PARASITE TRANSMISSION, WORM GENETICS, INFECTION AND PATHOLOGY IN FILARIASIS

该项目旨在解决目前对淋巴丝虫病流行病学和控制的认识中的一个关键空白，即传播异质性对（I）在个体宿主和家庭水平上观察到的感染，疾病和免疫反应模式的贡献以及（2）寄生虫的群体遗传学。最近对丝虫病和其他蠕虫的研究表明，更好地了解这一主题对于描述感染和疾病动态和分布的机制以及控制淋巴丝虫病的效果至关重要。将结合以下两种方法研究暴露变异性对各人群水平班氏丝虫感染、疾病和免疫反应模式的影响：（1）以家庭为基础的实地研究，以收集关于病媒叮咬率和宿主免疫流行病学变量的详细平行数据;（2）对来自家庭的平行蚊子和人类血液样本进行新的实验室分析，以量化个人的暴露率。实地研究将在巴布亚新几内亚的两个流行村（空间结构不同，因此传播模式不同）进行，但也将从肯尼亚的项目2现场收集寄生虫样本，以便比较这两个流行地区之间的寄生虫遗传差异。对W. bancrofii，包括估计传播模式对基因流动和药物选择的影响，将通过分离和应用微卫星进行。最后，理论分析，利用新的随机方法来模拟暴露变异性对蠕虫免疫流行病学和种群遗传学的影响，将被用来解释从实地研究的结果。这将具体解决感染的动态，蠕虫种群遗传学，包括驱虫药抗性的演变，以及观察到的空间传播模式的影响。

This project seeks to address a key gap in current understanding regarding the epidemiology and control of lymphatic filariasis, viz. the contribution of transmission heterogeneities to (I) patterns of infection, disease and immune response observed at the individual host and household levels and (2) the population genetics of the parasite. Recent studies in filariasis and other helminths indicate that gaining a better understanding of this topic will be crucial to characterizing the mechanisms underlying infection and disease dynamics and distribution, and hence the effects of control in lymphatic filariasis. The impact of exposure variability to bancroftian filarial infection, disease and immune response patterns at each population level will be studied using a combination of(1) a household-based field study to collect detailed parallel data on vector biting rates and host immuno-epidemiological variables and (2) novel laboratory analysis of parallel mosquito and human blood samples from households to quantify the exposure rate of individuals. The field study will be conducted in two endemic villages (differing in spatial configuration and hence transmission patterns) in Papua New Guinea, although parasite samples will also be collected from the Project 2 site in Kenya to enable a comparison of parasite genetic differentiation between these two endemic regions. The population genetics of W. bancrofii, including estimating the effects of transmission patterns on gene flow and drug selection, will be carried out via the isolation and application of microsatellites. Finally, theoretical analyses, utilizing new stochastic approaches to modeling the impact of exposure variability on helminth immunoepidemiology and population genetics, will be used to interpret the results from the field studies. This will specifically address the dynamics of infection, worm population genetics, including the evolution of anthelmintic resistance, and the impact of observed spatial transmission patterns.