EPIDEMIOLOGY AND OUTCOME OF GESTATIONAL HSV INFECTIONS

妊娠期 HSV 感染的流行病学和结果

• 批准号: 3076718
• 负责人: CHARLES G PROBER
• 金额: $ 6.94万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-09-30 至 1993-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3076718
• 关键词: G protein; communicable diseases; early diagnosis; epidemiology; genital herpes; gestational age; glycoproteins; herpes simplex virus 1; herpes simplex virus 2; molecular cloning; newborn human (0-6 weeks); nucleic acid sequence; plasmids; pregnancy disorder; prenatal diagnosis; recombinant DNA; sexually transmitted diseases; virus antigen; virus protein

Genita herpes simplex virus (HSV) infection is one of the most common sexually transmitted diseases (STD) in the United States. These infections are conspicuous by their painful course, frequent recurrence, high contagiousness, and persistent latency. The most grave consequence of genital herpes is infection of infants born to mothers who are excreting virus at delivery. Infants exposed to HSV may contract an infection with an untreated mortality rate of 70%. Despite the problem of neonatal HSV infection, there is a paucity of data on the epidemiology of genital herpes during pregnancy. Most of the available data concerns the incidence of asymptomatic shedding of SHV in women with histories of genital HSV. A major limitation of these data is exemplified by the observation that 50% of neonates who contract HSV are born to women with neither current symptoms nor a past history of genital herpes. There is a clear need for more information regarding the epidemiology of this STD in pregnant women. Although 10-15% of genital herpes infections are caused by HSV-1, the remainder are caused by HSV-2. Therefore, the prevalence of genital herpes can be approximated by determining antibody to HSV-2. Extensive antigenic homology between HSV-1 and 2 proteins has interfered with the serologic distinction of past HSV-1 and 2 infections. Recently, the gG protein of HSV-2 (gG-2) has been demonstrated to have type specific epitopes. The nucleotide sequence of the gene specifying gG-2 has been elucidated. A monoclonal antibody to gG-2 provides the basis for an ELISA serologic assay which can be used to define the true prevalence of HSV-2 infections. A limitation of the current gG-2 ELISA method is that it is indirect, requiring multiple incubation steps to perform. Although this assay is sensitive and specific, it is time-consuming and costly. The assay would be simpler, more rapid, and less expensive if a source of gG-2 antigen were available which did not require immunoaffinity steps for preparation. Recombinant DNA cloning provides a means whereby specified gene products can be expressed in large quantities, free of other viral proteins and antigens. We propose to develop a simple and rapid assay for the serologic diagnosis of HSV-2 infection based upon recombinant DNA methods. We will clone the gG-2 sequences into a plasmid suitable for expression in a mammalian cell system and use this source of gG-2 in an assay to detect HSV-2 specific antibodies. The failure of antepartum cultures to predict asymptomatic shedding at delivery in women with past recurrent genital herpes along with the fact that many mothers of infants with neonatal HSV have no history of genital herpes requires another approach to the problem of neonatal HSV. We propose to investigate the value of performing HSV-2 specific serologic testing early and late in gestation. Past or recent HSV-2 infection will be determined by testing paired sera from the first prenatal visit and 28 weeks gestation. The frequency of HSV-2 infections in consecutive pregnant women with or without a history of genital HSV and the proportion which are primary infections will be assessed. Cultures will be obtained from all mothers and infants at delivery. The frequency of asymptomatic shedding of HSV at delivery among women with or without serologic evidence of past or recent HSV-2 infections will be determined. The frequency of prematuity, low birth weight, and/or evidence of intrauterine HSV infections among neonates born to mothers with serologic evidence of HSV-2 infections will be assessed. Much of the continued morbidity and mortality of neonatal HSV is due to delayed diagnosis. While delivery cultures will not prevent the exposure of infants to asymptomatic maternal HSV, identification of exposed infants should allow early diagnosis and immediate therapy.

Genita单纯疱疹病毒(HSV)感染是最常见的 美国常见的性传播疾病(STD)。 这些感染以其痛苦的过程、频繁的感染而引人注目。 复发、高传染性和持续潜伏期。最多的 生殖器疱疹的严重后果是婴儿感染 在分娩时排泄病毒的母亲。婴儿暴露于 单纯疱疹病毒可能感染未经治疗的死亡率 70%。尽管存在新生儿单纯疱疹病毒感染的问题，但 年生殖器疱疹流行病学数据匮乏 怀孕了。大多数可用数据都与肺炎的发病率有关 有生殖器病史的妇女无症状的SHV脱落 单纯疱疹病毒。这些数据的一个主要局限性就是 观察发现，50%感染HSV的新生儿出生时 既无当前症状也无生殖器病史的妇女 疱疹。显然有必要提供更多关于 这种性病在孕妇中的流行病学。尽管10%-15%的 生殖器疱疹感染是由HSV-1引起的，其余的是 由HSV-2引起。因此，生殖器疱疹的流行可以 与单纯疱疹病毒2型抗体测定结果相近。广泛性 HSV-1和HSV-2蛋白之间的抗原同源性受到干扰 与过去HSV-1和HSV-2感染的血清学区别。 最近，单纯疱疹病毒2型(HSV-2，GG-2)的gG蛋白已被证实 拥有类型特定的表位。该病毒的核苷酸序列 GG-2基因已被阐明。一种单抗 TO GG-2为ELISA血清学检测奠定了基础 被用来定义HSV-2感染的真实流行率。一个 目前GG-2酶联免疫吸附试验方法的局限性在于它是间接的， 需要执行多个孵化步骤。虽然这件事 该方法灵敏、特异，耗时长、费用高。 如果有一种方法，这种分析将会更简单、更快速、更便宜 GG-2抗原源是可用的，不需要 制备的免疫亲和步骤。重组DNA克隆 提供了一种方法，借此特定的基因产品可以 大量表达，不含其他病毒蛋白和 抗原。我们建议建立一种简单、快速的检测方法 重组人单纯疱疹病毒2型感染的血清学诊断 DNA方法。我们将把GG-2序列克隆到一个质粒中 适合于在哺乳动物细胞系统中表达，并使用该 用于检测HSV-2特异性抗体的GG-2来源。 产前培养未能预测无症状 既往复发性生殖器疱疹患者分娩时脱皮 同时，许多新生儿的母亲 HSV没有生殖器疱疹病史需要另一种方法 新生儿单纯疱疹病毒的问题。我们建议调查 早期和早期进行HSV-2特异性血清学检测的价值 妊娠晚期的。过去或最近感染HSV-2的人将 通过检测第一次产前检查的配对血清和 怀孕28周。中国人群中单纯疱疹病毒2型感染的频率 有或无生殖器病史的连续怀孕妇女 单纯疱疹病毒和原发感染的比例将是 评估过了。培养将从所有母亲和婴儿那里获得 在送货时。单纯疱疹病毒无症状脱落率 既往有或无血清学证据的妇女分娩 或者近期的HSV-2感染将被确定。的频率 早产、低出生体重和/或宫内单纯疱疹病毒感染 患有血清学疾病的母亲所生新生儿的感染情况 将对HSV-2感染的证据进行评估。世界上大部分的 新生儿单纯疱疹病毒持续发病率和死亡率是由于 延迟诊断。虽然交付文化不会阻止 婴儿接触无症状的母体单纯疱疹病毒，鉴定 应允许早期诊断和立即 心理治疗。