Detection of asymptomatic Salmonella enterica serotype Typhi and Paratyphi A carriage by serum antibodies targeting YncE

项目总结 伤寒和甲型副伤寒沙门氏菌(伤寒和甲型副伤寒)是主要原因 全球肠道(伤寒/副伤寒)热，影响1100多万人，导致130,000多人死亡 每年的死亡人数。一小部分急性感染的人会发展成慢性但临床上 胆道中的无症状感染，可持续数十年。由于伤寒沙门氏菌和甲型副伤寒 人类限制的病原体，慢性携带者可能在一个社区内起到感染宿主的作用， 通过粪便和尿液中细菌的间歇脱落而传播，并作为传播媒介 这些生物进入了以前未受感染的群落。因此，正确识别和对待 无症状的慢性携带者对肠热病的长期控制至关重要。目前，没有 识别无症状携带者的最佳检测方法。在这里，我们建议解决这一不足，并评估 伤寒和甲型副伤寒的一个新的生物标志物。我们最近发现，靶向抗体 在一项初步研究中，YncE(一种假定的ATP结合蛋白)可以准确地识别慢性携带者。我们的建议 将包括三个互补但独立的目标，将进一步表征这一诊断潜力 抗原及其作为抗原靶标的价值，用于(1)基于社区的携带者筛查，(2)作为预测 在急性疾病后发生携带者的风险，以及(3)在消除 马车。在目标1中，我们将使用横断面分析来评估抗YncE反应的流行率和 伤寒/副伤寒流行社区内的携带。然后，我们将应用贝叶斯潜在类模型来 研究血清抗YncE反应作为检测无症状的有效筛查工具的实用性 伤寒沙门氏菌和甲型副伤寒沙门氏菌在社区一级携带。在目标2中，我们将执行一项预期队列 分析急性后YncE抗体反应的存在、持久性和动力学特征 感染和持续脱落伤寒沙门氏菌或甲型副伤寒沙门菌的相关反应在目标3中，我们将 择期手术后血清抗-YncE反应的存在、持续和动力学特征 胆囊切除术以确定抗YncE抗体的下降是否可以作为治愈的测试。这样做的结果 分析可以为伤寒控制计划提供重要信息。

PROJECT SUMMARY Salmonella enterica serovars Typhi and Paratyphi A (S. Typhi and S. Paratyphi A) are the predominant causes of enteric (typhoid/paratyphoid) fever globally, affecting over 11 million people and resulting in over 130,000 deaths each year. A small percentage of acutely infected individuals develop a chronic, but clinically asymptomatic infection in the biliary tract that can persist for decades. Since S. Typhi and Paratyphi A are human-restricted pathogens, chronic carriers may act as reservoirs of infection within a community, contribute to transmission through intermittent shedding of bacteria in feces and urine, and act as vehicles for introducing these organisms into previously uninfected communities. Therefore, correctly identifying and treating asymptomatic chronic carriers is critical for the long-term control of enteric fever. Currently, there are no optimal assays for identifying asymptomatic carriers. Here, we propose to address this deficiency and evaluate a novel biomarker of S. Typhi and Paratyphi A carriage. We have recently identified that antibodies targeting YncE (a putative ATP-binding protein) could accurately identify chronic carriers in a pilot study. Our proposal will include 3 complementary, but independent aims that will further characterize the diagnostic potential of this antigen and its value as an antigenic target for (1) community-based screening of carriage, (2) as a predictor of risk of developing carriage following acute disease, and (3) its use as a test of cure following elimination of carriage. In Aim 1, we will use a cross-sectional analysis to assess the prevalence of anti-YncE responses and carriage within a typhoid/paratyphoid endemic community. We will then apply a Bayesian latent class model to examine the utility of using serum anti-YncE responses as an effective screening tool to detect asymptomatic S. Typhi and S. Paratyphi A carriers at the community level. In Aim 2, we will perform a prospective cohort analysis to characterize the presence, persistence, and kinetics of antibody responses to YncE following acute infection and correlate responses with persistent shedding of S. Typhi or S. Paratyphi A. In Aim 3, we will characterize the presence, persistence, and kinetics of serum anti-YncE responses following elective cholecystectomy to determine if a fall in anti-YncE antibodies can be used as a test of cure. The results of this analysis could significantly inform typhoid control programs.