Ecology of Andes & Choclo Viruses

描述（由申请方提供）：汉坦病毒是NIH A类病原体，包括在北美、中美和南美引起汉坦病毒心肺综合征（HCPS）的病毒。智利（384例）和阿根廷（595例）报告的HCPS病例和死亡人数，尽管人口少得多，但超过了美国（379例）报告的病例数，北美和南美的病死率保持在36-38%。目前还没有有效的治疗方法或疫苗。在项目1“安第斯山脉生态学和Choclo病毒”中，我们将研究智利和巴拿马啮齿动物宿主的生态学，以开发预测模型和对远程监测结果的快速解释，指导公共卫生干预。在项目2“HCPS的治疗和预防”中，我们将完成一项在心肺阶段疑似HCPS患者中静脉注射甲泼尼龙的对照试验，继续通过血浆置换法收集安第斯山脉病毒感染幸存者的血浆，并使用具有高滴度安第斯山脉病毒中和活性（HIP）的免疫血浆进行三项临床试验。第一项HIP试验将是在a）正常成人和B）HCPS患者中进行的I期、剂量递增安全性和药代动力学试验。第二项试验将是一项在发生HCPS高风险人群（发生HCPS风险20%的HCPS索引患者的性伴侣）中进行的开放性HIP安全性和有效性试验。第三项试验将是一项在心肺阶段疑似HCPS患者中进行的HIP对照试验。在项目3中，我们将改进我们的研究，试图了解哪些因素使性伴侣比非性伴侣家庭接触者感染的风险高得多。我们将a）前瞻性地跟踪性伴侣的家庭接触者，B）发放调查问卷以评估风险，如共同源暴露、性行为和深吻，以及c）研究生殖器、口腔和皮肤分泌物，包括每天在家收集唾液拭子，以确定是否可以通过PCR鉴定出安第斯山脉病毒RNA，以及是否可以从PCR阳性样本中培养出病毒。 项目1：安第斯山脉生态学和Choclo病毒（Glass，G.） 项目1描述（由申请方提供）：认为由西半球任何一种汉坦病毒引起的汉坦病毒心肺综合征是通过吸入受感染的啮齿动物排泄物感染的。在智利南部和中部，安第斯山脉病毒感染了sigmodontine啮齿动物Oligoryzomys longicaudatus，并导致罕见但严重的人类感染，死亡率很高。在巴拿马西部，Choclo病毒感染啮齿动物Oligoryzomys fulvescens，并导致常见但通常轻微或不明显的人类感染，死亡率低。在这两个区域，传播风险似乎受到许多因素的影响，增加了受感染啮齿动物和易感人群之间密切接触的机会。我们将集中研究其中的三个因素，目的是获得对设计未来环境干预措施以减少汉坦病毒传播至关重要的见解。 首先，最近在智利和巴拿马进行的调查发现，感染风险与受感染的病媒啮齿动物喜欢的选定植被生境有关。在智利，可以通过遥感和卫星图像分析预测该国2/3地区的接触风险。在巴拿马，一项微型分析表明，受感染的啮齿类动物与农业活动之间存在复杂的关系。我们建议专注于啮齿动物和栖息地之间的空间关系随着时间的推移，使用标记-再捕获诱捕和无线电遥测标记啮齿动物的运动，特别是在peridomestic环境。其次，我们将创建一个动态模型，扩展我们当前的静态风险分析。新模型将应用图论来现场收集啮齿动物栖息地偏好和景观内运动的数据，以预测受感染啮齿动物的可能运动。我们将使用来自与创建模型不同的站点的数据来测试模型。将通过在冬季（低传播）和春季（高传播）季节定量啮齿动物血液、组织和尿液中的病毒载量来提高模型的时间精度。最后，对巴拿马高危人群的系列血清调查将量化啮齿动物密度和活动的时空变化对人类感染的影响。

DESCRIPTION (provided by applicant): Hantaviruses are NIH category A pathogens, including the viruses that cause hantavirus cardiopulmonary syndrome (HCPS) in North, Central and South America. Reported cases and deaths from HCPS in Chile (384) and Argentina (595), despite much smaller populations, outnumber cases reported in the United States (379), and case fatality rates remain at 36-38% in North and South America. There is no known effective treatment or vaccine. In Project 1, Ecology of Andes and Choclo Viruses, we will study the ecology of the rodent reservoirs in Chile and Panama to develop predictive models and rapid interpretation of results from remote monitoring to guide public health intervention. In Project 2, Treatment and Prevention of HCPS, we will complete a controlled trial of intravenous methylprednisolone in persons with suspected HCPS in the cardiopulmonary phase, continue collection of plasma by plasmapheresis of survivors of Andes virus infection and perform three clinical trials with immune plasma with high titers of Andes virus neutralizing activity (HIP). The first trial with HIP will be a phase I, dose-escalation safety and pharmacokinetics trial in a) normal adults and b) persons with HCPS. The second trial will be an open safety and efficacy trial of HIP in persons at high risk of developing HCPS (sex partners of index patients with HCPS who have a 20% risk of developing HCPS). The third trial will be a controlled trial of HIP in persons with suspected HCPS in the cardiopulmonary phase. In Project 3, we will refine our studies to try to learn what factors put sex partners at significantly higher risk of infection than nonsex partner household contacts. We will a) prospectively follow sex partner household contacts, b) administer questionnaires to assess risks such as common source exposure, sexual practices and deep kissing and c) study genital, oral and dermal secretions, including daily home collection of saliva swabs, to determine whether Andes virus RNA can be identified by PCR and whether virus can be cultured from PCR-positive samples. PROJECT 1: Ecology of Andes & Choclo Viruses (Glass, G.) PROJECT 1 DESCRIPTION (provided by applicant): Hantavirus cardiopulmonary syndrome resulting from any of a number of hantaviruses in the western hemisphere is thought to be contracted through inhalation of infected rodent excreta. In southern and central Chile, the Andes virus infects the sigmodontine rodent Oligoryzomys longicaudatus, and causes a rare but severe human infection with high mortality. In western Panama, the Choclo virus infects the rodent Oligoryzomys fulvescens and causes a common but usually mild or inapparent human infection with a low mortality rate. In both regions the risk of transmission appears to be influenced by many factors increasing the opportunity for close contact between infected rodents and susceptible humans. We will focus our investigations on three of these factors, with the goal of gaining insights critical for the design of future environmental interventions to decrease hantavirus transmission. First, recent investigations in Chile and Panama have associated risk of infection with selected vegetation habitats favored by the infected vector rodents. In Chile exposure risk can be predicted by remote sensing with satellite imagery analysis over 2/3 of the country. In Panama a micro scale analysis has suggested complex relationships between peridomestic infected rodents and agricultural activities. We propose to focus on spatial relationships between rodents and habitats over time, using mark-recapture trapping and radiotelemetry to mark rodent movements, particularly in peridomestic environments. Second we will create a dynamic model that extends our current static analysis of risk. The new model will apply graph theory to field collected data of rodent habitat preferences and movements within the landscape to predict the likely movement of infected rodents. We will test the model using data from sites different from those used to create the model. The temporal precision of the model will be improved by quantitating viral load in rodent blood, tissue, and urine in the winter (low transmission) and spring (high transmission) seasons. Finally, serial serosurveys of at-risk human populations in Panama will quantify the impact on human infection associated with spatial-temporal variations in rodent density and movement.