Improving polymerase chain reaction diagnostic rates for herpes simplex keratitis: results of a pilot study.

Background: Laboratory confirmation is crucial for diagnosis and management of herpes simplex virus (HSV) keratitis. However, the sensitivity of polymerase chain reaction (PCR) in keratitis is low (25%) compared with that of mucocutaneous disease (75%). We developed an educational intervention aimed at improving the diagnostic yield of PCR. Methods: The medical records of keratitis cases seen at the emergency department of a London tertiary ophthalmic referral hospital over two distinct periods, before and after an educational program on swab technique, were reviewed retrospectively. Results: A total of 252 HSV cases were included. Increases in the laboratory-confirmed diagnosis of HSV-1 were observed, in both first presentations (11.1%-57.7%) and recurrent cases (20%-57.6%). The rate of positive HSV-1 PCR in eyes with an epithelial defect increased from 19% pre-intervention to 62% post intervention. Notably, 3% were positive for varicella zoster virus DNA, and there was a single case of Acanthamoeba keratitis. Conclusion: Our results suggest that, with proper swabbing technique, PCR may be more sensitive than previously reported.

Neonatal herpes simplex virus encephalitis with intracranial bleeding in a newborn baby with concurrent rhesus incompatibility.

We report a baby with neonatal herpes simplex virus (HSV) encephalitis concurrent with Rrhesus (Rh) incompatibility. He was delivered by a Ggravida 2 mother with a history of miscarriage in her previous pregnancy at a gestation age of 4 months. She had Bblood group 0 and Rrhesus negative. The baby was noticed to have jaundice on day one1 of life accompanied by generalised petechiae on the face and upper chest. A full blood picture revealed severe anaemia and severe thrombocytopaenia and HSV 1/2 IgM was positive. MRI of the brain showed multiple extensive haemorrhagic lesions on the frontal-temporal regions.

Unilateral Acute Retinal Necrosis with Contralateral Non-necrotizing Herpetic Uveitis.

PURPOSE: The objective of this study is to report a case of unilateral acute retinal necrosis (ARN) with contralateral eye presenting as non-necrotizing herpetic uveitis. CASE REPORTS: Case 1: A 48-year-old female presented at our clinic with blurred vision in the right eye for 7 days. She was diagnosed with ARN in the left eye 2 weeks ago. Ophthalmic examination revealed reduced visual acuity in the right eye (20/33) with the presence of optic disc swelling and macular exudation without peripheral necrotic lesions. With systemic antiviral therapy, optic disc swelling of the right eye vanished gradually, and the visual acuity improved to 20/20. Loss of retinal nerve fiber layer (RNFL) and decreased retinal thickness in the corresponding area occurred during follow-up. CONCLUSION: Non-necrotizing herpetic uveitis may occur in the contralateral eye of unilateral ARN under rare conditions. Structure abnormities, including loss of RNFL and focal decreased retinal thickness, are irretrievable.

Fusobacterium nucleatum bacteremia complicated with intracranial Porphyromonas gingivalis and HSV-1 infection: a case report and literature review.

BACKGROUND: Fusobacterium nucleatum (F. nucleatum) belongs to the genus Fusobacterium, which is a gram-negative obligate anaerobic bacterium. Bacteremia associated with F. nucleatum is a serious complication, which is not common in clinic, especially when it is combined with other intracranial pathogenic microorganism infection. We reported for the first time a case of F. nucleatum bacteremia combined with intracranial Porphyromonas gingivalis (P. gingivalis) and herpes simplex virus type 1(HSV-1) infection. CASE PRESENTATION: A 60-year-old woman was admitted to our hospital with a headache for a week that worsened for 2 days. Combined with history, physical signs and examination, it was characterized as ischemic cerebrovascular disease (ICVD). F. nucleatum was detected in blood by matrix-assisted laser desorption/ionization time-offight mass spectrometry (MALDI-TOF-MS). Meanwhile, P. gingivalis and HSV-1 in cerebrospinal fluid (CSF) were identified by metagenome next generation sequencing (mNGS). After a quick diagnosis and a combination of antibiotics and antiviral treatment, the patient recovered and was discharged. CONCLUSION: To our knowledge, this is the first report of intracranial P. gingivalis and HSV-1 infection combined with F. nucleatum bacteremia.

The Evaluation and Treatment of an Infant Exposed to Nongenital HSV-2: A Case Report.

BACKGROUND: Pregnant persons with a primary genital herpes simplex virus (HSV) infection can transfer HSV to the fetus or infant through the placenta or birth canal, which can cause significant infant morbidity or mortality. Primary nongenital infections with HSV-1 or HSV-2 in pregnant persons and the risk of infant infection are not well documented, leaving the clinician to make non-evidence-based decisions on evaluation and treatment in such presentations. CLINICAL FINDINGS: A term newborn was delivered vaginally by a pregnant person with a nongenital HSV-2 infection. The pregnant person's rash first appeared around 32 weeks' gestation, started on their lower back, and terminated on the outer left hip. The rash improved but was still present at time of delivery, and this rash was their first known HSV outbreak. PRIMARY DIAGNOSIS: Prenatal exposure to HSV-2. INTERVENTIONS: Diagnostics included the pregnant person's rash surface culture, immunoglobulin G and immunoglobulin M for HSV-1 and -2; infant surface, cerebral spinal fluid (CSF), and serum HSV-1 and HSV-2 polymerase chain reactions (PCRs), infant CSF studies, blood culture, liver function tests, and treatment with intravenous acyclovir. OUTCOMES: This infant remained clinically well during hospitalization and was discharged home at 5 days of life when CSF, surface, and serum PCRs resulted negative. PRACTICE RECOMMENDATIONS: Risk for infant HSV infection versus parent/infant separation and exposure to invasive procedures and medications should be considered when pregnant persons present with primary versus recurrent nongenital HSV infections. Research is needed for the evaluation and treatment of infants born to pregnant persons with primary nongenital HSV infections in pregnancy.

Association Between Herpes Simplex Virus II Infection and Rheumatoid Arthritis in US Adults: A Population-Based Propensity Score-Matching Study.

BACKGROUND/OBJECTIVE: The potential correlation between herpes simplex virus (HSV) and human papillomavirus (HPV) infections and rheumatoid arthritis (RA) has not been definitively established. Further research is needed to determine the relationship between the development of RA and the presence of these viral infections. METHODS: A case-control study was conducted with data from the National Health and Nutrition Examination Survey between 2009 and 2014. Our analysis examined the association between HSV I, HSV II, HPV oral polymerase chain reaction (PCR), HPV vaginal PCR, and RA. We identified adults aged 20 to 49 years with a primary diagnosis of RA using the National Health and Nutrition Examination Survey database codes (MCQ191 = 1 [years 2009-2010]; MCQ195 = 2 [years 2011-2014]) and excluded patients with incomplete data on key variables and primary outcomes. RESULTS: The study included 8620 patients, with 150 patients diagnosed with RA and 1500 patients without RA. Patients with RA had a significantly higher prevalence of HSV II infection compared with those without RA (36.34% vs. 24.72%, p = 0.015) after propensity score matching. No significant differences were observed for HSV I, HPV oral PCR, and HPV vaginal PCR between the 2 groups. Patients with RA were older; were more likely to be female, obese, and non-Hispanic White; and had a higher prevalence of comorbidities than those without RA. CONCLUSIONS: This population-based propensity score-matching study provides evidence of an association between HSV II infection and RA in US adults. Further research is needed to fully elucidate the relationship between viral infections and RA, with the aim of developing effective risk reduction strategies and innovative treatments for RA.

The Infectious Uveitis Treatment Algorithm Network (TITAN) Report 1-global current practice patterns for the management of Herpes Simplex Virus and Varicella Zoster Virus anterior uveitis.

AIMS: To present current expert practice patterns and to formulate a consensus for the management of HSV and VZV AU by uveitis specialists worldwide. METHODS: A two-round online modified Delphi survey with masking of the study team was conducted. Responses were collected from 76 international uveitis experts from 21 countries. Current practices in the diagnosis and treatment of HSV and VZV AU were identified. A working group (The Infectious Uveitis Treatment Algorithm Network [TITAN]) developed data into consensus guidelines. Consensus is defined as a particular response towards a specific question meeting ≥75% of agreement or IQR ≤ 1 when a Likert scale is used. RESULTS: Unilaterality, increased intraocular pressure (IOP), decreased corneal sensation and diffuse or sectoral iris atrophy are quite specific for HSV or VZV AU from consensus opinion. Sectoral iris atrophy is characteristic of HSV AU. Treatment initiation is highly variable, but most experts preferred valacyclovir owing to simpler dosing. Topical corticosteroids and beta-blockers should be used if necessary. Resolution of inflammation and normalisation of IOP are clinical endpoints. CONCLUSIONS: Consensus was reached on several aspects of diagnosis, choice of initial treatment, and treatment endpoints for HSV and VZV AU. Treatment duration and management of recurrences varied between experts.

Cytokine storm and severe hepatitis in pregnancy due to herpes simplex virus 2.

CASE PRESENTATION: A pregnant woman developed hepatitis due to a herpes simplex virus 2 primary infection with a severe systemic inflammatory response. Treatment with acyclovir and human immunoglobulin was given and both mother and baby survived. PURPOSE: We provide the first description of the inflammatory response associated with herpetic hepatitis in pregnancy.

Congenital herpes simplex with ophthalmic and multisystem features: a case report.

BACKGROUND: Neonatal herpes simplex virus (HSV) infection is rare and has significant morbimortality rates. Approximately 85% of newborns are infected intrapartum, and risk factors for mother-to-child transmission include vaginal delivery, primary maternal infection, and prolonged rupture of membranes. Neonatal HSV can manifest with isolated mucocutaneous lesions, neurological involvement, or disseminated disease. In general, herpetic infection can cause blepharoconjunctivitis or keratitis. We report a rare case of congenital herpes with ophthalmologic manifestations and multisystemic involvement. CASE PRESENTATION: A preterm infant, born at 32 weeks and 2 days, with presumed neonatal infection developed intestinal and respiratory complications, as well as hyperemic lesions on the left nostril and oral mucosa. An ophthalmological assessment was requested and brought up the suspicion of HSV infection, indicating empirical treatment with endovenous acyclovir. Later, a new ocular examination was suggestive of panuveitis. Afterward, serum IgM antibodies to HSV-1 and HSV-2 were positive. Proper antiviral therapy led to an improvement in the condition. DISCUSSION: Neonatal herpes is associated with a high risk of persistent skin lesions, long-term neurological disability and other lasting sequelae. It is essential to consider HSV infection in cases of neonatal conjunctivitis, especially in patients with an epithelial defect and no improvement after initial treatment with topical or systemic antibiotics. CONCLUSIONS: In the management of neonatal HSV, early diagnosis is essential for the timely initiation of antiviral therapy. Our report highlights that ocular assessment can be crucial in the correct diagnostic investigation of this condition.

Comparison Between Two Types of Viral-Induced Anterior Uveitis In Vitro and In Vivo: A Stronger Response in Herpes Simplex Virus Type 1 Than in Murine Cytomegalovirus.

Purpose: To observe the similarities and differences between herpes simplex virus type 1 (HSV-1) and murine cytomegalovirus (MCMV)-induced viral anterior uveitis (VAU), both in vitro and in vivo. Methods: Primary rat trabecular meshwork cells (RTMCs) were infected by HSV-1 or MCMV to clarify the pattern of virus replication and the effect on cells. In vivo, intracameral injection of HSV-1 or MCMV was performed to establish the VAU rat models. The clinical manifestation, intraocular pressure (IOP), histological characteristics, ultrastructural changes, and the expression of inflammatory cytokines in the anterior segment were observed and compared between these two types of VAU models. Results: Both viruses could infect the RTMCs but HSV-1 exhibited an earlier and greater cytopathic effect in vitro. In vivo, both VAU rats showed typical acute VAU signs, and the IOP elevation seemed to be correlated with the inflammatory progression. Histopathological findings and ultrastructural changes revealed tissue damage and cell infiltration in the anterior chamber angle. In both models, similar proinflammatory cytokines were upregulated. HSV-1 and MCMV viral particles were identified under transmission electron microscopy. Conclusions: HSV-1 and MCMV infection share certain similarities but have significant differences both in vitro and in vivo. HSV-1 usually has a stronger anterior segment inflammation with a longer duration compared with MCMV in VAU models. Our results provided a valuable animal model for investigating pathogenesis and exploring therapeutic strategies for clinical VAU.

Ocular Involvement in Congenital Infections - TORCH. / Augenbeteiligung bei kongenitalen Infektionen ­ TORCH.

This review summarises the ophthalmological findings in congenital infections. Intrauterine infections are an important cause of childhood blindness. The most common infections are grouped under the acronym TORCH, which stands for Toxoplasma gondii, others, rubella, CMV, and herpes simplex. Overall, these infections are not very common in first-world countries during pregnancy, but are of particular importance because of the threat to vision. Diagnosis of infection or reactivation is a gynaecological challenge. However, ophthalmological examination of newborns can be appropriately targeted if the causative agent is known. The most important therapeutic agents used in the newborn are summarised.

The Association Between Herpes Simplex Virus and Alzheimer's Disease: A Systematic Review.

Alzheimer's disease (AD) is a significant public health concern, affecting more than 6 million Americans; and currently, there are no cure or effective treatment options. The underlying etiology and pathogenesis are not fully understood, presenting a barrier to therapy. A substantial amount of data exists associating infection with Herpes simplex virus 1 (HSV-1) and AD. This review of published studies highlights the epidemiological associations between HSV-1 and AD. A systematic search of PubMed, Embase, and Web of Science was conducted on January 6, 2022, using PRISMA guidelines. Articles that presented epidemiological data correlating HSV-1 with AD were included. Bibliographies were screened for additional relevant articles as well. After review, 21 studies were included: 2 review articles and 19 population-based studies including case control, cohort, and cross-sectional studies.  The quantitative data derived from the studies in this report substantiate a relationship between infection with HSV-1 and AD. Based on these results, it may be of reasonable benefit to more consistently treat latent or active HSV-1 infection with anti-viral medications to potentially reduce the risk of AD. Furthermore, a prospective randomized controlled clinical trial could elucidate the benefit of anti-viral therapy to prevent or limit AD.J Drugs Dermatol. 2023;22(10):1046-1052     doi:10.36849/JDD.6785.

Herpetic esophagitis in healthy young adult.

Herpetic esophagitis (HE) is common in immunocompromised patients but rarely reported in healthy young adults. A 28-year-old healthy male patient visited our clinic with a chief complaint of chest pain. An esophagogastroduodenoscopy revealed widely spread superficial multiple ulcers in the middle to the distal esophagus, and repeated biopsies from the ulcer were performed but revealed inconsistent findings with HE. Thus, he was clinically diagnosed with HE based on endoscopic findings and serologic tests of immunoglobulin M (IgM)/immunoglobulin G (IgG) for herpes simplex virus. He responded to valacyclovir, and all esophageal ulcers had scarred.

Neonatal herpes simplex virus infection: From the maternal infection to the child outcome.

This review examines the recent literature on the management of herpes simplex virus (HSV) infections in neonates. We summarized the three clinical categories of maternal HSV infection during pregnancy (primary first episode, nonprimary first episode, or recurrent episode) and the mechanisms of fetal damage. Considering when the transmission of the infection from the mother to the fetus/newborn occurs, three types of neonatal infection can be distinguished: intrauterine infection (5% of cases), postnatal infection (10% of cases), and perinatal infections (85% of cases). Neonatal presentation could range from a limited disease with skin, eye, and mouth disease to central nervous system disease or disseminated disease: the treatment with acyclovir should be tailored according to symptoms and signs of infection, and virological tests. These children need a multidisciplinary follow-up, to timely intercept any deviation from normal neurodevelopmental milestones. Prevention strategies remain a challenge, in the absence of an available vaccine against HSV.

Understanding Herpes Simplex Virus Type 1 Versus Herpes Simplex Virus Type 2 Encephalitis After Neurosurgery: A Case Series and Literature Review.

Abstract Background: Herpes simplex virus encephalitis (HSVE) is a rare post-operative infection that can be fatal if treatment is delayed. Herpes simplex virus type 1 (HSV-1) is a more common cause of encephalitis than herpes simplex virus type 2 (HSV-2), however, a significant overlap exists. The goal of this project was to understand the frequency and trend of HSVE after neurosurgery through a case series at our institution and in the literature with a focus on comparing HSV-1 versus HSV-2. Patients and Methods: A literature review of all published cases and case series of HSVE after neurosurgery was performed. Descriptive statistics comparing HSV-1 and HSV-2 encephalitis were computed. Data on demographics, symptoms, surgery, treatment, immunosuppression, imaging findings, steroids, and mortality were collected. Results: We identified 55 total cases of HSVE post-neurosurgery. These included 28 cases of HSV-1, 10 cases of HSV-2, and 17 cases of HSV-unspecified encephalitis. There were no differences in age, gender, symptoms, surgery, or latency between surgery and symptom onset between HSV-1 and HSV-2. Mortality was higher with HSV-1 versus HSV-2 although not statistically significant. The primary surgical indication varied substantially between HSV-1 and HSV-2. Conclusions: Herpes simplex virus encephalitis is often overlooked in the setting of encephalitis after surgery. A high index of suspicion is needed to prevent a delay in treatment.

Acute liver failure due to herpes simplex viral hepatitis diagnosed by skin lesions and blood tests: a case report.

BACKGROUND: The incidence of acute liver failure from herpes simplex virus is rare. CASE PRESENTATION: A 71-year-old Japanese man was diagnosed with acute liver failure and was transferred to our hospital. Steroid therapy, plasma exchange, and hemodiafiltration were started for liver failure, and antimicrobial therapy was initiated for pneumonia. Staphylococcus epidermidis was detected in blood culture. Skin rash appeared; a positive anti-herpes simplex virus result led to the diagnosis of acute liver failure from herpes simplex virus. Hence, acyclovir was started. After blood tests improved, treatments for acute liver failure were discontinued. Antimicrobial therapy was continued; however, he died. In this case, persistent bacteremia and drug-induced liver damage due to acyclovir may have contributed to his death. CONCLUSIONS: Acute liver failure can lead to complications and death. Thus, careful observation is crucial, even if the patient has shown some improvements.