Prospective Studies of Avian Influenza Transmission in Asia

描述（由申请人提供）：在亚洲肆虐多种物种的H5N1禽流感疫情现在威胁到美国。国家应对计划要求积极识别人间病例、使用抗病毒药物、隔离和可能的隔离。大流行计划所依赖的数学模型缺乏基本的客观数据，如传播率和病毒传染性。由于亚洲的人类疾病检测是基于临床接触，因此对亚临床感染或H5N1感染的危险因素知之甚少。我们在这项拟议研究中的长期目标是从流行病学角度描述临床和亚临床H5N1传播，以便公共卫生官员可以设计适当的H5N1监测和控制措施。在这项工作中，我们将在900名职业接触家禽的成年人（家禽养殖户、家禽业工人、肉类加工工人、家禽露天市场工人）和300名年龄和性别匹配的未接触者中开展一项为期三年的对照研究，调查H5N1传播情况。这些人生活在亚洲三个H5N1流行区：印度尼西亚丹格朗；印尼巴厘岛;以及柬埔寨的干达尔省。该研究将包括积极主动地监测研究参与者中的流感样疾病（使用鼻咽拭子和血清取样），每年对参与者进行系列血清学随访，并通过家访对暴露于研究受试者并发生流感感染的家庭成员进行类似的研究。微量中和血清学技术、RT-PCR和病毒培养将用于确定流感感染的结果。我们的目标是确定既往H5N1流感感染证据的血清流行率，估计H5N1流感感染的年发病率，估计继发性H5N1流感感染率，并确定H5N1流感感染的危险因素。根据初步数据，我们的主要假设是，H5N1流感感染将在这些工作人员中频繁发生，我们将能够估计H5N1感染的流行率和发病率，并且我们将能够确定H5N1感染风险最高的人。我们特别适合开展这项工作，因为我们在开展流感传播的流行病学和实验室研究方面拥有丰富的经验，而且我们在国家和地方的公共卫生官员之间在实地开展了出色的合作。这项研究的创新之处在于，没有在H5N1流行地点职业接触禽类的人员中进行此类禽流感感染的前瞻性研究。

DESCRIPTION (provided by applicant): The H5N1 avian influenza epidemic that has ravaged multiple species in Asia, now threatens the United States. National response plans call for aggressive human case identification, antiviral use, isolation, and possibly quarantine. The mathematical models upon which the pandemic plans rely lack fundamental objective data such as transmission rates and virus infectiousness. As human disease detection in Asia is based upon clinical encounters, little is known regarding subclinical infections or risk factors for H5N1 infection. Our long term goa/in this proposed research is to epidemiologically describe clinical and subclinical H5N1 transmission such that public health officials might design appropriate H5N1 surveillance and control measures. In this effort we will conduct a controlled, three-year, prospective study of H5N1 transmission among 900 adults occupationally exposed to poultry (poultry farmers, poultry industry workers, meat processing workers, open poultry market workers), and 300 age-group and gender matched non-exposed controls living in three H5N1 endemic areas in Asia: Tangerang, Indonesia; Bali, Indonesia; and Kandaal Province, Cambodia. The study will involve aggressive active surveillance for influenza-like illness among study participants (with nasopharyngeal swab and serum sampling), annual serial serological follow-up of participants, and through home visits, similar studies of the family members exposed to study subjects who develops influenza infection. Microneutralization serologic techniques, RT-PCR, and viral culture will be used to determine influenza infection outcomes. Our objectives are to determine the seroprevalence of evidence of previous H5N1 influenza infection, to estimate the annual incidence of H5N1 influenza infection, to estimate secondary H5N1 influenza infection rates, and to determine risk factors for H5N1 influenza infection. Based upon preliminary data, our central hypotheses are that H5N1 influenza infection will be frequent among these workers, that we will be able to estimate the prevalence and incidence of H5N1 infection, and that we will be able to identify persons at highest risk of H5N1 infection. We are particularly well-suited to conduct this work as we have extensive experience conducting both epidemiological and laboratory-based studies of influenza transmission, and we have exceptional cooperation among public health officials nationally and locally at the field sites. This study is innovative in that no such prospective studies of avian influenza infection have been performed among those person's occupationally exposed to poultry in H5N1 endemic sites.