17 March 2005
Events this week regarding apparently false-positive tests for anthrax warrant a brief update on key issues related to anthrax. The relevant CDC Health Advisory on March 15 and CDC Health Update on March 16 reported the following: on March 10th routine samples from an air sampling device at the Pentagon Remote Delivery Facility were collected and initial tests indicated possible anthrax, with the Department of Defense (DoD) being notified four days later, on March 14th. This initial sample "was tested by a non-Laboratory Response Network (LRN) lab, and found to be positive by PCR and culture. Repeat PCR testing of this same sample at the DHS Laboratory at Ft. Detrick was also positive. Testing of a second portion of the original sample by the DHS Laboratory was negative by PCR and culture".
By apparent coincidence an alarm at a second DoD mailroom in a separate facility, away from the Pentagon, in the Skyline complex, Virginia occurred on March 14th. However, this alarm "proved to be from a particle counter rather than a biological sensor, and no testing indicated B. anthracis", according to the CDC update March 16. Employees at these two DoD facilities as well as the civilian V-street postal facility in Washington, DC were initially placed on antibiotics prophylactically. No results of antibiotic susceptibility testing were given in the CDC documents for the initial sample that was found to be positive "by PRC and in culture" at the non-LRN lab. Being able to grow the Bacillus anthracis bacteria in culture, however, should prove critical in helping to subtype it, determine its susceptibility to multiple antibiotics, and possibly help identify its source.
A few of the salient points regarding anthrax "lessons identified"/"lessons learned" from 2001 and since could include:
1. Always draw blood cultures before giving any antibiotics to a person suspected of having anthrax. Blood cultures typically grow the Bacillus anthracis rapidly in <24 hours, and become sterile after even 1 or 2 doses of an antibiotic to which it is susceptible.
2. Either doxycycline or ciprofloxacin are recommended as equal initial choices for prophylaxis against inhalational anthrax, in the absence of known antibiotic susceptibility testing results.
3. It is critical that such antibiotic susceptibility testing is performed immediately once the first possible anthrax cultures are growing, as part of the standard operating procedure in either DoD-related labs, or non-DoD labs. In order to appropriately prophylax and treat persons for inhalational anthrax within the first hours to days after recognizing that an attack with anthrax has occurred, the antibiotic susceptibility of a broad array of drugs must already have been determined in the lab.
4. A search for symptomatic patients should be initiated immediately if a 'reasonable threat' of an attack has occurred, before final confirmation of multiple environmental samples has been completed. This search for symptomatic patients should include looking for skin manifestations of anthrax as well as respiratory, intestinal, and meningeal manifestations. In 2004, the WHO published updated guidelines on biological and chemical threats that included two tables listing the date of onset of symptoms for all 22 patients with anthrax in the 2001 attack in the USA. The 8th patient listed by date of onset of symptoms was the man who presented with anthrax meningitis in Florida, often thought of as the first case in 2001. However, 7 patients had onset of symptoms before this patient, and 6 of these 7 had anthrax of the skin, although understandably not recognized at the time.
5. Hemorrhagic pleural effusions, sometimes rapidly accumulating and recurrent, were the rule with the patients in 2001. These effusions sometimes required repeated needle drainage or chest tube placement.
6. Chest CT scans, without contrast, are more sensitive than chest x-ray at revealing the typical hemorrhagic mediastinal adenopathy that is highly suggestive of inhalational anthrax. This finding can occur before the patient is overwhelming ill.
7. Patients with mediastinal adenopathy, bloody pleural effusions (or "empyema" by definition when the Bacillus anthracis is found in the effusion), and positive blood cultures growing the organism CAN STILL BE CURED at this "intermediate-progressive" stage of inhalational anthrax.
8. The CDC recommends (unlike in 2001) investigational new drug (IND) use of anthrax vaccine, in conjunction with 60 days of antibiotics, after an aerosol release of Bacillus anthracis spores. This recommendation was posted on their website Sept 9, 2004 and again in 2005. The November 15, 2002 update on anthrax vaccine suggested that antibiotics be given for 7-14 days after the third dose of the anthrax vaccine. The 3 doses of vaccine are to be given over the course of one month (spaced apart at time 0, 2 weeks, and 4 weeks).
9. There is no FDA-licensed antitoxin against anthrax at this time. Several investigational products have been tested, including monoclonal and polyclonal antibodies, as well as antisera from persons vaccinated with the FDA-licensed vaccine (that is primarily composed of "Protective Antigen (PA),” the one common component of the anthrax binary toxins, named lethal toxin and edema toxin). Whether any of these investigational anthrax antitoxin products will have a role to play as either a prophylactic or therapeutic agent is still unclear.
Daniel R. Lucey, MD, MPH
Director, Center for Biologic Counterterrorism and Emerging Diseases
Washington Hospital Center