Proximal determinants of risk for tularemia outbreaks

描述（由申请人提供）：尽管对土拉热弗朗西斯菌的生物学了解很多，但调节其自然流行的因素仍未描述。我们试图检验“现任者统治”假说：通过与政治的类比，F。美国东北部的土拉热流行病受到与“统治”内共生弗朗西斯菌（Francisella sp.）（以前被归类为沃尔巴克氏体）相互作用的限制。常见于狗蜱的组织中，变异革蜱。最近在玛莎葡萄园岛爆发的兔热病为确定作为这种罕见感染传播增加的基础的因素提供了一个独特的机会，因为那里似乎是这种感染的长期自然疫源地。然而，检验这一假设需要确定这些自然疫源，这些自然疫源可能包括小块植被;在整个10万公顷的岛屿上，传播并不是均匀分布的。因此，我们首先试图通过（1）确定条纹臭鼬（Mephitismephitis）是否作为F。土拉热传播;以及（2）通过招募园艺师和职业上暴露于兔热病和其他蜱传播感染的其他人来积极地在真实的时间内报告在他们的工作期间遇到的动物尸体的存在，来补充基于臭鼬的预测。自然疫源地将通过密集的纵向流行病学分析（F.蜱和其他潜在病媒节肢动物中的土拉热感染;啮齿动物和其他动物中的接触证据）。通过这种方式，我们将积累可靠的研究地点和全面检验“现任者统治”假设所需的初步数据。此外，我们绘制的危险地点地图可作为当地公共卫生措施的基础。我们预计，在拟议的工作中开发或验证的流行病学和流行病学方法可能有助于加强对土拉菌疫情的调查;为那些有自然或非法土拉菌暴露风险的人制定新的预防策略;加强对F.环境中的土拉菌;最终，更好地了解F。土拉菌-宿主相互作用

DESCRIPTION (provided by the applicant): Although much is known about the biology of Francisella tularensis, the factors that regulate its natural prevalence remain un-described. We seek to test the 'rule of the incumbent' hypothesis: by analogy with politics, F. tularensis epizootics in the northeastern United States are limited by interactions with a 'ruling' endosymbiotic Francisella sp. (previously classified as Wolbachia sp.) common within tissues of dog ticks, Dermacentor variabilis. The recent outbreak of tularemia on Martha's Vineyard provides a unique opportunity for identifying factors that serve as the basis for increased transmission of this rare infection because sites there appear to be longstanding natural foci of this infection. However, testing this hypothesis requires identification of these natural foci, which may comprise small patches of vegetation; transmission is not homogeneously distributed over the entire 100,000-hectare island. Accordingly, we first seek to identify such natural foci by (1) determining whether striped skunks (Mephitis mephitis) serve as effective sentinels for F. tularensis transmission; and (2) complementing skunk-based predictions by enlisting landscapers and others who are occupationally exposed to tularemia and other tick borne infections to actively report, in real time, the presence of animal carcasses encountered during their work. Natural foci will be definitively confirmed by intensive longitudinal epizootiologic analyses (prevalence of F. tularensis infection in ticks and other potential vector arthropods; evidence of exposure in rodents and other animals). In this manner, we shall accumulate reliable study sites and the preliminary data required for a comprehensive test of the 'rule of the incumbent' hypothesis. In addition, our mapping of risky sites may serve as the basis for local public health measures. We anticipate that the epidemiologic and epizootiologic methods developed or validated during the proposed work may contribute towards enhanced investigations of tularemia outbreaks; new prevention strategies for those at risk of natural or illicit tularemia exposure; enhanced detection of F. tularensis in the environment; and, ultimately, a better understanding of F. tularensis-host interactions.