NATURE OF THE PROBLEMBW agents. The release of a biological weapon (BW) agent by a terrorist group or military force would likely be silent and undetectable or nearly so. As shown by anthrax attack during the fall of 2001 in the eastern United States, patients would begin appearing at hospitals and clinics within several days of exposure, most presenting with nonspecific flu-like symptoms. The first days of the outbreak might not even cause undue concern. However, depending on the type of agent and the method of dispersal, the public healthcare system would rapidly be stretched to capacity and beyond.The qualities that make a good BW agent are its relationship between aerosolization, infectivity, or toxicity and the amount of agent required to produce an effect (48). In addition, criteria such as environmental stability, ease of production, disease severity, and communicability determine which agents are the most likely to be utilized. For maximum effect, an optimal agent should be highly lethal and easily produced in large quantities and have limited options for preventive or prophylactic treatment. Given that the respiratory route is the most effective for most BW agents, stability in an aerosol form and the capability to be readily dispersed also in an aerosol (1-to 10-m particle size) are necessary. When potential agents are reviewed for these characteristics, Bacillus anthracis (anthrax) and variola major virus (smallpox) are considered to have the greatest potential for mass casualties and civil disruption. Also high on a prospective list of agents are botulinum neurotoxins, Yersinia pestis, and Francisella tularensis (48,91,92). Lower on the prospective list are Burkholderia pseudomallei and Burkholderia mallei, Rickettsia sp., Coxiella burnetii, Venezuelan equine encephalitis virus, Marburg and Ebola viruses, and influenza viruses (48,63,91,92).Emerging infectious disease agents. In addition to diseases caused by intentional epidemics, there are several emerging infectious diseases (ID) with the potential for significant public health consequences, including dengue fever, West Nile fever, and Rift Valley fever as well as the recent reemergence of malaria in the eastern United States (48,63,91,92). As with BW agents, emerging ID agents may be directly transmissible or vector borne (63). A complex interplay of factors can influence disease emergence, including genetic variation, environmental changes, and population pressures. Further compounding this already complicated situation, are the estimated 600 million international tourists annually, many with the potential to the spread disease globally in a matter of hours (63). Clearly, the challenges facing modern clinical microbiologists and immunologists are daunting enough without the added difficulties posed by the intentional release of BW/ID agents! Because of the threat posed by both BW and emerging or reemerging ID agents, there is a need to rapidly identify such agents in the clinical setting in order to treat the individuals at risk and to improve p...

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Immunoassays have evolved for a broad range of applications since the pioneering work of Yalow and Berson who developed the first competitive radioimmunoassay (RIA) for human insulin in 1959. Immunoassay detection of specific antigens and host-produced antibodies directed against such antigens constitutes one of the most widely used and successful methods for diagnosing infectious diseases (IDs). The number and variety of new assay systems that are continually being developed reflect the increasing demand for immunoassays possessing greater sensitivity, speed, and ease of use. This trend has been driven, in part, by the need for improved immunodiagnostic systems to perform rapid testing and counter emerging IDs and biothreat (BT) agents. Another factor driving this trend is the need to integrate immunoassays with more sensitive nucleic acid-based methods for a comprehensive approach. Here we examine the development of immunoassays, some of the key formats used for the detection and identification of BT/ID agents, and the application of these technologies under different scenarios.

* A positive quantitative or qualitative nucleic acid test result or molecular sequence data for an HIV-1 genotypic drug-resistance test.

In this special section of BioTechniques, we examine the role of rapid molecular technologies in the detection and identification of agents of infectious disease (ID) and biological weapons (BWs). Besides the threat posed by the global proliferation of BW technologies, there are numerous emerging and reemerging ID agents with significant public health consequences. Further compounding this already complicated situation are the estimated 600 million international tourists annually, many with the potential to the spread disease globally in a matter of hours. While clinical laboratories have key roles in the detection and identification of potential ID/BW agents, most staff are unfamiliar with these agents because of their rarity and the often laborious conventional methodologies needed to identify them. To meet this challenge, a vast array of rapid assay strategies has been developed for use in clinical diagnostics and environmental detection. Technologies have been developed or adapted to the challenges posed by these agents, permitting detection and identification in several minutes to hours. In particular, the development of improved reagents and detection systems has led to dramatic improvements in the sensitivity and specificity of immunological and nucleic acid-based systems, allowing an ever-increasing range of analytes to be identified and quantitated. In the accompanying articles, we have brought together experts from the many overlapping aspects of this arena in order to present a comprehensive and critical analysis of these technologies.