Biologic

(Table 53-4: Biologic Agents Used for Warfare)

Smallpox
1. Terrorists might consider using smallpox as weapon because an increasing number of people no longer carry immunity.
2. An unvaccinated person develops a prodrome of malaise, headache, and backache with an onset of fever to as high as 40°C. The fever decreases over the next 3 or 4 days at which time a rash develops.
  1. This progression is in contradistinction to chicken pox in which the rash develops at the same time as the fever.
  2. Unlike chicken pox, smallpox has a predilection for the distal extremities and face, although no part of the body is spared. Also, all lesions in a patient with smallpox are at the same stage, but with chicken pox, lesions are at multiple different stages, including papules, vesicles, pustules, and scabs.
Anthrax
1. Anthrax has appeal as a bioterrorism agent because it can be “weaponized” (normally, anthrax spores are inhaled).
2. There are three primary types of anthrax infection (cutaneous, inhalation, and gastrointestinal [GI]), and 95% of cases are cutaneous.
3. Anthrax has additional appeal to bioterrorists because inhalation it is hard to detect.
  1. It manifests as an influenza-like disease with fever, myalgias, malaise, and a nonproductive cough with or without chest pain.
  2. After a few days, the patient appears to get better, but then a couple of days later, the patient becomes much sicker with dyspnea, cyanosis, hemoptysis, stridor, and chest pain. The most notable finding on physical examination and laboratory testing is a widened mediastinum.
  3. Usually when a patient develops profound dyspnea, death ensues within 1 to 2 days.
  4. In the past, penicillin G was the treatment of choice, but because weaponized anthrax has been engineered to be resistant to penicillin G, ciprofloxacin or doxycycline is now more commonly used.
Plague
1. The organism is only viable for approximately 60 minutes after being distributed. If dispersed by an airplane, its viability would limit its infectivity for only 10 km from the dispersion site.
2. Rodents and fleas are its natural hosts, and they reinfect each other by fleas biting infected rodents.
3. There are two types of plague, bubonic and pneumonic.
  1. With bubonic plague, after a flea bite, there is a 2- to 6-day incubation period at which time there is a sudden onset of fever, chills, weakness, and headache. Intense painful swelling occurs in the lymph nodes, usually in the groin, axilla, or neck.
  2. Without treatment, patients become septic and develop septic shock with cyanosis and gangrene in peripheral tissues (“black death” descriptor that was used during the epidemics in Europe).
  3. The treatment of choice is streptomycin, but chloramphenicol and tetracycline are acceptable alternatives.
  4. Patients with pneumonic plague should be managed as one would manage a patient with drug resistance to tuberculosis because the respiratory secretions are highly infectious.
Tularemia
1. Francisella tularensis (tularemia) has some similarities to anthrax and plague but is not nearly as dangerous. There are several animal hosts, with the cotton-tailed rabbit being one of the most susceptible. Normally, humans acquire F. tularensis with direct contact with an infected animal or from the bite of an infected tick or deerfly.
2. Normally, a patient develops a cutaneous ulcer at the site of entry after contact with an animal. As the swelling continues, the skin eventually breaks, creating an ulcer, which develops a necrotic base that becomes black as it scars.
3. The treatment of choice for tularemia is streptomycin, although gentamicin, tetracycline, and chloramphenicol have also been used.
Botulism
1. After the first Gulf War, Iraq admitted to having more than 19,000 L of concentrated botulism toxin (enough to kill the world's population three times over) of which almost half was loaded on military weapons. Clostridium botulinum toxin is the most potent poison known to humans; the LD100 dose is only 1 picogram.
2. Botulism manifests as neuroparalysis caused by the toxin from C. botulinum. Unlike all the other biologic mentioned previously, it is not caused by a live organisms and is, therefore, not contagious.
3. Humans ingest C. botulinum without apparent effects until the organism begins to release toxins (distributed from the GI tract or from the lungs if inhaled in the bloodstream to cholinergic nerve endings, where they block the release of acetylcholine at muscarinic and nicotinic receptors).
  1. This mechanism is the exact opposite of the chemical nerve agents such as sarin that result in an increase in the amount of acetylcholine at the cholinergic receptors, but the end result is the same.
  2. Patients develop a progressive weakness and a flaccid paralysis that begins in the extremities and progresses until the respiratory muscles cease to contract.
4. Treatment of patients includes the use of a trivalent antitoxin. Patients with profound respiratory difficulty should have their airways protected and mechanical ventilation initiated.
Hemorrhagic Fevers
1. There are at least 18 viruses that cause human hemorrhagic fevers, which form a special group of viruses characterized by viral replication in lymphoid cells, after which patients develop fever and myalgia with an incubation of anywhere from 2 to 18 days, depending on the agent itself and the amount that is inhaled or inoculated across the dermis.
2. The viruses are single-stranded, ribonucleic acid (RNA) viruses that have a rodent or insect reservoir and are communicated to humans by inhalation of an aerosol, through contact with an infected animal, or through the bite of an infected insect. Humans are not a reservoir for the virus.
3. The incubation period is within several days of contact or inhalation of the agent, at which time patients present with fever, myalgia, and evidence of a capillary leak (systemic leak or pulmonary edema), thrombocytopenia, and disseminated intravascular coagulation.
4. There are no specific antiviral therapies, but ribavirin, interferon-α, and hyperimmunoglobulin are often administered, with ribavirin being more protective against some of the viruses than others.

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