Congenital HHV6 Infection: Characteristics and Outcome

描述（由申请人提供）：我们对> 6，000名儿童的前瞻性研究显示，大约所有儿童在3年内获得原发性HHV感染，导致20%的急诊室就诊，13%的住院治疗，并且是热性惊厥的最常见原因。继续的研究显示了两个重要的发现：（1）HHV 6先天性传播发生在1%的新生儿中，与巨细胞病毒（CMV）相同。(2)HHV 6先天性感染的婴儿与出生后感染的婴儿相比具有不同的病毒和临床特征，并且与先天性CMV感染的婴儿有些相似。因此，我们假设先天性HHV 6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HHV 6感染对HHV 6感染的控制和儿童的神经发育结局产生不良影响。 因此，我们的目的是（I）确定先天性与出生后感染的婴儿HHV 6的病毒学过程和（II）先天性HHV 6感染的神经发育结果。将从罗切斯特Strong Health System（7400-7800次分娩/年）的产科中心获得两组儿童，即先天性和产后感染的儿童，通过脐带血中是否存在HHV 6 DNA进行检测。237-265名脐带血DNA阳性的婴儿和237-265名脐带血阴性的匹配婴儿将在2周、4、6、12-15和24-30个月随访4年。将对脐带血和外周血、唾液和尿液样本进行评价，以描述HHV 6感染的相对持续性、其复制状态（潜伏或生产性）和病毒载量。将测量HHV 6 IgG和中和抗体水平以及针对破伤风的Thl和Th 2细胞因子应答的细胞免疫。这些联合检测将允许比较每个队列控制HHV 6感染的能力。在目标II中，我们将通过在2周、4、6、12-15和20-30个月时通过听力学测试和神经发育评估2个队列来确定先天性HHV 6感染（如CMV）是否会导致进行性神经发育障碍，这些评估是敏感的、针对年幼婴儿定制的，并描绘特定的神经发育区域和生长曲线。因此，可以检测到可能被全局测量遗漏的特定损伤区域。这些测量结果与Aim I中的病毒和临床特征的相关性可以早期识别预测未来残疾的风险因素。

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.