Socio-ecological determinants of Mpox transmission risk in Uganda: mapping community-level risk and protective factors, a multi-district cross-sectional study

<jats:p>Background Uganda is among the African countries most affected by the ongoing clade Ib Mpox (monkeypox) outbreak, with sustained community transmission since 2024. Effective community-level prevention depends on understanding how risk and protective factors are distributed across the social ecology. We applied a socio-ecological framework to map the determinants of Mpox transmission risk and protective practice in affected districts. Methods We conducted a multi-district, community-based cross-sectional survey of 3,960 community members aged 15–65 years across high- and low-burden districts in Uganda between February and March 2025. Participants were selected by multistage sampling and interviewed using a structured tool administered on tablets. Individual-, household-, community- and structural-level characteristics were summarised descriptively. A modified Poisson regression model with district-clustered robust standard errors was used to estimate crude and adjusted prevalence ratios (cPR, aPR) for adequate Mpox prevention and control practice; the multivariable model included 3,916 participants with complete covariate data. Analyses were performed in R version 4.5.0. Results The mean age was 32.0 years (SD 10.7); 51.9% (2,056/3,960) were female and most had secondary education (54.2%). Comorbidity burden was substantial (sexually transmitted infections 28.3%, HIV 13.9%, tuberculosis 8.2%, malnutrition 6.2%). Four in five participants (80.2%) resided in high-burden districts and 60.9% perceived themselves at risk, yet only 18.7% had comprehensive knowledge of Mpox and 53.8% reported adequate prevention practice despite near-universal message exposure (93.2%). In adjusted analysis, comprehensive knowledge (aPR 1.32, 95% CI 1.15–1.52) and message exposure (aPR 1.88, 95% CI 1.31–2.71) were by far the strongest protective determinants; several occupational, income, education and religious categories were also independently associated with practice, whereas biological comorbidities were not. Conclusions Mpox transmission risk in Uganda is concentrated in high-burden districts and overlaps with a heavy comorbidity burden. Although some social and structural factors were independently associated with protective practice, it was driven primarily by the modifiable cognitive factors of knowledge and message exposure rather than by biological characteristics. Community-level interventions that convert near-universal message reach into accurate, actionable knowledge are likely to yield the greatest protective gains.</jats:p>