Download Biological Threats - Georgia Poison Center

Biological Threats
Robert Geller, MD, FAAP, FACMT
Medical Director, Georgia Poison Center; Chief,
Pediatrics, Hughs Spalding Medical Center
Case Presentation
• A 25-year-old male patient presents
with fever, chills and malaise.
• He also complains of an unusual rash…
• As you prepare to see him, your
colleagues say that they have seen 5
patients today with a similar
presentation.
2
COULD THIS BE A BIOTERRORIST EVENT?
3
Chemical versus Biological Event
• Chemical
– Rapid onset (obvious)
– Field first response
• Police and Fire
• EMS
– Decon critical
– Antidotes
• Biological
– Slow onset (insidious)
– Medical response
• Hospital
• Office
– Decon usually not
needed
– Antibiotics and
vaccines
4
5
Relative cost of Terrorism Agents
•
•
•
•
Cost per km2:
Conventional
$2000
Nuclear
$800
Chemical
$600
Biological
$1
Biological Weapons are Dirt-Cheap!
Early Biological Warfare
• 1941 - Unit 731 spread
plague in China, killing
tens of thousands
• 1979 - explosion at a plant
in Sverdlosk was followed
by a massive outbreak of
anthrax
• 1978 death of Georgi
Markov from ricin
Bubonic plague - cause of the
end of the Roman Empire?
7
“Advantages” of Biological Agents as Weapons
• Large quantities of weapon material
can be produced in a short period of
time
• Access to biological agents not
difficult
– Aum Shinrikyo cult in Zaire
• Lower level of technical training
required*
.
• Psychological impact considerable
8
Domestic Biological Terrorism
• 1984: The Dalles, Oregon, Salmonella
(salad bar)
• 1997: Washington DC, “Anthrax” (hoax)
• 2001: US Anthrax Mailings
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Biological Agents
• Bacteria
• Anthrax
• Plague
• Tularemia
• Viruses
• Smallpox
• Filoviruses
• Toxins
• Botulinum
• Ricin
Mechanisms of Exposure
• Aerosol (Primary or Secondary)
– Primary route of exposure
– Must be dispersed in particles 1-5 microns
in diameter
• Ingestion
• Cutaneous
11
CDC Agent Classification
Basis for classification
– Public health impact based on illness and
death;
– Delivery potential
– Public perception
– Special public health preparedness needs
12
CDC Agent Classification
• Category A
–
–
–
–
Easily disseminated or transmitted person to person
Cause high rates of mortality
Could cause public panic
Requires special attention and public health awareness
• Category B
– Moderately easy to disseminate
– Moderate morbidity and lower mortality
– Require enhanced disease surveillance
• Category C
– Emerging pathogens; based on availability, ease of
production and dissemination, and potential for high
morbidity and mortality
13
CDC Category A agents
• Bacillus anthracis (anthrax)
• Clostridium botulinum toxin (botulism)
• Yersinia pestis (plague)
• Francisella tularensis (tularemia)
• Variola major virus (smallpox)
• Ebola, Marburg, Lassa, and South American
hemorrhagic fever viruses (viral hemorrhagic
fever)
14
CDC Category B and C Agents
• Category B agents
–
–
–
–
–
–
–
–
–
–
–
• Category C agents –
emerging infectious
diseases including;
Coxiella burnetti (Q fever)
Brucella species (brucellosis)
Burkholderia mallei (glanders)
Alphaviruses (VEE, EEE, WEE,
WNE)
Ricin toxin
Staphylococcus enterotoxin B
Foodborne or waterborne agents
Meliodosis
Cl. Perfringens epsilon toxin
Psittacosis
Typhus
– Nipah virus
– Hantaviruses
– Tickborne hemorrhagic fever
viruses
– Tickborne encephalitis
viruses
– Yellow fever virus
– Multidrug-resistant
Mycobacterium tuberculosis
15
Clinical Effects of These Agents
“Flu-like” illness (fever, sweats, nausea)
Cough and/or pneumonia
Skin ulcers (anthrax, tularemia, plague)
Rashes (smallpox, Ebola)
Paralysis (botulism)
Diarrhea & vomiting (food- and water-borne
agents)
• Headache, confusion
•
•
•
•
•
•
16
Anthrax: Overview
• Hardy spore exists in soil reservoir
• Humans “naturally” infected by
contact with infected animals or
contaminated animal products
• No person-to-person transmission
of inhalational anthrax
• Last naturally-occurring U.S. case
of inhalation anthrax in 2006
CDC
17
Anthrax: Case Definition
• An illness with acute onset characterized by
several distinct clinical forms
– Cutaneous: papule Æ vesicle Æ necrotic lesion
(most common)
– Pulmonary: highly fatal, hemorrhagic
mediastinitis
– Intestinal: abdominal pain, fever, septicemia
– Oral: mouth, pharynx, lymph nodes
18
Anthrax: Laboratory Diagnosis • Isolation – blood, lung or spinal fluid, skin
lesion
• Positive serology
• Immunofluorescence in clinical specimen
• Nasal swabs & serology – for assessing
exposure in epidemiologic investigation
19
Inhalational Anthrax: Clinical Features
• Incubation period: 1 to 43+ days
• Initial flu-like symptoms typically appear in 2-5
days
• Late symptoms
– Lung hemorrhage, shortness of breath
– Possible meningitis
– Rapid progression to shock, death
20
Cutaneous Anthrax
Clinical Progression
Day 5
Day 10-12
Day 7
Day 15
21
CDC
Inhalational Anthrax
Anthrax: Treatment and Prophylaxis
• Treatment of cases
– Antibiotics for 100 days
– Double or triple therapy for inhalational
anthrax or cutaneous anthrax with
systemic manifestations
• Prophylaxis for those exposed
– Antibiotics for 60 – 100 days
• Ciprofloxaxin or doxycycline
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
Plague: Epidemiology
• Caused by Yersinia pestis
– Gram negative bacillus
• About 10-15 cases/year U.S.
(mainly SW states)
• Human plague occurs from
bite of an infected flea
(bubonic) or rodent
• Only pneumonic form of
plague is spread person-toperson
25
Plague: Clinical Forms
• Bubonic plague
– Most common naturallyoccurring form
– Mortality 60% untreated, <5%
treated
• Septicemic plague
• Pneumonic plague
– Most likely BT presentation
– From aerosol or septicemic
spread to lungs
– Survival unlikely if treatment
not initiated w/in 24 hours of
the onset of symptoms
26
27
Bubonic Plague
• Incubation: 2-8 days
• Sudden onset nonspecific
symptoms: fever, chills,
malaise, muscle aches,
headache
• Painful Regional
lymphadenitis (buboes)
• Diagnosis: Culture
28
Plague: Medical Management
• Antibiotic therapy (Streptomycin, Chloramphenicol,
Tetracycline
• Supportive therapy
• Isolation with droplet precautions for pneumonic
plague
• Vaccine no longer available
29
Plague: Key Points
• The most likely presentation in a BT attack is
pneumonic plague.
• Unlike other forms of plague, pneumonic
plague is transmitted person to person, and
thus respiratory droplet precautions are
indicated in suspected cases until 48 hours
after the initiation of antibiotic therapy.
30
Other Category A Agents • Tularemia
• Viral Hemorrhagic Fevers
• Botulism
31
Tularemia
• Causative agent Francisella Tularensis
• Bacterium found in diverse animal hosts
32
Tularemia Epidemiology
Human infection:
– Handling contaminated animal tissues or fluids
– Bite of infective deer flies, mosquitoes, or ticks
– Direct contact with or ingestion of contaminated
water, food, or soil
– Inhalation of infective aerosols (most likely BT
route)
– No person-to-person transmission
– About 200 cases/year in the U.S.
33
Tularemia: Clinical Features
–
–
–
–
Intestinal (intestinal pain, vomiting,
diarrhea)
Pneumonic* (primary pleuropulmonary
disease)
Typhoidal (febrile illness without early
localizing signs & symptoms
Cutaneous lesions
*most likely BT presentation
MMWR 1997;46(RR-10)
34
Cutaneous exposure to F. Tularensis
35
Pneumonic Tularemia: Clinical Features • Initial clinical picture: systemic
illness with prominent signs of
respiratory disease
• Abrupt onset fever, chills,
headaches, muscle aches, nonproductive cough, sore throat
• Nausea, vomiting, diarrhea in
some cases
• Mortality 30% untreated; < 10%
treated
36
Tularemia: Summary of Key Points
• Naturally occurring tularemia virtually always
occurs in a rural setting.
• Tularemia is not transmitted person to person
• The most likely presentations of tularemia in a
BT attack are pneumonic and typhoidal disease,
as opposed to naturally occurring cutaneous cases
• Tularemia can be treated and prevented with
antibiotics
37
Smallpox: Overview
• WHO declared smallpox eradicated in 1980
• No effective treatment
• Person-to-person transmission
(aerosol/contact)
• Two strains: variola major and variola minor
– Variola minor – milder disease with case
fatality typically 1% or less
– Variola major – more severe disease with
average 30% mortality in unvaccinated
38
Findings: Pustules in same stage
39
Smallpox: Clinical Features
• Incubation: 12-14 d (range
7-17 d)
• High fever, malaise,
headache, backache,
prostration
– Delirium 15%
• Rash starts on face and
forearms → trunk and legs
• Crusts at day 8-9, scabs
separate leaving scars
CDC
Lesions most abundant on
face and extremities,
including palms/soles
40
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Smallpox: Medical Management
• Isolation
• Antibiotics:
– Secondary bacterial infections
• Supportive care
• Protect yourself
42
Smallpox Vaccine
•
Made from live Vaccinia virus
–
•
•
~ 200 million doses in U.S. stockpile
Intradermal inoculation with bifurcated
needle (scarification)
Immunity not life-long
WHO
43
Smallpox: Vaccination Complications
•
Most common outcome
– Inadvertent inoculation
(skin, eye)
•
Primary vaccination - 1
death/million*
•
Revaccination - 0.1
deaths/million*
44
Smallpox: Summary of Key Points
• transmitted person to person: airborne
precautions should be initiated in all suspected cases
• infectious from the onset of rash until all
scabs have separated.
• smallpox vs. chickenpox: differences in lesion
progression and distribution, illness course
and presence of a febrile prodrome.
45
Viral Hemorrhagic Fevers
CDC: Electron
micrograph of
Ebola virus
Viral Hemorrhagic Fevers
• Diverse group of viral illnesses
• Potential for aerosol dissemination, with human
infection via respiratory route (except dengue)
• Target organ: vascular bed
• Case fatality 0.5 - 90%, depending on agent
• Natural vectors virus specific – rodents, mosquitos, ticks
• Person-to-person transmission possible – fluids, air
(rare)
47
Viral Hemorrhagic Fevers:
Summary of Agents
Virus Family
Virus/Syndrome
Geographic
occurrence
Reservoir or
Vector
Humanhuman
transmission?
Arenaviridae
Junin (Argentine HF)
S.America
Rodents
Machupo (Bolivian HF)
S.America
Guanarito (Brazilian HF)
S.America
Lassa Fever –
yes, via body
fluids; others
– not usually
Sabia (Venezuelan HF)
S.America
Lassa (Lassa Fever)
West Africa
Yellow Fever
Tropical
Africa,Latin
America
Mosquitoes
Dengue Fever
Tropical areas
Yellow Fever
– blood
infective up to
5d of illness;
Others - No
Kyanasur Forest Disease
India
Omsk HF
Siberia
Flaviridae
Ticks
48
Viral Hemorrhagic Fevers:
Summary of Agents (cont.)
Virus Family
Virus/Syndrome
Geographic
occurrence
Reservoir or
Vector
Human-human
transmission?
Bunyaviridae
Congo-Crimean HF
Crimea, parts of
Africa, Europe
& Asia
Ticks
Rift Valley Fever
Africa
Mosquitoes
Hantaviruses
(Hemorrhagic Renal
Syndrome/
Hantavirus
Pulmonary
Syndrome)
Diverse
Rodents
Congo-Crimean
Hemorrhagic
Fever – yes,
through body
fluids;
Rift Valley Fever,
Hantaviruses – no
Ebola HF
Africa
Unknown
Marburg HF
Africa
Filoviridae
Yes, body fluid
transmission
49
VHF Surveillance: Clinical Identification of Suspected Cases
– Temperature 101°F(38.3°C) for <3 weeks
– Severe illness and no predisposing factors for
hemorrhagic manifestations
– 2 or more of the following:
•
•
•
•
•
•
Hemorrhagic or purple rash
Bleeding from nose
Vomiting blood
Blood in stools
Other hemorrhagic symptoms
No established alternative diagnosis
JAMA 2002;287
Adapted from WHO
50
Viral Hemorrhagic Fevers:
Summary of Key Points • Viral hemorrhagic fevers can be transmitted via
exposure to blood and bodily fluids.
• Airborne precautions are recommended for health
care workers caring for infected patients.
• Ribavirin doesn’t work )only for Lassa fever)
• No vaccine for Ebola / Marburg (only for yellow fever)
51
Botulinum toxin
• Toxins – “Great for assassinations and
cosmetic procedures”
Clostridium botulinum
•
C. botulinum spores worldwide in soil
•
Toxin causative agent of botulism
– Types A-G; A,B&E most commonly associated with
human disease
– Most potent toxin known (lethal dose 1ng/kg)
– Inactivated by chlorine, sunlight and heat
– Absorbed via mucosal surface or wound, not intact skin
– Interferes with nerve transmission Æ paralysis
53
Botulism Epidemiology
• Approximately 100 reported cases/year in the
U.S.
– Infant most common (72%)
– Food-borne not common
– Wound contamination
• Incubation (food-borne): 12-72hrs (range 2hr-8d)
– Dose dependent
– Could be less following a BT attack
• No person-to-person transmission
54
Botulism: Clinical Features
• Early nausea, vomiting, diarrhea without
fever
• Double vision, paralysis of facial muscles,
swallowing and speech difficulty
• Progressive flaccid paralysis Æ respiratory
failure
• Death 60% untreated; <5% treated
55
Botulism: Clinical Features
56
Botulism: Treatment/Prevention
• Ventilatory assistance, supportive care
• Antibiotics for wound botulism
• Vaccine under investigation
• Botulinum antitoxin – available from CDC
Emergency
Operations Center
770 – 488 - 7100
Botulism: Summary of Key Points • An outbreak of botulism with no common food
exposure would suggest a deliberate aerosol
exposure
• Inhalational botulism does not occur naturally
and suggests a deliberate source of infection
• Botulinum antitoxin must be administered
early for optimum results
58
Ricin
• A necrotizing cytotoxin
• Extracted from castor
beans
– Grow wild throughout
the Southeast
http://www.google.com/imgre
s?q=castor+beans+ricin
Biological attacks in the last decade
• 2001 – Anthrax mailed to senators and
media
• 2003 – Ricin found, addressed to Dept of
Transportation
• 2003 – Ricin mailed to White House
• 2004 – Ricin found in senator’s mail
• 2011 – ?
Ricin
• 0.5 mg is lethal
Likely
• Inhalation
• Pneumonia/pulmonary edema
• Injection
Possible • Liver/lympid necrosis
• Oral
Unlikely • Bloody diarrhea / abdominal pain
http://news.sky.com/
home/article/122194
05
No Antidote
Contagious Agents
(Person‐to‐Person Transmission) • Smallpox
• Plague pneumonia
• Some viral hemorrhagic fevers (e.g.,
Ebola)
• Food- and water-borne agents (e.g.,
salmonella & shigella)
62
Agents That May Require Antibiotics or Immunization to Prevent Disease • Antibiotics
– Anthrax
– Plague
– Tularemia
– Q Fever
– Brucellosis
• Immunization
– Smallpox
– Anthrax
63
Infection Control: Standard Precautions
• Standard precautions – all cases
–
–
–
–
Disposable, non-sterile gloves
Hand washing after glove removal
Disposable gown or apron, faceshield if splashing anticipated
Change protective gear between cases
• Contact precautions
– Standard precautions plus:
– Wear gloves and gown, change after contact with infectious
material
– Dedicate non-critical patient care items (e.g., stethoscope) to a
single patient or disinfect between patients
64
Infection Control: Droplet and Airborne Precautions
• Droplet precautions
– Standard precautions
plus:
– Wear mask within 6
ft of patient
• Airborne precautions
– Standard precautions
plus:
– Patient in negative
air pressure room
– Wear respiratory
protection (such as a
HEPA filter mask)
65
Questions?
• Bacteria
• Anthrax
• Plague
• Tularemia
• Viruses
• Smallpox
• Filoviruses
• Toxins
• Botulinum
• Ricin