Immunopathogenesis of Chlamydia trachomatis Infection

沙眼衣原体感染的免疫发病机制

• 批准号: 6098923
• 负责人: Thomas Quinn
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6098923
• 关键词: Chlamydia trachomatis; Chlamydiaceae; HIV infections; adolescence (12-20); atherosclerosis; azithromycin; chlamydial disease; clinical research; communicable disease diagnosis; communicable disease transmission; comorbidity; diagnosis design /evaluation; electron microscopy; epidemiology; female; human pregnant subject; human subject; human therapy evaluation; in situ hybridization; mass screening; pathologic process; polymerase chain reaction; sexually transmitted diseases; urinalysis; young adult human (21-34)

Chlamydia trachomatis is the most common sexually transmitted bacterial pathogen in the United States with an incidence of 4.5 million cases annually. The objectives of this project are to assess the frequency of C. trachomatis infections in selected populations, to develop and evaluate sensitive nucleic amplification assays for diagnosis, and to study the immunopathogenesis of C. trachomatis and C. pneumoniae infections. Using three new molecular amplification assays (PCR, LCR, and TMA), we screened over 2,000 male and 20,000 female patients in Baltimore. The overall prevalence of chlamydia ranged from 7% in family planning clinics to over 20% in adolescents. In a prospective study of 3,202 sexually active adolescents aged 12 to 19 years, chlamydia infection was found in 24% of first visits and in 14% of repeat visits; 29% of adolescent females have at least one positive test in a one-year period. Females aged 14 years had the highest age-specific chlamydia prevalence rate of 27.5%. The chlamydia incident rate was 28 cases per 1,000 person-months with a median time of 6 months to re-infection. With such high rates of infection, we recommend screening all sexually active adolescent females for chlamydia infection at least twice yearly regardless of prior infections, condom use from multiple partner risk. In a cost-effective analysis, we further documented that universal screening with non-invasive urine-based DNA amplification and use of self-administered vaginal swabs for other STDs offered the most cost-effective strategy for frequent screening of STDs, particularly in adolescents. Between January 1996 and December 1997, we screened by LCR for C. trachomatis urine in 13,204 new female U.S. Army recruits from 50 states and four territories. The overall prevalence was 9% with a peak of 12% in 17-year-old females. Recent vaginal sex, young age (< 25), being African American, having more than one sex partner, and inconsistent condom use were independently associated with chlamydia infection. In this national survey, we documented that the prevalence of chlamydia infection was very high in female military recruits and that all recruits should be screened and treated for chlamydia in order to reduce infection, transmission, and sequelae. Internationally, in a community-based trial of mass STD treatment in the Rakai district of Uganda, we documented relatively high rates of chlamydia and gonorrhea in 15-24 year-olds (5%). Ten months after mass antibiotic treatment, there was a 50% reduction in both chlamydia and gonococcal infection. This study demonstrates that the vast majority of STD infections are asymptomatic (80%), and that mass antibiotic treatment is effective in lowering infection rates. Future studies will address the effectiveness of mass treatment in limiting HIV transmission. In order to provide a cost savings for molecular amplification screening of urine in developing countries, we developed a pooling algorithm in which urine from ten individuals can be pooled and analyzed by molecular amplification for C. trachomatis or N. gonorrhoeae. The pooling algorithm demonstrated 59% reduction in costs and was sensitive and specific compared to testing individual samples. We recently demonstrated a direct correlation between C. pneumoniae and atherosclerotic heart disease by the recent isolation of C. pneumoniae in an explanted heart with severe coronary atherosclerosis. C. pneumoniae has also been demonstrated in nearly 50% of coronary and carotid atheromas by immunocytochemistry and/or PCR. In vitro studies have demonstrated that C. pneumoniae can infect and proliferate in coronary artery endothelial cells and aortic artery smooth muscle cells. In preliminary animal studies, C. pneumoniae-inoculated mice appeared to have an increased rate of atheroma formation in the carotid artery and aortic artery compared to control animals, suggesting an etiologic or co-factor role in the development of atherogenesis.

沙眼衣原体是最常见的性行为 在美国传播细菌病原体 每年450万例的发病率。目标的目标 项目是评估沙眼梭状芽胞庭感染的频率 选定的种群，开发和评估敏感的核心 放大测定法进行诊断，并研究 沙眼梭状芽孢杆菌和肺炎梭状芽胞杆菌的免疫病作用 感染。使用三个新的分子扩增测定法（PCR， LCR和TMA），我们筛选了2,000多名男性和20,000名女性 巴尔的摩的患者。衣原体的总体流行范围范围 从计划生育诊所的7％到青少年的20％以上。在 对3,202名12岁至12岁的性活跃青少年的前瞻性研究 19年，在第一次访问的24％和中发现了衣原体感染 重复访问的14％； 29％的青春期女性至少有一个 在一年的时间内进行阳性测试。 14岁的女性有 最高年龄特异性衣原体患病率为27.5％。这 衣原体事件率为每1000人28例 重新感染6个月的中间时间。如此高的比率 感染，我们建议筛选所有性活跃的青少年 衣原体感染的女性至少每年两次 事先感染，使用多个合作伙伴风险的安全套。在 具有成本效益的分析，我们进一步记录了通用 用非侵入性尿液基于尿液的DNA扩增和使用 其他性病的自我管理的阴道拭子最多 经常筛选性病的经济有效策略，特别是 在青少年。在1996年1月至1997年12月之间，我们 由LCR筛选为梭状芽孢杆菌尿液中的13,204个新女性 来自50个州和四个地区的美国陆军新兵。总体 17岁女性的患病率为9％，峰值为12％。 最近的阴道性别，年轻（<25），是非裔美国人， 拥有多个性伴侣，使用避孕套不一致 与衣原体感染独立相关。在这个 全国调查，我们记录了衣原体的患病率 女性军事新兵的感染非常高，所有人都 应筛选新兵和治疗衣原体 减少感染，传播和后遗症。在国际上， Rakai区的基于社区的大众性传播疾病治疗试验 在乌干达，我们记录了衣原体相对较高的率 15-24岁的淋病（5％）。质量十个月 抗生素治疗，两种衣原体都降低了50％ 和淋球菌感染。这项研究表明了广阔的 大多数性病感染无症状（80％），质量是 抗生素治疗可有效降低感染率。未来 研究将解决群众治疗在限制中的有效性 艾滋病毒传播。为了为分子节省成本 在发展中国家尿液的放大筛查，我们 开发了一种合并算法，其中十个人的尿液 可以通过分子扩增来汇总和分析。 沙眼或淋病。合并算法 表现出59％的成本降低，并且很敏感，具体 与测试单个样品相比。我们最近证明了 肺炎梭菌与动脉粥样硬化之间的直接相关性 心脏病通过最近在A的肺炎梭菌中分离出来 患有严重的冠状动脉粥样硬化的心脏。 C 肺炎也已在近50％的冠状动脉中得到证明 通过免疫细胞化学和/或PCR进行颈动脉瘤。在 体外研究表明，肺炎梭菌会感染和 冠状动脉内皮细胞和主动脉动脉增殖 平滑肌细胞。在初步动物研究中，C。 肺炎接种的小鼠似乎有增加的率 颈动脉和主动脉动脉中的动脉瘤形成 控制动物，表明病因学或共同因素在 动脉粥样硬化的发展。