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An Improved Clinical Staging System for Inhalational Anthrax

Topics in Clinical Biosecurity

By Daniel R. Lucey, M.D., M.P.H., November 8, 2005

Experience with victims of the anthrax attacks of 2001 suggests that patients present in three, rather than two, distinguishable clinical stages. An improved clinical staging system for the disease may have prognostic and therapeutic implications.

Historically, inhalational anthrax was described as a two-stage disease process, comprising early and late symptomatic clinical stages [1,2]. Following an asymptomatic incubation period, patients in the first, or early stage, “developed a spectrum of nonspecific symptoms, which could include fever, dyspnea, cough, headache, vomiting, chills, weakness, abdominal pain, and chest pain. Signs of illness and laboratory studies were also nonspecific.”

The “late stage developed abruptly, with sudden fever, dyspnea, diaphoresis, and shock... A chest radiograph most often showed a widened mediastinum consistent with lymphadenopathy. Up to half of patients developed hemorrhagic meningitis. In this second stage, cyanosis, and hypotension progressed rapidly; death sometimes occurred within hours” [2]. It was believed that fatality was almost certain for persons who did not receive prompt medical care after the earliest signs of disease. 

However, in 2001, of the 11 patients who developed inhalational anthrax, 6 survived. Based on clinical, radiologic, and microbiologic findings from these 11 patients, a new 3 level clinical staging system has been proposed [1]:   




Early-prodromal stage

Unchanged from original staging system

Cure rate is high with institution of appropriate antibiotics.

Intermediate-progressive stage

Any one of the following findings is defined as inclusion criteria for this stage:

  1. Positive blood cultures, or
  2. Mediastinal adenopathy, or
  3. Pleural effusion(s)

Non-specific and non-defining symptoms and signs in this stage may include high fever, dyspnea, confusion, syncope, increasing nausea and vomiting.

Cure rate is still high with rapid treatment with appropriate antibiotics, pleural fluid drainage, and meticulous supportive care.

Late-fulminant stage

Any one of the following findings is defined as inclusion criteria for this stage:

  1. Meningitis, or
  2. Respiratory failure requiring mechanical ventilation, or
  3. Shock

Findings in this stage may also include any of those from prior stages, for example positive blood cultures, mediastinal adenopathy, or pleural effusion(s).

Survival is much less likely.

In 2001, all 6 survivors presented for medical care in the “intermediate-progressive” stage [1,3]. This new proposed staging system can help distinguish those patients with a high probability of cure (intermediate-progressive stage) from those with a lower probability of cure (late-fulminant stage).

This new staging system has therapeutic implications as well, in that it may change the way we view treatment of patients with inhalational anthrax. To date, prompt antimicrobial therapy has been the mainstay of therapy. However, in 2001, all 6 surviving patients required meticulous supportive care, which included repeated drainage of large, bloody, and recurrent pleural effusions in five persons and a single chest tube to drain 900 ml of fluid in the remaining patient [3]. Large pleural effusions may contribute to respiratory failure and may contain residual Bacillus anthracis that can be a source of toxin production [3,4]. Thus, in addition to prompt antimicrobial therapy, in the future, hospitals should be prepared to offer meticulous supportive medical care that includes pleural fluid drainage, to a large number of patients, depending on the size of an attack.


  1. Lucey D. Anthrax. In Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 6th ed. Philadelphia: Elsevier Churchill Livingstone; 2005.

  2. Inglesby TV, O'Toole T, Henderson DA, et al. Anthrax as a biological weapon, 2002: updated recommendations for management. JAMA 2002;287(17):2236-52.

  3. Jernigan DB, Raghunathan PL, Bell BP, et al. Investigation of bioterrorism-related anthrax, United States, 2001: epidemiologic findings. Emerg Infect Dis 2002;8(10):1019-28.

  4. Brachman PS. Inhalation anthrax. Ann N Y Acad Sci 1980;353:83-93.

Dr. Daniel Lucey is the  Co-Director of the Master's Degree Program in Biohazardous Threat Agents and Emerging Diseases and an Adjunct Professor of Microbiology and Immunology at Georgetown University School of Medicine, Washington, D.C. He is also an affiliated clinician of the CBN.