Syphilis: Translating technology to understand a neglected epidemic

描述（由申请方提供）：梅毒仍然是一种全球不受控制的传染病，在某些高危人群中具有较高的患病率和发病率，影响秘鲁20%以上的男男性行为者（MSM）。梅毒也是新生儿发病和死亡的一个重要原因，并且与人类免疫缺陷病毒感染和传播的风险增加有关。尽管梅毒具有公共卫生重要性且易于医疗管理，但在许多低收入和中等收入国家，梅毒的控制仍是一项挑战。我们最近的研究表明，梅毒仍然控制不佳，治疗失败率和重复感染率很高。在秘鲁，男男性接触者中梅毒的发病率约为每100人年9例。我们建议进行一项研究，以提高我们对梅毒流行病学和分子生物学的理解，特别是在男男性接触者中。我们研究的关键将是接触患病率、发病率和重复感染率高的人群，以及我们机构与美国第一级研究人员和学术中心的合作。在目标1中，我们将招募一组梅毒高危的MSM和变性人，随访24个月以上，以测量梅毒的发病率。还将评估分子和免疫因素。在目标2中，我们将通过表征宿主、病原体和环境，以及随时间推移和组间比较的措施，确定持续反应性和治疗失败的分子和免疫学相关性。在目标3中，我们将利用目标1和2的研究结果开发一种改进的系统/算法，以加强梅毒感染的诊断和管理，通过技术和社区利益相关者的投入进行微调，并设计一项新的研究来评估其有效性。

DESCRIPTION (provided by applicant): Syphilis remains an uncontrolled infectious disease globally, with high prevalence and incidence in certain high risk populations, affecting more than 20% of men who have sex with men (MSM) in Peru. Syphilis is also an important cause of neonatal morbidity and mortality, and is associated with an increased risk of acquisition and transmission of the human immunodeficiency virus. Despite its public health importance and easy medical management, the control of syphilis represents a challenge in many low and middle income countries. We have shown recently that syphilis remains poorly controlled with high rates of treatment failure and repeat infection. The incidence of syphilis in MSM in Peru is about 9 cases per 100 person-years. We are proposing a study to improve our understanding of syphilis epidemiology and molecular biology, particularly among MSM. Key in our study will be access to a population with high prevalence, incidence and repeat infection, and the collaboration of our institution with first level researchers and academic centers in the U.S. In Aim 1, we will recruit a cohort of MSM and transgender persons at high risk for syphilis, for follow-up over 24 months, to measure incidence rates of syphilis. Molecular and immunological factors will also be assessed. In Aim 2, we will determine the molecular and immunologic correlates of persistent reactivity and treatment failure by characterizing the host, pathogen and environment, and comparing measures over time and between groups. In Aim 3 we will use the findings from Aims 1 and 2 to develop an improved system/algorithm to enhance the diagnosis and management of syphilis infection, fine-tune through input from technical and community stakeholders, and design a new study to assess its effectiveness.