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A. Organism and Transmissionnavigator

  1. Baccilus anthracis is a Gram positive, nonmotile, spore forming baccilus
  2. Cutaneous, gastrointestinal, and inhalational transmission
  3. B. anthracis endospores enter body through abrasions in skin, inhalation, or ingestion
  4. Inhalational form originally "woolsorter's" disease, from contaminated items
  5. Zoonosis transmitted from various mammels, usually grazing herbivores

B. Virulence Factors [2] navigator

  1. Major virulence factors carried on two plasmids: pXO1 and pXO2
  2. Plasmid pXO1 is 184.5kb and codes for toxin gene complex
  3. Toxin gene complex includes protective antigen, lethal factor, and edema factor
  4. Edema Toxin (A and B chains)
    1. Consists of edema factor (A chain, calmodulin dependent adenyl cyclase) and
    2. Protective antigen (B chain, binding moiety permits entry of toxin to host cell)
    3. Edema toxin disrupts water homeostasis by increasing cellular cAMP, leading to edema
  5. Lethal Toxin (A and B chains)
    1. Lethal factor (A or active chain), a zince metalloprotease
    2. Protective antigen (B or binding chain)
    3. Lethal factor inactivates mitogen activated protein kinase (MAPK) kinase
    4. This leads to macrophage release of TNFa and IL-1ß
    5. These cytokines initiate the sepsis like cascade seen in systemic anthrax
  6. Plasmid pXO2 is 95.3kb and codes for capB, capC, and capA, involved in the synthesis of the polyglutamyl capsule (inhibits phagocytosis of vegetative organisms)

C. Cutaneous Anthrax [8]navigator

  1. Most common form (95%), and is usually curable
  2. Anthrax means "coal", the black color of the eschar from cutaneous anthrax
  3. Primary skin lesion is usually painless, pruritic papule 3-5 days after inoculation
  4. After 24-36 hours, lesion forms a vesicle that undergoes central necrosis and drying
  5. Central necrotic region is black, usually surrounded by edema and purplish vesicles
  6. Cutaneous anthrax with microangiopathic hemolytic anemia reported in an infant [14]
  7. Antibiotic treatment is generally recommended although disease usually self-limited

D. Inhalational and Systemic Anthrax [9,10,11,12]navigator

  1. Inhalation and ingestion anthrax is very severe, with fatality close to 100%
  2. Initial Symptoms [13]
    1. Fever or chills 100%
    2. Elevated temperature 70%
    3. Malaise / fatigue 100%
    4. Minimally or Nonproductive cough 90%
    5. Shortness of breath 80% (rare in early influenza)
    6. Headache 50%
    7. Myalgias 50%
    8. Nausea or vomiting 80% (rare in early influenza)
    9. Rinorrhea 20% (70-80% in early influenza)
  3. Syndrome may be complicated by anthrax meningitis (very poor prognosis)
  4. Marked progression over 2-3 days
  5. Hemorrhagic pleural effusions and hemorrhagic meningitis may occur
  6. Prognosis
    1. Systemic anthrax is usually deadly unless very early therapy is instituted
    2. Age may be increase risk of fatal outcome

E. Diagnosis navigator

  1. High suspicion required even with symptoms consistent with viral infection [16]
    1. Fever and cough do not distinguish viral respiratory infection from anthrax
    2. Nonheadache neurolgoic symptoms, dyspnea, nausea/vomiting more common in anthrax
    3. Rhinorrhea and sore throat more common in viral respiratory infection
    4. Finding any abnormality on lung auscultation associated much more with anthrax
  2. Initial diagnosis by direct Gram's stain of skin lesion (vesicular fluid or eschar)
    1. Direct fluorescence-antibody staining with cell-wall specific antibodies is more sensitive
  3. Polymerase chain reaction (PCR) detection methods are being developed
  4. Rapid diagnosis with ELISA assay for anthrax toxin (4 fold increase in titer)
  5. Serum antibodies to capsule antigens found in >95% of infections within weeks
  6. Laboratory growth is restricted to Level B Laboratory Response Network for Bioterrorism

F. Treatment [5,6]navigator

  1. Early post-exposure therapy is required to be effective
  2. Quinolones
    1. Ciprofloxacin 400mg iv q12 hours is first choice for severe infections
    2. Ciprofloxacin 500mg po bid is effective early in course (okay in pregnancy)
    3. For children, ciprofloxacin 10-15mg/kg IV q12 hours (maximum 1gm per day)
    4. Second generations fluoroquinolones such as ofloxacin, levofloxacin also effective
    5. Norfloxacin should not be used
  3. Doxycycline
    1. In susceptible strains, as effective as fluoroquinolones
    2. Dose is 100mg po or IV bid (okay in pregnancy)
    3. All 2001 isolates in USA are sensitive
  4. Pencillins
    1. Penicillin 5 million units q6 hours IV is alternative first choice
    2. Amoxicillin 500mg po q8 hours also effective in suscpetible strains
    3. All 2001 isolates in USA are sensitive
  5. Erythromycin and chloramphenicol also effective
  6. Duration
    1. Ciprofloxacin 500mg bid or doxycycline 100mg bid are used
    2. For exposed persons, vaccine should be given
    3. Duration of antibiotics is 30 days for all exposed persons given vaccine
    4. Duration for exposed person without vaccination is 60 days
    5. Duration similar for immunocompromised persons
  7. Ineffective Antibiotics [6]
    1. Trimethoprim-sulfamethoxazole (Bactrim®, Septra®)
    2. Third generation cephalosporins
    3. Aztreonam (Azactam®)
  8. Glucocorticoids 1-2mg/kg prednisone recommended for (severe) edema

G. Vaccination [4,5,17]navigator

  1. Licensed vaccine available inactivated cell-free filtrate
    1. From cell-free filtrate of nonencapsulated attenuated B antracis
    2. Principle antigen for immunity is the Protective Antigen
  2. Showed >94% protection in rhesus monkeys (52 of 55 protected) with two injections
  3. Erythema and tenderness at injection site
  4. May be used for prevention or exposure to cutaneous or aerosolized anthrax
  5. For exposure, combination of vaccine and antibiotics is required
    1. Confirmed exposures should receive 3 doses of vaccine at 0, 2, 4 weeks
    2. Antibiotics are continued for all 4 weeks
    3. If vaccine not available, antibiotics are continued for 60 days
  6. Vaccine has no effect on pregnancy, birth rates or adverse birth outcomes [15]

References navigator

  1. Dixon TC, Meselson M, Guillemin J, Hanna PC. 1999. NEJM. 341(11):815 abstract
  2. Inglesby TV, O'Toole T, Henderson DA, et al. 2002. JAMA. 287(17):2236 abstract
  3. Holly JE, Bravata DM, Liu H, et al. 2006. Ann Intern Med. 144(4):270 abstract
  4. Friedlander AM et al. 1999. JAMA. 282:2104 abstract
  5. Drugs and Vaccines Against Biological Weapons. 2001. Med Let. 43(1115):87 abstract
  6. Post-Exposure Anthrax Prophylaxis. 2001. Med let. 43 (1116):91
  7. Schwartz MN. 2001. NEJM. 345(22):1621 abstract
  8. Roche KJ, Chang MW, Lazarus H. 2001. NEJM. 345(22):1611 (Image) abstract
  9. Bush LM, Abrams BH, Beall A, Johnson CC. 2001. NEJM. 345(22):1607 abstract
  10. Mayer TA, Bersoff-Matcha S, Murphy C, et al. 2001. JAMA. 286(20):2549 abstract
  11. Borio L, Frank D, Mani V, et al. 2001. JAMA. 286(20):2554 abstract
  12. Mina B, Dym JP, Kuepper F, et al. 2002. JAMA. 287(7):858 abstract
  13. Influenza and Anthrax. 2001. MMWR. 50:984 (Reprinted 2001. JAMA. 286(20):2537 abstract
  14. Freedman A, Afonja O, Chang MW, et al. 2002. JAMA. 287(7):869 abstract
  15. Wiesen AR and Littell CT. 2002. JAMA. 287(12):1556 abstract
  16. Hupert N, Bearman GML, Mushlin AI, Callahan MA. 2003. Ann Intern Med. 139(5):337 abstract
  17. Anthrax Vaccine. 1998. Med Let. 40(1026):52 abstract