Quantifying Heterogeneities in Dengue Virus Transmission Dynamics

描述（由申请人提供）：目前对登革热病毒（DENV）传播的知识最多只能部分了解一个复杂而动态的系统，其公共卫生记录失败多于成功。问题的一个重要部分是，当代干预措施的基础包括一系列长期存在但未经检验的假设，这些假设基于相对较小的一部分人口；即，由于临床表现出明显的疾病而便于研究的人。从患有显性疾病的人的角度来研究登革热已经产生了大量有价值的文献。然而，它没有完全接受病毒传播动力学中的异质性，而这种异质性日益被认为是在控制最重要的昆虫传播的人类病毒感染的斗争中缺少的关键信息。仅在过去的20年里，进行了大量的努力来开展全面的登革热纵向研究。我们的研究小组全面参与了秘鲁伊基托斯和泰国坎彭彭两个著名的登革热纵向研究项目。我们提出的POl代表了这条调查路线的下一个关键步骤。通过研究整个疾病连续体的人群，包括临床不明显和轻度感染的人群，我们的目标是量化影响DENV传播动态和预防的人类变量的异质性。为了做到这一点，我们将利用过去14年来在伊基托斯研究区域组装的基础设施。我们的POl旨在通过首次定义未被充分研究的大多数DENV感染者（估计有2.94亿人患有隐性和轻度感染）的贡献，以及流行病学，昆虫学和社会行为异质性来源对DENV传播动力学的贡献，帮助填补理解传播动力学和有效疾病预防之间的空白。通过计算每个人对传播的贡献差异的潜在因素，我们将能够更好地确定预防病毒传播所需努力的类型和程度，从而为改进登革热预防提供新的见解。相关性（见说明）：在128个高风险国家中，估计每年有3.9亿人感染DENV。登革热病毒比任何其他节肢动物传播的病毒造成更多的人类发病率和死亡率。它是世界上传播速度最快的病媒传播疾病，是一般病媒传播病原体的模式系统。提高对DENV传播动力学、概念和理论的理解将填补关键的知识空白，并显著改善疾病预防计划。

DESCRIPTION (provided by applicant): Current knowledge of dengue virus (DENV) transmission provides, at best, only a partial understanding of a complicated and dynamic system with a public health track record that has more failures than successes. An important part ofthe problems is that the foundation for contemporary interventions includes a series of longstanding, but untested, assumptions based on a relatively small portion ofthe human population; i.e., people who are convenient to study because they manifest clinically apparent disease. Approaching dengue from the perspective of people with overt illness has produced an extensive body of valuable literature. It has not, however, fully embraced heterogeneities in virus transmission dynamics that are increasingly recognized as key missing information in the struggle to control the most important insect-transmitted viral infection of humans. Only in the last 20 years there have been significant efforts to carry out comprehensive longitudinal dengue studies. Our research team was integrally involved in two prominent longitudinal dengue research projects in Iquitos, Peru and Kamphaeng Phet, Thailand. Our proposed POl represents the next crucial step in this line of inquiry. By studying people across the entire continuum of disease, including people with clinically inapparent and mild infections, we aim to quantify heterogeneities in human variables that affect DENV transmission dynamics and prevention. To do this, we will exploit the infrastructure we assembled over the past 14 years at our Iquitos study area. Our POl aims to help fill the void between understanding transmission dynamics and effective disease prevention by defining, for the first time, the contribution of the understudied majority of DENV infected people (the estimated 294 million with inapparent and mild infections) and the contributions of epidemiological, entomological, and socio-behavioral sources of heterogeneity to the dynamics of DENV transmission. By accounting for factors underlying variation in each person's contribution to transmission we will be able to better determine the type and extent of effort needed to prevent virus transmission and, thus, provide new insights for improved dengue prevention. RELEVANCE (See instructions): An estimated 390 million people in 128 at risk countries experience a DENV infection each year. Dengue viruses cause more human morbidity and mortality than any other arthropod-borne virus. It is the most rapidly advancing vector-borne disease in the world and it serves as a model system for transmission of vector-borne pathogens in general. An improved understanding of DENV transmission dynamics, concepts, and theory will fill critical knowledge gaps and significantly improve disease prevention programs.