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Pediatric Terrorism and Disaster Preparedness

Public Health Emergency Preparedness

This resource was part of AHRQ's Public Health Emergency Preparedness program, which was discontinued on June 30, 2011, in a realignment of Federal efforts.

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Chapter 4. Biological Terrorism

Background

History of Bioterrorism

Although recent world events have heightened awareness of bioterrorism and biowarfare, there are many historical accounts of both. During the middle ages, the Tartars are reported to have catapulted plague-infested cadavers into the walled city of Caffa. In the 15th century, Pizarro supplied the native people of South America with smallpox-contaminated clothing in an effort to gain control of land. During the Spanish-American war, the Spaniards are alleged to have supplied the American Indians with blankets infected with smallpox virus. Japanese researchers have admitted to feeding cultures of Clostridium botulinum to Chinese prisoners of war during the 1930s. During World War II (WWII), the Japanese again used bioterrorism against the Chinese when they dropped plague-infested fleas over China, causing outbreaks of plague.

Two more recent bioterrorist events in U.S. history involved contamination of the food supply. In 1984, in The Dalles, Oregon, an outbreak of 751 cases of Salmonella typhimurium was linked to the intentional contamination of restaurant salad bars by members of the Rajneesh religious cult. In 1996, an outbreak of Shigella dysenteriae type 2 among laboratory workers at a large Texas medical center was traced to muffins and donuts anonymously left in the break room. Shigella isolates from infected victims matched those found in an uneaten muffin and in the laboratory's stock strain.

There are reports that the Japanese cult Aum Shinrikyo has attempted bioterrorist attacks across Tokyo using anthrax, sarin gas, and botulinum toxin. In 1994, this cult succeeded in sickening 500 people and killing 7 with sarin gas. In 1995, again using sarin gas, Aum Shinrikyo injured 3,800 people and killed 12 by releasing the gas in five subway stations around Tokyo.

The anthrax attacks of October 2001, propagated through the U.S. Postal Service, led to infections in 22 people (11 cases of cutaneous anthrax and 11 cases of inhalational anthrax) and 5 deaths. These attacks affected thousands of people around the world, including those who were presumed exposed and required antibiotic prophylaxis and/or vaccination; the numerous anxious and worried individuals who flooded hospital emergency rooms, physicians' offices, and public health information hotlines; and the thousands of public health, medical, and law enforcement workers who investigated potential attacks.

For a video about the history of bioterrorism, go to:  http://www.bt.cdc.gov/training/historyofbt/index.asp.

Bioterrorism Research

Beginning in the 1920s, the Soviet biowarfare program reportedly conducted research on gas gangrene, tetanus, botulism, plague, and typhus. In the 1970s, this program was greatly expanded as the secret organization Biopreparat. At its height, this program involved 60,000 people working in more than 50 facilities across the former Union of Soviet Socialist Republics (USSR).  Plague, anthrax, smallpox, tularemia, brucellosis, glanders, Marburg virus, and Venezuelan equine encephalitis (VEE) virus were produced. Yersinia pestis, anthrax, and variola reportedly were prepared for use in intercontinental missiles. By WWII, the United States, the United Kingdom, Canada, Germany, Japan, and the USSR all had active biological weapons programs.

The Iraqi bioterrorist program, initiated in 1974, has been of recent interest. Although much is still unknown about this program, the United Nations Special Commission has information from Iraq that this program studied the use of botulinum toxin, B. anthracis, influenza virus, aflatoxin, trichothecene mycotoxins, and ricin. During the Gulf War, Iraq reportedly prepared missiles and bombs that contained aflatoxin, botulinum toxin, and B. anthracis, although they were never used.

Disarmament and Legislation

In 1969, the United Kingdom and the USSR began to call for bioweapons disarmament. That same year, the U.S. offensive bioterrorist program was dismantled, although the biodefense program continued. In 1971, the U.S. Army Medical Research Institute of Infectious Diseases was opened to research biological protective measures, diagnostic procedures, and therapeutics. By 1973, the United States had destroyed its entire arsenal of bioterrorist agents.

The Convention on the Prohibition of the Development, Production, and Stockpiling of Bacteriological (Biological) and Toxin Weapons and on Their Destruction, also called the Biological Weapons Convention (BWC), was opened for signature in 1972 and became effective in 1975. It was the first multilateral disarmament treaty banning an entire category of weapons. Although the BWC is an international agreement, there is no monitoring mechanism to ensure each party's adherence.

In 1979, a few years after the signing of BWC, there was a massive accidental release of aerosolized B. anthracis spores in Sverdlovsk, Russia; 79 people became ill and 69 died. The Soviets maintained that this outbreak was due to the ingestion of contaminated meat sold on the black market. However, President Yeltsin acknowledged in 1992 that in 1979 there had been an accidental release of an unspecified biological agent from a military facility. This is an important event in world history because it was the first major evidence that a nation was in direct violation of the BWC.

In the United States in 1995, a member of a white supremacist group attempted to buy Y. pestis from an Ohio laboratory supply company and later attempted to purchase anthrax from a Nevada company. This resulted in the passage of the Antiterrorism and Effective Death Penalty Act of 1996, commonly referred to as the "Select Agent Rule" (42 CFR Part 72.6, Fed Reg Oct. 24, 1996).

In June 2002, the Public Health Security and Bioterrorism Preparedness and Response Act of 2002 was signed into law (PL 107-188). This Act updated the existing Select Agent Rule by requiring facilities to register if they possessed select agents. Previously, only facilities that wanted to transfer select agents needed to register with the Centers for Disease Control and Prevention (CDC).

Epidemiology of a Terrorist Attack

Biological terrorism is the deliberate use of any biological agent against people, animals, or agriculture to cause disease, death, destruction, or panic, for political or social gains. A bioterrorist agent may be a common organism, such as influenza or Salmonella, or a more exotic organism such as Ebola virus or variola virus.

In June 1999, a panel of public health, infectious disease, military and civilian intelligence, and law enforcement experts was convened to determine which biological agents (microorganisms and toxins) posed the greatest potential for use in a bioterrorist attack, to be designated as "Category A" agents. These are the following:

  • Variola major (smallpox).
  • B. anthracis (anthrax).
  • Y. pestis (plague).
  • Francisella tularensis (tularemia).
  • Botulinum toxin (botulism).
  • Filoviruses and arena viruses (viral hemorrhagic fevers [VHF]).

Category A agents would have the greatest adverse public health, medical, and social impact if used as a bioterrorist agent for the following reasons:

  • They are infectious and stable in aerosol form.
  • The world population is highly susceptible to the infections they cause.
  • They cause high morbidity and mortality.
  • Some can be transmitted from person to person (smallpox, plague, VHF).
  • The illnesses they cause can be difficult to diagnose and treat.
  • They have been previously developed for biowarfare.

Although bioterrorist attacks ultimately could affect large numbers of people, disease in a single patient may be enough reason to investigate the possibility of biological terrorism. Although some bioterrorist events are subtle, a number of clues should heighten suspicion that a bioterrorist attack has occurred:

  • Disease caused by an uncommon organism (e.g., smallpox, anthrax, or VHF).
  • A less common presentation of infection with one of these organisms. For example, while a small number of cases of cutaneous anthrax occur naturally each year in the United States, cases of inhalational anthrax are highly unusual.
  • A disease identified in a geographic location where it is not usually found (e.g., anthrax in a non-rural area, or plague in the northeastern United States).
  • Unexpected seasonal distribution of disease (such as influenza in the summer).
  • Antiquated, genetically engineered, or unusual strains of infectious agents.
  • Multiple unusual or unexplained diseases in the same patient.
  • Disease in an atypical age group or population, such as anthrax in children or varicella-like rashes in adults.
  • Large numbers of cases of unexplained disease or death.
  • An unexplained increase in the incidence of an endemic disease that previously had a stable incidence rate.
  • An unusual condition striking a disparate population, such as respiratory illness in a large population.
  • A large number of people seeking medical care at a particular time (signaling they may have been present at a common site, timed with the release of an agent).
  • A large number of people presenting with similar illnesses, in noncontiguous regions (may be a sign that there have been simultaneous releases of an agent).
  • Animal illness or death that precedes, follows, or occurs simultaneously with human illness or death (may indicate release of an agent that affects both animals and people).

However, because no list of clues can be all inclusive, all health care providers should be alert for the possibility that a patient's condition may not be due to natural causes.  When there is no other explanation for an outbreak of illness, it may be reasonable to investigate bioterrorism as a possible source. Common sources of exposure to an agent may include the following:

  • Food and water that has been deliberately contaminated.
  • Respiratory illness due to proximity to a ventilation source.
  • Absence of illness among those in geographic proximity but not directly exposed to the contaminated food, water, or air.

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Agents Categorized by System Predominantly Affected

For  early clinical signs and symptoms after exposure to selected bioterrorist agents, go to Table 4.1.

Respiratory System

Anthrax, plague, and tularemia are all caused by infections with Category A agents and may present as respiratory illnesses.

Anthrax

The incubation period of inhalational anthrax is usually 1-6 days, although it can be longer. The initial symptoms are nonspecific and may resemble those of the common cold (low-grade fever, nonproductive cough, fatigue, malaise, fussiness, poor feeding, sweats, and chest tightness or discomfort), although rhinorrhea is absent. During this phase, chest auscultation usually reveals no abnormalities, although vague rhonchi may be heard. The chest radiograph may reveal pathognomonic mediastinal widening, pleural effusion, and rarely, infiltrates (Figure 4.1, 20 KB). The patient may seem to begin to recover and then become severely ill 1-5 days later. During this phase, sometimes called the "subsequent phase," there is an abrupt onset of high fever and severe respiratory distress, including dyspnea, stridor, diaphoresis, and cyanosis. Despite ventilatory support and antibiotic therapy, shock and death (75% case fatality rate) often occur within 24 to 36 hours. Patients with inhalational anthrax are not contagious, so the only infection control measure necessary is standard precautions.

Plague

Although natural plague can present in a number of forms (septicemic, bubonic, and pneumonic), aerosolization of Yersinia pestis causing pneumonic plague would be the most effective mode for a bioterrorist attack. The incubation period is short, about 2 to 4 days and is followed by fever, headache, malaise, cough, dyspnea, and cyanosis. The cough is productive and may be watery, purulent, or bloody. Chest radiographs often reveal bilateral infiltrates and lobar consolidation. Sometimes, gastrointestinal (GI) symptoms accompany pneumonic plague and include nausea, vomiting, diarrhea, and abdominal pain. The disease is rapidly progressive, often leading to disseminated intravascular coagulation, and 100% of patients die if untreated. Differential diagnoses include community-acquired pneumonias and hantavirus respiratory distress syndrome. The time from exposure to death may be as short as 2 days and is often between 2 and 6 days. Pneumonic plague is spread by respiratory droplet, so droplet precautions should be strictly enforced.

Tularemia

The presentations of tularemia include glandular, oculoglandular, oropharyngeal, septicemic, typhoidal, and pneumonic forms. Similar to plague, the most effective bioterrorist release would be aerosolization, causing the pneumonic form, although the typhoidal form is possible. The incubation period is 1 to 14 days, and the initial illness is often influenza-like, beginning 3 to 5 days later. Clinical findings include sudden onset of fever (38-40° C), headache, malaise, coryza, sore throat, and chills and rigors. A dry, nonproductive cough may progress to bronchiolitis, pneumonitis, pleuritis, pleural effusions, and hilar lymphadenitis and may not be accompanied by objective signs of pneumonia (dyspnea, tachypnea, pleuritic pain, purulent sputum, or hemoptysis). The earliest findings on chest radiograph are peribronchial infiltrates that progress to bronchopneumonia. Only 25 to 50% of patients have radiological evidence of pneumonia in the disease's early stages, and some patients show only minimal, discrete infiltrates. Other cases progress rapidly to respiratory failure and death. Mortality from tularemia pneumonia is 30% if untreated but drops to less than 10% with prompt antibiotic treatment.

Nervous System

Botulism is the category A disease most likely to present with central nervous system (CNS) findings. The toxin from the C. botulinum bacteria is the most lethal toxin known for people, with an LD50 of 1 ng/kg, 100,000 times more toxic than sarin gas. There are four forms of botulism:

  • Foodborne.
  • Wound.
  • Infant (the most common form, accounting for 72% of cases).
  • Inhalational (no natural occurrence).

Botulinum toxin can be disseminated through contamination of food or water or via aerosolization and inhalation. When botulinum toxin is ingested, it may cause GI symptoms including abdominal cramping, nausea, vomiting, and diarrhea. Inhalational botulism does not cause a pneumonic process.

Both ingestion and inhalation of the toxin lead to nervous system findings, i.e., an acute, afebrile, symmetrical, descending flaccid paralysis (Figure 4.2, 24 KB). The first signs may appear as quickly as 2 to 72 hours; however, the rate of progression is dose dependent. In natural exposure, the symptoms may be insidious and unapparent for months. In a bioterrorist event, doses may be high, with prompt onset of symptoms. The first manifestation is a cranial nerve palsy, which may present as double or blurred vision, dysphagia, dysarthria, dysphonia, dry mouth, ptosis, gaze paralysis, enlarged or sluggishly reacting pupils, and nystagmus. Sensory changes do not occur.

The paralysis eventually progresses to loss of head control, hypotonia, limb weakness, and respiratory muscle paralysis. Constipation often develops. Patients may appear comatose because of extreme weakness, but sensorium is intact. Deep tendon reflexes may be intact initially but eventually diminish. Without treatment, antitoxin, and ventilatory assistance, patients die of airway obstruction and inadequate ventilation due to respiratory muscle paralysis. Secondary respiratory infections due to aspiration pneumonia may also develop.

Differential diagnoses for botulism include Guillain-Barré syndrome, myasthenia gravis, stroke, other ingestions/intoxications, tick paralysis, viral syndromes, and hypothyroidism. Bioterrorism should be considered when a botulism outbreak occurs within a common geographic area, yet no common source of ingestion can be identified. Botulism is not transmissible from person to person, so standard precautions are sufficient infection control measures.

Gastrointestinal (GI) System

A number of infections caused by Category A agents present primarily as syndromes other than GI, although they may be accompanied by some GI complaints. Those that present as respiratory syndromes after aerosol exposure (anthrax, plague, and tularemia) may also present with GI symptoms caused by respiratory distress, especially in children. It is not unusual for children with pneumonia and some degree of respiratory compromise and accessory respiratory muscle use to feed poorly and have nausea, vomiting, mild to moderate abdominal pain, and diarrhea. Botulism, in any of its forms, is primarily a nervous system illness manifested by paralysis. Paralysis may cause some GI manifestations such as poor feeding and constipation.

GI anthrax can occur when food is purposefully contaminated with anthrax spores. The incubation period via this route ranges from a few hours to a week. Depending on where the spores are deposited and germinate, disease may affect the upper or lower GI system, causing acute inflammation and eschar formation, much like in cutaneous anthrax. Upper GI illness may result in an oral or esophageal ulcer, which may present with fever, drooling, dysphagia, regional lymphadenopathy, edema, and sepsis. Lower GI illness often affects the terminal ileum or cecum, and presents with fever, loss of appetite, vomiting, and malaise and progresses to vomiting, hematemesis, severe bloody diarrhea, an acute abdomen, or sepsis. Sometimes, massive ascites develops. This form of anthrax is not transmissible from person-to-person, and standard precautions suffice.

Dermatologic Manifestations

Almost all of the diseases caused by Category A agents (anthrax, smallpox, plague, tularemia, VHF) can cause skin lesions, although dermatologic findings may not be the primary finding in a bioterrorist attack using aerosol dispersion.

Anthrax

Anthrax spores mixed with a fine powder substrate can be used as a weapon to cause respiratory and cutaneous disease. Cutaneous anthrax is the most common form of naturally occurring disease and accounts for 95% of cases. The incubation period is a few hours to 12 days. A small pruritic papule, often mistaken for an insect bite, forms at the inoculation site and rapidly progresses to an ulcer (1-3 cm in diameter) over the course of 1-2 days and may be surrounded by small vesicles (1-3 mm). The organism may be isolated from the serosanguineous fluid in these vesicles. A painless, depressed eschar of dark necrotic tissue forms at the site, and toxin production causes surrounding edema (Figure 4.3, 28 KB). Adjacent lymph glands may become enlarged and painful. The eschar separates from the skin in 1 to 2 weeks, often leaving no scar. The mortality rate is 20% without treatment, although death is rare with prompt treatment.

Smallpox

Rash is the key feature of smallpox, whether the disease is contracted via mechanical aerosolization or from person-to-person transmission. In ordinary-type smallpox, the most common form, exposure to the virus is followed by an asymptomatic incubation period of 7 to 17 days (mean 12 to 14 days). The prodromal phase, lasting 2 to 4 days, begins with acute onset of high fever, malaise, head and body aches, and sometimes vomiting. The fever usually ranges from 101° F to 104° F, and patients are usually too ill to carry on their normal activities. The patient is not contagious during this period.

The first sign of rash is an enanthema in the mouth that lasts less than 24 hours. These macules break down and shed large amounts of virus into the mouth and throat, making the patient highly contagious. A macular rash then develops on the face and forearms and spreads to the trunk and legs. When the rash begins, patients may defervesce and begin to feel better.

Over 1 to 3 days, the lesions progress to papules, which within 1 to 2 days, progress to vesicles and then pustules. The pustules are painful and deep-seated, sometimes described as feeling like lentils or "BB" pellets under the skin. After about 8 to 9 days from onset of the rash, the lesions scab over and eventually separate from the skin. Once the scabs have separated (about 21 days from onset), the patient is no longer contagious, although extensive pitting scars may remain.

The rash of smallpox may be confused with rashes of other conditions such as the vesicular pustular rashes (such as varicella), herpes zoster, monkeypox, herpes simplex, drug eruptions, and impetigo. The rash of smallpox may be distinguished from that of chickenpox by physical distribution of the lesions; smallpox lesions tend to concentrate on the face and extremities including the palms and soles, while varicella lesions concentrate on the face and trunk, usually sparing the palms and soles (Figure 4.4, 33 KB). Other distinguishing features of the smallpox rash are a monotonous appearance, with deep-seated lesions in the same stage of development. The pustules may be umbilicated (Figure 4.5, 26 KB). Varicella lesions are superficial, sometimes described as "dew drops on rose petals," and appear in crops, resulting in lesions in different stages of development (Figure 4.6, 40 KB).

There are two clinical forms of smallpox. Variola major is the most severe and most common form of smallpox, with a more extensive rash and higher fever. There are four types of variola major smallpox:

  1. Ordinary (accounting for 90% or more of cases).
  2. Modified (mild and occurring in previously vaccinated individuals).
  3. Flat (malignant).
  4. Hemorrhagic.

Historically, 30% of patients with variola major smallpox die, usually during the second week of illness. Variola minor smallpox is a less common and less severe form of smallpox, with death rates historically of 1% or less.

Two types of variola major smallpox are both rare and very severe. Malignant and hemorrhagic smallpox progress rapidly and are usually fatal, with death occurring about 5 to 6 days after the rash begins. In malignant smallpox, the rash appears as soft, velvety, confluent vesicles that do not progress to pustules or scabs. In hemorrhagic smallpox, the rash is petechial, with hemorrhages into the skin and mucous membranes. Patients with all types of smallpox require immediate isolation with precautions for airborne infection.

The Centers for Disease Control and Prevention (CDC) has developed an "Acute, Generalized Vesicular or Pustular Rash Illness Protocol" to assist in the evaluation of patients for whom a diagnosis of smallpox is being considered. This algorithm classifies patients as at low, moderate, or high risk of smallpox, which in turn directs clinical laboratory testing. Before submitting laboratory specimens from patients suspected of having smallpox, consult your local and State health departments.

For the algorithm and an accompanying worksheet, go to: http://www.bt.cdc.gov/agent/smallpox/diagnosis/evalposter.asp.

For an interactive version of the algorithm, go to: http://www.bt.cdc.gov/agent/smallpox/diagnosis/riskalgorithm/index.asp.

For laboratory testing algorithms that complement the patient evaluation protocols, go to: http://www.bt.cdc.gov/agent/smallpox/diagnosis/pdf/rashtestingprotocol.pdf. PDF Help.

Tularemia

Although airborne Francisella tularensis would most likely cause pneumonic or typhoidal disease, ulceroglandular and oculoglandular forms may occur that have cutaneous manifestations. There is also a glandular form of the disease, which does not result in skin lesions. The rash of ulceroglandular tularemia begins with a papule at the inoculation site, accompanied by systemic symptoms (fever, chills, rigors, sore throat). The lesion forms a pustule that becomes a tender ulcer and may form an eschar. Regional lymph nodes become inflamed and fluctuant. The oculoglandular form of tularemia leads to conjunctival ulceration, blepharitis, chemosis, vasculitis, and regional lymphadenopathy.

Viral hemorrhagic fevers

Viral hemorrhagic fevers (VHFs) are caused by a variety of organisms, with a variety of presentations, making clinical diagnosis difficult. After an incubation period of 2 to 21 days, a rash develops that may range from a subtle cutaneous flushing to a nonpruritic maculopapular rash, similar to that seen in measles. The condition progresses to a bleeding diathesis of petechiae, mucosal and conjunctival hemorrhages, hematuria, hematemesis, and melena.

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