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A，B，C，D，E肝炎患者的临床样本，以用于传播药物的生物学，血清学或分子证据。暴发性非A到肝炎的患者仍然是诊断性的谜，可能感染了一种或多种先前未识别的病毒。我们试图发现这种疾病的病因。我们在印度，埃及和沙特阿拉伯的血清ePIDEMIologic研究中存在额外的水传播肝炎病毒的证据。我们正在尝试从此类患者的临床标本中传输药物。肝炎病毒可能比以前想象的更大。我们正在研究其在全球发展和工业化国家的流行病学。获得了肝炎病毒（HEV）感染猪的血清学证据。从受感染的猪中回收了一种新的独特的HEV菌株，并表征了。它被证明具有全球分布。对猪处理者和匹配的献血者的血清ePIDEMIologology研究表明，在猪处理程序中对HEV的抗体过多，这表明该病毒可能会在人畜共形上传播。还获得了类似的血清学证据，以感染HEV，并寻求感染剂。迄今为止，我们已经成功地从被困在洛杉矶的大鼠传播到了同一物种的实验室大鼠（Rattus Norvegicus）。但是，传播很困难，表明该病毒在低滴度上复制。我们已经在SCID大鼠中准备了一个相对较高的病毒池。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，现代的分子生物学技术已用于发现新病毒。这些现在正在用于从输血相关性肝炎患者的前瞻性收集的血清中，以寻找新的肝炎病毒，这些病毒可能会导致美国15％的此类肝炎。为了提高特定病毒发现技术的敏感性（即能够放大独特序列而不用考虑序列的技术的技术），我们对现有技术进行了修改，以提高了测定的灵敏度。使用新技术，我们发现了两种以前未被认可的牛细节病毒，它们污染了大多数牛血清。这一发现对用牛精华素制备的生物学的安全具有影响。川崎病是幼儿威胁生命的疾病。它具有传染病的流行病学特征。 HVS和MHS试图将川崎疾病儿童急性期临床样本的推定剂传输到非人类灵长类动物。初步结果是有希望的。