Aim and Background: Foot and Mouth Disease (FMD) is a prioritized transboundary animal disease, endemic in Ethiopia, and it has a high impact on cattle production and trade nationally and internationally. Methods: To ascertain the sero-prevalence and identify the exposure factors connected to a seropositive FMD in cattle, a cross-sectional study was conducted in three weredas of the West Omo Zone from January 2022 to February 2022. Multistage sampling was used to take one study wereda based on agroecology from the highland, midland, and lowland of the zone. Selection of cattle herd and blood samples from cattle were taken by using a simple random method. The Statistical Package for Social Science Version 25 was used to analyze the pertinent data once it had been entered and coded into Microsoft Excel. Results: The study area's FMD seroprevalence for individual cattle and at the herd level was 5.3% with a 95% confidence interval (3.51%–7.99%) and 77.78% (n= 9), respectively. The high herd level recorded during the current study was evidence that the disease has spread throughout the zone. Multinomial logistic regression analysis showed the age of the animal and study wereda are significantly(p<0.05) associated with the sero-prevalence of FMD in this study. High cattle movement to big markets and long exposure of old cattle to the disease may contribute to the significant association of the disease with these risk factors. Conclusion: This study showed that herd-level FMD seropositivity is high, necessitating the identification of specific FMD serotypes and the commencement of appropriate FMD prevention and control strategies in the zone.
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