Download Biological weapons agents

Biological warfare
Renaat A. A. M. Peleman, MD, PhD
Dept Internal Med, Div Infect Dis
University Hospital Ghent
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
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
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
Nominal lethality/1,000 kgs of different biological weapens
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
Covert vs. Overt Event
Recognition
Response
Treatment
Responders
Overt
Covert
Early
Delayed
Early
Delayed
Early
Delayed
Traditional First
Responders
Health Care
Workers
Diagnostic matrix:
chemical and biological casualties
Inhalational Anthrax, Plague, Tularemia:
Differential 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)
inhaled BWF bacteria
• Treatment
–
–
–
–
Fluoroquinolones (all)
Vibramycin
Penicillin
Aminoglycosides
• Prophylaxis
– Fluoroquinolones (all)
– Vibramycin
Anthrax Disease Complex
Summary
Inhalational
Tracheobronchial
Lymphadenitis
1-6
days
Hemorrhagic
Meningitis
50%
Cutaneous
ABRUPT
ONSET
Mediastinitis, cyanosis,
stridor, pulmonary
edema
Papule  vesicle
edema + eschar
24 - 36 hours
GI
Toxic shock
and
Death
20%
Resolve
Bacteria
Bacillus anthracis
•
•
•
•
Disease: anthrax
Incubation: 1 – 60 days
Length of illness:1 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/5*106: 250.000
•
MMWR-Weekly,
November 02, 2001 /
50(43);941-8
•
MMWR-Weekly,
November 02, 2001 /
50(43);941-8
Chest Radiograph
Inhalation Anthrax
Note:
• widened mediastinum
• diminished air space
Inhalational anthrax: evolution
Anthrax Case 3 / October, 2001
Anthrax Case 3/ October, 2001
Anthrax Case 4 / October 19, 2001
Anthrax Case 4 / October 19, 2001
Anthrax Case 4 / October 19, 2001
Anthrax Case 4 / October 19, 2001
Anthrax Case 4 / October 19, 2001
Specimen Collection: B. anthracis
Site
Cutaneous
Anthrax
Specimen
Comments
Vesicular stage Collect fluid from a previously unopened vesicle with dry sterile
Eschar stage
Feces
Roll swabs beneath the edge of the eschar without removing
Provides minimal recovery of agent
Nasal swab
Useful in later stages of disease. Collect prior to antibiotic use,
if possible.
Collect only within 24 h of exposure
Gastrointestinal
Anthrax
Blood cultures
Inhalation
Anthrax
Sputum
Collect if respiratory symptoms occur and sputum is being
produced. Provides minimal recovery of agent.
Blood cultures
Cultures collected 2-8 days post-exposure may yield the
organism. Collect prior to antibiotic use.
Cutaneous Anthrax
•black eschar
(anthracis, Greek
for “coal”)
• typical red
areola
Arm
Neck
Cutaneous anthrax, stemming from wear of infected wool scarf
Hemorrhagic Meningitis
Human autopsy, 1979, Sverdlovsk, hemorrhagic meningitis 2° to inhalation anthrax
Plague Disease Complex
Fever/rigors
Inhalational
Pharyngitis
2 -3 Sudden
days onset
Fever,
URI syndrome
APTT
ecchymosis
DIC
Tender bubo
1 - 10 cm
9%
24 hrs
Liver
enzymes
Fulminant
Pneumonia
6% late
meningitis
Erythema
Stridor, cyanosis,
productive cough,
bilateral infiltrates
Leukemoid
reaction
Gram - ve
rods in sputum
2 - 10 days
Systemic
Toxicity
Respiratory failure
& circulatory collapse
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
Plague: Specimen Collection
Site
Bubonic
Plague
Pneumonic
Plague
Specimen
Lymph node
aspirate
Comments
After applying a local anesthetic, obtain specimen by injecting
1 ml of sterile saline into lymph node and aspirating immediately
Blood cultures
Collect at least three cultures 15 – 20 minutes apart to detect
bacteremia
Minimal recovery from sputum. Bronchial or tracheal aspirate
preferred because of fewer contaminating organisms
Sputum,
bronchial or
tracheal
Blood cultures
Nasal swab
Lymphoid
tissue
Postmortem
Examinations Bone marrow
Lung tissue
Collect only within 24 h of exposure
Clinical clues
Anthrax
Plague
Brucella
Incubation 1 – 60 d
2 – 10 d
5–6d
Duration of 1 – 2 d
illness
1–2d
Variabel
Major S&S High fever, diff
breathing
pneumonia &
death in 2 – 3 d
High T°,
tender LN,
pneumonia
Flu-like,
aching joints,
myalgia
Minor S&S T° & fatigue
GI symptoms, GI symptoms
skin lesions
Specific
Gram-neg
pneumonia +
hemoptysis
Widened
mediastinum
Low WBC
and platelets
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
Tularemia Disease Complex
Summary
Inhalational
Papule®ulcer
Conjunctiva cutaneous
lesions
Oropharyngeal
pseudomembrane
2 - 10
days
50% Secondary
pleuropulmonary
Abrupt
onset
Fever, chills
headaches
7 - 10 days
Primary
pulmonary
+ 2 wks
duration
Alveolar septa
Necrosis & cavitation
Rhabdomyolysis
Infiltrates, rales
Lower nephrotic
syndrome
Mild liver
enzyme
Specimen Collection: F. tularensis
Specimen
Serum for
serology
Nasal swab
Comments
Collect an acute phase sample as soon as possible after onset of disease.
Collect convalescent phase sample 21-28 days after the acute sample.
(1ml min.)
Collect only within 24 h of exposure
Blood
Sputum
Collect or induce specimen from symptomatic patients. Bronchial or
tracheal wash may produce better yield.
Ulcer
Collect swab specimen from ulcer on skin or throat
Eye
Collect swab specimen if eyes affected
Q Fever –
Clinical Course Summary
CNS symptoms
and
neck stiffness
Meningitis
Inhalation
Osteomyelitis
Sudden onset
Fever (100 - 104º 3 - 6 days),
malaise, anorexia + headache
2 - 14 day
course
Mild
LFT
Mild primary
atypical pneumonia
“ground glass”
Late complications
Chronic
infective
endocarditis
(aortic valve)
Q fever: Clinical Features
AT
PRESENTATION
3 DAYS
LATER
Specimen Collection: Q. Fever
Specimen
Serum for
serology
Comments
Collect an acute phase sample as soon as possible after onset of disease.
Collect convalescent phase sample 10-14 days after the acute sample.
(10 -12 ml, 2.5ml minimum)
Clinical clues
Tularemia
Q-fever
Incubation
1 – 10 d
2 – 14 d
Duration of
illness
1 – 3 wks
2 – 14 d
Major S&S
T°, headache, Flu-like
Minor S&S
weightloss
Specific
irritating
cough
Elevated LFT
Influenza
Cough, T°,
Catarrh, loss
of appetite
Weariness
Aching limbs
Rickettsiae
Coxiella burnetti
• Symptoms: acute non-differentiated febrile illness
with cough, aches, fever, chest pain,
pneumonia
• Leukocytosis in 30%, elevated LFT
• Prophylaxis:
– Vaccine available
– Chemoprophylaxis:Doxycycline 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
Smallpox - Clinical Course
Summary
Exanthema on
Macules papules 
face, arms, hands pustular vesicles
Inhalational
8 - 10 days
Replication in regional node of airways
12 day incubation
2 - 3 days
Flat Smallpox
variants
Hemorrhagic
Smallpox
rapid death before
typical lesions
Viremia
Acute malaise, fever,
rigors, headache
+ mental status changes
Scabs separate
+ pt non-infective
Smallpox: Clinical Features
USAMRICD
Smallpox: Clinical Features
USAMRICD
Smallpox vs. Chickenpox
Incubation
Prodrome
Distribution
Progression
Scab formation
Scab separation
Variola
Varicella
7-17 days
2- 4 days
centrifugal
synchronous
10-14 d p rash
14-28 d p rash
14-21 days
minimal/none
centripetal
asynchronous
4-7 d p rash
<14 d p rash
Smallpox:
Medical 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 case’s symptoms
Specimen Collection: Smallpox
Specimen
Comments
Do not collect or ship any specimens without consultation from
MDCH or CDC
Vesicles
Vesicle fluid may be placed as a drop on a clean microscope slide. Store each
slide in a separate slide holder. As an alternative, collect fluid from separate
lesions onto separate swabs. Include cellular material from base of lesion.
Store at 4°C for for not more than 6 h. For longer periods store at –20 to –70 °C.
Scabs
Aseptically collect material or scrapings and place into a sterile, leakproof,
freezable container. Store at 4°C for not more than 6 h. For longer periods
store at –20 to –70°C.
Biopsy
Place tissue into a sterile, leakproof, freezable container. Store at 4°C for not
more than 6 h. For longer periods store at –20 to –70°C. Formalin fixed tissue
acceptable for histopathology.
Autopsy
Specimens
Place into sterile, freezable, leakproof container. Store frozen at –20 to –70°C.
VEE –
Clinical Course Summary
?? Inhalational
Mosquito born
1 to 5 day
incubation
Febrile
syndrome
lasting 3 days
100- 104º fever
chills, headache,
photophobia,
sore throat
20% Children
4% Adult
cases
Mild CNS symptoms
for 3 days
liver enzymes
Weakness for
1 - 2 weeks
Recovery
More severe
CNS signs
10 - 37% mortality
The VHF RNA Viruses
Acute onset
febrile illness
High fever, myalgia,
GI disturbances
Ebola
Major
organ
Marburg necrosis
Severe systemic illness
coagulation abnormalities
Lassa
Oropharyngeal
lesions
Machupo
Hantaan
Renal
failure
Pulmonary
Syndrome
Four Corners Agent
Severe bleeding
ecchymosis
Congo fever
Jaundice
Syndrome
Yellow fever
Dengue (2x)
Rift Valley
7 days
Rapid progression into
shock and death
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
Specimen Collection: Viral
hemorrhagic fever
Site
Specimen
Comments
Do not collect or ship any specimens
without consultation from MDCH or CDC
Ebola, Marburg, Argentine,
Junin, Bolivian hemorrhagic
fevers and Lassa fever
Serum
Collect 10 – 12 ml of serum
Clinical clues: viruses
Variola
Venezuelan Yellow
equine enc fever
Incubation
Approx 12 d
1–5d
3–6d
Duration of
illness
Major S&S
severa1 wks
1 – 2 wks
1 – 2 wks
Minor S&S
Specific
Malaise, T°,
Sudden T°,
chills, Lesions headache+,
after 2-3 d
musclepain
Nausea, sore
throat,diarrea
Highly
contagious
T°, myalgia,
prostration.
Easy bleeding
vasculitis
Clinical clues: toxins
Botulinum
Time to effect 12 – 36 hrs
Ricin
SEB
Few hrs
3 – 12 hrs
Duration of
illness
24 – 72 hrs
3d
Up to 4 wks
Major S&S
Cranial nerve
palsy, desc
flaccid
paralysis
Sudden T°,
weakness,
cough, APE
T°, chills,
headache,
nausea, cough
Minor S&S
Specific
Convulsions,
liver failure
Latent period
of 3 – 12 hrs
on exposure
Specimen Collection: C. boltulinum
Specimen
Comments
Testing must be arranged with MDCH prior to specimen
transport (517/335-8063)
Serum
Collect 10 ml (3-4 ml minimum) of serum as soon as possible after the
onset of symptoms and before administration of antitoxin.
Feces
15 – 25 g of stool should be collected. Store and ship at 4°C. DO NOT
FREEZE. Do not use preservative.
Food sample
Requires 0.5 cup of food. Food should be left in original container if
possible or placed in a sterile unbreakable container. Place containers in
leak-proof plastic bags. Store and transport at 4°C. If product was
originally frozen, do not thaw, ship frozen.
Wound or tissue
Place in an anaerobic collection device. Transport at room temperature.
Summary: important differentials
Conclusions
• The zebra card
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Unlikely is not unthinkable
Be suspicious
Protect thyself
Assess the patient
Decontaminate as
appropriate
Diagnose
Treat
Infection control
Alert authorities
Spread the gospel
Acknowledgements - references
• USAMRIID’S 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