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CBRNE - Staphylococcal Enterotoxin B

Author: Bruce A Gleason, MD, Resident Physician, Department of Emergency Medicine, C R Darnall Army Medical Center, Ft Hood, Texas
Coauthor(s): Kermit D Huebner, MD, FACEP, Research Director, Carl R Darnall Army Medical Center
Contributor Information and Disclosures

Updated: Apr 29, 2009

Introduction

Background

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. SEB normally exerts its effect on the intestines and, therefore, is termed an enterotoxin. Not all toxins result in a lethal outcome, but they may result in significant morbidity.¹

Staphylococcal enterotoxin B (SEB) is the toxin most commonly associated with classic food poisoning. It has also been demonstrated to cause a nonmenstrual toxic shock syndrome (TSS).² 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.³

Source

Staphylococcal enterotoxin B (SEB) is 1 of 7 originally identified enterotoxins produced by certain strains of the coagulase-positive S aureus bacteria, a gram-positive cocci that form clumps. Research has elucidated the structures of numerous enterotoxin-like superantigens, with two new enterotoxins, now known as SES and SET, just discovered in 2008.⁴ S aureus is known to colonize the nasal passages and axillae in humans.

Structure

Staphylococcal enterotoxin B (SEB) consists of 239 amino acid residues and has a molecular weight of 28 kd. It is 1 of the 6 least antigenically distinct enterotoxin proteins that have been identified (A, B, C, D, E, G). SEB has 2 distinct tightly "packed" domains that have a very complex tertiary structure. It is this compact structure that enables SEB to be highly resistant to proteases, including trypsin, chymotrypsin, and papain, which are all found in the intestinal lumen.

Properties

Staphylococcal enterotoxin B (SEB) is a relatively stable compound that is easily soluble in water. It is moderately resistant to temperature fluctuations and can withstand boiling at 100 º 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, and the lethal dose, or LD₅₀, is 0.02 mcg/kg.⁵

Pathophysiology

Mechanism of toxicity

Many of the effects of staphylococcal enterotoxin B (SEB) are mediated stimulation of T lymphocytes by the host's immune system. 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 b (TNF-b), and interferons. 

The cytokines not only cause a recruitment of additional inflammatory cells but 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.^1,3,6

Frequency

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.

Mortality/Morbidity

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

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

Age

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

Clinical

History

Historical clues are important in diagnosing enterotoxin-induced gastroenteritis.

• After either gastrointestinal or inhalational exposure, a nonspecific flu-like illness may develop, with symptoms to include myalgias, headache, chills, and fever.
• GI symptoms start within several hours of ingestion of contaminated foods, beginning with significant nausea, vomiting, and intestinal cramping, followed by urgency and profuse watery nonbloody diarrhea. Symptoms normally resolve within 12-24 hours. Multiple family members or patrons of the same eating establishment may be affected.

• The incubation period is 3-12 hours (rarely up to 18 h) after ingestion.
• Classic symptoms are an abrupt onset of intense nausea, vomiting, cramping abdominal pain, and diarrhea, which incapacitate the patient.
• Most cases are self-limited and resolve in 8-24 hours.

Inhalation of staphylococcal enterotoxin B (SEB) does not occur in the natural setting and should be considered a result of an intentional event.^1,8

• After respiratory exposure to aerosolized SEB, the clinician would most likely be presented with numerous patients of all ages within a short period of time (most likely within 1-6 h of an exposure) who were exposed at a common location and developed respiratory difficulty. Because of the difficulties in obtaining large quantities of the toxin and difficulty in efficient dispersion as an open-air aerosol, this location most likely would be an enclosed space, such as a gymnasium, arena, or office building.
• Symptom onset after inhaling SEB may vary from 3-12 hours. Sudden onset of headache, fever, myalgia, nonproductive cough, chills, shortness of breath, and retrosternal pain can be caused by SEB at low doses via inhalation.
• Respiratory symptoms may include dyspnea, nonproductive cough, and retrosternal chest pain. Disease may progress with increasing respiratory distress, hypoxia, and ultimately respiratory failure depending on the degree of systemic inflammation and resulting pulmonary edema.
• Fevers can range from 103º-106ºF and may last up to 5 days. 
• The cough may last up to 4 weeks.
• Vital signs should be followed closely in order to monitor for signs of multiorgan failure.
• Inhalational exposure to higher levels of SEB may lead to septic shock and death.

Physical

Physical examination in staphylococcal enterotoxin B (SEB) intoxication may be unremarkable, but, most likely, the patient presents with complaints of acute onset and either appears in significant abdominal pain or acutely short of breath. Symptoms are of abrupt onset.^3,7

• Gastrointestinal exposure
  • If the route of entry of the toxin is GI, patients may appear dehydrated, depending on the severity of nausea and vomiting, and often complain of acute abdominal cramping and diarrhea.
  • Physical examination may reveal hypotension, tachycardia, hyperperistalsis, and diffuse nonlocalizing abdominal pain. Any stool or diarrhea is hemoglobin negative, barring other pathology.
• Inhalational exposure
  • In inhalation of aerosolized SEB, patients are acutely and significantly short of breath and complain of severe substernal chest pain.  On examination, however, usually reveals clear lung fields with no evidence of consolidation or effusion. Other than a reflexive tachycardia, which is likely to be seen, cardiac examination is normal. 
  • With significant inhalational exposure, the patient may display pulmonary edema or signs and symptoms consistent with acute respiratory distress syndrome (ARDS).
  • Most patients also have a fever up to 103^o -106^o F if significant pulmonary involvement has occurred.

Causes

After toxin is produced in improperly refrigerated, stored, and handled foodstuffs, ingestion of staphylococcal enterotoxin B (SEB) causes food poisoning. Inhalational exposure would most likely be related to a terrorist or biologic warfare event. Case reports have been documented of intranasal exposure secondary to nasal packing after surgical procedures as S aureus does colonize the nasal passages.

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