NEEDLESTICK HCV EXPOSURE: VIROLOGIC & IMMUNOLOGIC EVENTS

丙型肝炎病毒(丙型肝炎病毒)通过针刺事件从患者传播给卫生保健工作者是一个重大且未得到充分认识的问题。在NIH资助的一项R03初步研究中，我们观察到，通过针头接触丙型肝炎病毒阳性患者的血液的医护人员中有6.6%获得感染；这一观察结果与先前报告的10%的传播是一致的，当时来源患者被记录为病毒携带者。随着住院患者中丙型肝炎病毒感染率的上升，特别是在像我们这样的城市环境中，这个问题的严重性将会增加。例如，在巴尔的摩医院联盟合作的这项提议中，在过去的一年里，卫生保健工作者报告了150多例接触丙型肝炎病毒的针头。此外，我们知道在过去的一年里，这些医院至少发生了5起丙型肝炎病毒传播。为了解决这个问题，我们将对巴尔的摩医院发生的针灸事件进行一项多中心前瞻性观察试验。我们将定义通过高危针刺事件传播丙型肝炎病毒的风险，并确定源患者病毒特征和丙型肝炎病毒特异性抗体反应对病毒传播的影响。接触过的卫生工作者将在接触时登记，并跟踪调查12个月。将在基线以及暴露后2、4、6、8、12、24和52周收集血清和外周血单个核细胞，以进行详细的病毒学和免疫学分析。还将对源患者丙型肝炎病毒进行特征分析，包括病毒滴度和基因型、准种多样性和抗体结合。为了验证来源患者血清中的中和抗体可能防止传播的假设，我们将检测来源血清中的抗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。我们将描述急性丙型肝炎病毒感染时发生的免疫学和病毒学事件。在感染初期采集的血液样本中，将测量外周血对免疫优势T细胞表位的增殖反应、外周血对特定多肽的CTL反应以及培养的淋巴细胞细胞因子反应谱(Th1/Th2/Th0)。随着时间的推移，将测量丙型肝炎病毒E2特异性抗体反应，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来探讨丙型肝炎病毒对外周血单核细胞群的趋向性，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，与全市一线员工健康从业者协同合作，我们将更好地定义丙型肝炎病毒传播的风险，定义急性丙型肝炎感染的早期事件，并创建一个未来可能评估预防性干预措施的平台。

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.