Mechanisms and Public Health Impact of Sylvatic Dengue Virus Emergence in Borneo

婆罗洲森林登革热病毒出现的机制和公共卫生影响

• 批准号: 9295929
• 负责人: Nikos Vasilakis
• 金额: $ 59.1万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-15 至 2020-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9295929
• 关键词: Aedes; Agriculture; American; Arbovirus Infections; Arboviruses; Asia; Blood; Blood Circulation; Borneo; Clinical; Collection; Culicidae; Dengue; Dengue Infection; Dengue Virus; Diagnostic; Disease; Disease Outbreaks; Disease Outcome; Ecology; Epidemic; Epidemiology; Etiology; Fever; Frequencies; Future; Genetic; Genetic Variation; Geography; Goals; Guidelines; Health; Human; Incidence; Infection; Intervention; Investigation; Laboratories; Lead; Location; Maintenance; Malaysia; Malaysian; Medical; Mentors; Modernization; Morbidity - disease rate; Nature; New Mexico; Outcome; Phylogenetic Analysis; Population; Preparation; Primates; Public Health; Research; Risk; Risk Factors; Rural; Sarawak; Scientist; Serotyping; Site; Source; Southeastern Asia; Surveillance Program; System; Testing; Texas; Time; Training; Universities; Vaccination; Variant; Viral Hemorrhagic Fevers; Viremia; Virus; Virus Diseases; Zika Virus; Zoonoses; anthropogenesis; arbovirus disease; burden of illness; enzootic; exposed human population; forest; human disease; improved; insight; land cover; land use; mortality; nonhuman primate; pathogen; progenitor; prospective; public health relevance; remote sensing; southeast Asian; transmission process; vaccine development; vector; vector mosquito; viral transmission

 DESCRIPTION (provided by applicant): The overall goal of our proposed research is to understand the mechanisms that allow zoonotic, sylvatic arthropod-borne viruses (henceforth referred to as 'arboviruses') to jump species boundaries and cause human disease. Dengue viruses (DENV) are by far the most important human pathogens, causing an estimated 50- 100 million annual infections in tropical and subtropical regions, where nearly a third of the global population is at risk. The four serotypes of DENV that circulate among humans each emerged from an ancestor that is maintained in a sylvatic transmission cycle between non-human primates and arboreal mosquitoes in Southeast Asia. This project will examine the vector ecology and mechanisms of DENV emergence from its sylvatic transmission cycle in Malaysian Borneo. Discerning the underlying mechanisms of dengue emergence will provide key insights into the epidemiology and risk of arboviral infections in Malaysia; our findings may also lead to the preparation of guidelines for arbovirus surveillance, control and outbreak management for the entire Southeast Asian region. Critically, the sylvatic transmission cycle contains virus variants that have not yet made the transition into the human cycle; we have recently discovered a fifth DENV serotype from the sylvatic cycle in Borneo. The identification of DENV-5 and perhaps additional sylvatic lineages could have profound implications for vaccine development and diagnostics. We therefore propose to prospectively investigate the nature and breadth of contact between humans and the sylvatic DENV transmission cycle, as well as the consequences of this contact in terms of human dengue disease. Our research will focus on the documented sylvatic transmission cycle in Sarawak, Malaysian Borneo The following hypotheses will be tested: (i) sylvatic DENV circulates continuously in the forests of Sarawak; (ii distinct suites of vector mosquitoes are responsible for maintenance of the sylvatic cycle in reservoir hosts and spillover into humans, (iii) Borneo, which has been separated from mainland Asia for approximately 12,000 years, contains DENV variants not found in either the human cycle or the sylvatic DENV cycle of mainland Malaysia (iv) both traditional practices, such as hunting and slash-and-burn agriculture, that necessitate entry into the forest as well as large-scale anthropogenic changes in land use constitute risk factors for sylvatic DENV infection and disease. The ICIDR consortium will include the University of Texas Medical Branch, the Universiti Malaysia Sarawak, and New Mexico State University. The projected outcomes of this proposal will broaden our understanding of sylvatic vector ecology and the mechanisms by which DENV and other arboviral pathogens emerge, thus providing a direct benefit to human health. Our results will also improve predictions of the risk of future emergence of DENV and other arboviruses, and result in the identification and characterization of various arboviral etiologies of febrile illness in Borneo where little is known about the zoonotic disease burden attributable to arboviruses. Thus, it will improve the clinical recognition of arbovirus illness at rural localities in Malaysia.

 描述（由适用提供）：我们拟议的研究的总体目标是了解允许人畜共患，sylvatic节肢动物 - 传播病毒（此后称为“ Arboviruses”）的机制，以跳高物种边界并引起人类疾病。登革热病毒（DENV）是迄今为止最重要的人类病原体，估计在热带和亚热带地区估计有50亿个年度感染，几乎三分之一的全球人口处于危险之中。 DENV的四种血清型在人类中流通，每个人类都来自一个祖先，该祖先在东南亚的非人类私密性和树木蚊子之间保持在Sylvatic的传播周期中。该项目将检查来自马来西亚婆罗洲的Sylvatic传播周期的DENV出现的矢量生态和机制。辨别登革热出现的基本机制将为马来西亚的流行病学和灰臂感染风险提供关键的见解；我们的发现还可能导致为整个东南亚地区的Arbovirus监视，控制和爆发管理制定指南。至关重要的是，Sylvatic传播周期包含尚未使过渡到人类周期的病毒变体。最近，我们从婆罗洲的Sylvatic Cycle中发现了第五个DENV血清型。 DENV-5的识别和可能的其他Sylvatic谱系可能对疫苗的开发和诊断具有深远的影响。因此，我们建议前瞻性地研究人类与Sylvatic DENV传播周期之间的接触性质和广度，以及这种接触的后果在人类的颈病方面。我们的研究将重点放在马来西亚婆罗洲砂拉越的记录的Sylvatic传输周期上，以下假设将进行测试：（i）Sylvatic DENV在砂拉越的森林中连续循环； （iii不同的矢量蚊子套件负责维持水库宿主中的Sylvatic循环，而spilover spilover又是人类，（iii）婆罗洲（（iii）婆罗洲，已从亚洲分离，大约12，000年，其中包含大约12，000年农业，对森林的必要条件以及土地使用的大规模人为变化构成了ICIDR财团的sylvatic Denv感染和疾病。病原体的出现，为人类健康提供了直接的好处。 马来西亚的农村地区。