HERPES SIMPLEX--PREGNANCY, NEONATAL RISK, HOST DEFENSE

单纯疱疹——妊娠、新生儿风险、宿主防御

• 批准号: 2066819
• 负责人: CHARLES G PROBER
• 金额: $ 29.88万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-15 至 1995-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2066819
• 关键词: Herpesviridae disease; amniotic fluid; antibody formation; antiviral agents; communicable disease control; communicable disease transmission; disease /disorder proneness /risk; female; genital herpes; glycoproteins; herpes simplex virus 1; herpes simplex virus 2; host organism interaction; human pregnant subject; human subject; infant human (0-1 year); leukocyte activation /transformation; microorganism disease chemotherapy; microorganism immunology; neutralizing antibody; newborn human (0-6 weeks); pregnancy immunology; prenatal diagnosis; rapid diagnosis; relapse /recurrence; serotyping; sexually transmitted diseases; virus antigen; virus classification; virus infection mechanism; virus protein

The incidence of neonatal HSV infections is increasing in parallel with the increase in genital HSV infections. Preventing most cases of neonatal HSV infections depends upon avoiding contact with the virus at delivery. If lesions are present, delivery by cesarean section is indicated. Unfortunately, most neonatal infections result from exposure to asymptomatic maternal excretion of HSV, often by women with no past history of genital herpes. 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. Most genital HSV infections are caused by HSV-2. Seroepidemiologic studies have been hampered by cross-reactivity between HSV-1 and 2 antigens until the development of serologic methods which detect antibodies to HSV-2 specific glycoproteins. We propose to investigate the value of taking viral cultures for HSV at all deliveries, regardless of maternal herpes history, and of 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 28-32 weeks gestation using an ELISA method to detect antibodies to the HSV-2 glycoprotein G, which has HSV-2 specific epitopes. 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 (approximately 5000/year). The sensitivity and specificity of shell vial culture and HSV antigen detection by enzyme immunofiltration for rapid diagnosis of neonatal HSV exposure will be compared with a standard tissue culture technique. 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 prematurity, 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 antiviral therapy of neonatal HSV. Infants known to be exposed to asymptomatic maternal HSV will be monitored to determine the frequency of subclinical and clinical HSV infections. Exposed neonates who do not contract HSV will be compared with HSV- infected neonates referred during the study period using assays for HSV neutralizing antibody, antibody mediating cellular cytotoxicity and antibodies to HSV glycoproteins. The failure of antepartum cultures to predict and therefore prevent neonatal exposures to HSV at delivery has made it critical to develop a rational approach to the problem of neonatal HSV infections.

新生儿HSV感染的发生率正在平行增加 随着生殖器HSV感染的增加。 防止大多数 新生儿HSV感染的病例取决于避免接触 分娩时病毒。 如果有病变，请通过 指示剖宫产。 不幸的是，大多数新生儿 暴露于无症状母体的感染导致感染 HSV的排泄，通常是由没有生殖器历史的女性 疱疹。 天体文化无法预测 过去经常性的女性分娩时无症状的脱落 生殖器疱疹以及许多婴儿母亲 新生儿HSV没有生殖器疱疹的历史 新生儿HSV问题的另一种方法。 最生殖器 HSV感染是由HSV-2引起的。 SeroEpidemiologic研究 HSV-1和2之间的交叉反应阻碍了 抗原，直到开发检测血清学方法 HSV-2特异性糖蛋白的抗体。 我们建议 研究根本接受病毒培养物的价值 分娩，无论母疱疹历史和HSV-2如何 妊娠的早期和后期特定的血清学测试。 过去或 最近的HSV-2感染将通过测试配对血清确定 从第一次产前访问和28-32周的妊娠 ELISA方法检测HSV-2糖蛋白G的抗体， 具有HSV-2特异性表位。 HSV-2的频率 有或没有A的连续孕妇感染 生殖器HSV的历史和主要的比例 将评估感染。 文化将从所有人那里获得 分娩时的母亲和婴儿（约5000/年）。 这 壳瓶培养和HSV抗原的敏感性和特异性 通过酶免疫过滤检测，以快速诊断 新生儿HSV暴露将与标准组织进行比较 文化技术。 无症状脱落的频率 有或没有血清学证据的妇女分娩时的HSV 将确定过去或最近的HSV-2感染。 这 早产，低出生体重和/或证据的频率 母亲出生的新生儿的宫内HSV感染 将评估HSV-2感染的血清学证据。 大部分 新生儿HSV的持续发病率和死亡率是由于 诊断延迟。 虽然交付文化不会阻止 婴儿暴露于无症状的母体HSV，识别 暴露的婴儿应允许早期诊断和立即诊断 新生儿HSV的抗病毒疗法。 已知暴露于 无症状的母体HSV将受到监测以确定 亚临床和临床HSV感染的频率。 裸露 不签约HSV的新生儿将与HSV- 在研究期间使用测定的感染新生儿感染的新生儿 对于中和抗体的HSV，介导细胞的抗体 对HSV糖蛋白的细胞毒性和抗体。 失败 天前培养物可预测并因此预防新生儿 交付时对HSV的暴露使开发一个 新生儿HSV感染问题的合理方法。