Cumulative burden of Chlamydia trachomatis and Mycoplasma genitalium in the US: implications for screening guidelines and antimicrobial resistance

摘要 沙眼衣原体(CT)和支原体与显著的发病率和医疗费用有关 生殖器(MG)感染。每一个都与男性和女性生殖道综合症有关，但每一个 给控制带来了独特的挑战。CT是国家报告的最常见的应通报的情况 它是导致盆腔炎和不孕症的已知原因之一。尽管长期控制着 方案，CT率处于历史最高水平，CT预防工作的效用和成本效益是 辩论过了。由于大多数CT感染都是无症状的，我们目前对流行病学和 CT控制程序的有效性完全取决于通过筛查发现病例，这只是 目标人群为选定人群(妇女及25岁及其他高危人群)。对CT的了解要少得多 不经常进行筛查的女性≥25，不建议与之发生性关系的男性进行筛查 女性(MSW)。我们在认识上的这些重大差距限制了我们有效地针对CT预防的能力 针对感染风险最高的男性和女性的方案。MG是一种较新出现的病原体， 对于20%-30%的男性尿道炎。没有全国性的MG监控，尽管人们普遍认为MG 导致男性尿道炎，关于它是否会对女性造成后遗症，还没有达成共识。有限的人口 基于对泌尿生殖道MG患病率的估计，然而流行的感染往往不能很好地预测生命 有产后不孕症和不孕症的经验，只允许对人群水平的流行病学有部分了解。 MG的抗菌素耐药性(AMR)正在迅速扩大-MG是CDC 2019年的三种细菌之一 AMR威胁观察列表-但AMR流行率估计来自高危STD诊所人群 而且也没有具有全国代表性的数据。更好地了解流行性出血热的人群流行病学 CT和MG对于提高各自的控制效果至关重要。为了实现这一点，我们将进行血清流行病学 在2017-2018年全国健康和营养检查调查(NHANES)周期中的研究，使用一种新的 用于CT的血清学检测，用于区分免疫球蛋白同型以区分近期和远程感染，以及更多 灵敏、特异的MG血清学检测。我们还将在MG阳性患者的尿样中鉴定AMR 在NHANES 2017-2018年。最后，我们将建立一个基于个体的CT和MG传播动力学模型。 使用这些结果，我们将(1)估计美国男性CT的终生患病率，并描述其影响因素 与男性和女性最近感染和既往感染有关；(2)估计血清阳性率和 美国男性和女性MG感染的相关性，确定既往MG感染与 自我报告的产后抑郁和不孕症，并评估大环内酯类和喹诺酮类药物耐药的患病率和相关性 在MG；(3)评估CT和MG筛查方案对生殖健康和治疗的影响 数学模型中的结果。这些数据将提供关键信息来支持或改变当前 CT筛查指南，并告知新的国家对MG的检测和治疗建议。

ABSTRACT Significant morbidity and health care costs are associated with Chlamydia trachomatis (CT) and Mycoplasma genitalium (MG) infections. Each is associated with male and female reproductive tract syndromes, yet each presents unique challenges for control. CT is the most commonly reported nationally notifiable condition in the US and is a known cause of pelvic inflammatory disease (PID) and infertility. Despite longstanding control programs, CT rates are at an all-time high and the utility and cost-effectiveness of CT prevention efforts are debated. As most CT infections are asymptomatic, our current understanding of the epidemiology and the effectiveness of CT control programs has depended entirely on case detection through screening, which is only targeted to select populations (women <25 years and other high risk persons). Much less is known about CT in women ≥25 who are infrequently screened, and screening is not recommended for men who have sex with women (MSW). These major gaps in our understanding have limited our ability to effectively target CT prevention programs to men and women at highest risk of infection. MG is a more recently emerged pathogen, responsible for 20-30% of male urethritis. There is no national MG surveillance and, despite general agreement that MG causes male urethritis, there is no consensus about whether it causes sequelae in women. Limited population based estimates of urogenital MG prevalence exist, yet prevalent infections are often a poor predictor of lifetime experience of PID and infertility and permit only partial understanding of population-level epidemiology. Antimicrobial resistance (AMR) in MG is rapidly expanding - MG is one of three bacteria on the CDC's 2019 Watch List of AMR threats - but AMR prevalence estimates are derived from high-risk STD clinic populations and there are no nationally representative data. A better understanding of the population-level epidemiology of CT and MG is critical to improving control efforts for each. To achieve this, we will conduct a seroepidemiologic study in the National Health and Nutrition Examinations Survey (NHANES) 2017-2018 cycle, using a novel serologic assay for CT that differentiates IgG isotypes to distinguish recent from distant infection, and a more sensitive and specific seroassay for MG. We will also identify AMR in urine specimens from MG-positive persons in NHANES 2017-2018. Finally, we will develop an individual-based CT and MG transmission dynamics model. Using these outputs, we will (1) estimate the lifetime prevalence of CT in US men and characterize factors associated with recent versus past infection among men and women; (2) estimate the seroprevalence and correlates of MG infection in US men and women, determine the association between prior MG infection and self-reported PID and infertility, and estimate prevalence and correlates of macrolide and quinolone resistance in MG; (3) evaluate the impact of CT and MG screening scenarios on reproductive health and treatment outcomes in mathematical models. These data will provide critical information to either support or change current CT screening guidelines, and to inform nascent national testing and treatment recommendations for MG.