Vector Biological Studies

摘要 印度次大陆内脏利什曼病(VL)消除战略，目前 到2017年将VL发病率降低到1/10,000人以下的目标包括快速检测 和VL病例的治疗，以减少人类感染库的数量，以及媒介控制 使用室内滞留喷洒(IRS)。为了实现VL的持续消除，适当的 需要进行监测计划，以检测抗药性种群的出现。 以及确定感染个体的贡献的研究 波谱，以及可能的非人类宿主，以维持多诺瓦尼乳杆菌的传播 周而复始。 为了解决这些问题，我们提出了一系列前沿研究，这些研究将利用 现在有特殊资源可用于在比哈尔邦开展与病媒有关的研究。这些资源 包括1)一种新的、功能齐全的杀虫剂，它将允许遏制、饲养、感染和 操纵野外捕获的沙蝇，2)已建立的工作群体的紫云杉，它有 已被认证用于异种诊断程序，以及3)昆虫学野外小组 在比哈尔邦捕获、分类鉴定和定居沙蝇方面有丰富的经验。 建议进行研究以调查大田种群对杀虫剂的抗性，建立一个 拟除虫菊酯抗性菌落，并开发基于生物标记物的检测方法，以快速识别紧急情况 比哈尔邦抗药性沙蝇种群。将进行向量能力研究 不同围岩环境中捕获的紫云杉及其相关关系的研究 中肠微生物区系图谱。元基因组测序和分析方法将与 项目1中提出的人体肠道微生物群的研究。可培养的细菌菌群似乎 对利什曼原虫发育的负面或正面影响将被用于细菌饲料，试图 在被殖民的苍蝇中操纵媒介能力。被殖民的苍蝇也将被用于 异种诊断分析，以确定可能在以下方面发挥更大作用的非人类宿主 由于IRS的结果，维持了多诺瓦氏杆菌的传播周期。最后， 项目1和项目3中提出的代谢和免疫学分析方法将应用于 由盖茨基金会赞助的正在进行的人类异种诊断调查，试图确定 与传播潜力相关的血浆和局部沙蝇叮咬部位的生物标志物 在受感染的人身上。

SUMMARY The visceral leishmaniasis (VL) elimination strategy in the Indian subcontinent, that has a current goal of reducing the incidence of VL to below 1/10,000 people by 2017, consists of rapid detection and treatment of VL cases to reduce the number of human infection reservoirs, and vector control using indoor residual spraying (IRS). To achieve sustained elimination of VL, an appropriate surveillance program is needed to detect the emergence of insecticide resistant populations of P. argentipes, as well as studies to define the contribution of individuals from across the infection spectrum, and of possible non-human reservoirs, to the maintenance of the L. donovani transmission cycle. To address these issues, we have proposed a series of cutting edge studies that will exploit the exceptional resources now available to carry out vector related research in Bihar. These resources include 1) a new, fully functional insectary that will permit containment, rearing, infection, and manipulation of field caught sand flies, 2) an established working colony of P. argentipes that has been certified for use in xenodiagnostic procedures, and 3) an entomological field team that has extensive experience in the capture, taxonomic identification, and colonization of sand flies in Bihar. Studies are proposed to survey insecticide resistance in field populations of P. argentipes, establish a pyrethroid resistant colony, and develop biomarker-based assays to quickly identify emergent populations of insecticide resistant sand flies in Bihar. Vector competency studies will be conducted on wild caught P. argentipes captured from different peridomestic settings and associated to their midgut microbiota profiles. Methods for metagenomic sequencing and analysis will interface with the studies of the human gut microbiome proposed in Project 1. Cultivable bacterial flora that appear to negatively or positively impact Leishmania development will be used in bacterial feeds in attempts to manipulate vector competence in colonized flies. The colonized flies will also be used in xenodiagnostic assays to identify possible non-human reservoirs that may be playing a greater role in the maintenance of the L. donovani transmission cycle as a consequence of IRS. Finally, the metabolic and immunologic profiling approaches proposed in Projects 1 & 3 will be applied to the ongoing human xenodiagnostic surveys sponsored by the Gates Foundation in attempts to identify biomarkers in plasma and localized sand fly bite sites that are associated with transmission potential in infected people.