Crimean-Congo Hemorrhagic Fever Infection in the Small Ruminant Population in N. Macedonia: A Seroepidemiological Study as a Step Towards Better Understanding of the CCHF Epidemiology in the Country.

Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne zoonotic disease of significant public health concern, particularly in endemic regions. However, data on the distribution and circulation of Crimean-Congo hemorrhagic fever virus (CCHFV) in animal populations remain limited, despite their importance for assessing virus circulation and infection patterns. A cross-sectional seroepidemiological study was conducted in North Macedonia (N. Macedonia) to determine the seroprevalence rates of CCHFV in small ruminants and to identify areas at increased risk of virus circulation. A total of 1992 sera samples from sheep and goats were tested for Crimean-Congo hemorrhagic fever virus (CCHFV) antibody using a commercial enzyme-linked immunosorbent assay (ELISA). Data on species, age, animal origin, and risk factors (questionnaire) were collected and analyzed. Overall, true seroprevalence, calculated by adjusting the apparent seroprevalence according to the diagnostic performance of the ELISA assay in order to estimate the actual prevalence in the studied population, was 25.02% (493/1992; 95% CI 23.11-26.94). Sheep showed higher seroprevalence rates, 27.34% (397/1452; 95% CI 25.11-29.69), compared to goats, 17.78% (96/540; 95% CI 14.78-21.23). Seroprevalence rates varied markedly across regions, ranging from 2.41% to 49.80%, with the highest values observed in the Eastern and Vardar regions. Seroprevalence rates increased with age, reaching the highest values in animals aged ≥ 5 years, 27.27% (81/297; 95% CI 22.52-32.60). Small ruminants, particularly sheep, may serve as useful indicators for defining the high-risk areas for CCHFV transmission, providing valuable support for a One Health approach.