Climate determines transmission hotspots of Polycystic Echinococcosis, a life- threatening zoonotic disease, across Pan-Amazonia

Polycystic Echinococcosis (PE), a neglected life-threatening zoonotic disease caused by the cestode Echinococcus vogeli, is endemic in the Amazon. Despite being treatable, PE reaches a case fatality rate of around 29% due to late or missed diagnosis. PE is sustained in Pan-Amazonia by a complex sylvatic cycle. The hunting of its infected intermediate hosts (especially the lowland paca Cuniculus paca) enables the disease to further transmit to humans, when their viscera are improperly handled. In this study, we compiled a unique dataset of host occurrences (similar to 86000 records) and disease infections (similar to 400 cases) covering the entire Pan-Amazonia and employed different modeling and statistical tools to unveil the spatial distribution of PE's key animal hosts. Subsequently, we derived a set of ecological, environmental, climatic, and hunting covariates that potentially act as transmission risk factors and used them as predictors of two independent Maximum Entropy models, one for animal infections and one for human infections. Our findings indicate that temperature stability promotes the sylvatic circulation of the disease. Additionally, we show how El Nino-Southern Oscillation (ENSO) extreme events disrupt hunting patterns throughout Pan-Amazonia, ultimately affecting the probability of spillover. In a scenario where climate extremes are projected to intensify, climate change at regional level appears to be indirectly driving the spillover of E. vogeli. These results hold substantial implications for a wide range of zoonoses acquired at the wildlife-human interface for which transmission is related to the manipulation and consumption of wild meat, underscoring the pressing need for enhanced awareness and intervention strategies. Significance The impact of climate on neglected tropical diseases (NTDs) has been extensively discussed, but there is a lack of mechanistic evidence establishing a direct link. In this paper, we compiled a unique dataset to investigate the factors driving the spillover dynamics of Polycystic Equinococosis (PE), a neglected zoonotic disease with high case fatality rates, in Pan-Amazonia. PE spillover occurs through complex wildlife-human interactions facilitated by hunting and wild meat manipulation. Our study demonstrates that temperature stability promotes the sylvatic circulation of PE, while El Nino-Southern Oscillation extreme events disrupt hunting patterns, thereby affecting the risk of PE spillover to humans. These findings provide evidence attributing the effects of climate to NTDs in Pan-Amazonia, with implications for similar hunting-related zoonoses.