When human illness results from an unintentional or intentional release of a toxin (chemicals produced by metabolism in an organism [e.g., ricin]) or a toxicant (natural or synthetic chemicals not metabolically produced by an organism [e.g., nerve agents]) into the environment, uniform reporting is necessary to direct appropriate resources, assess the extent of morbidity and mortality, track poisoned persons, and monitor response to intervention. In this report, CDC presents case definitions to facilitate uniform reporting among local, state, and federal public health agencies of illness resulting from a chemical release. The report also explains the rationale for the structure of the case definitions, the audience for whom it is intended, the setting in which the case definitions might be used, and reasons each chemical presented in the report was selected.
Clinical knowledge and diagnostic tools (e.g., biologic laboratory tests) for detecting chemical poisoning are likely to improve over time. CDC will create new case definitions and revise existing definitions to meet the needs related to emerging threats and to enhance case definition sensitivity and specificity, when possible, with developing clinical information.
Introduction
Toxins are chemicals that are produced by organisms as a result of cellular metabolism (e.g., marine toxins such as saxitoxin or plant toxins such as ricin). Toxicants are synthetic (i.e., manufactured) or naturally found chemicals that are not produced by organisms as a result of cellular metabolism (e.g., nerve agents or arsenic). When illness results from an intentional or unintentional chemical release (either known or suspected on the basis of a credible threat) into the environment, uniform reporting is paramount to direct appropriate resources, assess the extent of morbidity and mortality, track poisoned persons, and monitor response to intervention. In this report, CDC presents case definitions to facilitate uniform reporting of illness resulting from a chemical (i.e., toxin and toxicant) release.
How This Report Is Organized
The report provides an overview of 1) the settings in which the case definitions might be used, 2) the structure of the case definitions, 3) the rationale for choosing the particular chemicals, and 4) plans for revising the report. A list and description of the terms used in the report are also provided. In addition, case definitions, which include reference citations, are presented for the selected chemicals.
How To Use the Information in This Report
The case definitions in this report should be used by clinicians and public health officials in two settings: 1) after a credible threat of a chemical release or 2) after a known chemical release. The list of chemicals that have the potential for use as a terrorist weapon is extensive, and clinical presentation of poisoning from chemicals can be similar to that of common diseases (e.g., gastroenteritis). Therefore, use of these case definitions as a surveillance tool, in the absence of a credible threat or a known chemical release, typically results in excessive false-positive reports and is not recommended by CDC.
Case definitions are not sufficient for establishing a medical diagnosis and should not be relied upon to initiate therapy. They are also not meant to be used for persons who are exposed to a chemical agent but remain asymptomatic. Clinical manifestations of poisonings might vary as a result of interindividual differences (e.g., previous medical history, genetic differences, sex, or age), route of exposure, amount and duration of exposure, and length of time since the exposure. In addition, simultaneous exposure to >2 chemicals can result in symptoms that are not typical for either agent alone. Use of additional clinical, epidemiologic, and laboratory data might enable a physician to make a medical diagnosis, although the formal surveillance case definition might not be met.
Health-care providers should report suspect cases of intentional chemical exposure to their local poison-control center and to a public health agency. Local and state public health officials should notify CDC and law enforcement officials if they identify persons who might have been exposed to intentional chemical poisoning.
Structure of the Case Definition
CDC modeled the structure of the chemical poisoning case definitions in this report after the infectious disease case definitions that were previously developed by CDC and the Council of State and Territorial Epidemiologists (CSTE) (1,2). However, case definitions for chemical poisoning were modified to address the clinical and diagnostic challenges unique to chemical poisoning. A description of terminology used in the case definitions is presented in this report.
Each case definition is composed of three sections: 1) clinical description, 2) laboratory criteria for diagnosis, and 3) case classification. Individual case definitions differ in the structure of the clinical description and the laboratory criteria for diagnosis. However, for all case definitions, the clinical description and the laboratory criteria for diagnosis will determine the case classification. CDC used an algorithmic method to determine the structure of the clinical description and the laboratory criteria and to determine how the user might classify a case by using the case definition (Figure).
For case classifications, a case that is being considered as a chemical poisoning case is categorized as “suspected,” “probable,” or “confirmed.” A suspected case is one in which any potentially exposed person is being evaluated by health-care workers or public health officials for poisoning by a particular chemical agent; however, no specific credible threat exists. A probable case is 1) one in which a person has an illness that is clinically compatible with poisoning from a particular chemical agent and in which a credible threat exists (e.g., clinically compatible illness in an employee of a facility where a specific threat of a chemical release is made) or 2) one in which epidemiologic data link the person to a confirmed case (e.g., clinically compatible illness in a person who was at the same location as the subject of a case confirmed by biologic or environmental testing). A confirmed case is one in which a suspected or a probable case of exposure has been substantiated with laboratory testing of environmental or biologic specimens.
One of the key elements in determining whether a potentially exposed person will be categorized as a suspected case-patient or a probable case-patient is deciding whether the person’s illness is clinically compatible with exposure to a particular chemical. Providing the user of these case definitions with a specific set of clinical criteria (i.e., clinical criteria that objectively allow the user to decide whether the case is clinically compatible) is often not possible, because manifestations of chemical poisonings can vary on the basis of individual differences of the exposed persons (e.g., previous medical history, genetic differences, sex, or age), route of exposure, amount and duration of exposure, and length of time since the exposure. Therefore, the structure of the clinical description includes multiple possible clinical manifestations.
If a valid laboratory test is available to confirm the exposure for a particular agent (e.g., cyanide), the clinical description summarizes the most notable features of acute poisoning from that particular chemical, on the basis of the medical literature. If no available or valid laboratory method is available to detect the chemical in biologic or environmental specimens, the case will never be confirmed and will remain either in the suspected or probable category. Therefore, making an association between the clinical presentation and the suspected agent will primarily depend on the clinical description and the presence of a credible threat. For these agents (e.g., tetrodotoxin), the clinical description of the case definition includes specific criteria for clinical compatibility (including nonconfirmatory or nonspecific laboratory parameters [e.g., electrolytes and renal function tests]) that should be met before a case can be categorized as suspected or probable for chemical poisoning. Medical toxicologists and epidemiologists at CDC used clinical information from the literature on each agent to develop the specific criteria included in the clinical description for that agent. However, CDC recognizes that the criteria do not provide positive or negative predictive value for confirming or excluding poisoning from a particular chemical.
In certain instances, suspected or probable cases might exist for which laboratory (biologic or environmental) testing was not performed by the clinician or public health official. Reasons for not performing laboratory testing might include a predominant amount of clinical and nonspecific laboratory evidence of a particular chemical or a 100% certainty of the etiology of the agent, as might be the case with agricultural workers who are known to have been exposed to a particular fumigant and who then develop clinically compatible illness. For example, in the case of a Bulgarian dissident reported to have been poisoned with ricin, no laboratory confirmation ever occurred (3). If the case definitions in this report are strictly followed, this case might never be a confirmed case, although a predominant amount of evidence existed for ricin poisoning, and ricin poisoning is accepted as the cause of death. This case and similar scenarios may be considered as confirmed.
A suspected or probable case can become a confirmed case when excess exposure is verified by laboratory evidence (i.e., levels above the 95th percentile in CDC population studies or above a reference range). Laboratory evidence can be obtained from either biologic specimens (e.g., blood or urine) or environmental samples (e.g., water, air, soil, or a contaminated product such as food). Testing for chemicals in either environmental or biologic specimens is not universally available. In addition, results from field tests conducted by using hand-held assays intended for screening environmental samples and research tests are not considered confirmatory. CDC recommends that laboratory testing be used in conjunction with a state or CDC public health investigation for confirming exposure only when a valid laboratory test is available through 1) commercial resources, 2) the Laboratory Response Network (LRN), or 3) one of the following federal agencies (Appendix):
- Food and Drug Administration (FDA), Forensic Chemistry Center — Processes food samples for selected agents. Available athttp://www.fda.gov; telephone: 513-679-2700, extension 184.
- CDC, National Center for Environmental Health (NCEH), Division of Laboratory Sciences — Processes blood and urine for selected agents. Available at http://www.cdc.gov/nceh/dls; telephone: 770-488-7950.
- CDC, National Institute for Occupational Safety and Health (NIOSH) — Processes air, dust, and soil for selected agents from workplace exposures. Available at http://www.cdc.gov/niosh/homepage.html; telephone: 800-356-4674.
- CDC, National Center for Infectious Diseases (NCID), Bioterrorism Rapid Response and Advanced Technology Laboratory — Receives and processes clinical and environmental samples for biothreat agents and selected biotoxins. Telephone: 404-639-4910.
- Environmental Protection Agency (EPA) — Processes environmental samples for industrial chemicals. Available at http://www.epa.gov; telephone: 404-562-8700.
LRN includes multiple state laboratories capable of identifying select microbiologic agents, but only a limited number of state laboratories are capable of testing biologic specimens for chemical warfare agents.
Data for validation of commercially available analyses of certain chemicals in either biologic or environmental samples might be difficult for nonlaboratorians to access. If an intentional release occurs, CDC personnel will be able to advise local and state public health partners on whether valid analyses for biologic samples for specific chemicals exist. However, CDC does not provide guidance concerning commercial laboratory methods; for guidance regarding environmental or food samples, consultation with EPA and FDA is recommended. Laboratorians should ask their referral laboratories to provide confirmation that a method is analytically valid for precision, detection limits, and accuracy. Laboratorians should also ask their laboratories to confirm whether applications are environmental or clinical, for example.
A chemical agent probably will be detected in biologic specimens in traceable quantities in the absence of clinical findings. However, signs and symptoms consistent with poisoning should develop before an exposed person is considered a case-patient.
Because timely laboratory confirmation might not be available, clinicians should not wait for laboratory verification to report suspected or probable cases to appropriate public health agencies. Early involvement of public health agencies will enable monitoring of trends, detection of covert events in multiple locations, mobilization of resources (e.g., National Pharmaceutical Stockpile, laboratory resources, or legal investigation), and containment of further exposure. State health departments should continue to promptly report suspected cases to CDC, and records should be updated with the appropriate classification status when additional surveillance information becomes available.
Chemicals with Potential for Terrorist Use and Plans for Revision of This Report
The substantial number of chemicals with potential for terrorist use precludes the development of a case definition for each possible agent. Therefore, certain agents with a potential for use as a terrorist weapon are not included in this report. Medical toxicologists at CDC’s NCEH chose the chemicals presented in this report on the basis of knowledge of their accessibility, deliverability, lethality, potential to cause social disruption, or historic use. In certain cases, a category of agents with similar properties is represented (e.g., caustics/corrosives).
This report underwent an extensive review process by CDC’s Office of Security and Emergency Preparedness and Office of Terrorism Preparedness and Emergency Response, and by CDC’s stakeholders (e.g., FDA, EPA, and CSTE). This report is designed to be updated and revised as new information becomes available. CDC plans to compose, in conjuction with state public health agencies and other organizations (e.g., FDA or EPA), new case definitions and revise existing definitions to reflect information concerning emerging threats and agents, improvements in diagnostic technology, and increasing clinical knowledge regarding a particular chemical. In addition, when a chemical is released or the threat of a release exists, CDC will review literature regarding the implicated chemical and might update the case definition. The most up-to-date versions of case definitions and other public health documents will be posted on CDC’s Emergency Preparedness and Response Internet site (http://www.bt.cdc.gov/agent/agentlistchem.asp).
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