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名儿童进行的前瞻性研究显示，大约所有儿童在3年内都获得了原发HHV感染，导致20%的急诊室就诊，13%的住院，是最常见的热性惊厥原因。继续研究发现两个重要发现：(1)HHV6先天传播发生率为1%，与巨细胞病毒(CMV)相同。(2)HHV6先天感染与后天感染具有不同的病毒和临床特征，与先天性巨细胞病毒感染有一定的相似性。因此，我们假设先天性HHV6感染的婴儿与出生后感染的婴儿有不同的病程和结局，先天性HHV6感染会对HHV6感染的控制和儿童的神经发育结局产生不利影响。 因此，我们的目标是(I)确定先天和出生后感染HHV6的婴儿的病毒学过程，以及(Ii)先天性HHV6感染的神经发育结果。两组患有先天性和后天感染的儿童将通过脐带血中是否存在HHV6 DNA从罗切斯特强大卫生系统(7400-7800名新生儿/年)的产科中心获得。脐带血DNA阳性的237-265名婴儿和脐血阴性的237-265名匹配的婴儿将在2周、4、6、12-15和24-30个月进行为期4年的随访。将对脐带血和外周血、唾液和尿液样本进行评估，以描绘HHV6感染的相对持久性、其复制状态(潜伏期或生产性)和病毒载量。将测定破伤风后HHV6抗体和中和抗体水平以及Th1和Th2细胞因子反应的细胞免疫水平。这些联合化验将可以比较每个队列控制HHV6感染的能力。在AIM II中，我们将通过在2周、4、6、12-15和20-30个月通过听力学测试和神经发育评估来确定先天性HHV6感染是否像CMV一样导致进行性神经发育障碍，这些测试和神经发育评估是敏感的、为幼儿量身定做的，并描绘出特定的神经发育区域和生长曲线。因此，可以检测到全局测量可能遗漏的特定损害区域。将这些测量与AIM I的病毒和临床特征相关联，可能有助于及早识别预测未来残疾的风险因素。