Primary Herpes Simplex Research Articles

Primary herpes virus infection and ischemic stroke in childhood: A new association?

We describe, to our knowledge, the first case of arterial ischemic stroke after primary herpes simplex virus type 1 (HSV1) infection in a previously healthy child, without signs of encephalitis. A 10-year-old previously healthy girl was admitted to our hospital with acute left-sided hemiparesis which involved the lower half of her face. Submandibular lymphadenitis and oral vesicular lesions were present. MRI confirmed the suspicion of an acute ischemic stroke. Immunoglobulin M antibodies to HSV1 were detected. Cerebrospinal fluid polymerase chain reaction for herpes virus was negative. She was treated with aspirin (3mg/kg) and intravenous acyclovir (10mg/kg every 8hours) for 21days. Immunoglobulin G antibodies to HSV1 appeared 16days after admission. Twelve months after her hospitalization the patient’s examination was normal. Stroke should be considered a possible complication of HSV1 primary infection. Guidelines for the management of acute stroke in children are needed.

A Case of Peripheral Ulcerative Keratitis as Primary Herpes Simplex Infection in a Child

Purpose: To report a case of peripheral ulcerative keratitis in a case of primary herpes simplex infection. Case summary: A 7-year-old male complaining of pain, redness, and decreased vision in the left eye 5 days in duration visited our clinic. The patient had also vesicular lesions over the edematous left upper eyelid. Slit-lamp examination revealed peripheral ulcerative keratitis with stromal infiltration involving the superior peripheral cornea. Corneal sensation in the left eye was decreased. The patient was advised to use topical and oral antiviral agents and a topical steroid. After 5 days of follow-up, the corneal lesions were decreased and vesicles were absent. Six months later, only minor opacities remained in the cornea. Conclusions: We report the first case report in Korea of peripheral ulcerative keratitis with blepharoconjunctivitis presented as primary herpes simplex infection which responded to antiviral and steroid treatment in a young male. J Korean Ophthalmol Soc 2014;55(5):761-765

Characterization of Neuronal Populations in the Human Trigeminal Ganglion and Their Association with Latent Herpes Simplex Virus-1 Infection

Following primary infection Herpes simplex virus-1 (HSV-1) establishes lifelong latency in the neurons of human sensory ganglia. Upon reactivation HSV-1 can cause neurological diseases such as facial palsy, vestibular neuritis or encephalitis. Certain populations of sensory neurons have been shown to be more susceptible to latent infection in the animal model, but this has not been addressed in human tissue. In the present study, trigeminal ganglion (TG) neurons expressing six neuronal marker proteins were characterized, based on staining with antibodies against the GDNF family ligand receptor Ret, the high-affinity nerve growth factor receptor TrkA, neuronal nitric oxide synthase (nNOS), the antibody RT97 against 200kDa neurofilament, calcitonin gene-related peptide and peripherin. The frequencies of marker-positive neurons and their average neuronal sizes were assessed, with TrkA-positive (61.82%) neurons being the most abundant, and Ret-positive (26.93%) the least prevalent. Neurons positive with the antibody RT97 (1253 µm2) were the largest, and those stained against peripherin (884 µm2) were the smallest. Dual immunofluorescence revealed at least a 4.5% overlap for every tested marker combination, with overlap for the combinations TrkA/Ret, TrkA/RT97 and Ret/nNOS lower, and the overlap between Ret/CGRP being higher than would be expected by chance. With respect to latent HSV-1 infection, latency associated transcripts (LAT) were detected using in situ hybridization (ISH) in neurons expressing each of the marker proteins. In contrast to the mouse model, co-localization with neuronal markers Ret or CGRP mirrored the magnitude of these neuron populations, whereas for the other four neuronal markers fewer marker-positive cells were also LAT-ISH+. Ret and CGRP are both known to label neurons related to pain signaling.

The Scarlet H

The Scarlet H

Herpes simplex virus 2–induced activation in vaginal cells involves Toll-like receptors 2 and 9 and DNA sensors DAI and IFI16

The pathway by which herpes simplex virus 2 (HSV2) triggers the innate immune system in the urogenital system has not as yet been fully elucidated. In this study, we aimed to determine which pattern recognition receptors (PRRs) recognize HSV2 in primary vaginal epithelial cells. Once we deciphered the receptors involved, we aimed to target them to immunomodulate innate responses as a prophylactic or therapeutic intervention for early HSV2 infection. To determine which PRRs are involved, receptor silencing as well as confocal microscopy was utilized. For immunomodulation, PRR agonists were utilized to induce a strong, local response to limit the infection, and we used 2 quantitative methods, flow cytometry and plaque assays, to determine their effect on HSV2 replication. Our results show that HSV2 is detected by a plethora of PRRs: Toll-like receptors (TLR) 2 as well as deoxyribonucleic acid (DNA) sensors TLR9, DNA-dependent activator of interferon regulatory factors, and to a lesser extent interferon-inducible 16, which trigger cytokine secretion to protect the host. Using PRR agonists, such as lipoproteins, CpG DNA, and cyclic dinucleotides, we could significantly limit HSV2 replication. Different PRRs are strategically placed in different cell locations to detect virus invasion. Use of agonists that target and activate these PRRs appeared to be effective in preventing primary HSV2 infection in vaginal cells and could provide new insights in defense against HSV2 urogenital infections.

Longitudinal study on oral shedding of herpes simplex virus 1 and varicella‐zoster virus in individuals infected with HIV

Primary herpes simplex virus 1 (HSV-1) and varicella-zoster virus (VZV) infection leads to a life-long latent infection of ganglia innervating the oral mucosa. HSV-1 and VZV reactivation is more common in immunocompromised individuals and may result in viral shedding in saliva. We determined the kinetics and quantity of oral HSV-1 and VZV shedding in HSV-1 and VZV seropositive individuals infected with HIV and to assess whether HSV-1 shedding involves reactivation of the same strain intra-individually. HSV-1 and VZV shedding was determined by real-time PCR of sequential daily oral swabs (n = 715) collected for a median period of 31 days from 22 individuals infected with HIV. HSV-1 was genotyped by sequencing the viral thymidine kinase gene. Herpesvirus shedding was detected in 18 of 22 participants. Shedding of HSV-1 occurred frequently, on 14.3% of days, whereas solely VZV shedding was very rare. Two participants shed VZV. The median HSV-1 load was higher compared to VZV. HSV-1 DNA positive swabs clustered into 34 shedding episodes with a median duration of 2 days. The prevalence, duration and viral load of herpesvirus shedding did not correlate with CD4 counts and HIV load. The genotypes of the HSV-1 viruses shed were identical between and within shedding episodes of the same person, but were different between individuals. One-third of the individuals shed an HSV-1 strain potentially refractory to acyclovir therapy. Compared to HSV-1, oral VZV shedding is rare in individuals infected with HIV. Recurrent oral HSV-1 shedding is likely due to reactivation of the same latent HSV-1 strain.

Herpes simplex primo‐infection in an immunocompetent host with eosinophilic esophagitis

Eosinophilic esophagitis and herpes simplex esophagitis are separately well-described entities, but their simultaneous occurrence may pose a special challenge to the clinician, especially regarding the optimal therapeutic approach. The following case report describes a patient with a history of cow's milk and dairy products intolerance, but without an underlying immunologic defect, in whom eosinophilic esophagitis was diagnosed in the course of primary herpes simplex virus 1 (HSV1) infection that clinically presented as herpes labialis and severe esophagitis. The diagnosis was confirmed by a polymerase chain reaction from cytological brush and by immunohistochemical staining that detected the presence of HSV1 DNA in esophageal mucosa, and histologically by persistent eosinophil-predominant inflammation, typical of eosinophilic esophagitis. Despite severe clinical presentation, the HSV1 infection was self-limited. After a directed elimination diet was introduced, the clinical course was favorable, without the need for antiviral therapy.

Guidance on Management of Asymptomatic Neonates Born to Women With Active Genital Herpes Lesions

Herpes simplex virus (HSV) infection of the neonate is uncommon, but genital herpes infections in adults are very common. Thus, although treating an infant with neonatal herpes is a relatively rare occurrence, managing infants potentially exposed to HSV at the time of delivery occurs more frequently. The risk of transmitting HSV to an infant during delivery is determined in part by the mother's previous immunity to HSV. Women with primary genital HSV infections who are shedding HSV at delivery are 10 to 30 times more likely to transmit the virus to their newborn infants than are women with recurrent HSV infection who are shedding virus at delivery. With the availability of commercial serological tests that reliably can distinguish type-specific HSV antibodies, it is now possible to determine the type of maternal infection and, thus, further refine management of infants delivered to women who have active genital HSV lesions. The management algorithm presented herein uses both serological and virological studies to determine the risk of HSV transmission to the neonate who is delivered to a mother with active herpetic genital lesions and tailors management accordingly. The algorithm does not address the approach to asymptomatic neonates delivered to women with a history of genital herpes but no active lesions at delivery.

Clinical Practice in Prevention of Neonatal HSV Infection: A Survey of Obstetrical Care Providers in Alberta

ObjectiveTo identify the current practice patterns of physicians providing prenatal care in Alberta with respect to prevention of neonatal herpes simplex virus (HSV) infection. MethodA 22-item questionnaire was mailed to all obstetricians and family physicians providing obstetrical care in Alberta. The questionnaire included demographic and practice details, and details of management of patients with a history or symptoms of HSV lesions, including practice in prescribing antiviral therapy, recommending elective Caesarean section, and ordering serology. Two reminders were mailed as necessary. ResultsResponses were received from 89 obstetricians (57%) and 94 family physicians (54%). Antiviral therapy was prescribed for the prevention of neonatal HSV infection in the third trimester by 97% of obstetricians versus 84% of family physicians (P = 0.007), with acyclovir being the most commonly prescribed agent. Caesarean section was offered “most of the time” to women with primary HSV infection in the third trimester by 65% of physicians, to women with prodromal symptoms during the intrapartum period by 57% (no significant differences between groups), and to women with HSV lesions by 92% of obstetricians and 82% of family physicians (P = 0.032). Women with a negative HSV history but whose partner had known HSV were offered serological testing “most of the time” by 30% of physicians (no significant difference between groups). ConclusionDespite the encouraging survey results, obstetrical providers should be encouraged to offer Caesarean section to women with a primary HSV infection in the third trimester and to offer serological testing in discordant couples. These simple strategies can help to prevent neonatal HSV infection and its long-term consequences.

Epstein-Barr and other herpesvirus infections in patients with early onset type 1 diabetes treated with daclizumab and mycophenolate mofetil.

We assessed the morbidity of herpesviruses in patients with type 1 diabetes mellitus (T1D) enrolled in immunosuppressive treatment studies. Epstein-Barr virus (EBV), cytomegalovirus (CMV), herpes simplex virus (HSV), and varicella zoster virus (VZV) infections were monitored in 126 participants of a randomized, double-blind, placebo-controlled study of daclizumab (DZB) and mycophenolate mofetil (MMF) including DZB(+)MMF(+), DZB(-)MMF(+), DZB(+)MMF(-), and DZB(-)MMF(-). During the 2-year follow-up, herpesviral infections were monitored clinically, by serology and blood DNA polymerase chain reaction. Among 57 baseline EBV-seronegative participants, 9 developed EBV primary infections, including 2 with infectious mononucleosis syndrome. There were no appreciable differences in the course of the primary EBV infections across treatment groups. Among 69 baseline EBV-seropositive participants, 22 had virologic reactivations, including 1 symptomatic DZB(-)MMF(+) subject. Compared with 7 DZB(-)MMF(-) EBV reactivators, the 9 DZB(+)MMF(+) reactivators tended to have more prolonged viremia (11.4 vs 4.4 months; P = .06) and higher cumulative viral burden (14.2 vs 12.5 log EBV copies/mL; P = .06). Four of 85 baseline CMV-seronegative subjects developed asymptomatic primary CMV infections. There were no CMV reactivations. Of 30 baseline HSV-seropositive subjects, 8 developed ≥1 episode of herpes labialis; 1 subject had a primary HSV infection; and 1 subject without baseline serology information had a new diagnosis of genital HSV. There were no significant differences in the incidence of HSV recurrences across treatment groups. Of 100 baseline VZV-seropositive subjects, 1 DZB(-)MMF(-) subject developed herpes zoster and 1 DZB(-)MMF(+) subject had Bell's palsy possibly related to VZV. The use of DZB alone or in combination with MMF was not associated with increased morbidity due to herpesviruses. NCT00100178.

Postpartum Herpes Simplex Virus Endometritis and Disseminated Infection in Both Mother and Neonate

Herpes simplex virus (HSV) is an unusual cause of postpartum endometritis. We describe a rare case of primary disseminated maternal HSV in the postpartum period associated with endometritis. A previously healthy patient developed fundal tenderness and postpartum fevers after an uncomplicated vaginal delivery. Despite traditional broad-spectrum antimicrobial therapy, she had persistent fevers and systemic symptoms. Concurrently, her neonate developed fevers and a nonvesicular rash, with viral cultures ultimately returning positive for HSV. The patient developed active pharyngeal and genital herpetic lesions and was diagnosed with HSV endometritis and disseminated HSV. Symptoms and fevers in both the mother and neonate responded to antiviral therapy. Herpes simplex virus endometritis should be included in the differential diagnosis for postpartum fevers and fundal tenderness that are unresponsive to broad-spectrum antimicrobial treatment.

Heterozygous TBK1 mutations impair TLR3 immunity and underlie herpes simplex encephalitis of childhood

Childhood herpes simplex virus-1 (HSV-1) encephalitis (HSE) may result from single-gene inborn errors of TLR3 immunity. TLR3-dependent induction of IFN-α/β or IFN-λ is crucial for protective immunity against primary HSV-1 infection in the central nervous system (CNS). We describe here two unrelated children with HSE carrying different heterozygous mutations (D50A and G159A) in TBK1, the gene encoding TANK-binding kinase 1, a kinase at the crossroads of multiple IFN-inducing signaling pathways. Both mutant TBK1 alleles are loss-of-function but through different mechanisms: protein instability (D50A) or a loss of kinase activity (G159A). Both are also associated with an autosomal-dominant (AD) trait but by different mechanisms: haplotype insufficiency (D50A) or negative dominance (G159A). A defect in polyinosinic-polycytidylic acid-induced TLR3 responses can be detected in fibroblasts heterozygous for G159A but not for D50A TBK1. Nevertheless, viral replication and cell death rates caused by two TLR3-dependent viruses (HSV-1 and vesicular stomatitis virus) were high in fibroblasts from both patients, and particularly so in G159A TBK1 fibroblasts. These phenotypes were rescued equally well by IFN-α2b. Moreover, the IFN responses to the TLR3-independent agonists and viruses tested were maintained in both patients' peripheral blood mononuclear cells and fibroblasts. The narrow, partial cellular phenotype thus accounts for the clinical phenotype of these patients being limited to HSE. These data identify AD partial TBK1 deficiency as a new genetic etiology of childhood HSE, indicating that TBK1 is essential for the TLR3- and IFN-dependent control of HSV-1 in the CNS.

Diagnosis of primary herpes simplex in the upper lip with PCR and transmission electron microscopy: a case report

A 66-year-old man was admitted for a 7-day history of painful blisters and erosions in the upper lip.Real-time PCR with herpes simplex virus (HSV) type-specific primers showed that the blister fluid and crusts were positive for HSV-1,but negative for HSV-2.Observation of the blister wall with transmission electron microscopy (TEM) revealed 3 types of nucleocapsid in the karyoplast of epithelia cells,including the electron-translucent core,granular core and electron-dense core.Numerous matured viral particles with envelope were found in the cytoplasm,which were identified as HSV.The diagnosis was made as herpes simplex in the upper lip based on the above findings.PCR based molecular typing combined with observation of HSV particles via TEM may be an effective approach to the definite diagnosis of primary herpes simplex.

Primary Maternal Herpes Simplex Virus-1 Gingivostomatitis During Pregnancy and Neonatal Herpes: Case Series and Literature Review.

Neonatal herpes simplex virus (HSV) is a serious, life-threatening infection that is usually acquired during birth from contact with infected maternal genital secretions. Primary maternal HSV gingivostomatitis is a rare occurrence during pregnancy, and HSV type 1 (HSV-1) neonatal disease after primary maternal HSV gingivostomatitis during pregnancy has not been reported in detail. We reviewed the medical records of neonates (≤28 days of age) with a confirmed diagnosis of neonatal HSV-1 at a single pediatric center from January 1981 to January 2010 to identify cases in which the mother had primary gingivostomatitis during pregnancy or at term. Seven neonates whose mothers had primary HSV-1 gingivostomatitis during pregnancy were identified from a review of 48 neonates with laboratory-proven HSV-1 neonatal disease. Of the 7 women, 2 presented with symptoms of primary HSV-1 gingivostomatitis during the first trimester and 5 in the third trimester. Three of the neonates developed skin, eye, and mucous membrane disease, 2 developed central nervous system disease, and 2 developed disseminated disease. One of the neonates with disseminated HSV-1 disease died. Primary maternal HSV gingivostomatitis during pregnancy may lead to HSV-1 transmission to the neonate. Physicians caring for pregnant women should communicate the diagnosis of HSV gingivostomatitis to the neonate's primary provider to ensure proper surveillance, early evaluation, and prompt treatment.

Preventing Neonatal Transmission of Herpes Simplex Virus

Herpes simplex virus (HSV) infections are highly prevalent and may have devastating consequences if transmitted to newborns. The highest risk of transmission is when the mother has primary HSV infection (rather than recurrence of chronic infection) late in pregnancy. Clinicians should obtain a careful history, performing serologic testing and counseling as appropriate. Delayed diagnosis of neonatal HSV is associated with high mortality. Even with adequate treatment, permanent sequelae, such as cerebral palsy and developmental delay, may occur. Clinicians should develop prudent strategies to avoid primary HSV acquisition during pregnancy, and provide prophylaxis or treatment when indicated.

P80 Genitourinary medicine physicians need further training in the management of HSV in late pregnancy

BackgroundTransmission rates of neonatal herpes simplex virus (HSV) infection varies from 30% to 50% if shedding with primary infection during the third trimester of pregnancy, to <3% with active recurrent...

Bilateral vocal cord abductor paralysis associated with primary herpes simplex infection: A case report

To report a case of bilateral vocal cord abductor paralysis in the context of primary herpes simplex infection. A 63-year-old man was urgently admitted to hospital with laryngeal dyspnoea associated with dysphagia but without dysphonia. Physical examination demonstrated the vocal cords in a paramedian position with paralysis of abduction. The patient reported primary herpes simplex infection two weeks prior to this episode. HSV serology indicated recent infection and lumbar puncture demonstrated the presence of herpes simplex virus type 1 in the cerebrospinal fluid. Complete resolution of respiratory symptoms was observed after 21 days of treatment with intravenous aciclovir. Gerhardt syndrome comprises inspiratory dyspnoea without dysphonia. It used to be mainly due to syphilis, but is now mostly observed in the setting of neurodegenerative disease. The authors report a case of Gerhardt syndrome occurring after an episode of primary herpes simplex infection with the presence of herpes simplex virus in the CSF. Treatment by intravenous antiviral drugs allowed rapid resolution of the symptoms. The pathophysiology of Gerhardt syndrome remains unexplained, but the possible role of herpes simplex infection should be considered in cases of laryngeal palsy.

Gingivostomatitis herpetik primer pada anak Primary herpetic gingivostomatitis on children

Herpetic gingivostomatitis is an infection of primary herpes simplex virus (HSV) type-1 characterized byvesiculoulcerative lesion. This diseasae commonly seen in 1 until 5-year-old children, but occur in adultoccasionally. This paper reports a 5-year-old girl with chief complaint ulcerations in oral cavity. Fever and malaiseproceed ulcers five days before. The diagnosis primary herpetic gingivostomatitis was based on this first and manyulcers. Antivirus agent, multivitamin, benzydamine HCl gargle and high calorie and high protein diet was given tothe patient. Herpetic gingivostomatitis usually healed by time, but recurrent herpes simplex virus can avoid withproper therapy and monitoring.

Fulminant gestational hepatitis due to primary herpes simplex type 2 infection: use of serum HSV polymerase chain reaction for noninvasive diagnosis

Acute gestational hepatitis from herpes simplex virus (HSV) infection is a rare but potentially life-threatening condition. We present the first reported case of primary HSV type 2 hepatitis in a pregnant woman who was diagnosed by detection of HSV-2 viremia via real-time polymerase chain reaction. The patient was successfully treated with acyclovir and delivered a healthy infant.

50 Years Ago in The Journal of Pediatrics: Latent Virus Infection: Recurrent Herpes Simplex

Blattner RJ. J Pediatr 1961;59:784-6 In the section of The Journal “Comments on Current Literature,” Blattner gives a glimpse of the “state-of-the-thinking” on pathogenesis of herpes simplex virus (HSV) infections. Investigators and “thinkers” at the time had so much of it right (ie, most primary HSV infections are subclinical, yet whether clinical or subclinical, infection leads to establishment of latency and cycles of reactivation in most people). Presence of antibody does not prevent superficial recurrences (reactivations), which sometimes take on “zosteriform” characteristics by following nerve distribution. Investigators and clinicians even recognized (and made experimental models in animals to prove) some triggers of reactivation. One thing that they didn’t have quite right was the risk factors for occurrence of HSV encephalitis beyond the neonatal period. They thought that encephalitis would occur only with primary HSV infection and likely was associated with particularly neurotropic strains of HSV, neither of which is true. We now know that the host, rather than the virus, probably has the relevant influence on events. Abel et al have studied extensively and presented evidence that HSV encephalitis beyond the neonatal period, seemingly a rare but sporadic event, is not “bad luck” or “bad bug,” but is attributable at least in part to one or more organism-specific host innate immune defects.1Abel L. Plancoulaine S. Jouanguy E. et al.Age-dependent Mendelian predisposition to herpes simplex virus type 1 encephalitis in childhood.J Pediatr. 2010; 157: 623-629Abstract Full Text Full Text PDF PubMed Scopus (77) Google Scholar