: Malaria remains one of the most important infectious diseases in the world. Transmission of malaria is contingent on the sporogonic development of Plasmodium parasites within mosquitoes. Sporogony is a complex process involving several morphologically distinct life stages and can be described in terms of parasite population dynamics. Most of our knowledge about sporogony comes from laboratory model systems. There are very few studies that have attempted to examine in a rigorous, quantitative fashion the process of sporogony as it occurs in nature. The major hypotheses of this proposal are that 1) parasite sporogony is more efficient in the field than in the laboratory and 2) there are key life stage transitions that determine the probability of sporogonic success within the vector (i.e., developmental bottlenecks). The magnitude and anatomical site of these bottlenecks within the mosquito may differ for different parasites developing in different mosquito species. The objective of this proposal is to use a population dynamics approach to identify the key life stage transitions that most strongly influence the success of Plasmodium falciparum and P. vivax sporogony within indigenous vector populations. The experimental approach will involve controlled mosquito infections with naturally occurring Plasmodium falciparum and P. vivax parasites, using local anopheline species. The parasite populations developing within infected mosquitoes will be sampled throughout sporogonic development and the densities of key parasite life stages (i.e., gametocytes, ookinetes, oocysts and sporozoites) will be quantified. The relative efficiencies of life stage transitions (changes in abundance) and the degree of heterogeneity in mosquito susceptibility to infection (frequency distributions) will be compared among mosquito infections. The proposed studies will be conducted in a small village in western Thailand. Studies are in collaboration with existing U.S. military field research efforts and the Thai Ministry of Public Health in an effort to understand how the population dynamics of sporogony correlate to the epidemiology of local malaria transmission. This project represents the first long-term examination of the natural population dynamics of malaria parasites within their natural vectors and will lead to a better understanding of how plasmodial parasites survive and are maintained within mosquitoes in the field.
