Insights into Crimean-Congo hemorrhagic fever virus exposure probability: a period cross-sectional study in wild and domestic ungulates

Crimean-Congo hemorrhagic fever (CCHF) is an emerging tick-borne human disease in Spain. Although CCHF is mainly confined to humans, the CCHF virus (CCHFV) can infect several vertebrate species. To predict high-risk exposure areas for public health interventions, it is essential to understand the factors that determine the risk of exposure to CCHFV through animal models. We conducted a cross-sectional study over a defined period (1999 to 2022) on various wild and domestic ungulate species in Castilla-La Mancha (CLM), south-central Spain. We analyzed 6,236 sera of ungulates using a specific double-antigen ELISA to assess CCHFV exposure spatial distribution. We modeled exposure probability with host and environmental predictors using generalized linear mixed models with a binomial distribution. Anti-CCHFV antibodies were detected in 3,531 sera (56.6%; 95% CI: 55.4 to 57.9%), with the greatest exposure rates in western and southern CLM. The red deer (Cervus elaphus Linnaeus, 1758) exhibited the highest seroprevalence (76.45%; 95%CI: 75.1 to 77.7%), and the best-fit statistical model indicated that it was the species with the highest risk of exposure. The most relevant predictors of virus exposure risk were shrubland cover, small ruminant density, wild ungulate density, and woodland cover. The spatial projection of the best-fit model identified high-risk foci in most of western and southwestern CLM but also in limited areas across the region. Our results demonstrate that serological surveys conducted on various CCHFV vector hosts serve as a potent, robust, and highly informative resource for public health authorities to address and prevent human CCHF cases in enzootic and emergency situations.