Amazonian Center of Excellence in Malaria Research

尽管拉丁美洲的疟疾病例有所减少，但疟疾传播的热点仍然存在 异质分布在整个亚马逊地区，几乎所有这些都与初级 亚马逊媒介按蚊。亚马逊地区的疟疾传播与快速适应有关 一种。达林吉到人类驱动的环境变化。该项目将解决三个未被研究的问题 An的各方面。Darlingi将提供该媒介如何保持其在亚马逊语中的主导地位的关键细节 疟疾传播动态：1)描述人类繁殖地的重要性，人类繁殖地导致高 蚊子在人类栖息地附近的生产力和扩散；2)检查改良后的 咬人行为的地点(室内/室外)和夜间时间的景观；以及，3)展示了如何 蚊子物种的喜好/变化与间日疟原虫无症状的人相互作用以维持 低地方性传播。首先，我们将评估人工池塘和天然池塘对疟疾的贡献。 变速箱。在秘鲁疟疾流行地区年度寄生虫指数不同的村庄/城镇和 在巴西，我们将对疟疾相关房屋附近的繁殖点进行普查，并确定它们的物理特征 参数，并评估房屋内和周围的主机可用性。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 繁殖地类型与成虫从房子。我们预计附近地区的幼虫密度与 “热”(疟疾)的房子，在村子里经历最多的病例，无论在哪里滋生 打字。第二，在我们之前实验室连续繁殖成功的基础上。达林吉在 秘鲁亚马逊，我们将殖民行为独特的(食内性、外食性)种群。达林吉 并用间日疟原虫和恶性疟原虫对各自的媒介能力进行实验测试。我们预计会检测到 两个不同的种群，1)在自然繁殖地的野生、投机的蚊子，优先取血 从下午6点到9点在屋外；2)优先使用人工繁殖场所的嗜人蚊子， 从凌晨3点到6点在屋内寻找血液。第三，我们将量化和比较间日疟原虫的效率。 安氏杆菌感染。在不同的生物相关条件下，使用直接膜和标准膜 喂食化验。将对以下几组受试者进行研究：有症状，镜检阳性； 无症状，镜检阳性；和无症状，亚专利(镜检阴性，RT-PCR)， 无症状、未经治疗的受试者在治疗前的短时间内(每天一次)进行连续研究。 这些数据将使我们能够将间日疟原虫传播动力学的数学模型参数化，从而量化 与生物学有关的因素，如寄生虫血症和配子细胞症在几天内的波动，以及比较 昼夜节律。我们期望发现无症状的寄生虫个体在数量上是重要的。 保持疟疾传播的水库，无论是专利还是次专利。

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.