Global Health Security: Building Capacities for Early Event Detection,Epidemiologic Workforce,and Laboratory Response

Early Detection and Reporting

To meet the requirements of the IHR, countries must have early warning and response mechanisms that allow them to detect emerging events early and respond efficiently. ⁶ Data from 2 complementary types of surveillance, indicator-based surveillance (IBS) and event-based surveillance (EBS) inform a functional early warning and response system. ⁷

While the 2 types of surveillance are complementary, their primary objectives are somewhat different. ⁷ Indicator-based surveillance is more useful for observing general trends in disease incidence, while event-based surveillance is focused primarily on detection of outbreaks or events. The ability of indicator-based surveillance to detect outbreaks is limited by the problem of trying to distinguish true changes in transmission rates from random variability, or the level of “background noise,” in the data. In addition, there is a tendency to average out smaller events representing outbreaks in a very limited geographic area in large aggregated regional or national data sets. Indicator-based surveillance strategies may include universal disease reporting from healthcare facilities, sentinel site surveillance, and laboratory-based surveillance. Sentinel sites are limited by their limited geographic coverage, which requires that outbreaks occur in their catchment areas to be detected. For epidemics that require rapid response for effective control, detection is necessary before transmission becomes widespread or sustained. Sentinel surveillance systems, however, are the most cost-effective method to accomplish most of the primary surveillance objectives of indicator-based surveillance. A limited number of carefully selected sentinel sites can provide detailed case data and clinical specimens for pathogen characterization, represent disease transmission trends, and, if consistently applied, will provide data on relative severity from season to season. With additional work to define catchment populations, they can also be used to estimate disease burden. In small systems, they have the added advantage of allowing active monitoring for data quality. ⁸

Event-based surveillance can increase the sensitivity of a surveillance system by detecting signals before an event becomes large enough to be detected through indicator-based surveillance. ⁷ An event-based surveillance must have broad geographic coverage and a diverse source of information to be an effective national outbreak detection strategy. Information collected through event-based surveillance tends to be unstructured and less formal than data collected through indicator-based surveillance. ⁷ Historically, astute clinicians have been the primary reporters of something unusual happening in the community, such as an unusual disease presentation or change in transmission pattern, and their importance as a source for early detection of events cannot be overemphasized. Two recent examples include the newly discovered Middle Eastern respiratory syndrome coronavirus (MERS CoV), which was brought to the world's attention by an email from an Egyptian virologist working at a hospital in Jeddah in the Kingdom of Saudi Arabia (KSA), ⁹ and the first case of SARS, which came to the attention of public health authorities in 2002 following the report by a clinician of atypical pneumonia followed by a cluster of cases in a hospital in Guangdong province, China. ¹⁰

Nonprofessional community monitors have also played an important role in outbreak detection and reporting. These community monitors may be particularly valuable in areas of the world where access to health care is limited and patients affected by an outbreak present for treatment late in the course of the event. Community monitors have been used extensively for surveillance in eradication programs for smallpox, guinea worm, and polio.^11,12 A community monitor trained in detecting and reporting a wide range of signal events rather than disease-specific reporting may be more resource efficient. A pilot study assessing 2 years of implementation of community-based surveillance in 7 rural communes in Cambodia concluded that one of the benefits of trained community monitors was early detection of outbreaks. ¹³ Although not quantified, the study demonstrated that the community-based surveillance strategy consistently captured more comprehensive and representative data for major communicable diseases and detected disease outbreaks more frequently than indicator-based surveillance. The system triggered effective responses from both health staff and community monitors for both disease control and prevention and in outbreaks. Effective community surveillance programs require initial training of volunteers in the community, a mechanism for sustained refresher training, ongoing follow up and monitoring, and a sustainable mechanism for incentivizing the community monitors.

When working to raise the awareness of healthcare workers and community health monitors to the types of unusual events that should be reported, health systems should first identify the diseases of highest priority for detection in the country. Priority diseases for event-based surveillance might include those diseases that have or may have large public health impact in the country, are prone to develop outbreaks, pose a threat for importation from other countries, have previously been prevalent and may reemerge, and have been slated for eradication (eg, polio). Prioritization facilitates the defining of signal events, which are patterns of disease that should trigger immediate reporting. Signal events for event-based surveillance should focus on events or patterns that may indicate outbreak conditions, as such clusters tend to be the focus for surveillance rather than individual cases. The relationship of disease priorities to signal events is described in Table 1. Some flexibility in definition of signal events must be retained in the system to allow for reporting of unanticipated events. For example, the combination of clinical signs and symptoms including Kaposi's sarcoma and Pneumocystis jiroveci pneumonia in gay men that signaled the appearance of human immunodeficiency virus would have been impossible to predict in advance to define an alert signal. ¹⁴

Event-based surveillance may also make use of other signal sources, including news media and the internet, and direct and indirect community reporting, with each having advantages and disadvantages (Table 2). A classic example of an outbreak discovery by community reports in the United States was the discovery of Lyme disease, which was first brought to the attention of authorities by 2 concerned mothers who noticed that a large number of children in their community had been diagnosed with juvenile rheumatoid arthritis. ¹⁵ The Ebola virus disease outbreaks in West Africa were discovered by event-based methods that resulted in initial published reports of diarrheal diseases and hemorrhagic illness, ¹⁶ and the Madeira Island dengue fever outbreak was revealed by media reporting on increases in sales of mosquito repellants and dengue fever in the communities. ¹⁷ Studies from Bangladesh and India have shown that media scanning methods in surveillance are useful for early detection of outbreaks of foodborne illness, anthrax, rabies, and cholera.^18,19

Because of the wide variety of data sources, the mechanisms for event-based surveillance data collection are also varied. Information flows into the public health system through telephone hotlines, email, web-based reporting systems, text messaging, and by word of mouth. Once the signal events are reported, the epidemic intelligence process evaluates relevant information, verifies the signal, and carries out a risk assessment of the event.^20,21 Epidemic intelligence requires strong filter and validation capacities to avoid overwhelming the response system with information of varying degrees of credibility. After event verification, the event needs to be assessed for public health significance. Depending on the nature of the signal, the scope of the problem, the type(s) of disease(s) potentially involved, and the population of concern, initial assessment may require varying degrees of sophistication, from a follow-up phone call to a full-scale field response and containment. The IHR (2005) contain a decision instrument, Annex 2, to help assess whether or not an alert is of international concern. ²²

Figure 1 is a suggested example for the flow of information in an early warning system and the responsibilities of each level of reporting in a country. Signal events may be detected and reported by the different sources to the public health system, with reporting occurring at several levels of the public health system. For instance, community health workers will report to the community health units or stations, and the reports would be verified and, if further investigation is needed, reported to the district level units and above. Reports from hospitals may reach different levels of the system, depending on the system in each country. Similarly, media scanning capabilities could exist at regional levels and higher. Regardless of how the public health system is configured to receive the signals, once a signal has been detected and reported to the public health unit, reported events should be documented and responded to in a timely fashion, and response may be initiated at different levels of the public health system. The level of response will depend on the initial risk assessment, which estimates the likelihood of an event spreading or recurring and the potential public health impact it might have.

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Figure 1.

An Example of Information Flow and Role of Each Administrative Level of Public Health in Event-Based Surveillance System

Laboratory Network

Access to high-quality laboratory testing is a crucial component for response, and, depending on the country and the laboratory system capabilities, such testing can initially occur in clinical diagnostic labs and be confirmed in public health laboratories. The essential elements of a public health laboratory system that support event-based surveillance include collection of appropriate specimens, rapid transport to the testing laboratories, timely characterization of the pathogen, and quick return of results to enable appropriate response.

The type of specimens to be collected should be guided by epidemiologic data. Ideally, specially trained laboratorians are part of the outbreak investigation team to ensure proper collection, packaging, and transport of specimens. Training of laboratory personnel should include packaging and transport of dangerous goods, both domestically and internationally, compliant with International Civil Aviation Organization guidelines (often included as International Air Transport Association training). Pre-positioning of sample collection and transport kits at select sites in the laboratory network can decrease lag time in specimen collection during an event investigation. A case investigation form with unique identification number and necessary information to guide laboratory testing should accompany every specimen that is collected.

Specimen transport during event investigation can take advantage of existing transport systems for surveillance, such as the polio-measles specimen referral networks ²³ or the Hub transport systems for early HIV infant diagnosis supported by the President's Emergency Plan for AIDS Relief (PEPFAR).^24,25 During outbreak investigations, teams may choose to transport specimens directly to the diagnostic laboratory, bypassing routine shipping mechanisms, and in such cases vehicles and infrastructure should be in place to enable this ad hoc transport activity.

A directory that includes addresses of designated reference laboratories and laboratory contact information should be available to investigators. Designated reference laboratories should have the capacity to perform a wide battery of tests. Ideally, these laboratories should be accredited facilities or have a track record of participating in external quality schemes for a variety of pathogens.

Just as it does for specimen collection, epidemiologic evidence and a knowledge of differential diagnosis should guide the choice of pathogen-specific testing during outbreak investigation. Laboratory diagnostics are needed to confirm that the disease event is due to a recognized pathogen that may or may not be endemic to the region, to identify reemerging pathogens, and in rare cases to characterize novel pathogens. When the range of differential diagnoses is broad and the epidemiologic information less specific, laboratory testing is more complex and may add a time delay for results. Clusters of acute febrile illness being investigated in a community, for example, could represent dengue, malaria, leptospirosis, influenza A, Salmonella typhi, rickettsia, Japanese encephalitis, or chikungunya, depending on the region and the prevailing endemic conditions. ²⁶ In such instances, the battery of tests used may include culture-based tests for bacteria and viruses, polymerase chain reaction (PCR), and serological testing. In medium- to well-resourced countries, national public health laboratories could consider adding multiplex molecular detection methods to their repertoire of testing, as these methods may offer advantages in rapidly testing a wide range of pathogens. Recently, investigations of undiagnosed acute respiratory illness clusters in Cambodia by MassTag PCR (PCR based on mass spectrometric detection of end product), a high-throughput multiplex screening platform, revealed the emergence of enterovirus 68 in Cambodia. ²⁷ Similarly, an outbreak of respiratory disease in a nursing facility in the United States was quickly determined to be caused by human metapneumovirus by the use of multiplex molecular detection platforms after the failure of a series of single-plex pathogen-specific PCR assays to identify the cause of the outbreak. ²⁸ Several multiplex systems exist to detect a wide variety of pathogens. Selection of a system should take into consideration factors such as cost, availability of reagents, sustainability, compatibility with existing platforms, and training needs, including interpretation of data. Multiplex testing technologies could be increasingly used in resource-limited settings as such technologies become more affordable and robust.

Next-generation sequencing and metagenomics methods have substantially enhanced outbreak investigations. The previously described discovery of MERS CoV illustrates the utility of these methods. ⁹ In that case, indirect immunofluorescence assays and real-time polymerase chain reaction (RT-PCR) for widely occurring respiratory viruses failed to identify the etiologic agent. Sequencing and phylogenetic analysis at Erasmus Medical Centre in Rotterdam, The Netherlands, was used to demonstrate the presence of a novel coronavirus. As it is not feasible to have this advanced technology in low- to medium-resource countries, it is important that national public health reference laboratories are linked to an international reference laboratory. This external laboratory support will generally require preexisting agreements and established mechanisms of transport between national laboratories and global reference laboratories.

This strategy is consistent with IHR (2005) Core Capacity 8, Laboratory, requiring that laboratory services be a part of every phase of alert and response, including detection, investigation, and response, with laboratory analysis of samples performed either domestically or through collaborating reference laboratories internationally. An example of such a laboratory network is the WHO Emerging and Dangerous Pathogens Laboratory Network (EDPLN). The EDPLN is made up of global and regional EDPLN networks of high-security human and veterinary diagnostic laboratories and contributes to outbreak response and preparedness as well as rapid development of diagnostic assays for emerging and infectious pathogens globally. Recently, through EDPLN, specimens of suspect Ebola virus disease were rapidly transported to a central facility, where the pathogen was identified and sequenced and response initiated. ²⁹

Efficient communication of results to investigators is an important element of laboratory support to outbreak investigations. A laboratory information management system, quality management system, and biological threat management, including good process controls, supply chain, external quality assurance schemes, supply chain management, equipment maintenance, and trained laboratory workforce, are all important to the reliable functioning of a public health laboratory system but beyond the scope of this article and hence not discussed here. Characterization of the pathogen responsible for an outbreak will help to inform the risk assessment and target specific control measures. Periodic joint training of the laboratory and epidemiology workforce to increase understanding of the epi-lab linkages should be part of developing an early warning system.

Trained Epidemiology Workforce

The Field Epidemiology Training Program (FETP) was created in 1976, modeled after the Epidemic Intelligence Service (EIS) of the US Centers for Disease Control and Prevention, and a version of it is currently implemented in more than 70 countries around the world. The European Centers for Disease Control created a similar program in 1995 known as the European Program for Intervention Epidemiology Training. ³⁰ These programs provide a 2-year on-the-job training program for epidemiologists, and fellows often serve as frontline response personnel in responding to emerging public health events. Fellows receive hands-on training in outbreak detection and response, interpretation of epidemiologic data, and risk assessment under the auspices of the ministry of health. ³¹

These practical field training programs play a critical role in event-based surveillance and the epidemic intelligence process in 2 respects: contributing human resources to run outbreak detection systems and to respond to outbreaks, and ensuring sustainability by producing a continuous stream of trained epidemiologists to fill the ranks of the public health workforce. A skilled workforce is needed to make event-based surveillance work effectively. The trained epidemiologists are needed to define and validate signal events, evaluate reports from communities and clinicians, cross-reference reports with other data, and track events over time. Various data and information sources must be integrated and appropriate triage and quality risk assessment conducted for a timely response to be launched. Many of the needed skills are not a part of the routine education of epidemiologists in university-based programs, which tend to focus on study design and analytics. Field epidemiology training, in contrast, uses real-life events in which fellows are mentored by senior epidemiologists and provided with experience in evaluating and interpreting epidemiologic data and translating the data into public health interventions.

The GHSA has established a target of 1 trained field epidemiologist for every 200,000 population. ⁵ Achieving this goal is ambitious for many countries, and an intermediate step may include short-course training for staff of the ministry of health who can be mobilized during a response. The recent experience with Ebola in West Africa demonstrates the value of FETP fellows in an outbreak response, even during their period of training. ³² The first case of Ebola in Nigeria resulted in the deployment of 2 FETP resident advisors, 3 graduates, and 7 fellows. Ultimately, more than 100 people associated with the program participated in the response. The FETP graduates provided training in infection control, contact tracing, case investigation, development of communications materials, development of standard operating procedures, and overall coordination. These Nigerian FETP graduates identified nearly 900 people potentially infected by close contact with an Ebola patient, made 19,000 home visits to monitor for symptoms and fever, trained thousands of staff, and isolated and tested 43 people who showed symptoms. ³³ The rapid response to the outbreak, and particularly the availability of a workforce specifically trained or in training for field epidemiology, resulted in containment of Ebola in Nigeria, including in the densely populated city of Lagos, after just 19 cases. ³⁴

Challenges to Event-Based Surveillance

Many challenges exist for institutionalizing event-based surveillance in countries. There is often a lack of understanding among public health workers and political decision makers of the respective roles of indicator-based surveillance and event-based surveillance. Thus, there is often an emphasis on systems that collect and monitor routine indicator data in an attempt to detect changes in transmission patterns. In some situations, this results in an unrealistic push toward universal reporting and an attempt to “capture” all cases of an illness that occur in the community. While this is indeed a useful goal for some diseases, such as polio, rabies, or Ebola, for common syndromes such as influenza or dengue it is not only unproductive, it results in systems that are unmanageable and cannot be effectively monitored for quality, and datasets that are so large that outbreak signals become averaged out or lost in baseline “noise.”

In many situations, there is a strong economic or social disincentive for reporting, including negative impacts on trade and tourism. District health departments that are charged with providing immunization services or ensuring food and water safety may be reluctant to report outbreaks of vaccine-preventable or foodborne disease for fear that it would indicate a failure of their primary duties. Private sector corporations that experience outbreaks among employees may fear the impact that the event may have on their corporate image. Villagers may be reluctant to report poultry die-offs in their community for fear of reprisals from their neighbors after authorities come to cull their livestock, particularly when no compensation or reimbursement for lost livestock is offered. There are no simple solutions to these barriers, but effective communications and increasing awareness can help to address them.

There are system-related issues that may delay timely reporting of signal events. Poor connectivity from remote areas of a country and lack of transport are likely to be the most common. These barriers are rapidly disappearing as the world becomes increasingly connected and infrastructure improves. Emerging information system technology tools are being adapted to support the rapid transfer of public health information. A challenge will be to evaluate and strengthen information system infrastructures and resources and identify the most appropriate and sustainable technologies that can support the rapid communication of indicator-based surveillance and event-based surveillance data, the storage of field data collected as part of outbreak investigations, and the timely sharing of laboratory data to support appropriate decision making.

Rationalization of a system can help to increase cost-effectiveness. Laboratory services are often duplicated in the clinical and public health sectors. Making informed decisions regarding disease priorities, the logical testing capacities needed at each administrative level and in the clinical versus public health sectors, and creating referral networks and linkages can help to maximize efficiency of outbreak response.

As countries develop infrastructure and programs for early warning, most find it necessary to have a central location such as an emergency operations center (EOC) for monitoring, coordination, and information dissemination. EOCs need teams of trained epidemiologists to interpret data, information systems experts, logisticians, and communications officers to effectively manage information and coordinate response. Larger programs will generally find it cost-effective to establish permanent centers manned by full-time, specially trained staff. EOCs can also serve as critical information hubs to make data accessible in a timely way. As data are reported in a variety of formats, some integration platform such as a data warehouse can create a master data set accessible to all who are given access, and access can be limited as needed. Many products are available on the market including open-source products such as the District Health Information System 2 developed by the Health Information Systems Program, a global platform established, managed, and coordinated by the Department of Informatics at the University of Oslo. ²⁹ Many of these platforms also provide data display capabilities that can automate routine analyses, updating outputs as new data are added.

Conclusion

Experiences in the past decade, and most recently the Ebola outbreak of 2014-15, have demonstrated the importance of surveillance systems that would allow early recognition of signal events and a public health infrastructure that allows rapid notification and information sharing within countries and across borders. However, limited-resource countries still struggle to implement surveillance that is both timely and effective at detecting outbreaks early. In some countries, there exists a misguided belief that universal reporting of diseases from every healthcare facility is needed to provide the signals for outbreak detection. A more rational approach would be to focus initially on event-based surveillance that collects and analyzes data that are actionable, supported by a rational laboratory network and a system of sentinel sites that provide baseline data on disease incidence. To operate the system, a robust program of workforce development including field epidemiology training is needed to provide the trained personnel to interpret surveillance data and respond to events. The GHSA, with its broad scope of activity, long planning window, and multinational support, provides an opportunity to channel investments into infrastructure capacity building for surveillance, laboratory, and workforce development. These investments should improve the ability of countries to detect, prevent, and respond to outbreaks in a timely manner and to enhance overall public health preparedness, thus meeting the requirements of IHR (2005) and improving health security.