Congenital CMV Infection and Hearing Loss in Rural Indian Population

描述(由申请人提供)：先天性巨细胞病毒感染是导致儿童听力损失和脑部疾病的主要原因，医学研究所已将巨细胞病毒作为疫苗开发的目标。以前的研究表明，妊娠期的初级孕产妇感染是造成先天性感染的最重要的危险因素。然而，最近的研究，包括我们之前在Ballabgarh进行的MCHDR研究表明，先天性CMV感染在具有接近普遍CMV血清免疫的母体人群中的发生率较高(1%至2%)。这些研究还表明，在CMV血清阳性率高的人群中，CMV相关感音神经性听力损失(SNHL)的发生率与美国和北欧的观察结果相似。因此，在发展中国家人群中，先天性CMV感染对公众健康的影响可能是显著的。我们建议检验这一假设，即先天性CMV感染在印度SNHL中占很大比例。这一假设将以两个具体目标来解决：(1)通过筛查新生儿的CMV和听力损失，确定在印度巴拉布加尔邦综合农村卫生服务项目(CRHSP)出生的婴儿中CMV相关SNHL的贡献，以及(2)评估适用于资源匮乏环境下的新生儿CMV筛查的更新、快速、简单和简单的基于PCR的方法的实用性。CRHSP和Ballabgarh拥有一流的基础设施，便于接触CRHSP所服务的研究人群，UAB和AIIMS的研究人员之间的持续合作关系为拟议的研究提供了重大优势。此外，我们希望在农村人口中制定出生时SNHL的初步估计，并在社区层面测试新生儿听力筛查计划的可行性。拟议的研究将提供有关出生时听力损失的总体流行率和与巨细胞病毒相关的SNHL在人群中的贡献、及早识别SNHL风险增加的儿童以及制定SNHL儿童干预策略的关键信息。拟议的研究计划还纳入并强调了培训和技术转让部分。 公共卫生相关性：我们建议检验这样一种假设，即在印度，出生或新生儿期的SNHL有很大比例是先天性CMV感染的继发性疾病。这项拟议的研究还将研究在农村社区的初级卫生中心对新生儿进行听力功能筛查的可行性。预计这项研究的结果将为印度新德里附近低收入半城市人口出生时SNHL的患病率提供可靠的估计。此外，我们将评估在资源匮乏的环境中可以用于筛查婴儿先天性巨细胞病毒感染的简单和可靠的方法。

DESCRIPTION (provided by applicant): Congenital CMV infection is a leading cause of hearing loss and brain disease in children and the Institute of Medicine has targeted CMV for vaccine development. Previous studies have suggested that primary maternal infection during pregnancy was the most significant risk factor for damaging congenital infections. However, more recent studies including our previous MCHDR study at Ballabgarh have shown congenital CMV infection occurs at higher rate (1% to 2%) in maternal populations with near universal CMV seroimmunity. These studies have also suggested that CMV-related sensorineural hearing loss (SNHL) occurs in populations with high CMV seroprevalence at a rate similar to that observed in the U.S. and Northern Europe thus, the public health impact of congenital CMV infection in populations of developing countries could be significant. We propose to test the hypothesis that congenital CMV infection contributes to a significant proportion of SNHL in India. This hypothesis will be addressed in two specific aims: (1) To determine the contribution of CMV- related SNHL in infants born at the Comprehensive Rural Health Services Project (CRHSP) in Ballabgarh, India by screening newborns for CMV and hearing loss, and (2) To evaluate the utility of newer, rapid, simple and simple PCR-based methods suitable for newborn CMV screening in resource-poor settings. The presence of an excellent infrastructure at CRHSP, Ballabgarh providing ready access to the study population served by the CRHSP and the ongoing collaborative relationship between the investigators at UAB and at AIIMS provides significant advantage to the proposed studies. In addition, we expect to develop preliminary estimates of SNHL at birth in the rural population and to test the feasibility of newborn hearing screening program at the community level. The proposed studies will provide crucial information about the overall prevalence of hearing loss at birth and the contribution of CMV-related SNHL in the population, an early identification of children at increased risk for SNHL, and the development of intervention strategies for children with SNHL. The proposed research plan also incorporates and emphasizes the training and technology transfer components. PUBLIC HEALTH RELEVANCE: We propose to test the hypothesis that a significant proportion of SNHL at birth or neonatal period in India is secondary to congenital CMV infection. The proposed study will also examine the feasibility of screening newborns for hearing function at the primary health center setting in a rural community. It is expected that the results of this study to provide a reliable estimate of SNHL prevalence at birth in a low-income semi-urban population near New Delhi, India. In addition, we will evaluate simple and reliable methods that can be used in resource-poor settings to screen infants for congenital CMV infection.