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Canine Visceral Leishmaniasis (VL), caused by<jats:italic>Le. infantum<\/jats:italic>, is a natural disease process which offers a insight into the interaction of the host and resultant disease outcome. Canine VL results in the same altered pathophysiology and immunodysregulation seen in humans. VL in US dogs is likely to be transmitted primarily via nontraditional, nonvector means. VL mediated by<jats:italic>Le. infantum<\/jats:italic>is endemic in U.S. Foxhound dogs, with vertical transmission likely to be the novel primary means of transmission. This population of dogs offers an opportunity to identify host factors of natural disease. 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