Terrorism is the intentional use of indiscriminate violence to create fear and terror as a means to achieve an ideological, financial, religious, or political aim. It is often used against non-combatant targets[1]. Terror tactics may include biologic, chemical, nuclear, or explosive events.

Bioterrorism is the intentional release of biological agents to cause illness or death in humans, animals, or plants. These agents may be bacteria, fungi, toxins, or viruses. They may be naturally occurring or human-modified.

The agents are typically found in nature, but they may be altered in a laboratory to increase their resistance to antibiotics, and ability to spread in the environment. Biological and chemical agents may be spread through the air, food, or water. Terrorists use biological agents because they are often difficult to detect and illness onset may be delayed for hours to days increasing dispersal.

Bioterrorism agents are a common choice for terrorists because they easy and inexpensive to produce, easy to disseminate, and can cause widespread effects. The challenge with bioweapons is that they may affect both enemy and friendly forces. Terrorists use biologic weapons as a method of creating mass panic.

In the history of humanity, the intentional infliction of casualties on civilians was considered inappropriate. Civilians are usually not attacked for their own sake unless they happen to be living or working in an area that has tactical or strategic value. Unfortunately, bioterrorism agents are difficult to control and affect military personnel as well as civilian men, woman, and children.

In the last 100 years, the United States and the international community have experienced multiple acts of terrorism and bioterrorism which have targeted civilians.

• World War I: Germany launched a biological sabotage campaign in France, Romania, Russia, and the United States by infecting horses and mules with glanders, a virulent disease
• 1972: Two college students, Allen Schwander and Stephen Pera, were arrested for planning to poison the Chicago water supply with typhoid bacteria
• 1984: The Bhagwan Shree Rajneesh followers in Oregon attempted to affect a local election by infecting doorknobs and salad bars in restaurants with Salmonella typhimurium bacteria
• 1993: Aum Shinrikyo religious group released anthrax in Tokyo
• 1995: Bombing of the Murrah Federal Building in Oklahoma City
• 2001: Airline attack on the World Trade Center
• 2001: Anthrax-laced of infectious anthrax were delivered to news media offices and the US Congress
• 2009: Medical center attack at a Fort Hood, Texas
• 2014: Bombing of the Boston Marathon
• Present: Multiple bombings worldwide

During World War I there was widespread use of chemical weapons that often affected the civilian population resulting in many deaths. Since this war, most countries have agreed not to use chemical and biologic weapons. Unfortunately, with our present age of terrorism from individuals, splinter groups, and dictators, there is an ever-present risk that these agents will be used.

To date, other than the dropping of nuclear bombs by the United States to end World War II, there have been no recent acts of nuclear attack or nuclear terrorism. Nuclear terrorism is an act of terrorism in which a terrorist organization detonates a nuclear device. The possibility of terrorist organizations using nuclear is considered plausible as terrorists could acquire a nuclear weapon. However, despite thefts of small amounts of fissile material, all low-concern, there is no credible evidence any terrorist group has succeeded in obtaining the necessary multi-kilogram critical mass amounts of weapons-grade plutonium required to make a nuclear weapon.

It is, unfortunately, becoming a common event on an international scale when terrorists use explosive devices to inflict casualties on the civilian population.

What is terrorism? What is a mass casualty incident?

• The United Nations definition of terrorism describes it as “an anxiety-inspiring method of repeated violent action, employed by (semi-) clandestine individual, group, or state actors, for idiosyncratic, criminal, or political reasons, whereby—in contrast to assassination—the direct targets of violence are not the main targets.”
• The Department of Defense defines terrorism as “the unlawful use of violence or threat of violence, often motivated by religious, political, or other ideological beliefs, to instill fear and coerce governments or societies in pursuit of goals that are usually political.” 
• The Federal Emergency Management Agency defines terrorism as “the use of force or violence against persons or property in violation of the criminal laws of the United States for purposes of intimidation, coercion, or ransom. Terrorists often use threats to create fear among the public, to try to convince citizens that their government is powerless to prevent terrorism, and to get immediate publicity for their cause”. 
• The US Code of Federal Regulations defines terrorism as “the unlawful use of force and violence against persons or property to intimidate or coerce a government, the civilian population, or any segment thereof, in furtherance of political or social objectives.”
• A mass casualty incident is defined terrorist act that generates more patients than available resources can manage using routine procedures.

Terrorism is generally considered to be the use of force or violence outside the law to create fear among citizens with the intent to coerce some sort of action. Health professionals should be aware bioterrorism is a perfect vehicle for terrorists to strike fear into the hearts and minds of citizens in the hopes they will bend the will of the people to support their agendas. All health professionals need to be prepared for this potentially catastrophic event[2].

The goal or function of a terrorist is to create mass hysteria. Health professionals must learn to mitigate this effect by being able to recognize an attack and treat and calm victims.

Terrorist acts can be either covert or overt. In a covert attack, the terrorists are attempting to take advantage of the element of surprise. Health professionals must be diligent in evaluating the possibility of a covert attack when multiple patients arrive with similar signs and symptoms. In this setting, the healthcare system may be quickly overloaded unless the institution and staff have prepared and have systems in place to handle a large influx of patient volume. The sooner an event is recognized as an attack; the sooner additional resources can be activated to assist providers. Unless the system prepares in advance, the number of victims triaged may quickly overwhelm the system and result in the terrorist’s goal of creating mass panic.

In an overt attack, terrorists rely heavily on mass hysteria and panic as an impact multiplier. They may announce responsibility immediately for a large-scale event. The number of victims quickly overwhelms even prepared systems that have a well-defined emergency response plan. In either a covert or overt terrorist attack, the system may be flooded with victims.

Weapons of Mass Destruction

Weapons of mass destruction include biological, chemical, or nuclear weapons potentially causing mass casualties. The mnemonic CBRNE assists in remembering weapons of mass destruction:

• Chemical
• Biological
• Radiological
• Nuclear
• Explosives

Biological Weapons

Biological warfare agents are bacteria and viruses that infect humans, animals, and crops resulting in an incapacitating or fatal disease or crop destruction. Symptoms may not appear for days to weeks. Often the bacteria or virus is weaponized, and the changes will affect a broader segment of humans, animals, or crops than the normal pathogen.

In a biological warfare terror event, healthcare providers must deal with uncommon pathogens that rarely affect humans. Healthcare facilities will be inundated with victims. The arrival of one or more victims with an odd presentation may be the initial indication that an act of terrorism has occurred.

Biologic agents may be dispersed by several techniques including contaminated water and aerosol sprays. They can also infect individuals and place them on airplanes, buses, or large events that will disperse the virus quickly.

Surveillance

All healthcare providers should have the knowledge to identify and initiate a local response to an act of bioterrorism. The starting point is the status quo or their normal patient population. If there is a significant deviation from the norm, the provider should consider the fact that they may be on the cusp of an endemic deliberately perpetrated on society.

Providers must be aware of clinical features including:

• A cluster of persons with similar symptoms from a common geographical area
• A rapid increase in patients presenting with similar signs and symptoms
• An increase in patients who expire within 72 hours after hospitalization
• An unusual clinical presentation
• Increased dead animals
• Signs and symptoms of biologic warfare agents
• Sudden increases in calls or visits
• Sudden increases in the use of over-the-counter drug purchases

These factors reflect changes from the status quo in the community. An astute clinician with a sense of the community’s general normal health can make a significant difference in how soon a response to the threat begins. If the person admits to no foreign travel in endemic areas of rare viruses, and the suspicion is high, contacting the local health department or CDC is in order.

Classification of Bioweapon Diseases

The Center for Disease Control has identified 30 organisms that might be weaponized and has grouped them into three categories. Classification is based on ease of dissemination, morbidity and mortality, panic potential, and level of public health requirements.

• Category A: Highest priority diseases that pose a risk to national security, are easily transmitted, have high morbidity and mortality, would have a major public health impact and cause panic, and require special public health preparedness. 
• Category B: Moderate priority diseases with lower morbidity and mortality and more difficult to disseminate.
• Category C: High priority diseases that have the potential to cause significant morbidity and mortality and are emerging pathogens that could be engineered for mass dispersion.

Biologic Agents

Category A: High Risk

ANTHRAX: CUTANEOUS, GASTROINTESTINAL, AND INHALATIONAL

Bacillus anthracis is found in the soil and is normally transmitted by handling contaminated animals and animal products. It is a spore-forming organism. Anthrax spores are highly permeable to the porous skin. An anthrax vaccine does exist but requires many injections to be effective. Anthrax is one of the few biological agents for which federal employees receive vaccination. It may be diagnosed with Gram stain (gram + rod shaped)[3].

• Signs/Symptoms: (Cutaneous) Pruritic macule or papule, ulceration, and eschar; edema; lymphangitis and lymphadenopathy. (Gastrointestinal) abdominal pain, nausea and vomiting, hematemesis, and bowel perforation which may occur after eating contaminated food. (Inhalational) Cough, chest pain, dyspnea, fever, sepsis, hemorrhagic mediastinitis, ending in hemodynamic and respiratory failure.  Symptoms begin within 1 to 60 days of exposure
• Treatment: large early doses of intravenous and oral antibiotics for 60 days may be life-saving, such as ciprofloxacin, doxycycline, erythromycin, penicillin, or vancomycin. FDA-approved agents include ciprofloxacin, doxycycline, and penicillin.
• Biologic Warfare: Contact precautions if copious drainage. Hand hygiene with soap and water or 2% chlorhexidine gluconate for 60 seconds. Over 2000 cases annually worldwide. Fatality > 20% untreated, 1% if treated. Standard precautions as no person-to-person transmission. High risk for use as a biologic weapon.

BOTULISM [4]

Botulism is a neurologic disorder that causes life-threatening neuroparalysis as a result of a neurotoxin produced by Clostridium botulinum. The three main clinical presentations of botulism are as follows: Infant botulism, Foodborne botulism, and Wound botulism.

• Signs/Symptoms: In infants and children constipation, diminished gag reflex, weak neck muscles, lethargy, and respiratory failure. Adults – weak jaw clench, difficulty speaking and swallowing, drooping eyelids, descending proximal to distal muscle weakness, and respiratory failure.
• Treatment: Supportive and antitoxin for severe symptoms.
• Biologic Warfare: The neurotoxin Botulinum is one of the deadliest toxins. It is produced by the bacterium Clostridium botulinum. Passive immunity with human hyperimmune globulin or equine botulinum antitoxin, and endogenous immunity with botulinum toxoid. Standard precautions. High risk for use as a biologic weapon.

PLAGUE: BUBONIC

Bubonic plague is a highly contagious, acute,  febrile illness transmitted to humans by the bite of a rat flea. Human-to-human transmission is rare. The disease is caused by a rod-shaped bacteria known as Yersinia pestis. Plague is distributed worldwide and is more commonly reported in developing countries. Survival of the bacillus depends on flea-rodent interaction; human infection does not contribute to the bacteria's survival in nature[5].

• Signs/Symptoms: Enlarged tender lymph nodes called buboes, fever, chills, fatigue, myalgias, hypotension, pulmonary edema, abdominal pain, organ failure; may progress to septicemia, pneumonia, meningitis, ocular, or pharyngeal plague.
• Treatment: Ciprofloxacin, doxycycline, gentamycin, and streptomycin. Supportive care.
• Biologic Warfare: Yersinia pestis is a bacterium that causes the plague in humans. Rodents are the host, and the disease is transmitted by flea bites although it can be aerosolized. Droplet precautions until 48 to 72 hours of antibiotics then standard precautions. High fatality without treatment. It caused the Black Death in Medieval Europe. Due to its high death rate and potential for aerosolization, it is considered a to have a high potential for bioterrorism.

SMALLPOX (Variola Major) [6]

Smallpox is a highly contagious acute disease caused by the variola virus, an Orthopoxvirus in the Poxviridae family.

• Signs/Symptoms: Fever, myalgia, vesicular rash (all in the same stage of progression from papular to pustular) on the face and extremities developing over 2-4 days.
• Treatment: Supportive, fluids, antibiotics for secondary infection, vaccination with 2 to 5 days will decrease the incidence of the disease and decrease the incidence of death.
• Biologic Warfare: Smallpox is very contagious. Those infected need to be quarantined, and airborne and droplet precautions until scabs have separated at 3 to 4 weeks. The fatality rate is 20% to 40%. Smallpox was eradicated according to the WHO in 1980. As a weapon smallpox is particularly dangerous because it is highly contagious. Due to the infrequency with which vaccines are administered most people are unprotected in the event of an outbreak.

TULAREMIA OR “RABBIT FEVER”

Tularemia or rabbit fever is caused by Francisella tularensis which is a bacteria spread by ticks, deer flies, or contact with infected animals. It may be also be spread by breathing contaminated dust or drinking contaminated water[7].

• Signs/Symptoms: Fever, severe, life-threatening pneumonia and systemic infection.
• Treatment: Tularemia is difficult to diagnose and can easily be mistaken for other, more common, illnesses. Blood tests and cultures can help confirm the diagnosis. Antibiotics used to treat tularemia include streptomycin, gentamicin, doxycycline, or ciprofloxacin. Treatment usually lasts 10 to 21 days. Streptomycin is the drug of choice. Gentamicin is considered an acceptable alternative. Tetracyclines are an alternative to aminoglycosides for patients who are not as ill. Tetracyclines are static agents and should be given for at least 14 days to avoid relapse. Ciprofloxacin and other fluoroquinolones are not FDA-approved for treatment of tularemia but have shown good efficacy.
• Biologic Warfare - Low fatality rate if treated. The disease is caused by the Francisella tularensis bacterium through contact with insect bites, fur, inhalation, or ingestion of contaminated. If weaponized, the bacteria would likely be made airborne for inhalation infection

VIRAL HEMORRHAGIC FEVER (Marburg, Ebola, Lassa, and Machupo viruses)

Viral hemorrhagic fevers caused by a viral infection. They are caused by five families of RNA viruses: Arenaviridae, Bunyaviridae, Filoviridae, Flaviviridae, and Rhabdoviridae. Fever and bleeding disorders characterize all types, and all can progress to high fever, shock, and death[8].

• Signs/Symptoms: Fever and bleed, facial and chest flushing, petechiae, edema, hypotension, malaise, muscle pain, nausea, vomiting, headache, progresses to multiple organ failures and hypovolemic shock in the form of bleeding diathesis and circulatory compromise.
• Treatment: No cure exists, treatment is supportive.
• Biologic Warfare: Ebola virus is the most dangerous, with fatality rates ranging from 25% to 90%. The viruses are spread to humans through a respiratory route, and there is a potential for weaponization and aerosol dissemination.

Category B – Low Risk

ABRIN TOXIN FROM ABRUS PRECATORIUS (ROSARY PEAS)[9]

Abrin is a toxic toxalbumin that is found in the seeds of the rosary pea. It is more toxic than ricin. Abrin is a ribosome inhibiting protein similar to the ricin.

• Signs/Symptoms: The major symptoms depend on the route of exposure and the dose. Symptoms appear between hours to days after exposure. Initial symptoms of inhalation may occur within 8–24 hours; and may be fatal within 36 to 72 hours. Symptoms include a cough, fever, mouth pain, airway irritation, chest tightness, diaphoresis, pulmonary edema, nausea, vomiting, diarrhea, abdominal cramps, cyanosis, GI bleeding, hematuria, and respiratory failure. Abrin as a powder or mist can cause eye redness, lacrimation, retinal hemorrhage, vision impairment, blindness, and lead to systemic toxicity.
• Treatment: Supportive as there is no antidote, oxygen therapy, airway management, assisted ventilation, monitoring, IV fluids, and electrolyte replacement. For recent ingestion, administration of activated charcoal and gastric lavage are both options. Flushing the eye with saline helps to remove abrin.
• Biologic Warfare: Abrin is a ribosome inhibiting toxic protein toxalbumin found in the seeds of the rosary pea or jequirity pea, Abrus precatorius. It is approximately 30 times more toxic than ricin and has a potential to be weaponized.

BRUCELLOSIS (BRUCELLA SPECIES)

Brucellosis is a very contagious zoonosis that may be contracted by consumption of undercooked meat, unpasteurized milk, or contact with other secretions. It is also known as Mediterranean fever, Malta fever, or Undulant fever. Brucella is small gram-negative, nonmotile, non spore-forming, rod-shaped coccobacilli bacteria. It is a facultative intracellular parasite resulting in chronic disease.

• Signs/Symptoms: Fever, sweating (the foul smell of wet hay), arthralgia, myalgia, muscular pain, night sweats, nausea, vomiting, diarrhea, decreased appetite, weight loss, abdominal pain, constipation, an enlarged liver, liver inflammation, liver abscess, and an enlarged spleen. Duration of the disease from a few weeks to years. Blood tests reveal a low RBC and WBC, elevation of liver enzymes such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and demonstrate positive Bengal Rose and Huddleston reactions. Brucella infection may cause arthritis, spondylitis, thrombocytopenia, meningitis, uveitis, optic neuritis, endocarditis, and neurobrucellosis.
• Treatment: Tetracycline, rifampin, streptomycin, and gentamicin are effective if given for several weeks as bacteria incubate within cells. Multiple antibiotics may be necessary. The gold standard treatment is streptomycin 1 g for 14 days and oral doxycycline 100 mg twice daily for 45 days. Another regimen is doxycycline plus rifampin twice daily for 6 weeks. A triple therapy of doxycycline, with rifampin and co-trimoxazole, has been used successfully to treat neurobrucellosis.
• Biologic Warfare: In endemic areas, vaccination is used to reduce the incidence of infection. Brucella has been weaponized by several countries.

EPSILON TOXIN OF CLOSTRIDIUM PERFRINGENS

Epsilon toxin is produced by Clostridium perfringens types B and D is one of the most potent poisonous substances known. Epsilon toxin binds to endothelial cells of brain capillary vessels before passing through the blood-brain barrier.

• Signs/Symptoms: In humans expected development would be over 6 to 24 hours, a refined version might act quicker, it would quickly cause devasting neurologic signs and symptoms and might result in sudden death. If weaponized, it would probably be dispersed by aerosolizing.
• Treatment: There has been very little progress toward the assembly of a good human immunogen against C. perfringens or any type of anti-toxin, and within the event of a terrorist attack, no prophylactic measures would possibly be accessible to be used by the general public.
• Biologic Warfare: C. perfringens epsilon toxin could be a fatal bioterrorism weapon. If used effectively, this agent might cause important morbidity and mortality because of a lack of therapeutic or preventive measures exist as medical countermeasures.

FOOD BACTERIUM (ESCHERICHIA COLI O157: H7, SALMONELLA, SHIGELLA)

The foodborne disease usually results from food contaminated by pathogenic bacteria, viruses, or parasites; or toxins such those found in poisonous mushrooms. The incubation period ranges from hours to day depending on the agent and the amount of consumption.

• Signs/Symptoms: Nausea, vomiting, diarrhea, abdominal cramping, and severe dehydration.
• Treatment: Supportive with antibiotics for severe cases.
• Biologic Warfare: Infections created from consumed food have been a time-honored method of assassination, siege, and terrorism. The food system is vulnerable to adulteration and contamination. Food is a natural vehicle for pathogenic microbes and toxins.  Contamination of food and water for select target populations. Bioterrorists would be able to disrupt the life of localities by contaminating water supplies or food.  An outbreak of diarrheal disease could shut down schools, a police force, fire departments, an aircraft carrier, or a military base. Schools and military basis with their centralized kitchens are a prime target for a food bioterrorism.  Schools are such a public concern that any hostile act against them can destroy a community. Food-borne pathogens are a "natural" weapons. Using organisms as weapons require the opportunity to insert them into the food system so that they will be viable and virulent. All it takes to make food into a weapon is basic microbiologic information and access to soil, manure, and untreated water.

GLANDERS (BURKHOLDERIA MALLEI)

Glanders is an infectious disease usually affecting donkeys, horses, and mules but it can be contracted by cats, dogs, goats, and humans. It is caused by Burkholderia mallei from contaminated feed or water.

• Signs/Symptoms: Incubation 1 to 14 days, may cause septicemia, pulmonary infection, and acute localized infection. Nodules and abscesses with ulcers in the mucous membranes and lymphangitis with suppuration is common. Expect fever, chills, sweats, malaise, headache, nausea, vomiting, diarrhea, dizziness, myalgia, pustular rash, cellulitis, cyanosis, jaundice, photophobia, and tachycardia. Hepatomegaly and splenomegaly may develop. Disseminated infections often progress to septicemia and multi-organ failure is common; death can occur rapidly.
• Treatment: Use standard precautions to prevent human-to-human transmission. Oral amoxicillin/clavulanate, doxycycline, or trimethoprim/sulfamethoxazole may be used for 30 to 150 days depending on the degree of the infection. Add streptomycin when initiating treatment if plague cannot be excluded.
• Biologic Warfare: Due to the high mortality rate in humans it is regarded as a potential biological warfare agent.

MELIOIDOSIS (BURKHOLDERIA PSEUDOMALLEI)

Melioidosis is an infection caused by gram-negative Burkholderia pseudomallei found in the soil and water. It is phylogenetically related closely to Burkholderia mallei which causes glanders. 

• Signs/Symptoms: In acute melioidosis, the incubation period is 1 to 21 days, but can be decades. It is known as the "Vietnam time-bomb." There are 4 general types of infection: localized, pulmonary, blood-borne, or disseminated. Patients typically present with fever, cough pleuritic chest pain, bone or joint pain, with cellulitis. Intra-abdominal liver, splenic, or prostatic abscesses do not usually have focal pain. As a result, ultrasound or computed tomography should be performed. B. pseudomallei abscesses may have a characteristic "honeycomb" or "swiss cheese" architecture on CT. Parotid abscesses characteristically occur in Thai children, and prostatic abscesses are found in Australian males. Risk factors include diabetes, thalassemia, alcohol use, or renal disease. Chronic melioidosis occurs when symptoms last greater than 2 months. The clinical presentation of chronic melioidosis includes chronic skin infections, chronic lung nodule, and pneumonia. Chronic melioidosis closely mimics tuberculosis.
• Treatment: Initially intravenous ceftazidime should be administered 10 to 14 days. Meropenem, imipenem, and cefoperazone-sulbactam combination are also active. Intravenous amoxicillin-clavulanate may be used if none of the above four drugs is available. Eradication or maintenance treatment with co-trimoxazole and doxycycline is recommended for 12 to 20 weeks to reduce the rate of recurrence. Co-amoxiclav is an alternative for those unable to take co-trimoxazole and doxycycline (e.g., pregnant women and children under the age of 12), but is not as effective. Surgical drainage is usually indicated for prostatic and parotid abscesses and septic arthritis.
• Biologic Warfare: Melioidosis has the potential to be developed as a biological weapon. Without antibiotics, the septicemic form mortality rate exceeds 90%. With appropriate antibiotics, the mortality rate is about 10% for uncomplicated cases but up to 80% for cases with sepsis.

PSITTACOSIS (CHLAMYDIA PSITTACI)

Psittacosis, parrot fever, or ornithosis is caused by Chlamydia psittaci and contracted from infected parrots.

• Signs/Symptoms- Incubation period of 5–19 days, usually presenting as atypical pneumonia. Expect prostrating high fevers, cough, headache with nuchal rigidity, joint pains, diarrhea, conjunctivitis, nose bleeds, and low level of white blood cells. Rose spots (Horder's spots) may develop. Splenomegaly is common towards the end of the first week. Diagnosis should be suspected if respiratory infection associated with splenomegaly and/or epistaxis.
• Treatment: The infection is treated with tetracycline or chloramphenicol. For initial treatment of ill patients, doxycycline hyclate may be administered intravenously. Remission is usually evident within 48 to 72 hours, but treatment must continue for at least 10 to 14 days after fever subsides.
• Biologic Warfare: Psittacosis has been considered as a possible biologic weapon.

Q FEVER (COXIELLA BURNETII)

Coxiella burnetii causes Q fever. The bacteria is found in cattle, goats, sheep, cats, and dogs. Infection occurs from inhalation from a spore-like variant and contact with feces, milk, semen, and urine of infected animals. The disease may also tick-borne. The bacterium is an obligate intracellular parasite.

• Signs/Symptoms: Incubation is usually 2 to 3 weeks. Expect flu-like symptoms with fever, malaise, perspiration, headache, muscle pain, joint pain, loss of appetite, upper respiratory problems, dry cough, pleuritic pain, chills, confusion, nausea, vomiting, and diarrhea. It may progress to atypical pneumonia with life-threatening acute respiratory distress syndrome. It may cause granulomatous hepatitis, which may be asymptomatic or cause liver enlargement and pain in the right upper quadrant of the abdomen. Retinal vasculitis is a rare manifestation. The chronic form can cause endocarditis months to years later.
• Treatment: Antibiotics include doxycycline, tetracycline, chloramphenicol, ciprofloxacin, ofloxacin, and hydroxychloroquine. Chronic Q fever may require up to four years of treatment with doxycycline and quinolones or doxycycline with hydroxychloroquine.
• Biologic Warfare: C. burnetii has been developed as a biological weapon. It can be contagious and is stable in aerosols in a wide range of temperatures. Q fever microorganisms may survive on surfaces up to 60 days. It is considered a good agent in because its ID50 is considered to be one, making it the lowest known of any biologic toxin.

RICIN: RICINUS COMMUNIS (CASTOR BEANS)

Ricin is a toxic lectin produced by the castor oil plant and found in the seeds. A dose the size of a few grains of table salt can kill a human. The LD 50 is about 22 micrograms per kilogram of body weight. Injection or inhalation is more toxic than oral ingestion.

• Signs/Symptoms: Toxic if inhaled, injected, or ingested. It causes abdominal pain, coughing, diarrhea, fever, nausea, necrotizing pneumonia, pulmonary edema, shock, tracheobronchitis, vomiting, and weakness.
• Treatment: Charcoal lavage and supportive care.
• Biologic Warfare: Several countries have considered or attempted to weaponized ricin. Given ricin's extreme toxicity it is noteworthy that the production of the toxin is rather difficult to limit. The castor bean plant from which ricin is derived is a common ornamental and can be grown at home without any special care.

STAPHYLOCOCCUS AUREUS (Enterotoxin Type B)

S. aureus is a gram-positive bacterium frequently found in the flora of the nose, respiratory tract, and skin. It is a common cause of abscesses, food poisoning, respiratory infections and sinusitis. Pathogenic strains produce virulence factors such as protein toxins and cell-surface protein that binds and inactivates antibodies. Antibiotic-resistant methicillin-resistant S. aureus (MRSA) is a worldwide problem.

• Signs/Symptoms: Enterotoxin produced by the gram-positive Staphylococcus aureus causing severe diarrhea, nausea, and intestinal cramping within a few hours of ingestion. Gastroenteritis occurs because it is a superantigen, causing the immune system to release large cytokines that lead to significant inflammation that can result in toxic shock syndrome with high fever, hypotension, dizziness, rash, and peeling skin.
• Treatment: Antibiotics such as oxacillin, cefazolin, clindamycin, vancomycin, or linezolid with supportive care.
• Biologic Warfare: It is possible enterotoxin type B could be weaponized.

TYPHUS (RICKETTSIA PROWAZEKII)

Typhus, also known as typhus fever, is caused by Rickettsia prowazekii which is spread by body lice and Orientia tsutsugamushi, spread by chiggers, and Murine typhus, due to Rickettsia typhi spread by fleas.

• Signs/Symptoms: Sudden onset of fever with flu-like symptoms about 1 to 2 weeks after being infected. Once the symptoms have started, five to nine days later a rash typically begins on the trunk and spreads to the extremities sparing the face, palms, and soles. Signs of meningoencephalitis begin with the rash and continue with the development of photophobia, delirium, or coma. Untreated cases are often fatal.
• Treatment: Without treatment, death may occur in 10% to 60% of patients with epidemic typhus, with patients over age 60 having the highest risk of death. Death is rare if doxycycline and supportive care are provided.
• Biologic Warfare: Rickettsia prowazekii is highly infectious, but it cannot be passed from person to person. Numerous countries have considered it as a potential biological weapon.

VIRAL ENCEPHALITIS (VENEZUELAN EQUINE ENCEPHALITIS, EASTERN EQUINE ENCEPHALITIS, WESTERN EQUINE ENCEPHALITIS)

Encephalitis is an acute inflammation of the brain caused by either a viral infection or the immune system mistakenly attacking brain tissue. Encephalitis refers to an acute, diffuse, inflammatory process. While meningitis is an infection of the meninges, a combined meningoencephalitis can occur. An infection by a virus is the most common cause of encephalitis.

• Signs/Symptoms: Typically mosquito-borne viral pathogen that causes progressive central nervous system disorders. Patients experience flu-like symptoms, such as high fevers and headaches. People with weakened immune systems, the very young, and old can become severely ill and die. Diagnosing encephalitis is challenging because many of the symptoms are shared with other illnesses. Confirmations may require a sample of cerebral spinal fluid or brain tissue although CT scans and MRI scans are used to detect encephalitis.
• Treatment: Supportive
• Biologic Warfare: Many countries have considered weaponizing these viruses.

WATER SUPPLY THREATS (VIBRIO CHOLERAE, CRYPTOSPORIDIUM PARVUM)

The water supply and water treatment facilities are a possible target for terrorists.

• Signs/Symptoms: Ingestion of water born agents typically leads to nausea, vomiting, and diarrhea.
• Treatment: Depends on the pathogen. Most are supportive, but antibiotics may shorten the course.
• Biologic Warfare: Agents released into the water supply are a potential biologic weapon.

Category C [9]

Category C agents are emerging pathogens that could be engineered for mass dissemination because of their availability, ease of production and dissemination, mortality rate, and ability to cause a substantial health impact.

H1N1 INFLUENZA

Influenza A (H1N1) virus is a subtype of influenza A and a common cause of the human flu. It is an orthomyxovirus that contains haemagglutinin and neuraminidase. Haemagglutinin causes red blood cells to clump together. Neuraminidase is a glycoside hydrolase enzyme that moves the virus particles through the infected cell.

• Signs/Symptoms: Influenza-like illness with chills, fever, sore throat, muscle pains, headache, cough, weakness, and general discomfort. The recommended time of isolation is five days.
• Treatment: Supportive.
• Biologic Warfare: Due to high virulence and rapid distribution in the community it is possible it could be weaponized.

HANTAVIRUS

Hantaviruses or orthohantaviruses are single-stranded, enveloped, negative-sense RNA viruses within the Hantaviridae family of the order of Bunyavirales. These viruses have the potential to kill humans. Humans become infected from contact with rodent feces, saliva, or urine.

• Signs/Symptoms: Hemorrhagic fever with renal syndrome is caused hantaviruses. In hantavirus-induced hemorrhagic fever, incubation time is 2 to 4 weeks. The severity of symptoms depends on the viral load. Hantavirus pulmonary syndrome is an often-fatal pulmonary disease. Prodromal symptoms include flu-like symptoms such as fever, cough, muscle pain, headache, and lethargy. It is characterized by shortness of breath with rapidly evolving pulmonary edema that is often fatal despite mechanical ventilation.
• Treatment: Supportive treatment with oxygen and mechanical ventilation during the acute pulmonary stage. Administration of human neutralizing antibodies during acute phases of Hantavirus might also prove effective.
• Biologic Warfare: Hantavirus hemorrhagic fever has not been shown to transfer from person to person. Transmission is by aerosolized rodent excreta to humans, and in the hospital setting transmission would be unlikely with universal precautions. It is possible it could be weaponized.

HIV/AIDS

Human immunodeficiency virus and acquired immune deficiency syndrome are conditions caused by infection with human immunodeficiency virus.

• Signs/Symptoms: Acute seroconversion manifests as a flu-like illness, with fever, malaise, and a generalized rash. The asymptomatic phase is generally benign. Generalized lymphadenopathy is common and may be a presenting symptom.
• Treatment: Depends on the stage of the disease and any concomitant opportunistic infections. In general, the goal of treatment is to prevent the immune system from deteriorating using antiretroviral therapy (HAART). In addition, prophylaxis for specific opportunistic infections is indicated.

NIPAH VIRUS

Nipah virus (NiV) infection is a zoonosis that causes severe disease in humans. The natural host of the virus is the fruit bats of the Pteropodidae family, Pteropus genus. Human-to-human transmission has also been documented. NiV infection in humans has a range of clinical presentations, from asymptomatic infection to acute respiratory syndrome and encephalitis.

• Signs/Symptoms: Cough, fever, headache, drowsiness, abdominal pain, nausea, vomiting, weakness, difficulty swallowing, blurred vision, seizures, and about 60% become comatose and need mechanical ventilation. Patients with severe disease may develop hypertension, tachycardia, and a very high temperature.
• Treatment: Supportive measures as there is no definitive treatment. Ribavirin may help.
• Biologic Weapon: Transmission may be human-to-human transmission. The reservoir is Pteropid fruit bats, Pteropus vampyrus (Large Flying Fox), and Pteropus hypomelanus (Small flying fox), found in Malaysia. The transmission of Nipah virus from flying foxes to pigs is thought to be due to increasing overlap between bat habitats and pig farms. It is possible it could be weaponized.

SARS

Severe acute respiratory syndrome (SARS) is a zoonotic viral respiratory disease caused by the SARS coronavirus.

• Signs/Symptoms: High fever, body aches, diarrhea, and dry cough. Often progresses to pneumonia.
• Treatment: Supportive care with oxygen and ventilation. Antiviral medications and steroids may reduce lung swelling.
• Biologic Weapon: Spread is by close person-to-person contact. The virus that causes SARS is thought to be transmitted by respiratory droplets produced when an infected person coughs or sneezes. Due to its high infectivity, it is possible it could be weaponized.

CHEMICAL WEAPONS

A chemical weapon is a specialized munition that uses chemicals formulated to inflict harm or death. Chemical weapons are classified as weapons of mass destruction, and they are distinct from nuclear weapons, biological weapons, and radiological weapons. Chemical weapons can be dispersed in a gas, liquid, and solid forms.

• Lethal chemical agents and munitions are volatile, and they constitute a class of hazardous chemical weapons that have been stockpiled by many nations.
• Unitary agents are effective on their own and do not require mixing with other agents. The most dangerous of these are nerve agents (GA, GB, GD, and VX) and vesicant (blister) agents, which include sulfur mustard such as H, HT, and HD. They all are liquids at normal room temperature but become gaseous when released.

Under the Chemical Weapons Convention, there is a worldwide ban on the production, stockpiling, and use of chemical weapons. Notwithstanding, large stockpiles of chemical weapons exist, usually justified as a precaution against an aggressor.

Types of Chemical Agents [10]

BLISTER: Distilled mustard, mustard gas, lewisite, mustard/lewisite, mustard/T, nitrogen mustard, phosgene oxide, and sulfur mustard

A blister agent or vesicant is named for its ability to cause severe chemical painful water blisters on the bodies of those affected. Vesicants have potential medical uses including wart removal, but they are fatal if small amounts are ingested.

• Signs/Symptoms: Burning, itching, nausea, vomiting, shortness of breath, pulmonary edema, tearing, and upper airway sloughing.
• Treatment: Mustard no antidote, lewisite – British Anti-Lewisite and supportive care.
• Other: Vesicants are oily reactive chemicals that combine with DNA and proteins to cause cellular changes within minutes to hours after exposure. Garlic, onion, or mustard smell.

BLOOD AGENTS: Cyanogen chloride, hydrogen cyanide

A blood chemical agent is a toxic compound that affects the body by being absorbed into the blood. They are fast-acting, highly lethal toxins that are typically volatile colorless gases with a faint odor. They are usually either arsenic or cyanide-based.

• Signs/Symptoms: Convulsions, cyanosis, fatigue, headache, hyperventilation, hypotension, lightheadedness, loss of consciousness, metabolic acidosis, palpitations, nausea, vomiting, and death in 1 to 20 minutes.
• Treatment: 100% O2, sodium thiosulfate injection – 12.5 g/50 mL (2 vials), sodium nitrate – 300 mg/10 mL (2 ampules), amyl nitrite inhalant 0.3 mL (12 ampules), and hydroxocobalamin 5 g

CHOKING AGENTS: Chlorine, chloropicrin, nitrogen oxides, phosgene, and sulfur dioxide

Chemical agents which attack lung tissue, primarily causing pulmonary edema, are classed as lung-damaging or choking agents.

• Signs/Symptoms: Chest tightness, dermal irritation, laryngospasm, mucosal irritation, pulmonary edema, shortness of breath, and wheezing
• Treatment: Manage secretions, oxygen, intubate and treat pulmonary edema with PEEP to maintain pO2 greater than 60 mm Hg. High-dose steroids to treat pulmonary edema for nitrogen oxide.

INCAPACITATION: BZ, CS, CN, and LSD

An incapacitation agent that produces temporary physiological or mental effect which will render individuals incapable of the performance of their duties.

• Signs/Symptoms: Confusion, dizzy, dry mouth, hypertension, runny nose, shortness of breath, skin burns, sweating, tachycardia, and tremors
• Treatment: Flush eyes and skin, treat symptomatically

NERVE: Organic pesticides, sarin, soman, and tabun

Nerve agents are organic chemical (organophosphates) that disrupt nerve transfer messages to organs by blocking acetylcholinesterase, an enzyme that catalyzes the breakdown of acetylcholine. Nerve agents are easily vaporized, and may enter through the respiratory system. The skin can also absorb them. A full body suit is required for exposure protection.

• Signs/Symptoms: Bronchial constriction, cramps, diarrhea, dyspnea, increased secretions, miosis, respiratory arrest, sweating, tremors, convulsions, paralysis, and loss of consciousness.
• Treatment: Atropine every 5 to 10 minutes until secretions stop; 2-PAM CL up to 3 injections within minutes if possible.
• Other: The Military Mark I kit is often available and is preloaded with 2 mg of atropine and 600 mg of 2-PAM CL

NUCLEAR WEAPONS

Nuclear weapons are weapons of mass destruction. Nuclear warfare can produce destruction in a much shorter time and have a long-lasting radiological result. A major nuclear exchange would have long-term effects, primarily from the fallout released that could last for centuries. If a nuclear war occurs, it is expected many will die acutely followed by deaths from starvation and the international catastrophes to the health and welfare of citizens that would ensue. So far, 2 nuclear weapons have been used, both by the United States near the end of World War II. While it ended the war sooner, saving countless lives. These 2 bombings resulted in the immediate deaths of approximately 120,000 people.

There are two types of nuclear weapons: fission and fusion.

Fission

All existing nuclear weapons derive some of their explosive energy from a nuclear fission reaction. Weapons whose explosive output is exclusively from fission reactions are referred to as atomic bombs or atom bombs.

Fusion

Fusion weapons produce a large proportion of energy in nuclear fusion reactions. Such fusion weapons are referred to as thermonuclear weapons or hydrogen bombs. All such weapons derive a significant portion of their energy from fission reactions which are used to "trigger" fusion reactions. The primary pathologic effect of ionizing radiation causes damage to DNA. The common pathway of injury is radiation deposits energy into the electron orbitals of atoms in the biologic medium.

• Signs/Symptoms

Cutaneous

Localized exposure to high doses of radiation causes cutaneous burns. Blistering, desquamation, erythema, and ulceration may occur 2 to 3 weeks after irradiation with the onset and severity increased with exposure.

• 3 Gy: Epilation within 1 to 2 weeks
• 6 Gy: Immediate signs of burn
• 10-15 Gy: Dry desquamation
• 20-50 Gy: Wet desquamation within 2 to 3 weeks
• More than 50 Gy: Cutaneous syndrome, necrosis, and ulceration presenting for months to years after exposure

Acute Radiation Syndrome

Acute radiation syndrome occurs after exposure to substantial ionizing radiation. Acute radiation syndrome may occur at a minimum dose of 1 Gy and is fatal at doses greater than 10 Gy. At 3.5 Gy, 50% of those exposed die within 60 days without medical treatment.

Acute radiation syndrome progresses through 4 stages:

1. Prodrome
2. Clinical latency
3. Manifest illness
4. Recovery or death

Prodromal symptoms develop after irradiation, the greater the dose, the sooner the onset and the greater the duration and severity. Symptoms include nausea, vomiting, diarrhea, anorexia, abdominal cramping, and eventually dehydration.

• 1 to 3 Gy: Symptoms show up within 12 hours
• 10 Gy or more: Symptoms show up in 5 to 15 minutes with immediate nausea, vomiting, diarrhea, and hypotension

Early onset of prodromal symptoms indicates a poor prognosis.

Acute radiation syndrome has three subsyndromes: cerebrovascular, gastrointestinal, and hematopoietic.

Cerebrovascular

Greater than 30 Gy causes cerebrovascular syndrome which is uniformly fatal. Doses greater than 100 Gy results in death in a few hours. Vascular damage results in significant cerebral edema, resulting in cardiovascular collapse. The patient will develop nausea, vomiting, ataxia, hypotension, tachycardia, and convulsions followed by death.

Gastrointestinal

Exposures of 5 to 12 Gy result in gastrointestinal syndrome. Irradiation causes cell death of the intestinal mucosal stem cells in the crypts. After the loss of mucosal cells, the stem cells are unable to produce new cells, resulting in denudation of the gastrointestinal tract. As the normal cells are destroyed, bacterial growth proliferates, and nausea, vomiting, bloody diarrhea, dehydration, abdominal cramps, and weight loss develops. Often the prodrome is rapid, which is followed by a latent period. Treatment includes fluids, electrolytes, and antibiotics. Unfortunately, death usually occurs in 3 to 10 days.

Hematopoietic

Exposures of 2 to 5 Gy causes the hematopoietic syndrome. Lymphocytes die from radiation caused apoptosis, and precursor cells in the bone marrow are destroyed which prevents the production of leukocytes and platelets. Gradually circulating cells die off with no replacements; the syndrome progresses to infections and possible hemorrhage. Early supportive care, treatment and prevention of infections, and cytokine therapy may decrease morbidity and mortality. However, death commonly still occurs from multi-system organ failure.

Treatment of Acute Radiation Syndrome

Cutaneous

• Cutaneous radiation burns should be treated similarly to thermal burns. Severe burns may require amputations, grafts, or vasodilator therapy.

Internal

• Initially lavage with fluids and charcoal to minimize absorption of radioactive materials.
• Within a few hours of exposure, radioactive iodine can be used with a saturated solution of potassium iodide, a blocking agent that will decrease the uptake of the radionuclide in the thyroid. This may decrease the risk of future malignancies.
• Penicillamine is a chelating agent that binds to specific radioactive metals and results in decreased tissue uptake and increased excretion.
• Cesium exposure can be treated with ferric hexacyanoferrate which will decrease gastrointestinal absorption.
• Other agents to consider include Ca-DTPA and Zn-DTPA can be used to treat exposure to americium, curium, and plutonium.

Large-dose Radiation Exposure 

• Nausea, vomiting, and diarrhea should be treated with fluids and electrolytes.
• If the exposure is greater than 5 Gy consider antibiotics, cytokines, transfusions, and platelet transfusions.
• If the absolute neutrophil count is less than 500 cells/mm, consider prophylactic antibiotics, including coverage of gram-negative and gram-positive anti-bacterial agents; and antiviral, antifungal, and antipseudomonal coverage.

Hematopoietic Growth Factor 

• Filgrastim may be considered to treat hematopoietic syndrome of acute radiation syndrome. Colony-stimulating factors have also been considered as a possible therapeutic option.

Personal Protective Equipment[1]

Biological Agents

• First responders need to wear an OSHA Level A PPE if they are at risk of direct exposure to a biologic or chemical hazard. This is a total encapsulated chemical- and vapor-protective suit that includes positive pressure, full face-piece, self-contained breathing apparatus, or positive pressure supplied air respirator with escape SCBA which should be approved by the National Institute for Occupational Safety and Health.
• For hospital personnel, use standard precautions which include hand hygiene, and depending on the suspected biologic agent, a gown, gloves, mask, and face shield.
• If the is a potential of contamination from an aerosolized powder, PPE includes wearing an N95 mask or equivalent or a powered air-purifying respirator.

Chemical Agents

• First responders with the potential of direct exposure require an OSHA Level A PPE.
• The minimum PPE for a chemical agent in the hospital is also extensive. Respiratory protection must include a NIOSH-approved PAPR or a combination 99.97% high-efficiency particulate air/organic vapor/acid gas respirator cartridges. A chemical and resistant suit with double-layer protective gloves and boots should be worn that includes covering the head and face.
• For those working post-decontamination, work clothes and PPE, if necessary, to prevent infection.

Nuclear Agents

Emergency responders to a nuclear explosion may not know they are being exposed to radiation unless they utilize a radiation detecting device. There is no practical personal protective equipment to protect responders against penetrating gamma radiation. Monitoring devices are the only means to ensure that responders do not enter an area where exposure is excessive.

Personal protective equipment to prevent skin contamination is effective against particulate-borne radiation hazards (i.e., alpha and beta particles). Typical firefighter gear is adequate. Decontamination of personnel and equipment should follow exposure.

Protection of organs from radioactive particulates may be provided by wearing an appropriate particulate respirator.

• SCBAs will provide a high level of protection. Responders should utilize a full-face air-purifying respirator with a P-100 or HEPA filter.
• Respiratory protection approved by NIOSH for CBRN exposures is desirable. It should be noted that respiratory protection is designed only for protection against inhalation of radioactive particulates, and do not consider protection for other contaminants, such as chemical or biological agents.
• Particulate sampling can be performed to measure the radioactivity of dust in the air and to clarify exposures further.

Decontamination

Triage: Contaminated individuals are identified by proximity to the known release, signs, and symptoms. If the patient requires life-saving treatment, this supersedes decontamination. Staff must wear PPE and stabilize the victim before entry into decontamination.

Decontamination: The patient is monitored while contaminated clothing is removed and placed in hazardous waste containers and depending on the agent, appropriate decontamination techniques are deployed to remove the hazardous substance. Removing clothes alone may reduce 75% or more of the contamination. This should be followed by a water shower with liquid soap.

Post-decontamination: After the victim is decontaminated, a second clinical triage is conducted.

The facility should be prepared to handle wastewater and solid waste. Morgue services should be available for contaminated bodies.

Radiation Whole-Body Contamination

• Remove patient/victim's clothing working from head to toe can reduce contamination by 90%.
• Place all property in a single, airtight container, e.g., property bag and store in a secure location for appropriate disposal.
• Separate property bags to avoid creating high radiation areas.
• Mark patient's skin using waterproof felt tip marker identifying high-level contamination.
• Use tepid decontamination water with soap as cold water tends to close skin pores, trapping radioactive contamination and may also cause hypothermia.
• Avoid hot water which results in enhanced absorption of radioactive material through vasodilation and increased skin blood flow and may cause thermal burns.
• Directly contaminated wastewater away from the patient, rather than over the rest of the body.
• Stop the whole body external decontamination efforts after 2 decontamination cycles and handle patient with standard precautions.
• Cover areas of residual radiation contamination with waterproof dressings to limit the spread of contamination to other body sites.
• Persistently elevated levels of external contamination after adequate decontamination efforts may also be due to internal contamination.

Preparedness

Individual

Health professionals must be able to respond to an act of terrorism. This requires education and a working knowledge of the potential biologic and chemical agents that may be deployed and treatment options available to counter ill effects.

Institution

Facilities must evaluate the institution's role in a local biologic or chemical emergency. Facilities must assist in the coordination of activities of the emergency response agencies within the community. The best way to respond is to have a prepared plan and practice it before an untoward event.

Resources

The Center for Disease Control provides the Health Alert Network (HAN) to provide urgent information about public health incidents. HAN provides a mechanism for rapid distribution of health information to over 1 million email recipients. Messages are in four levels:

• Health Alert: For time-sensitive information of a specific incident or situation that requires immediate attention by health officials, clinicians, laboratorians, and the public and conveys a high level of importance.
• Health Advisory: Provides recommendations on actionable items for public health officials, clinicians, and laboratorians that may not require immediate action.
• Health Update: Provides updated information regarding a situation unlikely to require immediate action.
• Info Service: Provides general public information unlikely to require immediate action.

The ever-present potential of a terrorist bombing concerns as it may well lead to countless casualties; however, a biologic, chemical, or nuclear attack may rise to the level of an international catastrophe. Healthcare professional must prepare as individuals and as a team to care for the victims. It is important for each of us to acquire the information and skills needed to respond and to take steps to limit to the morbidity and mortality associated with a such an attack.

Unfortunately, many political organizations are using terrorism to try to achieve their goals. It is difficult to explain terrorism, we must live with it, and as health professionals prepare ourselves to deal with it.