Abstract
Crimean-Congo Hemorrhagic Fever (CCHF) is a tick-borne zoonosis of major public health concern, not only because of its potential for severe outcomes in humans, but also due to its endemic presence in many regions and its expanding geographic distribution. We report on the first serological survey conducted in mainland France to detect antibodies against the Crimean-Congo Hemorrhagic Fever Virus (CCHFV) in domestic and wild fauna, and provides critical insights into the virus's circulation. We analyzed 8,609 cattle sera and 2,182 wildlife sera collected across the French Mediterranean region from 2008 to 2022, using enzyme-linked immunosorbent assays (ELISA) and pseudo-plaque reduction neutralization tests (PPRNT) for antibody detection and confirmation. Seropositivity was detected in both cattle (2.04%) and wildlife (2.25%), with higher rates observed in specific regions including the Pyrénées-Orientales and Hautes-Pyrénées. These findings reveal spatial clusters of CCHFV circulation and suggest the existence of enzootic transmission cycles involving local tick vectors and animal hosts. Our multivariate analysis identified key factors that influence seropositivity, including animal age, habitat characteristics, and potential wildlife interactions. The presence of natural open habitats and coniferous forests was significantly associated with higher seropositivity in cattle, while sex and geographical variability played a role in wildlife seroprevalence. These findings highlight the importance of environmental and anthropogenic factors in shaping the dynamics of CCHFV transmission. This work demonstrates that CCHFV is actively circulating in parts of mainland France, emphasizing the need for enhanced surveillance and integrated approaches to monitor zoonotic pathogens. It also raises questions about the role of additional tick vectors, such as Hyalomma lusitanicum, in the transmission cycle. These results advance our understanding of CCHF epidemiology and offer valuable guidance for public health strategies to mitigate the risks associated with this emerging disease.