Search For New and Emerging Etiologic Agents

肝炎病毒。美国正在研究急性或慢性非甲、乙、丙、丁、戊型肝炎患者的临床样本，以寻找传播媒介的生物学、血清学或分子证据。暴发性非甲到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被识别的病毒。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另一种水传播肝炎病毒存在的证据。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一个比以前认为的更大的公共卫生问题。我们正在研究它在全世界发展中国家和工业化国家的流行病学。获得猪感染戊型肝炎病毒（HEV）的血清学证据。从感染猪中分离到一株新的独特HEV毒株，并对其进行了鉴定。它被证明具有世界范围的分布。对猪操作人员和匹配的献血者进行的血清流行病学研究显示，猪操作人员体内HEV抗体过量，表明该病毒可能通过人畜共患传播。也获得了野生大鼠感染戊型肝炎病毒的类似血清学证据，目前正在寻找感染源。迄今为止，我们已成功地将该媒介从洛杉矶捕获的大鼠传播到同一物种的实验室大鼠（褐家鼠）。然而，传播一直很困难，这表明病毒以低滴度复制。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，分子生物学的现代技术被用于发现新的病毒。目前正将这些方法应用于输血相关肝炎或社区获得性肝炎患者的血清中，以寻找可能导致美国高达2%的此类肝炎和发展中国家高达三分之一肝炎的新型肝炎病毒。为了提高病毒发现的敏感性，我们正在将微阵列技术应用于向黑猩猩传播新病原体的尝试，黑猩猩是除人类之外唯一对所有五种已知人类肝炎病毒敏感的物种。初步结果令人鼓舞。同样，大约一半的非细菌性肠胃炎病例没有明确的病因。在与LID流行病学科的合作下，我们正在应用同样的方法来尝试识别新的肠胃炎药物。川崎病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正试图将川崎病儿童急性期临床样本中的一种假定的病原体传播给黑猩猩。初步结果令人鼓舞，但确证性研究的结果是否定的，这可能是因为现有的黑猩猩以前可能接触过假定的川崎病病原体。最近有报道称，感染轮状病毒与川崎病发病之间存在关联。我们正在重新评估我们将川崎病传染给黑猩猩的尝试，以确定这种联系是否可以得到证实。

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. 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 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 are attempting 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. Recently an association between infection with rotaviruses and the onset of Kawasaki disease has been reported. We are re-evaluating our attempts to transmit Kawaski disease to chimpanzees to determine if such an association can be confirmed.