Leptospirosis in California sea lions: Population impacts and persistence in a long-term study of infectious disease in marine mammals

尽管越来越多的确凿证据表明，传染病对海洋生态系统有巨大影响，但海洋系统的疾病生态学研究仍落后于陆地系统。特别需要进行长期案例研究，利用定量准确的数据和明确的生物学特征，以便研究海洋学过程如何影响病原体传播以及气候变化将如何改变疾病影响。这个独特的项目将开展一个综合的现场、临床、实验室和建模研究方法，以建立一个加利福尼亚海狮（CSL; Zalophus California）审问钩端螺旋体动态的案例研究。至少自1984年以来，钩端螺旋体病在CSL引起周期性的季节性暴发，导致每3-4年发生一次重大疾病暴发。pi将调查钩端螺旋体病对CSL种群动态的定量影响，以及使L.询问者在过去三十年中持续存在的机制。该项目将回答以下假设：1。来自搁浅CSL的数据提供了在自由放养的人群中，询问乳杆菌流行的长期动态的定量信息2。在疾病爆发期间，L.疑问菌感染超过20%的CSL种群，并杀死1-2%的受感染CSL，从而影响CSL种群动态。该项目将利用这些数据开发一个数学模型，该模型集成了免疫学和搁浅数据，然后可以预测每年感染CSL的人口比例。疑问乳杆菌在CSL群体中持续存在，其持续存在的机制涉及慢性无症状携带者状态和随后CSL个体对疑问乳杆菌的脱落。一个长期存在的谜题是病原体如何在两次暴发之间的6-8个月内持续存在。pi将进行病理学研究，以确定CSL是否会成为疑问乳杆菌的慢性携带者，并将在疾病没有爆发时对自由放养的CSL个体进行抽样，以寻找无症状的脱落者。该项目将建立L.审问/CSL系统，作为海洋哺乳动物传染病的独特而有力的案例研究，使后续研究能够对气候变化的影响及其与更广泛的沿海生态系统的联系进行研究。这项研究的广泛影响将涉及跨学科科学的研究生、兽医和博士后的培训。与加州大学洛杉矶分校的一个项目合作，将通过制作有关研究的视频供课堂和在线观看，来吸引少数族裔和生活困难的本科生，从而促进未被充分代表的群体的接触和参与。调查结果将通过游客中心之旅和每年覆盖13万人的流动K-12课程进行传播。最后，这项研究将为全球钩端螺旋体病的水库控制提供信息，结果将通过美国海洋哺乳动物委员会和其他专业协会的pi领导职位与环境和健康研究人员和决策者分享。

Despite increasingly stark evidence that infectious diseases have dramatic effects on marine ecosystems, research on disease ecology in marine systems has lagged behind that in terrestrial systems. There is a particular need for long-term case studies, with quantitatively accurate data and well-characterized biology, to enable research into how oceanographic processes affect pathogen spread and how disease impacts will be altered by climate change. This unique project will carry out an integrated field, clinical, laboratory and modeling research approach to establish a case study for the dynamics of Leptospira interrogans in California sea lions (CSL; Zalophus californianus). Leptospirosis has caused recurrent seasonal outbreaks in CSL since at least 1984, resulting in major disease outbreaks every 3-4 years. The PIs will investigate the quantitative impact of leptospirosis on CSL population dynamics and the mechanism that has enabled L. interrogans to persist in the CSL population over the past three decades. The project will answer the following hypotheses: 1. Data from stranded CSL provide quantitative information on long-term dynamics of L. interrogans prevalence in the free-ranging population, 2. L. interrogans impacts CSL population dynamics by infecting more than 20% of the CSL population during disease outbreaks, and killing 1-2% of infected CSL. The project will use this data to develop a mathematical model that integrates immunological and stranding data, which will then allow for predictions of the fraction of the CSL population that is infected each year, 3. L. interrogans is persistent in the CSL population, and the mechanism of persistence involves a chronic asymptomatic carrier state and subsequent shedding of L. interrogans by individual CSL. A longstanding puzzle concerns how the pathogen persists in the 6-8 month interval between outbreaks. The PIs will conduct a pathology study to determine whether CSL can become chronic carriers of L. interrogans, and will also sample free-ranging CSL individuals when disease outbreaks are not occurring to search for asymptomatic shedders. This project will establish the L. interrogans/CSL system as a unique and powerful case study for infectious disease in marine mammals, enabling subsequent research into impacts of climate change and connections to the broader coastal ecosystem.The broader impacts of this study will involve training graduate, veterinary, and postdoctoral students in interdisciplinary science. Outreach and involvement of underrepresented groups will be facilitated by a partnership with a UCLA program to engage minority and life-challenged undergraduates by making videos about the research for classroom and online viewing. Findings will be communicated using visitor center tours and mobile K-12 programs reaching 130,000 people per year. Finally, the research will inform reservoir control for leptospirosis worldwide and the results will be shared with environmental and health researchers and policymakers via the PIs leadership positions in the U.S. Marine Mammal Commission and other professional associations.