Ricin and Staphylococcal Enterotoxin B: Potential Biologic Weapons

In 1978, a ricin-filled pellet—which was injected with a spring-loaded device disguised in an umbrella—was used to assassinate Bulgarian defector Georgi Markov. A similar device was employed unsuccessfully against a second defector in the same year.¹

The potential arsenal of biologic weapons is not limited to intact microorganisms, such as Bacillus anthracis, variola virus, and Yersinia pestis. Purified toxins also pose a threat. Here, we focus on ricin and staphylococcal enterotoxin B (SEB) (Table).

RICIN
Ricin is a potentially lethal toxin derived from the beans of the castor plant; cases of accidental intoxication are infrequent. Ricin is purified from castor bean mash, which is a by-product of castor oil production and is approximately 5% ricin by weight. Ricin toxin is a dimeric protein comprising a receptor-binding subunit and an enzymatic subunit that inhibits host cell protein synthesis and ultimately causes cell death. Most cases of accidental poisoning occur in children who ingest castor or related beans. Ricin is very stable and can be lethal by aerosol, enteric, or parenteral routes, although it is the aerosol route that is most hazardous.¹

Clinical manifestations. Experience with human intoxication is limited, but the clinical sequelae are potentially severe, begin within hours, and vary depending on dose and route of exposure. After inhalation of sublethal doses, symptoms include fever, tightness in the chest, cough, dyspnea, nausea, and arthralgias, beginning within 4 to 8 hours. More substantial aerosol exposures in animals lead to pulmonary necrosis and severe edema. Human exposures of this type are expected to cause progressive cough with severe pulmonary inflammation, cyanosis, and pulmonary edema. In animals, death occurs within 36 to 72 hours.¹

GI exposure causes local cytotoxicity with hemorrhage, as well as hepatic, splenic, and renal necrosis. Intramuscular injection of ricin causes severe tissue necrosis of muscle and lymph nodes as well as some distant organ involvement.¹

Diagnosis. A case of ricin toxicity would likely be missed without a high index of suspicion. Look for a rapidly progressing pulmonary syndrome that does not respond to antibiotics. In contrast to anthrax respiratory syndrome, ricin toxicity does not produce mediastinitis. ELISA testing of serum or immunohistochemical analysis of tissue samples can be diagnostic. The chest radiograph may show bilateral infiltrates; other features include hypoxemia and polymorphonuclear leukocytosis.

Therapy. Treatment options currently are limited to supportive care and management of pulmonary edema. GI decontamination is warranted in cases of ricin ingestion.¹

STAPHYLOCOCCAL ENTEROTOXIN B
SEB is most often associated with food-borne outbreaks of GI disease; however, SEB and other staphylococcal enterotoxins are also responsible for some cases of toxic shock syndrome. When present in the respiratory tract, SEB causes significant morbidity. Thus, it may not be surprising that SEB and other staphylococcal enterotoxins have been prepared as a powder for aerosol dispersal by various nations. Inhalation of SEB produces a quite different clinical picture from that produced by ingestion. While exposure of this type would probably not be fatal to most persons, victims would be rapidly incapacitated and some might experience life-threatening symptoms.

Mechanism of action. As a biologic weapon, SEB has the advantages of heat stability, a wide range of biologic activities, and high potency. SEB is a “superantigen,” and as such, belongs to a family of molecules that bind with high affinity to major histocompatibility complex class II receptors of monocytes and macrophages and to the T-cell receptor V βdomain.^2,3 This binding, in turn,production of interleukin-1, tumor necrosis factor α, and interferon- μ, as well as a host of physiologic effects.

Clinical manifestations. Following aerosol exposure to SEB, symptoms begin within 3 to 12 hours, with sudden onset of fever, headache, chills, myalgias, and a nonproductive cough.⁴ Dyspnea and retrosternal chest pain are sometimes evident, and a high-dose exposure can lead to hypotension, shock, multiorgan failure, and death. Toxin deposited in the mouth will be swallowed, leading to nausea, vomiting, and diarrhea. Fever may last for up to 5 days, with or without chills.

Diagnosis. There are usually no significant physical findings with SEB intoxication, although in more severe cases, there may be pulmonary edema with the expected manifestations on chest x-ray films. Laboratory findings are generally nonspecific. Soon after exposure, SEB or its metabolites can be detected in swabbings of the nasal mucosa (by ELISA) and in urine.

Therapy.With supportive care, most patients make a full recovery. Aside from supportive care, there is no widely available specific therapy for SEB toxicity at present; specific immune globulin may ameliorate the disease if given quickly. Efforts to develop a vaccine are under way⁵

REFERENCES:
1. US Army Medical Research Institute for Infectious Diseases. Medical Management of Biological Casualties Handbook. 3rd ed. Frederick, Md: USAMRIID; 1998.
2. Marrack P, Kappler J. The staphylococcal enterotoxins and their relatives. Science. 1990;248:705-711.
3. Schlievert PM. Role of superantigens in human disease. J Infect Dis. 1993;167: 997-1002.
4. Franz DR, Jahrling PB, Friedlander AM, et al. Clinical recognition and management of patients exposed to biological warfare agents. JAMA. 1997;278: 399-411.
5. Lowell GH, Colleton C, Frost D, et al. Immunogenicity and efficacy against lethal aerosol staphylococcal enterotoxin B challenge in monkeys by intramuscular and respiratory delivery of proteosome-toxoid vaccines. Infect Immun. 1996;64:4686-4693.
6. Relman DA, Olson JE. Bioterrorism preparedness: what practitioners need to know. Infect Med. 2001;18:497-514.