BIOLOGICAL TERRORISM PREPAREDNESS AND RESPONSE

Biological terrorism involves the use of a microorganism (or a toxin derived from it) that causes disease in persons, plants, or animals or causes the deterioration of material (DOD, 2021). These pathogens may be bacteria, fungi, toxins, parasites, protozoans, or viruses. They can be naturally occurring, and/or they may be altered in a laboratory to increase their resistance to antibiotics or their ability to spread in the environment.

Biological weapons are a common choice for terrorist organizations due to their ease of being deployed, the devastating effects they cause, and how inexpensive they are to produce. There is, however, an unpredictability in that these weapons may affect the intended victims and, inadvertently, the perpetrators (Rathish et al., 2021).

Mode of Transmission

Biological agents can be very difficult to detect, and many do not cause illness for several hours or even days. These agents are most likely to be dispersed as aerosols so as to spread among large populations more easily. Some, however, are spread from person to person or by vectors, ingestion, direct contact, or other methods. Water systems are rarely a target; however, water systems have received threats, and because the possibility exists that these threats could be carried out, they must be taken seriously.

While the standard chain of infection applies to diseases caused by exposure to a pathogen, the obvious difference is the mode of transmission link when it is used as a weapon.

• Naturally occurring disease is almost always spread unintentionally. In many cases, it occurs as part of carrying out normal daily activities, with a contaminated hand or uncovered sneeze passing on the infectious agent.
• Intentional spread indicates biological terrorism.
  (Rathish et al., 2021; Hayoun & King, 2021)

Bioweapon Classification Categories

The CDC has separated bioterrorism agents into three categories, depending on how easily they can be spread and the severity of illness or death they cause. Factors that contribute to these categories include:

• Ability to have a profound impact on health
• Ability to cause health fears
• Potential for spread
• Availability of protective vaccines or antimicrobial agents
• Secondary transmission potential
• Public health preparedness

CATEGORY A

These high-priority agents include organisms that pose the highest risk to the public and national security because they:

• Can be easily disseminated or transmitted from person to person
• Result in high mortality rates and have the potential for a major public health impact
• Might cause public panic and social disruption
• Require special action for public health preparedness

Category A agents and diseases include:

• Anthrax (Bacillus anthracis)
• Botulism (Clostridium botulinum toxin)
• Plague (Yersinia pestis)
• Smallpox (variola major)
• Tularemia (Francisella tularensis)
• Viral hemorrhagic fevers, including filoviruses (Ebola, Marburg) and arenaviruses (Lassa, Machupo)
  (CDC, 2020a)

CATEGORY B

Second highest priority agents include those that:

• Are moderately easy to disseminate
• Result in moderate morbidity rates and low mortality rates
• Require specific enhancements of CDC’s diagnostic capacity and enhanced disease surveillance

Category B agents/diseases include:

• Brucellosis (Brucella species)
• Epsilon toxin of Clostridium perfringens
• Food safety threats (Salmonella species, Escherichia coli O157:H7, Shigella)
• Glanders (Burkholderia mallei)
• Melioidosis (Burkholderia pseudomallei)
• Psittacosis (Chlamydia psittaci)
• Q fever (Coxiella burnetii)
• Ricin toxin from Ricinus communis (castor beans)
• Abrin toxin from jequirity (rosary) peas
• Staphylococcal enterotoxin B
• Typhus fever (Rickettsia prowazekii)
• Viral encephalitis (alphaviruses, such as eastern equine encephalitis, Venezuelan equine encephalitis, and western equine encephalitis)
• Water safety threats (Vibrio cholerae, Cryptosporidium parvum)
  (CDC, 2020a)

CATEGORY C

Third highest priority agents include emerging pathogens that could be engineered for mass dissemination in the future because of:

• Availability
• Ease of production and dissemination
• Potential for high morbidity and mortality rates and major health impact

Category C agents/diseases include:

• Emerging infectious diseases such as Nipah virus and hantavirus
  (CDC, 2020a)

Category A Diseases with Potential for Use as Bioweapons

ANTHRAX

Bacillus anthracis is a spore-forming organism, with the spores being the infectious element. In its natural state, it is present in the soil, where it may be ingested by grazing animals. It can be transmitted to humans by handling or ingesting contaminated animals, animal products, or soil. Unless exposure is due to an intentional release, anthrax infections are very rare. There are two types of anthrax: inhalation and cutaneous.

Inhalation Anthrax

Inhalation anthrax is considered to be the deadliest form of the disease. Infection usually develops within a week following exposure but can take up to two months. Without treatment, inhalation anthrax is almost always fatal. However, if treated aggressively, about 55% of individuals survive. Inhalation anthrax is not contagious.

INHALATION ANTHRAX

(Mayo Clinic, 2020a; OSHA, n.d.-a, Williams et al., 2021)
Signs/Symptoms	Initially: Flu-like symptoms, including sore throat, mild fever, fatigue, and muscle aches, which may last a few hours or days Mild chest discomfort Shortness of breath Nausea Hemoptysis Painful swelling Later: High fever Dyspnea Shock Meningitis
Treatment	Antibiotics for both adults and children singly or in combination for a period of 60 days, which may include ciprofloxacin, doxycycline, or levofloxacin 3-dose series of anthrax vaccine In some cases, treatment with monoclonal antibodies raxibacumab and oblitoxaximab Supportive intensive care
Personal Protective Equipment	First Responders: level A, B, or C, depending on circumstances of agent release; properly fitted N-95 face mask First Receivers: Standard Precautions

Cutaneous Anthrax

Cutaneous anthrax is the most common form of anthrax infection and is also considered to be the least dangerous. Infection usually begins 1 to 7 days following exposure. This can happen when anthrax spores enter the skin, usually through a cut or scrape, or while handling infected animals or contaminated animal products. Cutaneous anthrax is most common on the head, neck, forearms, and hands. Without treatment, up to 20% of people with cutaneous anthrax die. With proper treatment, almost all patients with this form of anthrax survive.

CUTANEOUS ANTHRAX

(Mayo Clinic, 2020a; Williams et al., 2021)
Signs/Symptoms	Within 2 weeks of exposure: Local edema in area of contact progressing to an itching macule or papule followed by ulceration and eschar formation Lymphangitis Lymphadenopathy
Treatment	Early administration of large-dose intravenous and oral antibiotics for 60 days Wound care
Personal Protective Equipment	First Responders: level A, B, or C, depending on circumstances of agent release First Receivers: Standard Precautions; Contact precaution may be added if there are uncontained, copious amounts of drainage present.

BOTULISM

Clostridium botulinum is also a soil-inhabiting, spore-forming organism. The neurotoxin it forms is extremely potent and is one of the deadliest toxins known; less than 1 microgram is fatal for adults. It causes difficulty breathing, muscle paralysis, and if untreated, possible death. Botulism can be contracted by ingesting contaminated canned, smoked, or vacuum-packed foods and also by inhaling spores. Human botulism may refer to inhalation, infant, foodborne, or wound botulism. Inhalation of the toxin is rare.

BOTULISM

(CDC, 2021b)
Signs/Symptoms in Adults	No matter how a person acquires botulism, the symptoms are usually the same, with the defining feature of weakness beginning on both sides of the face, going down the neck and to the rest of the body. Initially: Dysphagia Diplopia Blurred vision Ptosis Slurred speech Respiratory distress or failure Ocular palsy Other symptoms that can follow: Vomiting Abdominal pain Diarrhea Dysuria
Signs/Symptoms in Infants	Constipation Floppy movements Trouble controlling the head Poor feeding Ptosis Sluggish pupils Drooling Flattened facial expression Diminished suck and gag reflexes Weak and altered cry Respiratory distress or failure
Treatment	Adults: Heptavalent antitoxin Infants: Baby/Big antitoxin Supportive care: ventilation, if necessary, for both adults and infants
Personal protective Equipment	First Responders: Level A, B, or C depending on circumstances of agent release First Receivers: Standard Precautions plus Airborne Precautions, including fit-tested N-95 respiratory mask Decontamination required for victims presenting immediately after aerosolized exposure

PLAGUE

Yersinia pestis is a bacterium that causes acute, potentially fatal infections in both humans and animals. It is naturally occurring in environments in which rats and their fleas exist. Plague has occurred in rural and semi-rural areas of the western United States, primarily in semi-arid upland forests and grasslands. In addition, wild carnivores can become infected by consuming infected prey. Plague can be deadly if not treated promptly with antibiotics. The rarest and deadliest form of plague affects the lungs and can spread from person to person.

Plague is rarely naturally transmitted by inhalation, but that is the most likely means if the organism were to be released intentionally. If released as an aerosol, an outbreak of pneumonic plague is the anticipated result. A plague vaccine is no longer available in the United States. New vaccines are in development but are not expected to be commercially available in the immediate future.

Plague can take different clinical forms, but the most common are bubonic, pneumonic, and septicemic.

Bubonic Plague

Bubonic plague is an infection of the lymphatic system and is usually the result of an infected flea bite. The bacteria multiply in a lymph node near where the bacteria entered and can spread to other areas of the body. Without treatment, the mortality rate is 60%.

BUBONIC PLAGUE

(Minnaganti, 2021; CDC, 2021c)
Signs/Symptoms	In the first several days: Flu-like symptoms Abdominal pain Diarrhea 2–6 days following exposure: Grossly enlarged, extremely tender lymph nodes (“buboes”) appear in axilla, neck, or groin with drainage at inoculation site. If untreated, can progress to septicemia, secondary pneumonic plague, or plague meningitis.
Treatment	Antibiotics: streptomycin, moxifloxacin, doxycycline, ciprofloxacin Supportive measures: oxygen, IV fluids
Personal Protective Equipment	First Responders: Level A, B, or C depending on circumstances of agent release First Receivers: Standard Precautions

Pneumonic Plague

Pneumonic plague may develop from inhaling infectious droplets or from untreated bubonic or septicemic plague that spreads to the lungs. Pneumonic plague is the most serious form of the disease and is the only form of plague that can spread from person to person. Without treatment the mortality rate is 100%, and with treatment it is 50%.

PNEUMONIC PLAGUE

(Minnagranti, 2021; CDC, 2021c)
Signs/Symptoms	1–3 days after inhalation: Acute onset of fever and chills Malaise Myalgias Progressive lethargy Productive cough with purulent or bloody sputum
Treatment	Antibiotics: streptomycin, doxycycline, moxifloxacin, ciprofloxacin Supportive measures: oxygen and IV fluids
Personal Protective Equipment	First Responders: Level A, B, or C depending on circumstances of agent release First Receivers: Standard Precautions; Droplet Precautions until the patient has received a minimum of 48 hours of antibiotic treatment and until pneumonia has been ruled out or sputum culture shows negative results.

Septicemic Plague

Septicemic plague can occur as the first symptoms of plague or may develop from untreated bubonic plague. This form results from bites of infected fleas or from handling an infected animal. Septicemic plague is frequently associated with delayed diagnosis, and has a higher fatality rate than primary bubonic plague.

SEPTICEMIC PLAGUE

(CDC, 2021c)
Signs/Symptoms	Acute onset of: Fever Chills Prostration Abdominal pain Nausea Vomiting Diarrhea May progress to include: Purpura Disseminated intravascular coagulopathy Hypotension Shock Skin and other tissues may turn black and die, especially on fingers, toes, and nose
Treatment	Antibiotics: streptomycin, doxycycline, moxifloxacin, ciprofloxacin Supportive measures: oxygen, IV fluids
Personal Protective Equipment	First Responders: Level A, B, or C, depending on circumstances of agent release First Receivers: Standard Precautions

SMALLPOX

The variola virus causes smallpox in two forms. Variola major is the most common and most severe. It has an historical fatality rate of approximately 30%. Variola minor is less common and less severe, with an historical fatality rate of ≤1%.

Smallpox eradication, one of the greatest successes of modern public health, was officially declared worldwide in 1980. The last known case of naturally occurring smallpox was reported in 1977 in Somalia. The last known case in the United States occurred in 1949. Today the smallpox virus is known to exist only in secured research laboratory stockpiles in the United States and Russia. However, advances in synthetic biology have made it possible to create smallpox. Therefore, there is concern that it could someday be used as a biological warfare agent.

Smallpox can be transmitted directly and indirectly from person to person and via contaminated items. Transmission begins with virus particles being sloughed from the oropharyngeal lesions of an infected person. Inhalation of airborne droplets of this saliva introduces the disease to a new host.

The most important way to prevent transmission of smallpox is by vaccination (Harvard Health, 2021).

SMALLPOX (VARIOLA)

(Mayo Clinic, 2020b; Harvard Health, 2021)
Signs/Symptoms	Noncontagious incubation period averages 12 to 14 days. Patient feels fine and is usually asymptomatic or has mild symptoms that mimic a cold or flu. Initial symptoms over next 2 to 4 days. Patient may or may not be contagious, with High fever Head and body aches Severe fatigue Severe back pain Vomiting Early rash that lasts about 4 days (small, red spots in mouth and on tongue, changing to sores that break open and spread large amounts of virus into mouth and throat. At the same time, rash appears on face and spreads to arms, hands, legs and feet. Within 24 hours, rash spreads over entire body. By third day, rash changes to pustules and fill with thick fluid a day later. Fever may rise and remain high until scabs form. Patient is most contagious at this time. Three weeks later scabs fall off, leaving pitted scars; patient is no longer contagious.
Treatment	No specific treatment available Person placed in isolation Supportive treatment: fluid replacement, antibiotics for secondary skin infections
Personal Protective Equipment	First Responders: Level A, B, or C, depending on circumstances of agent release First Receivers: Standard Precautions

Category B Diseases with Potential for Use as Bioweapons

Ricin and abrin are both biological toxins derived from plants; they are classified as either a biological or chemical weapon. Ricin comes from the beans of the castor plant and abrin comes from jequirity (rosary) peas. One molecule of either toxin is capable of poisoning all of the ribosomes in a cell, leading to cell death. Abrin is more lethal than ricin.

Ricin has been used in injectable form in assassination attempts, but mass casualties would probably involve inhalation of aerosolized toxin.

RICIN AND ABRIN SYNDROME

(Madsen, 2021; Stoppler, 2020)
Signs/Symptoms	Inhalational exposure: Latent period of 4–8 hours, followed by: Cough Respiratory distress Fever Hypotension Pulmonary edema Multiple organ systems progressively affected over the next 12–24 hours, culminating in respiratory failure Ingestion exposure: CNS disturbances leading to hallucinations or seizures Abdominal pain Profuse vomiting Hematuria Diarrhea (may or may not be bloody) Multiple ulcerations and hemorrhaging of gastric and small intestinal mucosa Dehydration Multisystem organ failure and possibly death within 36–72 hours of exposure
Treatment	First responder: On-site decontamination On-site ALS care prior to transport First receiver: No vaccine or antidote Intensive care for symptom-related support Medications to control blood pressure and seizures
Personal Protective Equipment	First responders (regardless of location, release site or triage/treatment area, and until decontamination has been completed): Level A First receivers (once decontamination has been completed): Level C