BIOTHREATS  (IDs  +  TOXINS)  VS  CHEMICAL  AGENTS

Most toxins are complicated, multi-domain proteins in the tens to hundreds of kilodalton weight range, some are simpler organic molecules, and some are combinations of multiple toxic protein enzymes. The mechanisms of each toxin are unique and related to the chemical structure. Toxins that are enzymes, such as ricin and botulinum toxins, have very low LD50s (median lethal doses), making them more potent on a milligram-per-milligram basis than even the most powerful chemical weapons. Small organic molecule toxins, such as tetrodotoxin and saxitoxin, bind to molecular ion channels in mammalian cells and exert their effect by inappropriately opening or closing the ion channel, leading to higher-level tissue dysfunction. Anti-toxins are harvested antibodies designed to bind and neutralize specific toxins. If dosed early in the course of toxin-induced illness, then the illness can be halted (but usually not immediately reversed). Some protein toxins, such as botulinum toxins, can come in multiple different strains of genetic variations that result in protein structural differences that can affect the efficacy of anti-toxins or the sensitivity of immunoassay detectors.

Similar to chemical agents, toxins are of comparable or greater potency, have predictable dose-response effects, and start acting shortly after absorption into the body. Unlike chemical agents, toxins are relatively difficult to detect in the environment and can be hundreds of times larger in terms of molecular size and weight. Compared to infectious bio-agents, toxins are not transmitted person-to-person (though heavily contaminated patients could expose unprotected treatment teams) and do not replicate in the body. For that reason, toxins generally exert their effect much faster than infectious bio agents, with an asymptomatic latent period of minutes to a few days after exposure, versus the incubation period of multiple days to weeks for most infectious agents. Because toxins are generally more slowly absorbed than most chemical weapons and take time to exert their effect at a molecular level, the latent period for toxins is usually longer than that for chemical agents, most of which have noticeable clinical effects within minutes to hours. Anthrax and botulinum toxins can both be produced in the body by their associated bacteria, or introduced to the body as pre-formed toxin, though the latter is more likely with botulism, while infection with the causative bacterium is more likely with anthrax.

The clinical effects of organophosphate nerve agent poisoning can be challenging to distinguish from those of botulism toxin or Staphylococcal enterotoxin B (SEB).  Appendix E of the USAMRIID Medical Management of Biological Casualties Handbook, 9th Edition provides a comparison table. Nerve agents are generally faster acting, within seconds to minutes at high doses, while SEB can take several hours to exert effects and botulinum toxin up to several days. Nerve agents and SEB can both cause vomiting and diarrhea, while botulinum toxin exposure generally does not. Nerve agents will cause local fasciculations and generalized seizures, while botulism toxin causes gradual onset descending symmetrical flaccid paralysis with preserved mental status until the patient is hypoxic and/or hypercarbic, and SEB has minimal neurological effects. Nerve agents will cause noticeably increased oral secretions from salivary and mucous gland stimulation, while botulinum toxin can cause dry mouth and throat with swallowing dysfunction leading to aspiration. Death can occur in minutes from severe nerve agent exposures, and in days from botulinum toxin exposures, but death is rare in SEB exposure. Appropriately dosed atropine should improve peripheral, muscarinic effects of nerve agents but will have minimal effects on SEB gastrointestinal symptoms, and not improve botulism symptoms.

Clinical laboratory testing can help distinguish between illnesses caused by chemicals, toxins, and bio-agents and help identify the specific causative agent. Definitive clinical testing to identify exposure to chemical agents can take hours to days and often requires specific laboratory equipment; however, rapid testing with immunoassays is available for some agents, and indirect assessment of effects on blood or plasma acetylcholinesterase can strongly suggest the presence of nerve agent poisoning. Clinical presence and identification of bio-agents is discussed later but can provide results within hours through polymerase chain reaction techniques or immunoassays. Toxins can be relatively challenging to detect with standard clinical laboratory techniques, due to the relatively small numbers of toxin molecules required to cause clinical effects. Expert consultation is recommended to determine appropriate testing techniques and pre-testing treatment on a case-by-case basis, particularly for suspected botulinum toxin, ricin, or marine toxin exposure. Call your Poison Control Center for assistance (1-800-222-1222) if you are CONUS and the ADVISOR line if deployed.