Challenges for early diagnosis of neonatal herpes infection in Japan.

Background: This study aimed to analyze the recent prevalence of neonatal herpes simplex virus infection, maternal symptoms in the presence of neonate who has herpes simplex virus infection, and mode of delivery in Japan. Methods: We requested 2.078 obstetrical facilities that are members of the Japan Association of Obstetricians and Gynecologists (JAOG) to provide information on neonatal herpes simplex virus infection involving deliveries at or after 22 weeks of gestation between 2020 and 2022. Of these, 1.371 (66.0%) facilities responded with information that could undergo statistical analysis. Results: There were 10 cases of neonatal herpes simplex virus infection, and the incidence of neonatal herpes simplex virus infection in Japan was about 1 in 1.4 × 105 live births. There were no characteristic maternal findings common to cases of neonatal herpes simplex virus infection. Conclusion: The incidence of neonatal herpes simplex virus infection in Japan was low. We could not identify any characteristic maternal findings common to cases of neonatal herpes simplex virus infection.

Características de recién nacidos hijos de madre con IgM positiva para el Virus Herpes Simplex

Introducción: El herpes connatal es una entidad infrecuente asociada a elevada morbimortalidad. La probabilidad de transmisión al recién nacido va de 5% al 85%. El diagnóstico se dificulta por falta de clínica, serología no confiable y por la no disponibilidad de PCR en los servicios públicos de países en vías de desarrollo. La IgM en gestantes podría ser utilizada como un marcador de sospecha para evaluar al neonato. Objetivo: Caracterizar a los recién nacidos, hijos de gestantes con IgM positiva para HVS 1-2 y la frecuencia de encefalitis en los infantes. Materiales y métodos : Estudio observacional, descriptivo, prospectivo, realizado de mayo de 2020 a octubre de 2021. Se incluyeron recién nacidos (RN) de madres con IgM positiva para Herpes Virus Simplex (HVS) a partir de la segunda mitad del embarazo. En el RN se realizó serología IgG e IgM, y además, PCR- RT para HVS 1-2 en sangre y/o LCR, excluyéndose los nacidos en otras maternidades y/o sin datos de serología materna. Resultados: 36 pacientes. Edad materna 28 años (DS + 4), 5% con antecedentes de HVS, 61% cesárea. 36% prematuros, 13% RCIU. Síntomas agudos en el RN 22%. De ellos, 19% plaquetopenia, 44% alteración de GOT. 63% PCR HVS en sangre y 44% en LCR. Se encontró hemorragia, hidrocefalia, leucomalacia en 27%. No se encontró diferencias en la expresión clínica por tipo de parto. Conclusiones: Los RN hijos de gestantes con IgM positiva para VHS desde la segunda mitad del embarazo o periparto, presentaron infección por VHS determinada por PCR en sangre o LCR, independiente de la vía del parto. El diagnóstico serológico en embarazadas permite la pesquisa, diagnóstico y tratamiento temprano del RN.

Introduction: neonatal herpes is a rare entity associated with high morbidity and mortality. The probability of transmission to the newborn ranges from 5% to 85%. The diagnosis is difficult due to the lack of clinical signs, unreliable serology and the non-availability of PCR in public services in developing countries. IgM in pregnant women could be used as a suspected marker to evaluate the neonate. Objective: To characterize newborn children of pregnant women with positive IgM for HSV 1-2 and the prevalence of encephalitis in infants. Materials and methods: Observational, descriptive, prospective study, carried out from May 2020 to October 2021. Newborns (NB) of mothers with positive IgM for Herpes Virus Simplex (HSV) from the second half of pregnancy were included. In newborns, IgG and IgM were performed, and in addition, PCR-RT for HSV 1-2 in blood and/or CSF, excluding those born in other hospitales and/or without maternal serology data. Results: We included 36 patients. Maternal age was 28 years (DS + 4), 5% with a history of HSV. 61% were delivered via cesarean section, 36% were premature, 13% had IUGR. 22% of the newborns had acute symptoms. 19% had thrombocytopenia, 44% had GOT alteration. 63% were PCR positive for HSV in serum and 44% were CSF-positive. Hemorrhage, hydrocephalus and leukomalacia were found in 27%. No differences were found in clinical expression by type of delivery. Conclusions: Newborns born to pregnant women with positive IgM for HSV from the second half of pregnancy or peripartum, presented HSV infection as determined by PCR in blood or CSF, regardless of the route of delivery. Serological diagnosis in pregnant women allows early screening, diagnosis and treatment of the NB.

Sepsis and multi-organ failure due to genital herpes in a healthy person.

Herpes simplex virus type 2 (HSV-2) is highly prevalent in several regions of the world and is the main pathogen causing genital herpes, which is transmitted almost exclusively through sexual contact. Systemically disseminated infections caused by HSV-2 are rare and most often seen in newborns, pregnant women, or immunocompromised populations. The virus can invade multiple organs and cause damage. In this paper, we present an extremely rare case of an immunocompetent 36-year-old male who came to our hospital with a high fever with abdominal pain and died of sepsis and multiple organ dysfunction syndrome within a short period. After the exclusion of common pathogens such as bacterial and fungal infections during hospitalization, metagenomic next generation sequencing of the patient's peripheral blood and ascites gave us the answer, and very high nucleic acid sequence counts of HSV-2 were detected in both his peripheral blood and ascites, confirming HSV-2 as the causative virus. In addition, this paper provides a brief review of the relevant literature.

Two Cases of Herpes Gladiatorum Identified in a Korean Middle-School Wrestling Team: A Case Report.

For legal reasons, the publisher has withdrawn this article from public view. For additional information, please contact the publisher.

The Many Faces of Neurological Neonatal Herpes Simplex Virus Infection.

This case series explores the various manifestations of central nervous system (CNS) involvement in neonatal herpes simplex virus (HSV) infection and highlights the challenges involved in their diagnosis and treatment. Neonatal HSV infection is a rare but serious condition that can have significant neurological consequences. The article presents three cases of neonatal HSV infection, all involving the CNS, each characterized by distinct clinical features and outcomes. Case 1 describes a three-week-old male with severe HSV meningoencephalitis resulting in poor response to treatment and death. Cases 2 and 3 describe younger neonates who presented early in the disease course with disseminated infection and skin, eye, and mouth (SEM) lesions. Although both patients had CNS involvement, their outcomes were remarkably favorable. The wide range of clinical presentations of CNS manifestations in neonatal HSV infection, ranging from nonspecific to evident neurological symptoms, underscores the need for a high index of suspicion and comprehensive evaluation to ensure early diagnosis and appropriate treatment. However, it also notes that even with timely treatment, some cases may still have a poor prognosis.

Transmission of the Herpes Simplex Virus in the Preclinical Phase of Disease Progression during Childbirth.

Vertical transmission of the herpes simplex virus (HSV) in the preclinical phase of the disease progression is rare. Here, we present a case of perinatal-acquired herpes from an asymptomatic mother. Our findings suggest that clinicians should consider screening predisposed mothers for HSV as part of prenatal care to identify asymptomatic primary genital HSV infections.

Rapid-Onset Temporal Encephalitis With Negative Cerebrospinal Fluid Polymerase Chain Reaction Testing.

Herpes simplex encephalitis is a rare disease presentation that is usually characterized by its temporal involvement and positive cerebrospinal fluid (CSF) polymerase chain reaction (PCR) for the herpes simplex virus (HSV). HSV PCR has a sensitivity of 96% and specificity of 99%. Even when the test is negative, if clinical suspicion is high, acyclovir therapy should be continued with a repeated PCR within a week. In this case, we report a 75-year-old female patient who presented with signs of hypertensive emergency with rapid deterioration to seizure-like activity on electroencephalogram (EEG) and signs of temporal encephalitis on magnetic resonance imaging (MRI). The patient did not respond to the initial regimen of antibiotics but did show significant clinical response to acyclovir though she had a negative CSF PCR for HSV ten days after the start of her neurological symptoms. In this case, we argue that alternative methods of diagnosis should be considered in cases of acute encephalitis. Our patient had negative PCR but her computerized tomography (CT), EEG, and MRI results pointed to temporal encephalitis caused by HSV.

Herpes and Chest Pain: Two Atypical Monkeypox Cases.

The 2022 Monkeypox Outbreak has spread globally in just a few months and has raised great concerns regarding disease recognition due to frequent atypical presentations and questions regarding the possibility of sexual transmission. In endemic countries and prior outbreaks, the clinical manifestations of monkeypox have been well documented, with cutaneous findings following a set, synchronous pattern of evolution. We present two cases of atypical monkeypox presentations in individuals living with HIV, both complicated by herpes simplex virus type 2 (HSV-2) coinfection and elevated troponins, and both demonstrating the ease with which monkeypox can be overlooked in the current outbreak.

Frequency and visual outcomes of herpes simplex keratitis in a Kuwaiti tertiary referral center.

Background: Herpes simplex virus (HSV), a cause of many ocular pathologies, may affect the corneal epithelium, stroma, or endothelium, with the epithelium as the most frequently affected location. We aimed to determine the frequency and visual outcomes of HSV keratitis over a 1-year period at Farwaniya Hospital, Kuwait. Methods: This prospective observational case series included patients diagnosed with HSV keratitis who presented to the outpatient or eye casualty department between September 2022 and September 2023. Full history, demographic profile, detailed ocular and slit-lamp examinations, and visual acuity assessments were recorded prior to and after treatment. Baseline corneal sensation was assessed in the four corneal quadrants using the cotton wisp test. Results: Of the 227 patients who presented with infectious keratitis, 72 (31.7%) were diagnosed with HSV keratitis. The mean (SD) age was 45.86 (16.06) years, and 48 (66.7%) patients were male. The subtypes of HSV keratitis were endotheliitis in 27 (37.5%) patients, dendritic ulcer in 22 (30.6%), stromal keratitis with ulceration in 9 (12.5%) and without ulceration in 8 (11.1%), and geographic ulcer in 6 (8.3%). The mean baseline best-corrected distance visual acuity (BCDVA) differed significantly between the HSV keratitis subtypes (P < 0.001). Most patients (n = 70, 97.2%) had unilateral eye involvement, were treated within 1 - 2 weeks, and demonstrated improved BCDVA. Despite the improvement in BCDVA in all HSV keratitis subtypes, a significant difference in the median BCDVA remained after treatment (P < 0.001). Pairwise comparisons revealed a significantly better BCDVA after treatment in eyes with dendritic epithelial ulcers than in eyes with HSV stromal keratitis with ulceration (P = 0.003) or geographic epithelial ulcers (P = 0.005). After treatment, corneal haze and neovascularization were detected in 54 (75.0%) and 24 (33.3%) patients, respectively. Conclusions: We detected a substantial frequency of HSV keratitis in one of the governorates of Kuwait, with endotheliitis as the most common manifestation. Timely standard treatment interventions based on valid guidelines resulted in BCDVA improvement in all subtypes of HSV keratitis in our series, indicating the importance of early treatment. However, the BCDVA in eyes with dendritic epithelial ulcers remained substantially better than that in eyes with geographic epithelial ulcers or HSV stromal keratitis with ulceration, signifying the effect of the initial HSV keratitis subtype on visual outcomes. To our knowledge, this is the first study to highlight the frequency of HSV keratitis in a Kuwaiti hospital, and larger-scale research in this region is needed to further understand and manage the condition.

Herpes Simplex Encephalitis: Detection, Management, and Outcomes.

The pathophysiology of herpes simplex encephalitis (HSE) is incompletely understood and proposed to be secondary to the retrograde transport of the herpes simplex virus type 1 (HSV-1) via the trigeminal and/or olfactory nerves to the central nervous system (CNS). In this case report, we present a 68-year-old female who presents to our emergency department after a fall. Upon initial admission, her neurological examination was benign, and a computer tomography (CT) scan of her brain showed a subdural hematoma for which she was treated conservatively. Day 4 of her hospitalization marked a rapid decline in her course of illness, beginning with confusion and hallucinations, progressing to subclinical seizures, and culminating in irreversible brain damage and palliative extubation on day 16 of hospitalization. This case report discusses our insight into the challenges of early diagnosis and treatment of herpes encephalitis and their impact on improving patient outcomes.

Phototherapies for erythema multiforme secondary to viral infections: A case report of a child.

INTRODUCTION: Erythema multiforme (EM) is a reactive mucocutaneous disorder typically initiated by viral infections. Although the management of EM differs according to the clinical course and trigger factor, it is not clear whether antiviral suppressive therapies may be useful in cases related to such infections. Moreover, the treatment is most often based on supportive care directed towards only the symptoms. AIM: To present a clinical case of a child in which antimicrobial photodynamic therapy (aPDT) and photobiomodulation therapy (PBMT) were used for orofacial manifestations of EM secondary to viral infections. CASE REPORT: A Brazilian 1-year-old boy was admitted to an ICU due to a severe Influenza A H3N2 infection, pneumonia with pleural effusion, and sepsis. About 10 days later, it was noted bleeding lip lesions covered by crusts and bleeding tongue lesions, diagnosed as EM secondary to both H3N2 and herpes simplex virus infections, confirmed by serology tests. A combination of an aPDT session and six PBMT sessions was proposed and resulted in almost complete resolution of the lesion on the 7th day. CONCLUSION: Given the complexity of the present case, the combination of phototherapies seems to be a promising tool for treating acute orofacial mucosal lesions of viruses-induced EM. More studies, however, are needed to reach a definite conclusion.

Postinfectious Acute Disseminated Encephalomyelitis Associated With Antimyelin Oligodendrocyte Glycoprotein Antibody.

Myelin oligodendrocyte glycoprotein is a major target of the humoral immune response in children affected by inflammatory demyelinating diseases of the central nervous system. Although myelin oligodendrocyte glycoprotein causes autoimmune encephalitis in different animal models, the relevance of this mechanism in human autoimmune diseases of the central nervous system is unclear. We herein report a child with acute disseminated encephalomyelitis possibly triggered by central nervous system infection of primary herpes simplex virus in the presence of antimyelin oligodendrocyte glycoprotein antibody. A healthy 5-year-old Japanese boy suffered from acute disseminated encephalomyelitis. He was positive for antimyelin oligodendrocyte glycoprotein antibody in both the serum and the cerebrospinal fluid, and herpes simplex virus-1 DNA on polymerase chain reaction of the cerebrospinal fluid. We speculated that the central nervous system infection of primary herpes simplex virus disrupted the blood-brain barrier, and antimyelin oligodendrocyte glycoprotein antibody already present in serum was transferred to the cerebrospinal fluid, resulting in the onset of acute disseminated encephalomyelitis. This might be the mechanism underlying postinfectious acute disseminated encephalomyelitis associated with myelin oligodendrocyte glycoprotein antibody.

Neonatal Herpes Simplex Virus: The Long Road to Improved Outcomes.

Herpes simplex virus (HSV) acquired during delivery places the neonate at risk for mortality or long-term neurodevelopmental disability. Exposure generally occurs from recurrent genital herpes infection, although primary infections result in the highest risk of neonatal disease. Neonates generally present in the second or third week of life with lesions. Encephalitis with seizures indicates the presence of central nervous system involvement, and other end organs may also be impacted. Clinical suspicion for neonatal HSV infection warrants immediate initiation of appropriate antiviral therapy. In the last 50 years, antiviral therapy has progressed from agents with prohibitive toxicity or cumbersome administration to herpes virus-specific agents that dramatically improve clinical outcomes with manageable toxicity. Multicenter clinical trials have demonstrated the superiority of high-dose intravenous acyclovir for acute therapy, followed by long-term oral suppressive therapy. This work has dramatically reduced morbidity and mortality from neonatal HSV, representing the benchmark for future clinical trials in neonatal pharmacotherapy.

Genital herpes and pregnancy: Evaluating practices and knowledge of French health care providers.

BACKGROUND: Genital herpes during pregnancy is a frequent occurrence, whereas infection of newborns is rare but likely severe. In the absence of specific national guidelines from the CNGOF (French National College of Gynaecologists and Obstetricians) in France until December 2017, we supposed that knowledge of health care providers on the topic was not up to date. OBJECTIVE: To assess health care provider knowledge of genital herpes and management practices during pregnancy, before the publication of national recommendations edited by the CNGOF. STUDY DESIGN: A questionnaire on genital herpes during pregnancy was published on the CNGOF website and sent by e-mail to members of the French College of Fetal Ultrasound (CFEF). Questions focused on prevention and screening practices, epidemiological knowledge, and management of herpes infection during pregnancy and after birth. RESULTS: Between April and June 2017, 354 health care providers completed the survey (263/354 (75 %) Obstetrician-Gynaecologists, 85/354 (24 %) Midwives and 6/354 (2%) General Practitioners). Overall, obstetricians were better informed about epidemiology of Herpes Simplex Virus (HSV), midwives were more familiar with neonatal risks in case of maternal primary infection but overestimated risks in case of maternal recurrence. 21 % of health care providers never prescribed antiviral prophylaxis in the third trimester if genital herpes occurred during pregnancy. Finally, most practitioners were unaware of newborn management in case of maternal genital herpes at delivery. CONCLUSION: Management of genital herpes in pregnancy appears to be heterogeneous due to varying degrees of knowledge among French health care providers. This highlights the urgent need for national guidelines, that were published 5 months after this study. They should be broadly disseminated and adapted to the shortcomings of health professionals. It would be interesting to repeat this study later to evaluate the impact of national guidelines.

Natural Products-Derived Chemicals: Breaking Barriers to Novel Anti-HSV Drug Development.

Recently, the problem of viral infection, particularly the infection with herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), has dramatically increased and caused a significant challenge to public health due to the rising problem of drug resistance. The antiherpetic drug resistance crisis has been attributed to the overuse of these medications, as well as the lack of new drug development by the pharmaceutical industry due to reduced economic inducements and challenging regulatory requirements. Therefore, the development of novel antiviral drugs against HSV infections would be a step forward in improving global combat against these infections. The incorporation of biologically active natural products into anti-HSV drug development at the clinical level has gained limited attention to date. Thus, the search for new drugs from natural products that could enter clinical practice with lessened resistance, less undesirable effects, and various mechanisms of action is greatly needed to break the barriers to novel antiherpetic drug development, which, in turn, will pave the road towards the efficient and safe treatment of HSV infections. In this review, we aim to provide an up-to-date overview of the recent advances in natural antiherpetic agents. Additionally, this paper covers a large scale of phenolic compounds, alkaloids, terpenoids, polysaccharides, peptides, and other miscellaneous compounds derived from various sources of natural origin (plants, marine organisms, microbial sources, lichen species, insects, and mushrooms) with promising activities against HSV infections; these are in vitro and in vivo studies. This work also highlights bioactive natural products that could be used as templates for the further development of anti-HSV drugs at both animal and clinical levels, along with the potential mechanisms by which these compounds induce anti-HSV properties. Future insights into the development of these molecules as safe and effective natural anti-HSV drugs are also debated.

A case of congenital herpes simplex virus infection diagnosed at 8 months of age.

We present the case of an 8-month-old boy with the repeated recurrence of vesicles from the time of birth and who subsequently manifested psychomotor developmental delay. We retrospectively diagnosed the patient with congenital herpes simplex virus (HSV) infection. Computed tomography showed multiple calcifications in the periventricular white matter and thalami. The bilateral deep white matter showed an abnormally high signal intensity on T2-weighted magnetic resonance imaging. The patient required consecutive, suppressive therapy with valacyclovir to prevent the repeated recurrence of vesicles. This case presented a milder phenotype of congenital HSV infection in comparison to previous reports, and highlights the importance of the careful examination for this disease when neonates present with skin lesions.

Peculiar vegetative tumor-like genital herpes simplex nodules with brisk tissue eosinophilia in patients with human immunodeficiency virus infection.

Genital herpes simplex virus (HSV) infection in a human immunodeficiency virus (HIV) patient can present as a vegetative nodule. Clinical differential diagnoses of the nodule include condyloma latum, condyloma acuminatum, viral or fungal infection, and cutaneous neoplasms. Histological examination of herpetic nodules has been reported to show thick pseudoepitheliomatous hyperplasia with dense dermal lymphoplasmacytic infiltrate and multifocal multinucleated cells with herpetic viral cytopathic changes. We report two patients with HIV presenting with vegetative tumor-like HSV nodules with distinctive histopathologic pattern of inflammation that has not been described in the literature before. All samples displayed slightly acanthotic epidermis with focal ulceration, dense dermal sclerosis, scattered plasma cells, and a brisk lymphoeosinophilic infiltrate found dissecting between dense collagen bundles. This pattern of inflammation is an important clue that can guide the pathologist to look for focal herpetic viral changes in the epidermis, as patients with HIV possibly tend to amount a predominantly eosinophilic immune response in inflammatory skin conditions.

[Pitfall cryothermic dermatitis artefacta]. / Fallstrick kryothermische Dermatitis artefacta.

We present four clinicopathological correlated cases of young patients with cryothermic dermatitis artefacta. They were initially misdiagnosed as primary bullous dermatoses or fixed drug eruptions. Cryothermic dermatitis artefacta can imitate authentic dermatoses such as linear IgA bullous dermatosis, herpes virus infection, bullous pemphigoid or fixed drug eruption. It should be considered as differential diagnosis in uncommon cases of recurrent bullae in adolescent and young adult patients. We summarize helpful clinical and histopathological criteria for correct diagnosis and therewith causative treatment.

[Opportunistic infections by human herpes viruses]. / Opportunistische Infektionen durch humane Herpesviren.

Infections in immunosuppressed patients represent a particular challenge in the diagnostics and treatment. They often present with atypical and particularly severe courses, for which rapid diagnostics and treatment are decisive for treatment success. Opportunistic infections with human herpes viruses occur not only more frequently in immunocompromised patients compared to healthy people but also represent a special challenge. In the treatment of immunosuppressed patients, e.g. with human immunodeficiency virus infections and patients with solid organ transplantations, infections with herpes simplex virus, varicella zoster virus, Epstein-Barr virus and cytomegalovirus are particularly important. The symtoms are very variable, ranging from asymptomatic detection of viremia to vital life-threatening organ manifestations. This review article describes the most important clinical presentations of these opportunistic infections. Furthermore, the diagnostic, therapeutic and prophylactic strategies for human herpes viruses are summarized.

Critically Severe Case of Neonatal Herpes with High Viral Load and Hemophagocytic Syndrome.

Neonatal disseminated herpes simplex virus (HSV) infection is a severe disease with high mortality and morbidity; yet, the pathophysiology remains unclear. Here, we report a male infant with disseminated HSV type 1 (HSV-1) infection, complicated by hemophagocytic lymphohistiocytosis (HLH) and multiple organ failure. The infant, born at 39 weeks of gestation by normal delivery, developed fever (38.5˚C) with the high serum C-reactive protein levels on the 1st day of life, and exhibited tachypnea on the 3rd day. On the 5th day of life, the patient received mechanical ventilation and was transferred to our neonatal ICU. Real-time PCR for HSV-1 DNA revealed an extremely high serum concentration (1.0 × 109 copies/µL), and he was diagnosed with HSV-1 infection. Acyclovir (ACV) and corticosteroid pulse therapies with methylprednisolone were started. Continuous hemodiafiltration (CHDF) using cytokine-absorbing hemofilters was also initiated because of renal failure. These therapies, however, failed to control the disease, and the patient died on the 41st day of life. The dose of ACV on CHDF might not be adequate, although we could not measure the serum ACV concentrations. After the patient's death, we measured his serum cytokine concentrations taken four times during the clinical course. Serum concentrations of interleukin (IL)-6, IL-10, IL-1ß, and interferon (IFN)-γ were elevated at the time of admission and were remarkably decreased by 10 days after treatment. In particular, the concentrations of IL-1ß and IFN-γ were lower than the measurable ranges. It is therefore important to measure serum cytokine concentrations in real time to prevent excessive immune suppression.