Staphylococcal Enterotoxin B, Bioterrorism


Latent period of 3 to 12 hours after aerosol exposure is followed by sudden onset of:

  • Fever.

  • Chills.

  • Headache.

  • Myalgia.

  • Nonproductive cough.

Some patients may develop:

  • Shortness of breath .

  • Chest pain.

Patients tend to plateau rapidly to a fairly stable clinical state. Fever may last 2 to 5 days, and cough may persist for up to 4 weeks. Patients may also present with nausea, vomiting, and diarrhea if they swallow the toxin. Presumably, higher exposure can lead to septic shock and death.


Diagnosis is clinical. Patients present with a temperature producing respiratory syndrome without X-ray changes. Large numbers of patients presenting in a short period of time with typical symptoms and signs of SEB pulmonary exposure would suggest an intentional attack with this toxin.


There is no specific antidote. Treatment is limited to supportive care. Artificial ventilation might be needed for very severe cases, and attention to fluid management is important.


The only defense is to prevent exposure by wearing a protective mask and clothing. There is currently no human vaccine available to prevent SEB intoxication.


Standard precautions are recommended for healthcare workers. SEB is not dermally active and secondary aerosols are not a hazard from patients. Decontaminate with soap and water. Destroy any food that may have been contaminated.


Staphylococcus aureus produces a number of exotoxins, one of which is Staphylococcal enterotoxin B, or SEB. Such toxins are referred to as exotoxins since they are excreted from the organism, and since they normally exert their effects on the intestines they are called enterotoxins. SEB is one of the pyrogenic toxins that commonly causes food poisoning in humans after the toxin is produced in improperly handled foodstuffs and subsequently ingested. SEB has a very broad spectrum of biological activity. This toxin causes a markedly different clinical syndrome when inhaled than it characteristically produces when ingested. Significant morbidity is produced in individuals who are exposed to SEB by either portal of entry to the body.


SEB is the second most common source of outbreaks of food poisoning. Often these outbreaks occur in a setting such as a church picnic or other community event, due to common source exposure in which contaminated food is consumed. Although an aerosolized SEB toxin weapon would not likely produce significant mortality, it could render 80 percent or more of exposed personnel clinically ill and unable to perform their mission for 1-2 weeks. The demand on the medical and logistical systems could be overwhelming. For these reasons, SEB was one of the 7 biological agents stockpiled by the U.S. during its old bioweapons program, which was terminated in 1969.


Staphylococcal enterotoxins are proteins of 23-29 kd molecular weight (SEB is 28,494). They are extracellular products of coagulase-positive staphylococci. Up to 50% of clinical isolates of S. aureus produce exotoxins. They are produced in culture media and also in foods when there is overgrowth of the staph organisms. Related toxins include toxic shock syndrome toxin-1 (TSST-1) and exfoliative toxins. SEB is one of at least 7 antigenically distinct enterotoxins that have been identified. These toxins are moderately stable; SEB is inactivated after a few minutes at 100OC. SEB causes symptoms when inhaled at very low doses in humans: a dose of several logs lower (at least 100 times less) than the lethal dose by the inhaled route would be sufficient to incapacitate 50 percent of those exposed. This toxin could also be used to sabotage food or small volume water supplies.


Staphylococcal enterotoxins belong to a class of potent immune stimulants known as bacterial superantigens. Superantigens bind to monocytes at major histocompatibility complex type 2 receptors rather than the usual antigen binding receptors. This leads to the direct stimulation of large populations of T-helper cells while bypassing the usual antigen processing and presentation. This induces a brisk cascade of pro-inflammatory cytokines (such as tumor necrosis factor, interferon, interleukin-1 and interleukin-2), with recruitment of other immune effector cells, and relatively deficient activation of counter-regulatory negative feedback loops. This results in an intense inflammatory response that injures host tissues. Released cytokines are thought to mediate many of the toxic effects of SEB.


Symptoms of SEB intoxication begin after a latent period of 3-12 hours after inhalation, or 4-10 hours after ingestion. Symptoms include nonspecific flu-like symptoms (fever, chills, headache, myalgias), and specific features dependent on the route of exposure. Oral exposure results in predominantly gastrointestinal symptoms: nausea, vomiting, and diarrhea. Inhalation exposures produce predominantly respiratory symptoms: nonproductive cough, retrosternal chest pain, and dyspnea. GI symptoms may accompany respiratory exposure due to inadvertent swallowing of the toxin after normal mucocilliary clearance.

Respiratory pathology is due to the activation of pro-inflammatory cytokine cascades in the lungs, leading to pulmonary capillary leak and pulmonary edema. Severe cases may result in acute pulmonary edema and respiratory failure.

The fever may last up to 5 days and range from 103 to 106 degrees F, with variable degrees of chills and prostration. The cough may persist up to four weeks, and patients may not be able to return to duty for two weeks.

Physical examination in patients with SEB intoxication is often unremarkable. Conjunctival injection may be present, and postural hypotension may develop due to fluid losses. Chest examination is unremarkable except in the unusual case where pulmonary edema develops. The chest X-ray is also generally normal, but in severe cases increased interstitial markings, atelectasis, and possibly overt pulmonary edema or an ARDS picture may develop.


Diagnosis of SEB intoxication is based on clinical and epidemiologic features. Because the symptoms of SEB intoxication may be similar to several respiratory pathogens such as influenza, adenovirus, and mycoplasma, the diagnosis may initially be unclear. All of these might present with fever, nonproductive cough, myalgia, and headache. SEB attack would cause cases to present in large numbers over a very short period of time, probably within a single 24-hour period. Naturally occurring pneumonias or influenza would involve patients presenting over a more prolonged interval of time. Naturally occurring staphylococcal food poisoning cases would not present with pulmonary symptoms. SEB intoxication tends to plateau rapidly to a fairly stable clinical state, whereas inhalational anthrax, tularemia pneumonia, or pneumonic plague would all continue to progress if left untreated. Tularemia and plague, as well as Q fever, would be associated with infiltrates on chest radiographs. Other diseases, including Hantavirus pulmonary syndrome, Chlamydia pneumonia, and CW agent inhalation (mustard, phosgene), should also be considered.

Laboratory confirmation of SEB intoxication includes antigen detection (ELISA, ECL) on environmental and clinical samples, and gene amplification (PCR - to detect Staphylococcal genes) on environmental samples. SEB may not be detectable in the serum by the time symptoms occur; regardless, a serum specimen should be drawn as early as possible after exposure. Data from rabbit studies clearly show that the presence of SEB in the serum is transient; however, it accumulates in the urine and can be detected for several hours post exposure. Therefore, urine samples should also be obtained and tested for SEB. Respiratory secretions and nasal swabs may demonstrate the toxin early (within 24 hours of exposure). Because most patients will develop a significant antibody response to the toxin, acute and convalescent sera should be drawn for retrospective diagnosis. Nonspecific findings include a neutrophilic leukocytosis, an elevated erythrocyte sedimentation rate, and chest X-ray abnormalities consistent with pulmonary edema.


Currently, therapy is limited to supportive care. Close attention to oxygenation and hydration is important, and in severe cases with pulmonary edema, ventilation with positive end expiratory pressure, vasopressors and diuretics might be necessary. The value of steroids is unknown. Most patients would be expected to do quite well after the initial acute phase of their illness, but generally would be unfit for duty for one to two weeks. Severe cases risk death from pulmonary edema and respiratory failure.


Although there is currently no human vaccine for immunization against SEB intoxication, several vaccine candidates are in development. Preliminary animal studies have been encouraging. A vaccine candidate is nearing transition to advanced development for safety and immunogenicity testing in man. Experimentally, passive immunotherapy can reduce mortality in animals, but only when given within 4-8 hours after inhaling SEB. Because of the rapidity of SEB's binding with MHC receptors (less than 5 min. in vitro) active immunization is considered the most practical defense. Interestingly, most people have detectable antibody titers to SEB and SEC1, however, immunity acquired through natural exposure to SEB does not provide complete protection from an aerosol challenge (although it may reduce the emetic effect).

Most of this information is courtesy of US Government CDC. In times of an emergency much of this material may not apply when it comes to specialized care and testing. These are guidelines to help you when that care is not available. Some of this information is very technical and difficult to understand, but hopefully someone will be available for help in treatment and understanding.