Natural History of Anthrax: a Study of Primary Infected, Recovered, and Exposed Individuals (SPoRE); and Evaluation of AVA-Vaccinated Recipients

The intentional use of Bacillus anthracis in 2001 as a bioterrorism weapon with fatal consequences renewed interest in past epidemiologic and animal research about pathogenesis and posed new dilemmas about diagnosis and treatment. Cases in the October 2001 US outbreak were theoretically exposed via one dispersal method: aerosolization of Ames strain spores. While some developed the cutaneous anthrax form, others sustained the more serious inhalational disease. Inhaled spores are known to travel to alveolar macrophages and then onto the mediastinal lymph nodes where germination to the bacterium form and toxin release are thought to occur. Infective dose, significance of dormant spores after long-term antibiotic therapy, spectrum of disease and even precise cause of death remain unknown. This observational, prospective natural history study was developed during the 2001 outbreak and is set up to follow participants from the time of exposure through post-recovery (greater than ten years). Healthy vaccinated participants have been included to evaluate serum titers and cell markers in relation to dose and frequency of Anthrax Vaccine Adsorbed (AVA) vaccine.

• INCLUSION CRITERIA:

Subjects at least 3 years old, including pregnant women, are eligible for inclusion if they meet one of the five criteria listed below, are hemodynamically and clinically stable, and agree to stored samples. Women of child-bearing age or potential will not be excluded from participation but pregnancy status will be determined by serum or urine pregnancy test at time of enrollment in order to optimize subsequent evaluation and care.

Although the study is open to participants at least 3 years old, pediatric anthrax cases are historically rare and essentially of the cutaneous type. Therefore, few, if any pediatric subjects are expected.

Decisionally impaired subjects will be included in this study only if a Legally Authorized Representative (LAR) understands and is willing to sign a written informed consent document.

• Inhalation Anthrax (acute or recovering infection)

CONFIRMED:

--nonspecific febrile illness followed by sepsis and/or respiratory failure

AND

--B anthracis isolation (via culture) from any site OR 2 supportive lab tests

OR SUSPECTED:

--nonspecific febrile illness followed by sepsis and/or respiratory failure with no alternative diagnosis

AND

--one supportive lab test OR direct epidemiological link to a confirmed environmental exposure

• Cutaneous Anthrax (acute or recovering infection)

CONFIRMED:

--characteristic lesion (papule->vesicular->depressed black eschar plus or minus edema, erythema, necrosis, or ulceration)

AND

--B anthracis isolation (culture) from any site OR 2 supportive lab tests

SUSPECTED:

--Characteristic lesion with no alternative diagnosis

AND

--one supportive lab test OR direct epidemiological link to a confirmed environmental exposure

• Gastrointestinal Anthrax (acute or recovering infection)

CONFIRMED:

--Severe abdominal pain often associated with bloody vomiting/diarrhea followed by fever/septicemia

AND

--B anthracis isolation (culture) from any site OR 2 supportive lab tests

SUSPECTED:

--Severe abdominal pain often associated with bloody vomiting/diarrhea followed by fever/septicemia with no alternative diagnosis

AND

--1 supportive lab test OR direct epidemiological link to a confirmed environmental exposure

These definitions were subsequently updated by the CDC in 2010 to accept clinically compatible symptoms plus one of the following: a positive culture, a positive immunohistochemical stain for antigen, a 4-fold increase in anti-PA IgG or a positive documented exposure with detection of DNA via PCR (26).

• Exposed individuals who are clinically asymptomatic.
• Past or imminent vaccination in healthy (non-anthrax exposed).
• Hemodynamically and clinically stable at time of evaluation at NIH.

• Hemodynamically: stable vital signs
• Clinically: no obvious signs of disease progression (e.g. worsening pleural effusions or increasing cutaneous edema)
• acute/newly recovered patients must be receiving standard antimicrobial therapy
• Participant agrees to stored samples.

Exclusion criteria

Inability of subject or Legally Authorized Representative (LAR) to understand or subject not willing to sign a written informed consent document.