Anthrax: The Disease

by CDC

(Page 2 of 2)

Inhalational anthrax generally occurs after an incubation period of 1 to 6 days. During the Sverdlovsk outbreak, however, spontaneous cases appeared to arise as late as 43 days after the assumed release date. Such late cases are unexplained but have potentially serious implications for postexposure management of victims of aerosol exposure. After the incubation period, a nonspecific flulike illness ensues, characterized by fever, myalgia, headache, a nonproductive cough, and mild chest discomfort. A brief intervening period of improvement sometimes follows 1 to 3 days of these prodromal symptoms, but rapid deterioration follows; this second phase is marked by high fever, dyspnea, stridor, cyanosis, and shock. In many cases, chest wall edema and hemorrhagic meningitis (present in up to 50% of cases [15]) may be seen late in the course of disease. Chest radiographs may show pleural effusions and a widened mediastinum, although true pneumonitis is not typically present. Blood smears in the later stages of illness may contain the characteristic gram-positive spore-forming bacilli. Death is universal in untreated cases and may occur in as many as 95% of treated cases if therapy is begun more than 48 hours after the onset of symptoms.

While early recognition of anthrax is likely to require a heightened degree of suspicion, the diagnosis is supported by gram-positive bacilli in skin biopsy material (in the case of cutaneous disease) or in blood smears. A preponderance of gram-positive bacilli in swabs of the nares or in appropriate environmental samples might support a diagnosis of anthrax where intentional release is suspected. Chest radiographs exhibiting a widened mediastinum in the proper setting of fever and constitutional signs and in the absence of another obvious explanation (such as blunt trauma, deceleration injury, or postsurgical infection) should also lead to a diagnosis of anthrax. This finding is only likely to occur late in the course of disease. Confirmation is obtained by culturing B. anthracis from blood.

Disease Management

While endemic strains of B. anthracis are typically sensitive to various antibiotics, including penicillin G, antibiotic-resistant strains do (on rare occasion) occur naturally and can be readily isolated in laboratories. For this reason, as well as the convenience of twice-daily dosing, many experts consider ciprofloxacin (400 mg intravenously (i.v.) q 12 h) the drug of choice for treating victims of terrorism or warfare. Doxycycline (100 mg i.v. q 12 h) is an acceptable alternative, although rare doxycycline-resistant strains of B. anthracis are known. Conversely, however, the much lower cost of tetracyclines compared to quinolones may factor into therapeutic decisions, especially where large numbers of patients are involved. These recommendations are based solely on in vitro data and data from animal models; no human clinical experience with these regimens exists. In cases of endemic anthrax, or where organisms are known to be susceptible, penicillin G (2 million units i.v. q 2 h or 4 million units i.v. q 4 h) is recommended.

Postexposure prophylaxis against anthrax may be achieved with oral ciprofloxacin (500 mg orally q 12 h) or doxycycline (100 mg orally q 12 h), and all persons exposed to a bioterrorist incident involving anthrax should be administered one of these regimens at the earliest possible opportunity. In cases of threatened or suspected release of anthrax, chemoprophylaxis can be delayed 24 to 48 hours, until the threat is verified. Chemoprophylaxis can be discontinued if the threat is found to be false. Levofloxacin and ofloxacin would be acceptable alternatives to ciprofloxacin. In addition to receiving chemoprophylaxis, exposed persons should be immunized. On the basis of animal data (wherein an appreciable number of unvaccinated primates died when antibiotics were withdrawn after 30 days of therapy), chemoprophylaxis is best continued until the exposed persons has received at least three doses of vaccine (thus, for a minimum of 4 weeks). If vaccine is unavailable, some recommend that chemoprophylaxis be continued for 8 weeks. The available vaccine was licensed (for preexposure prophylaxis) by the U.S. Food and Drug Administration in 1970 and is prepared from a formalin-treated culture supernatent of an avirulent B. anthracis strain. It is given in a preexposure regimen at 0, 2, and 4 weeks, and at 6, 12, and 18 months. Persons at continuing risk for exposure should receive yearly boosters. Exposed persons should receive at least three doses (at 0, 2, and 4 weeks), assuming no further exposure is likely, before discontinuing chemoprohylaxis.

Recently, a number of hoaxes involving a threatened release of anthrax have been promulgated, and guidelines have now been published to assist in the management of such threats. When evaluating a threatened release of anthrax, the lack of volatility of the disease, as well as its inability to penetrate intact skin, should be taken into account. These factors make it unlikely, in most cases, that persons coming in contact with letters, packages, and other devices purported to contain anthrax will be at risk for aerosol exposure. Moreover, because energy is required to aerosolize anthrax spores, opening a letter, even if it contained anthrax, would be unlikely to place a person at substantial risk. For these reasons, postexposure prophylaxis may not be necessary in many cases of threatened anthrax dissemination.

Anthrax has little potential for person-to-person transmission; standard precautions are thus adequate for health-care workers treating anthrax patients. Anthrax, as well as other bacteriologic and viral weapons, has an incubation period of > 24 hours. This characteristic is not shared by conventional, chemical, and nuclear weapons and makes decontamination of infected persons admitted to hospitals days after exposure unnecessary in most cases. However, in certain cases, such as exposure to a threat letter involving an unidentified substance, where anthrax cannot readily be ruled out by Gram stain or other rapid diagnostic procedures, decontamination may be warranted. In such cases, decontamination may be accomplished by removing clothing, sealing it in a plastic bag, and showering with copious amounts of soap and water. Environmental surfaces and personal effects may be treated with 0.5% hypochlorite after the area in which the agent was released is investigated.

In summary, even though anthrax may be among the most viable of biological weapons, it is also a weapon for which a licensed vaccine and good antimicrobial therapy and postexposure prophylaxis exist. Given the relatively short incubation period, and rapid progression of disease, however, identification of the exposed population within 24 to 48 hours and employment of therapeutic and prophylactic strategies are likely to present a challenge. Good intelligence regarding the capabilities of terrorist groups, as well as heightened awareness of the threat on the part of clinicians, first responders, and public health personnel remains a cornerstone of bioterrorism defense.

About the Author

www.cdc.gov
The Centers for Disease Control and Prevention (CDC) is one of the 13 major operating components of the Department of Health and Human Services (HHS), which is the principal agency in the United States government for protecting the health and safety of all Americans and for providing essential human services, especially for those people who are least able to help themselves.