Prevention of HSV Morbidity in Pregnancy and the Newborn

新生儿疱疹仍然是生殖器疱疹感染的最具破坏性的后果， 这种频率在过去几十年里没有下降过。然而，还没有任何预防策略被 实施。在新感染HSV-2或以下人群中传播HSV的风险最高 生殖道中存在HSV-1，且血清呈阴性；在HSV-1血清阳性的女性中，患病风险也很高 新感染HSV-2或重新激活HSV-1的女性；已感染HSV-2的女性风险较低 感染。分娩时生殖器脱落的HSV与HSV的&gt；300的相对风险相关 变速箱。我们已经开发出一种灵敏和特异的HSV DNA聚合酶链式反应，可以在2分钟内完成 获得样本的时间；测试正在完成实施的验证研究，以便在 华盛顿大学医院临床实验室。我们建议使用这种分析方法来开发一种 婴儿分娩时接触单纯疱疹病毒的检测策略及实施的可行性评估 降低暴露新生儿感染HSV-1和HSV-2风险的干预措施。具体目标1是 目的：确定新生儿分娩时接触HSV的发生率。我们假设 用聚合酶链式反应检测单纯疱疹病毒DNA，结合单纯疱疹病毒血清学检测(孕妇常规进行 华盛顿大学的女性)，将准确地定义接触HSV的婴儿的高风险与低风险 患新生儿疱疹的风险。医疗团队将利用这些信息来降低HSV的风险 通过产科做法(剖腹产、减少使用胎儿监护设备、静脉注射)感染 阿昔洛韦)或随后对暴露于HSV的婴儿进行治疗。《特定目标2》将评估 产程中静脉注射阿昔洛韦，新生儿口服阿昔洛韦的可行性 HSV-2阳性产妇分娩时HSV排泄及其婴儿的处理方法 在出生时接触到单纯疱疹病毒。我们假设，给分娩中的妇女静脉注射阿昔洛韦将导致 脐带血中阿昔洛韦的治疗水平，以及新生儿口服阿昔洛韦将 通过临床和实验室评估是可行的，并为儿科医生和家长所接受。 这一方法改变了目前预防新生儿疱疹的模式，从临床上看 疾病对分娩时暴露于亚临床感染的婴儿的检测和管理。这个 该项目将首次收集目前美国儿科学会关于HSV指南的数据 并开发可在多中心试验中测试的预防新生儿单纯疱疹病毒的工具。 新生儿疱疹是新生儿的一种严重疾病。该项目将开发识别新生儿的工具 在出生时暴露于有风险的HSV，并为有新生儿疱疹风险的新生儿制定最佳护理方案。

Neonatal herpes continues to be the most devastating consequence of genital herpes infections, with a frequency that has not declined in the last several decades. Yet no prevention strategies have been implemented. The risk of HSV transmission is highest among women who have newly acquired HSV-2 or HSV-1 in the genital tract and who are seronegative; the risk is also high among HSV-1 seropositive women who have newly acquired HSV-2 or reactivation of HSV-1; the risk is low in women with established HSV-2 infection. Genital HSV shedding at the time of delivery is associated with a relative risk of >300 for HSV transmission. We have developed a sensitive and specific HSV DMA PCR that can be resulted within 2 hours of obtaining the sample; the test is completing validation studies for implementation for routine use in the University of Washington Hospital Clinical Laboratories. We propose to use this assay to develop a strategy to detect the infant exposed to HSV at delivery and to evaluate the feasibility of implementing interventions to reduce the risk of HSV-1 and HSV-2 infections in the exposed newborns. Specific Aim 1 is to determine the incidence of exposure of the neonate to HSV at the time of delivery. We hypothesize that HSV DMA detection by PCR, in combination with HSV serologic testing (performed routinely in pregnant women at the University of Washington), will accurately define HSV-exposed infants at high versus low risk of developing neonatal herpes. This information will be utilized by the medical team to reduce the risk of HSV infection either through obstetrical practices (C-section, reduced use of fetal monitoring devices, use of IV acyclovir) or subsequent management of the HSV exposed infant. Specific Aim 2 will evaluate the feasibility of intrapartum intravenous acyclovir, followed by oral acyclovir to the neonate, as an approach for managing HSV-2 seropositive women who shed HSV at delivery and their infants who are exposed to HSV during birth. We hypothesize that IV acyclovir given to women in labor will result in therapeutic levels of acyclovir in the cord blood, and that oral administration of acyclovir to the newborn will be feasible, as evaluated by clinical and laboratory measures, and acceptable to pediatricians and parents. This approach shifts the current paradigm for prevention of neonatal herpes from the women with clinical disease to the detection and management of the infant exposed to subclinical infection at delivery. The project will for the first time collect data on current American Academy of Pediatrics guidelines for HSV exposed infants and develop tools for prevention of neonatal HSV that can be tested in multicenter trials. Neonatal herpes is a serious disease among newborns. The project will develop tools to identify newborns exposed to HSV at birth at risk and develop optimal care for newborns who are at risk for neonatal herpes.