Amazonian Center of Excellence in Malaria Research

亚马逊疟疾研究卓越中心

• 批准号: 10441616
• 负责人: Jan E Conn
• 金额: $ 23.19万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10441616
• 关键词: Acute; Address; Adult; Anopheles Genus; Behavior; Behavioral; Biological Assay; Biomass; Bite; Brazil; Breeding; Case Study; Censuses; Chromosome inversion; Culicidae; Data; Diagnosis; Economics; Epidemiology; Exhibits; Feeding behaviors; Feeds; Female; Fishes; Frequencies; Genetic Drift; Genotype; Geography; Habitats; Habits; Hot Spot; Human; Immune; Immunology; Individual; Infection; Laboratories; Larva; Latin America; Lead; Legal patent; Link; Location; Malaria; Membrane; Microscopy; Movement; Parasitemia; Parasites; Parasitic Diseases; Pattern; Persons; Peru; Peruvian; Plasmodium; Plasmodium falciparum; Plasmodium vivax; Population; Population Genetics; Productivity; Research; Reverse Transcriptase Polymerase Chain Reaction; Risk; Risk Factors; Role; Sampling; Site; Source; Structure; Study Subject; Testing; Time; Variant; Vectorial capacity; anthropogenesis; base; biosignature; circadian; density; environmental change; experience; feeding; indexing; insight; light microscopy; malaria transmission; mathematical model; novel strategies; preference; rural setting; spatiotemporal; success; transmission process; vector; vector competence; virtual

Despite reductions in malaria cases across Latin America, malaria transmission hot spots remain heterogeneously distributed throughout Amazonia, virtually all of which are strongly linked to the primary Amazonian vector Anopheles darlingi. Malaria transmission in Amazonia is associated with rapid adaptation by An. darlingi to anthropogenically-driven environmental changes. This project will address three understudied facets of An. darlingi which will provide key details of how this vector maintains its dominant role in Amazonian malaria transmission dynamics by: 1) delineating the importance of anthropic breeding sites that lead to high mosquito productivity and dispersal near human habitation; 2) examining rapid adaptation in modified landscapes of both location (indoor/ outdoor) and nocturnal timing of biting behavior; and, 3) showing how this mosquito species’ preferences/ changes interact with Plasmodium vivax asymptomatic persons to maintain hypoendemic transmission. First, we will evaluate the contribution of artificial vs. natural ponds to malaria transmission. In villages/towns with varying annual parasitic indices in malaria endemic regions of Peru and Brazil, we will census breeding sites near malaria-associated houses and characterize their physical parameters, and assess host availability in and around houses. We will identify where mosquitoes bite infected individuals by identifying patterns of mosquito movement, particularly by comparing larval genotypes in breeding site types with adults from houses. We expect a strong correlation of larval density in proximity with “hot” (malarial) houses that experience the highest numbers of cases within village regardless of breeding site type. Second, based on our previous success in continuous laboratory propagation of An. darlingi in the Peruvian Amazon, we will colonize behaviorally distinctive (endophagic, exophagic) populations of An. darlingi and experimentally test each for vector competence using P. vivax and P. falciparum. We anticipate detecting two distinct populations, 1) wild, opportunistic mosquitoes in natural breeding sites, bloodseeking preferentially from ~6-9 PM outside houses; 2) anthropophilic mosquitoes that preferentially use artificial breeding sites, bloodseeking from ~3-6 AM inside houses. Third, we will quantify and compare the efficiency of P. vivax infection of An. darlingi under different, biologically-relevant conditions, using direct and standard membrane feeding assays. The following groups of subjects will be studied: symptomatic, microscopy positive; asymptomatic, microscopy positive; and asymptomatic, subpatent (microscopy negative, RT-PCR+), with asymptomatic, untreated subjects studied serially over short periods (diurnally over days) before treatment. These data will allow us to parameterize mathematical models of P. vivax transmission dynamics in quantifying biologically relevant factors such as fluctuations in parasitemia and gametocytemia over days and comparing circadian cycles. We expect to find that asymptomatic parasitemic individuals are quantitatively important reservoirs that maintain malaria transmission whether patent or subpatent.

尽管拉丁美洲的疟疾病例有所减少，但疟疾传播热点仍然存在 亚马逊流域分布异质，几乎所有这些都与主要地区密切相关 亚马逊媒介达林按蚊（Anopheles darlingi）在亚马逊地区的疟疾传播与疟疾的快速适应有关。 An. darlingi 到人为驱动的环境变化。该项目将解决三个尚未得到充分研究的问题。 An. darlingi 的各个方面，将提供该载体如何在亚马逊中保持主导地位的关键细节 通过以下方式了解疟疾传播动态： 1) 描述导致高疟疾传播的人为繁殖地的重要性 蚊子的生产力和在人类居住地附近的传播；2）检查改良后的快速适应 咬合行为的地点（室内/室外）和夜间时间的景观，以及，3）显示这是如何发生的； 蚊子种类的偏好/变化与间日疟原虫无症状者相互作用，以维持 首先，我们将评估人工池塘与自然池塘对疟疾的影响。 秘鲁和疟疾流行地区年度寄生虫指数不同的村庄/城镇中的传播。 巴西，我们将对与疟疾相关的房屋附近的繁殖地进行普查，并描述其物理特征 参数，并评估房屋内和周围宿主的可用性，我们将确定蚊子叮咬受感染的地方。 通过识别蚊子的运动模式，特别是通过比较蚊子的幼虫基因型来识别个体 繁殖地类型与房屋内成虫的关系我们预计附近的幼虫密度具有很强的相关性。 无论繁殖地点如何，村内病例数量最多的“热”（疟疾）房屋 其次，基于我们之前在实验室连续繁殖达林吉的成功。 秘鲁亚马逊，我们将殖民行为独特（内食性、外食性）的达林吉蚊种群。 并使用间日疟原虫和恶性疟原虫对每种载体的能力进行实验测试，我们预计可以检测到。 两个不同的种群，1）自然繁殖地的野生机会性蚊子，优先吸血 下午 6 点至晚上 9 点在屋外；2) 嗜人性蚊子，优先使用人工繁殖场所， 第三，我们将量化并比较间日疟原虫的效率。 使用直接和标准膜在不同的生物学相关条件下感染达林按蚊 将研究以下几组受试者：有症状、显微镜检查呈阳性； 无症状，显微镜检查呈阳性；以及无症状，亚显性（显微镜检查阴性，RT-PCR+）， 无症状、未经治疗的受试者在治疗前短期内（每天持续几天）进行连续研究。 这些数据将使我们能够参数化间日疟原虫传播动力学的数学模型，以进行量化 生物学相关因素，例如寄生虫血症和配子体血症的波动，并进行比较 我们期望发现无症状的寄生虫个体在数量上很重要。 维持疟疾传播的储存库，无论是专利的还是次级专利的。