typically associated with drugs like paracetamol, antibiotics, and non-steroidal anti-inflammatory drugs. However, recent cases have shown that doxycycline, commonly used for post-exposure prophylaxis (PeP) against sexually transmitted infections (STIs), can also induce FDE. The article presents 15 cases of doxycycline-induced FDE, with most cases occurring within the past 6 months. The authors recommend in situ repeated open application tests (ROAT) to confirm the diagnosis and avoid oral provocation tests (OPT), which can carry risks. They also suggest that all cyclin antibiotics, including doxycycline, be contraindicated for safety reasons. The article emphasizes the importance of recognizing doxycycline-induced FDE, particularly in cases of genital lesions that could be misdiagnosed as STIs. [Extracted from the article]

To report a case of alternate herpes simplex virus (HSV)-related inflammation in the cornea and retina in over two decades. Penetrating keratoplasty was performed for HSV stromal keratitis, which had occurred repeatedly over the earlier 7 years, in 2004, and vitrectomy was performed for acute retinal necrosis (ARN) in 2021 in the right eye of the patient. Systemic and topical antivirals and immunosuppressants were administered for HSV reactivation. The viruses remained quiescent for 17 years after keratoplasty until reactivation occurred and triggered ARN. The retina became reattached after vitrectomy. One year after the onset of ARN, the eye developed HSV epithelial keratitis. The opacified corneal graft recovered transparency 1 week after medical treatment. HSV may cause inflammation in different eye tissues within a long time. It is important to be aware of the possibility of uveitis or retinitis in patients with a history of HSV keratitis. [ABSTRACT FROM AUTHOR]

DNA nanostructures are well-established vectors for packaging diversified payloads for targeted cellular delivery. Here, DNA origami rectangular sheets were combined with Herpes Simplex Virus 1 (HSV1) capsids to demonstrate surface coverage of the particle via electrostatic interactions. The optimized origami:HSV1 molar ratios led to characteristic packaging geometries ranging from dispersed HSV1 pockets to agglomerated HSV1 sleeves. Pockets were disguised from cells in HeLa and B16F10 cells and were 44.2% less infective than naked HSV1 particles. However, the pockets were 117% more infective than naked HSV1 particles when the origami sheets were coated with folic acid. We observed infectivity from naked origami, but they are 99.1% less infective with respect to HSV1 and 99.6% less infective with respect to the pocket complexes. This work suggests that DNA origami can selectively modulate virus infectivity.