Etiology

Hundreds of biologic and chemical agents could theoretically be adapted for sinister use by terrorists, and attempts to ascertain which agents are most likely to be employed are fraught with difficulties. Accurate intelligence is often lacking. Terrorists may choose to use weapons of opportunity, agents that for some reason are readily available to some member of the terrorist group. The motives of terrorists often are obscure and difficult to predict. Strategies should concentrate response efforts not on those agents most likely to be used but, rather, on those agents that, if used, would constitute the gravest potential threats to public health and security.

Biologic agents, including pathogens and toxins, have been divided into three categories, with category A including diseases caused by those six agents posing the greatest threat: anthrax, plague, tularemia, smallpox, botulism, and the viral hemorrhagic fevers.

Terrorists could also procure and release a vast array of potentially harmful chemicals. Tank cars full of flammable industrial gases and liquids, corrosive industrial acids and bases, poisonous compounds such as cyanides and nitrites, pesticides, dioxins, and explosives traverse our railways and roads daily. Four classes of “military-grade” chemicals with a history of use in warfare or manufactured specifically for use as weapons are considered here. They are the organophosphate-based nerve agents, vesicants, “blood agents” (cyanides), and certain pulmonary irritants or “choking agents.”

Epidemiology and Pediatric-Specific Concerns

Large-scale attacks on civilian targets will likely involve pediatric victims, and children may be more susceptible than adults to the effects of certain biologic and chemical agents (Chapters 699 and 700). Thinner skin makes dermally active chemical agents, such as mustard, a greater risk to children than adults. A larger surface area per unit volume further increases the problem. A small relative blood volume makes children more susceptible to the volume losses associated with enteric infections such as cholera and to gastrointestinal intoxications such as might be seen with exposure to the staphylococcal enterotoxins. Children’s relatively higher minute ventilation than that of adults increases the threat of agents delivered via the inhalational route. The fact that children live “closer to the ground” compounds this effect when heavier-than-air chemicals are involved. An immature blood-brain barrier may heighten the risk of central nervous system toxicity from nerve agents. Finally, developmental considerations make it less likely that a child would readily flee an area of danger, thereby increasing exposure to these various adverse effects.

Children appear to have a unique susceptibility to certain potential agents that might be used by terrorists. Although adults generally suffer only a brief, self-limited incapacitating illness after infection with Venezuelan equine encephalitis (VEE) virus, young children are more likely to experience seizures, permanent neurologic sequelae, and death. In the case of smallpox, waning herd immunity may disproportionately affect children. Vaccine-induced immunity to smallpox probably diminishes significantly after 3 to 10 yr. Although most adults are considered susceptible to smallpox, given that routine civilian immunization ceased in the early 1970s, older adults may have some residual protection from death, if not from the development of disease. Today’s children are among the first to grow up in a world without any individual or herd immunity to smallpox.

Children also may experience unique disease manifestations not seen in adults; suppurative parotitis is a common characteristic occur among children with melioidosis but is not generally seen in adults with Burkholderia pseudomallei infection (Chapter 197.2).

Pediatricians are likely to experience unique problems in managing childhood victims of biologic or chemical attack. Many of the drugs useful in treating such casualties are unfamiliar to pediatricians or have relative contraindications in childhood. The fluoroquinolones and tetracyclines are commonly cited as agents of choice in the treatment and prophylaxis of anthrax, plague, tularemia, brucellosis, and Q fever. Both drug classes are often avoided in children, although the risk of morbidity and mortality from diseases induced by agents of bioterrorism far outweighs the minor risks associated with short-term use of these agents. Ciprofloxacin received, as its first licensed pediatric indication, U.S. Food and Drug Administration (FDA) approval for use in the prophylaxis of anthrax after inhalational exposure during a terrorist attack. Doxycycline is now licensed specifically in children for the same indication. Immunizations potentially useful in preventing biologic agent–induced diseases are often not approved for use in pediatric patients. The currently available anthrax vaccine is licensed only for those between 18 and 65 yr of age. The plague vaccine, currently out of production and probably ineffective against inhalational exposures, was approved only for individuals aged 18 to 61 yr. The smallpox vaccine, a live vaccine employing vaccinia virus, can cause fetal vaccinia and demise when given to pregnant women.

Many otherwise useful pharmaceutical agents are not available in pediatric dosing regimens. The military distributes nerve agent antidote kits consisting of prefilled autoinjectors designed for the rapid administration of atropine and pralidoxime. Many emergency departments and some ambulances stock these kits. The doses of agents contained in the nerve agent antidote kit are calculated for soldiers and thus are far in excess of those appropriate for young children, and pediatric pralidoxime autoinjectors are not yet available. Atropine autoinjectors specifically formulated for children have been approved by the FDA and are now widely available. To facilitate accurate field post-exposure dose administration for children based on age, weight, and level of exposure, the U.S. Public Health Service has prepared four pocket-sized “Weapons of Mass Destruction Pediatric Dosing Cards” for biologic agents, nerve agents, cyanide, and radiation (Fig. 704-1).

Figure 704-1 Fronts and backs of weapon of mass destruction pediatric dosing cards for post-exposure dosing for cyanide poisoning (A), nerve agents (B), c radiation exposure antidotes (C), and biologic agents (D).

(From Montello MJ, Tarosky M, Pincock L, et al: Dosing cards for treatment of children exposed to weapons of mass destruction, Am J Health Syst Pharm 63:944–949, 2006.)

Although physical protection probably would not be useful in a civilian setting, commercially available devices such as gas masks typically are not available in pediatric sizes. The Israeli experience during the first Gulf War suggests that frightened parents may improperly use such masks on their children, resulting in inadvertent suffocation.

In the event of a large-scale terrorist attack, there may be an insufficient number of pediatric hospital beds. In any large disaster, excess bed capacity might potentially be provided at civilian and Department of Veterans Affairs hospitals under the auspices of the National Disaster Medical System, but that system makes no specific provision for pediatric beds.

Clinical Manifestations

In the event of a terrorist attack, clinicians may be called on to make prompt diagnoses and render rapid life-saving treatments before the results of confirmatory diagnostic tests are available. Although each potential agent of terrorism produces its own unique clinical manifestations, it is useful to consider their effects in terms of a limited number of distinct clinical syndromes. This approach helps clinicians make prompt, rational decisions regarding empirical therapy. In general, casualties from a terrorist attack experience symptoms immediately upon exposure to an agent (or within the first several hours after exposure) or, alternatively, symptoms develop slowly over a period of days to weeks. In the former case, the sinister nature of the event is often obvious, and the etiology more likely to be conventional or chemical in nature. Biologic agents differ from conventional, chemical, and nuclear weapons (Chapters 699 and 700) in that they have inherent incubation periods. Patients are therefore likely to present removed in time and place from the point of an unannounced and unnoticed exposure to a biologic agent. Whereas traditional first responders such as firemen and paramedics may be at the forefront of a conventional or chemical terrorism response, the primary care physician is likely to constitute the first line of defense against the effects of a biologic agent.

Casualties can thus be categorized as either immediate or delayed in presentation. Within each of these categories, patients can be further classified as having primarily respiratory, neuromuscular, or dermatologic manifestations (Table 704-1). A limited number of agents may cause each particular syndrome, permitting institution of empiric therapy targeted at a short list of potential etiologies. The viral hemorrhagic fevers might manifest as fever and a bleeding diathesis; these agents are considered separately in Chapter 263. In most cases, supportive care is the mainstay of hemorrhagic fever treatment.