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

雪卡毒是一种复杂的临床综合症，由食用受毒素污染的鱼类引起，这些毒素来自热带地区的底栖甲藻Gambierdiscus toxicus。这是与有害藻华（HABs）相关的最常见的疾病形式，也是迄今为止对公共卫生和潜在经济影响最大的疾病。最近，随着人均海产品消费量的增加和区域间海产品贸易的增长，雪卡毒素事件已经超出了传统的毒素范围。在探索性研究小额赠款（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地区有毒甘比盘鱼物种的动态、雪卡毒素形成的机制、以及美属维尔京群岛（USVI）雪卡毒鱼中毒（CFP）对人类健康和经济的影响。 拟议研究的具体目的是：（1）评估美属维尔京群岛暴露于雪卡毒素对健康的影响和相关的经济影响;（2）调查环境因素和其他对美属维尔京群岛珊瑚礁系统的压力之间的关系、有毒甘比尾藻物种的动态，以及人类的相关CFP病例;以及（3）评估来自甘比尾藻的甘比尾藻毒素的能力。本研究将探讨鱼类毒素对鱼类生物转化酵素表达之影响，并将进行几项探索性研究以达成这些目标。 将把有关整个大西洋/加勒比海地区的雪卡毒素对健康影响的资料（已知的因接触雪卡毒素而致病的事件）与有关费用（治疗和生产力损失）的代表性数据结合起来，以产生与接触雪卡毒素有关的年度经济损失的初步估计，并区分各区域（佛罗里达、美属维尔京群岛等）。 其次，该小组将着手建立以下时间序列：1）已知该物种栖息地的两个关键地点的毒性甘比盘鱼的分布、丰度和种群结构; 2）这些地点珊瑚礁健康状况的变化（例如，（a）珊瑚漂白程度、大型藻类过度生长、风暴影响）;（b）鱼类毒素浓度和结构多样性;以及（c）医院和诊所中CFP造成的人类中毒发生率。 对鱼类的毒理学研究将作为了解来自G。毒素被鱼转化为更强的雪卡毒素，这是CFP的原因。这些实验将涉及使用克隆受体和报告基因的基于细胞的测定，以及使用微阵列分析暴露于冈比亚毒素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与人类健康中心（COHH）的范围，并将吸引目前不隶属于该中心的研究人员，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。由于后者是一个为少数群体服务的机构，拟议的活动将扩大COHH方案，以增加代表性不足的群体的参与，包括将作为这一努力的一部分接受培训的UVI学生。由于这个项目而建立的伙伴关系将导致长期的共同努力，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，特别是夏威夷的伍兹霍尔之间的联系。i，和迈阿密中心，他们现在都将在世界不同地区从事CFP的研究。现有的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.