Immunopathogenesis Of Chlamydia trachomatis Infection

沙眼衣原体感染的免疫发病机制

• 批准号: 9552526
• 负责人: Thomas Quinn
• 金额: $ 13.43万
• 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/9552526
• 关键词: 13 year old; Address; Age; Alaska; Antibiotic Therapy; Antibiotics; Antibodies; Antigens; Azithromycin; Biological Assay; Black race; Blindness; Blood; Censuses; Cervicitis; Child; Chlamydia; Chlamydia trachomatis; Clinic; Clinical; Collection; Communities; Community Surveys; Confidence Intervals; Conjunctivitis; Consent; Country; Disease; District of Columbia; Ectopic Pregnancy; Enrollment; Epidemiology; Epididymitis; Ethiopia; Event; Exposure to; Eye Infections; Family; Family Planning; Gambia; Gonorrhea; HIV Infections; Home environment; Household; Human immunodeficiency virus test; Incidence; Individual; Infection; Infertility; Inflammation; Internet; Intervention; Intervention Studies; Kinetics; Liquid substance; Longitudinal Studies; Maryland; Methods; Military Personnel; Molecular; Molecular Epidemiology; Molecular Immunology; Monitor; Neighborhoods; Niger; Nomads; Odds Ratio; Operative Surgical Procedures; Pathogenesis; Pelvic Inflammatory Disease; Persons; Pharmaceutical Preparations; Pneumonia; Population; Pregnancy; Premature Infant; Prevalence; Process; Proctitis; Public Health; Randomized Clinical Trials; Recruitment Activity; Reproductive Health; Resources; Risk; Risk Factors; Salpingitis; Sampling; Self Care; Serologic tests; Site; Source; Spottings; Surveillance Program; Surveys; Swab; Syphilis Serodiagnosis; Tanzania; Testing; Time; Trachoma; Trichomonas; Update; Urethritis; Vagina; Woman; Work; adverse outcome; aged; arm; community intervention; disorder control; experience; men; migration; oral HIV; pathogen; point of care; primary outcome; programs; rectal; reproductive tract; satisfaction; screening; tool; transmission process; web site

Chlamydia trachomatis is the most common sexually transmitted bacterial pathogen in the world, causing serious complications on women's reproductive health including ectopic pregnancy, pelvic inflammatory disease and infertility. C. trachomatis also causes infection of the eye resulting in inflammation and in some cases blindness. The objectives of this project are to define the epidemiology, risk factors, transmission kinetics, and pathogenesis of C. trachomatis infections in different population settings, including populations in resource constrained countries. We have used the Internet site www.iwantthekit.org since 2004 to offer sampling in Maryland, the District of Columbia and Alaska for chlamydia screening in over 7,500 women and over 4,000 men using self-obtained vaginal swabs, penile-meatal swabs and rectal samples. Samples were also tested for gonorrhea and trichomonas. Prevalence of chlamydia for women overall was 6.8% and 7.7% in men. Both young age and Black race have been statistically associated with chlamydia positivity. Trichomonas prevalence in women was 6.1% and 2.2% in men. For rectal chlamydia in men, the overall chlamydia prevalence was 6.9% while for gonorrhea it was 4.0%. Acceptance for self-collecting penile-meatal and rectal swabs has been very high. Rectal chlamydia and gonorrhea prevalence in women was 6.3% and 0.9%, respectively. In 2004 chlamydia prevalence was 10.0% which has declined to 3.2% in 2017, an indication of a successful public health program. To study the capability for performing a point-of-care self-test for trichomonas at home, we recently enrolled 102 women who performed the mailed point-of-care (POC) trichomonas test successfully at home. The test demonstrated high accuracy and high acceptability. Recently, as part of a consented-on-line study, 120 persons have requested and performed a POC HIV oral fluid test at home, with excellent satisfaction survey results. The IWTK website has over 10,000 page views per month. Plans are to add home collection of dried blood spots for syphilis and HIV testing which could make IWTK useful for PREP monitoring for STIs. Trachoma due to C. trachomatis infection is the most common cause of infectious blindness in the world. The WHO has recommended that three rounds of mass drug administration (MDA) with antibiotics be offered to control the disease in districts where the prevalence of follicular trachoma (TF) is >10% in children aged 1-9 years, with treatment coverage of at least 80%. We have conducted both surgical and antibiotic treatment intervention studies in Gambia, Niger, and Tanzania in efforts to control trachoma. However, the source of infection following mass treatment is often unknown. If migrants into a village undergoing MDA are shown to impede progress towards elimination, then a local strategy that addresses treatment of new families and a nationwide strategy that addresses migration will be needed. The purpose of this study was to quantify the effect of migrants on the prevalence of infection and clinical trachoma in communities. In four communities in Kongwa, Tanzania, all children were enrolled in a longitudinal study of infection and trachoma. New children were identified at census updates as having not been in the community at the previous census. Within communities, neighborhoods were defined as spatially close groups of households. Children who were migrants were more likely to be infected and to have trachoma than children who were resident in the community, which was significant by the time of the survey following the third year of MDA (odds ratio, OR, 2.49, 95% confidence interval, CI, 1.036.05). The neighborhoods where newcomers resided were more likely to have infection a year later than neighborhoods with no migrants, which was most pronounced following the third year of MDA (OR 2.86, 95% CI 1.077.65). In summary, migrants to communities may be an important source of re-emergent infection, especially as MDA lowers infection among residents. We therefore conducted a community-randomized, clinical trial to determine if a surveillance program that targeted newcomers and travelers, identified weekly, would result in more communities achieving levels of infection of 1%. 52 communities were randomly allocated 1:1 to the control (annual mass drug administration with azithromycin (MDA) alone if warranted) or intervention arm (annual MDA if warranted, plus a surveillance program to identify and treat newcomers and travelers). In each community, surveys were completed every six months on a random sample of 100 children ages 1-9 years for trachoma and infection. The primary outcome was the proportion of communities in the intervention arm, compared to the control arm, which had a prevalence of infection at 1% by 24 months. Intervention communities experienced an average of 110 surveillance events per month. At 24 months, 7 (27%) of 26 intervention communities achieved a prevalence of infection 1% compared to 4 (15%) of the 26 control communities (odds ratio = 26, 95%CI = 056-119). At 24 months, the average infection prevalence in the intervention communities was 48, compared to 69 in the control communities (p = 06). Despite surveillance programs for community newcomers and travelers, the proportion of intervention communities with a level of infection 1% was lower than expected and not significantly different from control communities Recent work on a test for antibodies to C. trachomatis pgp3 antigens suggests serology is a promising tool that indicates cumulative risk of exposure to C. trachomatis. In a trachoma-endemic district in Tanzania that stopped its program four years ago, we undertook a surveillance survey, adding to the assessment of TF a lab test for C. trachomatis infection, and a dried blood spot which was processed for antibodies to C. trachomatis antigen pgp3; antibody status may indicate cumulative past exposure to infection. The prevalence of TF was 0.4%, below the 5% cut-off indicating that trachoma elimination had been achieved with no re-emergence. The antibody positivity overall was low, 7.5%, and increased with age from 5.2% in 13 year olds, to 9.3% in 79 year olds (p = 0.015). In 16 of the 30 hamlets, no children aged 13 years old had antibodies to pgp3. The antibody status of the 13 year olds indicated low cumulative exposure to infection during the surveillance period. In summary, four years post -program, there is no evidence for re-emergence of trachoma using any indicator sufficient to indicate re-emergence.

沙眼衣原体是世界上最常见的性传播细菌病原体，对女性生殖健康造成严重并发症，包括宫外孕、盆腔炎和不孕症。沙眼衣原体还会引起眼睛感染，导致炎症，在某些情况下甚至导致失明。该项目的目标是确定不同人群（包括资源有限国家的人群）沙眼衣原体感染的流行病学、危险因素、传播动力学和发病机制。自 2004 年以来，我们一直使用互联网网站 www.iwantthekit.org 在马里兰州、哥伦比亚特区和阿拉斯加提供采样，使用自制的阴道拭子、阴茎肉拭子和直肠样本对 7,500 多名女性和 4,000 多名男性进行衣原体筛查。还对样本进行了淋病和滴虫检测。女性衣原体感染率为 6.8%，男性为 7.7%。在统计上，年轻和黑人种族都与衣原体阳性有关。女性滴虫感染率为 6.1%，男性感染率为 2.2%。男性直肠衣原体的总体患病率为 6.9%，而淋病的总体患病率为 4.0%。自采集阴茎肉和直肠拭子的接受度非常高。女性直肠衣原体和淋病患病率分别为 6.3% 和 0.9%。 2004 年，衣原体患病率为 10.0%，2017 年已降至 3.2%，这表明公共卫生计划取得了成功。 为了研究在家进行毛滴虫即时护理自检的能力，我们最近招募了 102 名女性，她们在家成功地进行了邮寄即时护理 (POC) 毛滴虫测试。测试结果显示出较高的准确性和较高的可接受性。最近，作为一项经同意的在线研究的一部分，120 人请求并在家中进行了 POC HIV 口腔液检测，满意度调查结果非常好。 IWTK 网站每月的页面浏览量超过 10,000 次。计划增加家庭收集干血斑用于梅毒和 HIV 检测，这可能使 IWTK 可用于性传播感染的 PREP 监测。 沙眼衣原体感染引起的沙眼是世界上感染性失明的最常见原因。世界卫生组织建议，在1-9岁儿童滤泡性沙眼（TF）患病率>10%的地区，开展三轮抗生素大规模药物管理（MDA）来控制疾病，治疗覆盖率至少80%。我们在冈比亚、尼日尔和坦桑尼亚进行了手术和抗生素治疗干预研究，以努力控制沙眼。然而，大规模治疗后的感染源往往是未知的。如果事实证明，进入村庄进行 MDA 的移民阻碍了消除的进展，那么就需要制定解决新家庭待遇的地方战略和解决移民问题的全国战略。本研究的目的是量化移民对社区感染和临床沙眼患病率的影响。在坦桑尼亚孔瓦的四个社区，所有儿童都参加了感染和沙眼的纵向研究。在人口普查更新中，新儿童被确定为在上次人口普查时没有出现在社区中。在社区内，邻里被定义为空间上接近的家庭群体。流动儿童比居住在社区的儿童更有可能被感染和患沙眼，这一点在 MDA 第三年进行调查时非常显着（比值比，OR，2.49，95% 置信区间） ，CI，1.036.05）。新移民居住的社区一年后比没有移民的社区更有可能感染，这一点在 MDA 第三年之后最为明显（OR 2.86，95% CI 1.077.65）。总之，社区流动人口可能是重新出现感染的重要来源，特别是当 MDA 降低了居民感染率时。 因此，我们进行了一项社区随机临床试验，以确定每周确定的针对新移民和旅行者的监测计划是否会导致更多社区达到 1% 的感染水平。 52 个社区按照 1:1 的比例随机分配到对照组（如果有必要，每年进行大规模药物管理，仅使用阿奇霉素 (MDA)）或干预组（如果有必要，每年进行 MDA，加上识别和治疗新移民和旅行者的监测计划）。在每个社区，每六个月对 100 名 1-9 岁儿童进行随机抽样调查，了解沙眼和感染情况。主要结果是干预组中的社区比例与对照组相比，对照组的 24 个月感染率为 1%。干预社区平均每月发生 110 起监控事件。 24 个月时，26 个干预社区中有 7 个 (27%) 的感染率达到 1%，而 26 个对照社区中有 4 个 (15%) （比值比 = 26，95%CI = 056-119）。 24 个月时，干预社区的平均感染率为 48，而对照社区的平均感染率为 69 (p = 06)。尽管对社区新移民和旅行者进行了监测，但感染水平为 1% 的干预社区比例低于预期，与对照社区没有显着差异 最近对沙眼衣原体 pgp3 抗原抗体测试的研究表明，血清学是一种很有前途的工具，可以指示暴露于沙眼衣原体的累积风险。在坦桑尼亚的一个沙眼流行区，四年前停止了该项目，我们进行了一项监测调查，除了对 TF 的评估之外，还增加了沙眼衣原体感染的实验室测试，以及经过处理的干血点以检测衣原体抗体。沙眼抗原pgp3；抗体状态可能表明过去累积的感染暴露情况。 TF 的患病率为 0.4%，低于 5% 的临界值，表明沙眼已经消除，没有再次出现。抗体阳性总体较低，为 7.5%，并随着年龄的增长而增加，从 13 岁的 5.2% 增加到 79 岁的 9.3% (p = 0.015)。在 30 个小村庄中，有 16 个村庄的 13 岁儿童没有 pgp3 抗体。 13 岁儿童的抗体状况表明，在监测期间，累积感染暴露程度较低。总之，在计划实施四年后，没有证据表明沙眼再次出现，使用任何足以表明沙眼重新出现的指标。