Quantifying Heterogeneities in Dengue Virus Transmission Dynamics

描述（由申请人提供）：目前对登革病毒（DENV）传播的了解充其量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人口比例;即，因为他们表现出临床上明显的疾病而便于研究的人。从显性疾病患者的角度探讨登革热产生了大量有价值的文献。然而，它还没有完全接受病毒传播动态的异质性，这些异质性越来越被认为是控制人类最重要的昆虫传播病毒感染的斗争中的关键缺失信息。仅在过去20年中，才作出重大努力进行全面的登革热纵向研究。我们的研究团队在秘鲁的伊基托斯和泰国的甘榜斐参与了两个重要的登革热纵向研究项目。我们提出的POl代表了这一调查路线的下一个关键步骤。通过研究整个疾病连续体中的人，包括临床上不明显和轻度感染的人，我们的目标是量化影响DENV传播动力学和预防的人类变量的异质性。为此，我们将利用我们在过去14年中在伊基托斯研究区组装的基础设施。我们的POI旨在通过首次定义未充分研究的大多数DENV感染者（估计有2.94亿人患有不明显和轻度感染）的贡献以及流行病学，昆虫学和社会行为来源的异质性对DENV传播动态的贡献来帮助填补了解传播动态和有效疾病预防之间的空白。通过考虑每个人对传播的贡献的潜在变化因素，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，从而为改善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，估计每年有3.9亿人感染登革病毒。登革病毒引起的人类发病率和死亡率高于任何其他节肢动物传播的病毒。它是世界上发展最快的病媒传播疾病，是一般病媒病原体传播的模式系统。对登革病毒传播动力学、概念和理论的更好理解将填补关键的知识空白，并显着改善疾病预防计划。

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.