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30,000 people and is estimated to have cost the 3 affected countries $2.8 billion in lost GDP.6 The 2003 SARS epidemic spilled over national borders to sicken more than 8,000 people in more than 20 countries and is estimated to have cost the global economy upwards of $40 billion.7 Had the virus been more easily transmissible outsid While the economic impact of pandemics, epidemics, and outbreaks depends, in part, on the severity of the health effects of these events, the actions that countries take in an attempt to control the spread of disease can also exacerbate its tolls. The 2009 H1N1 influenza pandemic, which was generally assessed to be mild in terms of its health effects (and therefore, for this report, would not qualify as a high-impact respiratory pathogen), offers a recent instructive example of this. In 2009, countries that were initially affected experienced drops in tourism revenues as other countries implemented bans and other restrictions on travel in response. Additionally, some countries responded by employing trade restrictions, which did little to alter the spread of the pandemic but increased its economic costs.8,9 Such actions are common during significant disease events. For example, during the West Africa Ebola outbreak, more than a third of States Parties to the International Health Regulations (IHRs) implemented restrictions on travel that exceeded recommendations made by the World Health Organization.10 From these experiences, we can expect that countries would likely be inclined to take similar measures in response to a high-impact respiratory pathogen. e of clinical environments, the public health impacts of this event would likely have been much greater. The potential for an epidemic or pandemic caused by a high-impact respiratory pathogen is increasing. Data show that the frequency of outbreaks of newly emerging diseases is rising.11 Novel pathogens continue to emerge, often first in animals, then with subsequent spillover into human populations living in close contact with animals, due to changing patterns of animal management and land use. Global conditions enable pathogens to spread widely and quickly in people. International travel, mass displacement, migration, and urbanization enable pathogens to spread in new, susceptible populations.9 The rising incidence of chronic illnesses and drug-resistant infections place individuals at greater risk of infection and complications from respiratory viruses.12 Declining levels of protection from vaccines due to the influence of anti-vaccination sentiments in some communities is enabling previously declining respiratory viruses to cause significant outbreaks.13 Climate-related changes have altered the geography of habitats suitable for spread of certain pathogens and have changed patterns of migration, as humans move to escape consequences of extreme weather events.14 All of these factors increase the chance that new high-impact respiratory pathogens will emerge and spread, raising the possibility that an epidemic or pandemic will occur. Novel high-impact respiratory pathogens have a combination of qualities that contribute to their potential to initiate a pandemic (see Figure 1). Respiratory pathogens can be particularly difficult to contain. Their tendency to have short incubation periods and their potential for asymptomatic spread can mean very small windows are available for interrupting transmission. Individuals infected with respiratory viruses may infect many more people at a time as compared to pathogens spread by other means. These factors increase both the pandemic potential of respiratory pathogens and the likelihood that there will be serious public health, economic, and social impacts with their spread. Some viral groups have characteristics that give them a higher probability of being a future source of a novel pandemic pathogen (see Box 1 and Table 1). In anticipating the implications of a high-impact respiratory pathogen, it is useful to consider, as an illustrative disease, the high-impacts of measles in the current world. If we start with naturally occurring measles, and then imagine that measles had an increased percentage of case fatalities and a decreased potential for containment (eg, the absence of a vaccine and the lack of herd immunity), this could reflect the conditions presented by a high-impact respiratory pathogen15 (see Box 2). Scientific developments have greatly advanced medical and public health tools to fight epidemic disease, as will be detailed later in this report. But scientific developments have also created the ability for pathogens to be engineered or recreated in laboratories. Should countries, terrorist groups, cults, or scientifically advanced individuals create or obtain 19 and then use biological weapons that have characteristics of a novel, high-impact respiratory pathogen, the consequences could be as severe as or greater than the consequences that would follow a naturally occurring pandemic with such pathogens16 (see Box 3). Similarly, a laboratory accident involving such pathogens could have a terrible impact if it led to a disease rapidly spreading in a community. Taken together, naturally occurring, accidental, or deliberate events caused by high-impact respiratory pathogens pose pandemic risks that elsewhere have been termed “global catastrophic biological risks.”17 Global efforts to prepare for significant disease outbreaks have revealed large national and international readiness gaps around detection and containment, including challenges related to tools, personnel, and surveillance systems. After-action reports conducted after recent events, such as the 2014-2016 Ebola epidemic in West Africa and the 2009 influenza H1N1 pandemic, showed systematic failures in global governance and response.18,19 High-impact respiratory pathogens—whether they are well known, novel strains of recognized diseases, or as-yet unrecognized (such as a “Disease X” noted by the World Health Organization Research and Development (R&D) Blueprint, or a Clade X, which was the subject of a recent tabletop simulation)—warrant special consideration, given the substantial global risks they pose.20,21 This report examines global progress toward and gaps surrounding preparedness for high-impact