Natural History of C. trachomatis urogenital and rectal infections

沙眼衣原体泌尿生殖道和直肠感染的自然史

基本信息

批准号：
10356116
负责人：
DEBORAH Anne DEAN
金额：
$ 80万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-03-20 至 2025-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10356116
关键词：
16S ribosomal RNA sequencing Address Age Anatomy Area Caring Centers for Disease Control and Prevention (U.S.)Characteristics Chlamydia Infections Chlamydia trachomatis Clinical Clinical Data Communities Country DNA Data Detection Diagnostic Ectopic Pregnancy Endocervix Epidemic Ethnic Origin Female Fiji Future Genetic Genitourinary System Infection Genitourinary system Genome Genomics Guam Hawaiian Hemorrhage Heterosexuals High Prevalence Immune Immune response Incidence Individual Infection Infertility Inflammation Inflammatory Response Intervention Knowledge Lead Life Lymphogranuloma Venereum Medical Methods Modeling Natural History Organism Other Genetics Outcome Pacific Islander Pacific Islands Pacific Ocean Papua New Guinea Pathogenicity Pelvic Inflammatory Disease Persons Play Population Premature Birth Prevalence Prevention Proctitis Rectum Recurrence Reporting Research Resource-limited setting Risk Role Samoa Sampling Severities Severity of illness Sexually Transmitted Diseases Shotgun Sequencing Signs and Symptoms Site Syndrome Taxonomy Teenagers Time Treatment Protocols Vagina Woman Work World Health Organization age group base chemokine cohort cytokine design dysbiosis fitness genetic variant health disparity host microbiota improved ineffective therapies infection rate innovation male men who have sex with men metagenome metagenomic sequencing microbiome microbiota neglect pathogen prospective rectal rectal microbiota screening transmission process treatment duration urogenital tract vaginal microbiota young adult

项目摘要

SUMMARY While U.S. CDC annual estimates of Chlamydia trachomatis (Ct) sexually transmitted infections (STIs) are about 3 million, global World Health Organization (WHO) estimates are >131 million. Over 61 million people are infected among the Pacific Island Countries and Territories (PICT) of the Western Pacific Ocean with a prevalence rate of ~40% among teens and young adults. These percentages reflect the fact that STIs are a major area of health disparity in the PICT as well as in other parts of the world. In the U.S., Hawaiian and other Pacific Islanders have the 3rd highest prevalence of STIs, which is 3.7 times that of Whites. In these resource- constrained regions, syndromic management of Ct is the norm. This is problematic because ~80% of females and 50% of males are asymptomatic and do not seek medical care. Transmission from these asymptomatic yet infected individuals to partners likely fuels the ongoing worldwide epidemic. Further, lack of treatment can result in serious sequelae such as pelvic inflammatory disease, infertility, ectopic pregnancy, and hemorrhagic proctitis. While the endocervix is considered the primary site of infection, female Ct rectal infections now outnumber those in the urogenital tract. Without adequate detection, the rectum, which requires 7 to 21 days of treatment with high rates of recurrence, is a potential reservoir of Ct for transmission within the host and to partners. Our unifying hypothesis is that the natural history of Ct STIs is defined by the interaction of the microbiomes, immune responses and pathogen populations of three key body sites: the vagina, endocervix and rectum. We will employ metagenome shotgun sequencing (MSS) to understand healthy, dysbiotic and Ct- associated microbiota in addition to host immune responses and Ct pathogen characteristics for a high- incidence cohort of Fijian women. This work will naturally transition to improving future Ct diagnostics that utilize metgenomic methods, and we will determine whether these data can predict protection from Ct and/or incident Ct and infection severity. With prospective samples and clinical data collected prior to and at incident Ct infection (or no Ct) from our cohort, we aim to: 1) identify taxonomic diversity, richness and abundance of DNA-based organisms in the endocervix, vagina and rectum using MSS cross-referenced to 16S sequencing at both time points; 2) quantitate immune responses in the context of the microbiota for each site, time point and clinical outcome; 3) determine microbiota/immune response profiles that correlate with incident Ct genomic strains and whether strain plays a role in clinical outcome at each site. Our research will aid in selecting optimal sites for Ct screening and designing strategies such as vaginal and/or rectal therapy with beneficial microbiota, especially for the latter site given the long and often ineffective treatment regimens. The steady global increase in Ct cases necessitates research especially among those who suffer from health disparities and are at increased risk for STIs. We have assembled a unique cohort of Fijian women with high rates of Ct (up to 38%) without which it would not be possible to study the natural history of Ct urogenital and rectal STIs.