Biological warfare

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Biological warfare

• Renaat A. A. M. Peleman, MD, PhD
• Dept Internal Med, Div Infect Dis
• University Hospital Ghent

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Index of Suspicion

• Are there an unusual number of patients
  presenting with similar symptoms?
• Is there an unusual presentation of symptoms?
• Many cases of unexplained diseases or deaths
• Patients presenting with similar set of
  exposures?
• Diseases normally transmitted by vector not
  present in area
• Is this an unexplained case of a previously
  healthy individual with an apparently infectious
  disease?
• Disease outbreak with zoonotic impact

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Biological Agents of Highest Concern

• Variola major (Smallpox)
• Bacillus anthracis (Anthrax)
• Yersinia pestis (Plague)
• Francisella tularensis (Tularemia)
• Coxiella burnetii ( Q Fever)
• Botulinum toxin (Botulism)
• Filoviruses and Arenaviruses (Viral hemorrhagic
  fevers)
• Report ALL suspected or confirmed illness due to
  these agents to health authorities immediately

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Why These Agents?

• Infectious via aerosol
• Organisms fairly stable in aerosol
• Susceptible civilian populations
• High morbidity and mortality
• Person-to-person transmission (smallpox, plague,
  VHF)
• Difficult to diagnose and/or treat
• Previous development for BW

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Nominal lethality/1,000 kgs of different
biological weapens
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The bioterrorism pathways matrix

• Motivation
• Number of casualties
• Level of panic
• Capabilities
• Group size
• Technical proficiency
• Financial resources

• Agents
• Availability
• Ease of growth
• Morbidity mortality
• Dissemination
• Ease of dissemination
• Efficacy of dissemination technique
• Target
• Number exposed at target
• Target vulnerability

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Covert vs. Overt Event

• Overt Covert
• Recognition Early Delayed
• Response Early Delayed
• Treatment Early Delayed
• Responders Traditional First Health
  Care Responders Workers

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Diagnostic matrixchemical and biological
casualties
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Inhalational Anthrax, Plague, TularemiaDifferent
ial Diagnoses

• Community acquired pneumonia (CAP)
• S. pneumoniae, H. influenzae, Klebsiella spp
• Pneumonic Anthrax, Tularemia, Plague, Melioidosis
• Brucellosis, Q Fever, Histoplasmosis
• Severe atypical CAP (Legionella, Mycoplasma)
• Hantavirus pulmonary syndrome (HPS)

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inhaled BWF bacteria

• Treatment
• Fluoroquinolones (all)
• Vibramycin
• Penicillin
• Aminoglycosides
• Prophylaxis
• Fluoroquinolones (all)
• Vibramycin

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Anthrax Disease Complex Summary
Inhalational
Tracheobronchial Lymphadenitis
Cutaneous
Mediastinitis, cyanosis, stridor, pulmonary edema
Hemorrhagic Meningitis
Papule Õ vesicle edema eschar
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24 - 36 hours
Toxic shock and Death
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Resolve
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Bacteria Bacillus anthracis

• Disease anthrax
• Incubation 1 60 days
• Length of illness1 to 2 days
• Mortality rate extremely high, death typically
  occurs within 24 36 hours after onset of severe
  symptoms
• Effective dosage 8.000-50.000 spores
• casualties/50 kg/city/5106 250.000

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• MMWR-Weekly, November 02, 2001 / 50(43)941-8

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• MMWR-Weekly, November 02, 2001 / 50(43)941-8

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• Chest Radiograph
• Inhalation Anthrax
• Note
• widened mediastinum
• diminished air space

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Inhalational anthrax evolution
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Anthrax Case 3 / October, 2001
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Anthrax Case 3/ October, 2001
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Anthrax Case 4 / October 19, 2001
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Anthrax Case 4 / October 19, 2001
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Anthrax Case 4 / October 19, 2001
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Anthrax Case 4 / October 19, 2001
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Anthrax Case 4 / October 19, 2001
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Specimen Collection B. anthracis
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Cutaneous Anthrax

• black eschar (anthracis, Greek for coal)
• typical red areola

Arm
Neck
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Cutaneous anthrax, stemming from wear of
infected wool scarf
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Hemorrhagic Meningitis
Human autopsy, 1979, Sverdlovsk, hemorrhagic
meningitis 2 to inhalation anthrax
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Plague Disease Complex
Erythema
Fever/rigors
APTT ecchymosis DIC
Tender bubo 1 - 10 cm
Inhalational
Pharyngitis
Sudden onset
2 -3 days
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2 - 10 days
24 hrs
Systemic Toxicity
Fever, URI syndrome
Stridor, cyanosis, productive cough, bilateral
infiltrates
Fulminant Pneumonia
6 late meningitis
Liver enzymes
Leukemoid reaction
Respiratory failure circulatory collapse
Gram - ve rods in sputum
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Pneumonic Plague Prevention of Secondary
Infection

• Secondary transmission is possible and likely

• Standard, contact, and droplet precautions for at
  least 48 hrs until sputum cultures are negative
  or pneumonic plague is excluded

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Plague Specimen Collection
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Clinical clues
Anthrax Plague Brucella
Incubation 1 60 d 2 10 d 5 6 d
Duration of illness 1 2 d 1 2 d Variabel
Major SS High fever, diff breathing pneumonia death in 2 3 d High T, tender LN, pneumonia Flu-like, aching joints, myalgia
Minor SS T fatigue GI symptoms, skin lesions GI symptoms
Specific Widened mediastinum Gram-neg pneumonia hemoptysis Low WBC and platelets
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Plague Differential Diagnosis

• Bubonic
• Staph/streptococcal adenitis
• Glandular tularemia
• Cat scratch disease
• Septicemic
• Other gram-negative sepsis
• Meningococcemia
• RMSF
• TTP

• Pneumonic
• Bioterrorism threats
• Anthrax
• Tularemia
• Melioidosis
• Other pneumonias (CAP, influenza, HPS)
• Hemorrhagic leptospirosis

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Tularemia Disease Complex Summary
Oropharyngeal pseudomembrane
Papuleulcer cutaneous lesions
Inhalational
Conjunctiva
2 - 10 days
50 Secondary pleuropulmonary
Abrupt onset
Fever, chills headaches
Alveolar septa Necrosis cavitation
7 - 10 days
Rhabdomyolysis
Infiltrates, rales
Mild liver enzyme
Lower nephrotic syndrome
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Specimen Collection F. tularensis
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Q Fever Clinical Course Summary
CNS symptoms and neck stiffness
Meningitis
Inhalation
Osteomyelitis
Sudden onset
Mild primary atypical pneumonia ground glass
Fever (100 - 104º 3 - 6 days), malaise, anorexia
headache
Late complications
2 - 14 day course
Chronic infective endocarditis (aortic valve)
Mild LFT
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Q fever Clinical Features
3 DAYS LATER
AT PRESENTATION
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Specimen Collection Q. Fever
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Clinical clues
Tularemia Q-fever Influenza
Incubation 1 10 d 2 14 d
Duration of illness 1 3 wks 2 14 d
Major SS T, headache, Flu-like Cough, T, Catarrh, loss of appetite Weariness Aching limbs
Minor SS weightloss
Specific irritating cough Elevated LFT
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Rickettsiae Coxiella burnetti

• Symptoms acute non-differentiated febrile
  illness with cough, aches, fever, chest pain,
  pneumonia
• Leukocytosis in 30, elevated LFT
• Prophylaxis
• Vaccine available
• ChemoprophylaxisDoxycycline 100 mg bid for at
  least 7 days but start only 8 12 days post
  exposure. If started too early, prophylaxis
  prolongs the disease
• Treatment Doxycycline 100 mg bid for 5 - 7 days

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Smallpox - Clinical Course Summary
Inhalational
8 - 10 days
Replication in regional node of airways 12 day
incubation
Scabs separate pt non-infective
2 - 3 days
Viremia Acute malaise, fever, rigors, headache
Flat Smallpox
variants
Hemorrhagic Smallpox rapid death before typical
lesions
mental status changes
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Smallpox Clinical Features
USAMRICD
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Smallpox Clinical Features
USAMRICD
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Smallpox vs. Chickenpox
Varicella
Variola

• Incubation 7-17 days 14-21 days
• Prodrome 2- 4 days minimal/none
• Distribution centrifugal centripetal
• Progression synchronous asynchronous
• Scab formation 10-14 d p rash 4-7 d p rash
• Scab separation 14-28 d p rash lt14 d p rash

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SmallpoxMedical Management

• Strict airborne precautions and contact isolation
  of patient
• Patient infectious until all scabs have separated
• Notify public health authorities immediately for
  suspected case
• Identification of contacts within 17 days of the
  onset of cases symptoms

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Specimen Collection Smallpox
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VEE Clinical Course Summary
20 Children 4 Adult cases
Febrile syndrome lasting 3 days 100- 104º
fever chills, headache, photophobia, sore throat
?? Inhalational Mosquito born
1 to 5 day incubation
Mild CNS symptoms for 3 days
liver enzymes
More severe CNS signs
Weakness for 1 - 2 weeks
10 - 37 mortality
Recovery
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The VHF RNA Viruses
Acute onset febrile illness
High fever, myalgia, GI disturbances
Ebola
Major organ necrosis
Lassa
Severe systemic illness coagulation abnormalities
Oropharyngeal lesions
Marburg
Machupo
Renal failure
Severe bleeding ecchymosis
Hantaan
Congo fever
7 days
Pulmonary Syndrome
Yellow fever Dengue (2x) Rift Valley
Rapid progression into shock and death
Jaundice Syndrome
Four Corners Agent
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VHF Patient Isolation

• Single room w/ adjoining anteroom (if available)
• Handwashing facility with decontamination
  solution
• Negative air pressure
• Strict barrier precautions including protective
  eyewear/faceshield
• Disposable equipment /sharps in rigid containers
  with disinfectant then autoclave or incinerate
• All body fluids disinfected

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Specimen Collection Viral hemorrhagic fever
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Clinical clues viruses
Variola Venezuelan equine enc Yellow fever
Incubation Approx 12 d 1 5 d 3 6 d
Duration of illness severa1 wks 1 2 wks 1 2 wks
Major SS Malaise, T, chills, Lesions after 2-3 d Sudden T, headache, musclepain T, myalgia, prostration. Easy bleeding
Minor SS Nausea, sore throat,diarrea
Specific Highly contagious vasculitis
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Clinical clues toxins
Botulinum Ricin SEB
Time to effect 12 36 hrs Few hrs 3 12 hrs
Duration of illness 24 72 hrs 3 d Up to 4 wks
Major SS Cranial nerve palsy, desc flaccid paralysis Sudden T, weakness, cough, APE T, chills, headache, nausea, cough
Minor SS Convulsions, liver failure
Specific Latent period of 3 12 hrs on exposure
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Specimen Collection C. boltulinum
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Summary important differentials
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Conclusions

• Unlikely is not unthinkable
• Be suspicious
• Protect thyself
• Assess the patient
• Decontaminate as appropriate
• Diagnose
• Treat
• Infection control
• Alert authorities
• Spread the gospel

• The zebra card

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Acknowledgements - references

• USAMRIIDS Medical Management of Biological
  Casualties Handbook. US Army Medical Research
  Institute of Infectious Diseases, Maryland. 4th
  Ed. Febr.2001.
• Bioterrorism Readiness Plan A Template for
  Healthcare Facilities. APIC Bioterrorism Task
  Force, CDC Hospital Infections Program
  Bioterrorism Working Group. 1999
• Textbook of Military Medicine. Office of the
  Surgeon General Dept Army, USA
• Bioterrorism in the US Threat, Preparedness and
  Response. Chemical and Biological Arms Control
  Institute. November 2000.
• Clinical Aspects of Critical Biological Agents.
  Powerpoint presentation sponsored by the Public
  Health Consortium Michigan
• Armed Forces Institute of Pathology and the
  American Registry of Pathology, Washington DC and
  INOVA Fairfax Hospital, Fairfax VA.
  http//anthrax.radpath.org/index.html