Immunopathogenesis Of Chlamydia trachomatis Infection

沙眼衣原体感染的免疫发病机制

• 批准号: 10272023
• 负责人: Thomas Quinn
• 金额: $ 7.17万
• 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/10272023
• 关键词: 1 year old; 11 year old; 19 year old; 5 year old; 8 year old; Adolescent; Age; Alaska; Alleles; Antibiotic Therapy; Antibiotic susceptibility; Antibiotics; Antimicrobial Resistance; Antimicrobial susceptibility; Azithromycin; Biological Assay; Black race; Blindness; Blood; Buffers; Cephalosporins; Cervicitis; Child; Chlamydia; Chlamydia Infections; Chlamydia trachomatis; Ciprofloxacin; Clinic; Clinical; Clothing; Collection; Communities; Conjunctivitis; Consent; Country; Cross-Sectional Studies; Cytomegalovirus; Cytomegalovirus Infections; DNA; Data; Detection; Disease; District of Columbia; Drug-resistant Neisseria Gonorrhoeae; Ectopic Pregnancy; Effectiveness; Environment; Epidemiology; Epididymitis; Ethiopia; Eye Infections; Face; Family Planning; Family member; Female; Furniture; Gambia; General Population; Genitourinary system; Genotype; Glycoproteins; Gonorrhea; HIV; HIV Infections; Hand; Handwashing; Home environment; Household; Human immunodeficiency virus test; Hygiene; Immunoglobulin G; Incidence; Individual; Infant; Infection; Infertility; Inflammation; Internet; Intervention Studies; Kinetics; Laboratories; Latrine; Liquid substance; Maryland; Methods; Military Personnel; Molecular; Molecular Epidemiology; Molecular Immunology; Monitor; Mosaicism; Mutation; National Health and Nutrition Examination Survey; Neisseria gonorrhoeae; Niger; Nigeria; Nigerian; Nucleic Acid Amplification Tests; Obesity; Odds Ratio; Operative Surgical Procedures; Oral; Organism; Pathogenesis; Pattern; Pelvic Inflammatory Disease; Penicillins; Persons; Pharmaceutical Preparations; Pilot Projects; Pneumonia; Population; Predisposition; Pregnancy; Premature Infant; Prevalence; Process; Proctitis; Public Health; Reproductive Health; Research; Resistance; Resources; Risk; Risk Factors; Salpingitis; Sampling; Sexual Transmission; Site; Sleep; Source; Spottings; Surveys; Swab; Syphilis; Syphilis Serodiagnosis; Tanzania; Testing; Thinness; Time; Trachoma; Trichomonas; United States; Urethritis; Urine; Vagina; Variant; Viral Load result; Visit; Woman; Work; adverse outcome; age group; aged; base; disorder control; environmental change; indexing; male; men; men who have sex with men; method development; oral HIV; pathogenic bacteria; penis; pre-exposure prophylaxis; programs; recruit; rectal; reproductive tract; satisfaction; screening; transmission process; urinary; vaccine development; viral transmission; 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 (IWTK) since 2004 to offer sampling in Maryland, the District of Columbia and Alaska for chlamydia screening in over 10,000 women and over 5000 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 6.3% 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 were 6.3% and 0.9%, respectively. In 2004 chlamydia prevalence was 10.0% which has declined to 3.2% in 2018, an indication of a successful public health program. Recent data indicate that between 2013-17 positivity for any STI was 10.7% and 19.9% of STIs would have been missed if urogenital sampling only had been done (22.0% of male and 11.9% of female chlamydia infections.). Recently, as part of a consented-on-line study, 200 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. A pilot study has begun to add to add home collection of dried blood spots for syphilis and HIV testing for monitoring for syphilis and HIV for a research PrEP study. There are limited nationally representative data on correlates of cytomegalovirus (CMV) shedding among children and adolescents. In addition, the genotype distribution of CMV infections has not been well characterized among general populations in the United States. We characterized urinary CMV shedding among CMV immunoglobulin G-positive 6- to 19-year-olds in the US household population using data from the 1999-2004 National Health and Nutrition Examination Survey (NHANES). Prevalence of urinary CMV shedding was significantly lower among 9- to 11-year-olds (20.6%; aPR = 0.61; 95% CI, 0.44-0.83) and 12- to 19-year-olds (7.0%; aPR = 0.21; 95% CI, 0.14-0.30) compared with 6- to 8-year-olds (34.4%). Among CMV shedders, the youngest age group also had the highest urinary CMV viral loads. The prevalence of urinary CMV shedding among obese individuals was significantly lower compared with lean individuals (aPR = 0.68; 95% CI, 0.47-0.99). Among CMV shedders, glycoprotein B (gB)1 (51%) was the most prevalent gB variant, followed by gB2 (29%), gB3 (21%), and gB4 (13%); glycoprotein H (gH)2 (60%) was more prevalent than gH1 (48%). Multiple (2) gB (14%) and multiple gH (7%) infections were detected among CMV shedders. This study underscores the importance of young children even above the age of 5 years as a potential source of CMV transmission. The detection of multiple CMV strains among CMV shedders may have implications for the transmission of viral diversity as well as vaccine development. 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. Environmental changes largely focus on facial hygiene and latrines, but further work to identify other possible transmission targets are needed. We sought to determine, in a cross-sectional survey of households of children with active trachoma, if we could detect the presence of Chlamydia trachomatis on household objects and on family members based on sleeping and caretaking patterns. In five villages in Kongwa, Tanzania, children <five years were randomly chosen for examination for trachoma, and households of all children with active trachoma were eligible for this study. Environmental swabs of bedding, furniture, clothing, and hands were taken and processed using Amplicor for detecting C. trachomatis DNA. Of 80 visited households, 13 (16%) had at least one swab from environmental sources positive for C. trachomatis DNA. A positive environmental swab was associated with the presence of ocular infection in the index child (Odds Ratio = 22.0, p = .007), the presence of an infant <1 year of age in the household, and whether the children's clothing had not been recently washed. C. trachomatis DNA is present in the environment of children with active trachoma, especially in households with an ocular infection. Specific findings also suggest that washing hands, clothing, and bedding may be important. Antimicrobial-resistant Neisseria gonorrhoeae (NG) is a global public health issue that threatens effectiveness of current treatments of NG. Increased use of nucleic acid amplification tests (NAATs) in lieu of cultures makes obtaining clinical isolates for susceptibility testing difficult and samples collected in commercial transport buffer for NAATs do not preserve viable organism, while molecular methods of assessing antibiotic susceptibility do not require viable organism. We evaluated 243 NG-positive samples in Aptima transport media including urine, oral, and rectal swabs from Nigerian men who have sex with men for markers to penicillinase-producing NG, ciprofloxacin ( GyrA and ParC mutations), and extended spectrum cephalosporins (ESCs, PenA mosaic allele X, PonA, mtrR, PorB mutations) by real-time PCR. NG DNA was recovered in 75% (183/243) of samples. Of these, 93% (171/183) were positive for at least one resistance marker. We observed a prevalence of dual resistance markers to penicillin and ciprofloxacin at 46.2% (79/171). Six percent of samples (10/171) tested positive for the PenA mosaic (allele X) ESC marker. These data indicate that antibiotic-resistant NG is common in Nigeria. Laboratory and clinical capacity building in Nigeria should include development of methods to culture NG and determine antimicrobial susceptibility.

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。 C. c. trachomatis还会引起眼睛感染，导致炎症和某些情况下失明。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。自2004年以来，我们已经使用互联网网站www.iwantthekit.org（IWTK）在马里兰州，哥伦比亚特区和阿拉斯加提供抽样，以对超过10,000名妇女进行衣原体筛查，并使用自我侵蚀的阴道拭子，阴茎医学拭子和直肠样品进行了10,000多名女性和5000多名男性。还测试了样品中的淋病和毛毛虫。男性全面为女性衣原体的患病率为6.3％和7.7％。从统计学上讲，年龄和黑人种族都与衣原体的阳性有关。女性的毛刺患病率为男性6.1％和2.2％。对于男性直肠衣原体，整体衣原体患病率为6.9％，而淋病为4.0％。接受自我收集的阴茎 - 棉签和直肠拭子的接受程度很高。女性的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％，2018年下降到3.2％，这表明成功的公共卫生计划。最近的数据表明，如果仅进行泌尿生殖器采样，则任何STI的2013 - 17年度阳性均为10.7％和19.9％的性传播感染（男性22.0％，女性衣原体感染的11.9％。）。最近，作为一项同意研究的一部分，有200人在家中要求并进行了POC HIV口服液体测试，并具有出色的满意度调查结果。 IWTK网站每月有超过10,000页的观看次数。一项试点研究已开始增加，以增加梅毒干燥斑点的家庭收集，并为监测梅毒和艾滋病毒的艾滋病毒测试，以进行研究预备研究。 关于儿童和青少年的巨细胞病毒（CMV）脱落相关性的全国代表性数据有限。此外，在美国的一般人群中，CMV感染的基因型分布尚未得到很好的特征。 我们使用1999 - 2004年国家健康和营养检查调查（NHANES）中的数据（NHANES）中的数据表征了CMV免疫球蛋白G阳性6至19岁的CMV脱落。在9至11岁的年轻人中，尿液CMV脱落的患病率明显降低（APR = 0.61; 95％CI，0.44-0.83）和12至19岁的孩子（7.0％; APR = 0.21; 95％CI，0.14-0.30）的患病率与6-至8岁的孩子（34.4％）（34.4％）相比。在CMV棚中，最年轻的年龄组也具有最高的尿CMV病毒载荷。与精益个体相比，肥胖个体中尿中CMV脱落的患病率显着降低（APR = 0.68； 95％CI，0.47-0.99）。在CMV茎中，糖蛋白B（GB）1（51％）是最普遍的GB变体，其次是GB2（29％），GB3（21％）和GB4（13％）；糖蛋白H（GH）2（60％）比GH1更普遍（48％）。在CMV棚中检测到多个（2）GB（14％）和多种GH（7％）感染。这项研究强调了幼儿的重要性，即使是5岁以上的CMV传播来源。 CMV棚中多个CMV菌株的检测可能对病毒多样性以及疫苗开发的传播有影响。 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。世卫组织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）的地区> 10％，治疗覆盖率至少为80％。我们已经在冈比亚，尼日尔和坦桑尼亚进行了手术和抗生素治疗干预研究，以控制沙眼瘤。但是，群众治疗后的感染来源通常是未知的。环境变化主要集中在面部卫生和厕所上，但需要进一步的工作来确定其他可能的传输目标。如果我们可以根据睡眠和照顾模式检测到对家庭物体和家庭成员对家庭成员的存在，我们试图在对患有活跃沙眼的儿童家庭的横断面调查中确定。在坦桑尼亚孔瓦的五个村庄中，随机选择了<五岁的儿童进行沙眼检查，所有活性沙眼儿童的家庭都有资格参加这项研究。使用放大器拿走并加工床上用品，家具，衣服和手的环境拭子，用于检测沙眼C.在访问的80个家庭中，有13个（16％）的环境来源至少有一只拭子，对沙眼梭状芽孢杆菌DNA呈阳性。环境拭子与指数儿童中的眼部感染存在有关（几率= 22.0，p = .007），家庭中婴儿<1岁的存在<1岁，以及最近没有洗儿童衣服。 C. c. c. trachomatis dna存在于活性沙丘瘤儿童的环境中，尤其是在眼部感染的家庭中。具体发现还表明，洗手，衣服和床上用品可能很重要。 抗菌抗菌淋病淋病（NG）是一个全球公共卫生问题，威胁到当前NG治疗的有效性。增加核酸扩增测试（NAAT）代替培养物的使用增加使得难以获得易感性测试的临床分离株，并且在商业传输缓冲液中为NAATS收集的样品不能保留可行的生物体，而评估抗生素易感性的分子方法不需要可行的生物体。 We evaluated 243 NG-positive samples in Aptima transport media including urine, oral, and rectal swabs from Nigerian men who have sex with men for markers to penicillinase-producing NG, ciprofloxacin ( GyrA and ParC mutations), and extended spectrum cephalosporins (ESCs, PenA mosaic allele X, PonA, mtrR, PorB mutations) by real-time pcr。在75％（183/243）样品中回收了NG DNA。其中，至少一个电阻标记物为93％（171/183）为阳性。我们观察到以46.2％（79/171）为46.2％（79/171）的双电阻标记物的患病率。 pena马赛克（等位基因X）ESC标记的样品中有6％（10/171）测试了阳性。这些数据表明抗生素的NG在尼日利亚很常见。尼日利亚的实验室和临床能力建设应包括开发培养NG的方法并确定抗菌敏感性。