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Crimean-Congo haemorrhagic fever (CCHF) is a tick-borne viral infection, characterized by haemorrhagic fever in humans and transient asymptomatic infection in animals. It is an emerging human health threat causing sporadic outbreaks in Uganda. We conducted a detailed outbreak investigation in the animal population following the death from CCHF of a 42-year-old male cattle trader in Lyantonde district, Uganda. This was to ascertain the extent of CCHF virus (CCHFV) circulation among cattle and goats and to identify affected farms and ongoing increased environmental risk for future human infections. We collected blood and tick samples from 117 cattle and 93 goats, and tested these for anti-CCHFV antibodies and antigen using an enzyme-linked immunosorbent assay (ELISA), quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and target enrichment next generation sequencing. CCHFV-specific IgG antibodies were detected in 110/117 (94.0%) cattle and 83/93 (89.3%) goats. Animal seropositivity was independently associated with female animals (AOR = 9.42, P = 0.002), and animals reared under a pastoral animal production system (AOR = 6.02, P = 0.019] were more likely to be seropositive than tethered or communally grazed animals. CCHFV was detected by sequencing in Rhipicephalus appendiculatus ticks but not in domestic animals. This investigation demonstrated very high seroprevalence of CCHFV antibodies in both cattle and goats in farms associated with a human case of CCHF in Lyantonde. Therefore, building surveillance programs for CCHF around farms in this area and the Ugandan cattle corridor is indicated, in order to identify opportunities for case prevention and control.

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