Congenital HHV6 Infection: Characteristics and Outcome

先天性 HHV6 感染：特征和结果

• 批准号: 6602202
• 负责人: Caroline Breese Hall
• 金额: $ 64.23万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6602202
• 关键词: audiometry; cell line; cellular immunity; child (0-11); clinical research; congenital infection; cytokine; developmental neurobiology; enzyme linked immunosorbent assay; epidemiology; hearing disorders; human herpesvirus 6; human subject; human tissue; humoral immunity; infant human (0-1 year); interview; longitudinal human study; polymerase chain reaction; tissue /cell culture; vertical transmission; virus load

DESCRIPTION (provided by applicant): Our prospective studies of >6,000 children showed about all acquire primary HHV infection by 3 years, resulting in 20% of emergency room visits, 13% of hospitalizations, and is the most frequent cause of febrile seizures. Continued studies showed 2 important findings: (1) HHV6 congenital transmission occurs in 1% of births, the same as for cytomegalovirus (CMV). (2) HHV6 congenitally infected infants have different viral and clinical characteristics than those with postnatal infection, and are somewhat similar to those of congenital CMV infection. We thus hypothesize that infants with congenital HHV6 infection have a distinctive course and outcome from infants with postnatal infection, and congenital HHV6 infection results in an adverse effect on the control of HHV6 infection and on the child's neurodevelopmental outcome. Hence, we Aim (I) to determine the virologic course of HHV6 in infants with congenital versus postnatal infection and (II) the neurodevelopmental outcome of congenital HHV6 infection. Two cohorts of children, those with congenital and postnatal infection, will be obtained from the obstetrical centers in the Rochester Strong Health System (7400-7800 births/year) by presence or absence of HHV6 DNA in cord bloods. 237-265 infants with cord bloods DNA positive and 237-265 matched infants with negative cord bloods will be followed over 4 years at 2 weeks, 4, 6, 12-15, and 24-30 months. Samples of cord and peripheral bloods, saliva, and urine will be evaluated to delineate the relative persistence of HHV6 infection, its replicative state (latent or productive), and viral load. HHV6 IgG and neutralizing antibody levels and cellular immunity for Thl and Th2 cytokine responses to tetanus will be measured. These combined assays will allow comparison of each cohort's ability to control HHV6 infection. In Aim II, we will determine if congenital HHV6 infection, like CMV, results in progressive neurodevelopmental impairments by evaluating the 2 cohorts at 2 weeks, 4, 6, 12-15, and 20-30 months by audiologic testing and neurodevelopmental assessments which are sensitive, tailored for young infants, and delineate specific neurodevelopmental areas and growth curves. Thus specific areas of impairment may be detected which could be missed with global measurements. Correlation of these measurements with the viral and clinical characteristics in Aim I may allow early identification of risk factors that are predictive of future disabilities.

描述（由申请人提供）：我们对> 6,000名儿童的前瞻性研究表明，所有收到原发性HHV感染3年，导致20％的急诊室就诊，13％的住院治疗，这是最常见的高温癫痫发作原因。持续研究表明了2个重要发现：（1）HHV6先天性传播发生在1％的出生中，与巨细胞病毒（CMV）相同。 （2）HHV6先天感染的婴儿的病毒和临床特征与产后感染患者不同，并且与先天性CMV感染的病毒和临床特征有些相似。因此，我们假设先天性HHV6感染的婴儿具有出生后感染的婴儿的独特病程和结果，而先天性HHV6感染会对HHV6感染和儿童神经发达预后的控制产生不利影响。 因此，我们的目的是（i）确定先天性与产后感染的婴儿的HHV6病毒学病程，以及（ii）先天性HHV6感染的神经发育结果。两名儿童将通过脐带血中的HHV6 DNA存在或不存在HHV6 DNA，将从罗切斯特强卫生系统（7400-7800出生/年）中的产科中心获得两个儿童。 237-265名脐带血DNA阳性和237-265匹配的婴儿的婴儿在2周，4、6、12-15和24-30个月时将在4年内伴随着阴性血液负血液。将评估绳索和外周血，唾液和尿液的样本，以描述HHV6感染的相对持久性，其复制状态（潜伏或生产性）和病毒载荷。将测量HHV6 IgG和中和抗体水平以及THL和Th2细胞因子对破伤风的反应的细胞免疫。这些组合测定将使每个队列控制HHV6感染的能力进行比较。在AIM II中，我们将通过评估2周，4、6、12-15和20-30个月的2个队列，通过听力学测试和神经脱发评估评估2周，4、6、12-15和20-30个月，确定先天性HHV6感染是否会导致渐进的神经发育障碍，这些群体对年轻的婴儿敏感，针对年轻的婴儿和DelineAteat和Deleineatee的增长和策展人进行了研究。因此，可以检测到特定的损害领域，通过全球测量可能会错过。这些测量值与目标I中的病毒和临床特征的相关性可能允许早日识别可预测未来残疾的风险因素。