Download Bioterrorism: A Medical Professional`s Perspective

Laboratory Criteria for
Identification of B. anthracis
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Chotani, 2003
From clinical samples, such as
blood, cerebrospinal fluid (CSF),
skin lesion (eschar), or
oropharyngeal ulcer
– Encapsulated gram-positive rods
on Gram stain
From growth on sheep blood agar:
– Large gram-positive rods
– Nonmotile
– Nonhemolytic
Laboratory Criteria for
Identification of B. anthracis
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Chotani, 2003
Rapid screening assay (PCR- and
antigen-detection based) for use on
cultures and directly on clinical
specimens
Confirmatory criteria for identification
of B. anthracis
– Capsule production
– Lysis by gamma-phage
– Direct fluorescent antibody assay
(DFA)
Gram Stain Morphology
of B. anthracis
Broad, gram-positive rod: 1–1.5 x
3–5 μ
 Oval, central to subterminal spores:
1 x 1.5 μ with no significant
swelling of cell
 Spores usually NOT present in
clinical specimens unless exposed
to atmospheric O2
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B. anthracis
 Gram-positive, spore-forming, non-motile bacillus
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Gram Stain of Blood in Culture Media
Gram-positive bacilli in long chains (original
magnification 20). Enlargement shows typical "jointed
bamboo-rod" appearance of Bacillus anthracis (original
magnification 100). Reprinted from Borio et al.36
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B. anthracis:
Presumptive Identification
Clinical specimen (blood, CSF, etc.)
Gram stain
Isolate on SBA
Capsule production Colony morphology
Hemolysis
Motility Gram stain
Spores
Malachite green
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B. anthracis:
Confirmatory Identification
Isolate
Phage
lysis
Capsule
Horse
blood
(M’Fadyean
Stain)
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Bicarbonate
media
(M’Fadyean stain
India ink stain)
DFA
Capsule antigen
Cell wall
Immune Protection
Against Anthrax
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Live cellular vaccines
– "Sterne" type live spore (toxigenic, noncapsulating)
– Former USSR STI live spore (toxigenic, noncapsulating)
– "Pasteur" type (mixed culture, reduced
virulence)
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Sterile, acellular vaccines
– US "anthrax vaccine adsorbed" (AVA)—not
licensed for use in civilian populations
– UK "anthrax vaccine precipitated" (AVP)
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Recombinant PA research vaccines
– AI3+; Freund’s; Saponin, Monophosphoryl
lipid A; Ribi
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Anthrax in the US - 2001
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In October 2001, the first inhalational anthrax
case in the United States since 1976 was
identified in a media company worker in
Florida.
A national investigation was initiated to identify
additional cases and determine possible
exposures to Bacillus anthracis.
Surveillance was enhanced through health-care
facilities, laboratories, and other means to
identify cases, which were defined as clinically
compatible illness with laboratory-confirmed B.
anthracis infection.
From October 4 to November 20, 2001, 22 cases
of anthrax (11 inhalational, 11 cutaneous) were
identified; 5 of the inhalational cases were fatal.
Epidemic curve for 22 cases of bioterrorismrelated anthrax, United States, 2001.
Anthrax Meningitis
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Hemorrhagic meningitis is a potential
complication of anthrax, and may
accompany cutaneous,
gastrointestinal, or inhalational anthrax
(seen in 50% of inhalational cases)
Death almost universal within 1-6 days
after onset of illness
Rare survivors have been treated using
appropriate antibiotics in combination
with antitoxin, prednisone or both
Recommended Postexposure Prophylaxis
to Prevent Inhalational Anthrax
Initial Therapy
Duration
Adults
Ciprofloxacin
60 days
(including pregnant
500 mg PO BID
women and
OR
immunocompromised)
Doxycycline
100 mg PO BID
Children
Ciprofloxacin*
60 days
10–15 mg/kg PO Q 12 hrs Change to
OR
amoxicillin
Doxycycline:
if susceptible
>8 yrs and >45 kg: 100 mg PO BID
>8 yrs and <45 kg: 2.2 mg/kg PO BID
<8 yrs: 2.2 mg/kg PO BID
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Cutaneous Anthrax Treatment Protocol*
for Cases Associated with Bioterrorist Events
Category
Adults
Initial Therapy (Oral)
Ciprofloxacin
(Including pregnant women
500 mg BID
and immunocompromised)
OR
Doxycycline
100 mg BID
Duration
60 daysw
Ciprofloxacin**
60 daysw
(including immuno10–15 mg/kg Q 12 hrs
compromised)
OR
Doxycycline:
>8 yrs and >45 kg: 100 mg BID
>8 yrs and <45 kg: 2.2 mg/kg BID
<8 yrs: 2.2 mg/kg BID
Children
Chotani, 2003
Inhalational Anthrax Treatment Protocol*
for Cases Associated with Bioterrorist
Events
Category
Initial therapy (intravenous)
Adults
Ciprofloxacin
(Including pregnant 400 mg Q 12 hrs
women** and
OR
immunocompromised) Doxycycline
100 mg Q 12 hrs
AND
One or two additional
antimicrobials
Duration
Switch to oral
therapy when
clinically
appropriate:
Ciprofloxacin 500 mg BID
OR
Doxycycline 100 mg BI
Continue for 60 days
(IV and PO combined)
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Smallpox
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Smallpox
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Worst-case scenario biological agent
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Highly contagious once rash present (not before)
World’s population is largely susceptible
Up to 30% case fatality rate in non-immune
Secondary attack rate of 25-40% (10-20 secondary
cases can be expected per index case)
 No specific treatment available
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Globally very few physicians currently
practicing have seen actual cases
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Virus has been weaponized by Soviets,
uncertain who exactly owns viable stocks
Smallpox
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Caused by Variola virus (Orthopox virus)
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Immunization of U.S. civilian population suspended
in 1980, U.S. military recruits in 1989
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Virus is stable in environment
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Spread primarily by respiratory droplets, also by
contact, fomites
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Two distinct types of smallpox:
 Variola Minor (Alastrim): diminutive lesions and mild
systemic toxicity
 Variola Major: Ordinary (subtypes discrete, semiconfluent, confluent), Modified, Flat, Hemorrhagic
Smallpox
Clinical Presentation
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7-17 day incubation period
Prodromal phase: 2-4 days of malaise, fever,
rigors, headache, backache, delirium
Rash then develops on face, hands, forearms
and legs, including palms and soles
(centrifugal distribution is important
distinguishing feature).
Initial rash is maculopapular. In 1-2 days,
lesions become vesicular, then evolve into
round, tense pustules deeply imbedded in the
dermis. Crusts form on 8th to 9th day of rash
Crusts separate to form depressed,
hypopigmented scars
Smallpox
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Smallpox Outbreak, Meschede Hospital,
Germany, 1970
Wehrle PF, Bull WHO 1970;43:669
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Meschede Hospital Outbreak
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Diagnosis of Smallpox
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Recognition of clinical features in early
index cases is key
Identification of a single case of smallpox
constitutes an international medical
emergency, and should be considered
evidence of a bioterrorist attack
Confirmation of diagnosis is made by
demonstration of characteristic virions
on electron microscopy of vesicular
scrapings
Management of Smallpox
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Immediate quarantine of affected and exposed
individuals for 17 days
Only supportive care is available. Cidofovir has
demonstrated in vitro activity
Immediate vaccination of all exposed persons
with Vaccinia virus vaccine by inoculation with a
bifurcated needle (scarification)
Administration of Vaccinia Immune Globulin
(VIG), 0.6 ml/kg intramuscularly, concomitant with
vaccination
Active and passive immunization is effective at
preventing disease and death if given within 7
days of exposure
For the past half-century the main concern was
a nuclear Armageddon caused by atomic
weapons. However, with the discovery of
various offensive biological warfare programs
around the globe, the concern regarding
intentional use of viruses and microorganisms
as weapons of mass destruction increased
during the past decade. The threat of biological
warfare is real. It is now widely acknowledged
that the biological weapons, in terms of
destructiveness and in the generation of panic
and civil disorder could produce an effect that
is equivalent to that of a nuclear weapon.
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Medical professionals globally
should make sure that the world
does not suffer a catastrophe as a
result of the use of biowarfare
pathogens
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War on Diseases
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The recent emphasis on bioterrorism:
important truth about infectious diseases
– Even without the element of intentional
terror, diseases are a huge source of
human suffering—and a tremendously
destabilizing force
– Nearly half of the world’s premature deaths
(deaths under the age of 45) are caused by
infectious diseases
– Some 30 million infants in developing
countries remain unprotected by the
lifesaving childhood vaccines that in the
rest of the world are administered
routinely; a million die each year from
measles alone
Chotani, 2003
Pathogens of BT do threaten
humanity but let us NOT loose sight
of the naturally occurring microbes
that threaten billions of people in a
world weakened by poverty, war, lack
of clean water, and inattention
specially during wars & complex
humanitarian emergencies
Chotani, 2003
Thank You
Chotani, 2003