Novel Bacterial Pathogens in Pelvic Inflammatory Disease

描述(由首席研究人员提供)：盆腔炎性疾病是年轻女性中的一种常见疾病，会导致严重的后遗症，包括不孕、复发和慢性盆腔疼痛。虽然淋病奈瑟菌和/或沙眼衣原体在大约1/3到1/2的患有盆腔炎的妇女中得到了恢复，但在其他妇女中，病因通常是不明的。一些研究已将细菌性阴道病(BV)与细菌性阴道病(PID)联系起来，但几种新发现的BV相关细菌，如血吸虫/羊膜细毛杆菌、阴道阿托波氏菌和细菌性阴道病相关细菌(BVAB)在PID中的作用还鲜有研究。解脲支原体与盆腔炎和不孕症有关，尽管结果喜忧参半。最近，解脲支原体被分成两个生物群，一些研究发现对男性无致病性的微小解脲支原体(Biovar 1)和与男性尿道炎有关的解脲支原体(biovar 2，UU-2)。UU-2在女性生殖疾病中的作用尚未得到充分研究。绝大多数疑似PID的美国妇女都使用针对淋病和衣原体PID的抗生素方案进行治疗。支原体已经对四环素类药物表现出相当大的耐药性，对新发现的BV病原体的治疗知之甚少。我们认为，在上生殖道感染了这些细菌的妇女，如果接受目前的PID方案治疗，可能会经历持续感染和生殖疾病。在正在进行的产后疾病评估和临床健康研究中，我们建议对831名妇女进行血吸虫/羊膜细毛杆菌、阴道念珠菌、BVAB和UU-2的聚合酶链式反应(PCR)研究。使用保存的基线和30天的宫颈和子宫内膜标本，我们建议：1)确定下生殖道和上生殖道感染的危险因素；2)确定这些病原体、子宫内膜炎和宫颈炎症之间的关联；3)确定这些细菌与BV之间的关联；4)评估这些感染对头孢西丁和多西环素的治疗反应；以及5)评估这些感染对生殖发病率的影响。探索新的病原体在产后感染中的作用，对于优化诊断和治疗，预防非淋菌性/非衣原体产后感染妇女的生殖发病率是非常必要的。公共卫生相关性：这项拟议的研究将首次比较使用当前推荐的抗微生物方案治疗的盆腔炎患者的不孕症、慢性盆腔疼痛和复发的盆腔炎(PID)。鉴于目前对患有血吸虫/羊膜肺炎、阴道念珠菌、BVAB、UP和UU-2的妇女的治疗有效性的信息匮乏，拟议的研究势在必行，以优化对所有患有PID的妇女的治疗，并设计有针对性的干预策略，无论是来自衣原体/淋球菌还是厌氧来源。了解血吸虫/羊膜肺炎、阴道念珠菌、BVAB和UU-2PID的危险因素、临床特征、治疗效果和发病率将指导未来的临床和公共卫生建议。

DESCRIPTION (provided by principal investigator): Pelvic Inflammatory Disease (PID) is a common disease among young women that results in serious sequelae including infertility, recurrence, and chronic pelvic pain. Although Neisseria gonorrhoeae and/or Chlamydia trachomatis are recovered from approximately a third to a half of women with PID, in the other women the etiologic agent is often unidentified. Several studies have linked bacterial vaginosis (BV) with PID, but the role of several newly identified BV-associated bacteria, such as Leptotrichia sanguinegens/amnionii, Atopobium vaginae, and Bacterial Vaginosis Associated Bacteria (BVAB) in PID has been little studied. The mycoplasma U. urealyticum has been associated with PID and infertility, although with mixed results. Recently, U. urealyticum has been split into two biovars, U. parvum (biovar 1), which has been found to be nonpathogenic in men in some studies, and U. urealyticum (biovar 2, UU-2), which has been associated with urethritis in men. The role of UU-2 in reproductive disease in women is understudied. The great majority of American women with suspected PID are treated with antibiotic regimens directed toward gonorrheal and chlamydial PID. Mycoplasmas have demonstrated considerable resistance to tetracyclines, and little is known about the treatment of newly identified BV pathogens. We propose that women infected with these bacteria in the upper genital tract who are treated with current PID regimens may experience persistent infection and reproductive morbidity. We propose a polymerase chain reaction (PCR) study of Leptotrichia sanguinegens/amnionii, A. vaginae, BVAB, and UU-2 among 831 women in the ongoing PID Evaluation and Clinical Health Study. Using stored baseline and 30 day cervical and endometrial specimens, we propose to: 1) identify the risk factors for infections of the lower and upper genital tract; 2) determine the associations between these pathogens, endometritis, and cervicitis; 3) determine the associations between these bacteria and BV; 4) assess the treatment response of these infections to cefoxitin and doxycycline; and 5) evaluate the impact of these infections on reproductive morbidity. Exploring the role of novel pathogens in PID is imperative to optimize diagnosis and treatment and to prevent reproductive morbidity among women with nongonococcal/nonchlamydial PID. PUBLIC HEALTH RELEVANCE: The proposed study will be the first to compare infertility, chronic pelvic pain, and recurrent pelvic inflammatory disease (PID) in PID patients treated with currently recommended anti-microbial regimens. Given the scarcity of information regarding the effectiveness of current PID treatment for women with L. sanguinegens/amnionii, A. vaginae, BVAB, UP, and UU-2, the proposed study is imperative in order to optimize treatment for all women with PID and design targeted intervention strategies, whether of chlamydial/gonococcal or anaerobic origin. Knowledge of the risk factors, clinical characteristics, treatment efficacy, and morbidity of L. sanguinegens/amnionii, A. vaginae, BVAB, and UU-2 PID will direct future clinical and public health recommendations.