A Cross-Sectional Study of Rift Valley Fever Exposure in Humans and Livestock in Southwestern Uganda Using a One Health Approach: Evidence of Elevated Seroprevalence Outside Recognized Outbreak Periods

Rift Valley fever (RVF) transmission has intensified in southwestern Uganda since 2016. To quantify human and livestock exposure and associated risks, we conducted a cross-sectional serosurvey in Isingiro, Kabale and Rubanda districts between October and November 2023. A total of 766 humans and 2383 livestock were sampled and tested for RVF antibodies using ELISA, with structured questionnaires capturing demographic, behavioral and environmental data. Human seroprevalence was 11.5% (88/766), varying by district (13.8% Isingiro, 11.8% Rubanda, 6.8% Kabale; <i>p</i> = 0.04). Independent predictors from the multivariate model included raw-meat consumption (aOR 6.11; 95% CI 1.16-27.80), cattle ownership (aOR 2.33; 95% CI 1.27-4.36), male sex (aOR 1.64; 95% CI 1.02-2.66) and younger age compared with ≥50 years (31-49 years: aOR 2.02; 95% CI 1.20-3.48; 18-30 years: aOR 2.37; 95% CI 1.04-5.14). Herd-level seroprevalence was 42.5% (204/480), associated with cattle presence (aOR 6.48; 95% CI 4.10-10.40), lack of carcass burial (aOR 15.70; 95% CI 4.23-63.60), on-farm slaughter (aOR 2.14; 95% CI 1.21-3.89) and increased mosquito activity (aOR 1.75; 95% CI 1.13-2.73). Animal-level seroprevalence was 14.6% (347/2383), highest in cattle (33.8%), with cattle having markedly higher odds than goats (aOR 6.73; 95% CI 4.96-9.14). These findings demonstrate substantial transmission and highlight cattle-centered interfaces as primary targets for control to humans.