This category includes multiple infectious agents that range from having a relatively broad to narrow incubation period (e.g., Ebola, 2–21 days; yellow fever 3–6 days). These diseases present with nonspecific prodromes that may have an insidious or abrupt onset. In severe cases, the prodrome is followed by hypotension, shock, central nervous system dysfunction, and a bleeding diathesis. The differential diagnosis includes a variety of viral and bacterial diseases. Establishing the diagnosis depends on clinical suspicion and the results of specific tests that must be requested from CDC or the U. S. Army Medical Research Institute of Infectious Diseases. The value of postexposure prophylaxis with antiviral medications is uncertain, and (with the exception of yellow fever, for which a vaccine is available) response measures are limited to isolation and observation of exposed persons, treatment with ribavarin (if the virus is one that responds to that antiviral drug), and careful attention to infection control measures (23
). Patients seen with symptoms during the prodromal phase may not clearly fit into a single syndrome category, but syndromic surveillance focused on the early signs of a febrile bleeding disorder would be more specific.
One of the biggest concerns about syndromic surveillance is its potentially low specificity, resulting in use of resources to investigate false alarms (6
). Specificity for distinguishing bioterrorism-related epidemics from more ordinary illness may be low because the early symptoms of bioterrorism-related illness overlap with those of many common infections. Specificity for distinguishing any type of outbreak from random variations in illness trends may be low if statistical detection thresholds are reduced to enhance sensitivity and timeliness. The likelihood that a given alarm represents a bioterrorism event will be low, assuming that probability of such an event is low in a given locality. Approaches used to increase specificity include requiring that aberrant trends be sustained for at least 2 days or that aberrant trends be detected in multiple systems (2
). Another approach to enhancing specificity would be to focus surveillance on the severe phases of disease, since the category A bioterrorism infections are more likely than many common infections to progress to life-threatening illness. For those diseases that are likely to progress rapidly, such as pneumonic plague, syndromic detection of severe disease (e.g., through emergency room visits, hospital admissions, or deaths) may be more feasible than detection aimed at early indicators before care is sought (e.g., purchases of over-the-counter medications) or when illness is less severe (e.g., primary care visits). Whether detection of syndromic late-stage disease offers an advantage over detection through clinical evaluation will depend on the attributes of the infections and diagnostic resources, as described above.
Predicting how the mix of relevant factors would combine in a given situation to affect the recognition of a bioterrorism-related epidemic is difficult, although mathematical models may provide further insight (5
). The most important factors affecting early detection are likely to be the rate of accrual of new cases at the outset of an epidemic, geographic clustering, the selection of syndromic surveillance methods, and the likelihood of making a diagnosis quickly in clinical practice.
Ongoing efforts to strengthen the public health infrastructure (34
) and to educate healthcare providers about bioterrorism diseases and reporting procedures should strengthen the ability to recognize bioterrorism outbreaks. For example, in New Jersey in 2001, reporting of two early cases of cutaneous anthrax was delayed until publicity about other anthrax cases prompted physicians to consider the diagnosis and notify the health department, suggesting that opportunities for earlier use of postexposure prophylaxis were missed (36
). In addition, while the importance of new diagnostic tools, including rapid tests, should be emphasized (37
), the essential role of existing diagnostic techniques should not be overlooked. Clinical suspicion is critical, and a key prompt for arousing clinical suspicion may be the microscopic examination of a routinely collected specimen, as occurred in the index case of the 2001 anthrax outbreak, when a Gram stain of the cerebrospinal fluid led to the diagnosis (15
). However, as recently highlighted by the Institute of Medicine, the use of basic diagnostic tests has decreased because of efforts to reduce the costs of care, the increasing use of empiric broad-spectrum antibiotic therapy, and federal laboratory regulations, such as the Clinical Laboratory Improvement Amendments of 1988, which have discouraged laboratory evaluation in some clinical settings (38
While we have focused on the role of syndromic surveillance in detecting a bioterrorism-related epidemic, other uses of syndromic surveillance include detecting naturally occurring epidemics, providing reassurance that epidemics are not occurring when threats or rumors arise, and tracking bioterrorism-related epidemics regardless of the mode of detection (4
). Syndromic surveillance is intended to enhance, rather than replace, traditional approaches to epidemic detection. Evaluation of syndromic surveillance to consider the spectrum of potential uses is essential. A certain level of false alarms, as the result of either syndromic surveillance or calls from clinicians, will be necessary to ensure that opportunities for detection are not missed. Efforts to enhance the predictive value of syndromic surveillance will be offset by costs in timeliness and sensitivity, and defining the right balance in practice, particularly in the absence of an accurate assessment of bioterrorism risk, will be essential.
Two committees of the National Academies have recommended more careful evaluation of the usefulness of syndromic surveillance before it is more widely implemented (5
). Because the epidemiologic characteristics of different bioterrorism agents may vary in ways that affect the detection of epidemics, these evaluations should address the epidemiology of specific bioterrorism agents. Efforts to detect bioterrorism epidemics at an early stage should not only address the development of innovative new surveillance mechanisms but also strengthen resources for diagnosis and enhance relationships between clinicians and public health agencies—relationships that will ensure that clinicians notify public health authorities if they suspect or diagnose a possible bioterrorism-related disease.