Biochemical terrorism

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Chapter 78 Biochemical terrorism

Biochemical terrorism is defined as the use of biological or chemical agents to intimidate, incapacitate or eradicate crops, livestock, civilian and military personnel.¹ It is well suited for attack by poorer nations against the rich, and is known as a poor man’s atom bomb, or asymmetric method of attack. The large scale use of mustard and nerve gases in the Iran/Iraq war,² the dissemination of nerve gas sarin on the Tokyo underground,³ and the discovery by UN inspectors in Iraq of SCUD missiles, rockets and aerial bombs primed with Botulinum and aflatoxins^4,⁵ have highlighted the need for planning.

CHARACTERISTICS OF BIOLOGICAL WEAPONS (TableS 78.1 and 78.2)

Intended target effects are due either to infection with disease-causing micro-organisms and other replicative entities, including viruses, fungi and prions, or to the toxins they elaborate. Their effects depend on the ability to multiply in the person, animal or plant attacked.⁶ Sequelae depend on host factors (state of nutrition, immunocompetence) and environment (sanitation, temperature, humidity, water quality, population density).⁷

Table 78.1 Potential weapons

Biological diseases	Chemical agents
Bacillus anthracis (anthrax)	Blisters/vesicants
Clostridium botulinum toxin (botulism)	Distilled mustard (HD)
Yersinia pestis (plague)	Lewsite (L)
Variola major (smallpox)	Mustard gas (H)
Francisella tularensis (tularaemia)	Nitrogen mustard (HN-2)
Viral haemorrhagic fever	Phosgene oxime (CX)
Coxiella burnetii (Q fever)	Blood
Brucella melitensis (brucellosis)	Arsine (SA)
Burkholderia mallei (glanders)	Cyanogen chloride (CK)
Ricin toxin (Ricinus communis – castor beans)	Hydrogen chloride
Staphylococcus enterotoxin B	Hydrogen cyanide (AC)
Niaph virus	Choking/pulmonary damage
Hantaviruses	Chlorine (CL)
	Nitrogen oxide (NO)
	Phosgene (CG)
	Nerve
	Sarin (GF)
	Soman (GD)
	Tabun (GA)
	VX
	Incapacitating
	LSD
	Cannabinoids

Table 78.2 Criteria for a successful biological weapon ⁶

Assailant

Has methods to treat own forces and population

Target population

Non-immune

Little or no access to immunisation or treatment

Bioweapon

Consistently produces disease/death

Highly contagious or infective in low doses

Short and predictable incubation period

Difficult to identify in target population

Suitable for mass production, storage and weaponisation

Stable during dissemination

Low persistence after delivery

CLASSIFICATION

Although classification of biological weapons can be taxonomy based (e.g. bacterial/viral/fungal), it is also useful to examine particular features such as:

• Infectivity: proportion of persons exposed to a given dose that become infected. This reflects the capability of an agent to enter, survive and replicate

• Virulence: ratio of the number of clinical cases to the number of infected hosts. May differ for strains of the same pathogen.

• Lethality: ability of agent to cause death in an infected population

• Pathogenicity: ratio of number of clinical cases to the number of exposed persons, which reflects the capability of an agent to cause disease

• Incubation period: time elapsing between exposure to the agent and first signs and symptoms of disease

• Contagiousness: number of secondary cases following exposure to a primary case in relation to the total number exposed

• Stability: ability of an agent to survive the environment

Another useful classification system available is that from the Centers for Disease Control and Prevention (CDC) Atlanta:

CATEGORY A

High-priority agents include organisms that pose a risk to national security because they can be easily disseminated or transmitted from person to person. They result in high mortality rates and have the potential for major public health impact, which might cause public panic and social disruption, and require special action for public health preparedness. Examples include anthrax, botulism, plague, smallpox, tularaemia and viral haemorrhagic fevers.

CATEGORY B

Second highest priority agents include those that are moderately easy to disseminate. They result in moderate morbidity rates and low mortality rates, and require specific enhancements of CDC’s diagnostic capacity and enhanced disease surveillance. Examples include brucellosis, salmonella, glanders, melioidosis, psittacosis, Q fever, ricin toxin, typhus, staphylococcal enterotoxin B and viral encephalitis.

ROUTES OF DISSEMINATION

• Inhalational exposure using sprays or aerosols: Optimal particle size for alveolar deposition is 0.6–5 microns. Particles larger than this are filtered by the nose, and smaller particles are exhaled. This can be achieved using aerosol generators mounted on stationary objects or primed onto trucks, cars, boats, cruise missiles and planes. Environmental factors such as wind velocity, cloud cover, rainfall and humidity affect the efficiency of dissemination.⁷

• Cutaneous: Via wounds and mucous membranes.

• Ingestion via food and water: Hand to mouth contact is a suitable vehicle, for example the Rajneeshee cult successfully disseminated Salmonella via salads, infecting 750 people in 1984.

SPECIFIC AGENTS

ANTHRAX

Anthrax ⁸ is an acute infectious zoonosis caused by Bacillus anthracis, a Gram-positive, spore-forming bacillus. The infective dose is 8000–50 000 spores and routes of transmission include inhalation, ingestion and skin contact. Person-to-person transmission does not occur for the pulmonary form but secondary cutaneous lesions may occur after direct exposure to vesicle secretions. As spraying by aircraft is a potential threat to a large city, pulmonary exposure is the most likely route in a mass casualty situation.

CLINICAL FEATURES

BOTULISM

Botulism ⁵ is caused by Clostridium botulinum, an anaerobic Gram-positive bacillus that produces a neurotoxin. Seven forms of the toxin have been identified from A to G, but human botulism is due mainly to strains A, B and E. The neurotoxin contains a zinc protease that acts at the presynaptic terminal of the neuromuscular junction to prevent the fusion of vesicles of acetylcholine with the presynaptic membrane, therefore preventing release of acetylcholine and causing a flaccid paralysis. The LD₅₀ for type A is 0.001 μg/kg.

Routes of exposure are either inhalation or ingestion, and there is an incubation period of 12–36 hours. Person-to-person transmission does not occur.

Clinical features include a responsive patient with no fever. There is a symmetric descending flaccid paralysis in a proximal to distal pattern without a sensory deficit. Cranial neuropathies (mainly bulbar) lead to diplopia, dysphagia, dysphonia and dysarthria. Respiratory dysfunction may occur due to upper-airway obstruction or muscle paralysis. The diagnosis is clinical, and confirmation is with the mouse bioassay in which mice are pretreated with antitoxin and exposed to the patient’s serum. A pentavalent toxoid vaccine is available for prevention, but routine immunisation is not recommended.

TREATMENT

Patients should be monitored with frequent assessment of gag, cough reflexes, inspiratory force and vital capacity. Mechanical ventilation may be protracted, and may be punctuated by nosocomial infections requiring antibiotics.

Aminoglycosides and clindamycin are contraindicated because of their ability to increase blockade.¹² Administration of the trivalent (A, B, E) antitoxin should not be delayed while awaiting confirmation of the diagnosis. This horse serum has < 9% hypersensitivity reactions, and < 2% incidence of anaphylaxis. Skin testing is advisable.¹³ A heptavalent antitoxin is under investigation. Passive administration of neutralising antibody minimises further damage.¹⁴

Treatment of children, pregnant women and immunocompromised patients should be no different; all have received equine antitoxin without short-term sequelae.

Prophylaxis of contacts involves close observation and, at the first sign of illness, treatment with antitoxin, neutralising antibody and administration of the pentavalent toxoid vaccine.

SMALLPOX

Smallpox ¹⁵ is an acute viral illness caused by variola virus (orthopoxvirus). The last documented case was in Somalia in 1977. It is transmitted from person to person via the airborne route. The infective dose is 10–100 virions, with an incubation period of 7–17 days.

In a non-immune society, the impact would be devastating ¹⁶ as the person-to-person spread would be difficult to check, and many countries have very poor health structures with overcrowding in the cities. In addition, the impact of global travel would change the epidemic and allow it to move rapidly from continent to continent.

There are two other major factors that may change the profile of a predicted epidemic: the potential use of new antiviral agents against smallpox and the HIV epidemic. Predictions are difficult.

CLINICAL FEATURES ¹⁷

There is a flu-like prodrome with malaise, fever and headache. There is also a synchronously evolving maculopapular rash forming pustules over the head and extremities; the mouth and pharynx may also be affected. Multiorgan failure commonly complicates smallpox. Diagnosis is clinical with confirmation by identification of brick-shaped virions from vesicular fluid using electron microscopy.

PREVENTION

Routine vaccination with vaccinia virus stopped in 1972. The immune status of vaccinated individuals is unclear, but if a single dose vaccine was administered it is assumed the subject is non-immune. A preventative vaccination programme is currently under review.

TREATMENT

Vaccination within 4 days of exposure.¹⁸ However, complications include:

• post-vaccinial encephalitis

• vaccinia gangrenosa

• eczema vaccinatum

• generalised vaccinia

• inadvertent inoculation

Five groups are considered high risk for these complications. These are pregnancy, HIV infection, chemotherapy, eczema and immune disorders.¹⁹ In these cases, vaccinia immune globulin should be given simultaneously. Other treatments include:

• supportive care with isolation

• antibiotics for secondary bacterial infections

• cidofovir, a nucleoside DNA polymerase inhibitor, is under investigation but needs to be given i.v. and causes renal toxicity.²⁰

PLAGUE

Plague ²¹ is an acute bacterial disease caused by the Gram-negative Yersinia pestis, from the enterobacter species.²² Although usually transmitted by fleas causing bubonic and septicaemic plague, a bioterrorist event is likely to be airborne resulting in pneumonic plague. The infective dose is < 100 organisms, and has an incubation period of 2–3 days. It is unlikely that spread would be person to person.

Plague presents with fever, haemoptysis, chest pain and dyspnoea. Gram-negative rods are found in mucopurulent sputum, and on Wright’s, Giemsa or Wayson stain appear as bipolar rods with a safety pin appearance. The diagnosis can be confirmed on blood culture, and with fluorescent antibody testing. There is radiographic evidence of bronchopneumonia, and multi organ failure soon develops. Until 72 hours of antibiotic therapy have been completed, plague is communicable.

A formalin-killed vaccine exists but is ineffective and unavailable. Post exposure immunisation has no benefit.

TREATMENT ²¹

Once the diagnosis is considered, isolation and universal precautions should be instituted. Historically, streptomycin (1 g b.d. i.m.) reduced mortality to 5%, and gentamicin (5 mg/kg per day) has also been used successfully. Tetracycline and doxycycline (100 mg b.d.) have been used, but in Madagascar 13% of strains were resistant to doxycycline. Animal studies have demonstrated efficacy of fluoroquinolones including ciprofloxacin (400 mg b.d.), ofloxacin and levofloxacin. No human trials exist so far. Chloramphenicol (25 mg/kg q.i.d.) is recommended for plague meningitis.

CHARACTERISTICS OF CHEMICAL AGENTS

The North Atlantic Treaty Organization definition of a chemical agent is a ‘chemical substance which is intended for use in military operations to kill, seriously injure, or incapacitate people because of its physiological effects’.² In addition to physiological effects, these agents promote psychological warfare.²³

ROUTES OF DISSEMINATION

The principal hazard is inhalation of liquid, vapour, or droplets (0.6–5 microns). Delivery may be by artillery shells, missiles or aerial bombing. In the Tokyo subway attack in 1995, terrorists left plastic bags on the subway filled with sarin after piercing them with umbrella tips. There were 3796 casualties and 12 deaths.³

Toxicity depends on the concentration and time of exposure, is measured in units of concentration and time (mg/min m³), known as the Haber product.⁷ Most chemical agents are designed to penetrate the skin, respiratory epithelium and cornea, unlike biological agents. Penetration is promoted by thinner, more vascular, moister, hairy skin, and by high humidity, spills and aerosols.

RICIN

Ricin is one of the most toxic biological agents known – a Category B bioterrorism agent and a Schedule number 1 chemical warfare agent. Ricin toxin can be extracted from castor beans, purified and treated to form a pellet, a white powder, or dissolved in water or weak acid to be released as a liquid. It is stable under ambient conditions. Particles of < 5 microns have been used for aerosol dispersion in animal studies. Ricin particles can remain suspended in undisturbed air for several hours, and resuspension of settled ricin from disturbed surfaces also may occur.

TRANSMISSION

Ricin would need to be dispersed in particles smaller than 5 microns to be used as an effective weapon by the airborne route. It is very difficult to prepare particles of this size. Routes of exposure include inhalation, parenteral (injection) ingestion, dermal contact (exposure risk is low, except where absorption is through non-intact skin or via a solvent carrier) or ocular contact. Although ricin may adhere to skin, person-to-person transmission through casual contact has not been reported. Despite the fact that ricin may adhere to clothing or be present on surfaces, there is low potential for transmission via contact with contaminated clothing or contaminated surfaces.

RISK GROUPS

• There is worldwide distribution of castor plants. Ricin is produced when castor oil is made from castor beans, but the general public is not considered at risk for exposure

• Persons in or around castor oil processing plants. However, it would take a deliberate act to make ricin and use it as a poison

• Persons in the dispersal area of a ricin aerosol release

• Persons who are victims of parenteral injection with ricin

• Persons who ingest castor beans, or food or water contaminated with ricin

• It is not known whether certain populations are more vulnerable to the health effects of ricin exposure (e.g. children, pregnant women, the elderly, those with immunosuppression, or underlying respiratory or gastrointestinal tract disease); however, persons with pre-existing tissue irritation or damage who are exposed to ricin may sustain further injury and greater absorption of ricin toxin

PATHOGENESIS

• Ricin is a toxalbumin, a biological toxin whose mechanism of action is inhibition of protein synthesis in eukaryotic cells; cell death results from the absence of proteins

• The effects of ricin poisoning depend upon the amount of ricin exposure, the route of exposure and the person’s premorbid condition

• Ingestion and mastication of three to six castor beans is the estimated fatal dose in adults. The fatal dose in children is not known, but is likely to be less

• Most cases of castor bean ingestion do not result in poisoning: ricin release requires mastication, and the degree of mastication is likely to be important in determining the extent of poisoning. Ricin is not as well absorbed through the gastrointestinal tract when compared to injection or inhalation

• Inhalation or injection of ricin would be expected to lead to a more rapid onset of symptoms of ricin poisoning and to a more rapid progression of poisoning compared to ingestion, given the same exposure amount

Data on inhalational exposure to ricin in humans are extremely limited, and systemic toxicity has not been described. Animal studies suggest that inhalation is one of the most lethal forms of ricin poisoning. Following severe ricin poisoning, damage to vital organs may be permanent or have lasting effects. No long-term effects are known to exist from ricin exposure that did not result in symptoms.

LABORATORY DIAGNOSIS

Non-specific laboratory findings in ricin poisoning include:

• metabolic acidosis

• impaired liver and renal function tests

• hematuria

• leukocytosis (two- to five-fold higher than normal value)

The presence of leukocytosis and/or abnormal liver and renal function tests may suggest ricin-associated illness in the correct clinical context but are not very specific. There are no specific clinically validated assays for detection of ricin that can be performed by the hospital/health care facility clinical laboratory, and no methods are available for the detection of ricin in biological fluids. However, tests for ricinine, an alkaloidal component of the castor bean plant, are being developed. The potential uses of tests for either ricin or ricinine in human biological samples would primarily be for purposes of confirming exposure or assessing the prevalence of exposure rather than diagnostic use.

Testing for ricin in environmental samples will most likely not be immediately available to assist in clinical decision-making. However, they may document the potential for exposure or affirm the exposure circumstances.

LABORATORY TESTING

Tests performed on ricin-suspicious samples include:

• time-resolved fluorescence immunoassay: antibody binds to ricin

• polymerase chain reaction: locates and makes copies of parts of the DNA contained in the castor bean plant. The search specifically identifies the DNA of the gene that produces the ricin protein

TREATMENT

As no antidote exists for ricin, exposure must be avoided if possible. Otherwise, all efforts must be directed to minimising exposure through decontamination. Supportive care is, in part, dictated by the route of exposure: inhalation, ingestion, skin or eye exposure, and includes measures such as ventilation, i.v. fluids, and treatment of seizure or hypotension.

SARIN

Sarin (C₄H₁₀FO₂P, isopropylmethylphosphofluoridate) is a colourless and odourless liquid at room temperature. It is volatile and incompatible with metals or concrete, which lead to production of hydrogen gas. Hydrolysis of sarin forms acids. It is thermally stable < 49°C, but clings to clothing and releases slowly for 30 minutes. Toxicity is through inhibition of the enzyme acetylcholinesterase.

The route of exposure determines which clinical features (Table 78.4) appear first.²⁴ Post inhalation respiratory and eye symptoms appear, whereas post cutaneous exposure diaphoresis and muscle fasciculation occur. Immediate first aid is to remove the patient from the area of danger to a well-ventilated area before removal of clothing and decontamination of the skin. This can be achieved using mists of water, or dilute sodium hypochlorite. Eyes are irrigated with water or normal saline.

Table 78.4 Sarin toxicity

Mild	Rhinorrhitis
	Dyspnoea
	Miosis
	Blurred vision
Moderate	Diaphoresis
	Drooling
	Bronchospasm
	Nausea, vomiting, cramps
	Weakness
	Twitching
	Headache
	Confusion
Severe	Involuntary defecation/urination
	Convulsions
	Respiratory arrest
	Coma, death

Assessment follows airway, breathing and circulation. Patients with compromised airways, due either to direct effects or secondary to reduced level of consciousness, require intubation and positive-pressure ventilation. Aggressive suctioning may be needed for bronchial secretions.

TREATMENT

• Anticholinergics to antagonise the muscarinic effects, usually i.v. atropine in 2 mg doses, every 3–5 minutes, until the patient is atropinised. It may need to be continued for 24 hours at 2 mg/h²

• Oximes to reactivate the anticholinesterase enzyme at nicotinic sites, e.g. pralidoxime mesilate 30 mg/kg by slow i.v. injection, up to 2–4 g. This should be prompt, as dealkylation of the inhibited enzyme renders it resistant to reactivation

• Prophylactic anticonvulsants to prevent seizures. Diazepam 5 mg by any route has been shown to reduce morbidity in animal studies

MUSTARD GAS

Mustard gas (C₄H₈Cl₂S, Bis-(2-Chloroethyl) sulphide) is a yellow oily liquid at room temperature. It has a faint garlic odour and evaporates to form a vapour that penetrates clothing. Although mortality is low, poisoning tends to incapacitate. It is a bifunctional alkylating agent that is carcinogenic (oral cavity, larynx, bronchus), and irritates skin and mucosa (Table 78.5). Mustard gas is also myelotoxic (pancytopenia) and teratogenic. Assessment is similar to sarin.²⁵

Table 78.5 Features of mustard gas toxicity

Eyes	Lacrimation, conjunctivitis, photophobia
Skin	Erythema, blistering, partial to full-thickness burns
Respiratory tract	Rhinorrhoea, tracheobronchitis, bronchopneumonia
Systemic	Nausea, vomiting, diarrhoea, bradycardia, hypotension

TREATMENT

Patients with large burns are resuscitated as any other burn; however, fluid losses are transudates, so protein losses are less.²⁶ Pain control is important and frequently requires analgesics, such as morphine. Tense blisters are dressed with silver sulfadiazine. Mustard burns take at least 12 weeks to heal, but early excision and grafting does not reduce healing time.^27,²⁸ Eye lesions usually heal in 2 weeks, and are aided by topical antibiotics and saline irrigation. Oxygen, antibiotics for secondary pneumonia, physiotherapy and ventilation are the mainstays of treatment for respiratory effects.

REFERENCES

1 Spencer R, Wilcox M. Agents of biological warfare. Rev Med Microbiol. 1993;4:138-143.

2 Evison D, Hinsley D, Rice P. Chemical weapons. BMJ. 2002;324:332-335.

3 KB O. Aum Shinrikyo: once and future threat? Emerg Infect Dis. 1999;5:513-516.

4 Zilinskas R. Iraq’s biological weapons: the past as future? JAMA. 1997;278:418-424.

5 Arnon SS, Schechter R, Inglesby TV, et al. Botulinum toxin as a biological weapon. Medical and Public Health Management. JAMA. 2001;285:1059-1070.

6 Beeching NJ, Dance DA, Miller AR, et al. Biological warfare and bioterrorism. BMJ. 2002;324:336-339.

7 WHO. Health Aspects of Chemical and Biological Weapons. Geneva: WHO, 2001;2.

8 Inglesby TV, Henderson DA, Bartlett JG, et al. Anthrax as a biological weapon. Concensus statement. JAMA. 1999;281:1735-1745.

9 Meselson M, Guillemin J, Hugh-Jones M, et al. The Sverdlovsk anthrax outbreak of 1979. Science. 1994;266:1202-1207.

10 Swartz M. Recognition and management of anthrax – an update. N Engl J Med. 2001;345:1621-1626.

11 English JF. Overview of bioterrorism readiness plan: a template for health care facilities. Am J Infect Control. 1999;27:468-469.