Syphilis: Translating technology to understand a neglected epidemic

描述(申请人提供)：梅毒在全球范围内仍然是一种不受控制的传染病，在某些高危人群中具有高流行率和发病率，影响秘鲁20%以上的男男性行为者(MSM)。梅毒也是新生儿发病率和死亡率的重要原因，并与感染和传播人类免疫缺陷病毒的风险增加有关。尽管梅毒对公共卫生很重要，而且易于医疗管理，但在许多低收入和中等收入国家，梅毒的控制是一项挑战。我们最近表明，梅毒的控制仍然很差，治疗失败和重复感染的比率很高。秘鲁男男性接触者梅毒发病率约为每100人年9例。我们正在提议进行一项研究，以提高我们对梅毒流行病学和分子生物学的了解，特别是在MSM中。我们研究的关键将是接触到高患病率、发病率和重复感染的人群，以及我们机构与美国一流研究人员和学术中心的合作。在目标1中，我们将招募一组MSM和变性人作为梅毒高危人群，进行超过24个月的随访，以衡量梅毒的发病率。还将评估分子和免疫学因素。在目标2中，我们将通过描述宿主、病原体和环境的特征，并比较不同时间和不同组之间的措施，来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和目标2的结果来开发一个改进的系统/算法，以加强梅毒感染的诊断和管理，通过技术和社区利益攸关方的意见进行微调，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.