What are the Potential BW and How are They Classified ?

Microorganisms and toxins used in bioterrorism and biological warfare have been placed in three different categories by the United States’ Centers for Disease Control and Prevention (CDC) based on various characteristics of the microorganisms. All the agents in these categories are called “Select Agents”. Select agents are biological agents/toxins considered to be a threat to the public, animal or plant health, or to animal or plant products (47).

BW are placed in one of three categories: categories A, B, and C. Microorganisms in category A are the most dangerous posing a threat to a nation's security and are called High Priority agents. Microorganisms in category B are less dangerous (Second Highest Priority agents) and microorganisms in category C (Third Highest Priority agents) are potentially dangerous microorganisms (47).

Category A BW have been the most frequently utilized of all the BW. The criteria for placing a microorganism in Category A are as follows. They pose a threat to national security because they:

can be easily disseminated or transmitted from person-to-person;
result in high mortality rates and have the potential for major public health impact;
might cause public panic and social disruption;
require special action for public health preparedness.

The diseases caused by (biological agents) on the A list are the following:

Anthrax (Bacillus anthracis)
Botulism (Clostridium botulinum toxin)
Plague (Yersinia pestis)
Smallpox (Variola major)
Tularemia (Francisella tularensis)
Viral hemorrhagic fevers (filoviruses [e.g., Ebola, Marburg] and arenaviruses [e.g., Lassa, Machupo])

Table 2: General Characteristics of Category A Biological Weapons (55, 56)

Disease	Transmit Person to Person	Infective Dose (Aerosol)	Incubation Period	Duration of Illness	Lethality	Persistence of Organism or Toxin in Environment	Chemotherapy	Vaccine
			Disease				Chemoprophylaxis*
Anthrax; bacterial; Bacillus anthracis	No	2,500-55,000 spores	1-6 days	3-5 days (usually fatal if untreated)	High (100% if untreated)	Very stable - spores remain viable for > 40 years	Ciprofloxacin; doxycycline or penicillin	Yes
			Pneumonia				Ciprofloxacin or Doxycycline
Botulinum toxin; bacterial toxin; Clostridium botulinum	No	0.001mg/kg is LD₅₀** for type A toxin	1-5 days	Death in 24-72 hours; lasts months if not lethal	70% without respiratory support; 6% with respiratory support	For weeks in still water and in food	Trivalent antitoxin for serotypes A, B, E toxins	Yes
			Muscle paralysis; Respiratory failure				None
Plague; bacterial; Yersinia pestis	Yes: Highly contagious	100-500 organisms	2-3 days	1-6 days (usually fatal)	70% unless treated within 12-24 hours	For up to 1 year in soil; 270 days in live tissue	Streptomycin, doxycycline or chloramphenicol	No
			Pneumonia				Tetracycline or doxycycline
Smallpox; viral; Variola virus	Yes: Highly contagious	Assumed low (10-100 virus particles)	7-17 days (ave. 12 days)	4 weeks	High to moderate (30%)	Relatively unstable	Cidofovir (efficacy unknown)	Yes
			Skin Rash				Vaccinia immune globulin (give within 3 days of exposure)
Tularemia; bacterial; Francisella tularensis	No	10-50 organisms	2-10 days (ave. 3-5)	> 2 weeks	30% if untreated	For months in moist soil or other media	Streptomycin, or gentamicin	No
			Pneumonia				Tetracycline or doxycycline
Viral Hemorrhagic Fevers; many different viruses (see table 5)	Yes: Moderately contagious	1-10 organisms	4-21 days	Death between 7-16 days	High for Ebola and Marburg viruses (60-90%)	Relatively unstable	Supportive therapy. Antisera are available for some of the viruses	Only one vaccine against: Yellow fever virus.
			Causes damage to blood vessels; hemorrhage				None

*Chemoprophylaxis= use of an antimicrobial agent to prevent disease development after exposure. **LD₅₀= dose that will kill 50% of people.

The criteria for placing agents in Category B are:

moderately easy to disseminate;
result in moderate morbidity rates and low mortality rates;
and require specific enhancements of CDC's diagnostic capacity and enhanced disease surveillance.

Table 3: General Characteristics of Category B Biological Weapons (55, 56)

Disease	Transmit Person to Person	Infective Dose (Aerosol)	Incubation Period	Duration of Illness	Lethality	Persistence of Organism or Toxin in Environment	Chemotherapy	Vaccine
			Disease				Chemopropylaxis
Brucellosis	No	10-100 organisms	5-60 days	Months or years if not treated	Low	Very stable	Doxycycline or rifampin	None
			Fever, tired, headache				Doxycycline or rifampin
Epsilon toxin; bacterial toxin; Clostridium perfringens	No	Not known in humans; 1.6 ug/kg for mice is the minimal lethal dose	8-12 hours	1-2 days	Low	Unknown	None	None
			Severe diarrhea, abdominal cramps and bloating				None
Food safety threats; bacterial; Salmonella, Escherichia coli O157:H7, Shigella	Yes	Salmonella about 1 million organisms, Escherichia coli, and Shigella around 10 organisms	Salmonella, Escherichia coli, and Shigella-12-72 hrs	Salmonella, Escherichia coli, and Shigella= 5-8 days	Low	Very stable in soil and water	Salmonella = None Shigella= ampicillin, trimethoprim/sulfamethoxazole nalidixic acid, or ciprofloxacin. Escherichia coli= None	None
			Diarrhea, abdominal pain, fever (little or no fever with E.coli) Shigella= bloody diarrhea				None
Glanders; bacterial; Burkholderia mallei	Yes	Assumed low	10-14 days by aerosol	Death in 7-10 days if it gets in bloodstream	High 90%	Unstable	Ceftazidime and trimethoprim/sulfamethoxazole	None
			Pneumonia and bloodstream infections				None
Melioidosis; Whitmore disease; bacterial; Burkholderia pseudomallei	Rare	Assumed low	10-14 days by aerosol	Death in 7-10 days if it gets in bloodstream	High 90%	Very stable	Ceftazidime and trimethoprim/sulfamethoxazole	None
			Pneumonia and bloodstream infections				None
Psittacosis; bacterial; Chlamydia psittaci	Rare	Unknown	5-14 days	6 weeks	15-20% without treatment	Unstable	Tetracycline or doxycycline	None
			Flu-like symptoms and pneumonia				None
Q fever; bacterial; Coxiella burnetii	Extremely rare	1 organism	18-21 days	Months if it becomes a chronic infection: endocarditis or hepatitis	<1%	Months in dust and feces	Doxycycline or chloramphenicol	None
			Flu-like symptoms then high fever and pneumonia				None
Ricin toxin; plant; Ricinus communis (castor bean)	No	3-5 ug/kg is an LD₅₀ in mice	18-24 hrs	Days	High	Stable	None	None
			difficulty breathing, fever, cough, nausea, and tightness in the chest within a few hours				None

Table 3: General Characteristics of Category B Biological Weapons Continued (55, 56)

Disease Disease	Transmit Person to Person	Infective Dose (Aerosol)	Incubation Period	Duration of Illness	Lethality	Persistence of Organism or Toxin in Environment	Chemotherapy
			Disease				Chemo-prophylaxis
Staphylococcal enterotoxin B; toxin; bacterial; Staphylococcus aureus	No	0.03 ug can incapacitate a person; 1.7 ug is lethal	1-6 hrs after inhalation	Hours	<1%	Resistant to freezing	Ventilatory support and supportive care
			fever, chills, headache, muscle aches, and dry cough				None
Typhus fever; bacterial; Rickettsia prowazekii	No	< 10 organisms	8 days	Weeks; treatment failures can result in chronic recurring disease called Brill-Zinsser disease	20% untreated	Long periods of time in rodents; unstable	Tetracycline, doxycycline or chloram-phenicol
			Fever, headache, rash				None
Viral encephalitis; viral; Venezuelan equine encephalitis VEE, eastern equine encephalitis EEE, western equine encephalitis WEE	No	10-100 organisms	VEE, 2-6 days, EEE/WEE, 7-14 days	1-2 Weeks	1%	Unstable	Supportive therapy, analgesics, anti-convulsants
			Fever, headache, vomiting, altered states of consciencess				None
Water safety threats; bacterial; Cholera; Vibrio cholerae, Parasite; Cryptosporidium parvum	Vibrio; No Crypto; No	Vibrio cholerae; 10⁶-10¹¹; Crypto; 200-300 organisms	Vibrio; 2-3 days. Crypto; 7 days	Vibrio; can last 3-4 days. Crypto; 2-4 days; immuno-compromised host months to years to rest of their lives.	Vibrio; 50%	Vibrio; Dust - 3 to 16 days; feces - up to 50 days; glass - up to 30 days; metal coins - 7 days; finger tip - 1 to 2 hours; soil - 16 days; survives well in waters. Crypto; 2-6 months in moist environment.	Vibrio; Tetracycline and plenty of fluids Crypto; spiramycin
			Vibrio; severe diarrhea and vomiting Crypto; chronic diarrhea				Vibrio; Tetracycline. Crypto; None

Category C includes emerging pathogens that could be engineered for mass dissemination in the future because of:

availability;
ease of production and dissemination;
and potential for high morbidity and mortality rates and major health impact.

Table 4: General Characteristics of Category C Biological Weapons (55, 56)

Disease Disease	Transmit Person to Person	Infective Dose (Aerosol)	Incubation Period	Duration of Illness	Lethality	Persistence of Organism or Toxin in Environment	Chemotherapy	Vaccine
			Disease				Chemo-prophylaxis
Nipah virus	Unlikely	Unknown	Unknown	6-10 days	40%	Unknown	None	None
			Infection of brain; fever, headache, vomiting, dizziness, altered states of consciousness.				None
Hantaviruses	Rare	Unknown	14-30 days	Weeks	HFRS; 5-15% HPS; 40-50%	A few days.	Ribavirin for HFRS; None for HPS	None
			Hemorrhagic fever with kidney damage (HFRS); Hantavirus pulmonary syndrome (HPS); Fluid floods lungs				None
Tickborne hemorrhagic fever viruses; Crimean-Congo hemorrhagic fever virus	No	10-100 organisms	6-13 days	10-14 days	30%	Unstable	Ribavirin	None
			Headache, chills, fever, vomiting and pain in muscle, skin rash				None
Tickborne encephalitis viruses	No	10-100 organisms	7-14 days	4-5 days; If the brain and meninges is affected then disease lasts 3-4 weeks.	1-2%	Unstable	None	Yes; but not available in the U.S.
			Fever, malaise, anorexia, muscle aches, headache, nausea, and/or vomiting, well period followed by damage to meninges and/or brain				None
Yellow fever virus	No	10-100 organisms	3-6 days	7-10 days	<5%	No	No	Yes
			Fever, aches, prostration, nausea, vomiting; weakened pulse, jaundice				No
Multidrug-resistant Mycobacterium tuberculosis	Yes	10 organisms	4-12 weeks	Weeks to months; can reactivate years later.	12%	45-70 days	isoniazid; streptomycin; rifampin; ethambutol; kanamycin; ethionamide; capreomycin; p-aminosalicylic acid, ofloxacin, cycloserine- May require up to 4 drugs to treat and still have treatment failure.	Yes
			Pneumonia				None

As you can see there are many possible microorganisms that could be considered significant threats. Even with such a long list it still helps to have some idea of what biological agents are more likely to be utilized. Knowing the disease manifestations associated with these microorganisms also helps health officials to detect and identify the BW attack earlier.

The emergency room physician caring for the Robert Stevens the photo-editor from “The Sun” tabloid realized something strange was happening when he saw a Gram-positive rod shaped (a purple stick shaped bacterium; Figure 1) bacterium (Bacillus anthracis) in the fluid surrounding the patient's brain (cerebrospinal fluid). Gram-positive rod-shaped bacteria do not normally infect an immunocompetent adult's brain unless they have anthrax. Knowledge in this case helped the physician alert public health officials earlier which may have saved many others exposed to the bacterium.

Some feel the response was still too slow however; inhalation anthrax is a very rare disease in the U.S. Only 18 cases of inhalational anthraxwere reported in the United States from 1900 to 1976 (57). As a result, training of physicians before 2001 mentioned little about anthrax and BW. Following the 2001 anthrax-containing letter attacks more medical schools are placing material on biological warfare and BW in their curricula.

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Neal Chamberlain, Ph.D. A. T. Still University of Health Sciences/Kirksville College of Osteopathic Medicine.

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