Search For New and Emerging Etiologic Agents

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，传播是困难的，这表明病毒以低滴度复制。 近年来，现代分子生物学技术已被用于发现新病毒。目前，这些技术正应用于输血相关或社区获得性肝炎患者的血清，以寻找可能导致美国2%的此类肝炎和发展中国家高达三分之一的肝炎的新肝炎病毒。为了提高病毒发现的敏感性，我们正在应用微阵列技术，试图将新的病原体传播给黑猩猩，黑猩猩是除人类以外唯一对所有五种公认的人类肝炎病毒易感的物种。初步结果是有希望的。同样，大约一半的非细菌性胃肠炎病例没有公认的病因。 我们与LID流行病学科合作，采用相同的方法来尝试识别新的胃肠炎病原体。 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试图将一种来自川崎患儿急性期临床样本的假定病原体传播给黑猩猩。初步结果是有希望的，但验证性研究一直是负面的，可能是因为现有的黑猩猩可能已经暴露于川崎病的推定代理人以前。

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 was difficult, suggesting that the virus replicates at low titer. Modern techniques of molecular biology have been used to discover new viruses in recent years. These are now being applied to sera from patients with transfusion-associated or community-acquired hepatitis in a search for new hepatitis viruses that may cause up 2% of such hepatitis in the US and up to one-third of hepatitis in developing countries. In an attempt to increase the sensitivity of virus discovery, we are applying microarray technology to attempts to transmit new agents to chimpanzees, the only species other than man that is susceptible to all five recognized human hepatitis viruses. Preliminary results are promising. Similarly, approximately one half of nonbacterial gastroenteritis cases have no recognized etiology. In collaboration with the Epidemiology Section, LID, we are applying the same approaches to attempts to identify new gastroenteritis agents. Kawasaki Disease is a life-threatening illness of young children. It has the epidemiologic characteristics of an infectious disease. The HVS and MHS have attempted to transmit a putative agent from acute phase clinical samples of children with Kawasaki Disease to chimpanzees. Preliminary results were promising but confirmatory studies have been negative, possibly because available chimpanzees may have been exposed to the putative agent of Kawasaki disease previously.