Signs and Symptoms: Incubation period is 1-6 days. Fever, malaise, fatigue, cough and mild chest discomfort is followed by severe respiratory distress with dyspnea, diaphoresis, stridor, and cyanosis. Shock and death occurs within 24-36 hours after onset of severe symptoms.
Diagnosis: Physical findings are non-specific. A widened mediastinum may be seen on CXR. Detectable by Gram stain of the blood and by blood culture late in the course of illness.
Treatment: Although effectiveness may be limited after symptoms are present, high dose antibiotic treatment with penicillin, ciprofloxacin, or doxycycline should be undertaken. Supportive therapy may be necessary.
Prophylaxis: An FDA licensed vaccine is available. Vaccine schedule is 0.5 ml SC at 0, 2, 4 weeks, then 6, 12, and 18 months for the primary series, followed by annual boosters. Oral ciprofloxacin or doxycycline for known or imminent exposure.
Isolation and Decontamination: Standard precautions for healthcare workers. After an invasive procedure or autopsy is performed, the instruments and area used should be thoroughly disinfected with a sporicidal agent (chlorine).
Bacillus anthracis, the causative agent of Anthrax, is a rod-shaped, gram-positive, sporulating organism with the spores constituting the usual infective form. Anthrax is primarily a zoonotic disease of herbivores, with cattle, sheep and horses being the usual domesticated animal hosts, but other animals may be infected. Human disease may be contracted by handling contaminated hair, wool, hides, flesh, blood and excreta of infected animals and from manufactured products such as bone meal, as well as by purposeful dissemination of spores. Infection is introduced through scratches or abrasions of the skin, wounds, inhalation of spores, eating insufficiently cooked infected meat, or by flies. All human populations are susceptible. Recovery from an attack of the disease may be followed by immunity. The spores are very stable and may remain viable for many years in soil and water. They will resist sunlight for varying periods.
HISTORY AND SIGNIFICANCE
Anthrax spores were weaponized by the United States in the 1950's and 1960's before the old U.S. offensive program was terminated. Other countries have weaponized this agent or are suspected of doing so. The anthrax bacterium is easy to cultivate and spore production is readily induced. Spores are highly resistant to sunlight, heat and disinfectants - properties which could be advantageous when choosing a bacterial weapon. Iraq admitted to a United Nations inspection team in August of 1991 that it had performed research on the offensive use of B. anthracis prior to the Persian Gulf War of 1991, and in 1995 Iraq admitted to weaponizing anthrax. This agent could be produced in either a wet or dried form, stabilized for weaponization by an adversary and delivered as an aerosol cloud either from a line source such as an aircraft flying upwind of friendly positions, or as a point source from a spray device. Coverage of a large ground area could also be theoretically facilitated by multiple spray bomblets disseminated from a missile warhead at a predetermined height above the ground.
Anthrax presents as three distinct clinical syndromes in man: cutaneous, inhalational, and gastrointestinal disease. The cutaneous form (also referred to as malignant pustule) occurs most frequently on the hands and forearms of persons working with infected livestock. It begins with a papule followed by formation of a blister-like fluid-filled vesicle. The vesicle typically dries and forms a coal-black scab, hence the term anthrax (Greek for coal). Sometimes this local infection will develop into a systemic infection which is often fatal. Endemic inhalational anthrax, known as Woolsorters’ disease, is a rare infection contracted by inhalation of the spores. It occurs mainly among workers handling infected hides, wool, and furs. The intestinal form, which is also very rare in man, is contracted by the ingestion of insufficiently cooked meat from infected animals. In man, the mortality of untreated cutaneous anthrax ranges up to 25 per cent; in inhalational and intestinal cases, the case fatality rate is almost 100 percent.
After an incubation period of 1-6 days, presumably dependent upon the dose and strain of inhaled organisms, the onset of inhalation anthrax is gradual and nonspecific. Fever, malaise, and fatigue may be present, sometimes in association with a nonproductive cough and mild chest discomfort. These initial symptoms are often followed by a short period of improvement (hours to 2-3 days), followed by the abrupt development of severe respiratory distress with dyspnea, diaphoresis, stridor, and cyanosis. Shock and death usually follow within 24-36 hours after the onset of respiratory distress. Physical findings are typically non-specific. The chest X-ray may reveal a widened mediastinum ± pleural effusions late in the disease in about 55% of the cases, but typically is without infiltrates. Bacillus anthracis will be detectable by Gram stain of the blood and by blood culture with routine media, but often not until late in the course of the illness. Only vegetative encapsulated bacilli are present during infection. Spores are not found within the body unless it is open to ambient air. Studies of inhalation anthrax in non-human primates (rhesus monkey) showed that bacilli and toxin appear in the blood late on day 2 or early on day 3 post-exposure. Toxin production parallels the appearance of bacilli in the blood and tests are available to rapidly detect the toxin. Concurrently with the appearance of anthrax, the WBC count becomes elevated and remains so until death.
Almost all inhalational anthrax cases in which treatment was begun after patients were significantly symptomatic have been fatal, regardless of treatment. 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 allergic patients. The vast majority of naturally-occurring 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 might not be difficult for an adversary 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 intravenous ciprofloxacin (400 mg q 8-12 hrs) or intravenous doxycycline (200 mg initially, followed by 100 mg q 12 hrs). Supportive therapy for shock, fluid volume deficit, and adequacy of airway may all be needed.
Standard Precautions should be practiced. After an invasive procedure or autopsy, the instruments and area used should be thoroughly disinfected with a sporicidal agent. Iodine can be used, but must be used at disinfectant strengths, as antiseptic-strength iodophors are not usually sporicidal. Chlorine, in the form of sodium or calcium hypochlorite, can also be used, but with the caution that the activity of hypochlorites is greatly reduced in the presence of organic material.
Vaccine: A licensed vaccine is derived from sterile culture fluid supernatant taken from an attenuated strain. The vaccination series consists of six 0.5 ml doses SC at 0, 2, and 4 weeks, then 6, 12 and 18 months, followed by yearly boosters. Limited human data suggest that the vaccine protects against cutaneous anthrax. There is insufficient data to know its efficacy against inhalational anthrax in humans, although studies in rhesus monkeys indicate that good protection can be afforded after only two doses (15 days apart) for up to 2 years. However, it should be emphasized that the vaccine series should be completed according to the routine 6 dose primary series. As with all vaccines, the degree of protection depends upon the magnitude of the challenge dose; vaccine-induced protection could presumably be overwhelmed by extremely high spore challenge.
Contraindications for use of this vaccine include hypersensitivity reaction to a previous dose of vaccine and age < 18 or > 65. Reasons for temporary deferment of the vaccine include pregnancy; active infection with fever; or a course of immune suppressing drugs such as steroids. Reactogenicity is mild to moderate. Up to 6 percent of recipients will experience mild discomfort at the inoculation site for up to 72 hours (e.g., tenderness, erythema, edema, pruritus), while less than 1 percent will experience more severe local reactions, potentially limiting use of the arm for 1-2 days. Modest systemic reactions (e.g., myalgia, malaise, low-grade fever) are uncommon, and severe systemic reactions such as anaphylaxis, which precludes additional vaccination, are rare. The vaccine should be stored between 2-6 oC (refrigerator temperature, not frozen).
Antibiotics: The choice of antibiotics for prophylaxis is difficult to make; for example, it seems relatively easy to induce penicillin and tetracycline resistance in the laboratory. Therefore, prophylaxis with ciprofloxacin (500 mg po bid) or doxycycline (100 mg po bid) is recommended. If personnel are 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 those exposed, and until all those exposed have received three doses of the vaccine. Two additional 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 of the primary series, within the previous six months. 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 and withdrawn under medical observation. Optimally, patients should have medical care available upon discontinuation of antibiotics, from a fixed medical care facility with intensive care capabilities and infectious disease consultants.
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