Course Objectives

By completing this course the healthcare professional will be able to:

1.  Describe acts of terrorism.

2.  Describe nuclear, biological and chemical weapons of mass destruction.

3.  Identify the symptoms associated with exposure to weapons of mass destruction.

4   Describe the Syndromic surveillance and reporting procedures for acts of terrorism.

5.  Describe personal protective equipment required for acts of terrorism.

6.  Describe the information available on the Health Alert Network.


As the United States and its allies continue the fight against international terrorist groups and the countries that support them, there are increasing fears that Americans at home will one day face the threat of weapons of mass destruction.

Such weapons include biological, chemical, nuclear and radiological devices, and range from the silent threat of a poison gas attack to a cataclysmic nuclear explosion. Those who would launch such attacks know thousands could die, of course, but their fundamental motive would be to strike fear and panic in tens of millions more.

In his State of the Union address on Jan. 28, President Bush instructed leaders of the FBI, CIA, Homeland Security Department and the Department of Defense to develop a Terrorist Threat Integration Center to merge and analyze all types of threat information in a single location so that the "right people are in the right places to protect our citizens."

Biological Warfare

History: Terrorism involving biological weapons — referred to along with chemical weapons as "the poor man's nuclear weapon" — can range from putting deadly substances in the nation's food supply to the aerosolized release of a contagious virus over a city the size of New York or San Francisco.

The Biological Weapons Convention, signed in 1972, prohibits the manufacture, stockpiling and use of biological weapons. But there are several countries that continue to make and study them. Some countries' stockpiles are unaccounted for, as is the case with Iraq.

Former President Nixon banned the production and use of biological warfare agents in 1969, ending the U.S. bio-warfare program. The Soviet Union's bio-warfare program, Bio-preparation, lasted until the 1990s.

The United States in January announced a bioterrorism detection system that would provide early warning if smallpox, anthrax or other deadly germs are released into the environment. The system was tested throughout 2002, including at the Winter Olympics in Salt Lake City, Utah.

On Jan. 28, Bush announced that he will ask for $6 billion in his fiscal 2004 budget to launch "Project Bioshield," a major research and production effort to make sure effective vaccines and treatments against bioterrorism agents are available. 

Anthrax, botulinum toxin, plague, ricin, smallpox, tularemia and viral hemorrhagic fevers are on the top of the Center for Disease Control and Prevention's list of biological weapons, considered "Category A" weapons most likely to be used in an attack.

"Category B" weapons are second-highest priority to the CDC, because they are fairly easy to disseminate, cause moderate amounts of disease and low fatality rates. But these weapons require specific public-health action such as improved diagnostic and detection systems. These agents include: Q fever, brucellosis, glanders, ricin, Enterotoxin B, viral encephalitis, food safety threats, water safety threats, meliodosis, psittacosis and typhus fever.

"Category C" weapons, described by the CDC as "emerging infectious disease threats," are fairly easy to obtain, produce and disseminate and can produce high rates of disease and mortality. These include the Nipah virus and Hantavirus.

Other agents some nations may use as weapons include: aflatoxin, trichothecene mycotoxins, multi-drug tuberculosis, bacteria such as trench fever and scrub typhus, viruses such as influenza and various forms of hemorrhagic fever, fungi and protozoa.

Agricultural bioterrorism could produce famine or widespread malnutrition. These include foot-and-mouth disease, mad cow disease, swine fever and karnal bunt of wheat.


Systems: Biological weapons can be aerosolized, meaning they can be easily spread into the air and inhaled by humans. These weapons can also be put into food or water supplies, where they would be ingested. Many will also cause harm if they contact human skin.

Symptoms: Symptoms can include flu-like symptoms, exhaustion, pneumonia, weight loss, stomach pain, diarrhea, respiratory failure and shock.

Treatment: Biological weapons often take weeks or months to take their toll. Public health systems often can't pinpoint bioterrorism right away, because symptoms often mirror ones exhibited by a person with the common cold or the flu.  Treatments include antidotes, antibiotics, vaccines and pumping of the stomach. 

Who Has Them:  Russia is known to have stockpiles of various biological weapons. The United States studies some substances, such as anthrax, in laboratories. Iraq, North Korea and Syria are a few nations thought to still possess biological weapons.

Chemical Warfare 

History:  The first major use of chemical weapons in modern times came when Germany launched a large-scale poison gas attack against French troops on the battlefield of Ypres in 1915. Allies responded with their own chemical weapons.  By the end of the war, chemical warfare had inflicted over 1 million casualties, of which around 90,000 were fatal.

Hydrogen cyanide and carbon monoxide were used by the Germans to murder millions of people in extermination camps during World War II.

During the Vietnam War, the United States used tear gas and several types of defoliants, including Agent Orange.

The 1925 Geneva Protocol prohibits "the use in war of asphyxiating, poisonous or other gases, and of bacteriological methods of warfare." But it didn't prohibit the manufacturing and stockpiling of these weapons. About 40 countries ratified the protocol.

More than 140 nations signed the Chemical Weapons Convention of 1993, which bans the development, production and possession of chemical weapons. Nonetheless, a number of nations are believed to have the weapons.

Chemical agents are classified according to the symptoms they cause, such as blistering and nerve agents.


Mustard Gas, Sarin (GB), VX, Soman (GD) and Tubun

Other forms of chemical agents include: blood agents, including cyanide, arsine, cyanogens chloride and hydrogen chloride; choking agents, including chlorine, diphosgene and phosgene; other nerve agents; and vesicants, such as distilled mustard, ethyldichloroarsine, mustard-lewisite mixture and forms of nitrogen mustard.

There are also "harassing agents," such as riot control chemicals and vomiting agents.

Toxic weapons are made from readily available material used in various industrial operations. The most common types of hazardous materials used in toxic weapons are irritants, choking agents, flammable industrial gas, water supply contaminants, oxidizers, chemical asphyxiates, incendiary gases and liquids, industrial compounds and organophosphate pesticides.

Various forms of toxic waste, such as petroleum spills, smoke, refuse, sewage and medical waste also can be used in toxic warfare. Toxic warfare has been used often in recent years.

 Delivery Systems:  Skin contact, inhalation and eye contact are possible delivery systems. Chemicals can also be deployed via commercial handheld agricultural sprayers, crop dusters, spray tanks on aircraft or ships, via munitions delivered in gravity bombs, or in warheads on ballistic or cruise missiles. Water and food contamination is also possible. Then there's the simple delivery system of opening a container full of harmful chemicals in a crowded area, such as a city subway.

 Symptoms:  Symptoms can range from burning or blistering of the skin and eyes, coughing, respiratory disease, dizziness, nausea, drowsiness, headache, convulsions, involuntary defecation and urination, twitching, water-like blisters jerking and miosis, which is the excessive contraction of eye pupils.

Indicators of a possible chemical incident include: numerous dead insects and animals in the area; mass human casualties soon after an attack; numerous surfaces having oily droplets or film; discolored or withered trees, shrubs, bushes, food crops or lawns; unexplained odors ranging from fruity to flowery, to sharp or pungent garlic or horseradish smells, bitter almond or peach odors and a smell of hay.

 Treatment:  Methods used to relieve suffering include antibiotics, antidotes, painkillers, dressings for skin burns, rinsing of eyes and skin and scrubbing of the skin with bleach or other household cleaning agents.

Who Has Them:  There are reports the Al Qaeda terror network has tried to make various chemical weapons. Russia and the United States have known stockpiles of sarin. It is also thought India, South Korea and Syria, among others, also have supplies of various nerve agents.

It is not clear how secure such nations can keep these supplies. Such weapons are attractive to terrorist groups because they are easily accessible, the parts to make them are generally legal and cheap to obtain. As a result, many military and terrorism experts believe there will be an increasing trend in the use of such weapons.

 Nuclear Warfare

 History: Nuclear weapons produce devastating and long-term effects on human and animal life, as well as the environments in which they live. These are the hardest of all types of weapons to make because the critical nuclear elements — plutonium and/or highly enriched uranium — are hard to come by, and are very expensive.

The United States dropped one atomic bomb each on Hiroshima and Nagasaki in 1945, bringing and end to World War II. The Soviet Union became the next country to develop atomic weapons, igniting an arms race and a global interest in nuclear fission devices.

Traditional nuclear weapons are not the only threat. Officials are concerned terrorists might also target the world’s nuclear power plants and supplies.

One worst-case scenario simulation estimated a one-megaton explosion in Detroit — equivalent to a million tons of TNT — could kill 250,000 people, injure half a million more, and flatten all buildings within a 1.7-mile radius.

Decades of arms control negotiations have greatly reduced the number of nuclear weapons around the world. Since 1991, the U.S. Nunn-Lugar Cooperative Threat Reduction program has deactivated 6,032 nuclear warheads and has destroyed 491 ballistic missiles, 438 ballistic missile silos, 101 bombers, 365 submarine-launched missiles, 408 submarine missile launchers, and 25 strategic missile submarines. It has sealed 194 nuclear test tunnels.

On May 1, 2000, five nuclear weapon states — China, France, Russia, Britain and the U.S. — issued a 23-point joint statement pledging their “unequivocal commitment to the ultimate goals of a complete disarmament under strict and effective international controls.”

Other nations known or believed to have nuclear weapons have not signed such agreements, however. Among those nations are India, Pakistan, Israel and North Korea.


 Atomic Bombs, Hydrogen Bombs, “Loose Nukes” and “Suitcase” Bombs

Delivery Systems: These weapons are most likely to be delivered in the form of ballistic missiles or bombs dropped by fly-over bombers. Terrorists could also cause accidents involving nuclear power plants, nuclear medicine machines in hospitals and vehicles used in the transportation of nuclear waste.

The size of an actual nuclear weapon can be quite small, however, and could easily fit into a large car or truck. That has sparked a fear among many experts that a nuclear warhead could simply be driven into a large city by terrorists and detonated by either a suicide bomber or by remote control.

 Symptoms: If people don't die from the initial impact of the blast, depending on the dose of radiation received, victims may experience vomiting, headache, fatigue, weakness, thermal burn-like skin effects, secondary infections, recurring bleeding and hair loss and long-term effects such as cancer or birth defects.

 Treatment:  Clothing is to be taken off immediately and sealed in an airtight container. Victims should wash themselves off completely with soap and water or with bleach, if necessary. Treatment may also include stomach pumping, laxatives and giving patients various substances to decrease the absorption of radiation in the body's cells and tissue.

 Who Has Them:

The United States has a stockpile of 12,500 nuclear weapons and 103 power plants. Russia has a similar supply. The United Nation's International Atomic Energy Agency oversees 900 of the world's nuclear facilities. Pakistan and India have both exploded nuclear devices in test blasts. Israel and North Korea are two countries believed to possess nuclear weapons.

Nuclear weapons continue to be a proliferation concern, particularly when North Korea recently announced it was continuing its nuclear arms program, and withdrew from the international Nuclear Nonproliferation Treaty.

One worry of the United States is not so much that North Korea itself will use what weapons it has, but that it will have no qualms about selling them to the highest bidder, whether that bidder be a nation such as Iraq, which sponsors terrorism, or individual terrorist groups like Al-Qaeda. 

Radiological Warfare

History:  Radiological weapons are thought by many to be the likely choices for terrorists. Unlike nuclear weapons, they spread radioactive material, which contaminates equipment, facilities, land and acts as a toxic chemical, which can be harmful, and in some cases fatal.

A "dirty bomb" is the likely choice for terrorists and can kill or injure people by exposing them to radioactive materials, such as cesium-137, iridium-192 or cobalt-60. Atomic experts say the explosion of a dirty bomb containing one kilogram of plutonium in the center of Munich, Germany, could ultimately lead to 120 cancer cases attributable to the blast.


Dirty Bomb

Delivery Systems:  Methods of detonating a dirty bomb include devices — such as bombs or artillery shells — used to disperse harmful radioactive material. This weapon can be used to contaminate livestock, fish and food crops. Most radioactive material isn't soluble in water, so that virtually rules it out as a way for terrorists to contaminate reservoirs or other water supplies

Terrorists could launch a systemic attack on a nuclear power plant by venting or overloading a reactor so it acts as a radiological weapon.

Suspicious containers may display a radiation symbol.

 Symptoms:  Symptoms can range from mild effects, such as skin reddening, to cancer and death.

Acute radiation syndrome — radiation sickness — is usually caused when a person gets a high dose of radiation in mere minutes and can cause nausea, vomiting and diarrhea; later, bone marrow depletion may lead to weight loss, loss of appetite, flu-like symptoms, infection and bleeding.

People should be suspicious of material that seems to emit heat without any sign of external heating source, as well as any glowing materials or particles. The glowing indicates a strongly radioactive substance.

 Treatment:  Radiation victims should take off their clothes and wash themselves with soap and water — using bleach if necessary. Hospital workers will provide treatment depending on the amount of radiation received.

 Who Has It:  Iraq and Al Qaeda are just two of the countries and/or terrorist groups believed to have dirty bombs. Virtually every country, however, has the materials to make them. Insecure nuclear facilities throughout the world compound the problem.

 Other Weapons

 History:  There are various weapons - many of which are still under development - that may not fall into the category of a "biological," "chemical," "radiological" or "nuclear weapon."


E Bomb

Delivery Systems:  An "E-bomb" most likely would be delivered via unmanned cruise missiles, fired from a long-range 155 mm artillery gun or MLRS rocket launcher.

 Symptoms:  An E-bomb knocks out electronic devices and communication systems, and melts or fuses electrical wiring together. Home computer or personal digital assistants would be warm to the touch, and their data would be destroyed. Lights would flicker on and off and phones would be scrambled. If a human were directly hit by high-powered microwaves and is near electrical equipment or has a pacemaker, he or she may suffer from serious burns or brain damage.

 Treatment:  Humans would receive treatment as needed for burns or other injuries.

 Who Has Them:  The United States may try to use an E-bomb to seize the Iraqi airwaves if a war is launched on that country. The e-bomb will knock out Saddam Hussein's ability to communicate with his military and the Iraq people.

 In the Case of a Nuclear or Radiological Attack:

If there were a threat of a nuclear or radiological attack, people living around potential targets such as military bases and chemical plants, may be advised to evacuate. Protection from radioactive fallout would require taking shelter in an underground area, or in the middle of a large building. Blast shelters offer some protection, but cannot withstand a direct hit from a nuclear detonation. Fallout shelters can be any protected space where the walls and roof are thick and dense enough to absorb radiation. The more distance and time you put between you and the fallout particles, the better. Some fallout shelters are designated by yellow and black shelter signs, although many were removed at the end of the Cold War.

During a nuclear attack, do not look at the flash or fireball. Take cover as quickly as possible — below ground, if possible — and stay there until instructed otherwise. If you can't get inside a building, take cover behind anything, lie flat on the ground and cover your head. Fallout may not arrive for 20 minutes or so after the blast but can be carried by wind for hundreds of miles, so seek a shelter that will offer a strong shield against harmful material that is farther away from where the device was detonated.

After a radiological or nuclear attack, people shouldn't leave their shelter until officials say so. The length of your stay can range from a day to two to four weeks, depending on the extent of contamination. People who are allowed to come out of hiding may be evacuated to unaffected areas within a few days. While in hiding, people are encouraged to use water and food prudently and cooperate with shelter managers.

Before returning to a home within range of a bomb's shock wave, check for signs of collapse or damage before entering. Immediately clean up spilled medicines, drugs or flammables. Listen to your battery-powered radio for instructions and information about community services. Do not turn gas back on in house and turn water back on only after you're sure the water system is working properly and isn't contaminated. Stay away from damaged areas and areas marked "radiation hazard" or "HAZMAT."

 Emergency Alert System:

In case of an emergency, such as some type of terrorist attack, state or local emergency officials would issue an emergency alert system message to the local media to tell citizens what actions to take. The Emergency Broadcast System is used for this. This sytem is used by local officials almost every day in cases of natural disasters, hazardous material spills and similar emergencies.

A national emergency alert system can be activated by FEMA at the direction of the White House. This would cause an emergency message to be sent out to a national network of radio stations, coast to coast. That message then filters down to smaller radio, TV and cable stations. This system has never been used.


 Section I. NUCLEAR

 4-1. General

 With small yield tactical nuclear weapons, there will be comparatively large numbers of casualties from initial radiation, possibly combined with the blast effects. Burn injuries will be more common as the weapon yield increases. The types of injuries associated with nuclear warfare are—

 a. Flash Injury. The intense light of a nuclear fireball can cause flash blindness. The duration of blindness depends upon the length of exposure and the light conditions. However, even at night it is unlikely that flash blindness will last more than a few minutes. Most individuals can continue their mission after the short recovery period. Severe cases may have retinal and optic nerve injuries that lead to permanent blindness; these cases will require evacuation to an MTF.

b. Blast Injury. Blast injuries consist of two types—

• Primary injuries due to overpressures such as ruptured eardrums and lungs.

• Secondary injuries such as lacerations and puncture wounds, as well as translational injuries from the severe winds.

c. Thermal Injury. Thermal injuries are generated by—

• Direct thermal radiation (flash burns and eye injuries).

• Indirect (flame) effects.

d. Radiation Injury. Casualties produced by ionizing radiation alone or with other injuries will be common. Radiation complicates treatment by its synergistic action. The short duration of field medical treatment limits the ability to determine the patient’s total radiation exposure. Additionally, total exposure may not be received at one time, but as the result of several operations in contaminated regions.

 Management of Nuclear Patients

 a. Management. Management of patients injured from the immediate effects of nuclear weapons (flash, blast, thermal) are the same as for conventional battlefield injuries, although the injury severity may be increased. First aid (self-aid, buddy aid, and combat lifesaver [CLS]) for lacerations, broken bones, and burns are performed.

b. Mass Casualty. Amass casualty situation is developed by a nuclear attack; that is, the number of patients requiring care exceed the capabilities of treatment personnel and equipment.

EXAMPLES: One combat medic has two patients requiring immediate lifesaving procedures; he can only provide needed procedures for one. Thus, correct triage and evacuation procedures are essential. Triage classifications for nuclear patients differ from conventional injured patients. Nuclear patient triage classifications are as follows:

Immediate treatment group (T1). Those requiring immediate lifesaving surgery.

Procedures should not be time-consuming and should concern only those with a high chance of survival, such as respiratory obstruction and accessible hemorrhage.

Delayed treatment group (T2). Those needing surgery, but whose conditions permit delay without unduly endangering safety. Life-sustaining treatment such as intravenous fluids, antibiotics, splinting, catheterization, and relief of pain may be required in this group.

Examples are fractured limbs, spinal injuries, and uncomplicated burns.

Minimal treatment group (T3). Those with relatively minor injuries who can be helped by untrained personnel, or who can look after themselves, such as minor fractures or lacerations. Buddy care is particularly important in this situation.

Expectant treatment group (T4). Those with serious or multiple injuries requiring intensive treatment, or with a poor chance of survival. These patients receive appropriate supportive treatment compatible with resources, which will include large doses of analgesics as applicable.

Examples are severe head and spinal injuries, widespread burns, or high doses of radiation; this is a temporary category.

Handling and Managing Radioactively Contaminated Patients

 a. Radiologically Contaminated Patients. Those persons from fallout areas may have fallout on their skin and clothing. Although the patient will not be radioactive, he may suffer radiation injury from the contamination. Removal of the contamination should be accomplished as soon as possible; definitely before admission into a clean treatment area. The distinction must be made between a radiation injured person and one who is radiologically contaminated. Although some may have received substantial radiation exposure, this exposure alone does not result in the individual being contaminated. Normally, contaminated individuals do not pose a short-term hazard to the medical staff, rather the contamination is a hazard to the individuals’ health. However, without patient decontamination, medical personnel may receive sufficient exposure to create beta burns, especially with extended exposure.

b. Handling Radiologically Contaminated Patients. To properly handle radiologically contaminated patients, medical personnel must first detect the contamination. Two detectors, the AN/PDR27 and the AN/VDR2, are used to monitor patients for contamination. Generally, a reading on the meter twice the current background reading indicates that the patient is contaminated. Monitoring is conducted when potentially contaminated patients arrive at the MTF. This monitoring is conducted at the MTFs receiving point before admitting the patient. Contaminated patients must be decontaminated before admission.

c. Decontamination. Radioactive deco lamination is easy. Removing all outer clothing and a brief washing or brushing of exposed skin will reduce 99 percent of contamination; vigorous bathing or showering is unnecessary. Do not let radiological contamination interfere with immediate lifesaving treatment or the best possible medical care.

 d. Treatment. Treatment procedures for radiation injuries are described in FM 8-9 and the NATO Handbook “Emergency War Surgery.”


 4-4. General

The impact of biological warfare on HSS may be a few patients with diarrhea, or a mass casualty situation. The first indication of a BW attack or use will most likely be patients arriving at an MTF with an illness. The routes of entry for BW agents are the same as endemic diseases (that is, through inhalation, ingestion, or percutaneous inoculation). Biological agents are most likely to be delivered covertly and by aerosol. Other routes of entry are thought to be less important than inhalation, but are nonetheless potentially significant.

a. Aerosol (1) Inhalation. Inhalation of agent aerosols, with resultant deposition of infectious or toxic particles within alveoli, provides a direct pathway to the systemic circulation. The natural process of breathing causes a continuing flux of biological agent to exposed individuals. The major risk is pulmonary retention of inhaled particles. Droplets as large as 20 microns can infect the upper respiratory tract; however, these relatively large particles generally are filtered by natural anatomic and physiological processes, and only much smaller particles (ranging from 0.5 to 5 microns) reach the alveoli efficiently.

 (2) Ingestion. Food and water supplies may be contaminated during an aerosol BW attack. Unwary consumption of such contaminated materials could result in disease.

(3) Percutaneous. Intact skin provides an excellent barrier for most, but not all, biological agents. However, mucous membranes and damaged skin constitute breaches in this normal barrier through which agents may readily pass.

b. Contamination of Food and Water. Direct contamination of food and water could be used as a means to disseminate infectious agents or toxins. This method of attack is most suitable for sabotage activities and might be used against limited targets such as water supplies or food supplies of a specific unit or base.

c. Other Considerations.(1) Arthropod-borne. The spread of diseases by releasing infected arthropods such as mosquitoes, ticks, or fleas. These live vectors can be produced in large numbers and infected by allowing them to feed on infected animals, infected blood reservoirs, or artificially-produced sources of a BW agent.

 (2) Long-term survival of infectious agents. Preservation of toxins for extended periods and the protective influence of dust particles onto which microorganisms adsorb when spread by aerosols have been documented. Therefore, the potential exists for the delayed generation of secondary aerosols from contaminated surfaces. To a lesser extent, particles may adhere to an individual or to clothing, creating additional exposure hazards.

(3) Person-to-person. The spread of potential biological agents by person-to-person has been documented. Man, as an unaware and highly effective carrier of a communicable agent, could readily become a source of dissemination (for example, plague or smallpox).

4-5. Management of Biological Warfare Patients

 a. Management. Management of patients suffering from the effects of BW agents may include the need for isolation. Barrier nursing for patients suspected of suffering from exposure to BW agents will reduce the possibility of spreading the disease to health care providers and other patients. Specimens must be collected and submitted to the designated supporting laboratory for identification.

b. Mass Casualty. A BW agent attack can produce a mass casualty situation at all echelons of HSS. A major problem with a BW mass casualty situation is that HSS personnel are more susceptible to becoming a casualty to BW agents. Also, the ill patient may be the first indicator that a BW agent has been dispersed.

c. Decontamination. Biologically contaminated patients require some degree of detail. Contamination can be removed by use of a diluted disinfectant solution, or a 0.5 percent chlorine solution

d. Treatment. Specific treatment is dependent upon the BW agent used. Patients are treated for symptomatic presentation.


 4-6. General

Health service support operations in a CW environment will be complex. In addition to providing care in protected environments or while dressed in protective clothing, medical personnel will have to treat chemical injured and contaminated patients in large numbers. Types of injuries associated with chemical warfare are—

a. Nerve Agent Injury. Nerve agent injuries are classified as mild, moderate, and severe. Classification is based upon the signs and symptoms presented in the individual. The individual may only be having minor problems, or may be convulsing and exhibiting severe respiratory distress. Some individuals return to normal after receiving a single injection of the Mark I; others may require multiple doses of the Mark I, CANA, and assisted ventilation.

b. Blister Agent Injury. Individuals exposed to blister agents may not know that they have been exposed to the agent for hours to days later. The first indication of exposure may be small blisters on the skin. Others will have immediate burning because of the high level of exposure. The individual with a few small blisters or reddening of the skin can continue the mission, An individual suffering mild injuries may require admission to a MTF for treatment.

c. Incapacitating Agent Injury. Incapacitating agents produce injury by depressing the CNS, or stimulating the CNS. These agents affect the CNS by disrupting the high integrative functions of memory, problem solving, attention, and comprehension. Relatively high doses produce toxic delirium which destroys the ability to perform any task.

d. Blood Agent Injury. Blood agents produce their effects by interfering with oxygen use at the cellular level. The agent prevents the oxidative process within cells. In high concentrations there is an increase in the depth of respiration within a few seconds. The patient cannot voluntarily

hold his breath. Violent convulsions occur after 20 to 30 seconds with cessation of respiration within 1 minute. Cardiac failure follows within a few minutes. Inhalation is the usual route of entry.

e. Lung-Damaging Agent Injury. Lung-damaging (choking) agents attack lung tissue, primarily causing pulmonary edema. The principle agents in this group are phosgene, diphosgene, chlorine, and chloropicrin.

4-7. Management of Chemical Agent Patients

 a. Management. Movement of chemical agent casualties can spread the contamination to clean areas. All casualties are decontaminated as far forward as the situation permits. All patients must be decontaminated before they are admitted into a clean MTF. The admission of one contaminated patient into an MTF will contaminate the facility; thereby, reducing treatment capabilities in the facility.

b. Mass Casualty. As with other NBC weapon/agent employment a mass casualty situation is presented when chemical agents are employed. Additional HSS personnel and equipment must be provided in a short period of time if the level of care is to be maintained. Treatment at far

forward MTFs is limited to life-or limb-saving care. Patients that can survive evacuation to the next echelon of care are not treated at the forward facility. This provides time for treating those patients that cannot survive the evacuation time.

c. Decontamination. Decontamination of chemically contaminated patients requires the removal of their contaminated clothing and the use of a variety of decontamination kits and solutions.

d. Treatment. Manual 8-285 provides treatment procedures for chemical agent patients.

Syndromic Surveillance and Bioterrorism-related Epidemics

James W. Buehler, Ruth L. Berkelman, David M. Hartley, and Clarence J. Peters

To facilitate rapid detection of a future bioterrorist attack, an increasing number of public health departments are investing in new surveillance systems that target the early manifestations of bioterrorism-related disease. Whether this approach is likely to detect an epidemic sooner than reporting by alert clinicians remains unknown. The detection of a bioterrorism-related epidemic will depend on population characteristics, availability and use of health services, the nature of an attack, epidemiologic features of individual diseases, surveillance methods, and the capacity of health departments to respond to alerts. Predicting how these factors will combine in a bioterrorism attack may be impossible. Nevertheless, understanding their likely effect on epidemic detection should help define the usefulness of syndromic surveillance and identify approaches to increasing the likelihood that clinicians recognize and report an epidemic.

Because of heightened concerns about the possibility of bioterrorist attacks, public health agencies are testing new methods of surveillance intended to detect the early manifestations of illness that may occur during a bioterrorism-related epidemic. Broadly labeled “syndromic surveillance,” these efforts encompass a spectrum of activities that include monitoring illness syndromes or events, such as medication purchases, that reflect the prodromes of bioterrorism-related diseases). The Centers for Disease Control and Prevention (CDC) estimates that, as of May 2003, health departments in the United States have initiated syndromic surveillance systems in approximately 100 sites throughout the country (T. Treadwell, CDC, pers. comm.). The goal of these systems is to enable earlier detection of epidemics and a more timely public health response, hours or days before disease clusters are recognized clinically, or before specific diagnoses are made and reported to public health authorities. Whether this goal is achievable remains unproved).

Establishing a diagnosis is critical to the public health response to a bioterrorism-related epidemic, since the diagnosis will guide the use of vaccinations, medications, and other interventions. Absent a bioterrorism attack, predicting whether syndromic surveillance will trigger an investigation that yields a diagnosis before clinicians make and report a diagnosis is not possible. Our objective is to consider the mix of hypothetical factors that may affect the detection of epidemics attributable to CDC category A bioterrorism agents).

Establishing a Diagnosis

Two pathways to establishing a diagnosis are described by the scenarios below and in, using a single, clandestine dissemination of an anthrax aerosol as an example.

Detection through Syndromic Surveillance

The early signs of inhalational anthrax include nonspecific symptoms that may persist for several days before the onset of more severe disease). Patients with prodromal illnesses seek outpatient care and are assigned nonspecific diagnoses such as “viral syndrome.” Data on patients fitting various syndromic criteria are transferred to the health department and tested for aberrant trends. This process “flags” that a statistical detection threshold has been exceeded. Epidemiologists conclude that a preliminary investigation is warranted and collect blood for culture from several patients. Within 18 hours, one culture yields a presumptive diagnosis of anthrax, prompting a full-scale response.

Detection through Clinician Reporting

Some persons in whom inhalational anthrax develops will have short incubation periods and prodromes). Respiratory distress occurs in one such person, and he is hospitalized. Routine admission procedures include blood cultures. Within 18 hours, a presumptive diagnosis of anthrax is made. The patient’s physician informs the local health department, prompting a full-scale response.

In practice, how a bioterrorism attack might be detected and diagnosed will probably be more complex. Published descriptions of 11 persons with inhalational anthrax in the United States in 2001) provide some insight into this issue and), even though that epidemic was too small and geographically diffuse to be detectable by syndromic surveillance. For six patients with known dates of exposure, the median duration between exposure and symptom onset was 4 days (range 4–6 days). The median duration between onset and the initial healthcare visit was 3 days) (range 1–7 days), and the median duration between onset of symptoms and hospitalization was 4 days (range 3–7 days). Two of the 11 patients visited emergency departments and were sent home with diagnoses of gastroenteritis or viral syndrome 1 day before admission. In one patient, a blood culture obtained in the emergency room was read as positive for gram-positive bacilli the following day, which prompted recall of the patient. The culture was subsequently confirmed as positive for Bacillus anthracis. Two other patients were seen by primary care physicians and sent home with diagnoses of viral syndrome or bronchitis 2–3 days before admission, including one patient who was begun on empiric antibiotic therapy. For seven other patients, initial emergency room or hospital visits led directly to admission. In addition to the patient whose blood culture was obtained in an emergency room, seven others had not received prior antibiotic therapy, and B. anthracis was presumptively identified from blood within 24 hours of culture. One of these seven patients was the index patient, in whom B. anthracis was also recognized in cerebrospinal fluid within 7 hours of specimen collection. Three other patients had received antibiotics before blood cultures were taken (one as an outpatient and two at the time of hospital admission), requiring alternative diagnostic methods.

Despite the small number of patients, their experience offers four lessons for detecting an epidemic of inhalational anthrax. First, a key objective of syndromic surveillance is to detect early-stage disease, but fewer than half of these patients sought care before hospitalization was necessary, and the interval between such care and admission was relatively narrow (1–3 days). This finding suggests that syndromic surveillance data must be processed, analyzed, and acted upon quickly if such data are to provide a clue to diagnosis in advance of late-stage disease. Second, emergency room data are a common source for syndromic surveillance, but detecting an increase in visits coincident with hospital admission may not provide an early warning because the time needed to process surveillance data and investigate suspected cases would be at least as long as the time for admission blood cultures to be positive for B. anthracis. Blood cultures are likely to be routine for patients admitted with fever and severe respiratory illness, regardless of whether anthrax is considered as a diagnostic possibility, and B. anthracis grows readily in culture in the absence of prior antibiotic therapy, as observed in most of these patients. Thus, if emergency room data are to be useful in early detection of an anthrax epidemic, those data would need to be for visits that occur before hospital care is required—a pattern observed in only two patients. Third, the four patients who received early care and were discharged to their homes were assigned three different diagnoses, which suggests that syndromic surveillance systems must address the potential variability in how patients with the same infection may be diagnosed during the prodrome phase. Fourth, rapid diagnosis after hospitalization was possible only in those patients who had not received antibiotics before cultures were taken. This finding emphasizes the importance of judicious use of antibiotics in patients with nonspecific illness.

In addition to the specific attributes of individual bioterrorism agents, multiple considerations will shape the recognition of a bioterrorism-related epidemic. Five of these attributes follow.


Syndromic surveillance would not detect outbreaks too small to trigger statistical alarms. Size would be affected by the virulence of the agent, its potential for person-to-person transmission, the extent and mode of agent dissemination, whether dissemination occurs in more than one time or place, and population vulnerability.

Population Dispersion

How persons change locations after an exposure will affect whether disease occurs in a concentrated or wide area, and thus whether clustering is apparent to clinicians or detectable through syndromic surveillance at specific sites.

Health Care

The more knowledgeable providers are about bioterrorism agents, the greater the likelihood of recognition. Routine diagnostic practices or access to reference laboratories may affect the timeliness of diagnosis for some diseases. Familiarity with reporting procedures would increase prompt reporting of suspected or diagnosed cases.

Syndromic Surveillance

Syndromic surveillance will be affected by the selection of data sources, timeliness of information management, definition of syndrome categories, selection of statistical detection thresholds, availability of resources for followup, recent experience with false alarms, and criteria for initiating investigations.


A fifth key attribute is seasonality. An increase in illness associated with a bioterrorism attack may be more difficult to detect if it occurs during a seasonal upswing in naturally occurring disease.

Agent- and disease-specific attributes may be among the most important factors affecting detection and diagnosis). The incubation period and its distribution in the population will affect the rate at which new cases develop and thus how quickly an alarm threshold is exceeded or whether clinicians recognize a temporal and geographic cluster. If a disease has a short prodrome, the chance is increased that a patient would be hospitalized and a definitive evaluation initiated before an increase in cases triggered a surveillance alarm. Alternatively, if a disease has a relatively long prodrome, chances are greater that prediagnostic events (e.g., purchase of medications or use of outpatient care for nonspecific complaints) would accrue to levels that exceed syndromic surveillance thresholds, before definitive diagnostic evaluations are completed among patients with more severe disease. Arousing clinical suspicion for a particular diagnosis will depend on the specificity of both the early and late stages of illness as well as the presence or absence of a typical feature that should alert clinicians to the diagnosis, such as mediastinal widening in inhalational anthrax. If a routinely performed test is apt to be diagnostic in a short time (e.g., the blood culture in anthrax), a rapid diagnosis is likely, even in the absence of clinical suspicion. If routine tests are unlikely to yield a rapid diagnosis (e.g., the blood culture for the cause of tularemia, Francisella tularensis, or if the diagnosis requires a special test (e.g., the hemorrhagic fever viruses, a diagnosis may be delayed if not immediately considered.

The public health benefit resulting from early detection of an epidemic is likely to vary by disease. If a disease has a relatively wide distribution of potential onsets, early recognition provides greater opportunity to administer prophylaxis to exposed persons. For example, based on data from the Sverdlovsk incident, Brookmeyer and Blades estimated that use of antibiotic prophylaxis during the 2001 anthrax outbreak prevented nine cases of inhalational disease among exposed persons. If the incubation period of a disease has a relatively narrow distribution, early recognition may offer little opportunity for postexposure prophylaxis, although a potential benefit would remain for alerting healthcare providers and informing their care of others with similar symptoms. This pattern of illness is apt to result from exposure to an F. tularensis aerosol, which would likely result in an explosive epidemic with an abrupt onset and limited duration.


As the United States and the rest of the world focus on the recognition that biowarfare has moved from a tentative threat to a real possibility, federal, state, and local authorities, along with public health agencies, have escalated preparation efforts ranging from surveillance to vaccine development to postexposure strategies.

Primary care clinicians are increasingly being recognized as an integral part of these preventive approaches to biowarfare. Since rapid diagnosis and treatment will be critical to combat a bioagent once released, physicians and other primary care clinicians will be among the first to encounter individuals exposed to these agents. As such, they are in one of the most important positions to aid in recognizing and curtailing a potential mass bioterrorist threat.

The importance of rapid detection is emphasized by predictions that a delay of even 1 day with certain diseases could mean the "...difference between the loss and salvage of as much as 90% of an exposed population." In addition to high morbidity and mortality costs, delayed detection could also incur an enormous cost in terms of resources. Estimates from a model of 100,000 people exposed to a large-scale release of aerosolized anthrax spores indicated that a delay in detection of 1 hour could incur a cumulative cost of $200 million per hour during the peak days of exposure.

Traditionally, surveillance work has been an activity of public health specialists tracking diseases, as these naturally emerge within a community. But this type of post-illness passive surveillance is inadequate for situations that require rapid diagnosis, infection control interventions, and treatment to curb a dangerous outbreak, whether from a naturally emerging infectious disease or from one caused by a bioterrorist event. In recognition of the fact that primary care clinicians will be among the first to encounter persons exposed to a bioterrorist agent or an emerging infectious disease, approaches to surveillance are being developed that more fully integrate front-line care providers into surveillance work. These newer surveillance systems are geared to rapid identification of the signs and symptoms of exposure to an agent in time to deliver appropriate prophylaxis or treatment, and to alert public health authorities in order to facilitate appropriate infection-control techniques.

The name commonly given to these rapid-detection surveillance systems is syndromic surveillance, or syndrome-based surveillance. Other related terms include prediagnostic surveillance, nontraditional surveillance, enhanced surveillance, drop-in surveillance, disease early warning systems, and health indicator surveillance. These systems employ an active approach, meaning that the organization conducting surveillance initiates procedures in order to obtain data. Syndromic surveillance systems rely on data available prior to disease diagnosis that can provide sufficient probability of a possible outbreak. Key to rapid detection of possible outbreaks is the identification of first cases and aberrant patterns of syndrome reports. Toward this end, the syndrome classifications are used to raise a clinician's "index of suspicion" when assessing a patient who presents with specific signs characteristic of a particular infectious disease.

The surveillance systems are tailored to the ways in which clinicians routinely encounter and identify illness in the clinical setting -- that is, by observation of the patient and through conducting a thorough patient history during the encounter. Another aspect of this approach is the recognition that signs and symptoms can be grouped into clusters, or syndromes, to help clinicians more rapidly and readily "quantify their index of suspicion" or differentiate disease possibilities. Equally important, the rapid identification of which cluster of symptoms or syndrome a patient exhibits allows clinician to alert public health authorities to both report the syndrome encountered and obtain information about other syndromes being reported. This in turn could help make a differential diagnosis. This approach also allows public health specialists to use "real-time" data to track a suspected outbreak.

Better communication between primary care clinicians and public health specialists is not only critical for rapid identification and notification of a possible bioterrorist attack, but also for detecting naturally occurring emerging infectious diseases that may threaten populations worldwide. Although physicians are already required to report a number of long established infectious diseases and newly emerging ones such as the West Nile virus to public health agencies, many diseases go unreported. This is often because the reporting systems in place are just one more bureaucratic obstacle that primary care clinicians have to face amid their already hectic clinical duties.

Currently, information about even common diseases that circulate in communities is not easily accessible to clinicians. This lack of information may lead to misdiagnosis, overtreatment, and waste of valuable resources. A good example of this is the consistently overprescribed use of antibiotics to treat viral infections. Therefore, along with facilitating rapid diagnosis, it is hoped that the syndrome-based surveillance approach will enhance information flow and bridge the gap in current disease surveillance between clinicians and public health agencies.

Current Surveillance Systems

A number of early-detection surveillance systems are currently under development and are in different stages of implementation throughout the United States. However, none of the surveillance systems have been extensively tested in primary care settings. Until outcomes data are available, it will be difficult to determine which systems are superior. Examples of different types of systems and links to Web sites that provide further information about each system are listed in Table 1.

Table 1. Examples of Early Detection and Rapid Notification Surveillance Systems



Electronic Surveillance System for Early Notification of Community-based Epidemics (ESSENCE)

Military GEIS/SurveillanceActivities/ ESSENCE/ESSENCE.asp

Lightweight Epidemiology Advanced Detection & Emergency Response System (LEADS)

Military sec_prod_leaders.html

Rapid Syndrome Validation Project (RSVP)

Sandia National Laboratories, New Mexico Department of Health (currently used in several western US states)

Electronic Surveillance System for the Early Notification of Community-Based Epidemics (ESSENCE II)

Johns Hopkins University GEIS/SurveillanceActivities/ ESSENCE/ESSENCE.asp

Supporting Public Health Surveillance Through the National Electronic Disease Surveillance System (NEDSS)

Centers for Disease Control and Prevention (CDC) docs/NEDSS%20Intro.pdf

Real-time Outbreak and Disease Surveillance (RODS)

University of Pittsburgh


Unlike traditional public health surveillance systems, which rely on diagnostic information to track possible disease epidemics, the systems listed in Table 1 use prediagnostic clinical and other data to evaluate a suspected outbreak. For example, systems like the Electronic Surveillance System for the Early Notification of Community-Based Epidemics (ESSENCE II) use data that imply levels of disease activity in a population, including International Classification of Disease, 9th Revision, Clinical Modification (ICD-9) codes used for billing patient visits, chief-complaint data from hospital emergency rooms, and telephone calls to nurse hotlines. Other systems, such as the Rapid Syndrome Validation Project (RSVP), rely more heavily on clinician judgement to evaluate the syndrome that a particular patient may present with. This information, combined with computerized disease prevalence and other data, may indicate a disease outbreak. Although each system differs with regard to how data are collected and the types of data collected, a common aspect is that all of the systems focus on rapid detection and automated reporting of data.

Surveillance System Approaches

In general, surveillance systems fall into 2 broad categories:

1. Those that primarily rely on clinical judgement to recognize disease syndromes found on patient presentation and that raise the index of suspicion of a bioterrorist-instigated or other emerging infectious disease outbreak (eg, RSVP), and

2. Those that primarily rely on data generated by clinical care (such as emergency room syndromes defined by ICD-9 codes) and individual behavior (such as pharmacy sales, ambulance calls, school absenteeism, and over-the-counter medication sales) to track possible disease outbreaks (eg, Essence II) (AP Zelicoff, personal communication, February 2003)

A more detailed description of a surveillance system in each category will help to further illustrate the different approaches. Both systems that will be described use syndrome groups to categorize nonspecific general conditions that represent early symptoms of certain infectious diseases. Classification of these syndromes is based on organ systems, as compared with the traditional surveillance approach, which is based on disease etiology.

The syndrome categories used by RSVP, a system that relies primarily on clinical judgement, and ESSENCE II, a system that relies primarily on data generated by clinical care, are listed in Table 2.

Table 2. Syndrome Categories

Syndromes used in RSVP

Syndromes used in ESSENCE II

- Influenza-like illness

- Fever with skin rash

- Fever with suspected central
nervous system infection

- Severe diarrhea

- Adult respiratory distress
syndrome (ARDS)

- Acute hepatitis

- Respiratory

- Gastrointestinal

- Fever

- Dermatologic, hemorrhagic

- Dermatologic, infections

- Neurologic

- Coma



RSVP was developed by scientists at Sandia National Laboratories in Albuquerque, New Mexico, with funding from the US Department of Energy's Chemical and Biological Weapons Non-Proliferation program. This system is currently being used in 45 large outpatient clinics and emergency rooms in several large western states, including Texas and California.

Reporting in the RSVP system is based on recognition of suspicious or novel symptoms that may or may not be part of a known disease or disease-complex. Six syndromes, thought to capture the majority of diseases important to public health, are used to help identify patients who warrant attention both in terms of medical care and public health surveillance (Table 2). Initial identification of the 6 syndromes was based on extensive input from practicing clinicians and public health officials, as well as a review of the main textbooks on infectious diseases, including Harrison's Textbook of Internal Medicine and Mandell, Douglas, and Bennett's Principles & Practices of Infectious Diseases (AP Zelicoff, personal communication, February 2003).

Unique to this system is reliance on physician judgement for capturing the severity of illness and for determining the category of disease. Once the clinician makes a judgment that a patient has presented with a cluster of signs and symptoms (a syndrome) that warrants attention, they enter that syndrome into the RSVP automated system to get updates on other reported cases that fit the particular syndrome identified. New disease outbreaks are continually updated on the system, and epidemiologic information can be accessed through a feedback screen that provides maps and graphs of disease patterns, as well as advisory messages from local public health authorities.

Unlike other surveillance systems that are employed primarily in emergency departments in hospitals, the RSVP system can be used by clinicians in both community and hospital-based settings (AP Zelicoff, personal communication, February 2003). It was designed specifically to be accessible and easy to use, in order to minimize demands of front-line healthcare professionals, while providing timely, useful information for busy clinicians.

Overall, the aim of the RSVP system is to establish strong communication between clinicians and public health authorities for the purpose of informing each other about unusual cases of disease or disease patterns. There are no patient identifiers, so confidentiality is protected. The system makes it very easy for clinicians to report suspicious diseases (i.e., a patient who is ill and fits into 1 of the 6 syndromes). It is also rewarding to use because it provides immediate feedback that can modify or verify a clinician's "index of suspicion," and may facilitate the rapid gathering and analyses of date by public health authorities (AP Zelicoff, personal communication, February 2003).


Sponsored by the Defense Advanced Research Projects Agency (DARPA) and developed by Johns Hopkins University Applied Physics Laboratory, ESSENCE II combines military and civilian healthcare information for the purpose of daily outbreak surveillance. It is currently being used in a multi-jurisdictional region with a large military population called the National Capital Area (NCA).

The major goal of this system is to improve early identification of an intentionally released bioagent into the community. An additional aim is to expand this system as a way to provide early warning of other abnormal diseases or conditions caused by naturally occurring infectious diseases.

Three types of data are collected and combined to evaluate the probability of an outbreak:

1. Sensitive healthcare data (data that require maintaining the privacy of individuals) - basic data that imply levels of disease activity in a population. Typically, these data are high in sensitivity (they can detect an outbreak), but have low specificity (they are limited in their ability to specify the exact cause of the outbreak). Such data include:


A. traditional surveillance data (laboratory results);

B. nontraditional clinical surveillance data -- clinical data generated from such areas as private practice billing codes grouped into syndromes, emergency room syndromes, veterinary syndromes, prescription drugs, calls to nursing hotlines and poison centers, etc; and

C. nontraditional, nonclinical surveillance data -- data provided by the community, such as data on school absenteeism and purchase of over-the-counter medications.

3. Publicly available information -- data needed to augment the data sources above to provide increased specificity of disease. For example, data on local endemic diseases and sales promotions can help evaluate the meaning of increased sales of over-the-counter medications.

4. Products of external surveillance -- data used to increase sensitivity, specificity, and timeliness of disease alerts.

Clinicians are primarily involved with the first type of data sources, particularly the nontraditional clinical data gathered in hospital or outpatient settings. Surveillance of these data is done by grouping the data sources (eg, emergency room visits, visits to private practice) into 1 of 7 syndrome groups, as listed in Table 2. Each syndrome group is defined by a specific set of ICD-9 codes. Typically, daily recording of syndrome groups reflects normal levels of common diseases within a community, which may vary by season and with the normal evolution of endemic disease strains. Surveillance therefore is based on the detection of abnormalities in syndrome group levels, compared with the typical normal "background levels" or noise over time, location, and population.[7] Data collected from all of the sources previously listed are automated and made available through secure Web sites to epidemiologists. In addition to early detection, another basic function of the ESSENCE II system is to deliver alerts and surveillance information to public health authorities.

Knowledge Base: Getting Clinicians to Think in Terms of Surveillance

Although surveillance systems may be useful for detecting naturally occurring infectious disease outbreaks, the development of many of these systems stem from the urgent need to better equip clinicians to recognize and report an outbreak caused by an intentional release of a pathogen or a bioagent. Toward this end, many of the educational efforts currently under way to involve clinicians in this type of disease surveillance are focusing on familiarity with the bioagents most likely to be used as weapons and on the clinical manifestations of diseases caused by these agents. This is an important step, because many clinicians have no training or experience in assessment, diagnosis, or treatment of illnesses caused by the majority of the potential bioagents.

Clinicians must also be educated to think in terms of syndromes that may represent infectious diseases and to help raise their index of suspicion. Combining this type of knowledge base with computerized systems that add epidemiologic and prevalence data can substantially improve the preparedness of front-line providers to accurately and rapidly detect an outbreak of one or multiple infectious processes.

Effective use of these surveillance systems for bioterrorism-related events will rely on:

  •   the ability to identify bioagents by recognizing early signs and associated symptoms and clinical syndromes,
  •        the ability to think in terms of syndromes when evaluating a patient, which includes considering potential bioterrorist agents in the index of suspicion,
  •        the ability to routinely use a computerized surveillance system to help validate the clinician's index of suspicion and correctly make a differential diagnosis, and
  •        the rapid notification of public health authorities of clinical syndromes or suspected clusters.

Identification of Bioagents and Specific Clinical Syndromes

On the basis of recommendations by a Working Group on Civilian Biodefense, the Centers for Disease Control and Prevention (CDC) has compiled a list of the bioagents determined to be the greatest threat if weaponized. In Table 3, the name of each agent type is followed by the disease associated with it, as well as a category of risk, which relates to the priority the agent is given in terms of the risk it poses if weaponized. Category A agents are thought to present the highest immediate risk to public health if turned into weapons, whereas category C agents pose the lowest immediate risk of these collective diseases.

Table 3. Potential Bioagents by Type of Agent, Associated Disease, and Category of Risk


Type of Agent

Associated Disease



Variola major


Category A

Viral hemorrhagic fevers

Ebola virus, Marburg virus, Lassa fever, Rift Valley fever, Omsk hemorrhagic fever, Kyasanur Forest disease

Category A


Venezuelan, Eastern, and Western equine encephalitis

Category B


Pneumonia, kidney failure

Category C

Nipah virus


Category C

Tickborne hemorrhagic fever

Crimean-Congo hemorrhagic fever

Category C

Tickborne encephalitis virus

Powassan virus encephalitis

Category C

Yellow fever

Hepatitis, fever, bleeding diathesis

Category C


Bacillus anthracis


Category A

Yersinia pestis


Category A

Francisella tularensis


Category A

Brucella spp


Category B

Vibrio cholerae


Category B

Burkholderia mallei


Category B

Coxiella burnetti

Q fever

Category B

Staphylococcus enterotoxin B

Form of food poisoning with vomiting

Category B

Multidrug-resistant tuberculosis

Cough, weight loss, hemoptysis, poor response to standard TB therapy

Category C


Clostridium botulinum


Category A

Ricinus communis

Ricin intoxication

Category B

Clostridium perfringens epsilon toxin

A form of food poisoning with diarrhea

Category B


Since most of the current focus is on category A agents, this article will describe only those clinical findings related to these agents. The specific purpose of this is to help clinicians make a rapid differential diagnosis.

Category A Agents

Category A agents are assigned the highest risk because they are easy to transmit and disperse, have the capacity to inflict substantial morbidity and mortality on large numbers of people, and can create widespread panic and social disruption among the general population. For all of the possible diseases in this category, early diagnosis is critical to providing the early treatment necessary to prevent or reduce morbidity and mortality in infected persons, as well as to prevent transmission.

 Anthrax. The organism that causes anthrax, Bacillus anthracis, is a bacteria found in soil worldwide. Humans contract the disease from close contact with animals or animal products infected with the bacteria. Of the 3 routes of exposure -- inhalational, cutaneous, and gastrointestinal -- the one that is of greatest concern as a bioweapon is inhalational anthrax (Table 4). Inhaled spores can germinate for up to 60 days in the mediastinal lymph nodes, so the time between exposure and onset of symptoms may be as long as several weeks.[11] The mortality rate for inhalational anthrax in the US cluster associated with mail contamination was 50%.

Table 4. Clinical Features of the 3 Forms of Anthrax


Incubation Period

Early Signs/

Later Signs/

Inhalational (primary involvement is the mediastinum)

2-60 days

Nonspecific flu-like symptoms, including fever, malaise, headache, cough, fatigue, and anorexia, but not rhinitis

Fever, chest pain, severe respiratory distress, diaphoresis, shock, and death


1-7 days, possibly up to 12 days

Fever and malaise; small papular or vesicular rash that may be pruritic

Painless ulceration with overlying eschar; localized edema -- often on head, forearms, or hands


1-7 days, typically 2-5 days

Fever, abdominal pain, bloody diarrhea, vomiting, and headache

Shock and death



As with anthrax, there are many routes of transmission for botulism. It can be acquired through exposure to 1 of the types of Clostridium botulinum toxin, the most potent toxin known to humans. Of the 7 antigentic types of C botulinum (A-G), human botulism is caused predominantly by types A, B, and E. The most common form of human botulism is acquired through the ingestion of toxin-contaminated food in which C botulinum spores have germinated (gastrointestinal). Other routes of transmission include the inhalation of aerosolized toxin and the germination of C botulinum in vivo in either a contaminated wound (wound botulism) or the gastrointestinal tract of infants (infant botulism). Although rarely described in the medical literature, it has been speculated that inhalational botulism would be the primary form of the disease if the botulinum toxin were weaponized. The clinical features are similar for each of these exposure routes, although incubation periods differ and are dependent on the level of toxin exposure.

Table 5. Clinical Features of Botulism



Early Signs/

Later Signs/

Botulism (all forms)

2-8 hours (if inhaled as an aerosol) (typically 12-72 hours for foodborne ingestion)

Incubation period for inhalational form not established

Generally no fever

Symmetric cranial neuropathies, such as drooping eyelids, difficulty swallowing or speaking

Mental status generally alert

Sensory exam generally normal

Blurred vision

Symmetric descending weakness - first paralysis of the arms, followed by respiratory muscles and legs.

Respiratory failure



Plague under natural conditions is generally transmitted to humans via rodent fleas infected with the bacterium Yersinia pestis, although humans can also contract it via direct contact with infected animal body and tissues or by inhaling infected droplets. Of the 3 types of plague -- bubonic, septic, and pneumonic -- primary pneumonic plague is the most feared as a possible weaponized agent. Transmitted person-to-person through the air via the respiratory route (primary) or caused by spread of untreated bubonic or septic plague (secondary), pneumonic plague is far more rare than the other plague types and more lethal. Early treatment is extremely important, as mortality rates rise considerably if treatment is not initiated within 24 hours of symptom onset (Table 6).

Table 6. Clinical Features of Pneumonic Plague



Early Signs/

Later Signs/

Pneumonic plague

1-4 days

Acute onset of high fever, cough, chest pain, dyspnea


Tachypnea (particularly in young children)


Bubo not present (rarely, cervical bubo may be noted)

Gastrointestinal symptoms (nausea, vomiting, abdominal pain, diarrhea)

Increasing dyspnea, stridor, and cyanosis

Rapidly progressive respiratory failure and sepsis within 2 to 4 days of illness onset.



Caused by the variola virus, smallpox is a fairly highly contagious acute viral illness. Communicability is by airborne droplet (something less than 10 particles are required for infection in susceptible hosts) and generally thought to start at onset of rash, which occurs about 2 days after onset of acute fever. An exposed person remains contagious for about 3 weeks, until scabs separate. The clinical syndromes that may result from inhalation of large quantities of smallpox (as could occur with an aerosol dispersion) are unknown, but on the basis of data from inhalation experiments conducted in monkeys, these are likely to be very severe and have an accelerated course, compared with person-to-person transmission. In macaques exposed to aerosolized monkeypox, pneumonia and/or disseminated-intravascular coagulation syndrome have been reported.

There are no known animal or insect reservoirs or vectors for the variola virus that causes smallpox. Of the 2 forms of disease -- variola major (ordinary smallpox) and variola minor (alastrim) -- the more virulent form, variola major, is of most concern as a possible biological weapon. Ordinary smallpox is the most common of the 5 clinical forms (accounting for 90% of cases); the other forms are flat-type, hemorrhagic, modified, and sine eruption (Table 7). The overall mortality rate of smallpox in fully susceptible humans is 30% to 50%, 11% in those immunized > 20 years ago and ~1% in individuals immunized < 10 years previously.

Table 7.  Clinical Features of Smallpox



Tularemia is a bacterial disease transmitted to humans primarily via contact with tissues and blood from animals infected with Francisella tularensis or from a bite from an infected arthropod, usually a tick or deerfly. Although highly transmissible because of the low number of organisms needed to cause infection, tularemia does not spread from person to person. The most common of the numerous forms of naturally occurring tularemia is ulceroglandular tularemia, which accounts for 45% to 85% of cases. Other forms of tularemia include glandular, pneumonic, oculoglandular, oropharyngeal, and typhoidal tularemia. If F tularensis were to be used as a biological weapon, concern would be most focused on an aerosolized release that would cause pneumonic tularemia (Table 8). Treatment of tularemia is critical to avoid progression to respiratory failure; meningitis; kidney, spleen, or liver involvement; sepsis; shock; and death.

Table 8. Clinical Features of Pneumonic Tularemia




Early Signs/

Later Signs/

Pneumonic tularemia

On average, 3-5 days, but can range from 1-14 days

Patients often present with community-acquired atypical pneumonia unresponsive to conventional antibiotic therapy

Predominant symptoms include abrupt onset of fever, nonproductive cough, myalgias (particularly low back)

Nausea, vomiting, and diarrhea may occur

Illness may be rapidly progressive and severe or may be indolent with progressive weakness and weight loss over several weeks to months

The progression of pneumonia tends to be slower than that of pneumonic plague

If left untreated, can progress to respiratory failure, meningitis, sepsis, shock, or death


Viral Hemorrhagic Fevers

The viral hemorrhagic fevers cover a diverse group of viruses, all of which share similar clinical signs and symptoms. Transmission to humans under natural conditions is through contact with infected arthropods or infected animal reservoirs. Dispersal through the air is highly infectious and can incur high rates of illness and death. The viruses that are considered the most dangerous if weaponized include the filoviruses (Ebola and Marburg), New World arenaviruses (Lassa fever, Junin, Machupo, Guanarito, Sabia), flaviviruses (Omsk hemorrhagic fever, Kyasanur Forest disease), and bunyaviruses (Rift Valley fever) (Table 9).

Table 9. Clinical Features of the Hemorrhagic Fevers



Early Signs/

Later Signs/

Ebola virus

2-21 days

Early signs include fever, severe prostration, headache, myalgias, abdominal pain, diarrhea; other symptoms may include chest pain, cough, pharyngitis, lymphadenopathy, photophobia, and conjunctival infection

Later symptoms include maculopapular rash, predominantly on trunk, appearing about 5 days after onset of illness; jaundice and pancreatitis often occur

As disease progresses, bleeding may develop, such as mucous membrane hemorrhages, hematemesis, bloody diarrhea, petechiae, ecchymoses, and oozing of blood at puncture sites

Marburg virus

2-14 days

Early signs include

fever, severe prostration, headache, vomiting, conjunctivitis, enanthem on soft palate, myalgias, backache, hyperesthesias, "clouded consciousness"

Later signs include maculopapular rash, appearing on 5th to 7th day on the trunk, face, neck, and proximal regions of extremities); nonpruritic

Jaundice and pancreatitis usually occur

As disease progresses, bleeding develops

Lassa fever

5-16 days

First signs are gradual development of fever, weakness, and generalized malaise

Later signs include arthralgias, back pain, nonproductive cough, and retrosternal pain, all of which often appear by 3rd to 4th day; severe exudative pharyngitis; maculopapular rash may be noted on some fair-skinned patients; severe prostration may occur by 6th to 8th day

As disease progresses, bleeding manifestations may develop

Rift Valley fever

2-6 days

Early signs include fever, headache, photophobia, retro-orbital pain

Subclinical infections are common and include undifferentiated fever, hemorrhagic fever

Later signs include hepatitis, bleeding, encephalitis, and retinitis

Kyasanur Forest disease

2-9 days

Early signs include sudden onset of fever, myalgias, and headache

Later signs (days 3 or 4) include diarrhea and vomiting

Enanthem with papulovesicular lesions occurs on soft palate

Ocular findings include conjunctival congestion, subconjunctival hemorrhage, superficial punctate keratitis, mild iritis, and retinal and vitreous hemorrhage

Cervical and axillary lymphadenopathy are usually present

Bleeding manifestations seen as early as 3rd day (bleeding from nose, gums, and gastrointestinal tract)

Omsk hemorrhagic fever

2-9 days

Early signs include fever, headache, vomiting, enanthem on palate, and hyperemia of skin on upper body and mucous membranes

Later signs include more severe fever, generalized lymphadenopathy and splenomegaly, and pneumonia in many patients

New World arenaviruses (Machupo, Junin, Guanarito, Sabia)

7-16 days

Gradual onset of signs, including fever, sore throat, myalgias, low back pain, and abdominal pain

As disease progresses, vascular or neurologic manifestations may occur (5-7 days after illness onset), including bleeding



Syndromic Surveillance as an Early Warning System for Biological Attacks

As shown in the previous tables, many of the early symptoms of exposure to a biological attack agent are generic, making an early diagnosis reasonably challenging. Thinking in terms of syndromes can assist a clinician to distinguish severely ill patients from those who may be presenting with self-limiting and benign illness. The syndromes, however, are most helpful to consider when the numbers of individuals with a particular syndrome surpass expected numbers. Table 10 illustrates the percentage of patients exposed to a given bioagent who will present with early signs associated with a particular syndrome. It must be kept in mind that a biological attack can be multifaceted and the mixture of syndromes can occur simultaneously or sequentially.

Table 10. Category A Agents and Associated Syndromes

Category A agent-
associated syndrome

% with influenza-
type illness

% with rapidly progressive pneumonia

% with acute bloody diarrhea or hemorrhagic disease

% with fever and rash or mental status changes or meningitis

% with acute hepatitis

Inhalational anthrax

50% to 90%

10% to 20%


10% to 50%



0% (not seen)

0% (not seen)

0% (not seen)

0% (not seen)

0% (not seen)

Viral hemorrhagic fevers

> 90%

10% to 50%

50% to 100%



Pneumonic plague

10% to 50%



< 10% (rare)

0% (not seen)


50% to 90%

< 10% (may be greater if variola aerosol is inhaled)

10% to 50%

> 90%


Pulmonary tularemia

25% to 50%






The following sections provide a brief synopsis of each type A agent with regard to signs/symptoms, clues that can increase the clinical index of suspicion of its use as a possible bioterrorist agent, and other diseases that share similar presenting symptoms. As shown in Table 10, patients may present with early symptoms that fit into more than 1 syndrome. For example, with smallpox, more than half of people will present with influenza-type illness and, following that, more than 90% will present with fever and rash. A comprehensive description and listing of these agents and information on making a differential diagnosis can be found at the Infectious Diseases Society of America Web site.

Index of Suspicion for Inhalational Anthrax

 Primary syndrome -- influenza-type illness. Several days of nonspecific flu-like symptoms accompanied by emesis, nausea, cough, and chest discomfort, with no evidence of coryza or rhinorrhea. This stage is followed by abrupt onset of respiratory distress, which may be accompanied by shock and/or mental status changes. The mental status changes, however, are generally a late event and represent a manifestation of anthrax meningitis.

Differential diagnosis. Influenza-type illness consistent with flu-like symptoms caused by a host of respiratory viruses will be prominent in the initial differential diagnosis. Other diseases with similar presentation may include bacterial mediastinitis, ruptured aortic aneurysm, psittacosis, and Legionnaires' disease.

Clues to suspected anthrax. Severe shortness of breath, chest pain, abdominal pain (less commonly), and early onset of nausea and vomiting are signs that distinguish inhalational anthrax from influenza. Chest x-ray finding of a widened mediastinum due to large, necrotic lymph nodes is highly suggestive. Anthrax should be low on the list of differential diagnoses in a patient presenting with symptoms of upper respiratory tract infection and rhinitis.

Index of Suspicion for Botulism

Primary syndrome. Disease generally begins with evidence of cranial nerve dysfunction and then progresses to muscle weakness (proximal muscle groups are affected first and may be more severely involved).[14] Dry mouth and blurred vision are common early symptoms. Patients generally do not have fever or sensory involvement, and mental status is normal.

Differential diagnosis. Guillain-Barré syndrome, myasthenia gravis, cerebrovascular accident (CVA), poisoning, tick paralysis, poliomyelitis, central nervous system infections, and psychiatric illness need to be considered.

Clues to suspected botulism. A number of features distinguish botulism from other diseases, such as ascending paralysis preceded by febrile illness. Distinguishing features of a CVA include asymmetric paralysis and altered consciousness. A distinguishing feature of poliomyelitis is asymmetric paralysis preceded by febrile illness. Central nervous system infections are distinguished by altered consciousness.[22]

Index of Suspicion for Pneumonic Plague

Primary syndrome -- rapidly developing pneumonia. Common early signs include acute onset of malaise, high fever, chills, headache, chest discomfort, dyspnea, and cough, accompanied or followed rapidly by clinical sepsis. Hemoptysis is a classic sign; other predominant signs include nausea, vomiting, diarrhea, and abdominal pain.[11]

Differential diagnosis. Inhalational anthrax, pneumonic tularemia, community-acquired bacterial pneumonia, and viral pneumonia need to be considered.

Clues to suspected pneumonic plague. Several features of pneumonic plague distinguish it from other types of pneumonia:

  • In patients with inhalational anthrax, true pneumonia is usually absent and hemoptysis is uncommon (its presence suggests plague);
  • In patients with tularemia, the clinical course is somewhat more slowly progressive; and
  • In patients with community-acquired bacterial or viral pneumonia, disease is rarely as fulminant.     

Despite the differences in these respiratory processes, substantial overlap in the syndromic presentation and progression can occur and, therefore, culture confirmation is vital. Clinical diagnosis should be made only in the setting of an already defined outbreak.

Index of Suspicion for Smallpox

Primary syndrome -- fever and rash. After an appropriate incubation period, early signs of early smallpox commonly include the acute onset of high fever, malaise, headache, backache, prostration, vomiting, and abdominal pain.[11] A rash appears 2 to 3 days later, beginning on the face and forearms. Initially maculopapular in character, the smallpox eruption becomes more typical in appearance within several days.

Differential diagnosis. Illnesses that cause fever and vesicular rash, particularly chickenpox (varicella), need to be considered. Other diseases that should be considered in the differential diagnosis include monkeypox, disseminated herpes zoster, disseminated herpes simplex, secondary syphilis, and impetigo.[14]


Clues to suspected smallpox. Recognizing the type and distribution of lesions can help differentiate a person with smallpox from an individual with chickenpox. In patients with smallpox, lesions are firm, round, well circumscribed, and deep-seated. Initial lesions will appear in the oropharynx (which may not be evident), face, or forearms, and the rash is centrifugal (ie, lesions are concentrated on the face and extremities [including palms and soles], with fewer lesions on the trunk). The lesions are quite painful and may become hemorrhagic. In patients with chickenpox, lesions are superficial and initially appear on the face, then on the trunk. Oral lesions may or may not occur, and the rash is distributed centripetally (ie, it is concentrated on the trunk, with less concentration on the face and extremities [including the palms and soles]). Chickenpox lesions are not painful but may become hemorrhagic. Importantly, all the lesions of smallpox will be at the same stage of development, whereas in chickenpox, any area of involvement will demonstrate lesions in various stages of progression.

Index of Suspicion for Pulmonary (Inhalational) Tularemia

Primary syndrome -- rapidly progressive pneumonia. Patients with pulmonary tularemia experience acute onset of symptoms that include fever, chills, myalgias, sweats, headache, and sore throat. Also common are nausea, vomiting, diarrhea, and abdominal pain.

Differential diagnosis. A variety of causes of community-acquired bacterial pneumonias need to be considered, including Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella pneumophila, Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Klebsiella pneumoniae, Moraxella catarrhalis, and the agent of Q fever.

Clues to suspected inhalational tularemia. Sudden clustering for severe pneumonias in previously healthy people is a primary clue indicating pulmonary tularemia, which should be confirmed by culture.

Index of Suspicion for Viral Hemorrhagic Fevers

Primary syndrome -- influenza-type illness. Early signs include fever, headache, myalgia, rash, nausea, vomiting, diarrhea, abdominal pain, and malaise.[11] The specific presentation of the numerous causes of this entity depends on the specific virus involved. Many illnesses, such as Ebola fever, are associated with a prominent bleeding diathesis. However, in others, such as Lassa fever, hemorrhage may be much less overt. When an agent is used as biological warfare, its distinct geographical distribution can no longer be used as a diagnostic reference point.

Differential diagnosis. Bacterial and rickettsial infections, (including staphylococcal and streptococcal toxic shock syndrome, meningococcemia, secondary syphilis, septicemic plague, typhoid fever, Rocky Mountain spotted fever, ehrlichiosis, and leptospirosis), viral infections (including influenza, hemorrhagic smallpox, measles, rubella, hemorrhagic varicella, and viral hepatitis), and parasitic conditions (including malaria and African trypanosomiasis) should be considered.

Clues to suspected viral hemorrhagic fevers. A high index of suspicion is warranted if a person presents with:

  • Acute onset of fever (< 3 weeks' duration);
  • Severe prostrating or life-threatening illness;
  • Bleeding manifestations that include at least 2 of the following: hemorrhagic or purpuric rash, petechiae (particularly in nondependent areas), epistaxis, hematemesis, hemoptysis, blood in stool, or other evidence of bleeding; and
  • No predisposing factors for a bleeding diathesis.[14]

Use of Surveillance Systems

Increasing clinicians' knowledge base of potential bioagents and their associated clinical syndromes is a fundamental step toward improving rapid detection of potential outbreaks. In addition to basing clinical judgment on syndrome assessment to raise the index of suspicion in the clinical setting, clinicians also need epidemiologic data to verify a suspected outbreak. The syndrome-based systems currently in development and discussed previously are designed to augment clinical judgment and to improve rapid detection of disease and subsequent notification to public health authorities. Information that can be enhanced by these systems for accurate disease detection includes:

  • presence of a large epidemic;
  • unusually severe disease or unusual routes of transmission;
  • unusual geographical distribution, unusual season, or absence of normal vector;
  • multiple simultaneous epidemics of different diseases;
  • outbreak of zoonotic disease;
  • unusual strains of organisms or antimicrobial resistance patterns;
  • higher attack rates in persons with common exposures;
  • credible threat of a biological attack, as determined by authorities; and
  • direct evidence of a biological attack.

Along with early detection, rapid notification to public health authorities of a suspected disease outbreak is also critical to successful surveillance outcomes. The syndromic surveillance systems are designed to bridge the communication lag between clinicians and public health authorities. This obviously is a critical step in producing early recognition and a subsequent reduction of a mass exposure to a biological agent, particularly those that can be transmitted from person to person. As demonstrated by both the RSVP and ESSENCE II systems, a primary goal of these systems is to facilitate exchange of information between clinicians gathering data in outpatient settings and hospitals and public health authorities tracking diseases by region and time frame. This reporting can then serve to generate alerts to such abnormal outbreaks in specific regions over time, greatly improving the way traditional surveillance programs work.

A number of challenges remain before any surveillance system can be used by clinicians providing direct care to patients. First, there must be easily available access to the surveillance system. This would require primary care clinicians to have computers and Internet access on site -- something that many practices and institutions are currently lacking. Second, although there are reporting systems already in place, particularly for certain areas of infectious disease control such as sexually transmitted diseases, actual reporting by clinicians has been generally poor and not constant. This response must be improved as emerging infectious diseases and bioterrorist threats grow in importance. Finally, it is important to determine which of the emerging systems would be most efficacious in rapidly detecting disease outbreaks. This will be difficult to determine until more data are available.

It is imperative that surveillance systems be continually tested and improved. For example, the designers of the ESSENCE II system noted a lag time of 1-3 days between patient visit and time of data receipt. However, they contend that with minor reprogramming, the automated transmission cycle can be made faster and data lag time can be decreased to 1 day or less.

Detecting Specific Bioterrorism Epidemics and Agents

The attributes of the CDC category A bioterrorism agents that affect their detection, as well as the benefits of early detection, are summarized below, on the basis of potential bioterrorism-related epidemic profiles developed by experts. These profiles reflect current knowledge of these diseases; their epidemiology might differ if novel modes of dissemination or preparation were employed. Each disease has attributes that could increase or decrease the likelihood of early outbreak recognition through either clinical diagnosis or syndromic surveillance.

Inhalational Anthrax

The distribution of the incubation period for inhalational anthrax can be relatively broad as observed in Sverdlovsk (2–43 days); most cases occur within 1–2 weeks after exposure. In the 2001 U.S. outbreak, the distribution of incubation periods was more limited, 4–6 days, although later-onset cases may have been averted by antibiotic prophylaxis. The nonspecific prodrome for anthrax may last from several hours to several days. Taken together, these data suggest that the initial slope of an epidemic curve may be comparatively gradual during the first week, leading to slower recognition through syndromic surveillance than for other infections caused by bioterrorist agents with pulmonary manifestations, such as tularemia or pneumonic plague. In contrast, mediastinal widening on chest x-ray or computed tomographic scan or Gram stain of cerebrospinal or pleural fluid should lead an alert and knowledgeable physician to consider the diagnosis of anthrax, even though these tests may not be conducted until relatively late in the clinical course. B. anthracis is likely to be detected quickly in cultures, favoring clinical recognition. Retrospective analysis of data from 2001 showed that inhalational anthrax can be distinguished from influenzalike illness or community-acquired pneumonia by using an algorithm that combines clinical and laboratory findings, although the practical utility of this approach is untested. In addition to permitting antibiotic use among ill persons, early recognition would enable postexposure antibiotic prophylaxis).


The typical incubation period for tularemia is relatively narrow after a person is exposed to aerosolized F. tularensis, with abrupt onset of nonspecific febrile illness, with or without respiratory symptoms, in 3–5 days (range 1–14 days), followed by rapid progression to life-threatening pneumonitis. This relatively narrow incubation period for most patients and rapid progression to severe disease would lead to a rapid increase in cases after a large and acute exposure. Finding a number of such cases in a short interval should trigger both syndromic surveillance alarms and clinical suspicion. F. tularensis is a slow-growing and fastidious organism and may take up to 5 days after inoculation to be detectable, if it is detected at all, in a routinely processed blood culture. The use of special laboratory techniques may be required, delaying the likelihood of detection in the absence of clinical suspicion. After an epidemic is recognized, specific antibiotic therapy is recommended for exposed persons in whom a febrile illness develops.

Pneumonic Plague

Exposure to aerosolized Yersinia pestis results in pneumonic plague, which has a typical incubation period of 2 to 4 days (range 1–6 days). The disease has a relatively short prodrome, followed by rapidly progressive pneumonia, which would lead to a rapid increase in cases at the onset of an epidemic. Standard clinical laboratory findings are nonspecific, which alone might not prompt clinical suspicion, but microscopic examination of a sputum smear may show characteristic findings, which should prompt consideration of the diagnosis. Cultures of blood or sputum are apt to show growth within 24 to 48 hours, but routine procedures may misidentify Y. pestis unless the diagnosis is suspected and special attention is given to specimen processing. Confirming the diagnosis depends on special tests available through reference laboratories. Treatment the first day of symptoms is generally considered necessary to prevent death in pneumonic plague, so early recognition of an aerosol plague attack would enable life-saving use of antibiotics in febrile patients and prophylaxis of contacts.


Foodborne botulism typically has a relatively narrow incubation period (12–72 hours), which may vary from 2 hours to 8 days, depending on the inoculum. For the three known cases of inhalational botulism attributed to a relatively low exposure to aerosolized toxin, the incubation period was approximately 72 hours. The characteristic clinical picture of descending paralysis should prompt consideration of botulism, and this unique pattern among bioterrorism agents lends itself to a specific syndrome category. However, the illness may be misdiagnosed, as observed in a large foodborne outbreak of botulism in 1985; 28 persons who had eaten at a particular restaurant and in whom botulism had developed were assigned other diagnoses before the geographically dispersed outbreak was recognized and publicized in the media. Symptoms of inhalational botulism, with choking, dysphagia, and dysarthria dominating the clinical picture, may differ from those associated with ingestion of toxin and complicate recognition of the disease. Specialized testing for botulinum toxin is available at a limited number of state laboratories and CDC. Postexposure prophylaxis is limited by the scarcity of, and potential for, allergic reactions to botulinum antitoxin, leading to recommendations that exposed persons be observed carefully for early signs of botulism, which should prompt antitoxin use. Antitoxin should be given as early as possible, another fact that highlights the importance of early detection. Depending on the level of exposure and the geographic dispersion of affected persons, syndromic surveillance for characteristic neurologic symptoms could aid outbreak detection, or the occurrence of an epidemic might be obvious to clinicians.


The incubation period of smallpox is usually 12–14 days but may range from 7 to 17 days. The early symptomatic phase includes a severe febrile illness and appearance of a nonspecific macular rash over a 2- to 4-day period, followed by evolution to a vesicular and then pustular rash over the next 4 to 5 days. Thus, the initial phase of smallpox may lend itself to detection through surveillance of a febrile rash illness syndrome. Once smallpox is suspected, the virus can be rapidly detected by electron microscopic examination of vesicular or pustular fluid, if laboratory resources for electron microscopy are available, or by polymerase chain reaction, if the necessary primers are available. Contacts can be protected by vaccination up to 4 days after exposure. Discourse is substantial about the relative merits of pre-event versus postevent vaccination. Syndromic surveillance may show an increase in febrile rash illness, although once the characteristic rash appears, the diagnosis should be quickly established.

Viral Hemorrhagic Fevers

This category includes multiple infectious agents that range from having a relatively broad to narrow incubation period (e.g., Ebola, 2–21 days; yellow fever 3–6 days). These diseases present with nonspecific prodromes that may have an insidious or abrupt onset. In severe cases, the prodrome is followed by hypotension, shock, central nervous system dysfunction, and a bleeding diathesis. The differential diagnosis includes a variety of viral and bacterial diseases. Establishing the diagnosis depends on clinical suspicion and the results of specific tests that must be requested from CDC or the U. S. Army Medical Research Institute of Infectious Diseases. The value of postexposure prophylaxis with antiviral medications is uncertain, and (with the exception of yellow fever, for which a vaccine is available) response measures are limited to isolation and observation of exposed persons, treatment with ribavarin (if the virus is one that responds to that antiviral drug), and careful attention to infection control measures. Patients seen with symptoms during the prodromal phase may not clearly fit into a single syndrome category, but syndromic surveillance focused on the early signs of a febrile bleeding disorder would be more specific.

One of the biggest concerns about syndromic surveillance is its potentially low specificity, resulting in use of resources to investigate false alarms. Specificity for distinguishing bioterrorism-related epidemics from more ordinary illness may be low because the early symptoms of bioterrorism-related illness overlap with those of many common infections. Specificity for distinguishing any type of outbreak from random variations in illness trends may be low if statistical detection thresholds are reduced to enhance sensitivity and timeliness. The likelihood that a given alarm represents a bioterrorism event will be low, assuming that probability of such an event is low in a given locality. Approaches used to increase specificity include requiring that aberrant trends be sustained for at least 2 days or that aberrant trends be detected in multiple systems. Another approach to enhancing specificity would be to focus surveillance on the severe phases of disease, since the category A bioterrorism infections are more likely than many common infections to progress to life-threatening illness. For those diseases that are likely to progress rapidly, such as pneumonic plague, syndromic detection of severe disease (e.g., through emergency room visits, hospital admissions, or deaths) may be more feasible than detection aimed at early indicators before care is sought (e.g., purchases of over-the-counter medications) or when illness is less severe (e.g., primary care visits). Whether detection of syndromic late-stage disease offers an advantage over detection through clinical evaluation will depend on the attributes of the infections and diagnostic resources, as described above.

Predicting how the mix of relevant factors would combine in a given situation to affect the recognition of a bioterrorism-related epidemic is difficult, although mathematical models may provide further insight. The most important factors affecting early detection are likely to be the rate of accrual of new cases at the outset of an epidemic, geographic clustering, the selection of syndromic surveillance methods, and the likelihood of making a diagnosis quickly in clinical practice.

Ongoing efforts to strengthen the public health infrastructure and to educate healthcare providers about bioterrorism diseases and reporting procedures should strengthen the ability to recognize bioterrorism outbreaks. For example, in New Jersey in 2001, reporting of two early cases of cutaneous anthrax was delayed until publicity about other anthrax cases prompted physicians to consider the diagnosis and notify the health department, suggesting that opportunities for earlier use of postexposure prophylaxis were missed. In addition, while the importance of new diagnostic tools, including rapid tests, should be emphasized, the essential role of existing diagnostic techniques should not be overlooked. Clinical suspicion is critical, and a key prompt for arousing clinical suspicion may be the microscopic examination of a routinely collected specimen, as occurred in the index case of the 2001 anthrax outbreak, when a Gram stain of the cerebrospinal fluid led to the diagnosis. However, as recently highlighted by the Institute of Medicine, the use of basic diagnostic tests has decreased because of efforts to reduce the costs of care, the increasing use of empiric broad-spectrum antibiotic therapy, and federal laboratory regulations, such as the Clinical Laboratory Improvement Amendments of 1988, which have discouraged laboratory evaluation in some clinical settings.

While we have focused on the role of syndromic surveillance in detecting a bioterrorism-related epidemic, other uses of syndromic surveillance include detecting naturally occurring epidemics, providing reassurance that epidemics are not occurring when threats or rumors arise, and tracking bioterrorism-related epidemics regardless of the mode of detection. Syndromic surveillance is intended to enhance, rather than replace, traditional approaches to epidemic detection. Evaluation of syndromic surveillance to consider the spectrum of potential uses is essential. A certain level of false alarms, as the result of either syndromic surveillance or calls from clinicians, will be necessary to ensure that opportunities for detection are not missed. Efforts to enhance the predictive value of syndromic surveillance will be offset by costs in timeliness and sensitivity, and defining the right balance in practice, particularly in the absence of an accurate assessment of bioterrorism risk, will be essential.

Two committees of the National Academies have recommended more careful evaluation of the usefulness of syndromic surveillance before it is more widely implemented. Because the epidemiologic characteristics of different bioterrorism agents may vary in ways that affect the detection of epidemics, these evaluations should address the epidemiology of specific bioterrorism agents. Efforts to detect bioterrorism epidemics at an early stage should not only address the development of innovative new surveillance mechanisms but also strengthen resources for diagnosis and enhance relationships between clinicians and public health agencies—relationships that will ensure that clinicians notify public health authorities if they suspect or diagnose a possible bioterrorism-related disease. 


Health Alert Network web pages provide important information to assist states in developing their health alert network information technology (IT) and distance learning (DL) capacity, including the IT and DL architectural standards, Information Technology Capacity Inventory for assessing current IT capacity, Distance Learning Assessment for assessing current DL capcacity, web-based PHPPO informatics course, other training opportunities, emergency contacts, and other important information to assist state and local health agencies with improving their public health IT and DL infrastructure.

The Health Alert Network (HAN) is a nationwide, integrated information and communications system serving as a platform for distribution of health alerts, dissemination of prevention guidelines and other information, distance learning, national disease surveillance, and electronic laboratory reporting, as well as for CDC=s bioterrorism and related initiatives to strengthen preparedness at the local and state levels.

When complete, the Health Alert Network will ensure:

  • High-speed, secure Internet connections for local health officials, providing access to CDC=s prevention recommendations, practice guidelines, and disease data; capacity for rapid and secure communications with first responder agencies and other health officials; and capacity to securely transmit surveillance, laboratory, and other sensitive data
  • On-line, Internet- and satellite-based distance learning systems
  • Early warning broadcast alert systems
  • That public health agencies achieve high levels of organizational capacity.


CDC is partnering with local and state health agencies and national public health organizations to:

  • Connect local health agencies to the Internet by funding initial purchase and installation of electronic computing and communications equipment, including equipment for satellite- and Internet-based training
  • Develop and deliver training in the use of information technology in order to prepare public health workers to respond to bioterrorist threats
  • Develop electronic tools to support preparedness for and response to bioterrorism and other disease threats, and rapid dissemination of health warnings
  • Deploy authoritative preparedness, diagnosis, and treatment guidelines
  • Develop science-based, local health department performance standards related to domestic terrorism and other essential health services


CDC is providing HAN funding and technical assistance to the following recipients:

  • All 50 state health agencies, the District of Columbia, the territory of Guam
  • Three metropolitan health departments (Chicago, County of Los Angeles Department of Health Services, and New York City)
  • Three Local Exemplar Centers for Public Health Preparedness (DeKalb County Board of Health, Georgia; Monroe County Health Department, New York; and Denver Health/Denver Public Health, Colorado)

Homeland Security Adopted Standards for First Responder Personal Protective Equipment

The Department of Homeland Security, through its Science and Technology division, has adopted the following standards for personal protective equipment to protect first responders against Chemical, Biological, Radiological, Nuclear and Explosive (CBRNE) threats.  These standards, which are outlined below were developed by the National Institute for Occupational Safety and Health (NIOSH) or the National Fire Protection Association (NFPA). Except where noted, these standards have been adopted by the InterAgency Board for Equipment Standardization and InterOperability (IAB), as listed in the organization's 2002 Annual Report:

NIOSH Chemical, Biological, Radiological and Nuclear (CBRN) Standard for Open-Circuit Self-Contained Breathing Apparatus (SCBA) (December 2001) - This standard establishes performance and design requirements to certify Self-Contained Breathing Apparatus (SCBA) for use in chemical, biological, radiological, and nuclear (CBRN) exposures for use by first responders.  The standard employs a three tier certification program.  The first two tiers of the program ensure the SCBA meets current minimum NIOSH requirements and the enhanced requirements of the NFPA 1981 standard, including greater flow, improved breathing resistance, environmental stresses, communications, and vision.  The third tier incorporates special testing conducted by NIOSH to identify the hazard a first responder is likely to encounter at a terrorist event and to define levels of respiratory protection required for the first responder.

NIOSH Standard for Chemical, Biological, Radiological, and Nuclear (CBRN) Full Facepiece Air Purifying Respirator (APR) (April 2003)** - The purpose of this standard is to specify minimum requirements to determine the effectiveness of full facepiece air purifying respirators (APR), commonly referred to as gas masks, used during entry into chemical, biological, radiological, and nuclear (CBRN) atmospheres not immediately dangerous to life or health (IDLH).  Atmospheres that are above IDLH concentrations require the use of Self-Contained Breathing Apparatus.

NIOSH Standard for Chemical, Biological, Radiological, and Nuclear (CBRN) Air-Purifying Escape Respirator and CBRN Self-Contained Escape Respirator (October 2003)** - Escape respirators, which are also known as escape hoods, come in two types.  In the first type, called an air-purifying escape respirator, a filter canister is mounted on the hood.  The user breathes outside air through the canister, which filters out harmful contaminants before the air is inhaled.  The second type, called a self-contained escape respirator, consists of a hood with a tightly fitting neck piece and a contained source of breathing air.  The hood provides a barrier against contaminated outside air, and the user breathes air from the attached source.  The purpose of this standard is to specify minimum requirements to determine the effectiveness of escape respirators that address CBRN materials identified as inhalation hazards from possible terrorist events for use by the general working population.

NFPA 1951: Standard on Protective Ensemble for USAR Operations, 2001 Edition - USAR operations in urban and other non-wilderness locations are complex incidents requiring specially trained personnel and special equipment to complete the mission.  NFPA 1951 establishes minimum requirements for garments, head protection, gloves, and footwear, for fire and emergency services personnel operating at technical rescue incidents involving building or structural collapse, vehicle/person extrication, confined space entry, trench/cave-in rescue, rope rescue, and similar incidents.  The requirements of the standard address the design, performance, testing, and certification of these ensembles and ensemble elements to protect against physical, environmental, thermal, chemical splash, and blood-borne hazards associated with USAR operations.

NFPA 1981, Standard on Open-Circuit Self-Contained Breathing Apparatus for Fire and Emergency Services, 2002 edition - This document specifies the minimum requirements for the design, performance, testing, and certification of SCBA for fire and emergency services personnel. The 2002 NFPA 1981 now sets requirements for heads-up displays (HUD) that provide the SCBA user with:

  •       Information regarding breathing air supply status
  •       Alerts that notify users when the breathing air supply is at 50 percent of full
  •       Where the HUD is powered by battery power source, a low battery alert that signals when the charge is reduced to the level where the HUD can operate only for 2 more hours.

This edition also includes new requirements for a Rapid Intervention Company/Crew (RIC) Universal Air Connection (UAC) (or RIC UAC) on all new SCBA. The RIC UAC provides a standard connection that allows a rescue breathing air supply to be connected to a victim fire fighter or other emergency services responder's SCBA to replenish the breathing air in the SCBA breathing air cylinder when the victim can not be rapidly moved to a safe atmosphere.

NFPA 1991: Standard on Vapor-Protective Ensembles for Hazardous Materials Emergencies, 2000 Edition  - NFPA 1991 specifies minimum requirements for design, performance, testing, and certification of elements of vapor-protective ensembles for emergency responders to hazardous materials incidents, and chemical or biological terrorism incidents, for protection from specified chemical vapor, liquid splash, and particulate exposures. The Standard also provides additional optional requirements for protection from chemical and biological agents that could be released during a terrorism incident, chemical flash fire protection, liquefied gas protection, and combined chemical flash fire and liquefied gas protection.

NFPA 1994: Standard on Protective Ensembles for Chemical/Biological Terrorism Incidents, 2001 Edition - NFPA 1994 establishes minimum requirements for ensembles and ensemble elements for fire and emergency services personnel exposed to victims and agents during assessment, extrication, rescue, triage, and treatment operations at chemical and biological terrorism incidents. The requirements of the standard address the design, performance, testing, documentation, and certification of these protective ensembles that provide protection for fire and emergency services personnel from terrorism agents including dual-use industrial chemicals, chemical terrorism agents, or biological terrorism agents.  The standard establishes three levels of protective ensembles, Class 1, Class 2, and Class 3 ensembles, that could be selected for protection of fire and emergency services personnel based on what the incident risk analysis indicates is necessary protection for the intended operations.

NFPA 1999: Standard on Protective Clothing for Emergency Medical Operations, 2003 Edition - NFPA 1999 establishes minimum performance requirements for ensembles and ensemble elements to protect first responders from contact with blood and body fluid-borne pathogens when providing victim or patient care during emergency medical operations. This standard specifies minimum documentation, design, performance, testing, and certification requirements for new-single use and new multiple-use emergency medical clothing used by fire and emergency services personnel during emergency medical service (EMS) operations. These items include:

  • Garments -- both full and partial, upper and lower torso protection
  • Three types of gloves -- examination gloves for patient care, work gloves for situations that post higher physical hazards such as extrication, and cleaning gloves for handling and cleaning contaminated EMS equipment
  • Footwear
  • Face protection

EMS personal protective equipment (PPE) must provide blood and body fluid pathogen barrier protection to whatever parts of the body they cover. While no partial protection is allowed for the EMS PPE item, the items might be configured to cover only part of the upper or lower torso, such as arms with sleeve protectors, torso front with apron styled garments, and face with face shields. ceu

Required Reading:   Guide for the Selection of Personal Protective Equipment for Emergency First Responders

Author: Center for Disease Control and Prevention


National Institute of Justice

Center for Disease Control and Prevention, Bioterrorism CEUs Nursing, Texas, Nevada


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