Anthrax (Bacillus spp.)
2025 Case Definition

Background

Anthrax has been a notifiable condition since 1944¹ and has historically been caused by the organism B. anthracis. Advances in whole genome sequencing (WGS) are redefining the Bacillus taxonomic nomenclature and additional Bacillus species that can produce anthrax toxins are being identified through advanced molecular methods. Although B. anthracis is a select agent and thus falls under the reporting requirements of both the National Select Agent Program² and the Laboratory Response Network (LRN), CDC also conducts case surveillance to identify anthrax caused by both B. anthracis and other Bacillus species.

Clinical Criteria

• Death of an unknown cause with organ involvement consistent with anthrax; OR
• In the absence of another more likely etiology,
  • At least one of the following specific signs and symptoms:
    • Evidence of pleural effusion
    • Evidence of mediastinal widening or hemorrhagic mediastinal lymphadenopathy on imaging
    • Blood in the CSF
    • Painless or pruritic papular or vesicular lesion or eschar, may be surrounded by edema or erythema
    • Pneumonia

OR 

• • At least two of the following non-specific signs and symptoms:
    • Abdominal pain
    • Abdominal swelling
    • Abnormal lung sounds
    • Altered mental status
    • Ascites
    • Cervical lymphadenopathy/Swelling of the neck
    • Coagulopathy
    • Cough
    • Diarrhea
    • Difficulty swallowing
    • Dyspnea
    • Edema
    • Fever
    • Headache
    • Hemoptysis
    • Hypotension
    • Lymphadenopathy
    • Meningeal signs
    • Nausea/vomiting
    • Sore throat
    • Tachycardia
    • Tachypnea

Laboratory Criteria

Confirmatory Laboratory Evidence: 

• Culture and identification of B. anthracis or Bacillus spp. expressing anthrax toxins from clinical specimens by Laboratory Response Network (LRN); ^{3, 4} OR 
• Evidence of a four-fold rise in antibodies to protective antigen (PA; one of the anthrax toxins) between acute and convalescent sera collected two-four weeks apart using quantitative anti-PA IgG ELISA testing in an unvaccinated person; OR 
• Evidence of a four-fold change in antibodies to protective antigen (one of the anthrax toxins) in paired convalescent sera collected two-four weeks apart using quantitative anti-PA IgG ELISA testing in an unvaccinated person; OR
• Detection of B. anthracis or anthrax toxin genes by the LRN-validated polymerase chain reaction and/or sequencing in clinical specimens collected from a normally sterile site (such as blood or CSF) or lesion of other affected tissue (skin, pulmonary, reticuloendothelial, or gastrointestinal); OR
• Detection of lethal factor (LF) in clinical serum specimens by LF mass spectrometry.

Presumptive Laboratory Evidence: 

• Demonstration of B. anthracis antigens in tissues by immunohistochemical staining; OR
• Gram stain demonstrating Gram-positive rods, square-ended, in pairs or short chains; OR
• Positive result on an anthrax test with established performance in a CLIA-accredited laboratory^{^.}

Note: The categorical labels used here to stratify laboratory evidence are intended to support the standardization of case classifications for public health surveillance. The categorical labels should not be used to interpret the utility or validity of any laboratory test methodology.

^ For example, the RedLine Alert test, http://tetracore.com/bacillus-anthracis- detection/Tetracore_RedLine_Alert_Test.pdf.

Epidemiologic Linkage

• Exposure to environment, food, animal, materials, or objects that is/are suspected or confirmed to be contaminated with B. anthracis or anthrax toxin-producing Bacillus spp.; OR 
• Exposure to the same environment, food, animal, materials, place of occupation, or objects as another person who has laboratory-confirmed anthrax.

Criteria to Distinguish a New Case from an Existing Case

A new case should be enumerated when:

• Person not previously enumerated as a case; OR 
• Person previously enumerated as a case AND newly meets confirmatory lab criteria after completing treatment for their previous infection AND had a new exposure to an anthrax-toxin producing Bacillus spp.

Suspect

• Meets vital records criteria only.

Probable

• Meets the clinical criteria AND meets presumptive laboratory evidence, OR 
• Meets vital records criteria AND meets presumptive laboratory evidence, OR 
• Meets the clinical criteria AND meets epidemiologic linkage criteria.

Confirmed

• Meets the clinical criteria AND meets confirmatory laboratory evidence, OR 
• Meets vital records criteria AND meets confirmatory laboratory evidence.

Vital Records Criteria

A person whose death certificate lists anthrax as a cause of death or a significant condition contributing to death.

Case Classification Comments

The following provides guidance for health departments to use for optional further sub-classification of anthrax cases. The type of anthrax case depends on the clinical manifestations that present as an illness or during a post-mortem examination per the clinical presentations listed below. All case classifications (i.e., confirmed, probable, and suspect) for anthrax may be further sub-classified by type of anthrax.

Cutaneous anthrax: Usually begins as a small, painless, pruritic papule on an exposed surface, which progresses through a vesicular stage into a depressed black eschar; the eschar is often surrounded by edema or erythema and may be accompanied by lymphadenopathy. Non-specific signs and symptoms include fever and localized edema.

Ingestion anthrax: Presents as one of two sub-types:

Oropharyngeal: When anthrax spores germinate in the oropharynx, a mucosal lesion may be observed in the oral cavity or oropharynx. Signs and symptoms are non-specific and include sore throat, dysphagia, swelling of the neck, fever, fatigue, shortness of breath, abdominal pain, and nausea/vomiting; the signs and symptoms may resemble a viral respiratory illness. Cervical lymphadenopathy, ascites, and altered mental status may be observed.
Gastrointestinal: When anthrax spores germinate in the lower gastrointestinal tract, signs and symptoms are mainly non-specific and include abdominal pain, nausea, vomiting or diarrhea (either of which may contain blood), abdominal swelling, fever, fatigue, and headache are also common. Altered mental status and ascites may be observed.

Inhalation anthrax: Often described as a biphasic illness. Specific signs and symptoms include pleural effusion or mediastinal widening, or hemorrhagic mediastinal lymphadenopathy. Early nonspecific signs and symptoms of inhalation anthrax include fever and fatigue. Localized thoracic signs and symptoms such as cough, chest pain, and shortness of breath follow, as may non-thoracic signs and symptoms such as nausea, vomiting, abdominal pain, headache, diaphoresis, and altered mental status. Lung sounds are often abnormal.

Injection anthrax: Usually presents as a severe soft tissue infection manifested as significant edema or bruising after an injection. No eschar is apparent, and pain is often not described. Nonspecific signs and symptoms such as fever, shortness of breath, or nausea are sometimes the first indication of illness. Occasionally patients present with meningeal or abdominal involvement. A coagulopathy is not unusual.

Welder’s anthrax: Usually presents as a pneumonia that may be accompanied by hemoptysis or pleural effusion. Unlike inhalation anthrax, mediastinal widening is not common. Non-specific signs and symptoms include fever or chills, cough, dyspnea, and hemoptysis. Lung sounds are often abnormal.

Additional considerations:

1) Signs of systemic involvement from the dissemination of either the bacteria and/or its toxins can occur with all types of anthrax and include fever or hypothermia, tachycardia, tachypnea, hypotension, and leukocytosis. One or more of these signs are usually present in patients with ingestion anthrax, inhalation anthrax, injection anthrax, and welder’s anthrax and may be present in up to a third of patients with cutaneous anthrax.
2) Anthrax meningitis: may complicate any form of anthrax and may also be a primary manifestation. Primary signs and symptoms include fever, headache (which is often described as severe), nausea, vomiting, and fatigue. Meningeal signs (e.g., meningismus), altered mental status, and other neurological signs such as seizures or focal signs are usually present. Most patients with anthrax meningitis have CSF abnormalities consistent with bacterial meningitis and is often described as hemorrhagic.

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