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 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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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.
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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.
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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.
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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.
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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
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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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