key: cord-0040670-1thivk4h
authors: ARTHUR, RAY R.; LEDUC, JAMES W.; HUGHES, JAMES M.
title: Surveillance for Emerging Infectious Diseases and Bioterrorism Threats
date: 2009-05-15
journal: Tropical Infectious Diseases
DOI: 10.1016/b978-0-443-06668-9.50020-x
sha: ea187eeb54000c7b341ec7a7acfe492e684f64b8
doc_id: 40670
cord_uid: 1thivk4h

nan

Despite advances in science, technology, and medicine that have improved disease prevention and management, endemic and emerging infectious diseases continue to pose threats to domestic and global health. Established diseases such as malaria, tuberculosis (TB), and human immunodeficiency virus (HIV) infection still proliferate, fueled in part by antimicrobial resistance. 1, 2 The increasing speed and volume of international travel, migration, and trade create new opportunities for microbial spread, and the prospect of a deliberate release of pathogenic microbes underscores the importance of preparedness to address the unexpected. 3 The example of severe acute respiratory syndrome (SARS), a previously unknown disease that spread rapidly across countries and continents in 2003, illustrates the vulnerability of the global community to new microbial threats and highlights the need for increased vigilance and strengthened response capacity. 4, 5 The current state of readiness to address new disease agents is outlined in the 2003 Institute of Medicine report, Microbial Threats to Health: Emergence, Detection, and Response. 6 Building on the Institute' s 1992 report, 7 which sought to dispel complacency about the risk of infectious diseases, the new report calls for raised awareness and aggressive global action to address the developments of the intervening decade. These developments include the continued evolution of antimicrobial resistance, the ongoing threat of an influenza pandemic, the increased transborder spread of contagious diseases, the upsurge in infections arising from animal reservoirs, and the threat of intentional biological attacks, as well as the availability of new technologies for diagnosing and preventing disease and for linking public health practitioners around the world.

Recent domestic challenges have included the introduction of West Nile encephalitis 8, 9 and monkeypox 10 into the United States, the anthrax episodes of fall 2001, 11 and multistate outbreaks involving contaminated food products. [12] [13] [14] Internationally, public health officials have faced the emergence of Nipah virus 15 and SARS, 4 the intensified global spread of dengue, 16, 17 Ebola outbreaks of unprecedented magnitude, 18 and the direct avian-to-human transmission of influenza. 19, 20 Each of these examples illustrates the global implications of local problems, the role of strong health intelligence networks in addressing emerging infections, and the importance of data on the incidence of natural background diseases in recognizing unusual disease events. 21

Public health surveillance is the continuous and systemic collection, analysis, interpretation, and feedback of systematically collected information used to inform public health decision making. 22 Timely community health information in the hands of trained experts is the foundation for recognition of threats to health. To intervene successfully to treat existing infections and prevent the onset of new ones, disease surveillance systems need to provide a continuous, accurate, and near real-time overview of a population' s health. Surveillance systems must be sensitive in terms of their ability to detect outbreaks and other significant changes in community health status over time, and they must be flexible in adapting to changing health intelligence needs. Given the increasing pace of international travel and globalization and the threat of intentional outbreaks, surveillance activities need to extend beyond the monitoring of disease burden to include the capacity to quickly recognize unusual, unexpected, or unexplained disease patterns. Because many emerging infectious agents are zoonotic, it is also important to integrate veterinary disease reporting networks into systems that monitor diseases of humans.

Astute clinicians and microbiologists are essential for early detection of threats at the clinical front lines. In the United States, surveillance for notifiable diseases is conducted by state and local health departments, which receive reports from physicians, nurses, and laboratorians who are often the first to observe and report unusual illnesses or syndromes. States voluntarily report nationally notifiable diseases to the Centers for Disease Control and Prevention (CDC) through the National Electronic Telecommunications System for Surveillance (NETSS). To expedite national disease reporting, CDC, in collaboration with the Council of State and Territorial Epidemiologists (CSTE), has developed a standards-based system for collecting and distributing electronic disease reports from local health departments to state and federal public health authorities. The infectious disease surveillance component of this developing Public Health Information Network (PHIN) is the National Electronic Disease Surveillance System (NEDSS). NEDSS is designed to standardize and facilitate the collection of electronic disease information on nationally notifiable diseases within local health jurisdictions directly from healthcare providers to local health authorities. 23 Limited resources have, however, precluded the establishment of a fully integrated health surveillance system that connects health departments and care providers.

Starting in 1994, CDC launched a two-phase initiative to strengthen domestic capacity to respond to the dual threats of endemic and emerging infections. The publication of two strategy documents 24,25 led to the launching of new surveillance initiatives, including the Emerging Infections Program (EIP), a national network for population-based surveillance and research 26 (Fig. 15-1) . Several provider-based sentinel surveillance networks were established in collaboration with emergency room physicians, infectious disease specialists, and travel medicine specialists to provide early warning of events that might be missed by public health surveillance. Additional enhancements to the surveillance effort include development of the National Molecular Subtyping Network for Foodborne Disease Surveillance (PulseNet) as an early warning system for foodborne diseases, support for the Gonococcal Isolate Surveillance Project (GISP) to monitor antimicrobial resistance in Neisseria gonorrhoeae, strengthened surveillance for diseases of current concern (e.g., West Nile encephalitis), and surveillance for outbreaks that might be due to acts of bioterrorism.

The CDC also works in partnership with the World Health Organization (WHO), ministries of health, foundations, development agencies, and other federal agencies to promote national, regional, and international disease surveillance. Recognition of the global nature of the emergence and spread of infectious diseases stimulated the development of a third strategy document focused on CDC' s efforts to enhance global capacity for disease surveillance and outbreak response. 27 The document presents six priority areas for protecting domestic and global health, among which are global initiatives for disease control, international outbreak assistance, and a global approach to disease surveillance. CDC' s international activities include creation of the United States-Mexico Border Infectious Disease Surveillance (BIDS) system, development of the Global Emerging Infections Sentinel Network (GeoSentinel), and provision of technical assistance to regional disease surveillance networks in Africa, Asia, Latin America, and the circumpolar regions of Canada and Europe, as well as to WHO' s disease-specific global networks.

WHO manages global disease surveillance and response through a composite of partnerships and networks for gathering, verifying, and analyzing international disease intelligence, mainly to support global and regional efforts to eradicate certain diseases, such as polio, and to protect the global community against diseases with pandemic potential. The oldest of these networks is the global influenza surveillance network, which was established more than 50 years ago and has served as the prototype for the design and implementation of subsequent systems (see later discussion). 28 A recent addition to the disease-specific surveillance approach is DengueNet, a webbased network for gathering and sharing information on dengue and dengue hemorrhagic fever.

To respond to the increasing number of emerging and rapidly spreading infectious diseases, WHO has developed a global "network of networks" that links local, regional, national, and international networks of laboratories and medical centers into a mega-surveillance network for early warning and response. 29 Formal partners include ministries of health, WHO Collaborating Centers, WHO country and regional offices, and international military groups such as the Global Emerging Infections System of the U.S. Department of Defense (DoD-GEIS). Outbreak reports are also received from nongovernmental organizations, relief workers, private clinics, individual scientists, and public health practitioners. Additional information is provided by Health Canada' s Global Public Health Intelligence Network (GPHIN), an electronic tool used by WHO since 1997, which scans Internet news sites for reports of outbreaks and unusual disease events. Global surveillance networks all operate within the framework of the International Health Regulations, which outline WHO' s authority and member states' obligations in reporting and preventing the spread of infectious disease. The International Health Regulations require official reporting of only three diseases: plague, cholera, and yellow fever. 30 Outbreaks of these diseases are reported in WHO' s Weekly Epidemiological Record and electronically through postings on the Internet. Recognizing the limitations of the regulations in the era of emerging and reemerging diseases and spurred by the SARS experiences of 2003, WHO and its member states have undertaken a revision of the document. During the 56th World Health Assembly (WHA), two resolutions were passed, one specific to SARS (WHA56.29) and the other adding impetus to the revision efforts (WHA56.28). The resolutions seek to secure enhanced collaboration with WHO in responding to infectious disease outbreaks. In recognition of the role of animals in the spread of human disease and the potential for infectious disease dissemination due to international travel and trade, the resolution prompted by the SARS experience also urges member states to "ensure collaboration, when appropriate, with veterinary, agricultural and other relevant agencies involved in animal care and research on, and planning and implementation of, preventive and control measures." 31 Whereas the International Health Regulations provide the legal framework for global control of infectious diseases, WHO' s Global Outbreak Alert and Response Network (GOARN) is the operational arm, that is, the mechanism by which WHO' s partners respond to outbreaks of international importance. 29 GOARN activities are described in the following section.

Established in 1952, this global network of more than 100 virus laboratories in 83 countries monitors influenza activity and collects the viral isolates that determine the composition of the following year' s influenza vaccines 32 (Fig. 15-2) . The isolates are characterized by WHO Collaborating Centers in the United Kingdom, Japan, Australia, and the United States. In addition to guiding the annual composition of recommended vaccines, the network operates as an early warning system for the appearance of influenza variants and novel strains that could signal the emergence of an influenza pandemic.

International disease eradication strategies include a strong surveillance component. To support the Global Polio Eradication Initiative, WHO established the Global Laboratory Network for Poliomyelitis Eradication, 33 which uses molecular techniques to determine whether wild-type polio is circulating in areas undergoing eradication efforts. Genomic sequencing capabilities and collaboration among network laboratories have allowed the tracking of virus Surveillance for Emerging Infectious Diseases and Bioterrorism Threats ■ 197 strains within and among countries and the identification of the origin of viruses imported into polio-free countries. 34

Started in 2000, WHO' s Global Salm-Surv is a global network of laboratories and individuals involved in isolation, identification, and antimicrobial resistance testing of Salmonella and surveillance of salmonellosis. The goal is to enhance the capacity and quality of Salmonella surveillance, serotyping, and antimicrobial resistance testing throughout the world. Global Salm-Surv conducts an electronic discussion group, international training courses for microbiologists and epidemiologists, external quality assurance testing, and focused research projects on topics such as surveillance enhancement and burden of illness. Member institutions enter their top 15 Salmonella serotypes yearly in a web-based country databank that can be searched for serotype frequency nationally, regionally, or globally.

Surveillance of antimicrobial resistance is fundamental for understanding trends, developing treatment guidelines, and assessing the effectiveness of interventions. In 1994, WHO, the International Union against Tuberculosis and Lung Disease (IUATLD), and other partners launched the Global Project on Antituberculosis Drug Resistance Surveillance in response to growing concern about drug resistance and its impact on TB control. The purpose of this network of reference laboratories is to measure the prevalence of anti-TB drug resistance in several countries using standard methods and to study the correlation between the level of drug resistance and treatment policies in those countries.

GOARN was launched in 2000 as a mechanism for combating international disease outbreaks, ensuring the rapid deployment of appropriate technical assistance to affected areas, and contributing to long-term epidemic preparedness and capacity building. GOARN electronically links more than 120 partner institutions and surveillance networks, which together possess the expertise, skills, and resources for rapid outbreak detection, verification, and response. 29 The coordinated response to the large Ebola hemorrhagic fever outbreak in Uganda in 2000 demonstrated the merit of the principles on which the network is based and functions. 18, 35 The importance of GOARN was also evident in 2003, when WHO coordinated the unprecedented global response to SARS. Through GOARN, WHO mobilized the international public health, clinical, and research communities to rapidly identify and characterize the causative agent and to contain the spread of this new infectious agent, providing a new standard for future responses to global microbial threats. 36

The Laboratory Response Network (LRN) was established by CDC in 1999 to respond quickly to acts of chemical and biological terrorism, emerging infectious diseases, and other public health threats and emergencies. The more than 120 federal, state, and local public health, veterinary, military, environmental, and international laboratories in the network have progressively stringent levels of safety, containment, and technical proficiency that enable them to recognize, rule out, confirm, or definitively characterize highly infectious agents using standardized protocols and reagents and to maintain communication through a secure web site.

The value of the LRN was demonstrated during the SARS epidemic, when validated reagents and protocols were rapidly distributed within weeks of the discovery of the etiologic agent (SARS-associated coronavirus [SARS-CoV7]) thereby providing diagnostic testing capability to each state.

Microbiology laboratories play a critical role in surveillance for emerging infectious diseases and bioterrorism threats by identifying the microbial cause of syndromes, detecting and reporting new or unusual pathogens, and assessing antimicrobial resistance. 6, 37 To carry out this role, laboratories require well-equipped and safe facilities, adequate human and financial resources, access to needed reagents, and robust quality control.

Accurate etiologic diagnosis is dependent on standardization of and scrupulous attention to a series of essential procedures. These include the collection of appropriate clinical specimens, careful handling of specimens, accurate and complete labeling, and access to relevant clinical information to guide the testing process. Laboratorians also benefit from knowledge of the local epidemiologic situation. The chain of events is completed when the laboratory provides results to the attending medical staff to guide clinical management of the patient and to the epidemiologist for trend analysis, monitoring, and response. Specimen collection requires an understanding of the samples needed (e.g., whole blood, serum, cerebrospinal fluid); proper containers for safe transport outside the clinical facility; complete labeling with information on the source and the time of collection relative to clinical status; proper packaging for shipping; and compliance with regulations for transport. The laboratory to which the specimens are being sent should be notified in advance about the shipment to facilitate assistance with customs clearance and transport.

The critical needs of the laboratory center around three basic resources: equipment and supplies to conduct the required tests, reagents to test for the pathogens of interest, and trained staff to perform the testing. Although each of these requirements may be a limiting factor in the recognition of emerging infections, the availability of high-quality diagnostic reagents may be the most critical, especially for viral diseases. Laboratories often have adequate reagents for diseases known to occur locally but not for viral illnesses that occur in other parts of the world. Ensuring the quality of serologic tests also requires inclusion of positive and negative control sera that might be difficult to obtain, especially for diseases of low incidence. If reagents are not commercially available, the laboratory must rely on its own locally produced reagents or on reagents supplied by others that may not have benefited from appropriate quality control during production.

For some agents, such as influenza, dengue, and hantaviruses, commercially available diagnostic kits that can be used in settings with minimal laboratory facilities have overcome this obstacle. Nonetheless, the user, who may not be a trained laboratorian, still needs to collect the specimen appropriately and interpret the results correctly.

One of the most important aspects of a global strategy for monitoring of emerging diseases, especially those caused by viruses, is ensuring the proper level of biosafety containment and strict adherence to biosafety procedures to allow safe handling of pathogenic organisms. The importance of biosafety precautions was demonstrated by the recurrence of SARS-CoV in Singapore, Taiwan, and China in late 2003 to early 2004 due to laboratory acquired infections. [38] [39] [40] Most organisms are classified in one of four distinct biosafety levels, depending on the seriousness of the disease they produce, their transmissibility, and the availability of effective treatment or vaccines. 41 Biosafety levels 3 and 4 are required for handling the most dangerous pathogens and require highly specialized facilities. The physical plant required to support a biosafety level 4 laboratory is considerable, and maintenance expenses are high. Consequently, only a few exist in the world, and all serve as major referral laboratories.

Laboratory diagnosis is not confined, however, to stateof-the-art facilities. The use of field laboratories can be a factor in the rapid containment of outbreaks of emerging infectious diseases. During the 2000-2001 outbreak of Ebola hemorrhagic fever in Uganda, laboratory testing was performed at a field laboratory established by CDC and supplemented by additional testing at CDC and other reference centers. 18 The availability of the field lab was determined to be a key logistic element in containing the outbreak rapidly. 42 Pathology laboratories also make critical contributions to the identification of new and emerging infectious diseases. 43 Pathologists have had a frontline role in identifying the causal agents, describing the pathogenetic processes, and guiding the early phases of the epidemiologic investigations of several recently described diseases, including hantavirus pulmonary syndrome, 44 new variant Creutzfeldt-Jakob disease, 45 and SARS. 46 Clinicopathologic studies have also been useful in delineating the pathogenesis of emerging infectious diseases such as West Nile virus encephalomyelitis. 47 Immunologic and molecular methods, including immunohistochemistry (IHC), in situ hybridization, and polymerase chain reaction (PCR), have revolutionized the ability of pathologists to diagnose and study infectious diseases and are likely to ensure an increasing role of pathology as an active partner in surveillance activities. 43

A final component of surveillance is the ability to rapidly and reliably exchange information on disease incidence and distribution, preferably in real time. Disease intelligence relies on formal and informal networks for dissemination and sharing of timely, accurate information on occurrences and outbreaks of infectious diseases and diffusion of prevention recommendations. One of the key lessons that emerged from the 2003 global SARS epidemic was the importance of networks of laboratory scientists, clinicians, and public health experts, aided by electronic communications, in rapidly generating the scientific basis for public health action. It was the "virtual" international network of laboratories, linked by a secure web site and daily teleconferences, that identified the causative agent and developed early diagnostic tests. The laboratory network served as a model for groups of clinical and epidemiologic experts who shared and compiled the data needed to track the outbreak and assess the effectiveness of containment measures.

In the current electronic era, countries are increasingly aware of the value of network-facilitated early warning systems, rapid information exchange, and technology transfer for the control of infectious agents. Technologies developed and enhanced over the last several years have stimulated the creation of web-based public health tools for improving national and international disease reporting and facilitating emergency communications. In the United States, CDC communicates breaking surveillance information to public health officials through two electronic networks: the Epidemic Information Exchange (Epi-X), a secure mechanism for sharing health surveillance information on outbreaks and other unusual events, and the Health Alert Network (HAN), which links local, state, and federal health agencies and provides an electronic platform for emergency alerts and long distance training. In similar fashion, the Eurosurveillance Project, funded by the European Commission, promotes the diffusion and exchange of information on communicable diseases in Europe. Globally, WHO shares information through the Outbreak Verification List distributed weekly by electronic mail, the WHO Disease Outbreak News on the WHO web site, and the Weekly Epidemiological Record. Supplementing these mechanisms are less formal networks of individuals and organizations, such as GPHIN, the web-based application that scans global electronic news media for information on health risks and the Program for Monitoring Emerging Diseases (ProMED), a webbased reporting system.

Another essential component of information exchange during infectious disease outbreaks is risk communication. Any outbreak of a novel or reemerging infectious disease is likely to be characterized by scientific uncertainties and high levels of concern that public health officials will be challenged to harness and guide. Since the 2001 anthrax attacks and the 2003 global SARS outbreaks, CDC and WHO have been actively involved in efforts to incorporate risk communication into public health practice.

Future challenges posed by infectious agents are difficult to predict but certainly include the continuing threat of an influenza pandemic, a recurrence of SARS, the emergence of other zoonotic agents that cross the species barrier to humans, the emergence of new bacterial strains that are more virulent or resistant to antibiotics, the possible deliberate release of pathogenic microbes by terrorists, and the likelihood of increased spread of dengue, cholera, West Nile virus, yellow fever, and foodborne diseases. The best defense against these mobile and resilient pathogens is timely and reliable infectious disease information obtained through global public health surveillance. 29 The international community has made important strides in developing networks for detecting and reporting infectious disease events and enhancing capacity for clinical and laboratory surveillance. Continued commitment and support are needed to optimize the use of these systems to improve the detection of unusual disease events, strengthen the ability to share disease intelligence, and inform prevention and containment efforts.

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