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.

生殖器单纯疱疹病毒（HSV）感染是最常见的感染之一 美国常见的性传播疾病（STD）。 这些感染因其痛苦的病程、频繁的感染而引人注目。 复发性、高传染性和持续潜伏期。 最 生殖器疱疹的严重后果是出生的婴儿受到感染 分娩时排出病毒的母亲。 婴儿接触过 HSV 感染后未经治疗死亡率可能很高 70%。 尽管存在新生儿 HSV 感染问题，但 缺乏关于生殖器疱疹流行病学的数据 怀孕。 大多数可用数据涉及以下情况的发生率： 有生殖器病史的女性无症状 SHV 排出 单纯疱疹病毒。 这些数据的一个主要限制是 观察发现，50% 感染 HSV 的新生儿出生时 当前既没有症状也没有生殖器病史的女性 疱疹。 显然需要更多有关 这种 STD 在孕妇中的流行病学。 虽然 10-15% 生殖器疱疹感染由 HSV-1 引起，其余为 由 HSV-2 引起。 因此，生殖器疱疹的流行 通过测定 HSV-2 抗体来近似。 广泛的 HSV-1 和 2 蛋白之间的抗原同源性干扰了 与过去 HSV-1 和 2 感染的血清学区别。 最近，HSV-2的gG蛋白（gG-2）已被证明 具有类型特异性表位。 的核苷酸序列 特异gG-2的基因已被阐明。 单克隆抗体 gG-2 为 ELISA 血清学测定提供了基础，该测定可以 用于定义 HSV-2 感染的真实流行率。 一个 当前 gG-2 ELISA 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 分析方法灵敏且特异，但耗时且成本高。 如果可以的话，该测定会更简单、更快速且更便宜 gG-2 抗原的来源是可用的，不需要 免疫亲和制备步骤。 重组DNA克隆 提供了一种可以将特定基因产物 大量表达，不含其他病毒蛋白， 抗原。 我们建议开发一种简单快速的检测方法 基于重组的HSV-2感染的血清学诊断 DNA 方法。 我们将 gG-2 序列克隆到质粒中 适合在哺乳动物细胞系统中表达并使用它 检测 HSV-2 特异性抗体的检测中 gG-2 的来源。 产前培养未能预测无症状 患有复发性生殖器疱疹的妇女在分娩时脱落 事实上，许多新生儿婴儿的母亲 HSV没有生殖器疱疹病史需要另一种方法 新生儿HSV问题。 我们建议调查 尽早进行 HSV-2 特异性血清学检测的价值 妊娠晚期。 过去或最近的 HSV-2 感染将 通过检测第一次产前检查的配对血清来确定 怀孕28周。 HSV-2 感染频率 有或没有生殖器病史的连续妊娠妇女 HSV 和原发感染的比例将是 评估。 将从所有母亲和婴儿处获得培养物 交货时。 HSV 无症状排出频率 在有或没有过去血清学证据的妇女中分娩 或近期 HSV-2 感染将被确定。 的频率 早产、低出生体重和/或宫内 HSV 证据 血清学检查母亲所生新生儿感染 将评估 HSV-2 感染的证据。 大部分的 新生儿 HSV 的持续发病率和死亡率是由于 延误诊断。 虽然分娩文化不会阻止 婴儿接触无症状母体 HSV 的情况、鉴定 接触过的婴儿应进行早期诊断并立即 治疗。