Genetic characterisation of Crimean-Congo Haemorrhagic Fever Virus Isolates from North Macedonia: Insights Behind Human Cases

For the first time in nearly fifty years, North Macedonia reported human cases of Crimean-Congo Hemorrhagic Fever (CCHF) in 2024. The establishment of the Balkan Association for Vector-Borne Diseases (BAVBD) and successful epidemiological investigations resulted in identifying and characterising these cases, emphasising the importance of heightened surveillance and diagnostic efforts in the area. Two new cases of CCHF were discovered in patients with no recent travel history beyond North Macedonia, indicating local transmission. The first patient, a herder from a rural location, had chronic nosebleeds, leukopenia, thrombocytopenia, and impaired kidney function. The second patient, also from a rural area, presented with fever, abdominal pain, and thrombocytopenia. According to the genomic and phylogenetic analysis, autochthonous strains were found to be co-circulating, with sequences belonging to the Europe-1 lineage (Genotype V). Notably, the M and L segments from one patient’s isolate clustered with Turkish sequences, suggesting a possible reassortment event. Based on this finding North Macedonia appears to be an interaction zone for different CCHFV isolates from nearby areas. The resurgence of CCHF in the country highlights the need for continued surveillance and rapid diagnostic capabilities to control and reduce the impact of zoonotic diseases. Our study underscores the critical role of the BAVBD in coordinating regional efforts to enhance clinical vigilance and epidemiological response. Future research should focus on the complex ecology of CCHFV in the area to estimate human and animal health risks. Our study shows the clinical variability and severity of CCHF infections and calls for sustained public health strategies to prevent and control future outbreaks. The identification of possible viral reassortment underscores the dynamic nature of CCHFV and the need for continuous genetic monitoring to understand transmission patterns and public health impacts.