Roughly 10% of the global population is at risk of schistosomiasis, a snail-22 borne parasitic disease that ranks among the most important water-based diseases of 23 humans in developing countries 1-3 . Increased prevalence, infection intensity, and spread of 24 human schistosomiasis to non-endemic areas has been consistently linked with water 25 resource management related to agricultural expansion, such as dam construction, which 26 has resulted in increased snail habitat 1,4-6 . However, the role of agrochemical pollution in 27 human schistosome transmission remains unexplored, despite strong evidence of 28 agrochemicals increasing snail-borne diseases of wildlife 7-9 and a projected 2-to 5-fold 29 increase in global agrochemical use by 2050 10 that will disproportionately occur in 30 schistosome-endemic regions. Using a field mesocosm experiment, we show that 31 environmentally relevant concentrations of fertilizer, the common herbicide atrazine, and 32 the common insecticide chlorpyrifos, individually and as mixtures, increase densities of 33 schistosome-infected snails by increasing the algae snails eat (fertilizer and atrazine) and 34 decreasing densities of snail predators (chlorpyrifos). Epidemiological models indicate that 35 these agrochemical effects can increase transmission of schistosomiasis. Hence, the rapid 36 agricultural changes occurring in schistosome-endemic regions 11,12 that are driving 37 increased agrochemical use and pollution could potentially increase the burden of 38 schistosomiasis in these areas. Identifying agricultural practices or agrochemicals that 39 minimize disease risk will be critical to meeting growing food demands while improving 40 human wellbeing 13,14 .41Main Text: The global human population is expected to reach approximately 9.7 billion 42 people by 2050 12 . To meet the food demands necessary to support this population, agricultural 43 production is projected to increase 60 to 70 percent globally, with fertilizer use increasing 2-to 44 4-fold and pesticide use 2-to 5-fold relative to levels in 2000 10,11 . Most of the increase in both 45 human population and agrochemical use will occur in developing regions of the world where 46 schistosomiasis is endemic 10-12 . For example, agricultural production is expected to nearly triple 47 in sub-Saharan Africa, the region experiencing the highest population growth rates 11 . 48 Schistosomiasis is caused by trematodes (flatworms) of the genus Schistosoma whose 49 transmission relies on freshwater snails that act as an intermediate host. Humans (and various 50 other mammal species) act as the definitive host (the host supporting the adult life stage of the 51 parasite) and are infected when cercariae (the free-swimming life stage of trematodes) released 52 from snails in infested waters penetrate through the skin of the definitive host and mature into 53 adult worms. Global control strategies generally rely on morbidity control through treatment 54 with praziquantel that kills adult worms harbored in human hosts, but drug t...

Global temperatures and infectious disease outbreaks are simultaneously increasing, but linking climate change and infectious disease to modern extinctions remains difficult. Thethermal mismatch hypothesispredicts that hosts should be vulnerable to disease at temperatures where the performance gap between themselves and parasites is greatest. This framework could be used to identify species at risk from a combination of climate change and disease because it suggests that extinctions should occur when climatic conditions shift from historical baselines. We conducted laboratory experiments and analyses of recent extinctions in the amphibian genusAtelopusto show that species from the coldest environments experienced the greatest disease susceptibility and extinction risk when temperatures rapidly warmed, confirming predictions of thethermal mismatch hypothesis. Our work provides evidence that a modern mass extinction was likely driven by an interaction between climate change and infectious disease.