Agri-food connectivity drives the resurgence and geographic expansion of human brucellosis in China.

Agri-food systems are increasingly recognised as drivers of zoonotic disease emergence, yet the mechanisms by which modern food production, trade, and distribution reshape pathogen transmission remain poorly quantified. Here we integrate two decades of nationwide surveillance, epidemiological modelling, and phylogenomic analyses of 4215 Brucella genomes from 79 countries and regions to elucidate the drivers of brucellosis re-emergence in China. Nationwide, human cases increased by 282.6% between 2005 and 2023, far exceeding the 8.1% increase in sheep inventory. This decoupling indicates a fundamental shift in transmission pathways. In northern China, livestock reservoir and production indicators accounted for 88.9% of the relative model contribution, consistent with direct occupational exposure; whereas in southern China, the agri-food logistics and market connectivity domain showed the largest contribution (64.1%), providing quantitative evidence that modern food-distribution infrastructure now drives brucellosis risk in those regions. Demographic shifts reaffirm this transition, with marked incidence increases among children and the elderly, indicating expanded foodborne and household exposures. Phylogenomics reveals that China's epidemic reflects long-term endemic amplification of a dominant Brucella melitensis clade (Lineage 2.4), with a hierarchical hub-and-spoke transmission network linking northern pastoral source regions to historically non-endemic southern provinces through national livestock and logistics networks. Comparative genomics further identifies lineage-specific gene acquisitions, adaptive variation in the outer membrane protein Omp2b, and recurrent convergent disruption of puuD enriched among winter isolates. Together, these findings reframe brucellosis resurgence as an emergent property of agri-food connectivity and highlight domestic supply chains, transport hubs, and cold-chain infrastructure as priority targets for surveillance and intervent ion.