1. Anthrax CDC, AFIP

2. Diseases of Bioterrorist Potential Learning Objectives Describe the epidemiology, mode of transmission and presenting symptoms of disease caused by the CDC-defined Category A agents Identify the infection control and prophylactic measures to implement in the event of a suspected or confirmed Category A case or outbreak

3. Primarily a disease of herbivores Hardy spore exists in soil reservoir Humans “naturally” infected by contact with infected animals or contaminated animal products In the early 1900s ~130 cases/yr in U.S. Woolsorter’s disease: inhalation anthrax Until 2001, 18 U.S.cases of inhalation anthrax reported in the 20th century Last naturally-occurring U.S. case of inhalation anthrax in 1976 Anthrax Overview CDC

4. Infectious dose in humans not precisely known Estimated 8-50,000 spores required for inhalation anthrax May be less in the context of bioterrorism May depend on host factors and bacterial strain Inhalational Anthrax Acquisition of Infection

5. Infectious aerosol particles >5  in size fall from atmosphere and bond to surfaces Secondary aerosolization unlikely Particles 1-5  behave like a gas and are deposited in small air sacs of the lungs No environmental residue Inhalational Anthrax Acquisition of Infection

6. Anthrax Case Definition An illness with acute onset characterized by several distinct clinical forms Cutaneous: a skin lesion evolving during a period of 2-6 days from a papule, through a vesicular stage, to a depressed black eschar Inhalation*: a brief prodrome resembling a viral respiratory illness, followed by development of hypoxia and dyspnea, with radiographic evidence of mediastinal widening *Presentation may vary in the context of bioterrorism MMWR 1997;46(RR-10)

7. Anthrax Case Definition, cont. An illness with acute onset characterized by several distinct clinical forms (continued) Intestinal: severe abdominal distress followed by a fever and signs of septicemia Oropharyngeal: mucosal lesion in the oral cavity or oropharynx, cervical adenopathy & edema, & fever Confirmed case: Clinically compatible with laboratory confirmation MMWR 1997;46(RR-10)

8. Anthrax Laboratory Criteria for Diagnosis Isolation of B. anthracis from a clinical specimen Blood, lung fluid, spinal fluid, skin lesion OR Positive serology* (after symptom onset) OR Demonstration of B. anthracis in a clinical specimen by immunofluorescence* Nasal swabs & serology – not useful for clinicians, but can help determine the extent of exposure in an epidemiologic investigation *testing at state public health labs or CDC MMWR 1997;46(RR-10)

9. Inhalational Anthrax Clinical Features Incubation period: 1 to 43 days or longer; may be related to dose and host factors Initial symptoms typically appear in 2-5 days Nonspecific: fever, dry cough, chest discomfort, muscle aches, malaise, profound fatigue, sweats Gastrointestinal symptoms Late symptoms Hemorrhagic mediastinitis, dyspnea Some cases develop meningitis Rapid progression to shock, death

10. Inhalational Anthrax Clinical Features No person-to-person transmission of inhalational anthrax Mortality rate 100% despite aggressive Rx in “advanced disease” but is lower with early treatment 6/11 cases in the 2001 outbreak survived with early aggressive therapy

11. Cutaneous Anthrax Presentation and Course Most common form (95%) under natural conditions Portal of entry: break in skin Incubation: hours - 12 days Papule  vesicle  ulcer/painless eschar Significant edema surrounding the lesion, and in nearby lymph nodes Fever, malaise, headache may be present Death 20% untreated; rare if treated CDC

12. Cutaneous Anthrax Clinical Progression Day 5 Day 7 Day 10-12 Day 15 CDC

13. 0 1 2 3 4 5 9/17 9/21 9/259/2910/310/710/1110/1510/19 10/2310/27 Cases Date of Onset NYC letters* Senate letters* *Postmarked date of known contaminated letters. Bioterrorism-Associated Anthrax Epidemiologic Curve NYC NJ* Inhalation Case FL DC Modified from: MMWR Nov 2, 2001; 50(43): MMWR Nov 2, 2001; 50(43) 11/14 CT *10/19 susp cutaneous case later removed

14. BT-related Inhalational Anthrax Distinguishing Anthrax from Other Influenza-Like Illnesses MMWR. Nov 9, 2001;50(44)

15. 2001 Anthrax Outbreak Outcome MMWR Weekly 50(48);1077-9

16. Anthrax Treatment Antibiotics are effective against germinating or vegetative B. anthracis but not against the spore form Disease development can be prevented as long as therapeutic levels of antibiotics are maintained to kill germinating organisms, or until spores are cleared or controlled by immune defenses (duration unclear)

17. Anthrax Treatment and Prophylaxis Treatment of cases Antibiotics x 60 days Can treat cutaneous disease for 7-10 days, if no potential aerosol exposure Standard precautions Cover cutaneous lesions, treat dressings as biohazard waste Prophylaxis for those exposed Antibiotics for 60 – 100 days Possible role for vaccine in combination with antibiotics

18. Anthrax Post-exposure Prophylaxis Beyond 60 days? Rationale: Viable spores demonstrated in mediastinal lymph nodes of monkeys 100d post-exposure ACIP Recommendations (December, 2000): If anthrax vaccine is available, antibiotics can be discontinued after 3 doses of vaccine (0, 2, and 4 weeks) Link to webcast MMWR 49(RR-15)

19. Anthrax Extension of PEP: CDC Options Earlier Recommendations – 60 days of antibiotics + medical monitoring Additional Option 1 – 40 additional* days of antibiotic treatment + medical monitoring Additional Option 2 – 40 additional* days of antibiotic treatment + 3 doses of anthrax vaccine over 4 weeks + medical monitoring CDC Responds, Dec 21, 2001*Total=100 days

20. Anthrax Letters Extension of PEP: CDC Options Both additional options investigational PEP approved by FDA for only 60 days Anthrax vaccine, 3-dose schedule and lot number not approved for this particular use Link to webcast

21. Anthrax Vaccine Current U.S. vaccine (FDA licensed): developed from attenuated strain of virus Protective against cutaneous (human data) and possibly inhalational anthrax (animal data) Injections at 0, 2, 4 wks & 6, 12, 18 mos; yearly boosters 3 dose schedule (0, 2, 4 wks) may be effective post- exposure, when given w/antibiotics 83% serologic response after 3 doses 100% after 5 Limited availability

22. Anthrax Vaccine Adverse Effects Safety profile similar to other licensed vaccines Up to 30% with mild discomfort (tenderness, redness, swelling, or itching) at inoculation site for up to 72 hours <2% with more severe local reactions, potentially limiting use of the arm for 1-2 days Systemic reactions uncommon

23. Anthrax Summary of Key Points The most likely presentation of anthrax in a BT attack is inhalational disease; cutaneous disease is also possible. Early in the course of illness, inhalational anthrax is not easily distinguished from an influenza-like illness due to other causes. Antibiotic prophylaxis can be used to prevent development of disease in infected persons. Anthrax is not transmitted person to person.

24. Case Reports Anthrax AN EPIDEMIC OF INHALATION ANTHRAX: THE FIRST IN THE TWENTIETH CENTURY American Journal of Hygiene 72, 6-23, 1960 THE SVERDLOVSK ANTHRAX OUTBREAK OF 1979 Science 266, 1202-1208, 1994 Anthrax Outbreak 2001 – UCLA SOPH website

25. Resources Centers for Disease Control & Prevention Bioterrorism Web page: CDC Office of Health and Safety Information System (personal protective equipment) USAMRIID -- includes link to on-line version of Medical Management of Biological Casualties Handbook http://www.usamriid.army.mil/ http://www.bt.cdc.gov/ http://www.cdc.gov/od/ohs/

26. Resources Office of the Surgeon General: Medical Nuclear, Biological and Chemical Information St. Louis University Center for the Study of Bioterrorism and Emerging Infections http://www.nbc-med.org http://bioterrorism.slu.edu