Immunopathogenesis Of Chlamydia trachomatis Infection

沙眼衣原体感染的免疫发病机制

• 批准号: 8745287
• 负责人: Thomas Quinn
• 金额: $ 112.61万
• 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/8745287
• 关键词: Aftercare; Age; Am 80; Antibiotic Therapy; Antibiotics; Area; Azithromycin; Biological Assay; Black race; Blindness; Cervicitis; Characteristics; Child; Chlamydia; Chlamydia Infections; Chlamydia trachomatis; Clinic; Clinical; Communities; Companions; Conjunctivitis; Country; Diagnostic; Disease; Ectopic Pregnancy; Enrollment; Epidemiology; Epididymitis; Ethiopia; Eye Infections; Family Planning; Gambia; Genital system; Gonorrhea; HIV Infections; High Prevalence; Household; Incidence; Individual; Infant; Infection; Infertility; Internet; Intervention Studies; Kinetics; Longitudinal Studies; Maryland; Methods; Military Personnel; Modeling; Molecular; Molecular Epidemiology; Molecular Immunology; Monitor; Niger; Operative Surgical Procedures; Participant; Pathogenesis; Pelvic Inflammatory Disease; Persons; Pharmaceutical Preparations; Pneumonia; Population; Pregnancy; Prevalence; Proctitis; Randomized; Recruitment Activity; Reproductive Health; Resources; Risk; Risk Factors; Salpingitis; Sampling; Sensitivity and Specificity; Sexually Transmitted Diseases; Surveys; Swab; Tanzania; Testing; Trachoma; Urethritis; Vagina; Woman; adverse outcome; age group; aged; arm; base; community intervention; community setting; disorder control; international center; meetings; men; pathogen; point of care; premature; programs; protective effect; screening; standard care; transmission process; treatment as usual; young woman

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. 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. In a multi-center international trial, we screened a total of 18,014 participants at baseline, 15,054 at 12 months, and 14,243 at 24 months for a variety of STDs using non-invasive molecular amplified assays. The incidence of chlamydia in men was 2.0 per 100 person years and 4.6 in women across the 5 countries. A high prevalence and incidence of asymptomatic sexually transmitted infections was identified among men and women in a wide variety of settings, prompting the need for more effective programs to identify and treat chlamydia and gonorrhea infections. We have used the Internet, www.iwantthekit.org, to offer sampling in Maryland and other areas in the U.S. for chlamydia screening in 4,500 women and over 2500 men using self-obtained vaginal swabs or self-obtained penile-meatal swabs. Prevalence for chlamydia for women has been 7.5% overall for women, and 15.3% in young women age 15-19 yr. Both young age and Black race were statistically associated with chlamydia positivity. For men, the overall prevalence has been 9.1%. Over 21% were positive for at least one STD with acceptance for collecting penile swabs being very high. 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 &#8805;10% in children aged 1-9 years, with treatment coverage of at least 80%. We have participated in both surgical and antibiotic treatment intervention studies in Gambia, Niger, and Tanzania in efforts to control trachoma. To evaluate a point of care molecular diagnostic for field use we determined the sensitivity, specificity, and field utility of the Cepheid GeneXpert C. trachomatis assay for ocular chlamydia infection compared to Roche Amplicor assay. In a trachoma-endemic community in Kongwa Tanzania, 144 children ages 0 to 9 were surveyed to assess clinical trachoma and had two ocular swabs taken. Of the 144 swabs taken the prevalence of follicular trachoma by clinical exam was 43.7%, and by evidence of infection according to Amplicor was 28.5%. The sensitivity of GeneXpert for C. trachomatis when compared to Amplicor was 100% and the GeneXpert test identified more positives in individuals with clinical trachoma than Amplicor. The GeneXpert test for C. trachomatis performed with high sensitivity and specificity and demonstrated excellent promise as a field test for trachoma control. To determine whether infection recurs after mass treatment, we re-examined individuals in Tanzania five years after initiation of the program. Treatment coverage was 80% for all ages in the first year. At five years, clinical trachoma rates were lower than at baseline, ranging from 45% compared to 81% at baseline. The prevalence of trachoma decreased in a linear fashion with number of years of mass treatment, and decreased prevalence of C. trachomatis infection was related to the extent of the previous years azithromycin coverage. Our model suggests that, for communities with baseline trachoma prevalence of 50% and annual treatment coverage of 75%, >7 years of annual mass treatment will be needed to reach a prevalence of trachoma of <5%. In a sub-study of the Tanzania program, all children under 9 years in 4 villages were followed from baseline pre-mass treatment to six months post treatment. 1,991 children under nine years were enrolled in the longitudinal study. Baseline infection was 23.7% and at 6 months was 10.4%, despite 95% coverage. Infection at baseline was positively associated with infection at 6 months (OR = 3.31, 95%CI 2.40-4.56) and treatment had a protective effect (OR = 0.45, 95%CI 0.25-0.80). The age group 2-4 years had an increased risk of infection at 6 months. The household characteristics predictive of infection at 6 months were increasing number of children infected in the household at baseline and increasing number of untreated children in the household. None of the intervention communities met criteria to stop MDA. There was no difference in infection (2.9% vs 4.7%; P = .25) between the usual care and cessation rule communities at 18 months. In this setting, communities with low (10%-20%) initial prevalence of active trachoma did not have MDA stopped before 3 annual rounds on the basis of monitoring for infection. Infection with C trachomatis in communities with average trachoma rates at 12% to 13% cannot be eliminated before 3 rounds of MDA with azithromycin. In a companion study in Gambia the baseline prevalence of TF and of Ct infection in the target communities was much lower at 6.5% and 0.8% respectively. At 36 months the prevalence of TF was 2.8%, and that of Ct infection was 0.5%. No differences were found between the arms in TF or Ct infection prevalence either at baseline, or at 36 months. The implementation of the stopping rule led to treatment stopping after one round of MDA in all communities in both SR arms. Mean treatment coverage of children aged 0-9 in communities randomized to standard treatment was 87.7% at baseline and 84.8% and 88.8% at one and two years, respectively. There was no evidence of any difference in TF or Ct prevalence at 36 months resulting from enhanced coverage or from one round of MDA compared to three. Thus the Gambia is close to the elimination target for active trachoma, whereas Tanzania will require prolonged MDA. In districts prioritized for three MDA rounds, one round of MDA reduced active trachoma to low levels and Ct infection was not detectable in any community. There was no additional benefit to giving two further rounds of MDA. Programs could save scarce resources by determining when to initiate or to discontinue MDA based on testing for Ct infection, and one round of MDA may be all that is necessary in some settings to reduce TF below the elimination threshold.

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。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。在一项多中心国际试验中，我们使用非侵入性分子放大检测对总共 18,014 名参与者进行了基线筛查，12 个月时筛查了 15,054 名参与者，24 个月时筛查了 14,243 名参与者，以检测各种 STD。在 5 个国家中，男性衣原体发病率为每 100 人年 2.0 例，女性为 4.6 例。在各种环境下，男性和女性中无症状性传播感染的患病率和发病率都很高，因此需要更有效的方案来识别和治疗衣原体和淋病感染。我们利用互联网 www.iwantthekit.org，在马里兰州和美国其他地区使用自取的阴道拭子或自取的阴茎肉拭子对 4,500 名女性和超过 2500 名男性进行衣原体筛查。女性衣原体感染率为 7.5%，15-19 岁年轻女性的感染率为 15.3%。年轻和黑人种族都与衣原体阳性率存在统计学相关性。对于男性来说，总体患病率为 9.1%。超过 21% 的人至少患有一种性病，并且对收集阴茎拭子的接受度非常高。 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%。我们参与了冈比亚、尼日尔和坦桑尼亚的手术和抗生素治疗干预研究，以努力控制沙眼。为了评估现场使用的护理点分子诊断，我们确定了 Cepheid GeneXpert 沙眼衣原体检测与 Roche Amplicor 检测相比的敏感性、特异性和现场实用性。在坦桑尼亚 Kongwa 的一个沙眼流行社区，对 144 名 0 至 9 岁的儿童进行了调查，以评估临床沙眼情况，并采集了两份眼部拭子。在采集的 144 份拭子中，临床检查显示滤泡性沙眼的患病率为 43.7%，根据 Amplicor 的感染证据显示，滤泡性沙眼的患病率为 28.5%。与 Amplicor 相比，GeneXpert 对沙眼衣原体的敏感性为 100%，并且 GeneXpert 测试在患有临床沙眼的个体中识别出比 Amplicor 更多的阳性结果。针对沙眼衣原体的 GeneXpert 测试具有高灵敏度和特异性，并显示出作为沙眼控制现场测试的良好前景。 为了确定大规模治疗后感染是否会复发，我们在该计划启动五年后重新检查了坦桑尼亚的个体。第一年所有年龄段的治疗覆盖率为 80%。五年时，临床沙眼发病率低于基线，从基线时的 45% 到 81% 不等。沙眼患病率随着大规模治疗的年数呈线性下降，沙眼衣原体感染患病率的下降与前几年阿奇霉素的覆盖范围有关。我们的模型表明，对于基线沙眼患病率为 50% 且年度治疗覆盖率为 75% 的社区，需要 >7 年的年度大规模治疗才能使沙眼患病率达到 <5%。在坦桑尼亚项目的一项子研究中，对 4 个村庄的所有 9 岁以下儿童进行了从群众治疗前基线到治疗后六个月的随访。 1,991 名 9 岁以下儿童参与了这项纵向研究。尽管覆盖率达到 95%，但基线感染率为 23.7%，6 个月时感染率为 10.4%。基线时的感染与 6 个月时的感染呈正相关（OR = 3.31，95%CI 2.40-4.56），并且治疗具有保护作用（OR = 0.45，95%CI 0.25-0.80）。 2-4岁年龄组在6个月时感染的风险增加。预测 6 个月时感染的家庭特征是基线时家庭中感染的儿童数量增加以及家庭中未经治疗的儿童数量增加。 没有一个干预社区符合停止 MDA 的标准。 18 个月时，常规护理社区和戒烟规则社区之间的感染率没有差异（2.9% vs 4.7%；P = .25）。在这种情况下，活动性沙眼初始患病率较低（10%-20%）的社区在感染监测的基础上，在 3 个年度轮次之前没有停止 MDA。在平均沙眼发病率为 12% 至 13% 的社区中，在使用阿奇霉素进行 3 轮 MDA 之前无法消除沙眼衣原体感染。 在冈比亚的一项配套研究中，目标社区中 TF 和 Ct 感染的基线患病率要低得多，分别为 6.5% 和 0.8%。 36个月时，TF感染率为2.8%，Ct感染率为0.5%。无论是基线时还是 36 个月时，各组之间的 TF 或 Ct 感染率均未发现差异。停止规则的实施导致两个 SR 组的所有社区在一轮 MDA 后停止治疗。随机接受标准治疗的社区 0-9 岁儿童的平均治疗覆盖率在基线时为 87.7%，在一年和两年时分别为 84.8% 和 88.8%。没有证据表明 36 个月时的 TF 或 Ct 患病率因覆盖范围的扩大或一轮 MDA 与三轮相比而导致。因此，冈比亚已接近消除活动性沙眼的目标，而坦桑尼亚则需要延长 MDA。在优先进行三轮 MDA 的地区，一轮 MDA 将活动性沙眼降低至低水平，并且在任何社区均未检测到 Ct 感染。再进行两轮 MDA 没有额外的好处。计划可以通过根据 Ct 感染检测确定何时启动或停止 MDA 来节省稀缺资源，并且在某些情况下，为了将 TF 降低到消除阈值以下，一轮 MDA 可能就足够了。