Persistent, Consistent, and Neglected: Investigating the Geographic Epidemiology and Vector Ecology of La Crosse virus Neuroinvasive Disease

La Crosse virus (LACV) causes more pediatric neuroinvasive disease than any other arbovirus in the United States (US). Despite decades of recognized LACV transmission, it remains a consistent and neglected public health burden due to limited public health resources, low community awareness, and a lack of actionable research. The broad objectives of this research were to investigate geographic disparities in LACV infection risk, assess biases in the surveillance of LACV vectors, evaluate the potential for community-engaged science to supplement LACV surveillance and control infrastructure, and to investigate the associations between land cover and vector abundances. County-level human disease data from 2003-2021 were used to confirm three persistent LACV-ND risk clusters in the eastern US, each within the Appalachian region. When human disease was investigated at a lower spatial scale within one of those persistent clusters, the results revealed that a disproportionate burden of disease occurred within a few focal areas, while other areas reported few-to-no cases. Common methods for vector surveillance were evaluated to identify potential trap-dependent biases in LACV vector surveillance. Trap type strongly influenced surveillance results, and no single trap was adequate for simultaneous surveillance of all major LACV vectors. The distribution of LACV vectors was also investigated in relation to a land cover gradient ranging from recreational forests to parks in urban areas. The principal LACV vector was the most abundant species in forested areas but was less abundant relative to an accessory vector in areas characterized by impervious surfaces, demonstrating the close relationship between urban land cover and LACV vector abundances. Additional research was conducted to investigate the potential for community engagement programs to produce high-quality vector surveillance data, with results demonstrating that community-driven surveillance can be used to obtain a reliable understanding of LACV vector population trends. Taken together, the results of these studies can be used to guide the detection and prevention of LACV infections in Appalachia to reduce the burden of pediatric disease in this region.