Practice Guidelines

CDC Issues Guidelines on Illnesses Associated with Intentional Release of Biologic Agents



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Am Fam Physician. 2001 Nov 15;64(10):1761-1764.

The Centers for Disease Control and Prevention (CDC) has issued a report on the investigation of recent cases of anthrax exposure. This update includes interim guidelines for postexposure prophylaxis for prevention of inhalational anthrax and other information to assist epidemiologists, physicians and laboratory personnel responding to intentional biologic agent exposures. The complete report appears in the October 19, 2001 issue of Morbidity and Mortality Weekly Report.

Anthrax is an acute infectious disease caused by the spore-forming bacterium Bacillus anthracis. It occurs most frequently as an epizootic or enzootic disease of herbivores (e.g., cattle, goats or sheep) that acquire spores from direct contact with contaminated soil. Humans usually become infected through direct contact with spores from infected animals or their products (e.g., goat hair), resulting in cutaneous anthrax. Inhalational and gastrointestinal forms also occur in natural settings. Human-to-human transmission has not been documented.

Clinical Forms of Anthrax

There are three clinical descriptions of anthrax based on experience in adults. The presentation of anthrax in infants is not well defined.

Inhalational

Inhalational anthrax begins with a brief prodrome resembling a viral respiratory illness followed by development of hypoxia and dyspnea, with radiographic evidence of mediastinal widening. It is the most lethal form of anthrax and results from inspiration of 8,000 to 50,000 spores of B. anthracis. The incubation period among humans typically ranges from one to seven days, possibly up to 60 days. Host factors, dose of exposure and chemoprophylaxis may affect the duration of the incubation period. Initial symptoms include mild fever, muscle aches, and malaise and may progress to respiratory failure and shock; meningitis frequently develops. Case fatality estimates for inhalational anthrax are extremely high even with all possible supportive care, including appropriate antibiotics.

Cutaneous

Cutaneous anthrax is characterized by a skin lesion evolving from a papule, through a vesicular stage, to a depressed black eschar. The incubation period ranges from one to 12 days. The lesion is usually painless, but patients may also have fever, malaise, headache and regional lymphadenopathy. The case fatality rate is 20 percent without, and less than 1 percent with, antibiotic treatment.

Gastrointestinal

Gastrointestinal anthrax is characterized by severe abdominal pain followed by fever and signs of septicemia. This form of anthrax usually occurs after eating raw or undercooked contaminated meat and can have an incubation period of one to seven days. An oropharyngeal and an abdominal form of the disease have been described. Involvement of the pharynx is usually characterized by lesions at the base of the tongue, dysphagia, fever and regional lymphadenopathy. Lower bowel inflammation typically causes nausea, loss of appetite and fever followed by abdominal pain, hematemesis and bloody diarrhea. The case fatality rate is estimated to be 25 to 60 percent. The effect of early antibiotic treatment on the case fatality rate is not established.

Laboratory personnel should suspect B. anthracis when the specimen is from a previously healthy patient with a rapidly progressive respiratory illness or a cutaneous ulcer. If anthrax is suspected, laboratories should notify the health care provider and local and state public health staff immediately. For rapid identification, state and local health departments should access the Laboratory Response Network for Bioterrorism (LRN). LRN links state and local public health laboratories with advanced capacity facilities, including clinical, military, veterinary, agricultural, water and food-testing laboratories.

Postexposure prophylaxis is indicated to prevent inhalational anthrax after a confirmed or suspected aerosol exposure. When no information is available about the antimicrobial susceptibility of the implicated strain of B. anthracis, initial therapy with ciprofloxacin or doxycycline is recommended for adults and children (see accompanying table). Tetracyclines and fluoroquinolones have adverse effects in children that must be weighed against the risk for developing a life-threatening disease. As soon as penicillin susceptibility of the organism has been confirmed, prophylactic therapy for children should be changed to oral amoxicillin, 80 mg per kg daily divided every eight hours (not to exceed 500 mg three times daily). Cephalosporins and trimethoprim/sulfamethoxazole should not be used because B. anthracis is not susceptible to them.

Interim Recommendations for Postexposure Prophylaxis for Prevention of Inhalational Anthrax After Intentional Exposure to Bacillus anthracis

Category Initial therapy Duration

Adults (including pregnant women and immunocompromised persons)

Ciprofloxacin, 500 mg orally twice daily

60 days

or

Doxycycline, 100 mg orally twice daily

Children

Ciprofloxacin, 10 to 15 mg per kg orally every 12 hours*

60 days

or

Doxycycline:

>8 years and >45 kg: 100 mg orally twice daily

>8 years and <45 kg: 2.2 mg per kg orally twice daily

<8 years: 2.2 mg per kg orally twice daily


*— Ciprofloxacin dosage should not exceed 1 g per day in children.

Interim Recommendations for Postexposure Prophylaxis for Prevention of Inhalational Anthrax After Intentional Exposure to Bacillus anthracis

View Table

Interim Recommendations for Postexposure Prophylaxis for Prevention of Inhalational Anthrax After Intentional Exposure to Bacillus anthracis

Category Initial therapy Duration

Adults (including pregnant women and immunocompromised persons)

Ciprofloxacin, 500 mg orally twice daily

60 days

or

Doxycycline, 100 mg orally twice daily

Children

Ciprofloxacin, 10 to 15 mg per kg orally every 12 hours*

60 days

or

Doxycycline:

>8 years and >45 kg: 100 mg orally twice daily

>8 years and <45 kg: 2.2 mg per kg orally twice daily

<8 years: 2.2 mg per kg orally twice daily


*— Ciprofloxacin dosage should not exceed 1 g per day in children.

Recognizing Illnesses Associated with Biologic Agents

The following guidelines are intended to help health care providers and public health personnel recognize illnesses and patterns that might be associated with intentional release of biologic agents.

HEALTH CARE PROVIDERS

The covert release of a biologic agent may not have an immediate impact because of the delay between exposure and illness onset, and outbreaks associated with intentional releases might closely resemble naturally occurring outbreaks. Indications of intentional release of a biologic agent include an unusual temporal or geographic clustering of illness or patients presenting with clinical signs and symptoms that suggest an infectious disease outbreak; an unusual age distribution for common diseases; and a large number of cases of acute flaccid paralysis with prominent bulbar palsies suggestive of a release of botulinum toxin.

The CDC defines three categories of biologic agents with potential to be used as weapons, based on ease of dissemination or transmission, potential for major public health impact, potential for public panic and social disruption, and requirements for public health preparedness. Agents of highest concern include B. anthracis (anthrax), Yersinia pestis (plague), variola major (smallpox), Clostridium botulinum toxin (botulism), Francisella tularensis (tularemia) and filoviruses (Ebola and Marburg hemorrhagic fevers).

Anthrax

Approximately two to four days after initial symptoms of anthrax, sometimes after a brief period of improvement, respiratory failure and hemodynamic collapse ensue. Inhalational anthrax also might include thoracic edema and a widened mediastinum on chest radiograph. Gram-positive bacilli can grow on blood culture, usually two to three days after onset of illness. Cutaneous anthrax follows deposition of the organism onto the skin, occurring particularly on exposed areas of the hands, arms or face. An area of local edema becomes a pruritic macule or papule, which enlarges and ulcerates after one to two days. Small, 1 mm to 3 mm vesicles may surround the ulcer. A painless, depressed, black eschar, usually with surrounding local edema, subsequently develops. The syndrome may also include lymphangitis and painful lymphadenopathy.

Plague

Clinical features of pneumonic plague include fever, cough with mucopurulent sputum (gram-negative rods may be seen on gram stain), hemoptysis and chest pain. A chest radiograph will show evidence of bronchopneumonia.

Botulism

Clinical features of botulism include symmetric cranial neuropathies (i.e., drooping eyelids, weakened jaw clench and difficulty swallowing or speaking), blurred vision or diplopia, symmetric descending weakness in a proximal to distal pattern and respiratory dysfunction from respiratory muscle paralysis or upper airway obstruction without sensory deficits.

Smallpox

The acute clinical symptoms of smallpox resemble other acute viral illnesses, such as influenza, beginning with a two- to four-day nonspecific prodrome of fever and myalgias before rash onset. Unlike varicella (chickenpox), the vesicular/pustular rash of smallpox is typically most prominent on the face and extremities and lesions develop at the same time.

Inhalational Tularemia

Inhalation of F. tularensis causes an abrupt onset of an acute, nonspecific febrile illness beginning three to five days after exposure, with pleuropneumonitis developing in a substantial proportion of cases during subsequent days.

Hemorrhagic Fever

Hemorrhagic fever, caused by the Ebola and Marburg viruses, usually has an incubation period of five to 10 days. Illness is characterized by abrupt onset of fever, myalgia and headache. Other signs and symptoms include nausea and vomiting, abdominal pain, diarrhea, chest pain, cough and pharyngitis. A maculopapular rash, prominent on the trunk, develops in most patients approximately five days after onset of illness. Bleeding manifestations, such as petechiae, ecchymoses and hemorrhages occur as the disease progresses.

CLINICAL LABORATORY PERSONNEL

When collecting or handling clinical specimens, laboratory personnel should use Biological Safety Level II (BSL-2) or Level III facilities and practices when working with clinical samples considered potentially infectious; handle all specimens in a BSL-2 laminar flow hood with protective eyewear (e.g., safety glasses or eye shields), use closed-front laboratory coats with cuffed sleeves, and stretch the gloves over the cuffed sleeves; avoid any activity that places persons at risk for infectious exposure, especially activities that might create aerosols or droplet dispersal; decontaminate laboratory benches after each use and dispose of supplies and equipment in proper receptacles; avoid touching mucosal surfaces with the hands, and never eat or drink in the laboratory; remove and reverse gloves before leaving the laboratory and dispose of them in a biohazard container, and wash hands and remove the laboratory coat.

INFECTION CONTROL PROFESSIONALS

Infection control professionals should ensure that hospitals have current telephone numbers for notification of internal (epidemiologists, infectious diseases specialists, administrators and public affairs officials) and external (state and local health departments, Federal Bureau of Investigation field office and CDC Emergency Response office) contacts and that they are distributed to the appropriate personnel. They should work with clinical microbiology laboratories, on- or off-site, that receive specimens for testing from their facility to ensure that cultures from suspicious cases are evaluated appropriately.

STATE HEALTH DEPARTMENTS

Strategies for responding to potential bioterrorism include providing information or reminders to health care providers and clinical laboratories about how to report events to the appropriate public health authorities; implementing a 24-hour-a-day, seven-day-a-week capacity to receive and act on any positive report of events that suggest intentional release of a biologic agent; investigating immediately any report of a cluster of illnesses or other event that suggests an intentional release of a biologic agent and requesting CDC assistance when necessary; implementing a plan, including accessing the LRN to collect and transport specimens and to store them appropriately before analysis; and reporting immediately to the CDC if the results of an investigation suggest release of a biologic agent.

Health care professionals, clinical laboratory personnel, infection control professionals and health departments play critical and complementary roles in recognizing and responding to illnesses caused by intentional release of biologic agents. The syndrome descriptions, epidemiologic clues and laboratory recommendations in this report provide basic guidance that can be implemented immediately to improve recognition of these events.

Additional information about responding to bioterrorism is available from the CDC at http://www.bt.cdc.gov; the U.S. Army Medical Research Institute of Infectious Diseases at http://www.usamriid.army.mil/education/bluebook.html; and the Association for Infection Control Practitioners at http://www.apic.org.



Copyright © 2001 by the American Academy of Family Physicians.
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