Characteristics. Anthrax is a zoonotic disease caused by Bacillus anthracis. Under natural conditions, humans become infected by contact with infected animals or contaminated animal products. Human anthrax is usually manifested by cutaneous lesions. A biological warfare attack with anthrax spores delivered by aerosol would cause inhalation anthrax, an extraordinarily rare form of the naturally occurring disease.
Clinical Features. The disease begins after an incubation period varying from 1-6 days, presumably dependent upon the dose of inhaled organisms. Onset is gradual and nonspecific, with fever, malaise, and fatigue, sometimes in association with a nonproductive cough and mild chest discomfort. In some cases, there may be a short period of improvement. The initial symptoms are followed in 2-3 days by the abrupt development of severe respiratory distress with dyspnea, diaphoresis, stridor, and cyanosis. Physical findings may include evidence of pleural effusions, edema of the chest wall, and meningitis. Chest x-ray reveals a dramatically widened mediastinum, often with pleural effusions, but typically without infiltrates. Shock and death usually follow within 24-36 hours of respiratory distress onset.
DIAGNOSIS
Routine Laboratory Findings. Laboratory evaluation will reveal a neutrophilic leucocytosis. Pleural and cerebrospinal fluids may be hemorrhagic.
Differential Diagnosis. An epidemic of inhalation anthrax in its early stage with nonspecific symptoms could be confused with a wide variety of viral, bacterial, and fungal infections. Progression over 2-3 days with the sudden development of severe respiratory distress followed by shock and death in 24-36 hours in essentially all untreated cases eliminates diagnoses other than inhalation anthrax. The presence of a widened mediastinum on chest x-ray, in particular, should alert one to the diagnosis. Other suggestive findings include chest-wall edema, hemorrhagic pleural effusions, and hemorrhagic meningitis. Other diagnoses to consider include aerosol exposure to SEB; but in this case onset would be more rapid after exposure (if known), and no prodrome would be evident prior to onset of severe respiratory symptoms. Mediastinal widening on chest x-ray will also be absent. Patients with plague or tularemia pneumonia will have pulmonary infiltrates and clinical signs of pneumonia (usually absent in anthrax).
Specific Laboratory Diagnosis. Bacillus anthracis will be readily detectable by blood culture with routine media. Smears and cultures of pleural fluid and abnormal cerebrospinal fluid may also be positive. Impression smears of mediastinal lymph nodes and spleen from fatal cases should be positive. Toxemia is sufficient to permit anthrax toxin detection in blood by immunoassays.
THERAPY
Almost all cases of inhalation anthrax in which treatment was begun after patients were symptomatic have been fatal, regardless of treatment. Historically, penicillin has been regarded as the treatment of choice, with 2 million units given intravenously every 2 hours. Tetracyclines and erythromycin have been recommended in penicillin-sensitive patients. The vast majority of anthrax strains are sensitive in vitro to penicillin. However, penicillin-resistant strains exist naturally, and one has been recovered from a fatal human case. Moreover, it is not difficult to induce resistance to penicillin, tetracyclines, erythromycin, and many other antibiotics through laboratory manipulation of organisms. All naturally occurring strains tested to date have been sensitive to erythromycin, chloramphenicol, gentamicin, and ciprofloxacin. In the absence of information concerning antibiotic sensitivity, treatment should be instituted at the earliest signs of disease with oral ciprofloxacin (1000 mg initially, followed by 750 mg po (orally) bid (twice daily)) or intravenous doxycycline (200 mg initially, followed by 100 mg q (every) 12 hrs). Supportive therapy for shock, fluid volume deficit, and adequacy of airway may all be needed.
PROPHYLAXIS
Vaccine. A licensed, alum-precipitated preparation of purified B. anthracis protective antigen (PA) has been shown to be effective in preventing or significantly reducing the incidence of inhalation anthrax. Limited human data suggest that after completion of the first three doses of the recommended six-dose primary series (0, 2, 4 weeks, then 6, 12, 18 months), protection against both cutaneous and inhalation anthrax is afforded. Studies in rhesus monkeys indicate that good protection is afforded after two doses (10-16 days apart) for up to 2 years. It is likely that two doses in humans is protective as well, but there is too little information to draw firm conclusions. As with all vaccines, the degree of protection depends upon the magnitude of the challenge dose; vaccine-induced protection is undoubtedly overwhelmed by extremely high spore challenge. At least three doses of the vaccine (at 0, 2, and 4 weeks) are recommended for prophylaxis against inhalation anthrax. Contraindications for use are sensitivity to vaccine components (formalin, alum, benzethonium chloride) and/or history of clinical anthrax. Reactogenicity is mild to moderate: up to 6% of recipients will experience mild discomfort at the inoculation site for up to 72 hours (tenderness, erythema, edema, pruritus), while a smaller proportion (less than 1%) will experience more severe local reactions (potentially limiting use of the extremity for 1-2 days); modest systemic reactions (myalgia, malaise, low-grade fever) are uncommon, and severe systemic reactions (anaphylaxis, which precludes additional vaccination) are rare. The vaccine should be stored at refrigerator temperature (not frozen).
Antibiotics. Choice of antibiotics for prophylaxis is guided by the same principles as that for treatment; i.e., it is relatively easy to produce a penicillin-resistant organism in the laboratory, and possible, albeit somewhat more difficult, to induce tetracycline resistance. Therefore, if there is information indicating that a biological weapon attack is imminent, prophylaxis with ciprofloxacin (500 mg po bid), or doxycycline (100 mg po bid) is recommended. If unvaccinated, a single 0.5 ml dose of vaccine should also be given subcutaneously. Should the attack be confirmed as anthrax, antibiotics should be continued for at least 4 weeks in all exposed. In addition, two 0.5 ml doses of vaccine should be given 2 weeks apart in the unvaccinated; those previously vaccinated with fewer than three doses should receive a single 0.5 ml booster, while vaccination probably is not necessary for those who have received the initial three doses within the previous 6 months (primary series). Upon discontinuation of antibiotics, patients should be closely observed; if clinical signs of anthrax occur, patients should be treated as indicated above. If vaccine is not available, antibiotics should be continued beyond 4 weeks until the patient can be closely observed upon discontinuation of therapy.
