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BIOTERRORISM UPDATE
FOR EMS
ANTONIO NAPOLITANO MD
ATTENDING BRIDGEPORT HOSPITAL
JHPC MEDICAL DIRECTOR
OUTLINE
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Overview
History
Agents most likely to succeed
What to look out for
What to do
WHAT ARE BIOLOGICAL WEAPONS?
• Microorganisms or biologic toxins used to
produce death and disease.
• Components of BW’s
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Payload
Munition
Delivery system
Dispersal mechanism: line source vs. point
source
WHAT MAKES A BIOLOGICAL
WEAPON DESIRABLE TO A
BIOTERRORIST????
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Stable
Deliverable as an aerosol
Respiratory transmission
Particle diameter of 1-5 microns
Highly infectious
Deadly
No effective vaccine
DELIVERY METHODS
• Missile warheads
• Aerosol generators
– Airplane/boat
– Fixed device
• Food/water contamination
• Percutaneously
WHAT TO LOOK OUT FOR ?
• Suspect a biological weapons attack if these signs
of unusual disease clustering is present:
– Large epidemic with unprecedented numbers of ill and
dying
– Common exposure site, common complaints in a large
number of people
– Unusual diseases for a particular region
– Multiple simultaneous outbreaks
– Reports of sick or dying animals/plants
– Single case of disease by uncommon agent ie smallpox,
VHF or inhalation anthrax
WHAT TO LOOK OUT FOR ?
• Disease associations to know
– Widened mediastinum = inhalation anthrax
– Hemorrhagic meningitis = inhalation anthrax
– Vesicular/pustular rash on face/hands with all lesions at
the same stage of development = smallpox
– Symmetrical bulbar palsies and descending paralysis =
botulism toxin
– Pneumonia and hemoptysis = pneumonic plague
CATEGORIES OF BW’s
• Category A are highest priority agents
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Anthrax
Botulism
Plague
Smallpox
Tularemia
Viral hemorrhagic fever
CATEGORY B
• Second highest priority agents
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Q fever
Brucellosis
Glanders
Ricin Toxin from Ricinus communis
Epsilon Toxin of Clostridium perfringens
Staphylococcus Enterotoxin B
CATEGORY C
• Third highest priority agents
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Nipah virus
Hantaviruses
Tickborne Hemorrhagic Fever Viruses
Tickborne Encephalitis Viruses
Yellow Fever
Multidrug-resistant Tuberculosis
History of Biological Warfare
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Poisoning of wells by Assyrians in 6th century B.C.
1346 – Battle of Caffa.
Smallpox-infested blankets given to Native Americans
Japanese biowarfare experiments in Manchuria during
WWII. Unit 731.
• “Yellow rain” in Laos, Kampuchea in 1970’s.
• Iraqi stockpiles found in Gulf War.
• Aum Shimbun released anthrax spores along with sarin into
Tokyo subway system in 1995.
ANTHRAX
• First described 3,500 years ago. The first
vaccine ever invented and milk Pasteurization were invented to combat this bug.
• Cutaneous, GI, and Pulmonary forms.
• Engineered in the Soviet Union to be
resistant to Doxycycline and Penicillin.
• A disease of herbivores. Endemic to
Balkans, Turkey, W. Africa, Spain, C Asia.
INCUBATIO N
• Spores break down at infection site, and the
organism is picked up by macrophages and
transported to lymph nodes where they cause
massive, often hemorrhagic, lympadenopathy..
• Organisms elaborate toxins as they multiply.
• Incubation usually 1-6 days but can be seen as
far as 60 days.
• 8000-50,000 spores necessary to cause disease
ANTHRAX PATHOPHYSIOLOGY
CUTANEOUS ANTHRAX
• Pruritic red papule that necroses after three
or 4 days and becomes a black eschar which
sloughs off after 2-3 weeks.
• 5-25% of cases become systemic or fatal.
Excising the eschar can cause
dissemination.
• Mortality untreated cases 20%.
Treated<1%.
GASTROINTESTINAL ANTHRAX
• Very rare, need to ingest spores in
contaminated meat or large numbers of
spores in water.
• Presentation depends on area of GI tract
affected
• Fulminant peritonitis, mesenteric
lymphadenitis and septicemia.
• Mortality25-60% all comers.
PULMONARY ANTHRAX
• Very rare but VERY LETHAL
• Early on easy to confuse with a viral illness.
• To date none of the 10 index cases have had rhinorrhea
associated with them. All had positive CXR”s
• After 2-3 days of the above ( The patient may actually
improve) the patient rapidly progresses to respiratory
distress,shock and death.
• Hemorrhagic meningitis is common
CXR OF PULMONARY ANTHRAX
• Widened mediastinum
shown at right.
• Pleural effusions
common, usually
hemorrhagic.
• Most toxic patients
also have hemorrhagic
meningitis.
• Chest wall edema.
PULMONARY ANTHRAXCONTINUED
• This disease is so rare that even as few as
two cases can be interpreted as evidence
that a biologic attack is being waged.
• Diagnosis mad by Blood, CSF, or pleural
fluid.
• Mortality 89- 100% (Pre antibiotic Critical
Care era.
TREATMENT
• Largely supportive
• Ciprofloxacin or Doxycycline the initial
therapy, given the high incidence of
Penicillin resistance. Can adjust therapy
based on culture results
• Therapy must be continued for 60 days
given the persistant germination of spores.
VACCINE
• Available in the UK and USA.
• Purified Protective Antigen adsorbed onto
aluminum adjuvant.
• Six .5 cc shots over 18 months; military feels
that a three shot series will protect individual for
6 months after series.
• Local reactions common.(6%) Don’t give to
people with prior exposure
NO DATA THAT ANY OF THESE
WILL PROTECT FROM AN
AEROSOL CHALLENGE!!!!!
ANTIBIOTIC PROPHYLAXIS
RECOMENDED FOR ANY
IMMINENT BIOLOGIC WEAPON!
PLAGUE
• Zoonotic disease transmitted by infected
fleas or by aerosol in a biologic. Person to
person also seen in Pneumonic plague.
• 30 types of fleas and over 200 different
mammals can harbor the bacteria.
• Move to Australia or Antarctica.
• Bubonic, septicemic, and inhalation
syndromes all known.
BUBONIC
• 1-10 day incubation period then high fever
malaise and purulent lymphadenopathy of
the groin, but also seen in cervical and
axillary lymph nodes, and a plethora of
rashes seen.
• 80% of these patients blood culture positive
but only 25% progress to the septicemic
form.
SEPTICEMIC PLAGUE
• These patients behave like your basic septic
patient; fever chills hypotension and shock
plus often nausea, vomiting and diarrhea.
• Often develop acral thrombosis; clotting
and gangrene of extremities, and skin with
more proximal purpura.
• Can progress to pnumonic both by
bloodstream and inhalation.
PNEUMONIC
• 2-3 DAY INCUBATION FOR BOTH.
• Cough, dyspnea sputum/blood, toxemia, rapidly
progressing to acute respiratory failure. CXR shows
patchy bilateral alveolar infiltrates
• Preterminal events are circulatory collapse hemorrhage
and peripheral thrombosis in septicemic and bubonic.
• Mortality 50%bubonic and septicemic, 100% for
pneumonic.
Pneumonic Plague
• 2-3 day incubation period
• Non-specific complaints, but hemoptysis is
common
• Secondary transmission is possible
• Treatment: streptomycin IM or IV gentamicin or
IV doxycycline
• Prophylaxis: po ciprofloxacin or doxycycline
MORTALITY FROM PLAGUE
• Pulmonary form still 50 % mortality even
with antibiotics. Less than 5% with the
other forms.
• Death most likely even with therapy if
treatment delayed beyond 18 hours of
infection. Again Cipro and Doxycycline.
• These facts plus a flea vector and person to
person make plague a serious threat.
OTHER BACTERIAL BIOLOGICS
• Tularemia- Non spore bacterium that spreads by
skin, mucosa, GI, and Pulmonary(as few as 50
organisms needed for pulmonary infection.)
• Arthropods, contact, ingestion, handling of meat
or inhalation are potential vectors.
• Glandular, septicemic, pneumonic,forms seen as
well as ulceroglandular and oculoglandular
OTHER BACTERIAL AGENTS
• Cholera; Darkfield and Phase contrast
microscopes and culture. IV therapy for vomiting,
losing greater than 7 liters a day, and shock. Killed
vaccine that only protects for 6 months. Bactrim,
Doxy, and TMP/SMX.
• Pssitacosis(Parrot fever) 1-2 weeks incubation
aerosolized dried droppings, aerosol and human to
human. Fever Nausea, vomiting,myalgias and
atypical pneumonia. Erythromycin and Doxycline.
• Brucellosis
THE VIRAL WEAPONS
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Smallpox
Q fever (rickettsial)
Venezuelan Equine Encephalitis
Anything else
SMALLPOX
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First described 2000 years ago.
? Origin in India, or Western Asia.
Reached Europe by 700 AD.
It killed more American Indians than
European bullets in its spread to North
America. (in the French Indian War we gave
Indians blankets known to have come from
smallpox patients).
SMALLPOX
• Variola virus and Orthopox virus.
• Last “wild case” reported in 1977.
• Transmitted by face-face, secretions, and
aerosols.
• Aerosols are deactivate by UV light within
24 hours. So SUPPOSEDLY patients
presenting ill probably not need to be
decontaminated.
THE FACE OF SMALLPOX
FACTS ABOUT SMALLPOX…
• Approximately 10-17 day incubation period
ending in a 2-3 day viral prodrome (fever,
headache, neck and backache).
• Rash follows soon afterwards. Starts as
macules, turning to papules, which become
vesicles and lastly pustules which crust over
by approximately the 10th day.
• If you have the rash you are infectious.
FACTS ABOUT SMALLPOX….
• Variola Major and minor. Major was displayed on the
previous slide and Minor is just less intense (look at day
3).
• Minor most likely manifestation in partially immunized
folks.
• Two variants; Hemorrhagic and Malignant. Both have
shorter prodromes. Former rapidly progresses to DIC
like picture, and the latter becomes fulminant before
vesicles/pustules form. Hemorrhagic Smallpox
especially common in pregnant females.
FACTS ABOUT SMALLPOX…
• Complications are scarring (keratitis with ocular
involvement), smallpox pneumonia, and arthritis which
can cause permanent deformities.
• Obviously if this got out, medical resources would be
severely depleted beyond the 25% mortality projected
for the disease.
• All pediatric and most adults not immune.
• Many more older, immunosuppressed people to deal
with than in the past.
FACTS ABOUT SMALLPOX…
• The one thing that slows its spread is the fact that
the patient is so ill that they are usually bed bound
by the time the rash appears.
• In a hospital this can be disastrous. In Germany
one case with a cough in isolation managed to
contaminate THREE FLOORS of a hospital.
Disease can pass 10-20 generations from a single
index case.
• Think about spring breaks and Disney World.
Therapy
• Ribavirin, cidfovir and a derivative of the latter are
available but have never actually been used in a
smallpox case.
• Vaccination within 4 days of exposure has been
shown to decrease both the course and mortality of
the disease.
• In the event of an outbreak we all need a shot.
• Diagnosis clinical, but DFA, electron microscopy
and culture are all available. Which depends on
facility.
SMALLPOX
• WHO has approximately 500,000 vaccines
available.
• USA approximately 10 million with an
additional 50-60 million in various locations.
• A question of potency and adequate storage
of these vaccines has been raised.
• Problem in the immunosuppressed.
• 18 deaths in the 1961-62 in UK epidemic
SMALLPOX
• All possessions of the patient need to be steam
cleaned or cleansed in bleach or other hospital
grade cleanser.
• Clothes and sheets should be autoclaved.
• This is where I disagree with recommendations
that patients presenting with smallpox don’t need
decontamination.
• Potential exposure with fever >101 is isolated
before they have a rash and infect others!!!!!!
Q FEVER
• Coxiella Burnetti, not a virus but a rickettsia; 10-20
day incubation followed by a self limited illness
2days to 2weeks. Pneumonia is common and
atypical in presentation, and hepatitis seen in 1/3 of
the cases. One inhaled organism can cause disease.
• Complications include chronic hepatis, endocarditis,
meningitis,encephalitis and osteomyelitis
• Diagnosis is by ELISA,Doxycycline and
Erythromycin.
Venezuelan Equine Encephalitis
• VEE for short. There is also Western and
Eastern (WEE and EEE).
• Arthropods and aerosol. No evidence of
Horse to Human or Human to Human
transmission. ELISA Tests for Dx.
• 1-6 day incubation, 24-72 hour acute phase
of fevers,rigors,headache,malaise,
photophobia and myalgias.
Viral Hemorrhagic Fever
• Ebola/Marburg/Lassa
• Easily grown/ highly infectious when aerosolized
• Symptoms: fever, malaise, signs of vascular
permeability
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Conjunctival injection
Hypotension
Flushing
Petechial hemorrhage
• Treatment: supportive
– ? ribavirin
Botulism Toxin
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Most potent toxin known
Easily isolated
Can be food-borne or aerosolized
IP = 3-8 days if acquired po, 24-36 hours if
inhaled
• Diagnosis: clinical
– Bulbar palsies, descending paralysis, respiratory
failure
– No fever
• Treatment: supportive
– Antitoxin available from CDC or military
ANY QUESTIONS???????
Thank you very much.