Chlamydia Infection as a Risk Factor for Cerebrovascula*

描述（由申请人提供）： 肺炎衣原体感染（C。肺炎）与 一般人群中脑血管疾病的风险增加。 儿童 镰状细胞性贫血（SCA）患者的患病率是其他患者的200倍， 脑血管疾病比正常儿童，并已知有改变 对许多传染性病原体的免疫反应。C.肺炎是主要的 急性胸部综合征的感染性原因，有趣的是，这是一个很好的- SCA儿童中风的既定危险因素。 我们的初步数据 表明SCA患者MRI记录的脑梗死是12 更有可能是C。肺炎感染的SCA患者， 核磁共振扫描正常 我们假设SCA患者有异常的免疫功能， 回应C。肺炎，导致持续感染，反过来， 引发脑血管疾病 经颅多普勒血流速度增高的镰状细胞性贫血患者 超声（TCD）是已知的高风险发展中风， TCD升高可能反映了潜在的血管疾病。 此外该 镰状细胞性贫血中风预防试验（STOP）表明， TCD升高的儿童中有40%有脑梗死的证据， 核磁共振 因此，TCD异常的儿童是一个合适的人群 探讨脑血管病与C. 肺炎感染。 作为STOP II试验的辅助研究，我们建议 1)确定C.肺炎感染与脑 SCA儿童梗死; 2）表征免疫应答 梭肺炎感染与SCA患者。 之间建立联系 C.肺炎感染和脑梗死将打开新的大门， 治疗和预防SCA中风的毒性较小的方法， 包括抗生素和疫苗。 本提案中获得的数据将提供必要的初步数据 来证明进一步的临床试验是正确的

DESCRIPTION (provided by applicant): Infection with Chlamydia pneumoniae (C. pneumoniae) is associated with an increased risk of cerebrovascular disease in the general population. Children with sickle cell anemia (SCA) are 200 times more likely to have cerebrovascular disease than normal children and are known to have an altered immune response to many infectious pathogens. C. pneumoniae is the leading infectious cause of acute chest syndrome which, interestingly, is a well- established risk factor for stroke in children with SCA. Our preliminary data indicates that SCA patients with MRI-documented cerebral infarction are 12 times more likely to have C. pneumoniae infection than SCA patients with normal MRI scans. We hypothesize that SCA patients have an abnormal immune response to C. pneumoniae that results in persistent infection which, in turn, triggers the development of cerebrovascular disease. Sickle cell anemia patients with an elevated velocity on transcranial doppler ultrasound (TCD) are known to be at high risk to develop stroke and an elevated TCD likely reflects underlying vascular disease. In addition, the Stroke Prevention in Sickle Cell Anemia Trial (STOP) demonstrated that almost 40% of children with an elevated TCD have evidence of cerebral infarction on MRI. Children with abnormal TCDs are, therefore, an appropriated population to investigate an association between cerebrovascular disease and C. pneumoniae infection. As an ancillary study of the STOP II trial we propose 1) To determine if C. pneumoniae infection is associated with cerebral infarction in children with SCA; 2) To characterize the immunological response to C. pneumoniae infection in patients with SCA. Establishing a link between C. pneumoniae infection and cerebral infarction will open the door to novel, less toxic approaches to the treatment and prevention of stroke in SCA, including antibiotics and vaccines. The data gained in this proposal would provide the preliminary data necessary to justify further clinical trials.