Amazonian Center of Excellence in Malaria Research

尽管整个拉丁美洲的疟疾病例有所减少，但疟疾传播热点仍然存在 在整个亚马逊河流域分布不均，几乎所有这些都与主要的 亚马逊媒介按蚊达氏。亚马逊地区的疟疾传播与快速适应有关， 一个. darlingi到生态驱动的环境变化。该项目将解决三个欠研究 一个方面。darlingi，这将提供关键的细节，这种载体如何保持其主导作用，在亚马逊河流域 疟疾传播动力学：1）描述导致高疟疾发病率的人类繁殖地的重要性， 蚊子在人类居住地附近的生产力和扩散; 2）检查修改后的快速适应 景观的位置（室内/室外）和夜间时间的叮咬行为;和，3）显示如何， 蚊子种类的偏好/变化与间日疟原虫无症状者相互作用， 低地方性传播。首先，我们将评估人工池塘与天然池塘对疟疾的贡献 传输在秘鲁疟疾流行区年寄生虫指数不同的村庄/城镇， 在巴西，我们将对与疟疾有关的房屋附近的繁殖地进行普查， 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感染的地方 通过识别蚊子的运动模式，特别是通过比较幼虫的基因型， 繁殖地点类型与成年人从房子。我们预计幼虫密度与邻近的 村庄内病例数最多的“热”（疟疾）房屋，无论其滋生地点如何 类型.第二，基于我们以前在实验室连续繁殖An。达林吉在 秘鲁亚马逊，我们将殖民行为独特（内食，外食）的人口。达林吉 并使用间日疟原虫和恶性疟原虫实验性地测试各自的载体能力。我们预计会发现 两个不同的种群，1）自然繁殖地的野生机会性蚊子， 从晚上6点到9点在屋外; 2）嗜热蚊子优先使用人工繁殖地点， 从凌晨3点到6点在房屋内寻找血液。第三，我们将量化和比较间日疟原虫的效率 感染一个。在不同的生物相关条件下，使用直接膜和标准膜 摄食测定。将研究以下受试者组：有症状、显微镜检查阳性; 无症状，显微镜检查阳性;和无症状，亚专利（显微镜检查阴性，RT-PCR+）， 在治疗前的短时间内（每天超过几天）连续研究无症状的未治疗受试者。 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， 生物学相关因素，如寄生虫血症和配子体血症随时间的波动， 生理周期我们期望发现无症状寄生虫血症个体在数量上是重要的 维持疟疾传播的水库，无论是专利或次级专利。

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.