Spatially Heterogeneous Land Cover/Land Use and Climatic Risk Factors of Tick-Borne Feline Cytauxzoonosis

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Abstract
Feline cytauxzoonosis is a highly fatal tick-borne disease caused by a hemoparasitic protozoan, Cytauxzoon felis. This disease is a leading cause of mortality for cats in the Midwestern United States, and no vaccine or effective treatment options exist. Prevention based on knowledge of risk factors is therefore vital. Associations of different environmental factors, including recent climate were evaluated as potential risk factors for cytauxzoonosis using Geographic Information Systems (GIS). There were 69 cases determined to be positive for cytauxzoonosis based upon positive identification of C. felis within blood film examinations, tissue impression smears, or histopathologic examination of tissues. Negative controls totaling 123 were selected from feline cases that had a history of fever, malaise, icterus, and anorexia but lack of C. felis within blood films, impression smears, or histopathologic examination of tissues. Additional criteria to rule out C. felis among controls were the presence of regenerative anemia, cytologic examination of blood marrow or lymph node aspirate, other causative agent diagnosed, or survival of 25 days or greater after testing. Potential environmental determinants were derived from publicly available sources, viz., US Department of Agriculture (soil attributes), US Geological Survey (land-cover/landscape, landscape metrics), and NASA (climate). Candidate variables were screened using univariate logistic models with a liberal p value (0.2), and associations with cytauxzoonosis were modeled using a global multivariate logistic model (p<0.05). Spatial heterogeneity among significant variables in the study region was modeled using a geographically weighted regression (GWR) approach. Total Edge Contrast Index (TECI), grassland-coverage, humidity conditions recorded during the 9(th) week prior to case arrival, and an interaction variable, "diurnal temperature range × percent mixed forest area" were significant risk factors for cytauxzoonosis in the study region. TECI and grassland areas exhibited significant regional differences in their effects on cytauxzoonosis outcome, whereas others were uniform. Land-cover areas favorable for tick habitats and climatic conditions that favor the tick life cycle are strong risk factors for feline cytauxzoonosis. Spatial heterogeneity and interaction effects between land-cover and climatic variables may reveal new information when evaluating risk factors for vector-borne diseases.

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