Persistent spatial clustering and predictors of pediatric La Crosse virus neuroinvasive disease risk in eastern Tennessee and western North Carolina, 2003–2020.

The combined region of eastern Tennessee and western North Carolina has a persistently high risk of pediatric La Crosse virus neuroinvasive disease (LACV-ND). To guide public health intervention in this region, the objectives of this retrospective ecological study were to investigate the geographic clustering and predictors of pediatric LACV-ND risk at the ZIP code tabulation area (ZCTA) level. Data on pediatric cases of LACV-ND reported between 2003 and 2020 were obtained from Tennessee Department of Health and North Carolina Department of Health and Human Services. Purely spatial and space-time scan statistics were used to identify ZCTA-level clusters of confirmed and probable pediatric LACV-ND cases from 2003–2020, and a combination of global and local (i.e., geographically weighted) negative binomial regression models were used to investigate potential predictors of disease risk from 2015–2020. The cluster investigation revealed spatially persistent high-risk and low-risk clusters of LACV-ND, with most cases consistently reported from a few high-risk clusters throughout the entire study period. Temperature and precipitation had positive but antagonistic associations with disease risk from 2015–2020, but the strength of those relationships varied substantially across the study area. Because LACV-ND risk clustering in this region is focally persistent, retroactive case surveillance can be used to guide the implementation of targeted public health intervention to reduce the disease burden in high-risk areas. Additional research on the role of climate in LACV transmission is warranted to support the development of predictive transmission models to guide proactive public health interventions. Author summary: La Crosse virus (LACV) is the most common cause of mosquito-borne neuroinvasive disease (e.g., encephalitis or meningitis) among children in the United States, but the spatial patterns and population-level risk factors for LACV infections are not well understood. In this study, we investigated the spatial patterns and areal risk factors of pediatric LACV neuroinvasive disease (LACV-ND) in eastern Tennessee and western North Carolina, a persistent hotspot of LACV-ND. We found that from 2003–2020, the highest risks of pediatric LACV-ND consistently occurred in a few areas within the study region. We also found that precipitation and temperature had positive but antagonistic relationships with area-level risk from 2015–2020, although the strength of those associations varied significantly across the study area. The results of this study have important implications for public health policy. Most notably, because LACV-ND consistently occurs in the same geographic areas over extended time periods, areas where cases have been previously reported should be prioritized for disease prevention programs to prevent continuous transmission. This study also provides initial evidence that climate may be related to the distribution of LACV-ND risk, but additional research is needed to better understand the complex relationship between climate and LACV epidemiology. [ABSTRACT FROM AUTHOR]