SGER: Ciguatera Fish Poisoning: Dinoflagellate Dynamics, Toxin Formation, and Economic Impacts

雪卡特拉是一种复杂的临床综合征，由食用被热带地区底栖恐鞭毛虫冈比亚毒素污染的鱼类引起。它是与有害藻华(赤潮)相关的最常见的疾病形式，也是迄今为止对公共健康和潜在经济影响最大的一种疾病。最近，随着人均海鲜消费量的增加和区域间海产品贸易的增长，雪卡特拉事件已经超出了传统的毒素范围。在这一小额探索研究拨款(SGER)的支持下，伍兹霍尔海洋研究所的研究人员将开始研究加勒比海有毒冈比亚圆盘鱼物种的动态，雪卡特拉毒素的形成机制，以及美属维尔京群岛(USVI)雪卡特拉鱼中毒(CFP)对人类健康和经济的影响。这项拟议研究的具体目的是：(1)评估暴露在USVI的雪卡特拉对健康的影响和相关的经济影响；(2)调查环境因素和其他压力对USVI珊瑚礁系统的关系、有毒冈比亚鱼物种的动态以及相关的人类CFP病例；以及(3)评估来自毒冈比亚的冈比亚毒素激活调节鱼类生物转化酶表达的信号通路的能力。将进行几项探索性调查以实现这些目标。关于整个大西洋/加勒比海地区接触雪卡特拉毒素对健康的影响(已知的疾病事件)的信息，将与关于成本(治疗和生产力损失)的代表性数据相结合，以初步估计与接触雪卡特拉毒素有关的年度经济损失，并区分不同地区(佛罗里达州、美国西弗吉尼亚州等)。其次，该小组将着手建立下列时间序列：1)已知的两个关键地点的冈比亚毒素的分布、丰度和种群结构；2)这些地点珊瑚礁健康的变化(例如，珊瑚漂白程度、大型藻类过度生长、风暴影响)；3)鱼类中的毒素浓度和结构多样性；以及4)医院和诊所中CFP引起的人类中毒发生率。对鱼类的毒理学研究将作为了解鱼类将毒藻中的冈比亚毒素转化为更有效的雪卡毒素的机制的第一步，而雪卡毒素是引起CFP的原因。这些实验将包括使用克隆的受体和报告基因进行基于细胞的分析，以及使用微阵列分析暴露在冈比亚毒素下的斑马鱼的基因表达。就更广泛的影响而言，这些研究将扩大伍兹霍尔海洋和人类健康中心(COHH)的范围，并将聘请目前与该中心无关的调查人员，包括美国食品和药物管理局(FDA)和维尔京群岛大学的科学家。由于后者是一家为少数群体服务的机构，拟议的活动将扩大COHH计划，以增加代表不足的群体的参与，包括将作为这一努力的一部分获得培训的UVI学生。由于这个项目而发展的伙伴关系将导致长期的、共同的努力，以了解CFP。该项目还将加强几个COHH中心的研究人员之间的联系，特别是伍兹霍尔、哈瓦伊和迈阿密中心之间的联系，这些中心现在都将在世界不同地区从事CFP的研究。现有和加强的关系将促进各中心和区域之间的信息交流和成果整合。

Ciguatera is a complex clinical syndrome caused by the consumption of fish contaminated with toxins that originate from the benthic dinoflagellate Gambierdiscus toxicus in tropical regions. It is the most common form of illness associated with harmful algal blooms (HABs), and the one with by far the greatest public health and potential economic impact. Recently, incidents of ciguatera have expanded beyond the traditional range of the toxin with increased per capita consumption of seafood and growing interregional seafood trade.With support from this Small Grant for Exploratory Research (SGER), researchers at the Woods Hole Oceanographic Institution will initiate studies on the dynamics of toxic Gambierdiscus species in the Caribbean, the mechanisms of ciguatera toxin formation, and the human health and economic impacts of ciguatera fish poisoning (CFP) in the U.S Virgin Islands (USVI). The specific aims of the proposed research are: (1) to assess the health effects and associated economic impacts from ciguatera exposure in the USVI; (2) to investigate the relationships between environmental factors and other stresses to coral reef systems in the USVI, the dynamics of toxic Gambierdiscus species, and associated cases of CFP in humans; and (3) to assess the ability of gambiertoxins from G. toxicus to activate signaling pathways regulating the expression of biotransformation enzymes in fish.Several exploratory investigations will be taken to accomplish these goals. Information on health effects (known incidents of illness resulting from ciguatera toxin exposure) throughout the Atlantic/Caribbean range of the toxin will be combined with representative data on cost (treatment and lost productivity) to generate an initial estimate of the annual economic loss associated with ciguatera exposure, distinguishing among regions (Florida, USVI, etc.). Secondly the team will initiate efforts to establish time series on: 1) the distribution, abundance, and population structure of Gambierdiscus toxicus in two key locations known to harbor populations of this species; 2) changes to reef health in these same locations (e.g., extent of coral bleaching, macroalgal overgrowth, storm impacts); 3) toxin concentrations and structural diversity in fish; and 4) incidence of human poisonings from CFP in hospitals and clinics. The toxicological studies with fish will serve as an initial step in understanding the mechanisms by which gambiertoxins from G. toxicus are converted by fish to the more potent ciguatoxins that are the cause of CFP. The experiments will involve cell-based assays using cloned receptors and reporter genes, as well as analysis of gene expression in gambiertoxin-exposed zebrafish using microarrays. In terms of broader impacts, these studies will expand the scope of the Woods Hole Centers for Oceans and Human Health (COHH) and will engage investigators not currently affiliated with the center, including scientists at the U.S. Food and Drug Administration (FDA) and University of the Virgin Islands. Because the latter is a minority-serving institution, the proposed activities will broaden the COHH program to increase the participation of under-represented groups, including UVI students who will obtain training as part of this effort. The partnerships developed as a result of this project will lead to longer-term, joint efforts to understand CFP. This project also will strengthen the ties between researchers at several COHH centers, and in particular between the Woods Hole, Hawai?i, and Miami centers, all of whom will now be engaged in research on CFP in different parts of the world. The existing and enhanced relationships will promote the exchange of information and integration of results across centers and regions.