Search For New and Emerging Etiologic Agents

肝炎病毒。来自美国急性或慢性非甲、乙、丙、丁、戊型肝炎患者的临床样本正在进行研究，以寻找可传播病原体的生物学、血清学或分子证据。暴发型非甲至戊型肝炎患者仍是一个诊断之谜，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。另一种水媒肝炎病毒存在的证据来自我们在印度、埃及和沙特阿拉伯的血清流行病学研究。我们正试图从这类患者的临床标本中传播一种病毒。戊型肝炎病毒可能正在成为一个比之前认为的更严重的公共卫生问题。我们正在研究其在全世界发展中国家和工业化国家的流行病学。获得了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、独特的HEV毒株，并对其进行了鉴定。它被证明在全球范围内都有分布。对猪饲养员和配对献血者的血清流行病学研究表明，猪饲养员对HEV的抗体过剩，这表明该病毒可能是通过人畜传播的。野鼠感染HEV的类似血清学证据也已获得，正在寻找感染剂。到目前为止，我们已经成功地将这种毒剂从被困在洛杉矶的老鼠身上传播给了同一物种的实验室老鼠(褐家鼠)。然而，传播一直很困难，这表明病毒以低滴度复制。确定老鼠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被用来发现新的病毒。这些药物现在正被应用于输血相关性肝炎或社区获得性肝炎患者的血清，以寻找新的肝炎病毒，这种病毒可能导致美国此类肝炎的2%，以及发展中国家高达三分之一的肝炎。为了提高病毒发现的敏感性，我们正在应用微阵列技术，试图将新的病毒传播到黑猩猩身上，黑猩猩是除人类之外唯一对所有五种公认的人类肝炎病毒敏感的物种。初步结果令人振奋。同样，大约一半的非细菌性胃肠炎病例没有公认的病因。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胃肠炎病原体。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推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否定的，可能是因为现有的黑猩猩可能以前接触过川崎病的推定病原体。最近，有报道称轮状病毒感染与川崎病的发病有关。我们正在重新评估我们将川崎病传播给黑猩猩的尝试，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.