Search For New and Emerging Etiologic Agents

寻找新的和正在出现的病原体

• 批准号: 6985036
• 负责人: Robert H. Purcell
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6985036
• 关键词: Ceboidea; Cercopithecidae; Pan; Parvoviridae; clinical research; communicable disease diagnosis; communicable disease transmission; diagnosis design /evaluation; disease /disorder etiology; emerging infectious disease; enzyme linked immunosorbent assay; hepatitis; hepatitis virus; human tissue; infectious hepatitis; laboratory rat; mucocutaneous lymph node syndrome; serology /serodiagnosis; zoonosis

Hepatitis viruses. Clinical samples from patients with acute or chronic non-A, B, C, D, E hepatitis in the United States are being studied for biological, serological or molecular evidence of transmissible agents. Patients with fulminant non-A to E hepatitis remain a diagnostic enigma and may be infected with one or more previously unrecognized viruses. We are attempting to discover the etiology of this disease. Evidence for the existence of an additional water-borne hepatitis virus has come from our seroepidemiologic studies in India, Egypt and Saudi Arabia. We are attempting to transmit an agent from clinical specimens of such patients. Hepatitis E virus may be emerging as a greater public health problem than previously thought. We are studying its epidemiology in developing and industrialized countries worldwide. Serologic evidence of infection of swine with hepatitis E virus (HEV) was obtained. A new and unique HEV strain was recovered from infected swine and characterized. It was shown to have a worldwide distribution. Seroepidemiological studies of swine handlers and matched blood donors have shown an excess of antibody to HEV in swine handlers, suggesting that the virus may be zoonotically spread. Similar serologic evidence for infection of wild rats with HEV has also been obtained and the infecting agent is being sought. To date we have successfully transmitted the agent from rats trapped in Los Angeles to laboratory rats of the same species (Rattus norvegicus). However, transmission has been difficult, suggesting that the virus replicates at low titer. We have prepared a relatively high-titered pool of the virus in SCID rats. Studies to determine if rat HEV is linked to human infection are in progress. Modern techniques of molecular biology have been used to discover new viruses in recent years. These are now being applied to prospectively collected sera from patients with transfusion-associated hepatitis in a search for new hepatitis viruses that may cause up to 15% of such hepatitis in the US. In an attempt to increase the sensitivity of specific virus discovery technologies (i.e., those capable of amplifying unique sequences without regard to the sequence), we have introduced modifications to existing techniques that have improved the sensitivity of the assay. Using the new technology, we have discovered two previously unrecognized bovine parvoviruses that contaminate most lots of bovine serum. This finding has implications for the safety of biologicals that are prepared with bovine serum. Kawasaki Disease is a life-threatening illness of young children. It has the epidemiologic characteristics of an infectious disease. The HVS and MHS are attempting to transmit a putative agent from acute phase clinical samples of children with Kawasaki Disease to nonhuman primates. Preliminary results have been promising.

肝炎病毒。正在研究美国急性或慢性非甲、B、C、D、E型肝炎患者的临床样本，以获得传染性因子的生物学、血清学或分子学证据。暴发性非甲至戊型肝炎患者的诊断仍然是一个谜，可能感染了一种或多种以前未识别的病毒。我们正试图找出这种疾病的病因。我们在印度、埃及和沙特阿拉伯进行的血清流行病学研究提供了存在另一种水传播肝炎病毒的证据。我们正试图从这些病人的临床标本中传播一种病原体。戊型肝炎病毒可能正在成为比以前认为的更大的公共卫生问题。我们正在全世界发展中国家和工业化国家研究其流行病学。获得了戊型肝炎病毒（HEV）感染猪的血清学证据。从感染的猪中回收了一种新的独特的戊型肝炎病毒株，并对其进行了表征。它被证明有一个世界性的分布。对猪处理者和匹配的献血者的血清流行病学研究表明，猪处理者中存在过量的HEV抗体，表明该病毒可能是动物源性传播的。也获得了野生大鼠感染戊型肝炎病毒的类似血清学证据，并正在寻找感染因子。到目前为止，我们已经成功地将这种病原体从洛杉矶的老鼠身上传播到同一物种的实验室老鼠（褐家鼠）身上。然而，传播一直很困难，这表明病毒以低滴度复制。我们已经在SCID大鼠中制备了相对高滴度的病毒库。确定大鼠HEV是否与人类感染有关的研究正在进行中。近年来，现代分子生物学技术已被用于发现新病毒。目前，这些方法正被应用于前瞻性收集的输血相关肝炎患者血清，以寻找可能导致美国15%此类肝炎的新肝炎病毒。为了增加特定病毒发现技术的灵敏度（即，能够扩增独特序列而不考虑序列的那些），我们已经引入了对现有技术的改进，这些改进已经提高了测定的灵敏度。利用这项新技术，我们发现了两种以前未被识别的牛细小病毒，它们污染了大多数批次的牛血清。这一发现对用牛血清制备的生物制品的安全性有影响。川崎是一种危及幼儿生命的疾病。它具有传染病的流行病学特征。HVS和MHS正试图将一种来自川崎患儿急性期临床样本的推定病原体传播给非人灵长类动物。初步结果令人鼓舞。