The natural history of C. trachomatis urethral infections in men who have sex with women
The natural history of C. trachomatis urethral infections in men who have sex with women
批准号:
10703828
负责人:
Stephen J. Jordan
金额:
$75.05万
依托单位国家:
美国
项目类别:
财政年份:
2023
资助国家:
美国
项目状态:
未结题
起止时间:
2023-07-05 至 2028-06-30
关键词:
AddressAntibioticsAntibodiesAntibody-mediated protectionAutomobile DrivingBacteriaBehavioralBiologicalBiological AssayBloodCenters for Disease Control and Prevention (U.S.)CharacteristicsChlamydiaChlamydia trachomatisClinicalCross-Sectional StudiesDiseaseEnrollmentEnzyme-Linked Immunosorbent AssayEpidemicEpidemiologyExposure toFemaleHeterosexualsHigh Risk WomanImmuneImmune responseImmune systemImmunityImmunologicsImmunologyIncubatedInfectionInflammationKnowledgeLongitudinal StudiesMeasuresMediatingMicrobiologyMicroscopyNatural HistoryNucleic Acid Amplification TestsOrganismOutcomeParticipantPatient Self-ReportPersonsPlayPredispositionPreventionProspective StudiesRecommendationRecording of previous eventsResistanceRiskRoleSex BehaviorSexual PartnersSexual TransmissionSexually Transmitted DiseasesShapesSigns and SymptomsSlideSpecimenSurveysSymptomsT cell responseT-Cell ActivationT-LymphocyteTestingTimeUrethraUrethritisUrineVisitWomanadaptive immune responseadaptive immunityagedcare seekingcervicovaginal microbiomecomorbiditydiariesexperienceimprovedinfection riskinsightmalemenmetagenomic sequencingmicrobiome compositionmicroorganismnovel strategiespathogenpreventreproductive tractroutine screeningscreeningscreening programseropositivesextransmission processurethral microbiome
中文摘要
摘要
沙眼衣原体(CT)是世界范围内最常见的细菌性传播感染(STI),
对女性生殖道造成不可逆的损害。由于大多数CT感染的妇女没有症状,
对于不知道自己已被感染的女性,CDC建议每年对<25岁及以上的女性进行CT筛查。
妇女有风险发现和治疗无症状感染并预防并发症;在男子中,
不推荐.尽管有30年的筛查计划,CT在美国的比率急剧上升,
这主要是由于CT再感染的增加。由于大多数CT感染的妇女是异性恋和例行
不推荐在男性中进行筛查,男性中未检测到的CT感染是推动
女性再感染。为了遏制CT的流行,我们必须了解男性是否会发展成
对CT的免疫力并确定促进CT再感染的因素(例如,无症状男性,
CT生物)。大约1/3的男性作为CT接触者接受治疗(即,他们的性伴侣
被证实是CT感染)未感染,这表明这些人要么通过免疫清除CT感染,
介导的机制或具有抵抗CT采集的尿道微生物组。预防CT再感染
妇女,这项建议的重点是男性接触CT感染的妇女,并将研究CT感染是否相关
与特定的微生物组组成,共病性传播感染,或适应性T细胞和抗体免疫。为此我们
将招募多达400名男性CT接触者,收集血液和尿液样本,用CDC推荐的
一线抗生素,并要求他们返回1个月的治愈测试(TOC)访问(目标1)。研究CT是否未感染
CT接触者具有持久的免疫力,以及尿道微生物组和免疫系统如何改变
届时,我们将重新招募100名男性进行为期6个月的纵向研究,每周收集尿液样本,
症状/性行为日记以及3个月和6个月筛选访视时的血液和尿液标本。
将储存每周一次的尿液样本,并在研究完成时进行检测,以创建自然史研究。通过
研究CT感染随时间的发生率,我们将能够阐明是否对CT感染有抵抗力,
目标1中定义的,与(1)访视之间自然清除率增加;(2)事件发生率降低相关
3个月或6个月时的CT感染;(3)事件CT感染微生物负荷降低;(4)发生率降低
同源的CT基因型。研究结果将为预防男性传播的新方法提供信息
并有助于遏制CT率和并发症的上升。
英文摘要
ABSTRACT
Chlamydia trachomatis (CT) is the most common bacterial sexually transmitted infection (STI) worldwide and
causes irreversible reproductive tract damage in women. As most CT-infected women have no symptoms and
are unaware that they are infected, the CDC recommends annual CT screening in women aged <25 and high
risk women to detect and treat asymptomatic infections and prevent complications; in men, routine screening is
not recommended. Despite 3 decades of screening programs, CT rates in the U.S. have dramatically increased,
driven primarily by increasing CT reinfections. As most CT-infected women are heterosexual and routine
screening in men is not recommended, undetected CT infections in men are the reservoir that propels
reinfections in women. To curb the CT epidemic, it is critical that we understand whether men can develop
immunity to CT and identify factors that promote CT reinfections (e.g., asymptomatic men who shed significant
CT organisms). Approximately 1/3 of men who present for treatment as a CT contact (i.e., their sex partner was
confirmed to be CT-infected) are uninfected, suggesting that these men either cleared CT infection by immune-
mediated mechanisms or have a urethral microbiome that resists CT acquisition. To prevent CT reinfections in
women, this proposal focuses on male contacts to CT-infected women and will study if CT infection is associated
with specific microbiome compositions, comorbid STIs, or adaptive T-cell and antibody immunity. To do this, we
will enroll up to 400 male CT-contacts, collect blood and urine specimens, treat them with the CDC-recommend
first-line antibiotic, and ask them to return for a 1-month test of cure (TOC) visit (Aim 1). To study if CT uninfected
contacts to CT have long-lasting immunity and how the urethral microbiome and immune system change over
time, we will re-enroll 100 men for a 6-month longitudinal study to collect weekly urine specimens and
symptom/sexual behavior diaries and blood and urine specimens at 3-month and 6-month screening visits.
Weekly urine specimens will be stored and tested at study completion to create a natural history study. By
studying the rates of incident CT infection over time, we will be able to elucidate if resistance to CT infection,
defined in Aim 1, correlates with (1) increased rate of natural clearance between visits; (2) decrease in incident
CT infection at 3- or 6-months; (3) decrease in incident CT infection organism load; and (4) decrease in the rate
of homologous CT genovars. Study findings will inform novel approaches to preventing transmission from men
to women and help curb rising CT rates and complications.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
The influence of rectal Chlamydia trachomatis infections on immunity and incident urogenital infections in women without an indication forrectal screening
-
批准号:10703789
-
项目类别:
-
资助金额:$77.09万
-
财政年份:2023
-
负责人:Stephen J. Jordan
-
依托单位:
Role of Interferon-gamma in Clearance of Chlamydia trachomatis Infection in Women
-
批准号:10160813
-
项目类别:
-
资助金额:$18.42万
-
财政年份:2019
-
负责人:Stephen J. Jordan
-
依托单位:
Role of Interferon-gamma in Clearance of Chlamydia trachomatis Infection in Women
-
批准号:10404647
-
项目类别:
-
资助金额:$18.42万
-
财政年份:2019
-
负责人:Stephen J. Jordan
-
依托单位:
Role of Interferon-gamma in Clearance of Chlamydia trachomatis Infection in Women
-
批准号:9806333
-
项目类别:
-
资助金额:$18.39万
-
财政年份:2019
-
负责人:Stephen J. Jordan
-
依托单位:
海外基金