A Mixed Methods Study of STI Co-Infections and Cervical Immune Microenvironment (

EPIC-STI项目3(Gravitt)：STI合并感染与宫颈免疫的混合方法研究 微环境 摘要 需要获得关于性传播感染负担的更好的基本流行病学数据，以及 并在人类群体中进行翻译研究，以扩大关于 生殖道的粘膜免疫是专家小组确定的几个关键研究空白之一。 召开会议，以确定有效预防和控制性传播感染及其疾病后遗症的障碍。使用 混合设计方法，性病流行病学预防跨学科中心(EPIC-STI)项目3 将在以下具体目标中解决这两个研究差距。AIM 1将利用一种新的数据和 Biospecimen资源，新墨西哥州HPV巴氏登记处(NMHPVPR)，进行基于人口的调查 四种常见性传播疾病--沙眼衣原体(CT)、淋病奈瑟菌(NG)、 阴道毛滴虫(TV)和生殖支原体(MG)。本项目目标1的结果和 在EPIC-STI项目4中得出的人类乳头瘤病毒(HPV)流行率估计将结合到 全面评估与最常见的年龄相关的混合感染的流行情况 种族和地理不同人群中的病毒、细菌和原虫性传播感染 在美国衣原体感染排名第八的新墨西哥州。与项目4、目标2协同 将调查CT、NG、TV和MG混合感染与高危(HR)-HPV在 高级别宫颈上皮内瘤变(CIN2+)的发生通过将目标1中的STI测试与 随着NMHPVPR的发展，我们将在先前评估CT感染的作用的研究基础上进行改进 CIN2+与宫颈癌的关系--将个体的混合感染与NMHPVPR可报告疾病联系起来 结果，为研究性传播感染和HR-HPV联合感染的长期后果提供了独特的机会。 感染。最后，将在目标3中进行前瞻性队列研究，以描述免疫学 CT感染妇女和未感染CT妇女的微环境通过测量一组 从顺序收集的60个可溶性免疫标志物(细胞因子、趋化因子、生长因子、抗体) 阿奇霉素治疗前后宫颈分泌物标本。通过广泛收集STI co- 感染和行为流行病学数据，这一目标也将提供机会，以评估在 (1)CT阳性的有症状和无症状的妇女，(2)抗生素前后的免疫图谱 治疗，(3)在治疗时持续感染与缓解感染的妇女，以及(4)有和没有感染的妇女 1年内再感染。AIM 3将为EPIC的项目1和2提供关键数据和生物材料- STI，在动物和人类研究之间建立了必要的桥梁，旨在更好地了解 对沙眼衣原体感染的免疫反应和有效疫苗的开发。

EPIC-STI PROJECT 3 (GRAVITT): A Mixed Methods Study of STI Co-infections and Cervical Immune Microenvironment SUMMARY The need to obtain better basic epidemiologic data on the burden of sexually transmitted infections (STIs) and co-infections and to conduct translational studies in human populations to expand the knowledge base on mucosal immunity in the genital tract were among several critical research gaps identified by expert panels convened to identify barriers to effective prevention and control of STIs and their disease sequelae. Using a mixed design approach, Project 3 of the Epidemiology Prevention Interdisciplinary center for STIs (EPIC-STI) will address these two research gaps in the following specific aims. Aim 1 will utilize a novel data and biospecimen resource, the New Mexico HPV Pap Registry (NMHPVPR), to conduct a population-based survey of age-specific prevalence of four common STIs - Chlamydia trachomatis (CT), Neisseria gonorrhea (NG), Trichomonas vaginalis (TV), and Mycoplasma genitalium (MG). The results from Aim 1 of this project and the human papillomavirus (HPV) prevalence estimates derived in Project 4 of the EPIC-STI will be combined to provide a comprehensive evaluation of the age-specific prevalence of co-infections with the most common viral, bacterial, and protozoal sexually transmitted infections in an ethnic and geographically diverse population in New Mexico, which ranks 8th in Chlamydia infection in the United States. In synergy with Project 4, Aim 2 will investigate the association between CT, NG, TV, and MG co-infections with high risk (HR)-HPV on the development of high grade cervical intraepithelial neoplasia (CIN2+). By linking the STI testing in Aim 1 with the NMHPVPR, we will improve on previous studies evaluating the role of CT infection with the development of CIN2+ and cervical cancer by linking co-infections on an individual basis to the NMHPVPR reportable disease outcomes, enabling a unique opportunity to study the long term consequence of STI and HR-HPV co- infections. Finally, a prospective cohort study will be conducted in Aim 3 to describe the immunological microenvironment in CT-infected women and a control group of CT uninfected women by measuring a panel of 60 soluble immune markers (cytokines, chemokines, growth factors, antibodies) from sequentially collected cervical secretion samples before and after azithromycin treatment. Through extensive collection of STI co- infection and behavioral epidemiologic data, this aim will also provide the opportunity to evaluate differences in immune profiles in (1) CT positive symptomatic and asymptomatic women, (2) before and after antibiotic treatment, (3) women with persistent vs. resolved infection at treatment, and (4) women with and without reinfection within 1 year. Aim 3 will provide critical data and biological material to Projects 1 and 2 of the EPIC- STI, creating a necessary bridge between animal and human studies targeting a better understanding of the immune response to CT infection and effective vaccine development.