Abstract

Chagas disease is a zoonose, with a wide range of vertebrate reservoir hosts, and the most important parasitic disease in South America for human morbidity and mortality infecting over 8 million with a lifelong infection. The causative agent of the disease is Trypanosoma cruzi. Human T. cruzi infections are predominated by an anomalous recombinant parasite (TcVI) that spans millions of years of evolutionary divergence between its parental genotypes. Reducing disease transmission requires twoobjectives: 1) understanding the transmission of T. cruzi between humans, its reservoir hosts and their interaction is a major objective to reduce disease incidence in humans; 2) understanding the genetic mechanisms deployed during its lifelong infection of the vertebrate host.Using molecular population genomic technology I demonstrate the epidemiology of South American Chagas disease: sylvatic (wild) Chagas disease is split between arboreal (tree) and terrestrial populations; humans can be infected from either source but human infections in Venezuela appeared to result from human to human transmission (Objective 1).

Using microarray genome technology I demonstrate parasite recombination between sylvatic (opossum) hosts and, moreover, the evolutionary selective pressure driving the formation of the human associated recombinant genotype TcVI.  I will  describe how this anomalous TcVI recombination event resulted in mass acquisition of surface proteins, viz. mucin and  mucin associated proteins (MASPs) (Objective 2).  An interesting and unexpected outcome of the research is that the  specific genetic tool used in the epidemiological studies herein (“dinucleotide microsatellites”) show enhanced rates of mutation, anomalous genome clustering and abundance in mucin genes for T. cruzi  and other medical trypanosomatids.