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ANTHRAX


Updated 2/2002

Agent: Bacillus anthracis is a very hardy Gram-positive spore-forming aerobic rod that causes cutaneous or pulmonary infection. Anthrax is the greatest known BW threat and has been weaponized by several countries, including Iraq, which tested weapons extensively on humans (Cieslak & Eitzen, 1999; Shoham, 2000). It has been estimated that release of 100 kilograms of anthrax spores upwind of Washington DC would result in up to 3,000,000 deaths (U.S. Congress, 1993).

Routes of Infection: Endemic or naturally occurring (cutaneous) anthrax accounts for more than 95% of cases and is contracted primarily through direct inoculation through a break in the skin in contact with an infected animal. Cutaneous is not an issue in a BW context. As a biological weapon, anthrax is delivered in an aerosol dust and is contracted via inhalation. Delivery systems range from bombs to disguised cigarette lighters. Person-to-person transmission is not known to occur. It is not known how long anthrax spores remain viable in the environment, but experience with accidents in Russia indicate a maximum of 45 days (Inglesby, Henderson, Bartlett, Ascher, Eitzen, Friedlander, Hauer, McDade, Osterholm, O'Toole, Parker, Perl, Russell, & Tonat, 1999: Shoham, 2000).

Incubation: The incubation period is 1-7 days; and up to 60 days (Chin, 2000).

CLINICAL FINDINGS & TREATMENT

Signs & Symptoms: Inhaled spores are carried by pulmonary macrophages to tracheobronchial or mediastinal lymph nodes where the B anthracis multiplies and produces at least three proteins: edema factor (or toxin) (EF), lethal factor (LF), and protective antigen (PA), the latter of which is a carrier molecule for EF and LF. These toxins (EF + PA and LF + PA) cause lymphatic tissue necrosis, which releases large numbers of B anthracis that cause overwhelming septicemia and death.

Inhalation anthrax is usually biphasic in presentation, beginning with a prodrome of nonspecific febrile flu-like illness with low-grade fever, malaise, headache, nonproductive cough, precordial discomfort or pressure, and myalgia. After one-four days there is sometimes a brief period of slight improvement, followed by rapid deterioration marked by fever and respiratory distress, including some or all of the following: dyspnea, stridor, cyanosis, increased chest pain, diaphoresis, and sometimes subcutaneous edema of neck and chest. Meningitis, usually hemorrhagic, occurs in about 50% of cases. Pneumonia is usually not present, pleural effusions may be present. Chest radiographs show a widened mediastnum as early as the second day after exposure. This second phase of respiratory distress is followed by shock and often death. No treatment produces a death rate of essentially 100% and treatment delayed more than 48 hours after symptoms appear results in a very high death rate (Cieslak & Eitzen, 1999; Friedlander, 2000; Henry, 2001; Inglesby et al, 1999; Shafazand, Doyle, Ruoss, Weinacker, & Raffin, 1999). Experience in treating isolated cases of inhalation anthrax in the Fall of 2001 indicates that death rates may be lower than previously thought. If mass exposures occur, yet another story may emerge.

Diagnosis: As we saw in the fall of 2001 anthrax attack, the first patients at the first stage would likely be misdiagnosed as having viral upper respiratory infections; and many people would simply self-medicate themselves with "flu-medicine." Some would seek care, and the influx of large numbers of otherwise healthy people with the above first stage symptomatology should arouse suspicion.

With large numbers of patients presenting in the second stage of illness, it would be clear that a disaster (either anthrax or pneumonic plague) is unfolding as otherwise healthy people present in a toxic febrile condition with severe respiratory distress and cyanosis without clinical evidence of pneumonia. The widened mediastinum on CXR is pathognomic of advanced inhalation anthrax. Gram's stain of cerebrospinal fluid or pleural fluid shows typical gram-positive bacilli and diagnosis is confirmed by culturing B anthracis from blood or on autopsy (Cieslak & Eitzen, 1999; Friedlander, 2000; Inglesby et al, 1999; Shafazand et al, 1999).

Differential Diagnosis: Initially, the differential is any flu-like upper respiratory infection unless very large numbers of patients seek care, in which case, anthrax might be suspected. At the second stage the differential is pneumonic plague.

Treatment: Early treatment is essential if there is to be reasonable hope of recovery. Naturally occurring strains can be successfully treated with penicillin, but in a BW attack, penicillin resistance is possible. All treatment is for a total of 60 days of therapy (or when sufficient vaccine has been received) due to the possibility of delayed spore germination.

Mass casualties or post-exposure:
Adults: Ciprofloxacin 500 mg po every 12 hours. If the strain of B anthracis is shown to be susceptible, adults and children over 20 kg can be given amoxicillin 500 mg po every 8 hours OR doxycycline 100 mg po every 12 hours.
Children: Ciprofloxacin 20-30 mg/kg/24 hours po every 12 hours (not exceeding 1 g/24 hours). If the strain of B anthracis is shown to be susceptible, children weighing 20 kg or more can be given amoxicillin 500 mg po every 8 hours. Children weighing less than 20 kg can be given amoxicillin 40 mg/kg/24 hours divided into 3 doses taken every 8 hours. Immunization should be used if available - unlikely for civilian populations (CDC, 1999; Friedlander, 2000; Inglesby et al, 1999).

Contained casualties:
Adults: The ideal treatment (for clinically evident anthrax) is ciprofloxacin 400 mg IV every 12 hours until the patient's condition improves, at which time oral ciprofloxacin is given. Other fluoroquinolones can likely be substituted for adults, but for children are not recommended by the CDC. If the strain of B anthracis is shown to be susceptible, adults and children over 45 kg can be given penicillin G 4 million u IV every 4 hours OR doxycycline 100 mg IV every 12 hours.
Children: IV Ciprofloxacin 20-30 mg/kg/24 hours every 12 hours (not to exceed one g/24 hours), and therapy is continued as above. Other fluoroquinolones are not recommended for children by the CDC. If the strain of B anthracis is shown to be susceptible, children over 12 years can be given penicillin G 4 million u IV every 4 hours OR doxycycline 100 mg IV every 12 hours. Children less than 12 years receive penicillin G 50,000 u/kg IV every 6 hours. Doxycycline can also be used: children >45 kg receive adult dose and children 45 kg or less receive 2.5 mg/kg IV every 12 hours.

Protection: Post-exposure prophylaxis is discussed above. Person-to-person transmission is not known to occur, hence standard precautions with hospitalized patients are sufficient. Environmental surfaces can be cleaned with standard hospital disinfectants. It is essential that bodies (human and animal) be disposed of quickly. Embalming is risky and cremation is the ideal means of body disposal.

Although anthrax spores can remain in the environment for years, based on experience with accidents in the Soviet Union and in animal processing plants, the risk of infection after the primary aerosolization becomes very small or even non-existent beyond a maximum of 45 days post aerosolization (Inglesby et al, 1999).

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