24 January 2005
The 2005 edition of the Principles and Practices of Infectious Diseases textbook, edited by Mandell, Bennett, and Dolin, contains an updated clinical staging system for inhalational anthrax. This staging system incorporates the clinical lessons from the anthrax attacks of 2001. It emphasizes that patients with mediastinal adenopathy, bloody pleural effusions, and/or blood cultures growing the bacteria that causes anthrax can still be cured with appropriate antibiotics, drainage of effusions, and close supportive care. This newly named stage of inhalational anthrax is referred to as the “intermediate-progressive” stage. In contrast, prior to 2001 it was believed that such patients had “late” inhalational anthrax and could not be cured.
This new clinical staging system for inhalational anthrax is summarized as:
1. “Asymptomatic”-incubation period: often lasts < 1 week, but rarely > 1 month.
2. “Early-prodromal” stage: Nonspecific malaise, low-grade fevers, flu-like with myalgias, nausea, and mild headache.
3. “Intermediate-progressive” stage: Any combination of higher fever, dyspnea, confusion or syncope, increasing nausea/vomiting. Blood cultures typically positive in < 24 hours IF drawn before antibiotics, mediastinal adenopathy present by CT scan (or less clearly by chest x-ray), and hemorrhagic pleural effusions that tend to reaccumulate and require drainage. Patients can still be cured at this stage, with bacteremia, mediastinal adenopathy, and effusions, as proven in 2001.
4. “Late-fulminant” stage: Respiratory failure requiring intubation within 24 hours of hospitalization, meningitis, shock. Cure is less likely at this stage. For example, in 2001 the need for intubation within 24 hours of hospitalization occurred in 4 of the 5 fatal cases of inhalational anthrax, but in none of the 6 nonfatal cases.
In 2001 the 11 patients with inhalational anthrax developed three common findings:
First, 10 demonstrated mediastinal adenopathy, with chest CT scan being more sensitive than chest X-ray. Thus, nearly all of the survivors (5/6) as well as the non-survivors (5/5) had mediastinal adenopathy.
Second, 8 of the 11 patients developed bloody pleural effusions, usually bloody or recurrent, and requiring treatment with thoracenteses or chest tube drainage. All 6 of the 6 survivors developed pleural effusions, whereas 2 of the 5 non-survivors developed effusions. Thus, the presence of pleural effusions, when managed appropriately with adequate drainage, was not associated with a fatal outcome.
Third, all 8 patients with blood cultures drawn before antibiotics grew the Bacillus anthracis bacteria very rapidly, i.e., within 24 hours. These 8 cases included 3 survivors and 5 non-survivors. Therefore, bacteremia should not preclude aggressive treatment because cure can still be achieved. One of the three survivors, a postal worker, had the blood culture drawn as an outpatient before being sent home, only to be called back and hospitalized for treatment when the blood culture began to grown the anthrax organism less than 24 hours later.
Consideration of this updated clinical staging system (proposed by this author) emphasizes rapid recognition and empiric treatment of patients with possible inhalational anthrax, even in the “intermediate-progressive’ stage, and the explicit linkage of “surveillance for symptomatic patients” with suspected environmental exposures to anthrax.
Daniel R. Lucey, MD, MPH
Director, Center for Biologic Counterterrorism and Emerging Diseases