Brucellosis has traditionally been considered an occupational zoonotic disease associated with direct contact with infected sheep, goats and other livestock. In China, the disease has historically been concentrated in northern pastoral regions. In recent years, however, cases have increasingly appeared in southern provinces where local sheep and goat production is relatively limited.
A research team led by scientists from Soochow University and the National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, investigated what is driving this changing geographic pattern.
The researchers integrated nationwide surveillance data with demographic, livestock-production, socioeconomic and logistics information, together with phylogenomic analyses of 4215 Brucella genomes from 79 countries. The study provides a comprehensive picture of how changing food-production and distribution systems may influence the resurgence and geographic expansion of brucellosis in China.
Human brucellosis has increased markedly over the past two decades. Annual reported cases rose from 19,721 in 2007 to 70,439 in 2023, while substantial increases were also observed in historically low-risk southern provinces, including Guangxi, Sichuan and Hunan.
One striking finding was the growing disconnect between livestock population size and human disease burden. Between 2005 and 2023, reported human cases increased by 282.6%, whereas the national sheep population increased by only 8.1%. The researchers therefore examined whether broader changes in agricultural production, trade and distribution could help explain the changing epidemic.
The analysis revealed a clear north-south contrast.
In northern China, where large sheep populations and pastoral production systems remain common, livestock reservoir and production indicators made the largest contribution to explaining provincial differences in disease burden. In southern China, however, agri-food logistics and market connectivity — including indicators of cold-chain market scale and freight circulation — showed the largest relative contribution to model performance, at 64.1%, compared with 10.2% for livestock production.
Demographic changes provided additional evidence that exposure patterns may also be broadening. From 2004 to 2024, the increase in incidence was particularly pronounced among children and older adults, groups that are less likely to experience traditional occupational livestock exposure. The findings are consistent with an increasing contribution of household and food-related exposure pathways alongside classical occupational transmission.
Genomes reveal a north-to-south transmission network
To determine whether the epidemiological patterns were also reflected in pathogen movement, the researchers analysed 1246 non-redundant clinical Brucella isolates collected across 30 Chinese provinces and integrated them with publicly available genomes, creating a global dataset of 4215 genomes from 79 countries.
Most Chinese B. melitensis isolates belonged to clade 2.4, indicating prolonged endemic circulation and diversification in China rather than the recent introduction of a single epidemic clone. The researchers further divided global B. melitensis diversity into 10 major clades and 47 subclades using a high-resolution genomic framework.
Phylogeographic reconstruction revealed a hierarchical and asymmetric transmission network. Northern pastoral regions were frequently inferred as sources, with Inner Mongolia emerging as a major source of several dominant subclades. Shanxi, Shaanxi, Shandong and Sichuan showed characteristics of intermediate relay hubs, whereas many southern provinces were more frequently identified as recipients.
Long-distance dissemination was particularly important. Approximately 78% of inferred interprovincial movements involved single-strain introductions. These events had an average geographic distance of more than 500 km, and 58% occurred between non-neighbouring provinces.Such events were especially common among introductions into historically non-endemic southern regions.
Shanxi and Shaanxi emerged as particularly important relay regions connecting northern pastoral areas with central and southern China. More than 70% of isolates in the two provinces were inferred to originate from Inner Mongolia, while Taiyuan appeared to act as an important gateway for lineage introduction and onward dissemination.
The authors caution that these phylogeographic movements are inferred from genomic relationships and should not be interpreted as direct proof that individual infections were transmitted through specific food products or supply chains. More detailed livestock-movement and animal-product surveillance will be needed to directly identify individual transmission pathways.
Tracking how the pathogen evolves
The study also examined how B. melitensis has evolved during its long-term circulation.The researchers identified 13 lineage-specific gene acquisition events involving functions related to carbohydrate metabolism, metal-ion transport and cell-envelope modification. They also detected signatures of episodic diversifying selection in the outer membrane protein genes omp2a and omp2b, suggesting that variation in surface antigens may contribute to lineage diversification.
Another notable finding involved puuD, a gene related to putrescine degradation. Loss-of-function mutations in puuD appeared repeatedly across different genetic backgrounds and were disproportionately detected among isolates collected during winter months, raising the possibility that the gene may be associated with adaptation to cold-season or high-latitude environments. The biological mechanism, however, requires further experimental validation.
Finally, the researchers developed a hierarchical SNP-barcode typing framework for high-resolution surveillance of B. melitensis. When tested on 82 metagenomic datasets, genotype assignments were fully concordant with those obtained from isolate-derived whole-genome sequences, suggesting that the system may eventually allow fine-scale pathogen tracking directly from complex clinical samples.
Together, the findings suggest that the contemporary resurgence of brucellosis in China cannot be understood solely in terms of local livestock populations. As livestock, animal products and food-distribution networks become increasingly interconnected, the infrastructure linking regions may also influence where zoonotic pathogens can spread.
The study highlights the importance of extending brucellosis surveillance beyond traditional pastoral regions to livestock transportation routes, wholesale markets, supply-chain hubs and cold-chain systems. Integrating human surveillance, animal surveillance, food-system monitoring and genomic epidemiology may provide a more effective framework for controlling zoonotic diseases in an increasingly connected world.
Journal
Science Bulletin