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减少，但疟疾传播热点仍然存在 异构分布在整个亚马逊尼亚，几乎所有这些都与主要相关 亚马逊矢量围绕着Darlingi。亚马逊中的疟疾传播与快速适应 一个。达令对人为驱动的环境变化。该项目将解决三个理解的 一个方面。达令（Darlingi 疟疾传播动力学作者：1）描述导致高高的人类繁殖地的重要性 蚊子生产力和近代人居住； 2）检查改良的快速适应 位置的景观（室内/室外）和咬人行为的夜间时间； 3）显示如何 蚊子物种的偏好/变化与疟原虫相互作用，以维持不对称的人 低血分传播。首先，我们将评估人工与天然PON对疟疾的贡献 传播。在秘鲁和 巴西，我们将人口普查繁殖地点在疟疾相关的房屋附近，并表征其身体 参数并评估房屋内外的主机可用性。我们将确定蚊子在哪里感染 通过识别蚊子运动的模式，特别是通过比较幼虫基因型 来自房屋的成年人的繁殖地点。我们期望与 “热”（疟疾）房屋，无论繁殖地点如何 类型。其次，基于我们以前在持续实验室传播an的成功。达令利在 秘鲁亚马逊，我们将在An的行为独特（内吞，外界）殖民。达令 并使用Vivax和Falciparum P. p. p. p. pershipally测试每个载体的能力。我们预计检测 两个不同的人群，1）自然育种场所中的野生机会蚊子，优先寻常的蚊子 从大约下午6点至9点室外房屋； 2）优先使用人造育种位点的人类蚊子， 从〜3-6 AM的房屋中进行鲜血。第三，我们将量化和比较息肉平的效率 感染darlingi使用直接和标准膜在不同的，生物学上与生物学相关的条件下 进食测定。以下受试者组将进行研究：有症状，显微镜呈阳性； 无症状，显微镜阳性；和无症状的亚比（显微镜阴性，RT-PCR+），带有 在治疗前，无症状的未经治疗的受试者在短时间内（几天）进行了串行的研究。 这些数据将使我们能够在量化时对疟原虫传输动力学的数学模型进行参数化。 生物学相关的因素，例如几天内寄生虫血症和配子细胞血症的波动，并比较 昼夜节律。我们希望发现不对称的寄生虫个体在定量上很重要 维持疟疾传播的水库无论是专利还是副标。