Overview

This study will examine pathophysiology and immune response of anthrax in infected or exposed individuals to learn more about the disease symptoms, prevention and response to treatment. In addition, it will evaluate immune response to the anthrax vaccine AVA (Anthrax Vaccine Adsorbed) in healthy, non-infected individuals.

The following individuals may be eligible for this study:

1. People with confirmed or suspected anthrax (inhalational, cutaneous or gastrointestinal, either acute or recovering);
2. People exposed to anthrax who have no clinical symptoms.
3. Healthy people who have not been exposed to anthrax and have been vaccinated with AVA.

Those enrolled in the study will undergo the following tests and procedures.

Infected and exposed individuals:

• Symptomatic participants will have the following clinical procedures if medically

  necessary

• a) blood tests for cell counts, chemistries and evidence of anthrax bacteria;
• b) nasal swab to test for evidence of anthrax
• c) chest X-ray;
• d) computed tomography (CT) scan (special X-rays to examine the lungs or abdomen);
• e) echocardiogram to examine the heart
• f) magnetic resonance imaging (MRI), a special imaging test using a magnetic field and radio waves to examine the infected area of skin and soft tissue for patients with cutaneous anthrax.
• All subjects (with or without symptoms) will have the following research procedures:
• a) blood tests to examine immune response to anthrax;
• b) throat swab to test for evidence of anthrax
• c) nasopharyngeal wash to test for anthrax. Water is sprayed into the nostrils and then allowed to drain for collection in a cup;
• d) induced sputum to test for presence of and immune response to anthrax. A mask with a saline mist is placed over the subject s mouth and nose, causing the subject to cough and produce sputum from the lungs. The sputum is collected in a cup this is for individuals 18 and older who do not undergo bronchoscopy, described below.
• Participants 18 years of age and older may have the following optional research

  procedures

• a) leukapheresis or plasmapheresis (see description under non-infected, vaccinated individuals above);
• b) lymph node biopsy. A sample of lymph node tissue is surgically removed under local anesthetic;
• c) bronchoalveolar lavage. This 15- to 30-minute procedure is done in the intensive care unit. The mouth, nasal passages, throat and airways are numbed with lidocaine and a thin flexible tube is passed through the nose into the lung airways. Samples of cells and secretions are obtained by rinsing (lavage) the airways with salt water. The fluid is analyzed for infection, inflammatory cells and inflammatory chemicals.

All infected and exposed individuals will have periodic medical history and physical exam evaluations and be offered treatment or prophylaxis (treatment to prevent infection) with antibiotics, according to the guidelines of the Centers for Disease Control and Prevention (CDC). Patients will be monitored for at least 24 months after antibiotic treatment, or longer if circumstances warrant.

Non-infected, vaccinated individuals

1. medical history and physical examination
2. blood tests-- between 10 and 50 ml (2-10 teaspoons) of blood will be drawn at a time, and not more than 450 ml will be taken in a 6-week period. Based on the blood test results, other optional research procedures may be requested
3. leukapheresis to collect white blood cells and plasmapheresis to collect plasma (the liquid part of the blood). For both of these procedures, blood is collected through a needle placed in an arm vein. The blood flows into a special machine that separates it into its components by spinning. The desired components (white cells or plasma) are removed and the rest of the blood is returned to the body through the same needle or a second needle in the other arm.

Eligibility

• 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.
          1. 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
          2. 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
          3. 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).
          4. Exposed individuals who are clinically asymptomatic.
          5. Past or imminent vaccination in healthy (non-anthrax exposed).
          6. 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
          7. 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.