Pediatric needs in the planning, preparation, and response to biological disasters or acts of terrorism is essential.1 Nearly all child health professionals can benefit from bioterrorism disaster training and education.2 Children remain potential victims of biological terrorism. In recent years, children have been specific targets of terrorists' acts.3 Consequently, it is necessary to address the needs of pediatric patients after a potential terrorist or disaster incident.
Specific to bioterrorism, more fulminant infectious diseases are possible in children because of immunologic immaturity and a more permeable blood–brain barrier. Furthermore, many drugs used to treat illness from bioagents were historically avoided during childhood because of potential developmental toxicity. Finally, it is anticipated that specific vulnerabilities such as lack of pediatric expertise, equipment, or facilities within disaster planning and EMS systems might be exacerbated by a terrorist attack involving children.4
In contrast to a chemical attack, a covert biological attack will simulate a natural outbreak, with an incubation period rather than producing immediate mass casualties.5 The Centers for Disease Control and Prevention (CDC) has developed a list of “critical agents for health preparedness” that encompasses organisms with the most potentially devastating consequences that would require the most critical medical responses if released by a bioterrorist.6 According to this classification scheme, the highest overall public health impact and requirement for intensive preparedness as well as intervention would stem from an aerosolized release of:
Each of these identified agents will be discussed in the following paragraphs. The remaining agents are identified in Table 68–1.
Although any of the highest risk biological agents listed above can be seen in the pediatric patient, several agents might closely resemble some of the more common childhood illnesses, particularly in their initial stages. The awareness of these similarities and, more importantly, their differences, are critical for all health care professionals.7
Anthrax occurs in nature following contact with infected animals or animal products. Ninety-five percent of naturally occurring anthrax is cutaneous disease. It is associated with less than 1% mortality if treated, but approximately 20% mortality if untreated. The risk is mostly occupational in nature from close contact with herbivores such as sheep, goats, and cattle. Naturally occurring inhalational anthrax accounts for less than 5% of reported cases. The historical mortality rate of inhalational anthrax is approximately 90%. The mortality from the US mail associated outbreak in 2001 was 45%. The decrease in mortality is most likely because of improved supportive care and the improved antibiotic treatment available today. Naturally occurring gastrointestinal (GI) anthrax accounts for less than 5% of reported cases. It is very difficult to diagnose and is frequently fatal.4,8
Figure 68–1 demonstrates the pathophysiology of disease development. The site of entry into the body is typically the skin, lungs, or GI tract. Low level germination at those sites occur leading to localized edema and necrosis. The agent is taken up by the macrophage where further germination occurs. The macrophage may carry the germinating bacteria to regional lymph nodes. The release of exotoxins, such as edema toxin and lethal toxin, can lead to cell death and necrosis in the affected areas (e.g., hemorrhagic adenitis). The resultant release of tumor necrosis factor (TNF) and other cytokines can affect other homeostatic mechanisms and contribute to shock and death. Once the local necrosis occurs, there can be a large release of anthrax bacilli into the blood stream causing septicemia and the seeding of other organs such as the meninges and lungs.
The pathophysiology of disease development in anthrax. (With permission from Dixon TC, Meselson M, Guillemin J, Hanna PC. Anthrax. N Engl J Med. 1999;341(11):815–826.)
The hallmark of cutaneous disease is a single or few lesions that are painless throughout all stages, starting with a papule or macule that may be pruritic. Over the next 1 to 2 days, single or multiple vesicles or large bullae appear with clear or serosanguineous fluid. This dries into an ulcer with surrounding gelatinous, often extensive, nonpitting edema. If the edema involves the head or the neck, airway compromise can occur. Several days later, this progresses to a black depressed eschar at the base of the ulcer (Fig. 68–2). Purulence or significant erythema and evidence of inflammation should raise the suspicion of secondary bacterial infection such as cellulitis.
Cutaneous anthrax. webs.wichita.edu/…/lecture20/anthrax_hand.jpg. (With permission from CDC public domain images)
B. anthracis spores are highly stable and highly infectious upon inhalation and it is this form that has been manufactured for use in biological warfare. Illness resulting from an aerosolized release of anthrax spores is likely associated with an incubation period of 1 to 60 days, followed by fever, myalgias, cough, and chest pain.
Children, particularly infants and toddlers, present with nonspecific symptom complexes primarily limited to fever, vomiting, cough, and dyspnea.9 Children with anthrax present with a wide range of clinical signs and symptoms, which differ somewhat from the presenting features of adults with anthrax. Like adults, children with GI anthrax have two distinct clinical presentations: upper tract disease characterized by dysphagia and oropharyngeal findings and lower tract disease characterized by fever, abdominal pain, and nausea and vomiting. Additionally, children with inhalational disease may have “atypical” presentations including primary meningoencephalitis. Children with inhalational anthrax have abnormal chest roentgenograms; however, children with other forms of anthrax usually have normal roentgenograms.10
With inhalational anthrax, transient clinical improvement might occur, but is followed by the abrupt onset of sepsis, hypotension, and death within 24 to 36 hours. Hemorrhagic meningitis is expected in 50% of cases, as would a very high overall case fatality rate. Hallmarks of the illness include gram-positive bacilli on tissue biopsy, blood smear, or spinal fluid microscopy, and chest radiograph findings of mediastinal widening from lymphadenitis. Pulmonary infiltrates or effusions may also be seen.
There are no clinical trials assessing the treatment of inhalational anthrax in humans. Early antibiotic administration is likely to be the most important determinant of outcome in the setting of anthrax infection. Cutaneous anthrax without systemic sequelae can be adequately treated with oral doxycycline or ciprofloxacin. Any other form or anthrax should be admitted and treated with intravenous antibiotics. Those patients potentially exposed to anthrax spores should receive antibiotic prophylaxis for 60 days. Treatment and prophylaxis recommendations are summarized in Table 68–2.4,8 Unlike plague, secondary transmission of inhalational anthrax does not occur, although it has been described with cutaneous anthrax. Standard blood and bodily fluid precautions are indicated.
Table 68-2. Initial Antibiotic Therapy for Selected Bacterial Agents of Bioterrorism in Children |Favorite Table|Download (.pdf)
Table 68-2. Initial Antibiotic Therapy for Selected Bacterial Agents of Bioterrorism in Children
Dose and Route
10–15 mg/kg IV q 12 h (max 400 mg/dose)
2.2 mg/kg IV (max 100 mg) q 12 h
10–15 mg/kg IV q 8 h
400–600K u/kg/d IV divided q 4 h
10–15 mg/kg po q 12 h (max 1 gm/d)
2.2 mg/kg po (max 100 mg) q 12 h
15 mg/kg IM q 12 h (max 2 g/d)
2.5 mg/kg IM or IV q 8 h (q 12 h in neonates younger than 1 wk)
2.2 mg/kg IV q 12 h (max 200 mg/d)
(Ciprofloxacin 15 mg/kg IV q12 h or chloramphenicol 25 mg/kg IV q 6 h (max 4 gm/d) might also be considered; especially chloramphenicol for plague meningitis)
15 mg/kg IM q 12 h (max 2 g/d)
2.5 mg/kg IM or IV q 8 h (q 12 h in neonates younger than 1 wk)
2.2 mg/kg IV q 12 h (max 200 mg/d)
(Chloramphenicol or ciprofloxacin may also be considered)
Mass Casualty Setting or Prophylaxis
10–15 mg/kg po q 12 h (max 1 g/d) × 60 d
2.2 mg/kg (max 100 mg) po q 12 h × 60 d
2.2 mg/kg po q 12 h (max 200 mg/d)
20 mg/kg po q 12 h (max 1 g/d)
2.2 mg/kg po q 12 h (max 200 mg/d)
15 mg/kg po q 12 h (max 1 g/d)
Y. pestis, the bacteria that causes plague, classically spreads in nature from infected fleas to humans. Historically, plague is most well known as the cause of Justinian's plague and the black death (during the middle 6th and 14th centuries, respectively), which were two devastating epidemics that killed millions of people. A third epidemic began in China and eventually spread to all continents. Between 1896 and 1930, more than 12 million deaths and almost 30 million cases were documented. Research during the last pandemic led to the discovery of Y. pestis as the causative agent. Transmission of bubonic plague occurs through a flea bite, bite or scratch of an infected animal, or direct contact from an infected carcass. Pneumonic plague occurs via inhalation of respiratory droplets from an infected animal or person-to-person spread. Pneumonic plague can be primary inhalational or secondary resulting from spread via the bloodstream in bubonic or septicemic cases.11 Naturally occurring plague most often is associated with the bubonic type, occurs in the southwest United States primarily during the months of April to October or during hunting season. Oftentimes, there is an associated rodent die off that precedes the presentation of the disease in humans. An aerosol-mediated bioterrorist attack would be associated with pneumonic plague and would not present with the same epidemiologic factors mentioned above.
Clinical manifestations include tender lymphadenopathy, if associated with bubonic plague, and multiorgan failure, if associated with septicemic plague. It often presents with nonspecific respiratory signs and symptoms beginning from 1 to 6 days after exposure. An intense cough with thin bloody sputum is a characteristic finding. GI signs and symptoms can be very prominent, and at times may mimic an acute abdomen. Petechiae, purpura, and an overwhelming picture of DIC may occur. Rapid progression to death occurs in those not treated with antibiotics within 24 hours of symptom onset. A clue to the diagnosis of Y. pestis is a classic bipolar, “safety pin”-staining bacilli on Gram's staining of the sputum or lymph node aspirate.
Treatment consists of antibiotic treatment with streptomycin, gentamicin, doxycycline, ciprofloxacin, or chloramphenicol. Doxycycline or ciprofloxacin are the antibiotic choices for postexposure prophylaxis. Because secondary transmission of pneumonic plague occurs, standard blood and bodily fluid, as well as droplet precautions are necessary as is postexposure prophylaxis for those exposed to pneumonic plague victims.12 Treatment and prophylaxis recommendations are summarized in Table 68–2.
A global campaign, begun in 1967 under the guidance of the World Health Organization (WHO), succeeded in eradicating smallpox in 1977. The last documented case worldwide was reported in Somalia. The last documented case of smallpox reported in the United States was in 1949. Routine smallpox vaccination in the United States was discontinued in 1972. Therefore, the majority of US citizens are susceptible to an outbreak. Samples of the virus have been stored in laboratory research freezers. If a terrorist had access to stored smallpox virus, a release could produce a chaotic situation.13
Smallpox is caused by a member of the Orthopoxvirus group. Smallpox afflicts only humans, as there are no known animal hosts. The diagnosis of smallpox is made clinically, with laboratory confirmation through the CDC.
Smallpox has an incubation period of 7 to 17 days. Clinical illness is characterized by a severe prodrome of high fever, rigors, vomiting, headache, and backache. The classic exanthem begins 2 to 4 days later, on the face (Fig. 68–3) and distal portions of the extremities (Fig. 68–4), with macules progressing to papules, umbilicated pustules, and then scabs. The centrifugal onset and synchronous nature of the rash helps to distinguish it from chickenpox (Fig. 68–5).
Facial smallpox. cache.view/images.com. (With permission from CDC public domain images)
If used as a biological weapon, smallpox represents a serious threat to the general population because it carries a high case-fatality rate of 30% or more among unvaccinated persons and there is no specific therapy. Although smallpox has long been feared as the most devastating of all infectious diseases, its potential for devastation today is far greater than at any previous time. In a now highly susceptible, mobile population, smallpox would be able to spread widely and rapidly throughout this country and the world.
Smallpox also has a high potential for secondary spread from person-to-person. Transmission occurs primarily through close face-to-face contact via droplet nuclei. However, smallpox can also be transmitted via an airborne route in the setting of an infected patient with a severe cough, and from direct aerosol inhalation. One of the most concerning things about smallpox is the potential for the disease to spread exponentially. The secondary attack rate is estimated to be 25% to 40% in unvaccinated contacts, meaning that at least one of every three or four persons exposed to smallpox would develop disease. Historically, three to four contacts were infected per index case. However, it is expected that up to 10 to 20 contacts in a mostly nonimmune population would be infected.4 There is also very high potential for nosocomial spread.
Vaccination with the smallpox vaccine within 3 to 4 days of exposure may prevent disease or lessen the severity of the disease.14 Historically, the vaccine was given to children. Currently, it is not being offered to children for preevent prophylaxis and it is not recommended for postexposure use in children younger than 1 year. In the United States, virtually all children, and adults younger than 35 years, are unvaccinated, and have no immunity to smallpox. Thus, their potential susceptibility to fulminant disease might actually be greater than in those older Americans who were immunized before 1972. The only currently available vaccine has been tested on adults, not children.13 A “ring vaccination strategy” is now being recommended by the CDC. With this plan, cases of smallpox are rapidly identified, infected individuals are isolated, and contacts of the infected individuals as well as their contacts are immunized immediately.15
As mentioned, there is no specific treatment for smallpox. The mainstay of treatment is supportive therapy plus antibiotics as indicated for treatment of any secondary bacterial infections. No antiviral substances have yet proven effective for the treatment of smallpox. Airborne, droplet, and standard blood and bodily fluid precautions are indicated when caring for victims until all their scabs separate. Universal fluid precautions are also recommended for close contacts of victims until 17 days from their last exposure.
Botulism is found throughout the world. Three forms of naturally occurring human botulism exist: foodborne, wound, and infantile (Fig. 68–6). Fewer than 200 cases of all forms of botulism are reported annually in the United States.16
Botulism is an obligate anaerobe, spore-forming, gram-positive rod. The bacteria produces its effect through botulinum toxin. All forms of botulism result from absorption of botulinum toxin into the circulation from either a mucosal surface (gut, lung) or a wound. Botulinum toxin does not penetrate intact skin. The toxin is taken up by skeletal muscle motor neurons where it irreversibly inhibits the release of acetylcholine, resulting in postsynaptic muscle paralysis. The paralysis persists until axonal branches regenerate. Wound botulism and intestinal botulism are infectious diseases that result from production of botulinum toxin by C. botulinum either in devitalized (i.e., anaerobic) tissue or in the intestinal lumen, respectively. Neither would result from bioterrorist use of botulinum toxin.
A fourth, man-made form, results from aerosolized and purified botulinum toxin and is called inhalational botulism. This mode of transmission has been demonstrated experimentally in primates, has been attempted by bioterrorists, and has been the intended outcome of at least one country's specially designed missiles and artillery shells. Inhalational botulism has occurred accidentally in humans. A brief report from West Germany in 1962 described three veterinary personnel who were exposed to aerosolized botulinum toxin while disposing of rabbits and guinea pigs whose fur was coated with aerosolized type A botulinum toxin.
Patients with botulism typically present acutely with an afebrile, symmetric, descending flaccid paralysis that always begins in bulbar musculature. It always presents with multiple cranial nerve palsies. Patients may complain of difficulty seeing, speaking, and/or swallowing. Prominent neurologic findings include ptosis, diplopia, blurred vision, often enlarged or sluggishly reactive pupils, dysarthria, dysphonia, dysphagia, and descending paralysis. The mouth may appear dry because of peripheral parasympathetic nervous system cholinergic blockade. The incubation period lasts anywhere from 2 hours to 8 days.
Because botulism is toxin mediated there is no transmission from person-to person. Respiratory isolation is not needed. The mainstays of treatment are supportive and passive immunization with one of two antitoxins. The trivalent botulinum antitoxin is available through the CDC and may be used to treat children of any age with subtypes A, B, or E. The heptavalent antitoxin (subtypes A, B, C, D, E, F, G) is available through US army. In 2006, the Department of Health and Human Services approved the delivery of the heptavalent antitoxin into the Strategic National Stockpile in 2007. Botulism immune globulin (BIG) is used to treat infant botulism.16
Tularemia is a zoonotic illness that most commonly manifests in an ulceroglandular form after exposure to diseased animal fluids or bites from infected deerflies, mosquitoes, or ticks. The classic animal reservoir is the lagomorphs (rabbits). While not highly fatal, its extremely high infectivity and its ability to escape laboratory detection make it an agent of potential use for bioterrorism.17 Typical symptoms occur following a 2- to 10-day incubation period. These include sudden fever, chills, diarrhea, dry cough, muscle aches, joint pain, and progressive weakness or prostration. The presentation of other symptoms such as ulcers on the skin or mouth, swollen and painful lymph nodes, and sore throat vary depending on how a patient is exposed to the bacteria. An aerosolized release (as would be implicated in a bioterrorist attack) would likely result in clinical findings similar to community-acquired pneumonia, often developing chest pain and difficulty breathing. Patchy infiltrates and hilar adenopathy might be seen on a chest radiograph.
Tularemia can be treated with several antibiotics. Currently, the treatment of choice is streptomycin administered by intramuscular injection. Alternatively, gentamicin, a more widely available aminoglycoside, can be given intravenously. Other antibiotics that are used include tetracyclines and chloramphenicol but they tend to have a higher primary failure and relapse rate. Mass casualty prophylaxis can be achieved with doxycycline or ciprofloxacin. Person-to-person transmission does not occur, and respiratory isolation is not required. Treatment and prophylaxis recommendations are summarized in Table 68–2.4,8
Several families of viruses that share similar and defining features cause viral hemorrhagic fevers. The two most noteworthy families are the Filoviridae and the Arenaviridae because they are both highly contagious and are associated with a high mortality rate. Filoviruses cause Ebola and Marburg hemorrhagic fevers and an arenavirus causes Lassa fever. These RNA viruses are dependent on a natural animal or arthropod reservoir. Rodents, ticks, and mosquitoes are common vectors; however, the vector for Marburg and Ebola viruses are unknown. Humans become infected by a bite or when they come into contact with an infected host vector. However, documented cases of human-to-human transmission occur with Ebola, Marburg, and Lassa hemorrhagic fever viruses. Symptoms most often include fever, dizziness, fatigue, exhaustion, and muscle aches. While not all hemorrhagic fevers cause bleeding, severe forms of the disease may present with bleeding under the skin, internal organ bleeding, and bleeding from body orifices. Fulminant illnesses will present with shock and, oftentimes, multiorgan system failure. Supportive care and blood product replacement are the mainstays of therapy. Ribavirin (an antiviral medication) is possibly effective in treating some patients with an arenavirus illness (Lassa fever). Secondary transmission is likely with Ebola, Marburg, and Lassa fever, necessitating airborne isolation with standard blood and bodily fluid precautions.18
A unique feature of previous Ebola outbreaks has been the relative sparing of children. In an African study from Uganda, analysis revealed that 90 out of the 218 national laboratory confirmed Ebola cases were children and adolescents with a case fatality rate of 40%. The mean age was 8 years, with the youngest child being 3 day old. Children younger than 5 years contributed to the highest admission rate (35%) and case fatality among children and adolescents. All (100%) of Ebola positive children and adolescents were febrile while only 16% had hemorrhagic manifestations. Strategies to shield children from exposure to dying and sick Ebola relatives are recommended in the event of future Ebola outbreaks. Health education to children and adolescents to avoid contact with sick and their body fluids should be emphasized.19