Immunopathogenesis Of Chlamydia trachomatis Infection

沙眼衣原体感染的免疫发病机制

基本信息

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
项目类别：
财政年份：
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

项目摘要

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 ≥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，导致女性生殖健康的严重并发症，包括异位妊娠，骨盆炎性疾病和不育。该项目的目的是定义不同人口环境中沙眼感染的流行病学，危险因素，传播动力学和发病机理，包括资源约束国家中的人群。在一项多中心国际试验中，我们使用非侵入性分子扩增的测定法对基线进行了总共18,014名参与者，12个月时15,054个，在24个月时为14,243个。男性衣原体的发病率为每100人2.0年，在这5个国家 /地区的女性中为4.6。在各种环境中，男性和女性发现了无症状性传播感染的高患病率和发病率，这促使人们需要更有效的计划来识别和治疗衣原体和淋病感染。我们已经使用互联网www.iwantthekit.org在马里兰州和美国其他地区提供抽样，以在4,500名妇女和2500多名男性中使用自我注射的阴道拭子或自我观察的阴茎擦拭。女性衣原体的患病率为女性的总体总体为7.5％，年轻女性为15-19岁的年轻女性。在统计学上，年龄和黑人种族都与衣原体的阳性有关。对于男性来说，总体患病率为9.1％。超过21％的人为至少一个性病，因为收集阴茎棉签很高，因此接受了阳性。由于沙眼梭状芽胞盘感染引起的沙眼是世界上传染失明的最常见原因。 WHO建议提供三轮大规模药物管理（MDA），并提供抗生素以控制1-9岁儿童卵泡性沙眼患病率（TF）≥10％的地区，治疗覆盖率至少为80％。我们已经参加了冈比亚，尼日尔和坦桑尼亚的手术和抗生素治疗干预研究，以控制沙丘瘤。为了评估用于现场使用的护理分子诊断点，我们确定了与罗氏放大器测定法相比，头exexexexpert C. c. trachomatis分析的敏感性，特异性和野外效用。在坦桑尼亚孔瓦（Kongwa Tanzania）的一个沙眼流行社区中，对144名0至9岁的儿童进行了调查以评估临床沙丘瘤，并进行了两只眼拭子。在144块拭子中，通过临床检查的卵泡性沙眼患病率为43.7％，根据扩增子的感染证据为28.5％。与放大器相比，Genexpert对沙眼曲霉的敏感性为100％，而GenExpert测试在临床性沙丘瘤患者中鉴定出比放大器的阳性更高。对气管梭状芽胞庭的GenExpert检验具有高灵敏度和特异性，并表现出极好的前景，作为对沙眼控制的现场测试。为了确定在大规模治疗后是否复发感染，我们在该计划启动五年后重新检查了坦桑尼亚的个体。第一年的所有年龄段的治疗范围为80％。在五年中，临床沙丘率低于基线，范围从45％，而基线为81％。随着群众治疗的数量，气管疾病的患病率降低了，沙眼曲霉感染的患病率降低与前几年阿奇霉素覆盖率有关。我们的模型表明，对于基线三气囊患病率且年度治疗覆盖率为75％的社区，将需要7年的年度质量治疗才能达到三方症的患病率<5％。在坦桑尼亚计划的一个子研究中，从基线前治疗到治疗后六个月，所有9岁以下的儿童都遵循4个村庄。纵向研究中招募了1,991名9岁以下的儿童。尽管承保范围为95％，但基线感染率为23.7％，6个月时为10.4％。基线时的感染与6个月时感染呈正相关（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岁的年龄组在6个月时感染风险增加。在6个月时预测感染的家庭特征是在基线时在家庭中感染的儿童数量增加，家庭中未经治疗的儿童数量增加。干预社区均未符合停止MDA的标准。在18个月时，感染没有差异（2.9％vs 4.7％； P = .25）。在这种情况下，活性沙眼的初始患病率较低（10％-20％）的社区没有在3年巡回赛之前停止MDA。在平均气管率（12％至13％）的社区中，C c沙眼的感染在3轮使用阿奇霉素的MDA之前不能消除。在冈比亚的一项同伴研究中，目标群落中TF和CT感染的基线患病率分别低得多，分别为6.5％和0.8％。在36个月时，TF的患病率为2.8％，CT感染的患病率为0.5％。在基线或36个月时，TF或CT感染患病率的臂之间均未发现差异。停止规则的实施导致治疗在两个SR武器的所有社区的MDA一轮后停止。在基线时随机分配到标准治疗的社区中0-9岁儿童的平均治疗覆盖率分别为87.7％，一年和两年分别为84.8％和88.8％。没有证据表明36个月的TF或CT患病率有任何差异，这是由于覆盖率增强或一轮MDA而导致的36个月，而3个月中的TF或CT患病率相比三个。因此，冈比亚接近活性沙眼的消除靶标，而坦桑尼亚将需要延长MDA。在优先考虑三轮MDA的地区，一轮MDA在任何社区中都无法检测到一轮活跃的沙丘瘤，CT感染均无法检测到CT感染。再提供两轮MDA没有其他好处。程序可以通过确定何时启动或基于CT感染的测试来节省稀缺资源，而在某些情况下，可能需要一轮MDA，以将TF降低到消除阈值以下。