NEEDLESTICK HCV EXPOSURE--VIROLOGIC & IMMUNOLOGIC EVENTS

丙型肝炎病毒（HCV）通过针刺事件从患者传播到卫生保健工作者（HCW）是一个重要且未被重视的问题。 在NIH资助的R 03试点研究中，我们观察到6.6%的卫生保健工作者通过针刺接触HCV阳性患者的血液获得感染;这一观察结果与之前的报告一致，即当源患者被记录为病毒血症时，传播率为10%。 随着住院患者中HCV感染的流行率上升，特别是在像我们这样的城市环境中，这个问题的严重性将增加。 例如，在巴尔的摩医院合作的联盟中，在过去的一年中，卫生保健工作者报告了150多起针头接触丙型肝炎病毒的事件。此外，我们知道，在过去一年中，这些医院至少发生了5起HCV传播事件。 为了解决这个问题，我们将进行一个多中心的前瞻性观察试验，针刺伤事件发生在巴尔的摩的医院。 我们将通过高危针刺事件定义HCV传播的风险，并确定源患者病毒特征和HCV特异性抗体应答对病毒传播的影响。 暴露的HCW将在暴露时入组，并随访12个月。 将在基线和暴露后2、4、6、8、12、24和52周采集血清和外周血单核细胞，用于详细的病毒学和免疫学分析。 还将对源患者HCV进行表征，包括病毒滴度和基因型、准种多样性和抗体结合。 为了检验源患者血清中的中和抗体可以防止传播的假设，我们将检测源血清中的抗E2抗体（NOB小于结合中和大于检测）。通过这些调查，我们将深入了解传播的风险因素以及与预防传播相关的因素。 我们将描述急性HCV感染后发生的免疫学和病毒学事件。将在感染最早期采集的血样中测量外周血CD 4对免疫显性T细胞表位的增殖反应;外周血CTL对特定肽的反应;以及培养的淋巴细胞细胞因子反应谱（Th 1/Th 2/Th 0）。 HCV-E2特异性抗体应答将随着时间的推移进行测量，根据病毒准种进化进行检查，并与感染结果相关。我们将通过早期感染过程探索HCV对外周血单个核细胞群体的嗜性，以确定宿主抗体对病毒/细胞相互作用的影响。通过创建参与医院联盟，与全市一线员工卫生从业人员协同合作，我们将更好地定义HCV传播的风险，定义急性HCV感染的早期事件，并创建一个平台，将来可以评估预防干预措施。

Transmission of Hepatitis C Virus (HCV) from patients to health care workers (HCW) through needlestick events is a significant and underappreciated problem. In an NIH funded R03 Pilot Study, we have observed that 6.6 percent of health care workers exposed through needlestick to blood from HCV positive patients acquired infection; this observation is in keeping with a previous report of 10 percent transmission when source patients were documented to be viremic. As prevalence rates of HCV infection among hospitalized patients rise, particularly in urban settings such as ours, this problem will increase in magnitude. For instance, among the coalition of Baltimore hospitals collaborating in this proposal, more than 150 needlestick exposures to HCV were reported by health care workers during the past year. Furthermore, we are aware of at least 5 episodes of HCV transmission occurring in those same hospitals over the past year. To address this problem, we will perform a multicenter prospective observational trial of needlestick events occurring at hospitals in Baltimore. We will define the risk of HCV transmission through high-risk needlestick events, and determine the influence of source patient virus characteristics and HCV-specific antibody responses on viral transmission. Exposed HCWs will be enrolled at the time of exposure, and followed through twelve months. Serum and peripheral blood mononuclear cells will be collected at baseline, and at 2, 4, 6, 8, 12, 24 and 52 weeks following exposure, for detailed virologic and immunologic analyses. Source patient HCV will also be characterized, including viral titer and genotype, quasispecies diversity, and antibody binding. To examine the hypothesis that neutralizing antibody in source patient sera may protect against transmission, we will assay source sera for anti-E2 antibodies (NOB less than neutralization of binding greater than assay). Through these investigations, we will gain insight into the risk factors for transmission, and factors associated with protection from transmission. We will characterize immunologic and virologic events occurring in response to acute HCV infection. Peripheral blood CD4 proliferative responses to immunodominant T cell epitopes; peripheral blood CTL responses to specific peptide; and cultured lymphocyte cytokine response profiles (Th1/Th2/Th0) will be measured in blood samples collected through the earliest stages of infection. HCV-E2 specific antibody responses will measured over time, examined in light of of viral quasispecies evolution, and correlated with outcome of infection. We will explore the tropism of HCV for peripheral blood mononuclear cell populations through the course of early infection, to determine the influence of host antibody on viral/cell interactions. Through the creation of the coalition of participating hospitals, in a synergistic collaboration with front-line employee health practitioners across the city, we will better define the risk of HCV transmission, define early events in acute HCV infection, and create a platform from which prophylactic interventions may be evaluated in the future.