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1.
Nat Commun ; 15(1): 4018, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38740820

RESUMO

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.


Assuntos
Dependovirus , Edição de Genes , Herpes Simples , Herpesvirus Humano 1 , Carga Viral , Eliminação de Partículas Virais , Animais , Edição de Genes/métodos , Feminino , Dependovirus/genética , Camundongos , Herpesvirus Humano 1/genética , Herpesvirus Humano 1/fisiologia , Herpes Simples/genética , Herpes Simples/virologia , Herpes Simples/terapia , Modelos Animais de Doenças , Latência Viral/genética , Humanos , Vetores Genéticos/genética , Células Vero , Terapia Genética/métodos , Herpes Genital/terapia , Herpes Genital/virologia , DNA Viral/genética
2.
Ann Hematol ; 101(3): 491-511, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34994811

RESUMO

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.


Assuntos
Neoplasias Hematológicas/virologia , Herpes Genital/terapia , Herpes Simples/terapia , Neoplasias/virologia , Infecção pelo Vírus da Varicela-Zoster/terapia , Ativação Viral , Aciclovir/uso terapêutico , Antivirais/uso terapêutico , Gerenciamento Clínico , Alemanha , Herpes Genital/diagnóstico , Herpes Genital/prevenção & controle , Herpes Simples/diagnóstico , Herpes Simples/prevenção & controle , Herpesvirus Humano 1/efeitos dos fármacos , Herpesvirus Humano 1/isolamento & purificação , Herpesvirus Humano 1/fisiologia , Herpesvirus Humano 2/efeitos dos fármacos , Herpesvirus Humano 2/isolamento & purificação , Herpesvirus Humano 2/fisiologia , Herpesvirus Humano 3/efeitos dos fármacos , Herpesvirus Humano 3/isolamento & purificação , Herpesvirus Humano 3/fisiologia , Humanos , Vacinação , Infecção pelo Vírus da Varicela-Zoster/diagnóstico , Infecção pelo Vírus da Varicela-Zoster/prevenção & controle , Ativação Viral/efeitos dos fármacos
3.
Epidemiol. serv. saúde ; 30(spe1): e2020628, 2021. tab
Artigo em Português | LILACS | ID: biblio-1154149

RESUMO

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.


Assuntos
Humanos , Masculino , Feminino , Úlcera/terapia , Cancroide/terapia , Infecções Sexualmente Transmissíveis/terapia , Infecções Sexualmente Transmissíveis/epidemiologia , Genitália/patologia , Brasil/epidemiologia , Herpes Genital/terapia , Linfogranuloma Venéreo/terapia , Sífilis/terapia , Protocolos Clínicos , Granuloma Inguinal/terapia
4.
Epidemiol. serv. saúde ; 30(spe1): e2020663, 2021. tab, graf
Artigo em Inglês, Português | LILACS | ID: biblio-1154153

RESUMO

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.


Assuntos
Humanos , Masculino , Feminino , Úlcera/terapia , Doenças Virais Sexualmente Transmissíveis/epidemiologia , Cancroide/terapia , Infecções Sexualmente Transmissíveis/terapia , Genitália/patologia , Brasil/epidemiologia , Herpes Genital/terapia , Linfogranuloma Venéreo/terapia , Sífilis/terapia , Protocolos Clínicos , Granuloma Inguinal/terapia
5.
Pediatr Rev ; 41(9): 455-468, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32873560

RESUMO

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.


Assuntos
Pediatria/métodos , Infecções Sexualmente Transmissíveis , Adolescente , Adulto , Condiloma Acuminado/diagnóstico , Condiloma Acuminado/patologia , Condiloma Acuminado/terapia , Diagnóstico Diferencial , Aconselhamento Diretivo , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/terapia , Infecções por HIV/transmissão , Herpes Genital/diagnóstico , Herpes Genital/patologia , Herpes Genital/terapia , Herpes Genital/transmissão , Humanos , Masculino , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/terapia , Infecções por Papillomavirus/transmissão , Relações Médico-Paciente , Prevenção Primária/métodos , Prevenção Secundária/métodos , Educação Sexual/métodos , Infecções Sexualmente Transmissíveis/diagnóstico , Infecções Sexualmente Transmissíveis/patologia , Infecções Sexualmente Transmissíveis/terapia , Infecções Sexualmente Transmissíveis/transmissão , Úlcera/diagnóstico , Úlcera/microbiologia , Úlcera/patologia , Úlcera/terapia , Adulto Jovem
6.
DST j. bras. doenças sex. transm ; 29(1): 25-27, 20170805.
Artigo em Português | LILACS | ID: biblio-878802

RESUMO

Úlceras genitais são manifestações clínicas de etiologias diversas, o que pode dificultar o diagnóstico. Este relato de caso trata­se de mulher de 64 anos, com histórico de úlcera genital dolorosa há 4 meses, progressiva apesar do uso prévio de antiviral. Apresentava lesão ulcerada com comprometimento perianal. Histopatológico revelou neovascularização, edema e infiltrado inflamatório. Realizou tratamento com aciclovir endovenoso por 14 dias, com melhora parcial. O herpes simples crônico manifesta­se como verruga ou úlcera de pelo menos um mês, geralmente em imunossuprimidas. A resistência a agentes antivirais é uma complicação encontrada, mas a resposta ao tratamento costuma ser mais lenta do que nas infecções comuns.


Genital ulcers are clinical manifestations of diverse etiologies, which can make diagnosis difficult. This case report is about a 64­year­old woman with a history of progressive genital ulcer pain for 4 months, despite prior antiviral use. The ulcerated lesion showed perianal involvement. Histopathology revealed neovascularization, edema and inflammatory infiltrate. Despite the use of intravenous acyclovir for 14 days, the improvement was partial. Chronic herpes simplex reveals wart or ulcer of at least one month, usually in immunosuppressed patients. A resistance to antiviral agents is a complication factor, but the treatment response to common infections is usually slower.


Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Antivirais , Herpes Genital/complicações , Herpes Genital/terapia , Terapia de Imunossupressão , Úlcera/complicações
9.
Hautarzt ; 68(3): 181-186, 2017 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-28197699

RESUMO

This review on herpes simplex virus type I and type II (HSV-I, HSV-II) summarizes recent developments in clinical manifestations and treatment interventions for primary and recurrent orolabial and genital herpes, as well as those regarding vaccination issues. Among the clinical presentations, the relationship between pyogenic granuloma and chronic HSV-I infection; HSV-related folliculitis; verrucous HSV-I and HSV-II lesions; the role of recurrent HSV-I infection in burning mouth syndrome; HSV-I and HSV-II infection of the periareolar area; zosteriform HSV; the "knife-cut sign"; and the preferential colonization and infection of preexisting dermatoses by HSV-I or HSV-II are discussed. The usual antiviral treatment regimens for primary and recurrent orolabial and genital herpes are compared to short-term and one-day treatment options. New anti-HSV-I and anti-HSV-II agents include amenavir, pritelivir, brincidofovir, valomaciclovir, and FV-100. Therapeutic or preventive vaccination against HSV-I and HSV-II infections still remains a highly desirable treatment aim, which, unfortunately, has no clinically relevant applications to date.


Assuntos
Antivirais/administração & dosagem , Herpes Genital/diagnóstico , Herpes Genital/terapia , Herpesvirus Humano 1/isolamento & purificação , Herpesvirus Humano 2/isolamento & purificação , Vacinas Virais/administração & dosagem , Medicina Baseada em Evidências , Humanos , Resultado do Tratamento
10.
Annu Rev Med ; 68: 401-411, 2017 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-27576009

RESUMO

The emergence of the CRISPR/Cas system of antiviral adaptive immunity in bacteria as a facile system for gene editing in mammalian cells may well lead to gene editing becoming a novel treatment for a range of human diseases, especially those caused by deleterious germline mutations. Another potential target for gene editing are DNA viruses that cause chronic pathogenic diseases that cannot be cured by using currently available drugs. We review the current state of this field and discuss the potential advantages and problems with using a gene editing approach as a treatment for diseases caused by DNA viruses.


Assuntos
Sistemas CRISPR-Cas , Infecções por Vírus de DNA/terapia , Vírus de DNA/genética , Edição de Genes , Infecções por HIV/terapia , HIV-1/genética , Terapia Genética/métodos , Vetores Genéticos , Vírus da Hepatite B/genética , Hepatite B Crônica/terapia , Herpes Genital/terapia , Herpes Simples/terapia , Herpesvirus Humano 1/genética , Herpesvirus Humano 2/genética , Humanos , Papillomaviridae/genética , Infecções por Papillomavirus/terapia
11.
Curr Opin Virol ; 17: 80-86, 2016 04.
Artigo em Inglês | MEDLINE | ID: mdl-26896782

RESUMO

Immunotherapeutic vaccines have emerged as a novel treatment modality for genital herpes, a sexually transmitted disease mainly caused by herpes simplex virus type 2. The approaches to identify potential vaccine antigens have evolved from classic virus attenuation and characterization of antibody and T cell responses in exposed, but seronegative individuals, to systematic screens for novel T cell antigens. Combined with implementation of novel vaccine concepts revolving around immune evasion and local recruitment of immune effectors, the development of a safe and effective therapeutic vaccine is within reach. Here, we describe the vaccine approaches that currently show promise at clinical and pre-clinical stages and link them to the evolving scientific strategies that led to their identification.


Assuntos
Herpes Genital/terapia , Vacinas contra o Vírus do Herpes Simples/imunologia , Herpesvirus Humano 2/imunologia , Imunoterapia/métodos , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Ensaios Clínicos como Assunto , Desenho de Fármacos , Descoberta de Drogas , Herpes Genital/imunologia , Herpes Genital/virologia , Vacinas contra o Vírus do Herpes Simples/administração & dosagem , Humanos , Evasão da Resposta Imune , Camundongos , Linfócitos T/imunologia , Proteínas do Envelope Viral/imunologia
12.
DST j. bras. doenças sex. transm ; 26(1/4): 29-31, 2014. ilus
Artigo em Inglês | LILACS | ID: lil-754445

RESUMO

Genital herpes is an infectious sexually transmitted disease that affects people from different socioeconomic strata, it is widespread throughout the world and a frequent cause of painful genital lesions in men and women. Objective and Methods: to report a case of a patient with penile ulcers initially treated with various topical and oral products, who finally used Uncaria tomentosa gel topically. The final diagnosis was genital herpes. Results:The symptoms of pain and burning had rapid remission. The clinical course was satisfactory and after a week, the patient, with no lesion, reported having had sexual intercourse without discomfort and returned to professional activities. Conclusion: the topical use of Uncaria tomentosa gel 50 mg/g in penile ulcers was well tolerated, and showed no side effects with relief of local symptoms.


Herpes genital é uma doença infectocontagiosa de transmissão sexual que acomete pessoas das mais diversas camadas socioeconômicas e está disseminada em todo o mundo, sendo uma causa frequente de lesões genitais dolorosas em homens e em mulheres. Objetivo e Métodos: descrever caso de paciente com úlceras penianas inicialmente medicado com vários produtos tópicos e orais que por último usou, topicamente, gel de Uncaria tomentosa e o diagnóstico final foi herpes genital. Resultados: os sintomas de dor e ardor tiveram rápida remissão. A evolução clínica foi satisfatória e após uma semana o paciente, já sem lesão, informou ter tido relação sexual sem incômodos e retomado as atividades profissionais de forma plena. Conclusão: o uso tópico de gel de Uncaria tomentosa 50 mg/g em úlceras penianas foi bem tolerado, não teve efeitos colaterais com alívio dos sintomas locais.


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Herpes Genital/terapia , Infecções Sexualmente Transmissíveis , Unha-de-Gato
13.
Clin Infect Dis ; 57(11): 1648-55, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24065320

RESUMO

BACKGROUND: In patients with human immunodeficiency virus (HIV) infection, genital herpetic lesions may be extensive and tend to persist for longer periods; in addition, atypical hypertrophic, ulcerative, or pseudotumor forms have been reported, frequently showing resistance to acyclovir (ACV) treatment. METHODS: Between 2003 and 2011, 10 HIV-1-infected patients presenting with chronic pseudotumoral anogenital herpes simplex type 2 (HSV-2) infections were studied. RESULTS: All patients developed chronic, hypertrophic HSV-2 anogenital lesions with multilesional presentation in 7 cases and involvement of 2 anatomical sites in 6 of them. At the time of diagnosis, the median CD3(+)CD4(+) absolute blood count was 480.5 cells/µL (range, 165-632 cells/µL), whereas the plasma HIV load was undetectable in all cases. Histopathologic analysis of lesion biopsies showed a moderately dense dermal polytypic plasma cell infiltrate. Detection of HSV-2 by culture and/or polymerase chain reaction was positive for all patients, with evidence for ACV-resistant strains in 6 of 8 cases. In addition, viral resistance to ACV was found only in HSV-2 isolated from ulcerative lesions, whereas purely pseudotumoral ones harbored sensitive strains. Durable control was observed with HSV DNA polymerase inhibitors in only 2 cases, and the immunomodulators imiquimod and thalidomide allowed 5 patients to reach sustained complete response. CONCLUSIONS: HSV-2-related pseudolymphoma in HIV-infected patients is characterized by a predominant polyclonal lymphoplasmacytic infiltration, and is frequently refractory to antiherpetic drugs. Immunomodulatory therapeutic strategies using thalidomide showed consistent efficacy, and should be considered early during the course of disease.


Assuntos
Infecções por HIV/virologia , Herpes Genital/terapia , Herpes Genital/virologia , Herpesvirus Humano 2/isolamento & purificação , Imunossupressores/uso terapêutico , Aciclovir/uso terapêutico , Adulto , Idoso , Antivirais/uso terapêutico , Farmacorresistência Viral , Feminino , Herpes Genital/patologia , Herpesvirus Humano 2/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Talidomida/uso terapêutico , Timidina Quinase/genética
15.
J Virol ; 87(7): 3930-42, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23365421

RESUMO

Immunotherapeutic herpes simplex virus 2 (HSV-2) vaccine efficacy depends upon the promotion of antigen-specific immune responses that inhibit reactivation or reactivated virus, thus controlling both recurrent lesions and viral shedding. In the present study, a candidate subunit vaccine, GEN-003/MM-2, was evaluated for its ability to induce a broad-spectrum immune response in mice and therapeutic efficacy in HSV-2-infected guinea pigs. GEN-003 is comprised of HSV-2 glycoprotein D2 (gD2ΔTMR340-363) and a truncated form of infected cell polypeptide 4 (ICP4383-766), formulated with Matrix M-2 (MM-2) adjuvant (GEN-003/MM-2). In addition to eliciting humoral immune responses, CD4(+) and CD8(+) T cells characterized by the secretion of multiple cytokines and cytolytic antigen-specific T cell responses that were able to be recalled at least 44 days after the last immunization were induced in immunized mice. Furthermore, vaccination with either GEN-003 or GEN-003/MM-2 led to significant reductions in both the prevalence and severity of lesions in HSV-2-infected guinea pigs compared to those of phosphate-buffered saline (PBS) control-vaccinated animals. While vaccination with MM-2 adjuvant alone decreased recurrent disease symptoms compared to the PBS control group, the difference was not statistically significant. Importantly, the frequency of recurrent viral shedding was considerably reduced in GEN-003/MM-2-vaccinated animals but not in GEN-003- or MM-2-vaccinated animals. These findings suggest a possible role for immunotherapeutic GEN-003/MM-2 vaccination as a viable alternative to chronic antiviral drugs in the treatment and control of genital herpes disease.


Assuntos
Adjuvantes Imunológicos/farmacologia , Herpes Genital/imunologia , Herpesvirus Humano 2/imunologia , Imunoterapia/métodos , Linfócitos T/imunologia , Vacinas Virais/imunologia , Análise de Variância , Animais , Baculoviridae , Western Blotting , Chlorocebus aethiops , Clonagem Molecular , Primers do DNA/genética , Ensaio de Imunoadsorção Enzimática , ELISPOT , Cobaias , Herpes Genital/terapia , Camundongos , Testes de Neutralização , Células Vero , Proteínas do Envelope Viral/imunologia , Vacinas Virais/farmacologia , Eliminação de Partículas Virais/imunologia
16.
J Virol ; 86(8): 4586-98, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22318147

RESUMO

A herpes simplex virus 2 (HSV-2) glycoprotein E deletion mutant (gE2-del virus) was evaluated as a replication-competent, attenuated live virus vaccine candidate. The gE2-del virus is defective in epithelial cell-to-axon spread and in anterograde transport from the neuron cell body to the axon terminus. In BALB/c and SCID mice, the gE2-del virus caused no death or disease after vaginal, intravascular, or intramuscular inoculation and was 5 orders of magnitude less virulent than wild-type virus when inoculated directly into the brain. No infectious gE2-del virus was recovered from dorsal root ganglia (DRG) after multiple routes of inoculation; however, gE2-del DNA was detected by PCR in lumbosacral DRG at a low copy number in some mice. Importantly, no recurrent vaginal shedding of gE2-del DNA was detected in immunized guinea pigs. Intramuscular immunization outperformed subcutaneous immunization in all parameters evaluated, although individual differences were not significant, and two intramuscular immunizations were more protective than one. Immunized animals had reduced vaginal disease, vaginal titers, DRG infection, recurrent genital lesions, and recurrent vaginal shedding of HSV-2 DNA; however, protection was incomplete. A combined modality immunization using live virus and HSV-2 glycoprotein C and D subunit antigens in guinea pigs did not totally eliminate recurrent lesions or recurrent vaginal shedding of HSV-2 DNA. The gE2-del virus used as an immunotherapeutic vaccine in previously HSV-2-infected guinea pigs greatly reduced the frequency of recurrent genital lesions. Therefore, the gE2-del virus is safe, other than when injected at high titer into the brain, and is efficacious as a prophylactic and immunotherapeutic vaccine.


Assuntos
Deleção de Genes , Vacinas contra o Vírus do Herpes Simples/imunologia , Herpesvirus Humano 2/genética , Herpesvirus Humano 2/imunologia , Neurônios/virologia , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/imunologia , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Linhagem Celular , Chlorocebus aethiops , DNA Viral , Feminino , Gânglios Espinais/virologia , Cobaias , Herpes Genital/mortalidade , Herpes Genital/prevenção & controle , Herpes Genital/terapia , Herpes Simples/mortalidade , Herpes Simples/prevenção & controle , Herpes Simples/terapia , Vacinas contra o Vírus do Herpes Simples/administração & dosagem , Vacinas contra o Vírus do Herpes Simples/efeitos adversos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos SCID , Medula Espinal/virologia , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/efeitos adversos , Vacinas Atenuadas/imunologia
17.
Obstet Gynecol Surv ; 66(10): 629-38, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22112524

RESUMO

Genital herpes is one of the most common sexually transmitted infections, affecting 1 in 6 people in the United States. Women are twice as likely to be infected as men and infections in women of reproductive age carry the additional risk of vertical transmission to the neonate at the time of delivery. Neonatal herpes infections can be devastating with up to 50% mortality for disseminated herpes simplex virus (HSV) infections in the newborn. Rates of transmission are affected by the viral type of HSV infection and whether the infection around delivery is primary or recurrent. Current management approaches decrease rates of active lesions at the time of delivery and thereby cesarean deliveries, but have not been shown to decrease the incidence of neonatal herpes infections. More research is needed to better elucidate the risk factors for transmission to the neonate and to improve our current management methodology to further decrease vertical transmission. In this review, we will discuss management of antenatal and peripartum herpes infections, considerations for mode of delivery, and the course of neonatal HSV infections.


Assuntos
Herpes Genital/diagnóstico , Herpes Genital/terapia , Herpes Genital/transmissão , Herpes Simples/diagnóstico , Herpes Simples/terapia , Herpes Simples/transmissão , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/terapia , Infecções Sexualmente Transmissíveis/diagnóstico , Infecções Sexualmente Transmissíveis/terapia , Infecções Sexualmente Transmissíveis/transmissão , Antivirais/uso terapêutico , Cesárea , Feminino , Herpes Genital/mortalidade , Herpes Simples/mortalidade , Humanos , Transmissão Vertical de Doenças Infecciosas , Programas de Rastreamento , Gravidez , Complicações Infecciosas na Gravidez/mortalidade , Diagnóstico Pré-Natal/métodos , Fatores de Risco , Índice de Gravidade de Doença , Infecções Sexualmente Transmissíveis/mortalidade
18.
Rev. Méd. Clín. Condes ; 22(6): 813-824, nov. 2011.
Artigo em Espanhol | LILACS | ID: lil-687043

RESUMO

Las Infecciones de Transmisión Sexual (ITS) son infecciones causadas por diversos agentes (bacterias, virus, parásitos, protozoos, entre otros) y cuyo mecanismo de transmisión es el contacto sexual: genital, oral o anal, condición que les da su principal característica y que tiene implicancias en la prevención, pues se relaciona directamente con el "comportamiento sexual" del ser humano, y por lo tanto, con un acto de decisión personal. Las ITS son "PROBLEMA DE TODOS" en razón de ser Universales, no respetando razas, sexos, edad, cultura, creencias religiosas, situación socioeconómica, etc. Constituyen aún un importante problema de Salud Pública en todo el mundo a pesar de los esfuerzos por controlarlas y eventualmente erradicarlas como ha sucedido con otras enfermedades infecto contagiosas. Las modernas tecnologías usadas en el diagnóstico de laboratorio permiten identificar con mayor eficiencia los agentes causales, y el desarrollo de nuevos antibióticos permiten tratar con mayor eficacia, interrumpiendo así la transmisión.


Sexually Transmitted Infections (STI) are sexually infections caused for many agents (bacterias, virus, parasites, protozoos, etc.) and where the transmission is the sexual contact, vaginal, anal or oral, condition who give them the principal characteristic. And that have very important implicancies in prevention, because is directed related with sexual behaviour of human being and finally with and act of personal decision. The STI are a problem of all, in reason of being universal, without respect of races, sex, age, culture, religious credences, social economical position, etc. Today are an important problem in public health in all the World in spite the efforts for control and eventually erradicate them in the way who has succeded with others infectious diseases. Moderns technologies used in the laboratory diagnosis allow us identified with more eficcacious the agents and the development of new antibiotics will be the key to treat with more eficciency our patients and by this way close the chain of transmission.


Assuntos
Humanos , Doenças Bacterianas Sexualmente Transmissíveis/epidemiologia , Doenças Bacterianas Sexualmente Transmissíveis/terapia , Doenças Virais Sexualmente Transmissíveis/epidemiologia , Doenças Virais Sexualmente Transmissíveis/terapia , Gonorreia/terapia , Herpes Genital/terapia , Sífilis/terapia , Chile/epidemiologia , Sífilis Cutânea , Sífilis Congênita/epidemiologia
19.
Artigo em Russo | MEDLINE | ID: mdl-21913390

RESUMO

AIM: Proof of therapeutic efficacy of a novel type of vaccine with a combination of natural Toll like receptor agonists (TLR) 1/2, 4, 5/6, 9 in infectious and noninfectious human pathology. MATERIALS AND METHODS: Immunovac-VP-4 vaccine, containing antigens of opportunistic microorganisms that are TLR 1/2, 4, 5/6, 9 ligands, was used for experiments and clinical trials. RESULTS: Immunovac-VP-4 activates innate immunity by inducing maturation of dendritic cells with expression of costimulating molecules on their membrane (CD40+, CD80+, CD86+), terminal differentiation molecules--CD83+ and antigen-presenting molecules (MHC class I and II); activates proinflammatory (TNFalpha, IL-6) and regulatory (IL-12, INFgamma) cytokine synthesis that programs T-lymphocyte differentiation by Th1 pathway; increases cytotoxic activity of natural killer cells, inhibits melanoma B16 growth and Lewis lung carcinoma metastasis. Therapeutic effect of Immunovac-VP-4 was evident regardless of pathology by a significant decrease of quantity and severity of recidives, improvement of all clinical parameters, reduction of quantity of administered pharmaceutical preparations including antibiotics and glucocorticosteroids. The rate of intercurrent acute respiratory viral illnesses and their bacterial complications decreased. Immunovac-VP-4 therapy modified course of illness from severe into milder forms. Positive therapeutic effect was 69.2 - 100%. CONCLUSION: High therapeutic effect of vaccine therapy is based on innate immunity activation by combining TLR agonists. Immunovac-VP-4 contains an optimal combination of natural TLR agonists that ensure high therapeutic effect in various nosological forms of infectious and noninfectious human pathology.


Assuntos
Vacinas Bacterianas/imunologia , Vacinas Bacterianas/uso terapêutico , Imunidade Inata , Imunoterapia Ativa/métodos , Receptores Toll-Like/agonistas , Animais , Antígenos de Bactérias/imunologia , Asma/terapia , Carcinoma Pulmonar de Lewis/terapia , Criança , Pré-Escolar , Herpes Genital/terapia , Humanos , Hipersensibilidade ao Látex/terapia , Ativação Linfocitária/imunologia , Melanoma/terapia , Camundongos , Infecções Respiratórias/terapia , Receptores Toll-Like/imunologia , Vacinas Combinadas/imunologia , Vacinas Combinadas/uso terapêutico
20.
Acta Derm Venereol ; 91(3): 333-6, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21369687

RESUMO

This paper reports survey-based data on the diagnosis and management of genital herpes simplex virus (HSV) infection in 14 countries of the Eastern European Network for Sexual and Reproductive Health (EE SRH). Only 43% of the countries could provide the number of genital HSV cases recorded at national level. Eighty-six percent of countries employed syndromic management in cases of genital ulcer disease. Most countries performed type-specific and/or non-type-specific enzyme immunoassays to detect HSV antibodies. Non-type-specific serology for diagnostic purposes should be actively discouraged. Direct detection methods for HSV, such as PCR, antigen detection and culture, are available in the region, but their usage was extremely low. Their use in Eastern European countries should be actively promoted. The availability of laboratory services must be improved, and countries in the region should implement consensus recommendations for the laboratory diagnosis of genital HSV infections in order to improve clinical practice.


Assuntos
Técnicas de Laboratório Clínico/estatística & dados numéricos , Serviços de Diagnóstico/estatística & dados numéricos , Herpes Genital/diagnóstico , Simplexvirus , Virologia/métodos , Anticorpos Antivirais/sangue , Antígenos Virais/sangue , Biomarcadores/sangue , Europa (Continente)/epidemiologia , Pesquisas sobre Atenção à Saúde , Herpes Genital/epidemiologia , Herpes Genital/terapia , Herpes Genital/virologia , Humanos , Técnicas Imunoenzimáticas/estatística & dados numéricos , Testes Obrigatórios , Reação em Cadeia da Polimerase/estatística & dados numéricos , Valor Preditivo dos Testes , Kit de Reagentes para Diagnóstico/estatística & dados numéricos , Testes Sorológicos/estatística & dados numéricos , Simplexvirus/genética , Simplexvirus/imunologia , Simplexvirus/isolamento & purificação , Inquéritos e Questionários , Virologia/estatística & dados numéricos
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