Transmission Project

摘要 尽管已将疟疾传播率降至历史最低水平，但在许多亚太国家，疟疾仍在流行 地区传播仍在继续，常见的病媒控制工具似乎无法中断传播。这个 疟疾传播具有弹性的原因尚不清楚，但很可能不仅与寄生虫有关，而且 还有宿主和媒介因子。在低传播率时，无症状感染占感染的90%。 如果它们能够有效传播，它们可能成为感染性水库的关键组成部分。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，并测定比率 以及蚊子中肠的感染密度。这种异种诊断研究严重缺乏，#年。 尤其是在以间日疟原虫为主的流行区。我们现在提议进行一项深入的解剖 宿主、寄生虫和媒介因素对维持疟疾传播的作用 结合使用直接膜评估具有良好特性的现场样本的感染性的研究 在3个传播情景截然不同的地点进行深入的实验室研究，以喂养(DFMA)。 首先，我们将调查无症状和有症状感染的相对传染性，建立 寄生虫和配子体密度与传染性的关系及传播阻断效果的研究 蚊虫免疫逃避相关基因的免疫、载体微生物群和寄生虫类型 青蒿素和配对药物耐药性的反应和标志物，以确定它们对传播的影响 潜力。由于寄生虫和配子体随着时间的推移而波动，它们的传染性也可能会随着时间的推移而变化。因此，我们将决定 传染性的时间变化在巴新的深入队列研究中，无症状携带者将是 随访3周，蚊虫每隔3~4天喂食一次。此外，我们将确定预付款和 治疗后对青蒿素耐药和敏感症状性恶性疟原虫的感染性。与我们的 大型流行病学数据集(见项目1)，这将使我们不仅能够澄清 无症状的感染传播，也可能伴随着抵抗力的传播而来 成本，这可能会减缓耐药性的传播。人类和媒介的行为都可能限制人类媒介 在亚太地区接触，那里的媒介经常/主要在户外叮咬，导致传播 远离人们的住处。咬合率低，人与媒介接触的位置不清楚，这使得它很难 以确定其决定因素。我们将通过确定人类媒介接触的存在来研究人类媒介接触的模式 抗唾液腺蛋白抗体的抗体。迪鲁斯。一种。Minimus和An.法拉乌蒂在 项目1中横断面和队列研究的样本。通过提供对 我们每个站点的传播特征，拟议的研究不仅将有助于开发 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 即使在很难追踪的人群中传播这种无症状的携带者。

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.