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1.
Nat Commun ; 15(1): 4018, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38740820

ABSTRACT

Anti-HSV therapies are only suppressive because they do not eliminate latent HSV present in ganglionic neurons, the source of recurrent disease. We have developed a potentially curative approach against HSV infection, based on gene editing using HSV-specific meganucleases delivered by adeno-associated virus (AAV) vectors. Gene editing performed with two anti-HSV-1 meganucleases delivered by a combination of AAV9, AAV-Dj/8, and AAV-Rh10 can eliminate 90% or more of latent HSV DNA in mouse models of orofacial infection, and up to 97% of latent HSV DNA in mouse models of genital infection. Using a pharmacological approach to reactivate latent HSV-1, we demonstrate that ganglionic viral load reduction leads to a significant decrease of viral shedding in treated female mice. While therapy is well tolerated, in some instances, we observe hepatotoxicity at high doses and subtle histological evidence of neuronal injury without observable neurological signs or deficits. Simplification of the regimen through use of a single serotype (AAV9) delivering single meganuclease targeting a duplicated region of the HSV genome, dose reduction, and use of a neuron-specific promoter each results in improved tolerability while retaining efficacy. These results reinforce the curative potential of gene editing for HSV disease.


Subject(s)
Dependovirus , Gene Editing , Herpes Simplex , Herpesvirus 1, Human , Viral Load , Virus Shedding , Animals , Gene Editing/methods , Female , Dependovirus/genetics , Mice , Herpesvirus 1, Human/genetics , Herpesvirus 1, Human/physiology , Herpes Simplex/genetics , Herpes Simplex/virology , Herpes Simplex/therapy , Disease Models, Animal , Virus Latency/genetics , Humans , Genetic Vectors/genetics , Vero Cells , Genetic Therapy/methods , Herpes Genitalis/therapy , Herpes Genitalis/virology , DNA, Viral/genetics
2.
Ann Hematol ; 101(3): 491-511, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34994811

ABSTRACT

Clinical reactivations of herpes simplex virus or varicella zoster virus occur frequently among patients with malignancies and manifest particularly as herpes simplex stomatitis in patients with acute leukaemia treated with intensive chemotherapy and as herpes zoster in patients with lymphoma or multiple myeloma. In recent years, knowledge on reactivation rates and clinical manifestations has increased for conventional chemotherapeutics as well as for many new antineoplastic agents. This guideline summarizes current evidence on herpesvirus reactivation in patients with solid tumours and hematological malignancies not undergoing allogeneic or autologous hematopoietic stem cell transplantation or other cellular therapy including diagnostic, prophylactic, and therapeutic aspects. Particularly, strategies of risk adapted pharmacological prophylaxis and vaccination are outlined for different patient groups. This guideline updates the guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO) from 2015 "Antiviral prophylaxis in patients with solid tumours and haematological malignancies" focusing on herpes simplex virus and varicella zoster virus.


Subject(s)
Hematologic Neoplasms/virology , Herpes Genitalis/therapy , Herpes Simplex/therapy , Neoplasms/virology , Varicella Zoster Virus Infection/therapy , Virus Activation , Acyclovir/therapeutic use , Antiviral Agents/therapeutic use , Disease Management , Germany , Herpes Genitalis/diagnosis , Herpes Genitalis/prevention & control , Herpes Simplex/diagnosis , Herpes Simplex/prevention & control , Herpesvirus 1, Human/drug effects , Herpesvirus 1, Human/isolation & purification , Herpesvirus 1, Human/physiology , Herpesvirus 2, Human/drug effects , Herpesvirus 2, Human/isolation & purification , Herpesvirus 2, Human/physiology , Herpesvirus 3, Human/drug effects , Herpesvirus 3, Human/isolation & purification , Herpesvirus 3, Human/physiology , Humans , Vaccination , Varicella Zoster Virus Infection/diagnosis , Varicella Zoster Virus Infection/prevention & control , Virus Activation/drug effects
3.
Enferm. infecc. microbiol. clín. (Ed. impr.) ; 39(5): 234-240, May. 2021. tab, graf
Article in English | IBECS | ID: ibc-208606

ABSTRACT

Introducción: El virus herpes simple tipo 2 (VHS-2) es la causa más frecuente de herpes genital (HG), pero la infección genital por el virus herpes simple tipo 1 (VHS-1) está en aumento. El objetivo del estudio fue analizar las características epidemiológicas de pacientes con HG. Métodos: Estudio retrospectivo desde enero del 2004 hasta diciembre del 2015 de pacientes con HG atendidos en 2 consultas de enfermedades de transmisión sexual (ETS) en la Organización Sanitaria Integrada Bilbao-Basurto, en el norte de España. Se revisaron y analizaron los datos de interés de los pacientes. Resultados: Mil tres pacientes (524 hombres y 479 mujeres) fueron incluidos. El 74% tenía infección por VHS-2. El VHS-1 aumentó durante el periodo estudiado, significativamente en hombres (28% en 2004-2007 vs. 50% en 2012-2015). El VHS-1 fue mayor en mujeres en comparación con hombres (56% vs. 44%). La infección primaria fue más frecuente en los infectados con VHS-1 comparado con VHS-2 (79% vs. 21%). En pacientes con VHS-1, la infección primaria fue superior en hombres (86%) y en menores de 30 años. El 63% de las infecciones por VHS-2 fueron recurrencias. En el análisis multivariante, la edad, el origen extranjero, la recurrencia, el contacto previo con HG de la pareja sexual, la infección previa por Neisseria gonorrhoeae y la prostitución se asociaron con mayor riesgo de infección por VHS-2. Conclusiones:El VHS-2 fue la causa principal del HG, pero la proporción de VHS-1 aumentó. El antecedente de ETS y las conductas sexuales de riesgo fueron predominantes en los pacientes con HG por VHS-2.(AU)


Background: Herpes simplex virus type 2 (HSV-2) is the most common cause of genital herpes (GH), but genital infection by herpes simplex virus type 1 (HSV-1) is increasing. The aim of this study was to analyze and compare epidemiological characteristics of patients with GH. Methods:Retrospective study conducted from January 2004 to December 2015 in patients with GH attended at two Sexually Transmitted Diseases (STDs) medical consultation of Bilbao-Basurto Integrated Health Organisation in Northern Spain. Patient's medical history was reviewed and data of interest was analyzed. Results: One thousand three patients (524 male and 479 female) were reviewed. HSV-2 was detected in 74%. The proportion of HSV-1 increased during the study period, significantly in men (28% in 2004–2007 vs. 50% in 2012–2015). More female than male had HSV-1 infection (56% vs. 44%). The proportion of primary infection was higher among HSV-1 compared to HSV-2 (79% vs. 21%). Among the patients with HSV-1, primary infection was higher among men (86%) and in younger than 30 years. Recurrent GH was higher among HSV-2 infections (63%). In a multivariate model older age, geographic origin outside Spain, recurrent infection, prior contact with a partner's genital herpetic lesions, previous N. gonorrhoeae infection and prostitution were significantly associated with HSV-2 infection. Conclusions: HSV-2 was the most common causative agent of GH, but the proportion of HSV-1 increased. Overall, antecedent of STD and sexual risk behaviors were more frequent in patients with genital HSV-2 infection.(AU)


Subject(s)
Humans , Male , Female , Sexually Transmitted Diseases/diagnosis , Sexually Transmitted Diseases/drug therapy , Herpes Genitalis/diagnosis , Herpes Genitalis/drug therapy , Herpes Genitalis/therapy , Simplexvirus , Retrospective Studies , Communicable Diseases , Microbiology , Spain/epidemiology
4.
Epidemiol. serv. saúde ; 30(spe1): e2020628, 2021. tab
Article in Portuguese | LILACS | ID: biblio-1154149

ABSTRACT

Este artigo tem como objetivo apresentar conceitos e práticas clínicas recomendados para a abordagem da pessoa com vida sexual ativa. Esses conceitos são parte integrante das recomendações do Protocolo Clínico e Diretrizes Terapêuticas para Atenção Integral às Pessoas com Infecções Sexualmente Transmissíveis (IST) publicado pelo Ministério da Saúde do Brasil em 2020. O artigo propõe uma abordagem abrangente da sexualidade para promoção da saúde e apresenta aspectos importantes do processo de comunicação, que deve ocorrer de forma clara, sem preconceitos ou juízos de valor, com foco na saúde sexual e reprodutiva. Destacam-se pontos relevantes acerca do exercício da sexualidade em fases específicas da vida, recomendando avaliação dos riscos e vulnerabilidades, bem como o rastreamento de IST e o uso de preservativos. Dessa maneira, é possível contribuir para que as pessoas possam exercer sua sexualidade de forma plena, responsável e segura.


This article aims to present concepts and clinical practices recommended to approach people with an active sex life. These concepts are an integral part of the recommendations of the Clinical Protocol and Therapeutic Guidelines for Comprehensive Care for People with Sexually Transmitted Infections (STI), published by the Ministry of Health of Brazil in 2020.The article proposes a comprehensive approach to sexuality for health promotion and presents important aspects of the communication process that must develop clearly, without prejudice and judgment, with a focus on sexual and reproductive health. It also highlights relevant points about the exercise of sexuality at specific stages of life, recommending assessment of risks and vulnerabilities, as well as screening for STI and condom use. In this way, it is possible to contribute so that people can exercise their sexuality fully, responsibly and safely.


Este artículo tiene como objetivo presentar los conceptos y las prácticas clínicas recomendados para un abordaje de la persona con una vida sexual activa. Estos conceptos son parte de las recomendaciones contenidas en el Protocolo Clínico y Directrices Terapéuticas para la Atención Integral a Personas con Infecciones de Transmisión Sexual (ITS), publicado por el Ministerio de Salud de Brasil en 2020. El artículo propone un abordaje amplio de la sexualidad para la promoción de la salud. Presenta aspectos importantes del proceso de comunicación, que debe ocurrir con claridad, sin prejuicios y juicios de valor, con un enfoque en la salud sexual y reproductiva. Destaca puntos relevantes sobre el ejercicio de la sexualidad en etapas específicas de la vida, recomendando evaluación de riesgos y vulnerabilidades, así como el rastreo de ITS y el uso de preservativos. De esta forma, es posible contribuir para que las personas puedan ejercer su sexualidad de manera plena, responsable y segura.


Subject(s)
Humans , Male , Female , Ulcer/therapy , Chancroid/therapy , Sexually Transmitted Diseases/therapy , Sexually Transmitted Diseases/epidemiology , Genitalia/pathology , Brazil/epidemiology , Herpes Genitalis/therapy , Lymphogranuloma Venereum/therapy , Syphilis/therapy , Clinical Protocols , Granuloma Inguinale/therapy
5.
Epidemiol. serv. saúde ; 30(spe1): e2020663, 2021. tab, graf
Article in English, Portuguese | LILACS | ID: biblio-1154153

ABSTRACT

As infecções que causam úlcera genital são um dos temas que compõem o Protocolo Clínico e Diretrizes Terapêuticas para Atenção Integral às Pessoas com Infecções Sexualmente Transmissíveis, publicado pelo Ministério da Saúde do Brasil em 2020. Tal documento foi elaborado com base em evidências científicas e validado em discussões com especialistas. Este artigo aborda a síndrome clínica de úlcera genital causada por infecções sexualmente transmissíveis e seus agentes etiológicos mais comuns: Treponema pallidum (sífilis), vírus herpes simples 2 (herpes genital) e vírus herpes simples 1 (herpes perioral), Haemophilus ducreyi (cancroide), Chlamydia trachomatis sorotipos L1, L2 e L3 (linfogranuloma venéreo) e Klebsiella granulomatis (donovanose). São apresentados aspectos epidemiológicos e clínicos dessas infecções, bem como orientações para seu diagnóstico e tratamento, além de estratégias para as ações de vigilância, prevenção e controle, com a finalidade de subsidiar gestores e profissionais de saúde na qualificação da assistência.


Infections that cause genital ulcers are one of the themes comprising the Clinical Protocol and Therapeutic Guidelines for Comprehensive Care for People with Sexually Transmitted Infections, published by the Brazilian Ministry of Health in 2020. The Protocol and Guidelines have been developed based on scientific evidence and validated in discussions with specialists. This article addresses clinical genital ulcer syndrome caused by sexually transmitted infections, and its most common etiological agents: Treponema pallidum (syphilis), herpes simplex virus-2 (genital herpes) and herpes simplex virus-1 (perioral herpes), Haemophilus ducreyi (chancroid), Chlamydia trachomatis serotypes L1, L2 and L3 (venereal lymphogranuloma), and Klebsiella granulomatis (donovanosis). Epidemiological and clinical aspects of these infections are presented, as well as guidelines for their diagnosis and treatment, in addition to strategies for surveillance, prevention and control actions, with the purpose of supporting health managers and professionals in the qualification of care.


El tema de las infecciones que causan úlcera genital hace parte del Protocolo Clínico y Directrices Terapéuticas para Atención Integral a las Personas con Infecciones de Transmisión Sexual, publicado por el Ministerio de Salud de Brasil en 2020. Dicho documento fue elaborado con base en evidencias científicas y validado en discusiones con especialistas. Este artículo trata del síndrome de úlcera genital clínica provocada por infecciones de transmisión sexual, con sus agentes etiológicos más comunes: Treponema pallidum (sífilis), virus del herpes simple-1 (herpes genital) y virus del herpes simple-2 (herpes perioral), Haemophilus ducreyi (chancro blando), Chlamydia trachomatis, serotipos L1, L2 y L3 (linfogranuloma venéreo), y Klebsiella granulomatis (donovanosis). Se presentan aspectos epidemiológicos y clínicos de esas infecciones, bien como pautas para su diagnóstico y tratamiento, además de estrategias para acciones de monitoreo epidemiológico, prevención y control, a fin de contribuir con gestores y personal de salud en la cualificación de la asistencia.


Subject(s)
Humans , Male , Female , Ulcer/therapy , Sexually Transmitted Diseases, Viral/epidemiology , Chancroid/therapy , Sexually Transmitted Diseases/therapy , Genitalia/pathology , Brazil/epidemiology , Herpes Genitalis/therapy , Lymphogranuloma Venereum/therapy , Syphilis/therapy , Clinical Protocols , Granuloma Inguinale/therapy
6.
Pediatr Rev ; 41(9): 455-468, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32873560

ABSTRACT

Sexually transmitted infections (STIs) affect young people in a disproportionate way, with more than half of the infections occurring in 15- to 25-year-olds, although as an age group they constitute only 25% of the sexually active population. Pediatricians should be familiar with the social, behavioral, and biological factors that predispose adolescents to STIs. Preventive visits for teens and pre-teens should incorporate education and counseling about sexuality, safe sexual behavior, and STIs. Pediatricians should be able to identify, diagnose, and manage STIs presenting as genital "bumps" and genital "ulcers." Pediatricians should also offer human immunodeficiency virus testing and expedited partner treatment to all adolescents who are diagnosed as having an STI.


Subject(s)
Pediatrics/methods , Sexually Transmitted Diseases , Adolescent , Adult , Condylomata Acuminata/diagnosis , Condylomata Acuminata/pathology , Condylomata Acuminata/therapy , Diagnosis, Differential , Directive Counseling , Female , HIV Infections/diagnosis , HIV Infections/therapy , HIV Infections/transmission , Herpes Genitalis/diagnosis , Herpes Genitalis/pathology , Herpes Genitalis/therapy , Herpes Genitalis/transmission , Humans , Male , Papillomavirus Infections/diagnosis , Papillomavirus Infections/pathology , Papillomavirus Infections/therapy , Papillomavirus Infections/transmission , Physician-Patient Relations , Primary Prevention/methods , Secondary Prevention/methods , Sex Education/methods , Sexually Transmitted Diseases/diagnosis , Sexually Transmitted Diseases/pathology , Sexually Transmitted Diseases/therapy , Sexually Transmitted Diseases/transmission , Ulcer/diagnosis , Ulcer/microbiology , Ulcer/pathology , Ulcer/therapy , Young Adult
7.
Obstet Gynecol ; 135(5): 1236-1238, 2020 May.
Article in English | MEDLINE | ID: mdl-32332408

ABSTRACT

Genital herpes simplex virus (HSV) infection during pregnancy poses a risk to the developing fetus and newborn. Genital herpes is common in the United States. Among 14- to 49-year-old females, the prevalence of HSV-2 infection is 15.9%. However, the prevalence of genital herpes infection is higher than that because genital herpes is also caused by HSV-1 (1). Because many women of childbearing age are infected or will be infected with HSV, the risk of maternal transmission of this virus to the fetus or newborn is a major health concern. This document has been revised to include that for women with a primary or nonprimary first-episode genital HSV infection during the third trimester of pregnancy, cesarean delivery may be offered due to the possibility of prolonged viral shedding.


Subject(s)
Herpes Genitalis/therapy , Infectious Disease Transmission, Vertical/prevention & control , Pregnancy Complications, Infectious/therapy , Pregnancy Complications, Infectious/virology , Prenatal Care/standards , Adolescent , Adult , Antiviral Agents/therapeutic use , Cesarean Section/methods , Female , Herpes Genitalis/epidemiology , Herpes Genitalis/transmission , Humans , Infant, Newborn , Male , Middle Aged , Pregnancy , Pregnancy Complications, Infectious/epidemiology , Pregnancy Trimester, Third , Prevalence , Simplexvirus , United States/epidemiology , Young Adult
8.
Obstet Gynecol ; 135(5): e193-e202, 2020 May.
Article in English | MEDLINE | ID: mdl-32332414

ABSTRACT

Genital herpes simplex virus (HSV) infection during pregnancy poses a risk to the developing fetus and newborn. Genital herpes is common in the United States. Among 14- to 49-year-old females, the prevalence of HSV-2 infection is 15.9%. However, the prevalence of genital herpes infection is higher than that because genital herpes is also caused by HSV-1 (). Because many women of childbearing age are infected or will be infected with HSV, the risk of maternal transmission of this virus to the fetus or newborn is a major health concern. This document has been revised to include that for women with a primary or nonprimary first-episode genital HSV infection during the third trimester of pregnancy, cesarean delivery may be offered due to the possibility of prolonged viral shedding.


Subject(s)
Herpes Genitalis/therapy , Infectious Disease Transmission, Vertical/prevention & control , Pregnancy Complications, Infectious/therapy , Pregnancy Complications, Infectious/virology , Prenatal Care/standards , Adolescent , Adult , Antiviral Agents/therapeutic use , Cesarean Section/methods , Female , Herpes Genitalis/epidemiology , Herpes Genitalis/transmission , Humans , Infant, Newborn , Male , Middle Aged , Pregnancy , Pregnancy Complications, Infectious/epidemiology , Pregnancy Trimester, Third , Prevalence , Simplexvirus , United States/epidemiology , Young Adult
9.
Eur J Obstet Gynecol Reprod Biol ; 249: 84-91, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32122691

ABSTRACT

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.


Subject(s)
Health Knowledge, Attitudes, Practice , Health Personnel/psychology , Herpes Genitalis/therapy , Pregnancy Complications, Infectious/therapy , Prenatal Care/psychology , Antiviral Agents/therapeutic use , Female , France , Herpes Genitalis/transmission , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical/prevention & control , Pregnancy , Pregnancy Complications, Infectious/virology , Pregnancy Trimester, Third , Simplexvirus
10.
Vaccine ; 37(43): 6470-6477, 2019 10 08.
Article in English | MEDLINE | ID: mdl-31515143

ABSTRACT

Genital herpes is a sexually transmitted disease representing a major global health concern. Currently, there is no approved vaccine and existing antiviral therapies exhibit limited efficacy. Herein, we describe an intranasal (IN) vaccine comprised of HSV-2 surface glycoproteins gD2 and gB2 formulated in a nanoemulsion adjuvant (NE01-gD2/gB2). Using the HSV-2 genital herpes guinea pig model, we demonstrate that IN NE01-gD2/gB2 induces higher levels of neutralizing antibody compared to a monovalent IN NE01-gD2 vaccine, but less than an intramuscular (IM) Alum/MPL-gD2 vaccine. Following intravaginal (IVag) challenge with HSV-2, the group immunized with IN NE01-gD2/gB2 exhibited significantly reduced acute and recurrent disease scores compared to placebo recipients. Significantly, latent virus was only detected in the dorsal root ganglia of 1 of 12 IN NE01-gD2/gB2-vaccinated animals compared to 11 of 12 placebo recipient. In the therapeutic model, IN NE01-gD2/gB2 immunized guinea pigs exhibited a significant reduction in the recurrent lesions scores (64%, p < 0.01), number of animal days with disease (64%, p < 0.01), number of animals with viral shedding (50%, p < 0.04) and reduction in virus positive vaginal swabs (56%, p < 0.04), These data suggests that the treatment may be effective in treating chronic disease and minimizing virus transmission. These results warrant advancing the development of IN NE01-gD2/gB2 as both a prophylactic and therapeutic vaccine against HSV-2.


Subject(s)
Antibodies, Viral/blood , Herpes Genitalis/prevention & control , Herpes Genitalis/therapy , Herpes Simplex Virus Vaccines/administration & dosage , Herpes Simplex Virus Vaccines/therapeutic use , Adjuvants, Immunologic/administration & dosage , Administration, Intranasal , Animals , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Disease Models, Animal , Emulsions/administration & dosage , Emulsions/chemistry , Female , Guinea Pigs , Herpes Genitalis/immunology , Herpesvirus 2, Human , Nanoparticles/administration & dosage , Nanoparticles/chemistry , Vaccines, Subunit/administration & dosage , Vaccines, Subunit/therapeutic use , Virus Shedding
11.
PLoS One ; 14(7): e0219305, 2019.
Article in English | MEDLINE | ID: mdl-31310628

ABSTRACT

A monogalactosyl diacylglyceride (MGDG) was isolated as an antiviral component from Coccomyxa sp. KJ (IPOD FERM BP-22254) via bioassay-guided fractionation. α-Linolenic acid (C18:3) and 7,10,13-hexadecatrienoic acid (C16:3) accounted for approximately 72% and 23%, respectively, of the MGDG total fatty acids of the MGDG. The MGDG showed virucidal activity against herpes simplex virus type 2 (HSV-2), a pathogen that causes genital herpes. Physical changes in HSV-2 shape were observed after treatment with MGDG, including a decrease in particle size, and possible damage to the viral envelope, as assessed using electron microscopy. In accordance with the morphological findings, virus particles lost their ability to bind to host cells. HSV-2 treated with high concentrations of MGDG resulted in no pathogenicity in an animal model, indicating that MGDG exhibits irreversible virucidal activity against HSV-2 particles. In the animal model of HSV-2-induced genital herpes, intravaginally administered MGDG exerted a prophylactic effect by suppressing viral yields in the genital cavity and formation of herpetic lesions, resulting in a higher survival rate in treated mice than control mice administered solvent. Thus, MGDG offers a novel prophylactic option against HSV infections.


Subject(s)
Antiviral Agents/pharmacology , Galactolipids/pharmacology , Herpes Genitalis/therapy , Herpesvirus 2, Human/drug effects , Microalgae/chemistry , Administration, Intravaginal , Animals , Antiviral Agents/analysis , Chlorocebus aethiops , Disease Models, Animal , Fatty Acids, Unsaturated/analysis , Female , Galactolipids/analysis , Herpes Genitalis/virology , Mice , Mice, Inbred BALB C , Particle Size , Vero Cells , alpha-Linolenic Acid/analysis
12.
Dermatol Ther ; 32(3): e12847, 2019 05.
Article in English | MEDLINE | ID: mdl-30693632

ABSTRACT

Erythema multiforme (EM) is an immune-mediated reaction characterized by target lesions and with possible mucosal involvement. Its most frequent cause is HSV, with HSV-1 more common than -2. It is usually self-limited but it can show recurrences. We report a peculiar case of recurrent herpes-associated erythema multiforme (HAEM) in a 35-year-old man. The patient was affected by both herpes labialis and genitalis, but the typical target lesions were only associated with recurrent herpes labialis. Here, we hypothesize about the pathogenic differences between HSV-1 and HSV-2, and discuss the therapeutic management of HAEM.


Subject(s)
Erythema Multiforme/virology , Herpes Genitalis/complications , Herpes Labialis/complications , Adult , Erythema Multiforme/therapy , Herpes Genitalis/therapy , Herpes Labialis/therapy , Herpesvirus 1, Human/isolation & purification , Herpesvirus 2, Human/isolation & purification , Humans , Male , Recurrence
13.
J Infect Dis ; 218(12): 1890-1899, 2018 11 05.
Article in English | MEDLINE | ID: mdl-29982727

ABSTRACT

Background: GEN-003 is a candidate therapeutic vaccine for genital herpes simplex virus type 2 (HSV-2). We compared virologic and clinical impact of varying GEN-003 doses. Methods: Adults with symptomatic HSV-2 received placebo or GEN-003 (30 or 60 µg antigen with 25, 50, or 75 µg adjuvant). Viral shedding and lesion rates before vaccination were compared with those measured immediately after vaccination, then at weeks 29-33 and 53-57 after last dose. Results: Compared with baseline shedding rates, the rate ratios for viral shedding immediately after treatment were as follows: 0.82 (95% confidence interval [CI], 0.49-1.36), 30 µg antigen/25 µg adjuvant (30/25) dose; 0.64 (95% CI, 0.45-0.92), 30/50 dose; 0.63 (95% CI, 0.37-1.10), 30/75 dose; 0.56 (95% CI, 0.36-0.88), 60/25 dose; 0.58 (95% CI, 0.38-0.89), 60/50 dose; 0.45 (95% CI, 0.16-0.79), 60/75 dose; and 0.98 (95% CI, 0.76-1.26), placebo. Lesion rate reductions by GEN-003 ranged from 31% to 69%, but lesion rates also decreased among placebo recipients (62%). Reductions in shedding and lesion rate were durable for 12 months for the 60 µg antigen plus 50 or 75 µg adjuvant groups. No serious adverse events occurred with vaccination. Conclusions: The most efficacious vaccine combinations for GEN-003 were the 60 µg/50 µg and 60 µg/75 µg doses.


Subject(s)
Herpes Genitalis/therapy , Herpesvirus 2, Human/immunology , Immunotherapy , Viral Vaccines/therapeutic use , Adjuvants, Immunologic , Adolescent , Adult , Female , Herpes Genitalis/virology , Humans , Male , Middle Aged , Vaccination , Viral Vaccines/administration & dosage , Virus Shedding , Young Adult
14.
JBI Database System Rev Implement Rep ; 16(5): 1087-1094, 2018 May.
Article in English | MEDLINE | ID: mdl-29762300

ABSTRACT

REVIEW QUESTION: The review questions are:The specific objectives are:This mixed methods review seeks to develop an aggregated synthesis of quantitative and qualitative data on the HRQOL implications of genital herpes for the individual in order to derive conclusions and recommendations for clinical practice and policy decision making.


Subject(s)
Herpes Genitalis/psychology , Herpes Genitalis/therapy , Quality of Life/psychology , Adolescent , Adult , Antiviral Agents/administration & dosage , Humans , Recurrence , Systematic Reviews as Topic
15.
Gynecol Obstet Fertil Senol ; 45(12): 642-654, 2017 Dec.
Article in French | MEDLINE | ID: mdl-29146286

ABSTRACT

OBJECTIVES: To analyze the consequences of genital herpes infections in pregnant women. METHODS: The PubMed database and the recommendations from the French and foreign obstetrical societies or colleges have been consulted. RESULTS: The symptomatology of herpes genital rash is often atypical (NP2) and not different during pregnancy (Professional consensus). It is most often due to HSV2 (NP2). Seventy percent of pregnant patients have a history of infection with Herpes simplex virus, without reference to genital or labial localization, and this is in most cases type 1 (NP2). The prevalence of clinical herpes lesions at birth in the event of recurrence is about 16% compared with 36% in the case of initial infection (NP4). In HSV+ patients, asymptomatic herpetic excretion is 4 to 10%. The rate of excretion increases in HIV+ patients (20 to 30%) (NP2). The risk of HSV seroconversion during pregnancy is 1 to 5% (NP2), but can reach 20% in case of sero-discordant couple (NP2). Questioning is not always sufficient to determine the history of herpes infection of a patient and her partner (NP2) and the clinical examination is not always reliable (NP2). Herpetic hepatitis and encephalitis are rare and potentially severe (NP4). These diagnoses should be discussed during pregnancy and antiviral therapy should be started as soon as possible (Professional consensus). There is no established link between herpes infection and miscarriages (NP3). There appears to be an association between untreated herpes infection and premature delivery (NP3) but not in the case of treated infections (NP4). Herpetic fetopathies are exceptional (NP4). There is no argument for recommending specific prenatal diagnosis for herpes infection during pregnancy (Professional consensus). Condom use reduces the risk of initial infection in women who are not pregnant (NP3). There is no evidence to justify routine screening during pregnancy (Professional consensus). CONCLUSION: There is a strong discrepancy between the prevalence of herpetic excretion at the time of delivery and the scarcity of neonatal infections. There is a lack of data on the impact of herpes infections during pregnancy in France. Fetal and maternal consequences are potentially serious but rare.


Subject(s)
Herpes Genitalis/complications , Pregnancy Complications, Infectious , Female , Fetal Diseases/virology , France , Herpes Genitalis/therapy , Herpes Genitalis/transmission , Herpesvirus 2, Human , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical/prevention & control , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/prevention & control , Pregnancy Complications, Infectious/therapy
17.
Gynecol Obstet Fertil Senol ; 45(12): 664-676, 2017 Dec.
Article in French | MEDLINE | ID: mdl-29132767

ABSTRACT

OBJECTIVE: To provide guidelines for the management of first episode genital herpes during pregnancy and in the immediate postpartum period. METHODS: MedLine and Cochrane Library databases search and review of the main foreign guidelines. RESULTS: In case of first episode genital herpes during pregnancy, antiviral treatment with acyclovir (200mg 5 times daily) or valacyclovir (1000mg twice daily) for 5 to 10 days is recommended (grade C). The patient should be tested for HIV if not previously done (grade B). Daily suppressive antiviral treatment with acyclovir (400mg 3 times daily) or valacyclovir (500mg twice daily) is recommended from 36 weeks for women who have had a first episode genital herpes during pregnancy (grade B). A cesarean section should be performed in case of suspicion of first episode genital herpes at the onset of labor (grade B) or premature rupture of the membranes at term (professional consensus), or in case of first episode genital herpes less than 6 weeks before delivery (professional consensus). In the event of first episode genital herpes highlighted in the postpartum period, the neonatologist should be informed (professional consensus). The patient may be treated according the scheme described above. CONCLUSION: A cesarean section should be performed in case of first episode genital herpes less than 6 weeks before delivery.


Subject(s)
Herpes Genitalis/complications , Pregnancy Complications, Infectious/therapy , Acyclovir/analogs & derivatives , Acyclovir/therapeutic use , Antiviral Agents/therapeutic use , Cesarean Section , Female , France , Herpes Genitalis/therapy , Humans , MEDLINE , Postpartum Period , Pregnancy , Valacyclovir , Valine/analogs & derivatives , Valine/therapeutic use
18.
Gynecol Obstet Fertil Senol ; 45(12): 705-714, 2017 Dec.
Article in French | MEDLINE | ID: mdl-29132768

ABSTRACT

OBJECTIVE: Identify measures to diagnose, prevent and treat genital herpes infection during pregnancy and childbirth and neonatal infection. METHODS: Bibliographic search from Medline, Cochrane Library databases and research of international clinical practice guidelines. RESULTS: Genital herpes lesion is most often due to HSV2 (LE2). The risk of HSV seroconversion during pregnancy is 1 to 5% (LE2). Genital herpes ulceration during pregnancy in a woman with history of genital herpes corresponds with a recurrence. In this situation, there is no need for virologic confirmation (grade B). In case of genital lesions in a pregnant woman that do not report any genital herpes before, it is recommended to perform a virological confirmation by PCR and HSV type specific IgG (Professional consensus). In case of first episode genital herpes during pregnancy, antiviral treatment with acyclovir (200mg 5 times daily) or valacyclovir (1000mg twice daily) for 5 to 10 days is recommended (grade C). In case of recurrent herpes during pregnancy, antiviral therapy with acyclovir (200mg 5 times daily) or valacyclovir (500mg twice daily) can be administered (grade C). The risk of neonatal herpes is estimated between 25% and 44% in case of initial episode (LE2) and 1% in case of recurrence (LE3) at the time of delivery. Antiviral prophylaxis should be offered for women with first episode genital herpes or recurrent genital herpes during pregnancy from 36 weeks of gestation and until delivery (grade B). In case of a history of genital herpes without episode of recurrence during pregnancy, it is not recommended routinely offer a prophylactic treatment (professional consensus). A cesarean section should be performed if there is a suspicion of first episode genital herpes at the onset of labor (grade B), in the event of premature rupture of the membranes at term (professional consensus), or in case of first episode genital herpes less than 6 weeks before delivery (professional consensus). In case of recurrent genital herpes at the onset of labor, cesarean delivery will be all the more considered if the membranes are intact and vaginal delivery will be all the more considered in case of prolonged rupture of membranes (professional consensus). Neonatal herpes is rare and mainly due to HSV-1 (LE3). In most of the case of neonatal herpes, the mothers have no history of genital herpes (LE 3). In case of suspicion of neonatal herpes, different samples (blood and cerebrospinal fluid) for HSV PCR must be carried out to confirm the diagnosis (professional consensus). Any newborn suspected of neonatal herpes should be treated with intravenous acyclovir (60mg/kgs/day 3 times daily) (grade A) prior to the results of HSV PCR (professional consensus). The duration of the treatment depends on the clinical form (professional consensus) CONCLUSION: There is no formal evidence that it is possible to reduce the risk of neonatal herpes in genital herpes during pregnancy. However, appropriate care can reduce the symptoms associated with herpes, the risk of recurrence term and the cesarean rate performed to decrease the risk of neonatal herpes.


Subject(s)
Herpes Genitalis/complications , Herpes Simplex/prevention & control , Pregnancy Complications, Infectious/virology , Acyclovir/administration & dosage , Antiviral Agents/administration & dosage , Cesarean Section , Female , Fetal Membranes, Premature Rupture , Gestational Age , Herpes Genitalis/prevention & control , Herpes Genitalis/therapy , Herpesvirus 2, Human/classification , Herpesvirus 2, Human/genetics , Herpesvirus 2, Human/immunology , Humans , Infant, Newborn , MEDLINE , Polymerase Chain Reaction , Pregnancy , Pregnancy Complications, Infectious/prevention & control , Pregnancy Complications, Infectious/therapy , Recurrence , Risk Factors , Serotyping
19.
Gynecol Obstet Fertil Senol ; 45(12): 677-690, 2017 Dec.
Article in French | MEDLINE | ID: mdl-29132770

ABSTRACT

OBJECTIVE: To provide guidelines for the management of woman with genital herpes during pregnancy or labor and with known history of genital herpes. METHODS: MedLine and Cochrane Library databases search and review of the main foreign guidelines. RESULTS: Genital herpes ulceration during pregnancy in a woman with history of genital herpes correspond to a recurrence. In this situation, there is no need for virologic confirmation (Grade B). In case of recurrent herpes during pregnancy, antiviral therapy with acyclovir or valacyclovir can be administered but provide low efficiency on duration and severity of symptoms (Grade C). Antiviral treatment proposed is acyclovir (200mg 5 times daily) or valacyclovir (500mg twice daily) for 5 to 10 days (Grade C). Recurrent herpes is associated with a risk of neonatal herpes around 1% (LE3). Antiviral prophylaxis should be offered for women with recurrent genital herpes during pregnancy from 36 weeks of gestation and until delivery (Grade B). There is no evidence of the benefit of prophylaxis in case or recurrence only before the pregnancy. There is no recommendation for systematic prophylaxis for women with history of recurrent genital herpes and no recurrence during the pregnancy. At the onset of labor, virologic testing is indicated only in case of genital ulceration (Professional consensus). In case of recurrent genital herpes at the onset of labor, cesarean delivery will be all the more considered if the membranes are intact and/or in case of prematurity and/or in case of HIV positive woman and vaginal delivery will be all the more considered in case of prolonged rupture of membranes after 37 weeks of gestation in an HIV negative woman (Professional consensus). CONCLUSION: In case of recurrent genital herpes at the onset of labor and intact membranes, cesarean delivery should be considered. In case of recurrent genital herpes and prolonged rupture of membranes at term, the benefit of cesarean delivery is more questionable and vaginal delivery should be considered.


Subject(s)
Herpes Genitalis/complications , Herpes Genitalis/therapy , Pregnancy Complications, Infectious/virology , Antiviral Agents/administration & dosage , Cesarean Section , Delivery, Obstetric/methods , Female , Fetal Membranes, Premature Rupture , France , Gestational Age , Herpes Genitalis/transmission , Herpes Simplex/prevention & control , Humans , Infectious Disease Transmission, Vertical/prevention & control , MEDLINE , Pregnancy , Pregnancy Complications, Infectious/prevention & control , Pregnancy Complications, Infectious/therapy , Recurrence
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