Transmission Project

输变电工程

• 批准号: 10368199
• 负责人: Amélie VANTAUX
• 金额: $ 6.75万
• 依托单位: WALTER AND ELIZA HALL INST MEDICAL RES
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-28 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10368199
• 关键词: Transmission; Project

Summary Despite having reduced malaria transmission to historically low level, in many Asia-Pacific countries endemic areas transmission continues and common vector control tools seem not able to interrupt transmission. The reasons for the resilience of malaria transmission are on unclear but are likely to involve not only parasite but also host and vector factors. At low transmission, asymptomatic infections account for up to 90% of infections and it they are able to transmit efficiently they could be a key component of the infectious reservoir. The only way to accurately ascertain if an infection can transmit is to feed the blood to mosquitoes and determine rate and density of infections of the mosquito midgut. Such xenodiagnostic studies are severely lacking, in particular in predominantly P. vivax endemic area. We are now proposing to conduct an in-depth dissection of the contribution of host, parasite and vector factors to maintaining malaria transmission by conducting a set studies that combine assessment of the infectivity of well characterized field samples using direct membrane feeding (DFMA) with in-depth laboratory studies in 3 sites with substantially different transmission scenarios. Initially we will investigate the relative infectivity of asymptomatic and symptomatic infections establish the association of parasite and gametocytes density with infectivity and study effect of transmission blocking immunity, vector microbiome and type parasite for gene associated with evasion of mosquito immune responses and markers of artemisinin and partner drugs resistance to determine their effect on transmission potential. As parasite and gametocyte fluctuate over time, so may their infectivity. We will therefore determine the temporal variation in infectivity an in-depth cohort study in PNG, where asymptomatic carriers will be followed for 3 weeks and mosquitoes fed every 3-4 days. Addition, we will determine proportion of pre- and post-treatment infectivity in in artemisinin-resistant and sensitive symptomatic P. falciparum. Together with our large epidemiological datasets (see Project 1), this will allow us not only clarify the contribution of asymptomatic infections to transmission but also resistance may come with a transmission associated fitness cost, which may slow down the spread of resistance. Both human and vector behavior may limit human-vector contact in the Asia-Pacific, where vectors are frequently / predominantly outdoor biting, leading to transmission away from people’s dwelling. The low biting rate and unclear location of human-vector contact makes it difficult to identify its determinants. We will we study patterns of human vector contact by determining the presence of antibodies against salivary gland protein antibodies proteins from An. dirus. An. minimus and An. Farauti in samples from cross-sectional and cohort studies in Project 1. By providing an in-depth understanding of the transmission characteristics at each of our sites, the proposed studies will not only contribute to developing biologically accurate transmission models but will help us design better methods to track and eliminate transmission even in hard to track populations such asymptomatic carriers.

总结 尽管疟疾传播已降至历史最低水平，但在许多亚太国家， 该地区的传播仍在继续，普通病媒控制工具似乎无法阻断传播。的 疟疾传播恢复力的原因尚不清楚，但可能不仅涉及寄生虫， 还有宿主和媒介因素。在低传播时，无症状感染者占感染者的比例高达90% 如果它们能够有效传播，它们可能是传染源的关键组成部分。唯一的 准确确定感染是否可以传播的方法是将血液喂给蚊子， 和蚊子中肠感染的密度。这种异种诊断研究严重缺乏， 尤其是间日疟原虫流行区。我们现在建议对 宿主、寄生虫和病媒因素对维持疟疾传播的贡献， 使用直接膜联合收割机对充分表征的现场样品的感染性进行评估的研究 通过在3个具有显著不同传播情况的地点进行深入的实验室研究， 最初，我们将调查无症状和有症状感染者的相对传染性， 寄生虫和配子体密度与感染性的关系及传播阻断效果的研究 蚊子免疫逃避相关基因免疫、载体微生物组和寄生虫分型 青蒿素和伙伴药物抗药性的反应和标志，以确定其对传播的影响 潜力由于寄生虫和配子体随时间波动，因此它们的传染性也可能波动。因此我们将决定 感染性的时间变化是在巴布亚新几内亚进行的一项深入的队列研究， 随后3周，每3-4天喂一次蚊子。此外，我们将确定预处理和 治疗后在青蒿素耐药和敏感症状恶性疟原虫的感染性。连同我们 大型流行病学数据集（见项目1），这将使我们不仅能够澄清 无症状感染者要传播还要耐药，可能与传播相关联的健身 成本，这可能会减缓阻力的蔓延。人类和病媒的行为都可能限制人类病媒 在亚太地区，病媒经常/主要在户外叮咬，导致传播 远离人们的居所。低叮咬率和不清楚的位置，人与病媒接触， 以确定其决定因素。我们将研究人类病媒接触的模式， 抗唾液腺蛋白抗体来自安氏按蚊的蛋白。dirus。一个. minimus和An.法劳蒂因 来自项目1中的横断面和队列研究的样本。通过深入了解 根据我们每个站点的传输特性，拟议的研究不仅有助于开发 生物学上准确的传播模型，但将帮助我们设计更好的方法来跟踪和消除 即使在难以追踪的人群中，如无症状的携带者，也会传播。