CBRNE – Staphylococcal Enterotoxin B

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Toxins are poisons produced by living organisms. Staphylococcal enterotoxin B (SEB) is an exotoxin excreted by the Staphylococcus aureus bacterium. Staphylococcus species thrive and produce toxins in unrefrigerated meats, dairy, and bakery products. S aureus is also a major human pathogen responsible for numerous infections, including skin and soft tissue infections and pneumonia.

The effect of SEB this article is concerned about normally exerts its effect on the intestines and, therefore, is termed an enterotoxin. More recent research has identified additional superantigens that have been subclassified into enterotoxin serotypes and enterotoxin-like serotypes. Although staphylococcal enterotoxins A, B, and C (SEA, SEB, SEC) and toxic shock syndrome toxin–1 are now believed to all be responsible for clinically significant toxic shock in humans, SEB remains the prototypical superantigen.  Not all toxins result in a lethal outcome, but they may cause significant morbidity. ^{[1, 2]}

SEB is the toxin most commonly associated with classic food poisoning. ^{[3, 4]} It has also been demonstrated to cause a nonmenstrual toxic shock syndrome (TSS). ^[5]  Researchers have implicated SEB in the pathophysiology of chronic atopic dermatitis, chronic rhinitis, and ulcerative colitis. ^[6]

SEB has been studied as a potential biological warfare agent because it can easily be aerosolized; it is very stable; and it can cause widespread systemic damage, multiorgan system failure, and even shock and death when inhaled at very high dosages. However, SEB is classified as an incapacitating agent because in most cases aerosol exposure does not result in death but in a temporary, though profoundly incapacitating, illness lasting as long as 2 weeks. ^[7]

SEB is 1 of 7 originally identified enterotoxins produced by certain strains of coagulase-positive S aureus, a gram-positive coccus that forms clumps. S aureus is known to colonize the nasal passages and axillae in humans. Research has elucidated the structures of numerous enterotoxin-like superantigens, with two new enterotoxins, now known as SES and SET, discovered in 2008. ^{[8, 9, 10]}

SEB consists of 239 amino acid residues and has a molecular weight of 28 kd. It is 1 of the 7 least antigenically distinct enterotoxin proteins that have been identified (A, B, C, D, E, I, and toxic shock syndrome toxin–1). SEB has 2 distinct tightly “packed” domains that have a very complex tertiary structure. This compact structure enables SEB to be highly resistant to proteases, including trypsin, chymotrypsin, and papain, which are all found in the intestinal lumen.

SEB is a relatively stable compound that is easily soluble in water. It is moderately resistant to temperature fluctuations and can withstand boiling at 100º C for several minutes. In the freeze-dried state, SEB can be stored for more than a year. For aerosol exposures, the effective dose, or ED₅₀ (dose capable of incapacitating 50% of the exposed human population), is 0.0004 mcg/kg of body weight, and the lethal dose, or LD₅₀, is 0.02 mcg/kg. ^[11]

Many of the effects of staphylococcal enterotoxin B (SEB) are mediated stimulation of T lymphocytes by the host’s immune system. ^[12] The toxin binds directly to the major histocompatability complex (MHC) class II proteins on target cells, subsequently stimulating the proliferation of large numbers of T lymphocytes. SEB is a “bacterial superantigen” because it can form a “bridge” between the MHC II on the antigen-presenting cells and the T-cell receptors on both CD4 and CD8 T cells, thereby bypassing the normal antigen processing and presenting mechanism. This bridging effect causes the release of massive amounts of cytokines, specifically interleukin 2 (IL-2), tumor necrosis factor alpha (TNF-α), and interferons.

The cytokines cause a recruitment of additional inflammatory cells. In addition, there is a relative deficient activation of negative counter-regulatory feedback loops. Taken together, the body’s own inflammatory response most likely mediates many of the toxic effects of SEB.

Ingestion of SEB produces profound gastrointestinal (GI) symptoms, including anorexia, nausea, vomiting, and diarrhea, which are believed to be mediated through the release of cytokines from T cells in the lamina propria of the intestines. Animal studies have shown that the severe pulmonary edema associated with aerosol exposure is likely secondary to T-cell proliferation within the respiratory mucosa and not the toxin itself. ^{[1, 7, 13]}

SEB has been studied in multiple animal models over the past 40 years. Some of the most recent studies in rabbits and pigs, like others in the past, involve direct inoculation with intravenous administration of SEB. In these studies, GI symptoms began as early as 4 hours post injection followed by terminal shock at 96 hours. ^[14]

United States

The actual incidence of SEB-related food poisoning is unknown; many cases are so mild that patients do not seek treatment. Additionally, diagnoses in the emergency department are usually presumptive, and a number of other diseases may mimic SEB-induced gastroenteritis.

The gastrointestinal form of staphylococcal enterotoxin B (SEB) toxicity, while potentially debilitating for short durations, is rarely fatal with adequate hydration.

No relevant aggregate data are available regarding the mortality and morbidity of inhalational SEB exposure.

Updated CDC search revealed a report from the Minnesota Department of Health in 1986 where six cases of toxic shock syndrome were reported after infection with influenza B.  Two of the six died; four patients were identified after two initial cases were reported, of those four only one developed erythroderma (rash), and three of the four eventually desquamated. 

Very young and elderly persons are likely the most susceptible to a complicated course.

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Bruce A Gleason, MD Chief, Department of Emergency Medicine, William Beaumont Army Medical Center, Ft Bliss, Texas

Bruce A Gleason, MD is a member of the following medical societies: American College of Emergency Physicians, Emergency Medicine Residents’ Association

Disclosure: Nothing to disclose.

Kermit D Huebner, MD, FACEP Research Director, Carl R Darnall Army Medical Center

Kermit D Huebner, MD, FACEP is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, Association of Military Surgeons of the US, Society for Academic Emergency Medicine, Society of United States Air Force Flight Surgeons

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Duane C Caneva, MD, MSc Senior Medical Advisor to Customs and Border Protection, Department of Homeland Security (DHS) Office of Health Affairs; Federal Co-Chair, Health, Medical, Responder Safety Subgroup, Interagency Board (IAB)

Disclosure: Nothing to disclose.

Jerry L Mothershead, MD Medical Readiness Consultant, Medical Readiness and Response Group, Battelle Memorial Institute; Advisor, Technical Advisory Committee, Emergency Management Strategic Healthcare Group, Veteran’s Health Administration; Adjunct Associate Professor, Department of Military and Emergency Medicine, Uniformed Services University of the Health Sciences

Jerry L Mothershead, MD is a member of the following medical societies: American College of Emergency Physicians, National Association of EMS Physicians

Disclosure: Nothing to disclose.

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author, Danielle M Pesce, DO, to the development and writing of this article.

CBRNE – Staphylococcal Enterotoxin B

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