The agents most likely to be used in bioterrorism attacks are reviewed in a new Review Article, “Clinical Management of Potential Bioterrorism-Related Conditions,” along with the clinical syndromes they produce and their treatment. This article comes from University of Pittsburgh’s Drs. Amesh Adalja, Eric Toner, and Thomas Inglesby.
On the basis of historical incidents coupled with information on ease of dissemination, contagiousness, mortality rates, public health impact, ability to engender panic, and the need for special preparedness, the Centers for Disease Control and Prevention (CDC) stratifies pathogens and toxins into three risk categories — A, B, and C — with category A meriting the highest level of concern and preparedness.
- What is the most lethal form of anthrax, and what are its clinical features?
Anthrax is caused by infection with the spore-forming, exotoxin-producing, gram-positive bacillus Bacillus anthracis. In humans, three forms of anthrax are recognized: cutaneous (the most common), gastrointestinal and inhalational (the most deadly).
Inhalational anthrax results from the inhalation of bacterial spores that later germinate in the lung. Disease onset begins with nonspecific influenza-like symptoms; with the exception that rhinorrhea is absent. After the disease progresses through this stage, which lasts hours to days, a severe advanced phase occurs and includes high fever, shock, and respiratory distress. Inhalational anthrax does not cause pneumonia but nevertheless can progress to the acute respiratory distress syndrome. Hemorrhagic mediastinitis, as well as toxin-laden pleural and pericardial effusions, can be present. Spread of the disease to the meninges, with resultant hemorrhagic meningitis, is a frequent complication of systemic forms of anthrax, occurring in up to 50% of cases; this complication confers a higher degree of mortality. Traditionally, inhalational anthrax has carried a 90% case fatality rate; however, during the 2001 attacks in which anthrax spores were sent through the U.S. mail, the case fatality rate was halved, to 45%. The reason for the decrement in mortality is probably multifactorial and includes the benefits of modern critical care, the drainage of toxin-laden pleural effusions, and the use of antimicrobial therapies.
- What is the recommended treatment for systemic anthrax?
Anthrax-specific treatments include combination antimicrobial therapy. If meningitis has not been ruled out, the CDC recommends a regimen including a fluoroquinolone, such as ciprofloxacin; a drug that inhibits protein synthesis, such as linezolid; and a drug that penetrates the central nervous system, such as meropenem. If meningitis has been ruled out with the use of a lumbar puncture, a two-drug regimen that includes a fluoroquinolone plus linezolid or clindamycin is recommended. The CDC recommends antitoxin as adjunctive treatment in cases of systemic anthrax.
Morning Report Questions
Q: What are the clinical features of smallpox, and are there any FDA [Food and Drug Administration]-licensed therapies?
A: Infection with the smallpox virus, variola, occurs through droplet or aerosol exposure. After an incubation period of 10 to 14 days, a prodrome of fever and constitutional symptoms begins. Rash appears 1 to 4 days after the onset of fever. The rash is characteristically centrifugal, with lesions progressing synchronously from macules to papules to vesicles (umbilicated) to pustules to scabs over a period of a couple weeks. A person is contagious during the period when the rash is present, and infectiousness ceases after the scabs have sloughed. The fatality rate of smallpox is approximately 25%, and severe complications such as blindness can also occur. There are currently no FDA-licensed treatments for smallpox, although two compounds are in late development stages. Indications for their use are not yet available, but their availability during an outbreak would probably be through emergency-use authorization.
Q: What type of illness would result from a deliberate release of tularemia, and how might it be treated?
A: Several forms of tularemia occur; however, a deliberate release would be expected to cause pneumonic tularemia rather than the more common ulceroglandular form. After an average incubation period of 3 to 5 days, pneumonic tularemia would manifest with signs and symptoms similar to those of community-acquired pneumonia, including fever, cough, and dyspnea. However, septic shock, acute respiratory distress syndrome, and respiratory failure can ensue. Because there is no distinguishing characteristic of pneumonic tularemia, clinical suspicion must be high. The treatment of tularemia consists of a 10-day course of an aminoglycoside antibiotic, such as streptomycin or gentamicin. Ciprofloxacin and doxycycline are alternatives.