Introduction The burden of brucellosis among smallholder farmers is poorly-documented in Uganda. The disease burden is likely to be high, given the high levels of endemicity, lots of exposures and due to lack of control measures. In order to designate appropriate control measures, the magnitude and risk factors for brucellosis need to be known. We established the burden of and risk factors for Brucella seropositivity in cattle, goats, and humans in Iganga district, eastern Uganda. Methods A cross-sectional study was conducted in in Kigulamo Parish, Iganga District. We enrolled 226 households and administered a structured questionnaire to heads of households to capture data on socio-demographic characteristics, human brucellosis-related risk factors, and livestock farming practices. Human, cattle, and goat blood samples were collected and tested serologically using commercial indirect-ELISA kits manufactured by USDA, USA. Results Of 451 human blood samples, 20 (4.4%) were positive. Among 345 cattle blood samples, 4 (1.2%) were positive and among 351 goat blood samples, one (0.3%) was positive. Persons who reported consuming locally-made dairy products had 4 times higher odds of Brucella seropositivity (OR = 4.0, CI = 1.14-14.03, p = 0.031) than those who did not. None of the risk factors we asked about were significantly associated with seropositivity in cattle and goats. Conclusion The seroprevalence of brucellosis in humans in smallholder households in Kigulamo was relatively low and associated with consumption of locally made dairy products. No risk factors were significantly associated with seropositivity in livestock, likely due to the small number of seropositive animals. We recommend a One Health approach to control brucellosis simultaneously in animals and humans needed to sustainably reduce the burden of brucellosis in Uganda and beyond.
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