Ashley Pevia Surveillance and Attribution Investigations COLLAPSE Biosurveillance Systems Biosurveillance focuses on developing effective surveillance, prevention and operational capabilities for detecting and countering biological threats. The system works closely with hospitals, health care providers and various laboratories to identify disease cases, investigate the potential spread and guide actions (CLS). The Department of Homeland Security’s Apex Programs is a screening process that look strategically at the nations security and address future biological threats. The Apex Screening at Speed is a program that efficiently screens people for concealed explosive threats (APEX). Created specifically for United States airport TSA, the detection system screens carry on bags and uses X-Ray’s to surveillance further risks. Another example of a biosurveillance system is The Global Biosurveillance Portal. The Biosurveilance Portal is an international system that is mainly focused on coordinating and synchronizing information with international and federal organizations. The system assist in biological defenses by allowing users to organize web applications receives data from various facilities. The data is then taken and analyzed and sent to organizations to development strategies to counter biological threats. Importance of Biosurveillance Biosurveillance is imperative for public health preparedness. The Nation is confronted by an array of health threats with natural, accidental and deliberate origins. Public health professionals are responsible for addressing health on consequences of all types of disaster. Emerging biological threats could wipe out many plant and animal species and could drastically cause a decline in the human population. Biosurveilance for human health includes 3 functional components including detecting baseline disease outbreaks, investigate potential threats and respond when a threat is confirmed. It is important to prepare for biological threats and implementing response measures for adequate communication and counter bioterrorism measures. Michael Enright was an English Actor known for his role in The Pirates of the Caribbean and other popular movies. Michael gave up acting to work towards the fight against bioterrorism. He worked on the field in Syria combating ISIS and he also worked with the U.S immigration system to combat bioterrorism (Franzia, 2019). Policy Directives & Investigations After the Anthrax attack in 2001, new laws aimed to boost public health was proposed. Congress in conjunction with Public Health Security administration proposed the Public Health Security and Bioterroism Prepardness and Response Act of 2002. The bill authorized more than $1.5 billion in grants to develop improved planning, enhanced laboratory capacity, training personnel and prevention efforts. Attribution investigations are conducted through data collection systems. Analyzing data can aid in investigation for biological attacks. The CDC helps various agencies investigate possible terrorist attacks to prevent the country from future harm. Resources Anderson, J. A., Rosenzweig, C. N., Roos, J., & Flores, B. (2015). The Global Biosurveillance Portal: Biosurveillance for the Department of Defense. Online Journal of Public Health Informatics, 7(1), e63. doi:10.5210/ojphi.v7i1.5729 Center for Disease Control, 2010. Biosurveillance: Smart Investments for early Warning. Retrieved from: https://www.cdc.gov/washington/testimony/2010/t20100225.htm Ross, Robert. 2002. New bioterrorism law aims to boost public health, guard food and water. Center for Infectious Disease Research and Policy. Retrieved from: http://www.cidrap.umn.edu/news- perspective/2002/06/new-bioterrorism-law-aims-boost-public-health-guard-food-andwater Franzia. 2019. A British actor left Hollywood to fight ISIS. Now he’s marooned in Belize. The Washington Post. Retrieved from: https://www.washingtonpost.com/lifestyle/2019/10/15/british-actor-left-hollywoodfight-isis-now-hes-marooned-belize-its-quite-story/?arc404=true Shineca Solomon Surveillance and Attribution Investigations COLLAPSE Current Domestic and International Systems Available for Biosurveillance Current systems utilized in the US include the National Biosurveillance Integration Center (NBIC) and Biowatch. NBIC hosted by the Department of Homeland Security (DHS) has used several systems to integrate and analyze data from human health, animal, plant, food, and environmental monitoring to create a single picture of bio-related activities (Katz & Banaski, 2019). This program has challenges due to information not readily being shared, translation of varying formats, and uninformed analyses. DHS also operates Biowatch, an environmental monitoring program that detects when biological agents are present in the environment (Katz & Banaski, 2019). In a 2009 review, the National Biosurveillance Advisory Subcommittee (NBAS) concluded that there are more than 300 separate biosurveillance efforts in existence among federal, state, and local government agencies; many of which aredisease specific, are not integrated, and may be duplicative (Toner et al., 2011). The current biosurveillance system in place in the US is uncoordinated, utilizes multiple separate date collections systems, and is challenged by governmental infrastructure that allows states to voluntarily share notifiable diseases with federal entities (Katz & Banaski, 2019). Global systems include the Global Public Health Information Network (GPHIN), Promed, and HealthMap. They are designed to be coordinated at the international level by the World Health Organization (WHO) through the Global Outbreak Alert and Response Network (Katz & Banaski, 2019). GPHIN is a system developed in Canada set up as a global network of connected professionals working to rapidly detect, identify, assess, prevent and mitigate threats to human health (Government of Canada, 2017). Promed is similar to GPHIN, but on a global level and HealthMap visually depicts events around the world (Katz & Banaski, 2019). There is considerable variation in system capability, data analyzed, and products disseminated, and similarities and differences among the systems described above suggest that combining these approaches into a single system can provide a powerful biosurveillance resource (Hartley et al., 2010). Importance of Biosurveillance for Public Health Preparedness There have been several instances of US health security threats within the past 10 years, including Ebola, Zika, Middle East respiratory syndrome (MERS) and the 2009 influenza outbreak. In each of these events, inadequate information has delayed initial detection of the outbreak, and a lack of understanding about the underlying epidemiology of the viruses hindered control efforts (Nuzzo, 2017). Biosurveillance efforts must be domestic and international in scope, because health threats that emerge anywhere may cross borders quickly and threaten people worldwide (National Biosurveillance Advisory Subcommittee, 2011). Biosurveillance systems may gather and analyze data from a variety of human, animal, plant, and environmental health sources with the goal of providing situational awareness with respect to the occurrence of biological threats and to guide efforts to control them (Nuzzo, 2017). Policy Directives that Support Biosurveillance The Public Health Security and Bioterrorism Preparedness and Response Act of 2002 initiated the call for an integrated, functional domestic biosurveillance system (Katz & Banaski, 2019). Priority was placed on developing a biosurveillance strategy following the September 11, 2001, terrorist attacks on the United States and the 2001 anthrax attacks (Planning Committee on Information-Sharing Models and Guidelines for Collaboration, 2011). The Pandemic and All-Hazards Act (PAHPA) of 2006 and the Implementing Recommendations of the 9/11 Commission Act of 2007 both reinforced the need for strong biosurveillance systems (Katz & Banaski, 2019). There have been several Homeland Security Presidential Directives (HSPD) addressing biosurveillance, including HSPD-21, HSPD-9, and HSPD-10. HSPD-21 charged the U.S. Department of Health and Human Services (HHS) with establishing “an operational national epidemiologic surveillance system for human health, with international connectivity where appropriate, that is predicated on state, regional, and community-level capabilities and creates a networked system to allow for two-way information flow between and among Federal, State, and local government public health authorities and clinical health care providers.” HSPD-9 (Defense of United States Agriculture and Food) and HSPD-10 (Biodefense for the 21st Century) charged the Secretary of Homeland Security to “integrate all federal agency efforts” and to “create a new biological threat awareness capacity” that would detect biological attacks early (Planning Committee on Information-Sharing Models and Guidelines for Collaboration, 2011). Attribution Investigations Attribution assessments are used to determine verify the origin or source, sponsorship, delivery, and responsible party associated with an intentional use event (Katz & Banaski, 2019). They are conducted by law enforcement officials who will identify if a crime occurred, what exactly happened, when, and why. Microbial forensics may be used if biological agents are involved. If biological weapons are used, it is usually first recognized by the public health surveillance system, who will determine if it is domestic or international (Katz & Banski, 2019). If domestic, public health officials will investigate and if it is found to be intentional, local law enforcement will become involved and collect evidence. If it is found to be international, it will be reported to the national level authorities and then to either the World Health Organization or United Nations (Katz & Banaski, 2019). References Government of Canada. (2017). About GPHIN. Retrieved from https://gphin.canada.ca/cepr/aboutgphin-rmispenbref.jsp?language=en_CA Hartley, D., Nelson, N., Walters, R., Arthur, R., Yangarber, R., Madoff, L., … Lightfoot, N. (2010). Landscape of international event-based biosurveillance. Emerging Health Threats Journal, 3. https://doi.org/10.3134/ehtj.10.003 National Biosurveillance Advisory Subcommittee. (2011). Improving the Nation’s Ability to Detect and Respond to 21st Century Urgent Health Threats: Second Report of the National Biosurveillance Advisory Subcommittee. Retrieved from https://www.cdc.gov/about/advisory/pdf/NBASFinalReport_April2011.pdf Nuzzo, J. B. (2017). Improving Biosurveillance Systems to Enable Situational Awareness During Public Health Emergencies. Health Security, 15(1), 17–19. https://doi.org/10.1089/hs.2016.0097 Toner, E. S., Nuzzo, J. B., Watson, M., Franco, C., Sell, T. K., Cicero, A., & Inglesby, T. V. (2011). Biosurveillance Where It Happens: State and Local Capabilities and Needs. Biosecurity and Bioterrorism: Biodefense Strategy, Practice, and Science, 9(4), 321–330. https://doi.org/10.1089/bsp.2011.0049 Planning Committee on Information-Sharing Models and Guidelines for Collaboration. (2011). Applications to an Integrated One Health Biosurveillance Strategy—A Workshop. Introduction and Overview. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK189584 Uyen Tran Surveillance and Attribution Investigations COLLAPSE Domestic and international systems available for biosurveillance The social, political and economic atmosphere that has been disrupted by natural and man-made public health emergencies have become a catalyst for efforts to expand biosurveillance to increase its quality, timeliness, and comprehensive nature to better detect disease, alerting, response and future predictions. The definition of "biosurveillance" is all encompassing and different based which interagency it comes from: "...collection and integration of timely health related information for public health action" (Khan, Fleischauer, Casani, & Groseclose, 2010). One domestic example is the DHS BioWatch Program which is managed by the DHS Countering Weapons of Mass Destruction Office, established in 2003 (DHS, 2019). This system provides early warning of bioterrorist attacks servicing more than 30 city areas across the country and helps decision makers plan for an effective, coordinated, rapid response. An international global system that I found was the Global Biosurveillance Portal which looks at having the collective knowledge and beneift of sharing biosurveillance information with partnerships internationally, deferally, state, local, etc. Biosurveillance and Public Health Preparedness Biosurveillance is important to public health preparedness because it provides officials with a system to anticipate a disaster as well as the consequences that come with it. Each function in the system would gives the information, creates data that can inform actions to enhance preparedness (Allen , 2018). It also provides those who are in the occupation of disaster relief more situation awareness which is difficult to have in heighten situations. It also does to enhance understanding of the prevention strategies that exist, what all needs to be changed and the needed information to affect policy change. Policy directives that support biosurveillance In the consecutive years after the U.S biological attacks of anthrax and other isolated incidences like samonella and E coli, Congress passed several policies. For example in 2006, there was the Pandemic and All Hazards Preparedness Act which proposed for an electronic nationwide public health situational awareness capability system (Toner et.al., 2011). The following year Congress passed the Implementing Recommendations of 9/11 Commission Act which led to the creation of the National Biosurveillance Integration Center at the DHS. Attribution investigations are conducted and the different entities involved in the investigation Attribution investigations are conducted by looking at situation awareness of an incident and analyzing the data to find the point source where an incident has occurred. To put it into perspective, in the instance of a cyber security attribution investigators (i.e anaylsts) use information taken from the process along with previously known information about malicious attackers to attempt to back track the operation to it's orginal source of attack (Office of the Director of National Intellgience, 2018). Analysts compare and contrast the data collected and based weighing the evidence they will decide on a confidence level to determine their judgements for an incident. References: Department of Homeland Security. (2019, Nov 8). Detecting Bioterrorist Attacks. Retrieved from https://www.dhs.gov/biowatch-program Khan, A. S., Fleischauer, A., Casani, J., & Groseclose, S. L. (2010). The next public health revolution: public health information fusion and social networks. American journal of public health, 100(7), 1237–1242. doi:10.2105/AJPH.2009.180489 Toner, S.E. Nuzzo, J.B. Watson, M. Franco, C. Sell, Tara, Cicero, Anita and Inglesby. V.T. (2011, December 1). Biosurveillance Where It Happens: State and Local Capabilities and Needs. Biosecurity and Bioterrorism: Biodefense Strategy, Practice, and Science, 9(4). Retrieved from https://www.liebertpub.com/doi/pdf/10.1089/bsp.2011.0049 NAT IONA L S T R AT E G Y F OR BIO S U RV E I L L A NCE J U LY 2 0 1 2 THE WHITE HOUSE WASHINGTON July 31, 2012 There is no higher priority than the security and safety of the American people. As a Nation, we must be prepared for the full range of threats, including a terrorist attack involving a biological agent, the spread of infectious diseases, and food-borne illnesses. The effective dissemination of a lethal biological agent, for instance, could endanger the lives of hundreds of thousands of people and result in untold economic, societal, and political consequences. In my National Security Strategy, I committed the United States to new approaches to counter biological threats. Specifically, I called for "obtaining timely and accurate insight on current and emerging risks." Such biosurveillance -- including early detection -- is one of our first lines of defense against these threats. As we saw during the H1N1 influenza pandemic of 2009, decisionmakers -- from the President to local officials -- need accurate and timely information in order to develop the effective responses that save lives. The sooner we can detect and understand a threat, the faster we can take action to protect the American people. This first-ever National Strategy for Biosurveillance builds on the capabilities already in place and further institutionalizes our efforts to ensure that we are doing everything possible to identify and understand threats as early as possible. Its goal is to provide the critical information and ongoing situational awareness that enables better decisionmaking at all levels. It calls for a coordinated approach that brings together Federal, State, local, and tribal governments; the private sector; nongovernmental organizations; and international partners. It challenges us to take full advantage of the advanced technologies, new vaccines, the latest science, and social media that can help keep our citizens safe. It describes the core functions and critical capabilities we need to succeed. As a next step, I am directing that a strategic implementation plan be completed within 120 days to lay out the specific actions that are required and the responsibilities of all partners in this mission. In the event of a biological outbreak or incident, the threat will move rapidly and transcend boundaries and borders. So must our response. Guided by this Strategy, I am confident that we can meet our shared responsibility and deepen the collaboration we need to keep our country safe and secure. Table of Contents Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Overview of the National Strategy for Biosurveillance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 The Threat Environment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Guiding Principles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Leverage Existing Capabilities . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Embrace an All-of-Nation Approach . . . . . . . . . . . . . . . . . . . . . . . . . 4 Add Value for All Participants . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Maintain a Global Health Perspective . . . . . . . . . . . . . . . . . . . . . . . 5 Biosurveillance Goal and Core Functions . . . . . . . . . . . . . . . . . . . . . . . . 5 Scan and Discern the Environment . . . . . . . . . . . . . . . . . . . . . . . . 5 Identify and Integrate Essential Information . . . . . . . . . . . . . . . . . . . . . 5 Alert and Inform Decisionmakers . . . . . . . . . . . . . . . . . . . . . . . . . 6 Forecast and Advise Impacts . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 Enablers for Strengthening Biosurveillance . . . . . . . . . . . . . . . . . . . . . . . 7 Integrate Capabilities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 Build Capacity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 Foster Innovation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 Strengthen Partnerships . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 Way Forward . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ★ iii ★ 8 Introduction A well-integrated, national biosurveillance enterprise is a national security imperative. Our ability to detect quickly and characterize a potential incident of national significance that affects human, animal, or plant health is of paramount importance. Rapid detection and enhanced situational awareness are critical to saving lives and improving incident outcomes, whether the result of a bioterror attack or other weapons of mass destruction (WMD) threat, an emerging infectious disease, pandemic, environmental disaster, or a food-borne illness. Beyond our need to protect domestic interests, and because health threats transcend national borders, the United States also plays a vital role within an international network of biosurveillance centers across the globe. For years, there have been dedicated efforts to promote and strengthen biosurveillance capabilities. There exists a strong foundation of capacity arrayed in a tiered architecture of Federal, State, local, tribal, territorial, and private capabilities. We can strengthen the approach with focused attention on a few core functions and an increased integration of effort across the Nation. In these fiscally challenging times, we seek to leverage distributed capabilities and to add value to independent, individual efforts to protect the health and safety of the Nation through an effective national biosurveillance enterprise. A key to improving all-hazards incident management is to focus efforts on collecting, analyzing, and disseminating information to facilitate timely decisionmaking, whether a health incident is a naturally occurring phenomenon, accidental, or deliberate in nature. From the individual, to primary care providers, to hospital practitioners, to state and local health officers, to Federal entities responsible for health emergency response, to the President of the United States, there exists an imperative to identify incidents early and to make decisions swiftly to save lives, even amidst great uncertainty. The goal is to achieve a well-integrated national biosurveillance enterprise that saves lives by providing essential information for better decisionmaking at all levels. Our Strategy is to integrate and enhance national biosurveillance efforts to answer specific key questions that guide decisionmaking in times of crisis; enable more rapid detection and foster improved situational awareness by further extending a dynamic, distributed national network of expertise and capabilities; and put into practice new thinking to facilitate decisionmaking processes in conditions of significant ambiguity. This enhanced national biosurveillance capability will be applied broadly to identify and understand potential human, animal, or plant health impacts resulting from chemical, biological, radiological, and nuclear (CBRN) and environmental incidents, as well as influenza and other public health trends, all of which may also be leveraged in the service of global health efforts. We must be resolved to strengthen life-saving biosurveillance capabilities within our existing resources. We can do this by leveraging more effectively our existing national network of expertise and capabilities, and through targeted enhancements that provide benefits across the enterprise. There are no higher priorities than the health, well being, and security of the American people. ★ 1 ★ NAT I O NA L S T R AT E G Y F O R B I O S U RV E I LL A N C E Overview of the National Strategy for Biosurveillance The National Strategy for Biosurveillance sets forth the United States Government approach to strengthen our national biosurveillance enterprise and describes a core set of functions critical to this Strategy’s success. The approach builds on existing biosurveillance concepts and capabilities in seeking to enable more rapid detection, knowledge, and characterization of human, animal, or plant disease activity to enhance incident situational awareness. At the same time, this Strategy outlines an approach that is more selective and deliberate in its intent. The Strategy defines biosurveillance as the process of gathering, integrating, interpreting, and communicating essential information related to all-hazards threats or disease activity affecting human, animal, or plant health to achieve early detection and warning, contribute to overall situational awareness of the health aspects of an incident, and to enable better decisionmaking at all levels. This definition is consistent with that of Homeland Security Presidential Directive-21 and now emphasizes an all-hazards scope and informed decisionmaking.1 This National Biosurveillance Strategy flows from the National Security Strategy, which highlights the importance of disease surveillance for public health threats, and is consistent with the National Strategy for Countering Biological Threats, which emphasizes information sharing among Federal departments and agencies to identify biological threats. The Federal Government seeks to galvanize action across the Nation to further extend and integrate our distributed national biosurveillance enterprise. Where efforts since the tragic terrorist attacks of September 11, 2001, have focused largely on threats associated with the deliberate use of CBRN weapons, this Strategy embraces the need to engage in surveillance for WMD threats and a broader range of human, animal, and plant health challenges, including emerging infectious diseases, pandemics, agricultural threats, and food-borne illnesses. Therefore, we seek to strengthen biosurveillance capabilities to enhance all-hazards incident management by providing essential information for timely decisionmaking at all levels, whether an incident is deliberate, accidental, or naturally occurring. Essential information is derived from a specific set of key questions that are common elements of any health emergency. These questions will be developed as part of a strategic implementation plan. This information is intended to help identify an incident, and to inform decisionmaking and time-sensitive actions at all levels to navigate health emergencies effectively. Identifying key questions and focusing our national enterprise on providing and sharing essential information is intended as a smarter, faster way to triage a health emergency and is a fundamental aspect of our Strategy. 1.  Homeland Security Presidential Directive-21 remains in effect and defines biosurveillance as the process of active data-gathering with appropriate analysis and interpretation of biosphere data that might relate to disease activity and threats to human or animal health – whether infectious, toxic, metabolic, or otherwise, and regardless of intentional or natural origin – in order to achieve early warning of health threats, early detection of health events, and overall situational awareness of disease activity. ★ 2 ★ NAT I O NA L S T R AT E G Y F O R B I O S U RV E I LL A N C E Structure of the Strategy. This Strategy articulates an overarching goal supported by core functions. It also includes guiding principles that provide a foundation for biosurveillance activities and specific enablers to achieve a well-integrated, national biosurveillance enterprise. Through a deliberate emphasis on the identified core functions and enabling focus areas, the aim is to enhance the Nation’s ability to detect, track, investigate, and navigate incidents affecting human, animal, and plant health, thereby better protecting the safety, well being, and security of the American people. The Guiding Principles serve as the Strategy foundation and inform biosurveillance efforts. The Core Functions focus and prioritize our biosurveillance efforts. The crosscutting Enablers are aimed at facilitating the successful implementation of our Strategy. The Threat Environment The deliberate use or accidental release of CBRN materials remains an enduring threat to the safety and security of the American people. One needs only to recall the terror and feelings of vulnerability caused by the anthrax letters of 2001. More recently, the Japan nuclear emergency resulting from an historic earthquake and tsunamis in 2011 reminded us of the social, economic, environmental, and health impacts of a radiological release incident. Beyond CBRN-related concerns, the 2009-H1N1 influenza pandemic and the Severe Acute Respiratory Syndrome outbreak were clear demonstrations of the potential threat that pandemics and other emerging infectious diseases can pose to the American people. These incidents highlighted the challenges of ascertaining the course or impact of infectious diseases. Innovative developments mark the advent of threats of a new kind. Specifically, recent breakthroughs in synthetic biology offer the promise but also potentially the peril of technological progress, where the field is advancing at a staggering pace. Our security and public health concerns are intertwined. Through science and technology developments, while it is increasingly possible to manufacture new and improved vaccines and therapeutics, it is equally possible to create genetically modified organisms that can evade our current countermeasures. In addition to various forms of biologic threats, intentional use of a chemical agent or radiologic device, along with the potential for chemical or radiologic industrial accidents, add to the spectrum of threats. Overall, the threat environment is dynamic and unpredictable. To address the challenge, this Strategy seeks to evolve our ability to detect rapidly and track incidents affecting human, animal, and plant health to save lives by informing decisionmaking at all levels. Guiding Principles Our national biosurveillance approach must address both near- and long-term information needs for a wide variety of decisionmakers and consider the context in which the overall enterprise is operating. The threat is dynamic and fiscal constraints are an everyday reality. As such, this Strategy focuses intentionally on existing, multipurpose capabilities. In addition, our biosurveillance approach emphasizes teamwork between and within Federal departments, across all layers of government, and with private sector partners. ★ 3 ★ NAT I O NA L S T R AT E G Y F O R B I O S U RV E I LL A N C E This Strategy also aims to prompt action that will add value for individual contributors comprising our national biosurveillance enterprise. And where resources are constrained, we aim to leverage existing, distributed capabilities more fully. The Strategy intends to add value across our national enterprise and beyond, where global health security activities are an inextricably linked and necessary aspect of strengthening of our domestic biosurveillance approach. Specific guiding principles form the foundation of our Strategy aimed at evolving and enhancing our national biosurveillance enterprise: (1) leverage existing capabilities; (2) embrace an all-of-Nation approach; (3) add value for all participants; and (4) maintain a global health perspective. 1. Leverage Existing Capabilities – Taking full advantage of the resources we have, to include making key capabilities available more broadly across the enterprise, is a core principle. Extending electronic reporting of health information, including laboratory results, to public health serves as an example of rapidly communicating useful information. Another example is better integrating knowledge of human, animal, or plant health by leveraging social media and widely available tools to facilitate rapid information sharing domestically and globally. Routine, daily use of such capabilities may be leveraged to address critical requirements in the context of an emergency. 2. Embrace an All-of-Nation Approach – A wide array of participants can enhance the Nation’s ability to detect, track, and navigate incidents affecting human, animal, and plant health. By consciously distributing biosurveillance activities, embracing novel community information sources, and prioritizing the development of a broader array of point-of-care diagnostics, as examples, we can expand exponentially the number of “sentinels” that may detect an incident of national significance. Establishing simple protocols and institutionalizing the sharing of discrete, essential information will enable us to achieve a meaningful integration of effort. 3. Add Value for All Participants – With reduced resources a reality, a key tenet of our biosurveillance approach is to pursue deliberately a set of identified core functions and enablers across a distributed national architecture. This pursuit of core functions and focus areas should not radically alter current responsibilities or burden enterprise participants, and should provide a mutual benefit for participants. Even as we query others for information, or provide data ourselves, we can and should be mindful of how the exchange of information can enable efficiencies, to include leveraging the input of others to address local requirements. For example, providing information to the health care system can substantially benefit decisions regarding patient treatment, infection control measures, and hospital staffing. Maximizing the value of biosurveillance information at the community level will encourage greater participation and effectiveness across the national enterprise. There can be a value proposition for all with conscious attention. ★ 4 ★ NAT I O NA L S T R AT E G Y F O R B I O S U RV E I LL A N C E 4. Maintain a Global Health Perspective – Recent incidents have demonstrated consistently the global connections and our collective vulnerability to transnational health and security threats. In our interdependent world, where disease recognizes no borders, and where CBRN and other threats may emanate from abroad, our domestic biosurveillance approach must necessarily have an eye toward our shared participation in global health security. We should reinforce international connections with our national enterprise as the global biosurveillance network continues to grow. And we should encourage other countries to integrate their surveillance and situational awareness systems and make this information available to the global community, creating a network of information nodes enhancing global response to incidents. Biosurveillance Goal and Core Functions With the guiding principles as the foundation of our efforts, the National Biosurveillance Strategy articulates the overarching biosurveillance goal of the United States along with four core functions. Together, they promote deliberate focus and a common compass heading for our collective approach. Our biosurveillance goal is to achieve a well-integrated national biosurveillance enterprise that saves lives by providing essential information for better decisionmaking at all levels. Four core functions form the basis of the National Biosurveillance Strategy: (1) scan and discern the environment; (2) identify and integrate essential information; (3) inform and alert decisionmakers; and (4) forecast and advise potential impacts. These core functions are interrelated, multidimensional, and it is intended that they are pursued simultaneously, informing and influencing each other as part of a dynamic process. They are intended to increase incident understanding and to inform decisionmaking at all levels, even where significant ambiguity exists. Accomplishing these functions will help us to achieve the overall goal of biosurveillance. 1. Scan and Discern the Environment – This core function emphasizes attention to factors affecting the health and security of our citizens and the rapid evaluation of information to speed incident detection. Information from a range of sources, including those outside of human health or security disciplines – animal, plant, and environmental health sector information – may enhance the effectiveness of this function. The practice of actively scanning and discerning the environment involves efforts to confirm conditions and identify rapidly the emergence of new patterns or trends, while assessing their significance. 2. Identify and Integrate Essential Information – Our Strategy calls for the identification, sharing, and integration of essential information to expedite incident detection and assessment. Although all incidents have unique aspects, there are common elements of any national public health emergency. As with a health care provider and a new patient, there are certain key questions asked to identify symptoms and narrow probable causes to assist with patient treatment. Similarly, essential information can be derived from a discrete set of key questions to speed incident detection and awareness. Information sharing and integration will be easier to achieve and to institutionalize across the national biosurveillance enterprise by focusing on these key questions. ★ 5 ★ NAT I O NA L S T R AT E G Y F O R B I O S U RV E I LL A N C E Beyond essential information to detect and characterize an incident of national significance affecting human, animal, or plant health, our Strategy emphasizes purposeful integration across disparate information sources, including data derived from intelligence, law enforcement, environmental, plant, animal, and other relevant areas. The intent is not to share all information with all participants in the national biosurveillance enterprise, but rather to seek opportunities to add value for others by thinking more broadly about what information may be useful to enterprise participants and to share this information and analysis proactively. By identifying, sharing, and integrating diverse information sources and expert analysis, collectively we will be more likely to identify trends signaling an incident and better able to answer key questions. The initial priority is to detect the earliest signs of potential security and health threats, then focus biosurveillance activities on the characterization and validation of the identified threat, and finally, track the threat and provide ongoing situational awareness. 3. Alert and Inform Decisionmakers – There exists an enduring requirement that our national biosurveillance enterprise be able to alert rapidly and inform decisionmakers of a potential incident of national significance, providing early warning and critical updates throughout any evolving incident. This function to alert and inform is iterative. And alerts do not necessarily mandate definitive action. A tension often exists between certainty and timelines for action, so it is necessary to find a balance among entities responsible for providing incident information and decisionmakers responsible for action regarding the information. 4. Forecast and Advise Impacts – Decisions made during an incident require an accurate comprehension of the knowable facts of the current situation and benefit from a forecast of the probable trajectory, duration, and magnitude of that incident into the future. This forecasting capability can assist in addressing the need to act quickly to save lives and prevent negative economic consequences in certain situations, even amidst great uncertainty and ambiguity. This function involves identifying the most likely and probable impact and outcomes, and where applicable, the most dangerous and worst case scenarios. Forecasting is a cognitive process informed by facts and models, and honed with experience. Similar to economic forecasting, improvement in forecasting is not solely reliant on better modeling and simulation, but in cultivating skills derived through experience and professional development. An efficient, effective, and well-integrated biosurveillance enterprise depends on all participants focusing their programs toward implementation of these functions. The core functions are the specific and priority areas of focus for enhancing the coordination and management of incidents of national significance affecting human, animal, and plant health, and serving as a key node in an emerging international network focused on global health. The deliberate pursuit of these carefully selected core functions is aimed at strengthening the national biosurveillance enterprise, adding value for all, and expediting decisionmaking at all levels. ★ 6 ★ NAT I O NA L S T R AT E G Y F O R B I O S U RV E I LL A N C E Enablers for Strengthening Biosurveillance Enabling capabilities are identified as part of our Strategy for a well-integrated national biosurveillance enterprise. Emphasis on empowering a distributed architecture and advances in relevant science and technology capabilities are a priority. These enabling capabilities are identified to facilitate the specified biosurveillance core functions. They represent ongoing focus areas to strengthen further the coordination and management of incidents of national significance affecting human, animal, and plant health. 1. Integrate Capabilities – Seek out new and creative ways to integrate biosurveillance capabilities, such as regional information sharing arrangements combining human, animal, and plant health trends. Emphasize efforts to transcend regular boundaries and across traditional organizational lines. Consider social media as a force multiplier that can empower individuals and communities to provide early warning and global situational awareness. 2. Build Capacity – Prioritize capacity building across our distributed national biosurveillance architecture, including development and use of point-of-care and multipathogen diagnostics, and the integration of fusion centers, law enforcement, intelligence, and other information collection and sharing activities. Develop a professional work force with multidisciplinary education, familiarization with information technology, and mentorship that emphasizes the four functions of biosurveillance, particularly forecasting. 3. Foster Innovation – Identify science and technology capabilities that will facilitate biosurveillance activities, including new detection and health information exchange approaches. There is substantial opportunity with the evolution of information technology to create distributed networks and empower individuals to enhance the value of biosurveillance information. In addition, encourage new thinking and the development of revised methodologies aimed at forecasting likely CBRN incidents, food-borne illness, environmental disasters, and outbreak trajectories in the absence of definitive data. As with economic and weather forecasting, there are innovative ways to combine information and known facts to project what is likely to transpire. 4. Strengthen Partnerships – Pursue biosurveillance activities that purposefully mix and match efforts and the sharing of information between and among Federal, State, local, tribal, territorial, private, nongovernmental, academic, and other national enterprise participants. Seek out an awareness of the interests of others and find ways to provide mutual benefit through existing and new partnerships and consideration of all aspects of the biosphere. Develop connections through collaborative international biosurveillance activities that will accelerate effective response to domestic and international incidents. ★ 7 ★ NAT I O NA L S T R AT E G Y F O R B I O S U RV E I LL A N C E Way Forward A strategic implementation plan shall be completed within 120 days of the issuance of this Biosurveillance Strategy, which will include specific actions and activity scope, designated roles and responsibilities, and a mechanism for evaluating progress. During the development of the implementation plan, we will delineate the key questions that identify biosurveillance essential information for decisionmaking. Current and planned activities and capabilities-based planning will complement the Presidential Policy Directive-8 – “National Preparedness” implementation process, where biosurveillance is identified as a key capability for national preparedness. Conclusion Protecting the health and safety of the American people through a well-integrated national biosurveillance enterprise is a top national security priority. It requires that we focus on core functions to make further progress. It also necessitates that we embrace an all-of-Nation approach and indeed a global health security intent, as the effects of any deliberate CBRN attack or accident, or emerging infectious disease, can transcend national borders. There exists an imperative that we expand our efforts to detect rapidly a potential incident of national significance affecting human, animal, or plant health, whether resulting from a bioterror attack or other CBRN threat, an emerging infectious disease, pandemic, or a food-borne illness. Rapid detection is critical to save lives and improve incident outcomes, and the United States serves as a key node as part of an international network of biosurveillance centers across the globe. Our National Strategy for Biosurveillance seeks to leverage existing capabilities across the Nation yet emphasizes a discrete focus on specified core functions. It articulates that essential information can be derived from a specific set of questions to speed the detection of a deliberate or accidental CBRN incident or naturally occurring disease outbreak. This Strategy further articulates that when the collection and sharing of this essential information is prioritized, decisionmaking can be expedited at all levels of government and beyond. This is the essence of our approach. While other activities are integral to everyday local biosurveillance efforts that can and should continue, our Strategy calls for a national focus on fewer issues so that more can be achieved collectively. Our approach also seeks to inspire new thinking and revised methodologies to “forecast” that which we cannot yet prove, so that timely decisions can be made to save lives and reduce impacts during an emergency incident. This is our Strategy. It is our plan of action to protect the health, well being, and safety of the American people as part of the global community. ★ 8 ★ rna Jou l of B e odef nse Bi errorism & iot ISSN: 2157-2526 Journal of Bioterrorism & Biodefense Shulman et al., J Bioterr Biodef 2012, S4 DOI: 10.4172/2157-2526.S4-004 Commentary Open Access Bioterrorism and Surveillance for Infectious Diseases - Lessons from Poliovirus and Enteric Virus Surveillance L M Shulman1,2*, Y Manor1, D Sofer1 and E Mendelson1,2 1 Central Virology Laboratory, Public Health Services, Israel Ministry of Health Sheba Medical Center, Tel Hashomer, Israel 52621 Dept. of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel, 69978 2 Abstract Early recognition and rapid response are crucial for control of infectious diseases introduced by bio-error, bio-terror or Mother Nature. Early recognition requires surveillance. Surveillance includes methods for identifying the presence of infectious agents or the symptoms caused by the presence of such agents. Overlapping of different surveillance strategies improves the chances for success. Results from enteric virus surveillance of acute viral gastroenteritis in sentinel children wards and outbreaks and environmental surveillance for polio and non-polio enteroviruses in Israel are presented to exemplify surveillance for infectious disease agents and for use as yardsticks for evaluating response to intervention and to introduction of new vaccination programs and for their potential for evaluating acute gastroenteris syndromic surveillance. Introduction Highly infectious pathogenic organism may be introduced into a region by bio-error, bio-terror, or Mother Nature. Bio-error is the accidental release of an infectious organism into the region. Examples include release from a vaccine production or storage facilities, archived biological material collected at the time when the organism was endemic, or from lab stocks either of the original organism or an extinct organism recreated by genetic engineering. Bio-terror is the intentional release of the infectious agent into the region from these sources. Finally, introduction by Mother Nature refers to the natural release of infectious organisms into a region. This most commonly occurs when infected hosts bring the organism into the region from an external reservoir or when changing living conditions increase the chance for zoonotic exposure within regions. Less common is reappearance as a result of release of an organism preserved in permafrost or by genetic evolution or genetic recombination in endogenous low pathogenic organisms that cause alterations in antigenicity reduce recognition by the immune system of individual hosts or host populations and/or which alter pathogenic organism-host interactions enabling the organism to change its host range or even the location within the host where that the organism can replicate. Included among low pathogenic organisms are live attenuated vaccines where evolution can lead to phenotypic reversion to a highly pathogenic form during infection of primary vaccines with functional immune systems, during persistent infections that may occur after vaccination or exposure of immune deficient individuals, and during subsequent person-to-person transmission to contacts of either of these types of individuals. Early detection of the presence of the highly pathogenic infectious organisms is essential for containing the spread of these organisms in the flora or fauna within a given geographical region and for their elimination. This is true regardless of whether the infectious organism was introduced through bio-error, bio-terror, or Mother Nature. Early detection and measurement of efficacy of response requires high quality surveillance over extended periods of time. Integration of different surveillance strategies performed in parallel improves reliability and strengthens interpretation of data. The relatively unique combination of surveillance strategies for enteric viral infections in general and poliovirus infections in particular in Israel will be presented as a model for early detection of highly pathogenic organisms and subsequent monitoring of the efficacy of response. The main strategy that will be J Bioterr Biodef presented in detail uses environmental surveillance (reviewed in [1]) to identify the presence of pathogenic polioviruses in large populations before symptomatic cases occur. The second strategy that will be briefly reviewed is the systematic investigation of acute gastroenteritis in symptomatic cases from outbreaks and some or all admissions to sentinel departments in hospitals. Both approaches provide data about pathogenic organisms and provide a picture of what is going on at the community level. More importantly, both need to be in place for years to establish the base lines for recognizing the sudden appearance of unusual events. This depth is required to take into account seasonal and annual variations. Data gathered from these surveillance systems will also provide the basis for calibration and evaluation of a third approach, looking for unusual changes in the number and pattern of syndromespecific admissions to hospital emergency wards or visits to HMO physicians. Specific examples will be provided to illustrate how classical and molecular data gathered from identification of pathogen-based strategies provide the epidemiological data needed for identification, response and follow up to bio-error, bio-terror, or Mother Nature triggered event. Materials and Methods Surveillance Environmental surveillance for poliovirus and enteroviruses: Composite sewage samples have been routinely collected monthly from sentinel sites covering 30-40% of the Israeli population since 1989 using computerized automatic samplers that collect and pool aliquots hourly over a 24 hour period. When automatic sampling was not possible, peak hour grab samples were collected instead. Concentration, selection *Corresponding author: Lester M. Shulman, Central Virology Laboratory, Chaim Sheba Medical Center, Tel-Hashomer, 52621, Israel, Tel: +972-3-530-2341; Fax: +972-3-535-0436; E-mail: lester.shulman@sheba.health.gov.il Received November 18, 2011; Accepted February 05, 2012; Published February 18, 2012 Citation: Shulman LM, Manor Y, Sofer D, Mendelson E (2012) Bioterrorism and Surveillance for Infectious Diseases - Lessons from Poliovirus and Enteric Virus Surveillance. J Bioterr Biodef S4:004. doi:10.4172/2157-2526.S4-004 Copyright: © 2012 Shulman LM, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Bioterrorism: Infectious Diseases ISSN:2157-2526 JBTBD, an open access journal Citation: Shulman LM, Manor Y, Sofer D, Mendelson E (2012) Bioterrorism and Surveillance for Infectious Diseases - Lessons from Poliovirus and Enteric Virus Surveillance. J Bioterr Biodef S4:004. doi:10.4172/2157-2526.S4-004 Page 2 of 5 and isolation of polio and enteroviruses and downstream molecular epidemiological and phylogenetic characterization were as previously reported [2-5]. Acute viral gastroenteritis surveillance for enteric viruses: The enteric viral surveillance of severe acute gastroenteritis in sentinel children’s ward and outbreaks reviewed in the discussion was performed as published for rotavirus [6-8]. The norovirus was assayed by semiquantitative Real Time RT-PCR for the amplification and detection of norovirus genotype GII RNA by TaqMan technology as previously described [9]. Sydnromic surveillance for community physician visits for patients presenting with acute gastroenteritis from any cause: All Israelis are registered in one of four HMOs: Clalit, Maccabi Health Care Services, Kupat Holim Meuhedet, and Leumit. The HMOs maintain computerized records that include the ICD-9-based code reason for the visits. The Israel Center for Disease Control has received this data from the Maccabi Health Care Services, the second largest HMO covering approximately 25% of the population and Hospital Emergency Rooms on a daily basis for many years and prepares a weekly report on the rates of visits or admissions based on the ICD-9 codes. In this manuscript we present the weekly and monthly visits to the Maccabi Health Care Service community physicians of patients who presented between January 2004 and June 2008 with acute gastroenteritis from any cause [protozoal intestinal disease uns, bacterial enteritis uns, viral enteritis uns, enteritis uns, infectious colitis, acute gastroenteritis, proven gastroenteritis infection, and presumed gastroenteritis infection] and for nausea and vomiting from any cause. Electron microscopy: 10 µl of clarified stool suspension was dried on Smart grids (Dune Sciences, Or, USA). The material on the grids was negatively stained with uranyl acetate and then viewed on a Jeol LS200 EX II transmission electron microscope (Jeol LTD, UK) at a magnification of 30,000 to 40,000. Final identification on the basis of size and morphology was made at a magnification of 100,000. VP1 Sequences: The VP1 sequences of the type 1 WP isolates represented in the phylogenetic tree in Figure 1 were submitted to the EMBL/GenBank/DDJB data bank. The accession numbers are listed in parenthesis after the short name (as it appears in Figure 1) and the full isolate name. Isolates from the Gaza District: P-1 = PV1/2335_1/ PAL91 (JQ228553); P-2 = PV1/2252_1/PAL91 (P2 JQ228554); P-3 = PV1/3313_25/PAL94 (JQ228555); P-4 = PV1/3313_27/PAL94 (JQ228556); P-5 = PV1/3380_7/PAL94 (JQ228557); P-6 = PV1/3381_3/ PAL94 (JQ228558); P-7 = PV1/3381_9/PAL94 (JQ228559); P-8 = PV1/3432_5/PAL95 (JQ228560); P-9 = PV1/3431_21/PAL95 (JQ228561); P-10 = PV1/3431_21/PAL95 (JQ228562); and P-11= PV1/3455_27/PAL95 (JQ228563). Israeli isolates: Is-1 = ISR87-5483 (AF528790) and Is-2 = PV1/3615/ISR95 (JQ228564). Results and Discussion Environmental surveillance for polioviruses Symptomatic and asymptomatic individuals excrete virus progeny into sewage during enteric viral infections. This is the basis behind the use of environmental surveillance to document poliovirus infections in populations [10]. More importantly from the public health point of view, sewage surveillance can detect silent poliovirus virus circulation before appearance of the first case of irreversible poliomyelitis [1] since less than 1% of infections of naïve children even with highly pathogenic wild poliovirus cause poliomyelitis, whereas >90% are asymptomatic. Most surveillance procedures involve concentrating the J Bioterr Biodef E Jun ’95 Mar ‘95 Feb ‘95 Dec ‘94 Oct ‘94 P-11 N. Gaza Sch. Raduan 162g->a* 570a->t 588g->t* P-8 7.81c ->t Beit Lahia D P-6 Rafah 183g->a P-7 P-4 177 t->c 444 a->g 543 a->g 849 g->a** B P-10 834c->t 864t->c 216a->g 867c->a 342c->t 378c->t 813c->g 76 g->a ** P-5 390 t->c 414 a->g ** Qualquilia 16c->t P-3 N. Gaza P-9 33c->t 354a->g ~ ~6 Gaza P-1 P-2 4 ~ ~ ~ ~5 2 ~ ~ ~ ~ Total Transition 1 2 3 4 5 6 7 8 19 44 30 5 5 11 20 17 19 41 27 3 3 18 14 ~ ~7 ~ ~ ~ ~3 A Nov ‘ 87 8~ ~ 738 t- >c SEP‘91 Is-2 Beit Lahia C ~ ~ Ashdod ~ ~1 Is-1 Transversion 0 3 3 2 2 3 2 3 back * 0 0 0 0 0 0 0 3 parallel ** 0 1 1 0 0 0 4 1 Figure 1: The phylogenetic relationships among WP isolates between 1991 and 1996 The upper panel is a schematic representation of the phylogenetic relations among type 1 WP isolated from sewage after Israel became poliomyelitis free. The short names of actual isolates appear in the ovals (see materials for the full isolate names and accession numbers). The vertical axis is proportional to the month of isolation. The lengths of the branches are scaled to the number of nucleotide substitutions. The small circles represent hypothetical intermediates along the evolutionary pathways. Very long branches have been discontinued in their middle and each such “break” has been numbered. The actual nucleotide substitutions between each branch point are listed on the tree (format: nucleotide, previous nucleotide->substituted nucleotide; example: 543a->g) for short branches. The numbers and types of substitutions for longer branches are indicated in the lower table according to the numbers that appear beside each breakpoint in the long branches. The types of substitutions listed are the total number, and the numbers of transitions, transversions, substitutions back to previous nucleotides (example A->G->A), or independent parallel substitutions in separate lineages. All isolates in the tree were rooted to the 1987 isolates from the last type 1 WP outbreak that occurred in 1987-88 [13]. The patterns of nucleotide substitutions along branches between isolates were then compared to that for short outbreaks [5] to determine whether or not the substitutions that were observed could have arisen during local endemic person-to-person transmission. Those substitutions in isolates within the gray box (Group C) were consistent with local transmission, whereas the differences in sequence between isolates in C versus D and E were not, i.e. they represent separate introductions. virus in a sewage sample followed by a biological amplification of the viruses on tissue culture before molecular analysis [1,11]. Countrywide routine monthly environmental surveillance for poliovirus in sewage was initiated in Israel in 1989 and is the longest running national comprehensive surveillance program to date [1]. Approximately 3040% of the entire population lives within the catchment areas of the surveillance sites. Since the initiation of surveillance, tourists and businessmen have traveled to and from regions were polio was still endemic. In addition there was a large influx of Palestinian families from poliovirus endemic regions into the West Bank and Gaza District in 1994-1995 after the signing of the Oslo Peace accords. Bioterrorism: Infectious Diseases ISSN:2157-2526 JBTBD, an open access journal Citation: Shulman LM, Manor Y, Sofer D, Mendelson E (2012) Bioterrorism and Surveillance for Infectious Diseases - Lessons from Poliovirus and Enteric Virus Surveillance. J Bioterr Biodef S4:004. doi:10.4172/2157-2526.S4-004 Page 3 of 5 When polioviruses replicate, they have very high rates of nucleotide miss-incorporation because their RNA primed RNA polymerase lacks a proofreading capability [12]. The genomic regions encoding the entire VP1capsid protein from isolates from the last outbreak of poliomyelitis in Israel that occurred in 1987-1988 [13,14] were sequenced to establish the first high-resolution, full VP1 gene, molecular analysis of the rate and pattern of nucleotide changes that occur during short outbreaks arising from a single founder [5]. Jorba et. al. [12] analyzed additional outbreaks, some extending over many years, to establish a series of rates suitable for characterizing the relatedness of polioviruses isolated at very short to very long intervals depending on the classes of substitutions measured. These classes include synonymous third codon position substitutions, non-synonymous substitutions and transversion. These rates and the 10:1 ratio of transitions to transversions [12] can be used as a benchmark to distinguish between the possibility that two polioviruses isolated within a short time interval arose during personto-person transmission during an outbreak or resulted from two separate introductions from an external reservoir or different external reservoirs [2]. Introduction from an external reservoir is further supported when the pair-wise comparison of nucleotide sequence homology among isolates in the surveillance area is lower than between some of these isolates and isolates from external reservoirs [2]. Based on the performance of long-term environmental poliovirus surveillance (reviewed in [1]), the WHO has recently recommended that routine sewage surveillance be established in more countries (17th Informal Consultation on the Global Polio Laboratory Network, 2011, Geneva) based on standards previously recommended for environmental surveillance for polioviruses [11]. All of the recommended methods required a biological amplification and selection step. Specifically growing poliovirus in tissue cultures and using transgenic L20B marine cells. L20B cells express the human receptor for polioviruses and selectively amplify poliovirus but not other human non-polio enteroviruses [15,16]. Many of the countries that have or will institute environmental surveillance are wild poliovirus free and most or all samples should be negative for polioviruses. Sample integrity is especially important for the interpretation of a negative isolation. It was therefore important to introduce a control to ensure that the quality and integrity of the sample was maintained from the time of collection, during transport, and during processing in the laboratory. The control that was recommended [11] was to also test for the presence of nonpolio enteroviruses using cell lines that support growth of most human enteroviruses. The reasoning behind such a control is that the lability of other enteroviruses is similar to that of polioviruses and enterovirus infections are common everywhere. The type of poliovirus in sewage depends in part on the vaccination program in use. There are three types of poliovirus: vaccine, wild (WP) and vaccine-derived poliovirus (VDPV) [17]. An isolate was defined as a vaccine strain if the difference between the nucleotide sequence encoding its VP1 capsid protein and its respective Sabin serotype was 15% divergence were considered to be WP. Recently the upper limit for VDPVs was modified to include isolates with >15% divergence that could be phylogenetically related to VDPVs with 15% divergence were genotypically related to previously isolated VDPVs from long standing environmental surveillance programs carried out by Israel (discussed below) and Finland (reviewed by Hovi et al [1]). J Bioterr Biodef Isolation of vaccine virus Between 1989 and 2005, all children in Israel were vaccinated by the age of 15 months with three doses of inactivated polio vaccine (IPV) and three doses of live attenuated Sabin vaccine (OPV) [13]. From 1990 they were also vaccinated with an additional IPV dose at 6-7 years of age [13]. Annual vaccine coverage of at least three doses exceeded 95%. During the period when OPV was included in early childhood vaccination schedules, most of the live vaccine virus actually ended up in sanitary dumps because of the use of diapers, however some especially from older contacts routinely entered the sewage system. During this time >95% of the polioviruses isolated from sewage were vaccine strains. After 2005 Israel switched to exclusive use of IPV. OPV strains then rapidly disappeared from the sewage as had occurred in other countries that made a similar shift to exclusive use of IPV in their vaccination policies [1]. Isolation of WP The appearance of wild poliovirus isolates in sewage collected from a poliomyelitis free region indicates the silent presence or transmission of wild virus. The longer the poliomyelitis free period, the more likely that the WP has been introduced from an external reservoir. No specific intervention is required when there is herd immunity sufficient to prevent local transmission, for example when documented vaccine coverage is >95%. Rapid intervention (vaccination) is required, however, when coverage levels are below this level or when there is evidence of local circulation. Wild type 1 polioviruses were recovered from sewage collected from various sites in the Gaza District in 1991, 1994, 1995, 1996, 1999 and 1992 and from Ashdod, Israel in 1995. The entire VP1 of representative isolates were sequenced. The phylogenetic relationships among WP isolates collected between 1991 and 1996 are shown in Figure 1. The time course and pattern of nucleotide substitutions among the WP isolates was compared to the pattern from the 1987-1988 outbreaks [5]. The number of nucleotide differences between isolates in groups C (1994-5), D (1994) and E (1995) was much higher than the 1% per year expected for isolates from the same outbreak [2,12]. This large deviation from the expected rate for nucleotide substitutions and somewhat smaller deviations from the 10:1 transition to transversion ratios allowed us to infer that the isolates in group C, D and E in Figure 1 were progeny from separate introductions. In contrast, the kinetic pattern among group C isolates was consistent with the pattern of local transmission that occurred during the outbreak in 1987-1988 [5]. Furthermore, these WP isolates appeared during the peak in the influx of whole families with unknown vaccination histories into the Gaza District. This combination of events triggered an immunization response. Sewer surveillance was able to document the efficacy of the immunization response [1,4]. Specifically, there was a rapid decrease and disappearance of genotype-related WP isolates from subsequent samples from these positive sites. In 2002, two WP isolates were recovered within a four-month interval from the Gaza District. Using the same approach for analysis, these were considered to be from separate introductions [2]. Namely there was a much higher difference in nucleotide substitutions than could be expected to occur within four months for an outbreak with a single founder, the transition transversion ratios were inconsistent, and the relative homology indicated that each isolate was more homologous with isolates from different regions of Egypt than the Gaza District isolates were to each other. Bioterrorism: Infectious Diseases ISSN:2157-2526 JBTBD, an open access journal Citation: Shulman LM, Manor Y, Sofer D, Mendelson E (2012) Bioterrorism and Surveillance for Infectious Diseases - Lessons from Poliovirus and Enteric Virus Surveillance. J Bioterr Biodef S4:004. doi:10.4172/2157-2526.S4-004 Page 4 of 5 Two important principles that apply to bio-defense are illustrated from these WP surveillance studies. Advanced molecular analysis can indicate when virus isolates are introduced into a virus-free region, can infer whether such isolates represent subsequent local circulation or separate introductions, and can identify their probable external reservoir. This in turn can trigger the type of response in the surveillance region, and the same surveillance program can then monitor the efficacy of the response. A further advantage is that response can also be extended to the region of the external reservoir. Isolation of VDPVs In May of 1998, a serotype two VDPV (VDPV2) was isolated from a sewage sample collected at the entrance to the Shaf Dan wastewater treatment plant in central Israel [18]. Surveillance sites that were subsequently introduced throughout the catchment area of this sewage system are shown in Figure 2. In 1998, the catchment area of the Shaf Dan Plant encompassed a population of 1,600,000 individuals. Sequence analysis of the VP1 of the 1998 VDPV2 indicated that it had diverged by 8% from Sabin 2 and that extensive amino acid substitutions were present in neutralizing antigenic epitopes of the capsid proteins. Between May 1998 and Sept 2011, 62 phenotypically related Reading Aya lon R B c Line C KavB C75 C121 C109 C107 C108 S Shaf Dan Figure 2: Schematic representation of surveillance sites along the sewage system in central Israel Sewage in the Shaf Dan catchment area in central Israel flows north by gravitation to the Reading pumping plant. The sewage is pumped upwards at the Reading Station as well as at a point stream so that it can then flow south by gravitation to the Shaf Dan Waste Water Treatment Plant. Sewage is collected at the mouth of the Shaf Dan Treatment Plant by an inline automatic composite sampler. The direction of the flow is indicagted by the black arrows. Upstream samples are collected by portable automatic composite samplers lowered into the system at Reading, the mouth of Kav B and along the Ayalon trunk line at sites indicated by the circles. Samples are treated and analyzed for the presence of polio and non-polio enteroviruses as described in Materials. The collection sites in the figure correspond to the sites listed in Table 1. The Ayalon site in Figure 3 is located at the mouth of the Ayalon Line C just before it enters the Reading Pumping Station. J Bioterr Biodef After a half-year trial, surveillance schedules were returned to previous frequencies since the increase in sampling frequency added considerably to the workload without increasing the frequency of recovery. In contrast, adding upstream surveillance sites proved effective in increasing isolations. Contributing to this was that VDPV2 virus from the excretor progressively increased as the site of excretion was approached. The catchment population of the first major positive junction site, Redding, was reduced to 800,000 and successive addition of upstream sites along the Ayalon trunk line, one of five that fed into the Reading site, have further reduced the population including the excretor to approximately 25-50,000 individuals. The VP1 of each isolate was sequenced. Samples that contained VDPV2 isolates that were phenotypically related to the 1998 VDPV2 are represented by the pink boxes in Table 1. On Feb 2006, a phenotypically unrelated VDPV2 with 6.6% VP1 divergence was recovered from a single collection in Jerusalem. No related isolates have been found to date from that site in Jerusalem, however by Sept 2011, eleven phenotypically related isolates (represented by blue boxes in Table 1) have been recovered from eight samples from the Shaf Dan catchment area in Tel Aviv, starting with one from the Redding site that was isolated one month after the isolation in Jerusalem. The next ten related isolates were recovered from the Redding site or trunk line, Kav B, which is a different upstream trunk line from the sites that were positive for isolates related to the 1998 VDPV2. The catchment area of Kav B includes most of the major Mediterranean Sea shorefront hotels in north Tel Aviv and represents a 50,000 population. A change in the sewage system but not surveillance site has since reduced the catchment population for the Kav B positive site to 25,000. C58 C103 VDPV2s were intermittently isolated from an additional 43 sewage samples. During this period of surveillance, two strategies were pursued to increase isolations: sampling frequency was increased at established sites and additional sites were successively added at points above positive sites where major trunk lines converged (see Figure 1). Sewage samples that contained VDPV2s are shown by collection date in Table 1. Colored squares (pink, blue, and yellow) indicate a site that was positive for VDPV, white boxes indicate negative sites that were sampled within a month of the positive site, while grey boxes indicate a negative finding at a site that was sampled on the same day as the positive site. From left to right, columns in Table 1 represent the progressive spatial transition from the mouth of the Shaf Dan treatment plant to the most upstream site (see Figure 2). The rightmost two columns represent a positive VDPV2 site from Jerusalem and the only site from where a type 1 VDPV was isolated, a site in Haifa. The Shaf Dan-like isolates (pink boxes in Table 1) and the Jerusalem-Redding like VDPV isolates (blue boxes in Table 1) belong to two separate epidemiological events, i.e. persistent infection of two different immune individuals after separate exposures to serotype two Sabin vaccine [19]. The nucleotide substitutions within the VP1 genes from the VDPV2 isolates steadily increase from 8% to16.7% as time progressed. The VPDV2 isolates were shown to be highly neurovirulent in mice model systems and neutralizing antibody titers in the general public were three-fold lower than against respective Sabin strains [3,19]. Fortunately, despite the high nucleotide and amino acid divergence, these isolates were still as sensitive in vitro as the Sabin 2 strain to the antiviral effects of isoflavenes [20]. The identity of the individuals excreting the aVDPVs has not yet been established. To infer more about the excretors, additional segments of the 7400 nt genome of each isolate were sequenced. These Bioterrorism: Infectious Diseases ISSN:2157-2526 JBTBD, an open access journal Citation: Shulman LM, Manor Y, Sofer D, Mendelson E (2012) Bioterrorism and Surveillance for Infectious Diseases - Lessons from Poliovirus and Enteric Virus Surveillance. J Bioterr Biodef S4:004. doi:10.4172/2157-2526.S4-004 Page 5 of 5 1 Date 1A 1A1 Saf Dan Reading Kav B S 1.6 million B 0.05 million R 0.8 million 1A3 Surveillance Sitea 1A3.3 1A3.2 1A3.4 Ayalon Ayalon Ayalon Yad Ayalon Rakevet Eliahou Hatkiva C 0.35 million C-58 C-75 1A3.5 Ayalon Park Darom 1A3.6 Ayalon Park Darom 1A4 Ayalon Park Darom 1A5 Ayalon C-103 C108 C-109 C-114 2 3 Jerusalem Haifa 0.75 0.27 million million 29-Sep-11 20-Jul-11 29-May-11 27-Apr-11 15-Mar-11 14-Mar-11 15-Nov-10 15-Nov-10 24-Jun-10 21-Apr-10 27-Jan-10 20-Oct-09 30-Aug-09 22-Feb-09 20-Jan-09 23-Dec-08 25-Nov-08 17-Nov-08 29-Jul-08 30-Jun-08 24-Jun-08 24-Feb-08 29-Jan-08 17-Sep-07 28-Aug-07 27-Aug-07 23-Jul-07 20-Mar-07 06-Dec-06 18-Oct-06 04-Oct-06 06-Sep-06 09-Aug-06 14-Mar-06 02-Feb-06 20-Jul-05 13-Apr-05 22-Apr-04 15-Dec-99 06-Dec-99 03-Nov-99 06-Sep-99 05-May-98 KEY TYPE 2; EPI GROUP 1 TYPE 2; EPI GROUP 2 TYPE 1; EPI GROUP 3 NEGATIVE Not done on this date a See Fig 2 for the location of the sites Table 1: Intermittent isolation of vaccine-derived polioviruses from environmental samples in Israel. additional regions included the 5’untranslated region and VP2, VP3 and VP4 capsid protein genes located 5’ of the VP1 capsid gene, and the RNA primed RNA polymerase, 3D, located at the 3’ end of the single open reading frame of the poliovirus genome. Phylogenetic analysis of all of the environmental aVDPV isolates indicated that excretion was limited to one individual and/or a very limited number of contacts for each of the epidemiological events. In the absence of identification of the excretor or excretors, this conclusion was based on the following lines of reasoning. (1) Most nucleotide substitutions that accumulate during evolution of poliovirus are random and most are silent third codon position substitutions [12,21,22]. Two J Bioterr Biodef different patterns involving high numbers of identical substitutions spread throughout the genome, despite overall sequence diversion of >10% among isolates indicated that there were two, and only two epidemiological events [19]. (2) Progeny that arose during person-toperson transmission in populations of immune competent individuals, cVDPVs, have very few amino acid substitutions in antigenic sites and most rapidly undergo multiple recombination with other polioviruses and non-polio enteroviruses [21,22]. In contrast, progeny that arise during persistent infections in immune deficient individuals have many amino acid changes in antigenic epitopes and most had not undergone any genomic recombination [21,22]. The Israeli aVDPV isolates were Bioterrorism: Infectious Diseases ISSN:2157-2526 JBTBD, an open access journal Citation: Shulman LM, Manor Y, Sofer D, Mendelson E (2012) Bioterrorism and Surveillance for Infectious Diseases - Lessons from Poliovirus and Enteric Virus Surveillance. J Bioterr Biodef S4:004. doi:10.4172/2157-2526.S4-004 Page 6 of 5 Downstream sites are frequently negative when upstream sites are positive, and detection is intermittent even at the most upstream sites. This is shown by the surveillance entries for March 14th and 15th, May 29th, and July 20th of 2001 (Table 1) where multiple sites (see Figure 2) were simultaneously monitored at hourly intervals by automatic samplers; three sites for two successive 24 hour period and two sites for just the first 24 hour period. At four of the sites, composite samples were obtained for each 24-hour period by pooling samples. At the 5th site (C-75), hourly samples were collected and analyzed separately. On March 14th, starting from downstream sites and proceeding to upstream sites, no VDPVs were recovered from the Shaf Dan site, two VDPV2s were isolated from the Reading site, three of the first set of 24 hourly samples from C-75 located upstream contained a single VDPV2, two VDPV2s were isolated from site C-108 and one from C-109. On March 15th, no VDPV2s were recovered from the Shaf Dan site, one VDPV2 was recovered from one of the 24 individual samples from C-25 and one from site C-108. All of the isolates from the Ayalon line sites (C-75, C108, and C109) were related to previous Shaf Dan-Ayalon isolates. One of the two Reading VDPV2 isolates was related to these Shaf Dan-Ayalon VDPVs, while the other was related to the JerusalemKav B isolates. The isolates from C-75 were obtained from samples collected at 09:00, 10:00, 04:00 and 08:00 AM suggesting that the virus is excreted from a residential site or less likely from a nighttime job. These VDPV studies illustrate four additional principles and some limitations of environmental surveillance [1] that can be applied toward bio-defense. (1) Environmental surveillance is sensitive enough to detect virus excreted by one or a very small number of individuals in very large populations. (2) A negative finding does not mean the absence of the virus since the sensitivity is at the limits of detection. Most virus positive sewage samples contained one or at most a few poliovirus isolates, whereas it is estimated that 107 viruses are excreted per gram of feces [1]. Intermittency may also reflect the finding that poliovirus was isolated in most but not every stool sample collected from an identified, persistently infected individual [25]. (3) When enough surveillance sites are re-sampled for sufficiently long intervals it may even be possible to follow movements of the infected individual within large populations. This is illustrated by the shift from Jerusalem J Bioterr Biodef to Tel Aviv of the source of the second event (blue boxes in Table 1), and the shift within Tel Aviv of the source of the first event, i.e. the two times when progeny from the first event (pink boxes in Table 1) were isolated from the site on the Kav B branch, rather than along the Ayalon branch. And (4) The ability of environmental surveillance to determine the pattern of excretion within a region, specifically whether one individual or more than one is infected and when there is more than one, whether they live or at least excrete in different regions of the city. This is most clearly illustrated by the isolation of two unrelated VDPVs in the same sample (blue and pink box Table 1) from Reading site on March 14th 2001 and the exclusive finding of isolates related to only one at simultaneously sampled upstream sites along the Ayalon trunk line. For reference, the Reading site is located downstream of the Ayalon and Kav B trunk lines from which most epidemiological event one and two VDPV2s were previously isolated, respectively. Enteric viral surveillance The WHO has recommended that a minimum of 30% of the sewage samples in a surveillance program be enterovirus positive to ensure that collection, transport and sample processing meet quality standards [11]. The annual rate of enterovirus positive samples in Israel has varied between 75 and 90% by plaque assay. Variations in the number of plaques provide a rough indication of the pattern of community enteroviral infections, since some enteroviruses may not grow on the cell line used for screening the sewage samples and others may not grow in tissue cultures at all. An example of the plaque counts from a single site representing a catchment population of 350,000 in central Israel over a 3-year period (2007 to 2009) is presented in Figure 3. Three samples also contained type 2 VDPVs (indicated by black arrows). Routine investigations of hospitalized cases from neurological wards for enteroviral infections compliment these findings and identify those viruses causing severe infections. 90 Number of Enterovirus Plaques inferred to have come from persistent infections of either of two immune deficient individuals since the aVDPVs from each event had many amino acid substitutions in antigenic sites and there was different single recombination event within the polymerase gene for isolates of each event [19]. (3) Immune deficient persistently poliovirus infected individuals are rare; only 40 identified throughout the world to date [17]. (4) Vaccine excretion in healthy individuals is self-limiting and measured in weeks at most [23,24]. During the twelve-year interval of aVDPV isolations, the annual polio vaccine coverage of the Israeli population was >95% [13]. Thus the conditions for establishment of herd immunity were in place meaning that there would have been an insufficient number of naïve immune competent individuals available to maintain a chain of transmission over the 12 years during which the excretor or excretors were present in the catchment area, or the 24 years during which the virus evolved. And (5) the consistent recovery of each group of event-related isolates at separate geographical locations within the same city, e.g., at surveillance sites along different branches of the sewage system in a single city, when 30-40% of the entire country-wide population has been subjected to monthly surveillance throughout this period argues for minimal person-to-person spread. These arguments rely on one of the basic tenets of a good surveillance program, namely that in order to discover or rule out occurrence of an unusual event, there must be sufficient data from long-term routine surveillance. 80 70 60 50 2007 2008 2009 40 30 20 10 0 Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Month Figure 3: Enterovirus isolations from the Ayalon surveillance site (1A3) between 2007-2009 by month Sewage was collected at hourly intervals over 23-hour periods by an automatic composite sewage sampler that was lowered into the sewage system at the mouth of the Ayalon line just upstream of the Reading pumping station (see Figure 2). The catchment area of this site includes 350,000 individuals. The samples (1 L) were processed as reported [2]. A 2.5 ml aliquot of each concentrated sewage sample was plated on BGM cell monolayers under plaque forming conditions. The number of plaques from each sample is graphed according to the month that the sample was taken. The three black arrows indicate samples that also contained VDPV2 isolates belonging to epidemiological group 1. Bioterrorism: Infectious Diseases ISSN:2157-2526 JBTBD, an open access journal Citation: Shulman LM, Manor Y, Sofer D, Mendelson E (2012) Bioterrorism and Surveillance for Infectious Diseases - Lessons from Poliovirus and Enteric Virus Surveillance. J Bioterr Biodef S4:004. doi:10.4172/2157-2526.S4-004 Outbreak investigation requires close coordination between the National Center of Viral Gastroenteritis at the Central Virology Laboratory and District Health Officers and/or the staff of hospital Infectious Disease Departments. Real Time RT-PCR (rRT-PCR) was used to identify and quantify viral loads of norovirus infections, while rotavirus was identified by immuno-chromatographic (dipstick) assays and genotyped by RT-PCR. Stool suspensions from some of the outbreaks were first screened by electron microscopy (EM). Results based on size and morphology can be obtained in less than two hours using negative staining techniques and can focus the specific molecular identification tests that need to be carried out. On the down side, the limit of detection is 104 to 105 particles depending on the pathogen [26]. One hundred and one acute gastroenteritis outbreaks were investigated between 2005 and 2011. Genotype II.4 noroviruses accounted for all 67 (66.3%) of the outbreaks (Figure 4) and reovirus for another (1.0%). These outbreaks were due to the introduction of virus into groups of naïve individuals (Mother Nature). No viral etiology was found for 32 outbreaks (31.6%). Finally, stools from individual cases from one community-wide acute gastroenteritis outbreak contained different bacterial and viral agents including rotavirus and adenovirus and stools from some individuals actually contained more than on enteric pathogen. Subsequent investigation, in part directed by the pattern of pathogenic agents discovered during surveillance, revealed that bioerror (not bio-terror or Mother Nature) had caused the outbreak. In this case, inadvertent channeling of sewage into the community drinking water caused the outbreak. The current protocols for concentration, amplification in tissue culture and analysis of polioviruses takes 14 to 21 days. Genotyping of individual enterovirus plaques from the sewage samples is labor and resource intensive and is not practical for rapid routine surveillance (see discussion of timeliness in relation to syndromic surveillance below). Studies are underway to test the possibility of drastically decreasing processing time by eliminating tissue culture amplification and trying different concentration strategies. For example, directly extracting the nucleic acids from concentrates prepared with current procedures that take less than two days will be compared to extraction from virus in ultracentrifugation pellets, prepared after mid-speed clarification to remove larger particulate matter. The advantage of eliminating the tissue culture amplification step is two fold, a large reduction in time and the fact that fastidious enteroviruses and other enteric viruses would be included in the population sequenced. The main disadvantages are a significant decrease in the amount of nucleic acid available for testing, mixtures of many closely related viruses and the need to make nucleic acid extractions from materials that are known to contain high amounts of inhibitors of RT and PCR enzymatic amplification reactions that might be co-extracted. The use of next generation sequencing that can be completed within days on some of the smaller platforms currently available, should overcome some of the difficulties from analyzing mixtures of viruses from sewage but would not be able to determine whether or not individual virus isolates were excreted by humans. Bar coding of samples would allow for simultaneous analysis of viruses from different samples, but at the cost of reduced depth of sequencing J Bioterr Biodef 30 A Rotavirus Hospitalizations B Norovirus Outbreaks 20 10 0 10 5 0 30 Rate of Visits (visits/10,000) The viral etiology of acute gastroenteritis outbreaks between 2005 and 2011 has been systematically investigated, as has the etiology of all admissions between 2007 and 2011 of children less than five years of age for acute gastroenteritis at three sentinel hospitals in the northern Israel. These studies have provided information on the annual and seasonal pattern of severe rotavirus and norovirus infections in Israel [6,7]. Laboratory Confirmed AGE (Number) Page 7 of 5 C Gastroenteritis (weekly) D Gastroenteritis (monthly) E Nausea/Vomiting 20 10 100 80 60 12 (weekly) 8 4 2004 2005 2006 Year 2007 2008 Figure 4: Preliminary comparison of syndrome surveillance for gastroenteritis and clinical diagnosis for rotavirus and norovirus infections in Israel Community physician visits for diarrheal gastroenteritis and for vomiting were compared with laboratory confirmed severe acute rotaviral gastroenteritis in children < 5 yrs requiring hospitalization and norovirus outbreaks among adults in Israel between January 2004 and June 2008. A. Bi-weekly number of laboratory confirmed, severe cases of rotavirus infections in children < 5 yrs who were admitted to a hospital in central Israel between July 2004 and June 2008 (adapted from the Annual Reports of the Central Virology Laboratory, Public Health Services, Israel Ministry of Health). B. The bi-weekly number of laboratory confirmed outbreaks of norovirus among adults in hospitals, assisted living and old age care facilities in Israel between January 2005 and June 2008 (adapted from the Annual Reports of the Central Virology Laboratory, Public Health Services, Israel Ministry of Health). The numbers of individuals infected during each out break varied from a few individuals to more than two thirds of the patients and staff at each institution. The duration of the outbreak rarely lasted more than two to three weeks. C. Weekly rate of visits in cases per 10,000 members of the Maccabi Health Care Services in Israel to physicians in community clinics of patients who presented between January 2004 and June 2008 with symptoms of gastroenteritis from any cause (based on anonymous ICD-9-based data provided by the Maccabi Health Care Services, and the Israel Center For Disease Control, Israel Ministry of Health). D. Monthly rate of visits in cases per 10,000 members of the Maccabi Health Care Services in Israel to physicians in community clinics of patients who presented between January 2004 and June 2008 with symptoms of acute diarrheal gastroenteritis from any cause (based on anonymous ICD-9-based data provided by the Maccabi Health Care Services, and the Israel Center For Disease Control, Israel Ministry of Health). E. Weekly rate of visits in cases per 10,000 members of the Maccabi Health Care Services in Israel to physicians in community clinics of patients who presented between January 2004 and June 2008 with vomiting and nausea from any cause (based on anonymous ICD-9-based data provided by the Maccabi Health Care Services, and the Israel Center For Disease Control, Israel Ministry of Health). Bioterrorism: Infectious Diseases ISSN:2157-2526 JBTBD, an open access journal Citation: Shulman LM, Manor Y, Sofer D, Mendelson E (2012) Bioterrorism and Surveillance for Infectious Diseases - Lessons from Poliovirus and Enteric Virus Surveillance. J Bioterr Biodef S4:004. doi:10.4172/2157-2526.S4-004 Page 8 of 5 (the number of times that a given sequence is sequenced). The next generation sequencing techniques will include resequencing (specific primer based amplification in a multiplex reaction that simultaneously targeting many viral amplicons) and sequence independent deep sequencing (ligating amplification specific oligonucleotide sequences to the ends of randomly amplified and/or randomly sheared nucleic acids). Finkbeiner and colleagues demonstrated the feasibility of this approach by identifying known and previously unidentified enteric viruses in human stools collected from patients with acute gastroenteritis [27]. The challenge will be to succeed in sewage where viral concentrations will be orders of magnitude lower. The screening of all admissions to the three sentinel pediatric departments of the three children’s hospitals to determine the etiology of severe acute gastroenteritis is part of an ongoing cooperative epidemiology study by the TAU-HCLV Study group (Tel Aviv University Epidemiology Department, the Hillel Yoffe, Carmel and Laniado Medical Centers, and the Central Virology Laboratory). The aim of the study was to characterize severe enteric infections in children before, during partial and after universal administration of rotavirus vaccines to newborn infants. This study has provided information on the economic burden caused by these viral agents [6] as well as preliminary information on rotavirus vaccine effectiveness [7]. It is mentioned here because the study has also provided annual molecular epidemiological surveillance data on the rotavirus and norovirus genotypes causing severe acute gastroenteritis in children and the prevalence and incidence of these viral infections that are of relevance for evaluating syndrome surveillance. Syndrome surveillance BT surveillance systems are usually based on analyzing changing patterns of symptoms and/or on programs based on the identification of specific pathogens [28]. Some examples of the latter have been described above. Their disadvantage is that they are limited to specific pathogens and would miss some bioterror or Mother Nature driven events. Syndrome surveillance has been studied as a means of identifying unusual or unexpected changes in rates of illness that may indicate the start of a bio-error, bio-terror or Mother Nature triggered event. Syndromic surveillance is predicated on (1) the observation that during these epidemiological events, people develop symptoms that lead to changes in behavior patterns (for example absence from work or school, increased purchases of over-the-counter palliative medicines), followed by visits to physicians where they present at first with general symptoms and later in the event with more specific symptoms, before the event is recognized and diagnosed [29] (2) the belief that it would be possible to develop effective methods to measure these changes in the pattern of symptoms as a means for early identification of the initiation of such an event and (3) that most pathogens that trigger bioerror, bio-terror or Mother Nature related events share symptoms with events caused by endemic or “routine” pathogens, particularly at early stages of their activity. Two requirements for effective syndrome based surveillance are (1) timeliness of data acquisition, analysis, and reporting and (2) high sensitivity and specificity [28]. The potentially faster identification of unusual events through computer assisted syndromic surveillance compared with the labor intensive and time consuming surveillance for specific antigens described in the sections above and its ability to recognize unusual events because of symptom overlap with expected events are arguments in favor of its use or addition to existing surveillance programs. The number of people who will be infected and the difficulty in succeeding with intervention increase in relation to the J Bioterr Biodef time that elapses between initiation of the BT event and the notification that such an event is taking place [28]. A good case definition is needed to increase the signal to noise ratio [30]. However, too broad a definition will result in frequent false positive signals wasting limited resources and manpower in investigation. Conversely, too narrow a definition may exclude actual events. Integration of multiple data sources can significantly improve detection accuracy of syndrome-based surveillance systems [31]. Accuracy can be gauged and improved when syndromic surveillance programs are run in parallel with infectious agent surveillance. The use of laboratory confirmed influenza, especially pandemic influenza, to evaluate respiratory syndrome surveillance is one such example (see [28,3234]). Some of these models have proven more successful at predicting Mother Nature triggered events than others. Similar evaluations can be conducted for acute gastroenteritis. Known pathogen driven events, such as laboratory confirmed hospital admissions with acute rotaviral gastroenteritis and norovirus outbreaks in adults, can be compared with community visits to physicians by patients presenting with acute diarrheal gastroenteritis or nausea or vomiting as shown for Israel (Figure 4). The most common cause for severe acute gastroenteritis in Israeli children under 5 years is rotavirus [6] followed by norovirus. The major symptom associated with rotavirus is diarrhea, while vomiting and nausea is more common for norovirus. There was a clear annual correlation between seasonality of severe rotaviral gastroenteritis requiring hospitalization in Israel (Figure 4a) and the second seasonal peak of physician visits (Figure 4C and D), In contrast there was none with the rate of visits for non-diarrheal vomiting and nausea. The causative agent of the first of the two annual diarrheal-triggered visits has not yet been identified. It is difficult to correlate norovirus outbreaks (Figure 4B) in adults with unusual activities of either diarrheal (Figure 4C and D) or non-diarrheal-triggered visits (Figure 4E) because of the low numbers of reported outbreaks. However, the small rise in visits at the end of the second peak of physician visits during the 2006-2007 winter season may reflect possible circulation of norovirus in the communities prior to the peak in a nationwide spike of norovirus outbreaks that occurred in hospitals and old age facilities between November 2006 and February 2007. These preliminary comparisons for acute gastroenteritis in Israel illustrate some of the difficulties in val...
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