Dry Season Ecology of Malaria Vectors

疟疾媒介的旱季生态学

• 批准号: 10014227
• 负责人: Thomas E Wellems
• 金额: $ 52.16万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10014227
• 关键词: Address; Adult; Affect; African; Agriculture; Altitude; Animals; Aptitude; Arboviruses; Area; Asians; Bacteria; Behavioral; Biological Assay; Biology; Blood; Collaborations; Collection; Communities; Culicidae; DNA; Data; Data Analyses; Deuterium; Diapause; Distant; Ecology; Entomology; Environmental Wind; Evaluation; Evolution; Experimental Designs; Female; Fluorescent Dyes; Flying body movement; Follow-Up Studies; Genetic Transcription; Goals; Hour; Human; Insecta; Intercept; Isotopes; Laboratories; Laboratory Study; Larva; Leafhoppers; Life; Link; Lipids; Location; Maize; Malaria; Mali; Manuscripts; Measurement; Methods; Migrant; Millet; Molecular; Movement; Nature; Paper; Parasites; Phenotype; Photoperiod; Physiological; Placebos; Population; Process; Publishing; Rain; Research; Rice; Rift Valley Fever; Role; Sampling; Seasons; Site; Sorghum; Source; Surface; Temperature; Testing; Tigers; Time; Variant; Vector-transmitted infectious disease; Virus; Water; West Nile virus; Work; Writing; base; design; disease transmission; disorder control; experimental study; field study; filaria; fly; food security; human pathogen; improved; innovation; malaria mosquito; malaria transmission; member; migration; novel; pathogen; prevent; spectrograph; stable isotope; stress tolerance; success; tool; trait; transcriptomics; transmission process; transmission-blocking vaccine; vaccine efficacy; vector; vector control; vector mosquito

Despite extensive research on malaria for over a century, critical gaps remain in our understanding of the vectors; gaps that also limit our success in malaria control. We address some of the most critical gaps, namely the strategies used by African malaria mosquitoes to persist through the long dry season without surface waters for several months. Combining field and laboratory studies, our results provide compelling evidence that malaria vectors persist locally through the dry season by a form of dormancy (aestivation) and also engage in wind-assisted migration probably over hundreds of kilometers per night. These facets of vector biology have been controversial and, until now, were ignored due to insufficient evidence. Conventional and novel malaria and vector control strategies cannot afford to ignore aestivation and long-distance migration as processes that may hinder or aid the ultimate control of the disease. This year, we have published a study on a novel method to track mosquitoes over extended time based on enrichment of natural larval sites with stable isotopes (deuterium, 2H), which results in adults mosquitoes that are marked, for life, by a higher concentration of the 2H: (Faiman et al. 2019: Methods in Ecology & Evolution). A follow up of this study to evaluate the contribution of aestivation in the Sahel by tracking mosquitoes from the end of the wet season through the dry season and until the beginning of the subsequent wet season is being completed. Our results reveal a dramatic picture. By early November 2017, when the last larval sites dried up, we marked 60% of the adult mosquitoes in two Sahelian villages. Isotope ratio mass spectrograph (IRMS) analysis has revealed that 25-40% of the mosquitoes appearing in March during the late dry season peak had levels of 2H above natural levels, i.e., they grew up as larvae in the enriched larval sites 4 months earlier and >15% had elevated levels of 2H after the first rains (end of June 2018). The complete results, present direct evidence that (i) A. coluzzii appearing during the late dry season peak consists of aestivators, rather than long-distance migrators, (ii) the survival of local mosquitoes for 4 months strongly supports aestivation as the main persistence strategy of A. coluzzii, and (iii) this novel way of marking mosquitoes is powerful to elucidate other critical problems in vector-borne disease. Additional mosquitoes are analyzed by IRMS. The paper describing these exciting results is being written. Novel methods were also used to mark and track adult mosquitoes using a combination of novel fluorescent dye (SmartWater) containing DNA tags. This application of this method was developed in the laboratory, showing great adventages over conventional methods. In collaboration with LMIV (Patrick Duffys Lab), we are providing entomological evaluation of the movement of mosquitoes between houses in the Malian village, Doneguebougou, which were assigned for transmission-blocking-vaccine in comparison to placebo treatment. This mark-release-recapture experiment has a unique design tailored to determine quantitate the movement of mosquitoes that can undermine the measurement of the vaccine efficacy. Further, our experimental design is aimed to identify the units of malaria transmission in a village and determine how many such units exist in a typical village. Our first paper the on aerial sampling of mosquitoes entitled: Windborne long-distance migration of malaria mosquitoes in the Sahel is Nature: In Press). The results focus on primary and secondary malaria mosquitoes that were found flying in altitudes (40-290 m above ground). These important and findings include evidence that most mosquitoes are females after their blood meal, indicating that human and animal pathogens are being transported by these mosquitoes over hundreds of kilometers per night. In additional to anopheline mosquitoes, we collected approximately 2,500 culicine mosquitoes, many of which might be vectors of arboviruses. Using COI barcode analysis carried out in our lab and in the Walter Reed Biosystematics Unit (Yvonne Lintons group). The identification, which has recently been completed reveal >30 mosquito species including vectors of filariae and arboviruses (e.g., Rift Valley Fever, West Nile). This second paper is being drafted. Among the insects collected in high altitude, we identified and quantified pest species in agriculture affecting food security, such as leafhoppers vectors of viruses and bacteria to rice, maize, sorghum, and millet. These are also analyzed to demonstrate the value of this aerial collection and linked data to the scientific community and encourage members to use the collection their own independent studies. Our manuscript on diverse insect taxa collected in high altitudes is circulating among co-authors. It will be submitted later this year. A paper describing innovative work on mosquito tolerance to pathogens, that was carried out in the lab in 2011, entitled Variation in Tolerance to Parasites Affects Vectorial Capacity of Natural Asian Tiger Mosquito Populations has been reviewed favorably by Current Biology. After revision, we are awaiting final decision. Experiments to simulate aestivation in the laboratory has have yielded encouraging results, with a combination of photoperiod, temperature, and priming of larvae leading to survival of A. gambiae s.l. over 100 days. These results are now being replicated with subsamples assays for variation in transcription, stress tolerance, and lipid content to further test the relation of this long-lived phenotype with aestivation. A transcriptomic analysis of mosquitoes samples representing different seasons from the Sahel and perennial area in the wet savanna of Mali is underway. Data analysis and writing is being completed on a study on flight aptitude of >1200 wild mosquitoes bio-assayed in Mali. The results reveal that mosquitoes fly over the 9 hours night assay, with maximum total flight of 5 hours. Variation between species over different seasons and relationships to morphometric traits may help clarify if some of the flights represent long distance migration. In brief, we carry out a set of novel studies to address the roles of dormancy and windborne migration in African mosquito vectors and develop new tools to better understand vector-borne disease transmission and control.

尽管对疟疾进行了一个多世纪的广泛研究，但我们对媒介的理解仍然存在重大差距。差距也限制了我们在疟疾控制方面取得的成功。我们解决了一些最关键的差距，即非洲疟蚊在没有地表水的情况下持续几个月的漫长旱季所采用的策略。结合实地和实验室研究，我们的结果提供了令人信服的证据，表明疟疾媒介通过一种休眠（夏眠）形式在旱季持续存在，并且还参与风助迁徙，每晚可能超过数百公里。媒介生物学的这些方面一直存在争议，并且到目前为止，由于证据不足而被忽视。传统和新型的疟疾和病媒控制策略不能忽视夏眠和长途迁徙，因为它们可能阻碍或有助于疾病的最终控制。 今年，我们发表了一项关于长期追踪蚊子的新方法的研究，该方法基于用稳定同位素（氘，2H）富集天然幼虫位点，从而使成年蚊子终生受到更高浓度的标记2H：（Faiman 等人，2019：生态学与进化方法）。这项研究的后续工作正在完成，通过跟踪从雨季结束到旱季直到随后雨季开始的蚊子，评估萨赫勒地区夏眠的贡献。我们的结果揭示了一幅戏剧性的画面。到 2017 年 11 月初，当最后的幼虫栖息地枯竭时，我们在两个萨赫勒村庄标记了 60% 的成蚊。同位素比质谱仪（IRMS）分析显示，3月份旱季高峰期末期出现的蚊子中有25-40%的水平比自然水平高出2H，即它们在4个月前就在幼虫富集区长大为幼虫。超过 15% 的地区在第一次降雨后 2 小时内气温升高（截至 2018 年 6 月）。完整的结果提供了直接证据，表明（i）在旱季高峰期后期出现的 A. coluzzii 由夏眠者组成，而不是长距离迁徙者，（ii）当地蚊子在 4 个月内的存活有力地支持了夏眠作为主要的持久性A. coluzzii 的策略，以及（iii）这种标记蚊子的新方法能够有效地阐明媒介传播疾病的其他关键问题。通过 IRMS 分析其他蚊子。描述这些令人兴奋的结果的论文正在撰写中。 还使用了包含 DNA 标签的新型荧光染料 (SmartWater) 组合来标记和追踪成年蚊子的新方法。该方法的应用是在实验室中开发的，与传统方法相比显示出巨大的优势。我们与 LMIV（Patrick Duffys 实验室）合作，对马里 Doneguebougou 村房屋之间的蚊子活动进行昆虫学评估，这些房屋被分配使用阻断传播疫苗，并与安慰剂治疗进行比较。这种标记-释放-重新捕获实验采用独特的设计，专门用于确定可能破坏疫苗功效测量的蚊子运动的定量。此外，我们的实验设计旨在确定一个村庄中疟疾传播的单位，并确定一个典型村庄中有多少个这样的单位。 我们的第一篇关于蚊子空中采样的论文，题为：萨赫勒地区疟疾蚊子的风传播长距离迁移，《自然》：正在出版）。结果集中于在高海拔地区（距地面 40-290 m）飞行的原发性和继发性疟疾蚊子。这些重要的发现包括证据表明大多数蚊子在吸血后都是雌性，这表明这些蚊子每晚将人类和动物病原体传播数百公里。 除了按蚊之外，我们还收集了大约 2,500 只蚊子，其中许多可能是虫媒病毒的载体。使用我们实验室和 Walter Reed 生物系统学部门（Yvonne Lintons 小组）进行的 COI 条形码分析。最近完成的鉴定揭示了超过 30 种蚊子，包括丝虫和虫媒病毒载体（例如裂谷热、西尼罗河病毒）。第二份文件正在起草中。 在高海拔地区收集的昆虫中，我们鉴定并量化了影响粮食安全的农业害虫种类，例如将病毒和细菌传播给水稻、玉米、高粱和小米的叶蝉。还对这些数据进行分析，以向科学界展示这种空中收集和链接数据的价值，并鼓励成员使用这些收集进行自己的独立研究。我们关于在高海拔地区收集的多种昆虫类群的手稿正在共同作者之间流传。它将在今年晚些时候提交。 2011年，实验室发表了一篇论文，描述了蚊子对病原体耐受性的创新工作，题为“寄生虫耐受性变化影响自然亚洲虎蚊种群的矢量能力”，该论文受到了《当代生物学》的好评。修改后，我们正在等待最终决定。 在实验室中模拟夏眠的实验已经取得了令人鼓舞的结果，光周期、温度和幼虫的启动相结合，导致冈比亚 A. gambiae s.l. 的存活。超过100天。这些结果现在正在通过转录、胁迫耐受性和脂质含量变化的子样本测定进行复制，以进一步测试这种长寿表型与夏眠的关系。 目前正在对萨赫勒地区和马里潮湿稀树草原常年地区代表不同季节的蚊子样本进行转录组分析。 对马里超过 1200 只野生蚊子的飞行能力进行生物测定的研究的数据分析和撰写工作即将完成。结果显示，蚊子在夜间测试中飞行了 9 小时，最长总飞行时间为 5 小时。不同季节物种之间的变化以及与形态特征的关系可能有助于澄清某些飞行是否代表长距离迁徙。 简而言之，我们开展了一系列新颖的研究，以解决非洲蚊媒休眠和风媒迁移的作用，并开发新工具以更好地了解媒介传播疾病的传播和控制。