Biological threats that could result in catastrophic consequences exist in many forms and arise from multiple sources. For example, several known biological agents could be made into aerosolized weapons and intentionally released in a transportation hub or other populated urban setting, introduced into the agricultural infrastructure and food supply, or used to contaminate the water supply. Concerned with the threat of bioterrorism, in 2004, the White House released HSPD-10, which outlines the structure of the biodefense enterprise and discusses various federal efforts and responsibilities that help to support it. The biodefense enterprise is the whole combination of systems at every level of government and the private sector that can contribute to protecting the nation and its citizens from potentially catastrophic effects of a biological event. It is composed of a complex collection of federal, state, local, tribal, territorial, and private resources, programs, and initiatives, designed for different purposes and dedicated to mitigating various risks, both natural and intentional. Biodefense is organized into four pillars—threat awareness, prevention and protection, surveillance and detection, and response and recovery— and multiple federal agencies have biodefense responsibilities within the pillars. Each of these pillars comprise numerous activities—such as controlling access to dangerous biological agents used in research—that generally require coordination across federal departments as well as with state, local, and international governments, and the private sector. Protecting humans, animals, plants, air, soil, water, and critical infrastructure from potentially catastrophic effects of intentional or natural biological events entails numerous activities carried out within and among multiple federal agencies and their nonfederal partners (see fig. 1). Emerging infectious diseases represent an ongoing threat to the health and livelihoods of people and animals worldwide. Many advances in medical research and treatments have been made during the last century, but infectious diseases are nevertheless a leading cause of death worldwide. In addition to causing nearly one in five human deaths worldwide, infectious diseases impose a heavy societal and economic burden on individuals, families, communities, and countries. Infectious diseases are a continuous threat for reasons that include: (1) emergence—at times rapid—of new infectious diseases; (2) re- emergence of previously-known infectious diseases; and (3) persistence of intractable infectious diseases. In an era of rapid transit and global trade, the public health and agricultural industries, as well as natural ecosystems including native plants and wildlife, face increased threats of naturally occurring outbreaks of infectious disease and accidental exposure to biological threats. According to the World Health Organization, infectious diseases are not only spreading faster, they also appear to be emerging more quickly than ever before. The ongoing outbreak of Zika virus in the Americas has heightened travel-related concerns regarding the spread of the virus. As of March 23, 2016, 273 cases of continental U.S. travel-associated Zika virus disease have been reported, according to Centers for Disease Control and Prevention (CDC). Figure 2 shows passenger arrivals from five regions of the world and the top five airports receiving passengers whose travel originated from each of these regions in 2014. According to the World Health Organization, about 75 percent of the new diseases that have affected humans in recent years are zoonotic and have been caused by pathogens originating from an animal. These emerging and reemerging diseases transmit between animals—including domestic animals and wildlife—and humans. Many of these diseases have the potential to spread through various means over long distances and to become global problems. In some cases, disease transmission is direct, in others the animals act as intermediate or accidental hosts, while in others transmission occurs, for example, via mosquitoes or ticks. Examples of emerging and zoonotic diseases include: Zika, chikungunya, and dengue viruses, West Nile virus, H1N1 (swine) influenza, severe acute respiratory syndrome (SARS), avian influenza, and rabies. Habitat loss and human encroachment on rural and wildlife environments are bringing populations of humans and animals, both farmed and wild, into closer and more-frequent contact. Increasingly, wildlife are involved in the transmission of diseases to people, pets, and livestock, and managing wildlife transmitters is an integral part of efforts to control the spread of zoonotic diseases. Diseases among wildlife can also provide early warnings of environmental damage, bioterrorism, and other risks to human health. Finally, potential bioterrorism threats also include the use of zoonotic diseases as weapons of mass destruction, such as anthrax, plague, tularemia, and brucellosis. Transmission and detection of Zika, chikungunya, and dengue viruses Zika, chikungunya, and dengue viruses are all spread by the Aedes aegypti mosquito, pictured below. These mosquitoes typically lay eggs in and near standing water in containers like buckets, bowls, animal dishes, flower pots, and vases. They prefer to bite people, and live both indoors and outdoors. Mosquitoes that spread dengue, chikungunya, and Zika are aggressive daytime biters, but also bite at night. Mosquitoes can become infected when they feed on a person already infected with the virus. Diagnosing Zika virus infection is complicated because it is difficult to differentiate it from other similar diseases, such as dengue or yellow fever, and some tests for Zika virus antibodies suffer from cross-reactivity with antibodies to similar viruses. For example, a person previously infected with another flavivirus such as dengue could be falsely identified as also having been exposed to the Zika virus (and vice-versa). Numerous federal, state, local, and private sector entities have roles and responsibilities for monitoring for pathogens in human, animal, plant, food, and the environment. Federal departments, such as the HHS, USDA, DHS, and the Department of Interior, play leading biosurveillance roles for certain domains such as human and animal health, food, and air, but they also rely on support from state and local authorities or partner with other federal agencies. In other cases federal departments or agencies play supporting roles. Officials at all levels of government, as well as Homeland Security Presidential Directive-21’s (HSPD-21) vision of a national biosurveillance capability, acknowledge that state and local capabilities are at the heart of the biosurveillance enterprise. According to federal, state, and local officials, early detection of potentially serious disease indications nearly always occurs first at the local level, making the personnel, training, systems, and equipment that support detection at the state and local level a cornerstone of our nation’s biodefense posture. While there is variation in organization and structure among public-health, animal-health, and wildlife functions at the state, tribal, local, and insular levels they all share in the nation’s biosurveillance responsibility. Some of the nonfederal partners with key responsibilities in the biosurveillance enterprise are presented in table 1. Bipartisan and independent commissions have identified a range of issues facing the biodefense enterprise, many of which mirror our findings. In October 2011, the WMD Center reported its assessment of various capabilities within the U.S. biodefense enterprise in which a team of leading biodefense experts assigned letter grades to each of the capabilities for different types of outbreak. The report assigned low marks to nearly all the capabilities for address large-scale and global disease outbreaks. For example, the team assigned the grade of D (meets few expectations) to the capability for detecting large-scale infectious outbreaks and the grade of F (fails to meet expectations) to the capability for detecting global contagious outbreaks. In 2014, a Blue Ribbon Study Panel on Biodefense (Study Panel) was established to assess gaps and provide recommendations to improve U.S. biodefense. The panel’s October 2015 final report identified 33 recommendations to execute over the short, medium, and long term. The Study Panel report echoed many of the same challenges highlighted in the WMD Center’s report, and highlighted a sense of urgency to address the ongoing and persistent biological threats—both naturally occurring, like Ebola and Zika, and from enemies, like The Islamic State of Iraq and the Levant (also known as ISIL and Da’esh) who have advocated for the use of biological weapons. The panel’s report identified several themes we have also highlighted in our biosurveillance work, including the lack of a centralized leader, no comprehensive national strategic plan, and no all- inclusive dedicated budget for biodefense. In 2011, we reported that reducing fragmentation in the biodefense enterprise could enhance assurance that the nation is prepared to prevent, detect, and respond to biological attacks with potentially devastating consequences in terms of loss of life, economic damage, and decreased national security. We reported that there are more than two dozen presidentially appointed individuals with some responsibility for biodefense. In addition, numerous federal agencies, encompassing much of the federal government, have some mission responsibilities for supporting biodefense activities. However, there is no individual or entity with responsibility, authority, and accountability for overseeing the entire biodefense enterprise. Because none of the federal departments has authority over the entire biodefense enterprise, in 2011 we reported that the Homeland Security Council (HSC) should consider establishing a focal point to coordinate federal biodefense activities. In December 2014 officials from National Security Council (NSC) staff, which supports the HSC told us that two of its directorates work together as the focal point for federal biodefense efforts. According to NSC staff, these focal points provide strategic leadership on all federal biodefense efforts, with responsibilities to coordinate across domestic and global priorities to prevent, detect, and rapidly respond to biological threats. The focal points are to host ongoing meetings with the federal biodefense enterprise to ensure a comprehensive and coordinated approach to biodefense.