Dry Season Ecology of Malaria Vectors

疟疾媒介的旱季生态学

• 批准号: 10692178
• 负责人: Tovi Lehmann
• 金额: $ 164.98万
• 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/10692178
• 关键词: Address; Adult; Aedes; Affect; Africa; African; Altitude; Animals; Anopheles Genus; Arboviruses; Area; Bacteria; Behavioral; Biology; Blood; Cessation of life; Chest; Color; Culex (Genus); Culicidae; DNA; Databases; Dengue; Destinations; Detection; Deuterium; Development; Disease Surveillance; Disease model; Distant; Doctor of Philosophy; Ecology; Ecosystem; Environmental Wind; Epidemiology; Evolution; Female; Flavivirus; Flying body movement; Frequencies; Genes; Ghana; Goals; Health; High Prevalence; Hour; Infection; Insecta; Intercept; Laboratories; Location; Malaria; Mali; Mansonia; Maps; Measurement; Metagenomics; Methods; Migrant; Modality; Molecular; Mosquito Control; Mosquito-borne infectious disease; Movement; Nature; Nematoda; Nutritional; Parasites; Pathogen detection; Pattern; Physiological; Placebos; Plasmodium; Public Health; Rain; Reporting; Ribosomes; Rift Valley Fever; Risk; Role; Saline; Sampling; Seasons; Site; Source; Specimen; Surface; Testing; Time; Trypanosoma; Variant; Vector-transmitted infectious disease; Virus; Water; Wolbachia; avian plasmodia; base; climate change; disease transmission; disorder control; experimental study; food security; forest; frontier; improved; infection rate; insight; literature survey; malaria mosquito; male; migration; mosquito-borne pathogen; novel; pathogen; prevent; programs; success; survivorship; synthetic construct; tool; transmission process; transmission-blocking vaccine; vaccine efficacy; vaccine evaluation; vector; vector competence; vector control

With a billion cases and one million deaths annually, vector borne diseases remain important. Malaria is still prevalent worldwide with an especially heavy burden in Africa. Outstanding gaps remain in our understanding of vector biology, including the strategies used by African malaria mosquitoes to persist through the long dry season. 1. We evaluated the contribution of aestivation to the persistence of mosquitoes in the Sahel by tracking mosquitoes marked by deuterium (2H) from the end of the wet season until the beginning of the subsequent wet season. If local aestivation is the only way An. coluzzii persists, the frequency of marked mosquitoes should remain stable, whereas finding no marked mosquitoes would be evidence against aestivation. After an initial enrichment, 33% of An. coluzzii were strongly marked. Seven months following enrichment, multiple analysis methods supported the ongoing presence of marked mosquitoes, compatible with the prediction that the fraction of marked mosquitoes should remain stable throughout the dry season if local aestivation is occurring. The results suggest that aestivation is a major persistence mechanism of An. coluzzii, contributing at least 20% of the adults at the onset of rains. This persistence strategy could influence mosquito control and malaria elimination campaigns. Faiman et al. 2022:Nature Ecology and Evolution:In Press. 2. Using aerial sampling of insects 40-290 m above ground in the Sahel, we have demonstrated regular and massive migration of Anopheles (Huestis et al. 2019: Nature) and showed that wild Anopheles withstood >11 hours high-altitude flight and subsequently reproduce and blood-feed on new hosts (Sanogo et al. 2021). Here, we describe this migration modality across Malian Culicidae. As well as Anopheles, 6 genera- Culex, Aedes, Mansonia, Mimomiya, Lutzia, and Eretmapodites comprised 90% of the 2,340 mosquitoes intercepted at altitude. Of the 50 species identified, 33 represented by multiple specimens were considered high-altitude windborne migrants. At altitude, females outnumbered males 6:1, and 93% of the females have taken at least one blood meal on a vertebrate host prior to departure. High-altitude flight coincided with peak disease transmission between June and November. These hallmarks bolster the role of windborne mosquitoes as carriers of mosquito-borne pathogens (MBPs). The infection rate in these high-altitude migrants for animal plasmodia was 2.4%, providing a proof of concept that vertebrate pathogens are transported by windborne mosquitoes at altitude. Fourteen of the 33 windborne mosquito species had been reported as vectors to 25 MBPs in West Africa, which represent 32% of the MBPs known in that region and include malaria, dengue, and Rift Valley fever. Further development of surveillance to map the sources and destinations of vectors and pathogens is key to understand, predict, and mitigate threats for public health. Yaro et al. 2022: bioRxiv: preprint & Frontiers in Epidemiology: Under Review. 3. To determine if mosquitoes engage in high-altitude flights beyond the Sahel, we have expanded aerial sampling into the savannas ecozones (Mali) and into the woodland and equatorial forests (Ghana). A total of 36 mosquito species were found (in 516 sequenced >150 m), belonging to 7 genera. Windborne mosquitoes occurred more commonly above perennial ecosystems including the equatorial forests than above the Sahel. Twelve mosquito species (33%) were found in a single ecozone, and 6 (17%) prevailed across all ecozones, suggesting that most mosquito species move between neighboring ecozones. Yet, movement between the equatorial forest to the Sahel >750 km also occur. 4) Dr. Bamou has been working on pathogen detection in the mosquitoes collected at altitude. Metagenomics analysis of few specimens indicated infection with insect specific viruses e.g., Aedes phasmavirus and Araticum virus, bacteria e.g., Wolbachia spp. and Asaia spp., a Trypanosoma spp. and Plasmodium spp. Targeted pathogen detection using pan-Plasmodium primers revealed 49 positives of 1,003 samples tested and confirmed using primers targeting the ribosomal 18S gene. Infectiousness ratemeasured as thoracic infectionwas 2.8%. Culex perexiguus, a known vector of avian plasmodia showed the highest prevalence (50%). The variation among ecozones was not significant (P>0.12) as expected if these pathogens are spread by mosquitoes that cross all ecozones (above). Additionally, infection of high-altitude mosquitoes with filariid nematodes was 0.7% (N=300) and several positives for flaviviruses. For the first time, we report detection of arboviruses, bacteria, and eukaryotic pathogens in high-altitude mosquitoes, thus providing proof of concept for their long-distance spread by windborne mosquitoes. 5. Mrs. Rita Frimpong, who has started a PhD program working on the insects collected at altitude in Mali and Ghana, focusing on species impacting public health and food security and comparing them to other taxa in terms of their seasonal and spatial high-altitude flight patterns. 6) To understand the scope of mosquito windborne migration, a literature survey of African mosquito borne diseases has been undertaken to generate a unique database of the African mosquito borne diseases from a One Health perspective. Initial analysis of the database produced important new insights into disease surveillance and for assessment of new regional and global threats of mosquito borne diseases. Lehmann et al. 2021: a preprint in bioRxiv. 7) Dormancy (aestivation) in Anopheline mosquitoes through the long dry season was demonstrated in An. coluzzii by several studies, but it has not been replicated in laboratory conditions, hindering progress on key questions such as how this state affects malaria vector competence. Following on progress made in our lab (Krajacich et al. 2020), Mr. Kouam (Postbac) compares survivorship and nutritional reserves of mosquitoes under conditions that mimic the late rainy and dry seasons and include specific larval priming conditions including increased salinity. 8) Mark release recapture experiments (MRRE) are key to address vector dispersal and survival. Our new marking method using synthetic DNA tags in a fluorescent solution (Faiman et al. 2021) was used in to track movement of mosquitoes between clusters of houses assigned to transmission-blocking-vaccine (TBV) or placebo. Tailored to determine if the movement of mosquitoes can undermine the measurement of the vaccine efficacy, we marked 33,922 Anopheles spp. and recaptured 253. Dispersal across the village, spanning 700 m was common within 3-7 d after releasethe maximum distance between release and capture, showing that mosquito movement undermine this TBV evaluation between clusters of compounds at the same village. Most MRREs on mosquitoes have been carried out within a single village with <2 km between the most distant possible capture and release sites. To assess inter-village dispersal, we used our new marking method (Faiman et all 2021) in 3 focal villages and 4 satellite villages from August to November 2021. Every 3 days, mosquitoes were captured in each focal village, marked, and released with unique color/DNA tags, identifying their date and site of release. The satellite villages extended the distance of capture to 12 km. A total of 42,367 mosquitoes were marked/released and 645 were recaptured. Preliminary results revealed that 2.1-3.6% found 3-6 km away, and 0-1% found 12 km away. Given the area around the focal villages, we estimate the fraction of mosquitoes that successfully emigrated from their village to others is 20%, with 7% reaching between up to 6 and up to 12 km. These results will impact models of disease spread by changing dispersal and survival distribution kernels.

每年有十亿例病例和一百万人死亡，媒介传播的疾病仍然很重要。疟疾在世界范围内仍然普遍存在，非洲的负担尤其沉重。我们对媒介生物学的理解仍然存在巨大差距，包括非洲疟蚊在漫长的旱季中持续存在的策略。 1. 我们通过跟踪从雨季结束到下一个雨季开始期间用氘 (2H) 标记的蚊子，评估了夏眠对萨赫勒地区蚊子持续存在的贡献。如果当地的夏夏是唯一的出路。 coluzzii 持续存在，有标记的蚊子的频率应该保持稳定，而没有发现有标记的蚊子将是不适合夏眠的证据。经过初步富集后，An 的含量为 33%。 coluzzii 被强烈标记。富集后七个月，多种分析方法支持标记蚊子的持续存在，这与如果发生局部夏眠，标记蚊子的比例在整个旱季应保持稳定的预测相一致。结果表明，夏眠是An的主要持久机制。 coluzzii，在降雨开始时贡献了至少 20% 的成虫。这种持久性策略可能会影响蚊子控制和消除疟疾运动。费曼等人。 2022：自然生态学与进化：正在出版。 2. 通过对萨赫勒地区地面以上 40-290 m 的昆虫进行空中采样，我们证明了按蚊的定期和大规模迁徙（Huestis et al. 2019：Nature），并表明野生按蚊能够承受 >11 小时的高空飞行，随后在新宿主上繁殖并吸血（Sanogo et al. 2021）。在这里，我们描述了马里库蚊科的这种迁徙方式。除按蚊外，库蚊属、伊蚊属、曼蚊属、米莫宫属、路兹蚊属和按蚊属等 6 个属占在高海拔截获的 2,340 只蚊子中的 90%。在已识别的 50 个物种中，有 33 个由多个标本代表的物种被认为是高空风传候鸟。在高海拔地区，雌性与雄性的数量比例为 6:1，并且 93% 的雌性在出发前至少吸食过脊椎动物宿主的血粉。高空飞行恰逢 6 月至 11 月期间的疾病传播高峰。这些特征增强了风媒蚊子作为蚊媒病原体（MBP）携带者的作用。这些高海拔迁徙动物疟原虫的感染率为2.4%，这为脊椎动物病原体在高海拔地区通过风传播的蚊子传播提供了概念证明。据报道，33 种风传播蚊子中有 14 种是西非 25 MBP 的媒介，占该地区已知 MBP 的 32%，包括疟疾、登革热和裂谷热。进一步发展监测以绘制病媒和病原体的来源和目的地是了解、预测和减轻公共卫生威胁的关键。亚罗等人。 2022：bioRxiv：流行病学预印本和前沿：正在审查中。 3. 为了确定蚊子是否参与萨赫勒地区以外的高空飞行，我们将空中采样范围扩大到了稀树草原生态区（马里）以及林地和赤道森林（加纳）。总共发现了 36 种蚊子（测序长度 >150 m 的 516 种），分属 7 个属。风媒蚊子在包括赤道森林在内的常年生态系统上方比萨赫勒地区更常见。在一个生态区中发现了 12 种蚊子（33%），其中 6 种（17%）在所有生态区中盛行，这表明大多数蚊子种类在相邻生态区之间移动。然而，赤道森林到萨赫勒地区之间也发生超过 750 公里的移动。 4）Bamou博士一直致力于在高海拔地区采集的蚊子中进行病原体检测。对少数样本的宏基因组学分析表明，感染了昆虫特异性病毒，例如伊蚊病毒和阿拉蒂克病毒，以及细菌，例如沃尔巴克氏菌属。和 Asaia spp.，锥虫属。和疟原虫属。使用泛疟原虫引物进行靶向病原体检测，使用针对核糖体 18S 基因的引物进行测试和确认的 1,003 个样本中有 49 个呈阳性。胸部感染的感染率为2.8%。特克库蚊（Culex perexiguus）是一种已知的鸟类疟原虫载体，其患病率最高（50%）。如果这些病原体是通过穿越所有生态区的蚊子传播的（上图），那么生态区之间的差异并不显着（P>0.12）。此外，高海拔蚊子丝状线虫的感染率为 0.7% (N=300)，并且有一些黄病毒呈阳性。我们首次报告在高海拔蚊子中检测到虫媒病毒、细菌和真核病原体，从而为它们通过风传播的蚊子进行长距离传播提供了概念证明。 5. Rita Frimpong 女士启动了一个博士项目，研究在马里和加纳高海拔地区收集的昆虫，重点关注影响公共卫生和粮食安全的物种，并将它们与其他类群的季节和空间高海拔进行比较飞行模式。 6) 为了了解蚊子经风传播的迁徙范围，对非洲蚊媒疾病进行了文献调查，从“同一个健康”的角度生成了非洲蚊媒疾病的独特数据库。对数据库的初步分析为疾病监测和蚊媒疾病新的区域和全球威胁评估提供了重要的新见解。莱曼等人。 2021 年：bioRxiv 上的预印本。 7)按蚊在漫长的旱季中的休眠（夏眠）在按蚊中得到了证实。 coluzzii 已被多项研究证实，但尚未在实验室条件下得到复制，这阻碍了关键问题的进展，例如这种状态如何影响疟疾媒介的能力。继我们实验室取得的进展（Krajacich 等人，2020）之后，Kouam 先生（Postbac）在模拟雨季末期和旱季的条件下比较了蚊子的存活率和营养储备，包括特定的幼虫启动条件（包括盐度增加）。 8) 标记释放重新捕获实验 (MRRE) 是解决载体扩散和生存的关键。我们的新标记方法在荧光溶液中使用合成 DNA 标签（Faiman 等人，2021），用于跟踪分配给传播阻断疫苗 (TBV) 或安慰剂的房屋群之间蚊子的移动。为了确定蚊子的移动是否会破坏疫苗功效的测量，我们标记了 33,922 个按蚊属。并重新捕获 253。释放后 3-7 天内，跨越 700 m 的整个村庄的扩散很常见（释放和捕获之间的最大距离），表明蚊子的移动破坏了同一村庄的化合物群之间的 TBV 评估。 大多数针对蚊子的 MRRE 都是在一个村庄内进行的，最远的捕获点和释放点之间的距离小于 2 公里。为了评估村庄间的传播，我们从 2021 年 8 月到 11 月在 3 个焦点村庄和 4 个卫星村使用了新的标记方法（Faiman 等人 2021）。每 3 天，在每个焦点村庄捕获蚊子，进行标记，并用独特的颜色/DNA 标签，可识别其发布日期和地点。卫星村将捕获距离延长至12公里。总共标记/释放了 42,367 只蚊子，并重新捕获了 645 只。初步结果显示，2.1-3.6%的人发现了3-6公里以外的地方，0-1%发现了12公里之外的地方。考虑到重点村庄周围的区域，我们估计成功从本村庄迁移到其他村庄的蚊子比例为 20%，其中 7% 的蚊子传播范围可达 6 至 12 公里。这些结果将通过改变传播和生存分布内核来影响疾病传播模型。