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The following comments are adapted from Health Alert No. 6, October 5, 2001, from the city of New York’s Department of Health. We feel they will be of value to our readers who must be aware of issues presented by potential bioterrorist events.
By Frank Bia, MD, MPH
Health care providers in travel medicine should be alert to illness patterns and diagnostic clues that might signal an unusual infectious disease outbreak due to the intentional release of a biological agent and should report these concerns immediately to their local health authorities and to the Geosentinal Alert Network. More detailed references with information on the clinical presentation, laboratory diagnosis, medical management, and preventive measures for the more likely bioterrorist agents (eg, anthrax, plague, or smallpox) are provided at the end of this section.
Unlike a chemical or nuclear release, the covert release of a biological agent will not have an immediate impact because of the delay between exposure and illness onset. Consequently, the first indication of a biologic attack may only be recognized when ill patients present to physicians or other health care providers for clinical care.
Look for the following clinical and epidemiological clues that may be suggestive of a possible bioterrorist event:
• Any unusual increase or clustering in patients presenting with clinical symptoms that suggest an infectious disease outbreak (eg, > 2 patients presenting with an unexplained febrile illness associated with sepsis, pneumonia, adult respiratory distress, mediastinitis, or rash; or a botulism-like syndrome with flaccid muscle paralysis, especially if occurring in otherwise healthy individuals).
• Any case of a suspected or confirmed communicable disease that is not endemic in your immediate area (eg, anthrax, plague, tularemia, smallpox, or viral hemorrhagic fever) or that occurs in a person without a travel history to an endemic area.
• Any unusual age distributions for common diseases (eg, a cluster of severe chickenpox-like illness among adult patients who all report a previous history of varicella infection).
• Any unusual temporal and/or geographic clustering of illness (eg, persons who attended the same public event or religious gathering).
• Any sudden increase in the following nonspecific syndromes, especially if occurring in previously healthy individuals and if there is an obvious common site of exposure:
Some infections caused by potential bioterrorist agents present with distinctive signs that can provide valuable diagnostic clues. In previously healthy persons presenting with a febrile illness, the following signs and symptoms are highly suggestive of infection with certain biological agents:
Most pathogens that could be used as a biologic weapon (eg, anthrax, plague, and smallpox) would present initially as a nonspecific influenza-like illness. Therefore, an unusual pattern of respiratory or influenza-like illness (eg, occurring out of season or in large numbers of previously healthy patients presenting simultaneously) should prompt clinicians to alert health authorities. These disease patterns might represent an early start to the influenza season or the introduction of a new pandemic strain of influenza, or could be the initial warning of a bioterrorist event.
For more detailed clinical information on specific pathogens that might be used in a bioterrorist event, please consult the following references or web sites:
— American College of Physicians. www.acponline.org/bioterr/
— American Society of Microbiology. www.asmusa.org/pcsrc/bioprep.htm
— Association for Infection Control Practitioners. www.apic.org/bioterror/
— CDC Bioterrorism Preparedness and Response. www.bt.cdc.gov
— Infectious Disease Society of America. www.idsociety.org
— Johns Hopkins Center for Civilian Biodefense. www.hopkins-biodefense.org (The Johns Hopkins Center for Civilian Biodefense has written consensus guidelines on the medical and public health management of the primary bioterrorist agents, including smallpox, anthrax, botulism, plague, and tularemia. These guidelines were published in the Journal of the American Medical Association and archived copies are available at http://jama.ama-assn.org).
— US Army Medical Research Institute of Infectious Diseases: www.usamriid.army.mil/education/bluebook.html
• Anthrax can be transmitted by inhalation, ingestion, or inoculation. (Inhalation is the most likely route during a bioterrorist attack.)
• The spore form of anthrax is highly resistant to physical and chemical agents; spores can persist in the environment for years.
• Anthrax is not transmitted from person to person.
• Incubation period is 1-5 days (up to 43 days reported in the literature).
• Biphasic illness, with initial phase characterized by nonspecific flu-like illness followed by an acute phase with a rapid clinical deterioration characterized by acute respiratory distress and toxemia (sepsis).
• Inhalational anthrax presents as acute hemorrhagic mediastinitis.
• Chest x-ray findings: Mediastinal widening in a previously healthy febrile patient is highly suggestive of anthrax. Parenchymal infiltrates are uncommon.
• Mortality rate for inhalational anthrax approaches 90%, even with antibiotic treatment.
• Laboratory specimens should be handled in biosafety level 2 facilities.
• Gram stain shows large, Gram-positive encapsulated bacilli, occurring singly or in short chains, often with squared off ends (safety-pin appearance). In advanced disease, a gram stain of unspun blood may be positive.
• Distinguishing characteristics on culture include: non-hemolytic, nonmotile, capsulated bacteria that are susceptible to gamma phage lysis, with a characteristic consistency of "beaten egg whites" when colonies are picked with an inoculating loop.
• Positive specimens would be sent to the Centers for Disease Control and Prevention for additional testing.
• Prompt initiation of antibiotic therapy is essential, and antibiotic susceptibility testing is key to guiding treatment.
• Ciprofloxacin (400 mg IV q 12 h) is the antibiotic of choice for penicillin-resistant anthrax or for empiric therapy while awaiting susceptibility results (alternative: doxycycline).
• Females who are pregnant (or who may be pregnant) and children younger than 8 years old also can be treated empirically with a quinolone (alternative: doxycycline).
• Natural strains of anthrax are resistant to extended-spectrum cephalosporins, trimethoprim, and sulfamethoxasole.
• Antibiotic treatment should continue for 60 days.
In the event that an outbreak of inhalational anthrax was confirmed or suspected, all exposed persons should receive antibiotic prophylaxis.
• Start antibiotic prophylaxis as soon as possible after exposure with either ciprofloxacin 500 mg p.o. b.i.d. or doxycycline 100 mg p.o. b.i.d. (If strain is penicillin-susceptible, therapy can be switched to penicillin or amoxicillin).
• Currently, anthrax vaccine is in limited supply and not available to the general public. If vaccine is made available in the event of a confirmed outbreak, exposed persons can be vaccinated with 3 doses of anthrax vaccine (Days 0, 14, and 28) at the same time that they are taking antibiotic prophylaxis. If this dual regimen is followed, antibiotics need to be administered for a total of 30 days.
• Standard precautions. Patients with anthrax of any form do not require isolation.