BIOTERRORISM UPDATE FOR EMS

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BIOTERRORISM UPDATE FOR EMS

• ANTONIO NAPOLITANO MD ATTENDING BRIDGEPORT
  HOSPITAL
  JHPC MEDICAL DIRECTOR

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OUTLINE

• Overview
• History
• Agents most likely to succeed
• What to look out for
• What to do

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WHAT ARE BIOLOGICAL WEAPONS?

• Microorganisms or biologic toxins used to produce
  death and disease.
• Components of BWs
• Payload
• Munition
• Delivery system
• Dispersal mechanism line source vs. point source

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WHAT MAKES A BIOLOGICAL WEAPON DESIRABLE TO A
BIOTERRORIST????

• Stable
• Deliverable as an aerosol
• Respiratory transmission
• Particle diameter of 1-5 microns
• Highly infectious
• Deadly
• No effective vaccine

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DELIVERY METHODS

• Missile warheads
• Aerosol generators
• Airplane/boat
• Fixed device
• Food/water contamination
• Percutaneously

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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

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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

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CATEGORIES OF BWs

• Category A are highest priority agents
• Anthrax
• Botulism
• Plague
• Smallpox
• Tularemia
• Viral hemorrhagic fever

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CATEGORY B

• Second highest priority agents
• Q fever
• Brucellosis
• Glanders
• Ricin Toxin from Ricinus communis
• Epsilon Toxin of Clostridium perfringens
• Staphylococcus Enterotoxin B

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CATEGORY C

• Third highest priority agents
• Nipah virus
• Hantaviruses
• Tickborne Hemorrhagic Fever Viruses
• Tickborne Encephalitis Viruses
• Yellow Fever
• Multidrug-resistant Tuberculosis

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History of Biological Warfare

• 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 1970s.
• Iraqi stockpiles found in Gulf War.
• Aum Shimbun released anthrax spores along with
  sarin into Tokyo subway system in 1995.

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ANTHRAX

• First described 3,500 years ago. The first
  vaccine ever invented and milk Pasteur-ization
  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.

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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

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ANTHRAX PATHOPHYSIOLOGY
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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. Treatedlt1.

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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.

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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
  CXRs
• 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

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CXR OF PULMONARY ANTHRAX

• Widened mediastinum shown at right.
• Pleural effusions common, usually hemorrhagic.
• Most toxic patients also have hemorrhagic
  meningitis.
• Chest wall edema.

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PULMONARY ANTHRAX- CONTINUED

• 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.

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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.

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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) Dont give to people
  with prior exposure

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NO DATA THAT ANY OF THESE WILL PROTECT FROM AN
AEROSOL CHALLENGE!!!!!

• ANTIBIOTIC PROPHYLAXIS RECOMENDED FOR ANY
  IMMINENT BIOLOGIC WEAPON!

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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.

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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.

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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.

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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 50bubonic and septicemic, 100 for
  pneumonic.

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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

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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.

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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

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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

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THE VIRAL WEAPONS

• Smallpox
• Q fever (rickettsial)
• Venezuelan Equine Encephalitis
• Anything else

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SMALLPOX

• 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).

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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.

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THE FACE OF SMALLPOX
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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.

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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.

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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.

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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.

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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.

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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

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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 dont need
  decontamination.
• Potential exposure with fever gt101 is isolated
  before they have a rash and infect others!!!!!!

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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.

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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.

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Viral Hemorrhagic Fever

• Ebola/Marburg/Lassa
• Easily grown/ highly infectious when aerosolized
• Symptoms fever, malaise, signs of vascular
  permeability
• Conjunctival injection
• Hypotension
• Flushing
• Petechial hemorrhage
• Treatment supportive
• ? ribavirin

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Botulism Toxin

• 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

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ANY QUESTIONS???????

• Thank you very much.