Integrated Disease Investigations and Surveillance planning: a systems approach to strengthening national surveillance and detection of events of public health importance in support of the International Health Regulations

The international community continues to define common strategic themes of actions to improve global partnership and international collaborations in order to protect our populations. The International Health Regulations (IHR[2005]) offer one of these strategic themes whereby World Health Organization (WHO) Member States and global partners engaged in biosecurity, biosurveillance and public health can define commonalities and leverage their respective missions and resources to optimize interventions. The U.S. Defense Threat Reduction Agency’s Cooperative Biologica Engagement Program (CBEP) works with partner countries across clinical, veterinary, epidemiological, and laboratory communities to enhance national disease surveillance, detection, diagnostic, and reporting capabilities. CBEP, like many other capacity building programs, has wrestled with ways to improve partner country buy-in and ownership and to develop sustainable solutions that impact integrated disease surveillance outcomes. Designing successful implementation strategies represents a complex and challenging exercise and requires robust and transparent collaboration at the country level. To address this challenge, the Laboratory Systems Development Branch of the U.S. Centers for Disease Control and Prevention (CDC) and CBEP have partnered to create a set of tools that brings together key leadership of the surveillance system into a deliberate system design process. This process takes into account strengths and limitations of the existing system, how the components inter-connect and relate to one another, and how they can be systematically refined within the local context. The planning tools encourage cross-disciplinary thinking, critical evaluation and analysis of existing capabilities, and discussions across organizational and departmental lines toward a shared course of action and purpose. The underlying concepts and methodology of these tools are presented here.

Enhancing disease surveillance systems requires the integration of multiple technical disciplines and stakeholders in a structured and informed design process. Th e fi nal design and set of interventions ought to diff er based on the context and challenges existing locally, therefore requiring customizable and adaptable implementation strategies to ensure the feasibility and eff ectiveness of the interventions. Because surveillance and preparedness require coordination and collaboration among various programs, fi rst line providers (veterinarians or clinicians), epidemiologists, information system specialists and laboratory personnel, design eff orts must consider each of these groups' needs, capabilities, limitations, logistical assets, budgetary realities and legal requirements. Th e Integrated Disease Investigations and Surveillance (IDIS) tools enable planning eff orts for a robust and functional capability backbone on which specialized tactical net works aimed at preparedness and rapid response can be built. Th e success of this approach lies in execution of a systemwide design process that fosters communication and collaboration amongst the multiple stakeholders operating within a surveillance system, two elements that are pivotal for building eff ective and agile coordinated national response to local and international public health emergencies.

Methodology
As mentioned, the IDIS tools are set up to guide a design eff ort aimed at developing a comprehensive and sustainable local solution for improved disease detection and surveillance. Th e format compels informed discussions across human and animal networks, bridging together the clinical and veterinary worlds with epidemiological, laboratory and program elements. Th e plans provide a framework and tools for multidisciplinary teams of experts to apply a broader "system thinking" approach [4,5] when working to improve existing biosurveillance systems. Th eir primary purpose is to provide a deliberate planning process that will capture system-wide critical information that can be later used for immediate and long-terms goals development (e.g. modifi cations of testing strategy and reporting, training, strategic planning, operational research, procurement/infrastructure and regulatory framework, and targeted interventions).
Th e tool contains two parts: (1) a template and guidance for the system-wide review of the existing biosurveillance environment and (2) a series of pathogenspecifi c plans, organized in syndrome clusters to refl ect the importance of having diff erential diagnostic capabilities in order to rule-in or rule-out specifi c diseases. Th e rule-in or rule-out testing strategies will be dependent on the country's existing capability, endemicity of the pathogen, infrastructure requirements, biosafety regulations and the benefi t to risk ratio of adding capacity at various tiers of the disease surveillance networks.
Emphasis is placed on determining cross-cutting weaknesses or obstacles such as overall stewardship and manage ment issues, lack of established standards of operations, or critical resources issues (human or material), as these tend to often be underestimated and can lead otherwise well-planned interventions to failure [6]. In addition, it is clear that even the simplest change within the system may have a butterfl y eff ect as health systems are dynamic, complex, and interrelated systems with the capacity to amplify small changes. Improved mechanisms for communication, enhanced understanding of the system interfaces and processes, and ultimately a system that can eff ectively go through iterative processes and organizational improvements are the true measures of success.

System assessment
Because surveillance and biosecurity covers a wide range of technical disciplines, a diverse group of qualifi ed international experts working with the program implementers may be called upon to support discussions during the early phase of engagement. Th e resulting operational assessments provide the baseline on which to delineate the system design. Gathering information related to the regulatory framework (i.e., the current standards, statues, and regulations that control the surveil lance system); the organizational components of the health system; the surveillance and epidemiology capacity and the framework for outbreak and emergency preparedness; workforce competency and human resources capacity at each tier of the health system; key research activities and global partnership engagement in the country or region prior to the planning process is essential.
CBEP and CDC use a collection of tools to evaluate and gather the information on existing capabilities, namely modifi ed versions of the "National Inventory of Core Capabilities for Pandemic Infl uenza Preparedness and Response" [7], the "OIE tool for the Evaluation of Performance of Veterinary Services" [8] and the IHR Monitoring Framework [9] as they provide monitoring and evaluation frameworks to assess improvements of the core capacities over time.
Th e information gathered should reach a level of granularity that is consistent with one's ability to make informed recommendations during the design process. It should capture existing strategies or initiatives being implemented in country by the diverse health sectors, and outline potential confl icts that could arise from the implementation of system-wide modifi cations.
Early information-gathering visits are critical and may be done in parallel with workshops focused on bringing managers responsible for the various sectors of the health system together to discuss existing connectivity and systems approach to improving biosurveillance and health outcomes. Forums should be established that bring together various stakeholders to work toward a comprehensive understanding of the existing landscape and refl ect on where the system could and should be improved, and how to best coordinate and leverage partner ship in country. Recognized outside experts from these various disciplines may act as moderators of these discussions to shape the dialogue.

Mapping of existing detection and surveillance systems
At the national level, surveillance and detection systems for human and animal infectious diseases are typically under the responsibility of diff erent departments and ministries. Understanding the inter-relationship between existing networks of these ministries and their interaction with the private sector is critical to mapping multisectorial linkages and coordination. Th ese fi ndings will inform the needs for broader involvement in discussions about system strengthening and sentinel detection, reinforcing the importance of linking syndromic recognition, case defi nitions, laboratory capacity, testing algorithms, and reporting mechanisms. Th is knowledge should be an early product of system evaluation activities.
Mapping of the system linkages can be done in writing or using fl ow diagrams. Th e key is to capture enough details to make the information relevant and usable during the planning process. Examples are provided within the tools to guide this activity.

System recommendations and design
Focused discussions with senior leadership need to outline the pros and cons of making changes to the existing system, address fi nancing and governance implications, and identify sustainability strategies. Th ese discussions may require performing additional fact fi nding and may be facilitated by the use of case scenarios of routine infectious disease reporting and testing, and of a rapid response to a suspected case or cluster of cases. A high level of detail is required at this stage to avoid creating parallel systems, unfeasible or impractical requirements, or unrealistic expectations. Th e outcome of this phase should be an agreed upon architecture of inter-connected networks capable of monitoring, detecting, assessing, and reporting events, while being sustained within the constraints defi ned during the evaluation process.
Th e recommendations should go beyond detection capability, and require addressing the impact and value added of implementing changes. Larger system-wide issues should be addressed early on in order to improve the overall eff ectiveness of focused interventions. Strength ening management, use of recognized standards and best practices that will guide the entire network, as well as focus on workforce development and strategic workforce planning are critical elements of the establishment of sustainable systems. While planning for the design of a sustainable inter-related detection system, it is important to consider the high costs of responding to false alarms, while balancing the risks of delaying a case investigation. Finding a balance between faster, often less-sensitive but aff ordable diagnostic tools, and more specifi c and more complex methods is critical, as these decisions have a tremendous impact on the eff ectiveness of the system.
Th e IDIS planning tools provide design guides to lead the team(s) through an iterative evaluation and decision making process. Each iteration of the process will address a lower level of detail within the design until the capacity building objectives and implementation strategies are clearly defi ned for their program. In the early stages of the process, high level relationships between ministries and major facilities involved in the detection and reporting process are articulated. During follow-up iterations, the operations and standards that govern the system may be addressed, until facility level operational plans and standard operating procedures and policies are developed.
Th e pathogen-specifi c templates in IDIS provide a framework to move from one element to the next to point out the inter-relationship between disciplines and support a consensus building environment where clinical or veterinary program, epidemiology and laboratory leader ship can understand the importance of the continuum of activities to improve surveillance outcomes. Templates have been developed for a number of pathogens of interest to the biosecurity community, and are organized to summarize the existing and desired capacities as follows: 1) the existing capability section contains the agent summary, country-adapted case defi ni tion, local epidemiological landscape, current system mapping and testing strategies, standard operating procedures (SOPs), and reporting structures; 2) the desired capability section provides background information on tests available for the detection of the pathogen, and a section that summarizes the recom mended changes discussed during the planning process. Th ese pathogen-specifi c templates are designed to prompt the user to develop and link a complete set of activities and documents that are customized to the specifi c local requirements.
Th e laboratory plays a critical role in ruling in or out the etiological cause of an event. Even though there are more and more rapid fi eld tests available, their use remains limited to selected groups of infectious agents. Determining the need for referral of samples and the role and responsibility of the country's laboratory network will vary from setting to setting and from pathogen to pathogen. Th e ability of the local system to absorb and maintain a specifi c technology or laboratory diagnostic test is governed by such critical variables as cost, logistics, human resources, and clinical/veterinary outcomes. Laboratory capability remains essential for confi rmation, characterization and further preventive actions, but may not need to be available in country [10]. Linkages to existing reference centers may be a better alternative in some settings and should not be ignored, nor should political and regional sensitivities. Th e continuing issues associated with the reporting of a false positive result may be a motivation for laboratory confi rmation capability to be established in a country, but care needs to be given to the ability of the local system to produce reliable and timely data so that alerts can be trusted and acted upon eff ectively.

Products and outcomes of IDIS planning
Th e key products and outputs from these interactions and the planning process include agreements on: • Syndromic clusters for early assessment of events: Starting with syndromic characteristics is helpful as it allows categorizing diseases by clusters, reinforces the notion that diff erential diagnosis needs to be in place in order to recognize an event in a timely fashion, and reinforces the need for continuous clinical, veterinary and basic laboratory competencies of the fi rst line providers. • Case Defi nitions: Th e use of standard case defi nitions increases the specifi city of reporting and improves the comparability of events reported from diff erent geographical areas. [11] Establishment of case defi nitions is therefore critical to the surveillance and detection systems, more so in the case of events of global importance. Th e case defi nitions represent a body of work in itself, and if not already existing, will require the attention of subject matter experts working with country leadership to develop locally-adapted case defi nitions on which the system can be built. Th e presence of laboratory and program leaders during the development of the case defi nition is often helpful as it engages each group to better understand their role and responsibilities as well as provide critical information to guide the recommendations. • Testing strategy: Th e testing strategy is the summary of the sequence of tests to be conducted at each tiered level of laboratory (local, regional, national) based on existing and anticipated capabilities. It represents the rule-in and rule-out laboratory strategies that are decided upon in order to confi rm a case. For this reason, the capacities and competencies for each service level should be defi ned in advance of the implementation of the surveillance network. Facilitating discussion of the limitations of each of the testing options by epidemiologists and laboratory managers as a team is critical. Th e intrinsic properties of a diag nostic test or a technology will infl uence the usefulness of the data, and are often neglected topics of discussions that epidemiology and laboratory communities need to concertedly address in advance. • Testing algorithms: Th e algorithms implemented are derived from testing strategies based on the procurement system and availability of resources. A testing strategy may lead to multiple testing algorithms depending on locally available test kits and reagents, and available resources. • Standard Operating Procedures (SOPs): Decisions regarding testing algorithms are directly linked to procurement needs and standard operating procedures. SOP templates have been developed for a majority of the techniques used in the detection of especially dangerous pathogens of interests to CBEP. Although the development of locally-owned and adapted SOPs represent the lowest level of detail in the design process, institutionally-based review and adaptation processes for the establishment of these core documents are critical to standardize procedures within an institution or network. Th ese documents provide facility specifi c guidance in the execution of specifi c tests and procedures, but retain critical processes that allow for comparability of the data for appropriate decision making. Th ey are key elements in the establishment of a quality management system aimed at increasing reliability and accuracy of the data generated by the network. Th ese agreed-upon elements provide the building blocks for the integrated implementation of a quality management system reaching passed the institution-level to the surveillance system as a whole. Monitoring and evaluation strategies and metrics have been developed by the program to assess improvement of the performance and outcomes of the system as a whole, and are based on internationally recognized tools [7,8,9].

Indirect outcomes
In addition to the tangible design outputs, the overall planning process will inform the need for modifi cations to the foundation of the system and build within the partner country new mechanisms to facilitate continuous improvement. Th ese outcomes typically fall under one of the following three categories: • Workforce capacity and competency: Personnel with skills and ability to recognize unusual disease patterns and surveillance systems linkages among fi rst line providers, epidemiologists and laboratory experts. • Organizational and systems capacity: Essential infrastructure, resources, and strategic planning, as well as inter-relationships, management, organizational structure, laws, policies, rules and regulations that govern the system.
• Information and data system: Organized reporting and fl ow of information. Th ese indirect outcomes and processes can be leveraged by the partner to address other disease detection pro grams needs due to their cross-cutting nature. Mecha nisms and pathways for broader reforms can be under taken. Communication strategies can focus on improving vertical and horizontal linkages throughout the system, with the impacts of change in one sector being under stood and accounted for by the supporting sectors. A strategic framework for the country can then be developed around which international technical assis tance can be harmonized.

Conclusion
CBEP and CDC have partnered to develop methodologies and tools to guide the design and execution of locallyowned capacity building activities to improve disease surveillance systems. Th ese tools focus on a systems approach to integrated disease investigations and surveillance planning. Th e complexity of multiple networks and vertical programs within a country requires a holistic approach to ensuring reliability and timeliness across the entire health system. Often, linkages between each level of the health system and the processes that should ensure recognition and communication of a suspicious event are non-functioning or fall within a vertical network unable to react or appreciate the importance of an event.
Th e international community has long bemoaned the diffi culties of the vertical approaches on which they often rely. Th e IHR (2005) [1] and the FAO-OIE-WHO collabora tion [2] are refreshing strategic directions that create a paradigm shift and demand a holistic commitment to health strengthening by the global community. By emphasizing sound governance and leadership, quality systems, management competencies targeted at comprehensive and complex networks, workforce development and retention and adoption of internationally-recognized standards, the international community supports countries in developing a more robust and adaptable backbone on which specialized programs and disease specifi c networks can be successfully established.
Th e lack of adequate mechanisms for linking programs and leveraging shared interests has often resulted in CBEP and CDC working at cross purposes in the past, competing for the attention and talents of the same individuals in partner country, while providing uncoordinated directives. Such narrowly focused eff orts may also have failed to appreciate potential ripple eff ects they have created across the larger system of networks, or recognize the limitations of larger networks to absorb the changes being implemented. Th is resulted in a waste of time and eff orts, the inability of countries to leverage or sustain the improvements, and/or missed opportunities to positively aff ect health outcomes.
By investing up front in thoughtful holistic design eff orts that bring a broader stakeholder community to the table, the system becomes more aware of its own multifaceted nature and complexity, and those who strive to assist partner countries in continuously improving the outcomes of the surveillance activities can do so synergistically. Th e systems approach presented here, if done correctly, will strengthen the interfaces within and between networks, building core competencies and capabilities within the system, and focus on the fundamental cross-cutting elements governing the networks. Focusing technical assistance on supporting the development of comprehensive, nationwide, systematic and robust core elements and processes can ensure specifi c disease detection challenges are addressed more eff ectively and can rely on a well-articulated and function ing architecture; an architecture that can learn and grow to respond adaptively to a dynamic environment in which new and unanticipated events can be detected and assessed-a capability at the heart of the IHR.