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research protocols. • Pre-identified networks of researchers could help facilitate and prioritize research that is conducted. 13 8. Frameworks and plans articulating the evidence and role for nonpharmaceutical interventions need to be established. • Nonpharmaceutical interventions (NPIs) have a greater likelihood of being implemented effectively if well analyzed ahead of time than if considered ad hoc during a crisis. Countries and international organizations need to better analyze the potential value and impact of NPIs; determine in which contexts, if any, a particular NPI would be effective; and conclude in which contexts they are likely do more harm than good. • WHO and other public health authorities should have the capacity to provide risk/ benefit analysis to national governments, driven by scientific evidence where it exists, before NPIs are initiated in a crisis. • During an emergency, it should be expected that implementation of some NPIs, such as travel restrictions and quarantine, might be pursued for social or political purposes by political leaders, rather than pursued because of public health evidence. WHO should rapidly and clearly articulate its opposition to inappropriate NPIs, especially when they threaten public health response activities or pose increased risks to the health of the public. • WHO and national authorities will need to provide strong evidenced-backed reasoning for the necessity of NPIs in order to effectively implement them and to communicate their role and necessity to the public, especially for NPIs such as social distancing that inherently limit civil liberties. Therefore, they should undertake directly or support research on NPIs and disseminate their findings on these analyses. 9. National governments should strengthen biosaftey around high-impact respiratory pathogens. • Biosafety needs to become a national-level political priority, particularly for countries that are funding research with the potential to result in accidents with pathogens that could initiate high-impact respiratory pandemics. • All nations should be advised to adopt national-level comprehensive biosafety norms for research involving high-impact respiratory pathogens. • Countries that fund such research should have oversight systems in place that consider the risks and benefits of this kind of work, and they should have maximally stringent biosafety requirements for any laboratory that is allowed to pursue this type of research. • WHO should develop stronger interest and capability in monitoring research with the potential to result in accidents involving high-impact respiratory pathogens, and it should advise member nations about the risks and benefits related to this work. 14 10. National governments need to prepare for the deliberate use of a respiratory pathogen. • Preparation for a deliberate event must include recognition that the deliberate release of a high-impact respiratory pathogen could substantially add to the extraordinary consequences that would follow a naturally occurring pandemic event with the same agent. • The United Nations (UN), WHO, and the international community will need to take steps to better understand their respective roles during a deliberate event, including greater clarity on which international agency would lead the response. • Countries should support the adoption of synthesis screening approaches intended to identify work being done on high-impact respiratory pathogens. • National governments and WHO should plan to engage in a coordinated and collaborative response to deliberate events. For example, pre-event planning is needed among public health officials, military, law enforcement, and/or intelligence communities in order to set expectations about appropriate roles and responsibilities and best practices for data sharing. • Continued research into the science of attribution, as well as the strengthening of surveillance systems, international collaboration, and implementation of treaty agreements, particularly the Biological Weapons Convention (BWC), are all needed for an effective response to the deliberate use of a biological weapon with a high-impact respiratory pathogen. 15 RISKS POSED BY HIGH-IMPACT RESPIRATORY PATHOGENS The far-reaching tolls of epidemics and pandemics caused by high-impact respiratory pathogens* have been documented throughout history. Just over 100 years ago, a new influenza virus spread across the globe, sickened an estimated one third of the world’s population, and killed upwards of 50 million people. The toll of this event extended well beyond its health impacts. High burdens of illness and rapid transmission led to high rates of worker absenteeism, which had effects on communities’ abilities to maintain public safety and basic infrastructure.1 Occurring in the midst of a world war, influenza and pneumonia killed more soldiers than did armed conflict, according to US military reports, and the need to care for the sick and the dead diverted resources from combat operations.2 Though there have been many medical advances since 1918 that would aid in a response to a high-impact respiratory pathogen event, were such an event to occur again, it would still have severe societal consequences. Today’s global population is more than 4 times greater than it was 100 years ago. In 1918, shipping played an important role in spreading influenza around the world, but today’s travelers can travel anywhere in the world in less than 36 hours, meaning that global spread would be likely to be far more rapid.3,4 The World Bank has estimated that a severe pandemic such as the one that occurred in 1918 could cost the modern economy from 1% to 4.8% of global gross domestic product. Even if the next pandemic is not as severe as the one in 1918, it will likely have significant consequences. The World Bank estimates that “mild” and “moderate” pandemics, such as those that occurred in 1957 and 1968, could still cause more than 10 million deaths and reduce global economic activity by 0.7%.5 National and regional epidemic events, though geographically limited in scope, are capable of taking significant tolls and causing major international disruption. The Ebola epidemic in West Africa in 2014-2016 sickened more than