Prospective Studies of Avian Influenza Transmission in Asia

描述（由申请人提供）：H5N1 禽流感疫情已在亚洲肆虐多个物种，目前正威胁着美国。国家应对计划要求积极进行人类病例识别、使用抗病毒药物、隔离，并可能进行隔离。大流行计划所依赖的数学模型缺乏传播率和病毒传染性等基本客观数据。由于亚洲的人类疾病检测是基于临床情况，因此对于亚临床感染或 H5N1 感染的危险因素知之甚少。在这项拟议研究中，我们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，我们将对居住在亚洲三个 H5N1 流行区（印度尼西亚唐格朗）的 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、开放家禽市场工人）和 300 名年龄组和性别匹配的非接触对照者进行 H5N1 传播的对照、三年期前瞻性研究。印度尼西亚巴厘岛；和柬埔寨坎大省。该研究将包括对研究参与者中的流感样疾病进行积极主动的监测（通过鼻咽拭子和血清采样），对参与者进行年度系列血清学随访，并通过家访，对接触过流感感染研究对象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，我们的中心假设是，H5N1 流感感染在这些工人中会频繁发生，我们将能够估计 H5N1 感染的患病率和发病率，并且我们将能够识别 H5N1 感染风险最高的人员。我们特别适合开展这项工作，因为我们在进行流感传播的流行病学和实验室研究方面拥有丰富的经验，并且我们在现场的国家和地方公共卫生官员之间有着出色的合作。这项研究的创新之处在于，尚未对在 H5N1 流行地区因职业接触家禽的人员进行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.