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The increase in both the number of events and diversity of emerging infectious diseases is threatening public and animal health.1 Over the last decade alone, the global community has experienced the repeated burden of emerging diseases, from pandemic influenza to Ebola and Zika virus epidemics. Other pathogens, notably influenza A (H7N9), Middle East respiratory syndrome coronavirus and Nipah virus, have demonstrated their capacity to become global threats. In parallel, the increasing incidence of multidrug-resistant pathogens has become a pressing global health threat that challenges both the human and animal health sectors. The prospect of a post-antibiotic era prompted a high-level consultation on antimicrobial resistance at the 2016 United Nations General Assembly. It was only the fourth such occasion Member States convened and issued a declaration associated with a developing health crisis.2 Infectious disease emergence and multidrug-resistant pathogens are among this century’s defining global health challenges. The magnitude of their present and potential impact is sobering. In addition to the disease burden and social impact on families and communities, economic losses due to epidemics and pandemics are often more significant than the direct immediate and longer-term medical expenses. The World Bank estimates the global cost of the 2003 severe acute respiratory syndrome pandemic at 30 billion United States dollars (US$).3 The 2013–2016 Ebola virus disease outbreak was associated with US$ 2.2 billion in lost economic growth for Guinea, Liberia and Sierra Leone alone.4 Total costs attributable to both income loss and premature mortality from a moderately severe influenza pandemic are projected at US$ 570 billion annually, which is within the range of the annual cost associated with global climate change.5 Without intervention, the cumulative economic impact of antimicrobial resistance through 2050 is anticipated to exceed US$ 100 trillion, two-thirds of which would be in lowand middle-income countries, substantially more than current annual global economic output.6 Increasingly, the evidence base suggests that the accelerated rate at which infectious diseases of pandemic potential and antimicrobial resistance are emerging is strongly correlated with anthropogenic change on the planet.7 Rapid population growth and demographic shifts, coupled with soaring demand for animal-sourced nutrition, changes in food-production systems, global travel and trade, and an increasing remodelling of our natural landscapes, are opening new pathways to emerging and re-emerging diseases. The World Bank and health and development institutions have made the case for investing in proactive, preventive measures that directly address these drivers, and for enhancing capacities that can contribute to averting the worst of their consequences. A yearly investment of US$ 1.9–3.4 billion to strengthen animal and human health systems would yield an estimated global public benefit of over US$ 30 billion annually, because it would avoid the economic damages associated with pandemics.3 High return on investment is expected even if only some pandemics are prevented. Strengthened multidisciplinary national capacities would bring additional benefits by improving prevention and control of endemic disease in human and animal populations. This improvement would initiate a cascade effect that would be expected to include lower rates of infectious disease-associated morbidity, reduced antimicrobial demand and ultimately, a scaling back of pressures fostering drug resistance. Yet, despite the pattern of costly responses and a compelling investment case for prevention, global postures remain primarily response-driven and reactive to a dynamic and volatile emerging disease landscape. New epidemics are often met with an emergency response, after-action reviews and a promise to rethink prevention. So what can we learn from the failure to implement prevention and preparedness plans built on the premise that such events are avoidable? Both cost–benefit and return on investment analyses have long been used for prioritizing public health resources, however, the use of these analyses in the complex human–animal–ecosystem health context is at an early stage. Where the analyses have been performed, results have not always gained support from budget decision-makers, limiting their translation into policies. In part, this resistance can be attributed to the dual constraints of competing priorities for human and veterinary health systems funding, and to the difficulty in mobilizing sufficient resources to fund infrastructure and risk mitigation efforts. Furthermore, there is limited investment in evidence-based animal reservoir surveillance and research of wildlife and environmental factors associated with emergence of infectious diseases. This limitation has frequently resulted in a general lack of awareness among policymakers of upstream prevention opportunities, indirectly adding to resistance in adjusting priorities. Considering the broad array of factors contributing to the emergence of infectious disease, bridging inequitable distribution of costs and benefits across sectors and stakeholders also remains an obstacle. A framework for stimulating economic investments to prevent emerging diseases Daniel L Schar, Gavin Mark Yamey, Catherine C Machalaba & William B Karesh