Anthrax

1. Anthrax CDC, AFIP

2. Diseases of Bioterrorist PotentialLearning 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. AnthraxOverview • 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 CDC

4. Inhalational AnthraxAcquisition of Infection • 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

5. Inhalational AnthraxAcquisition of Infection • 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

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. AnthraxLaboratory 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 AnthraxClinical 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 AnthraxClinical 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 AnthraxPresentation 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 AnthraxClinical Progression Day 5 Day 10-12 Day 7 Day 15 CDC

13. Inhalation Case NYC NJ* FL DC Bioterrorism-Associated AnthraxEpidemiologic Curve CT NYC letters* Senate letters* 5 4 3 Cases 2 1 0 9/17 9/25 9/29 10/3 10/7 10/11 10/15 10/19 9/21 10/23 10/27 11/14 Date of Onset *Postmarked date of known contaminated letters. *10/19 susp cutaneous case later removed Modified from: MMWRNov 2, 2001; 50(43)

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

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

16. AnthraxTreatment • 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) MMWR 49(RR-15) Link to webcast

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 *Total=100 days CDC Responds, Dec 21, 2001

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 VaccineAdverse 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.bt.cdc.gov/ http://www.cdc.gov/od/ohs/ http://www.usamriid.army.mil/

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