Zoonotic Barrier Disruption and the Rise of the Third Plague Pandemic: A One Health Analysis of 19th-Century Yunnan and the Emergence of Yersinia Pestis Strain 1.ORI

The emergence of the Third Plague Pandemic in 19th-century Yunnan, linked to Yersinia pestis strain 1.ORI, remains incompletely understood. Applying a One Health framework, this study investigates how human-driven ecological and societal disruptions during the 19th century compromised zoonotic barriers, facilitating initial spillover and a bottleneck event that enabled global spread. Our interdisciplinary methodology analyzes Qing dynasty gazetteers, historical medical records, and environmental data, integrated with biological evidence on transmission dynamics involving commensal rats and the flea vector Xenopsylla cheopis. Results indicate that convergent factors—including widespread deforestation, intensified mining/agriculture, population growth, high synanthropic rat densities, and the disruptions of the Panthay Rebellion—collectively created a high-risk interface for zoonotic transfer. Critically, comorbidities such as malnutrition, heavy metal exposure, and opium use likely eroded host immune resilience in both rodent and human populations, amplifying transmission. Yunnan’s rapid socio-ecological transformation was thus a critical catalyst for pandemic emergence. This analysis underscores how historical land-use, demographic shifts, and public health conditions shaped zoonotic risk. Crucially, a One Health assessment must analyze interactions across time and space, recognizing that environmental, biological, and socioeconomic changes occur on non-uniform temporal scales.