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.
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