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Medical and Public Health Responses to Bioterrorism:

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Title: Medical and Public Health Responses to Bioterrorism:


1
Medical and Public Health Responses to
Bioterrorism
  • George W. Rutherford, M.D.
  • Institute for Global Health
  • University of California, San Francisco

2
Unconventional Warfare and Terrorism
  • Nuclear
  • Biologic
  • Bacteria
  • Viruses
  • Biologic toxins
  • Chemical
  • Biological agents can be directed against humans,
    livestock and plants

3
Prior Uses of Biological Warfare
  • 14th century, Crimea Catapulting of cadavers
    with plague into a city under siege
  • 18th century, North America Distribution by
    British of blankets and a handkerchief from
    smallpox patients to Native Americans hostile to
    the British
  • World War I Attempts by Germany to infest
    livestock and contaminate animal feed with B.
    anthracis and B. mallei
  • World War II Japanese in China used B.
    anthracis, V. cholerae, Shigella, Salmonella and
    Y. pestis in food, water, aerial spraying and
    release of fleas (Unit 731, Ping Fan)

4
Biological Warfare/Bioterrorism
  • Is the threat real?
  • U.S. Offensive biowarfare program at Fort
    Detrick, Maryland, discontinued in 1969
  • U.S.S.R./Russia Biopreparat - still conducting
    offensive biowarfare research?
  • Other countries Known or suspected of
    having/doing research on biowarfare Iraq, Iran,
    Libya, Syria, North Korea, China, India,
    Pakistan, South Africa and Israel

5
Biological warfare/Bioterrorism
  • Is the threat real?
  • Alleged/rumored Russian advances
  • An engineered strain of anthrax resistant to
    antimicrobial agents and against which the
    current vaccine ineffective
  • Mass production of smallpox virus
  • A multi-drug resistant strain of Y. pestis
  • A recombinant Ebola-smallpox chimera
  • Variant strain of Marburg virus

6
Biological Warfare/Bioterrorism
  • Is the threat real?
  • IraqAcknowledged offensive weapons program that
    included research on B. anthracis, C. perfringens
    (gas gangrene), rotavirus, camelpox virus, yellow
    fever, Congo-Crimean hemorrhagic fever virus,
    aflatoxin, botulinum toxin, mycotoxin, and
    anti-crop biological agents. 8,500L of a
    solution containing an anthrax spore count of
    109/ml was produced, 6,500L of which was used to
    fill weapons (SCUD warheads and bombs).

7
Biological Warfare/Bioterrorism
  • Is the threat real?
  • 1995
  • Aum Shinrikyo cult (which released nerve agent
    sarin in the Tokyo subway system) was conducting
    research with B. anthracis, C. botulinum, and C.
    burnettii had attempted to use B. anthracis in
    the Tokyo subway system and had drone aircraft
    equipped with spray tanks. In 1992, cult members
    had traveled to Zaire in an attempt to obtain
    Ebola virus.

8
Biological Warfare/Bioterrorism
  • Can it happen here?
  • Salmonella typhimurium 751 cases, The Dalles,
    Oregon, 1984
  • B. anthracis 23 cases 4 deaths 10,000
    treated with antibiotics prophylactically
    Florida, New York, New Jersey, Virginia,
    Washington DC, 2001

9
Biological Warfare/Bioterrorism
  • What are the characteristics of a good agent?
  • Dispersible in aerosols of 1-5 µ for penetration
    of bronchioles and alveoli
  • Predictably high number disease-to-infection
    ratio in a few days
  • Immunization or prophylaxis exist
  • Maintains viability/infectivity in environment
    (spores and toxins ideal)
  • Causing illness better than causing death

10
Biological Warfare/Bioterrorism
  • Category A agents
  • Bacillus anthracis (anthrax)
  • Botulinum toxins (Clostridium botulinum)
  • Brucella suis and melitensis (brucellosis)
  • Francisella tularensis (tularemia)
  • Smallpox
  • Yersinia pestis (plague)
  • Category A biologic agents (High-priority
    agents that pose a risk to national security
    because they can be easily disseminated or
    transmitted person-to-person, cause high
    mortality with potential for major public health
    impact, might cause public panic and social
    disruption, and require special action for public
    health preparedness)

11
Biological warfare/Bioterrorism
  • Anthrax
  • Three clinical forms
  • Cutaneous anthrax
  • Inhalational anthrax
  • Gastrointestinal anthrax
  • Previously occupational disease in US
    (woolsorters disease)
  • Cutaneous anthrax least serious and may be a
    sentinel event for a larger release

12
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13
Biological warfare/Bioterrorism
  • Cutaneous anthrax
  • Cutaneous inoculation of spores on exposed areas
    (forearms, hands, neck)
  • Incubation period, 0.5-12 days
  • Painless papule progressing to fluid-filled
    vesicle in 1-2 days that erodes to a depressed
    coal-black eschar (hence, anqrax Greek, coal)
    with circumferential edema, erythema, satellite
    vesicles, regional adenopathy systemic symptoms
  • Untreated case fatality rate, 20

14
Cutaneous Anthrax
From the UCSF Infection Control Website
15
Biological Warfare/Bioterrorism
  • Inhalational Anthrax
  • Incubation period, 1 to 5 days (up to 44 d)
  • Initial phase nonspecific prodrome -
  • malaise, fatigue, mild fever, non-productive
    cough, chest pain or chest constriction
  • Acute phase (toxin-mediated causing hemorrhagic
    lymphadenitis) 2-4 days later, sudden onset of
    severe respiratory distress, dyspnea, cyanosis,
    CXR evidence of widened mediastinum, meningitis
    (50)
  • Not transmitted person-to-person
  • Case-fatality rate approaches 100

16
Inhalational anthrax
17
Sverdlovsk anthrax outbreak, 1979
  • April - May, 1979
  • Outbreak of anthrax among people
  • and livestock living in and up to 50 km south of
    Sverdlovsk (now Yekaterinburg), a city of
    1,200,000 people 1400km east of Moscow and site
    of a military microbiology facility.

18
Sverdlovsk anthrax outbreak, 1979
  • A 1993 pathology report showed that fatal cases
    had inhalation anthrax
  • Follow-up investigation most consistent with a
    release of an aerosol of anthrax from military
    microbiology facility on April 2, 1979
  • 77 patients (66 died)
  • Incubation period, 2-43 days (9-10 modal)
  • Mean time onset to death, 3 days
  • Estimated total weight of spores was between a
    few milligrams and nearly a gram

19
Onset of fatal cases by week post exposure,
Sverdlovsk, 1979
Meselson M, Guillemin J, Hugh-Jones M, et al.
The Sverdlovsk anthrax outbreak of 1979. Science
1994 2661202-8.
20
Prevention and treatment of anthrax
  • Prevention
  • Pre-exposure
  • Anthrax vaccine
  • 6-dose series (0, 2, 4 wks 6, 12, 18 mos) then
    annually
  • Postexposure
  • Ciprofloxacin or doxycycline x 60 d
  • Military uses 4-wk regimen plus vaccine
  • Treatment
  • Antibiotics
  • Ciprofloxacin or doxycycline
  • 1-2 additional antibiotics for inhalational
    anthrax
  • Steroids?
  • Antitoxin?

21
Complications of anthrax prophylaxis
  • Ciprofloxacin prophylaxis in 3,428 postal workers
  • Complications
  • 666 (19) severe nausea, vomiting, diarrhea or
    abdominal pain
  • 484 (14) fainting, light headedness or
    dizziness
  • 250 (7) heartburn or acid reflux
  • 216 (6) hives or itchy skin
  • 287 (8) discontinued ciprofloxacin
  • 116 (3) because of adverse reactions

CDC. MMWR 2001 501051-4.
22
Smallpox
From the UCSF Infection Control Website
23
Smallpox
From the UCSF Infection Control Website
24
Biological Warfare/Bio-Terrorism
  • Smallpox
  • Incubation period, 7 to 17 days
  • Prodrome, non-specific illness with high fever
    (102-106F) for 3-4 days before rash with
    headache, back ache, vomiting defervescence with
    rash onset. Rash is erythematous to
    maculopapular to vesicular all lesions are the
    same age (unlike varicella) rash is centripetal
  • Case fatality ratio 25 - 30
  • Infectious for few hours before rash onset
    until scabs fall off (airborne contact)

25
Biological Warfare/Bio-terrorism
  • Smallpox vaccination
  • Vaccination with live vaccinia virus (cowpox, a
    related orthomyxovirus) intradermal
    administration on left deltoid
  • Routine vaccination of civilians in the U.S.
    was stopped in 1972
  • Routine vaccination of U.S. military stopped in
    1989
  • Less than 10 of the U.S. civilian population
    is currently immune to smallpox

26
Biological Warfare/Bio-terrorism
  • Smallpox vaccination
  • Approximately 15 million doses of smallpox
    vaccine are currently stored in a single location
    in the U.S. Up to half may be expired. The
    number of doses available may be able to be
    increased by giving a smaller dose.
  • Current plans call for the manufacture of
    300,000,000 doses of a new vaccine.
  • Post-exposure prophylaxis with vaccine (lt3d) and
    vaccinia immune globulin 0.6 ml/kg), cidofovir?,
    ribavirin?

27
Biological Warfare/Bio-terrorism
  • Infectivity of smallpox
  • Yugoslavia, 1972
  • A single case of smallpox transferred multiple
    times before the diagnosis was made infected 11
    others, who in turn infected 138 more people,
    leading to isolation of 10,000 people and
    vaccination of 20,000,000 people.

28
At present, only two. . . laboratories in the
world contain smallpox virus. If for any reason
this virus were once again introduced to humans,
the resulting disease could be easily contained
by vaccination of identified contacts.
  • Principles and Practice of Infectious Diseases
  • Fourth Edition, 1995
  • Editors Mandell, Bennett, and Dolin

29
Smallpox, 1998
  • Smallpox has been eradicated, but the etiologic
    agent is not extinct. The virus continues to
    exist in freezers in secure facilities at one
    institution in the United States and another in
    the Russian Federation. During the past 10
    years, various individuals and three WHO
    committees have recommended destruction of virus
    stocks on the grounds that the world needs to be
    assured that smallpox will never again be a
    threat to humankind. In opposition to virus
    destruction are equally strong views that
    laboratory stocks serve as a counterbalance to
    terrorism and a source of unknown future benefits
    to humankind. In May, 1996, the World Health
    Assembly recommended, subject to further review,
    that all stocks be destroyed in June, 1999.
    MMWR, 10/24/97
  • Editorial note accompanying the re-publication of
    MMWR reports from 1978, to commemorate twenty
    years of freedom from smallpox.

30
Smallpox, 2001
  • Stocks of smallpox virus were not destroyed in
    June, 1999 because of concerns that vials of the
    virus may have gone to and still be in the hands
    of other governments or groups. The World Health
    Assembly has called for the destruction of
    smallpox viral stocks in December, 2002.

31
Biological Warfare/Bio-terrorism
  • Current U.S. plans for smallpox control
  • Immediate identification and isolation of
    infected persons
  • Ring vaccination of close contacts of case and
    secondary contacts -- initial strategy now
    apparently replaced by nationwide vaccination
  • Cautious use of vaccine pre-attack

32
Biological Warfare/Bio-terrorism
  • ACIP recommendations
  • Under current circumstances, with no confirmed
    smallpox, and the risk of an attack assessed as
    low, vaccination of the general population is not
    recommended, as the potential benefits of
    vaccination do not outweigh the risks of vaccine
    complications.

33
Biological Warfare/Bio-terrorism
  • ACIP recommendations
  • Persons who would conduct investigation and
    follow-up of initial cases that would necessitate
    direct patient contact
  • Selected personnel in facilities pre-designated
    to serve as referral centers to provide care for
    the initial cases of smallpox

34
Biological Warfare/Bioterrorism
  • Challenges to responding promptly to an act of
    bioterrorism
  • Recognition/diagnosis of the illness
  • Availability of isolation beds/facilities
  • Availability of vaccines/therapeutics
  • Dealing with panic and public safety

35
Biological Warfare/Bioterrorism
  • Prevention
  • Secondary prevention
  • Immunization
  • Smallpox?
  • Anthrax?
  • Vaccine development efforts
  • Tertiary prevention
  • Improved detection
  • Improved post-exposure prophylaxis and treatment
    regimens

36
Handling of suspicious packages or envelopes
  • Do not shake or empty the contents
  • Do not carry it, show it to others or allow
    others to examine it
  • Put it on a stable surface do not sniff, touch,
    taste or look closely at it or any contents that
    may have spilled
  • Alert others in the area. Leave the area, close
    any doors and take actions to prevent others from
    entering the area. If possible, shut off the
    ventilation system.

37
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38
Biological Warfare/Bioterrorism
  • Prevention
  • Primary prevention
  • Restriction of access to potential weaponizable
    agents
  • Biological warfare treaties
  • Enforcement
  • Inspection
  • Smallpox destruction
  • Other?

39
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40
Inhalational and Cutaneous Anthrax Outbreak,
October-November 2001
  • Investigation (November 30, 2001)
  • 18 confirmed and 5 suspected cases of anthrax in
    CT, DC, FL, NJ, NY from intentional exposure
  • Newest cases in CT, NJ, NY unrelated to mail or
    media
  • 11 inhalational, 12 cutaneous 4 deaths
  • 9/11 inhalational cases in mail carriers or
    sorters
  • 4 letters (2 to NY, 2 to DC) known to contain
    anthrax spores - weaponized?
  • 12 isolates are indistinguishable (Ames, 1950) -
    susceptible to ciprofloxacin, doxycycline,
    penicillin similar to US military-grade strains

41
Inhalational and Cutaneous Anthrax Outbreak,
October-November 2001
  • Recommendations
  • Unknown number of letters mailed (4 identified)
  • Anthrax spores probably can leak out of sealed
    envelopes during automated sorting
  • What does a suspicious package or letter look
    like?
  • Inappropriate or unusual labeling
  • Strange return address or no return address
  • Postmarks from a city or state different from the
    return address
  • Excessive packaging material
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