Staphylococcal enterotoxin B (SEB) is one of many enterotoxins produced by the Staphylococcus organism. Staphylococcus species and other bacterial organisms produce many enterotoxins that are responsible for a myriad of effects in the animal or human serving as host for the organism. Due to their clinical effects and mode of action, these are sometimes referred to as superantigens or pyrogenic toxins. In total, seven enterotoxins have been identified. The type B serotype is the agent that has been most extensively studied as a biological weapon. The U.S. military considered SEB as a weapon in the 1960s (1, 2).

SEB is frequently classified as an “incapacitating agent” because it does not in general produce mortality. Its military usefulness is based on the belief that this agent would be effective to halt troop movements; within the civilian population, it would produce a large number of ill persons over a short period of time. This wave of patients could overwhelm the medical care system, and the enterotoxin could also be mistaken for more lethal biological agents, promoting fear and terror.

Enterotoxins in general are exotoxin products of bacteria, that is, secreted toxins. “Entero” means these toxins are predominantly identified as causing illness to the gastrointestinal system. Some clinicians may not be familiar with the term “SEB”; however, most are well acquainted with the toxin-caused staphylococcal food poisoning syndrome: abdominal pain, nausea, vomiting, and diarrhea with onset within a few hours of ingestion of the offending food product. With staphylococcal food poisoning, enterotoxins are responsible for the clinical syndrome. Naturally occurring strains of staphylococcus aureus produce enterotoxins when allowed to grow in milk products, meats, and bakery products. Staphylococcal enterotoxins are protein complexes, many with similar amino acid sequences (1). Other enterotoxins are identified as having distinct protein compositions from staphylococcus aureus. These are classed as A through G, but type B can be taken as an example of the entire class.

Another enterotoxin to produce disease is the toxic shock syndrome toxin (TSST-1). This toxin shares some structural relations to SEB as well as other staphylococcal toxins. Streptococcal species produce several toxins as well.

The concept of SEB classification as incapacitating agents is reflected in the differences between the effective dose versus the lethal dose of this toxin. Effective dose is also considered the incapacitating dose. This is represented by the concepts of effective/incapacitating dose for 50% of an exposed population (ED50) and lethal dose for 50% of an exposed population. The reported incapacitating dose for 50% of a population exposed to SEB is 0.0004 micrograms/kg with inhalation exposure, as compared to the lethal dose (LD50), which is an exponentially larger dose of 0.02 micrograms/kg (2). These doses are less than lethal doses for many chemical exposures.

SEB, like many similar toxins in its family, causes its effects by its tendency to activate the immune system nonspecifically. The chemical interaction responsible for this stimulation occurs on multiple levels; SEB affects both T-cell antigen receptors and MHC (major histocompatibility complex) class II components of the immune system. The MHC class II molecules are found on the cell surfaces of what is frequently termed “antigen presenting cell” macrophages, dendritic cells, and B-cells. The subsequent stimulation of CD-4 helper T-cells results in the release of cytokines and further activation of the immune system. Proliferation of these stimulated T-cells is believed to be at the heart of the effect of SEB (4). The end result of this immune system activation is release of cytokines. Cytokines released include interferon gamma, interleukin-6, and tumor necrosis
factor (3). The effect of this “cytokine storm” is to produce the inflammation and hence clinical syndrome of SEB poisoning. Gastrointestinal disease from SEB may also result from the release of other substances such as histamine and leukotrienes.

In addition to SEB’s ability to generate release of cytokines and activate an immune system response that results in a clinical syndrome, it possesses other characteristics that make it plausible for use as a biological weapon. One of these characteristics is the toxin’s stability with respect to temperature, solubility in water, and stability in air. SEB could be delivered by an aerosol mechanism or solubilized in water, representing an ingestion hazard from contaminated foodstuffs or potable water. (Note: Chlorination of water should eliminate the toxin.)

In addition to recognition of the clinical signs of SEB exposure, detection of SEB is possible in environmental and biological samples. Available technologies include ELISA and TRF (time-resolved fluorometry). Note that other biological weapons of concern detected by TRF techniques include Francisella tularensis and Clostridium botulinum toxin A/B (5). Reverse passive latex agglutination (RPLA) tests can identify SEB in food. Polymerase chain reactions can be used to identify the staphylococcal aureus genome. Retrospective diagnosis can be attempted with the use of serological tests for SEB in victims.

Signs and symptoms of illness differ by the route of exposure to this superantigen. Because SEB is one of the frequently suspected etiologies of naturally acquired food-borne illness, it could be difficult to differentiate between exposure to SEB as acquired from a culinary misadventure or illness as the result of an intentional contamination of food products. One leading point might be the type of food ingested because naturally occurring staphylococcal enterotoxin food poisoning typically is seen in dairy products, pastry (especially cream-filled pastry), custard, ham, and potato salad. The clinician should be cognizant of the potential for victims exposed to inhalational SEB to have combined symptoms of inhalational exposure and signs and symptoms of ingestion of SEB, if during the inhalational exposure the victim swallowed the toxin in addition to inhaling.

Ingested SEB food-borne illness is typically self-limited. Incubation period can be as short as 1 hour after ingestion of the food substance, with a general range of 1 to 6 hours after exposure for the onset of symptoms. Predominating symptoms are nausea and vomiting with abdominal cramping (9). Fever and diarrhea are not seen in all patients. Many patients begin to recover after 24 hours. Other food-borne toxins that present with nausea and vomiting as predominant symptoms are Bacillus cereus and Norwalk-like virus. Bacillus cereus is typically associated with starch-rich foods such as rice and recognized as the etiology of a vomiting illness associated with fried rice dishes. Norwalk-like virus (norovirus) is a common source of food-borne illness (10). Norwalk-like virus can be contracted via food products and has been associated with shellfish. It can also be contracted via contact with contaminated surfaces, then through hand-to-mouth activity that transmits the virus. The presenting symptoms are similar to SEB ingestion. Norwalk-like virus (norovirus) has an incubation time of 24 to 48 hours. Vomiting and diarrhea are typically both present. With SEB, diarrhea is less prevalent and generally nonbloody. Other symptoms found with all of these exposures may include fever, generalized myalgias, and fatigue (11). Several outbreaks of norovirus on cruise ships have been documented and may give a sense of how a localized bioterrorism outbreak may present. In one report, vomiting and diarrhea were present in the majority of the patients stricken (12).