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

项目摘要 伤寒和甲型副伤寒沙门氏菌血清型。伤寒和沙门氏菌。甲型副伤寒是主要的病因 肠（伤寒/副伤寒）热在全球范围内蔓延，影响超过1 100万人， 每年死亡。一小部分急性感染者会发展为慢性，但临床上 胆道无症状感染，可持续数十年。自S.伤寒和甲型副伤寒是 人类限制的病原体，慢性携带者可以作为社区内的感染宿主， 通过粪便和尿液中细菌的间歇性脱落传播，并作为引入的媒介 这些生物进入以前未感染的社区。因此，正确识别和治疗 无症状的慢性带菌者对长期控制肠热病至关重要。目前没有 用于识别无症状携带者的最佳检测方法。在这里，我们建议解决这一缺陷，并评估 一种新的S.伤寒和副伤寒一辆马车。我们最近发现， 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3个互补的，但独立的目标，将进一步表征诊断潜力， 抗原及其作为抗原靶点的价值，用于（1）以社区为基础的携带筛查，（2）作为 急性疾病后发展为携带的风险，以及（3）其作为消除后的治愈测试的用途， 马车在目标1中，我们将使用横断面分析来评估抗YncE应答的患病率， 伤寒/副伤寒流行社区内的传播。然后，我们将应用贝叶斯潜在类模型， 检查使用血清抗YncE应答作为检测无症状性 S.伤寒和沙门氏菌。社区一级的甲型副伤寒携带者。在目标2中，我们将进行前瞻性队列研究， 分析，以表征急性免疫后对YncE的抗体应答的存在、持续性和动力学。 感染和相关反应与持续脱落的S.伤寒或S.甲型副伤寒在目标3中，我们 表征选择性免疫后血清抗YncE应答的存在、持续性和动力学 胆囊切除术以确定抗YncE抗体的下降是否可用作治愈的测试。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.