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Treatment
• There is no specific treatment for smallpox and the only
prevention is vaccination.
• All individuals that are diagnosed with smallpox should be
isolated immediately due to the highly contagious nature of the
virus. Isolation should occur in the home or a non-hospital
facility because widespread contamination in hospitals is a
potential threat.
• The most that can be done for patients infected with small pox is
supportive therapy and antibiotics to treat secondary bacterial
infections that could occur.
• Some studies suggest that Cidofovir (nucleoside analog DNA
polymerase inhibitor) could possibly prevent smallpox infection
if administered within 1 or 2 days after exposure. The potential
use of this drug is limited because it is administered
intravenously and can cause serious renal toxicity.
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Identification
PCR
• In 1995, a new method of identification using PCR was developed at
the Center for Disease Control.
• Family-specific primers are used first, then subgroup-specific primers
are used if the former is not successful in producing the PCR product.
– TaqI restriction enzyme is used to differentiate variola from other
orthopoxviruses.
– HhaI restriction enzyme is used to differentiate between the
different strains of variola.
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Differential Diagnosis I
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Differential Diagnosis II
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Eradication
In 1967 the World Health Organization embarked on a World
Eradication Program.
Smallpox is a good candidate for eradication because:
1. smallpox virus has a single, stable, serotype
2. there is no animal reservoir and humans are the only hosts
3. the antibody response is prompt, so that exposed persons can
be protected
4. the disease is easily recognized clinically, so that exposed
persons can be immunized promptly
5. there is no carrier state or subclinical infection
Smallpox 04.01.03 :: W4158 Microbiology
Vaccination
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• Smallpox vaccine is made from live vaccinia
virus and does not contain variola virus, the
virus that causes smallpox. Vaccinia virus is a
member of the orthopox virus family.
• Vaccination is performed using a bifurcated
needle. A sterile needle with a droplet of
vaccine held by a capillary, is held at right
angles to the skin, while the wrist of the
vaccinator rests against the arm. 15 vigorous
strokes are rapidly made in an area
approximately 5 mm in diameter. Blood
should appear at the vaccination site after 15 to
30 seconds. The site of vaccination is covered
with a loose bandage to prevent individuals
from touching the area and spreading the virus
to other parts of their body.
• Neutralizing antibodies developed provide the
vaccinated individual with immunity, but
levels of antibodies decline substantially
during a 5 to 10 year period following
vaccination.
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Calf-Lymph Vaccine
Production:
1. A cow is intentionally infected with the cowpox virus.
2. The lymph from the virus filled pustules on the cow’s udder are then
collected.
3. The virus is separated from any existing bacteria and other impurities.
•
•
•
Dryvax is a stored calf-lymph vaccine manufactured in the 1970’s by
Wyeth Laboratories.
It is freeze dried and requires dilution before use.
It contains antibiotics and preservatives.
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Tissue Culture Cell Vaccine
• As of October 2002, tissue culture cell vaccines are in
preparation by Acambis-Baxter Laboratories.
• Two types of cells being used for propagation of vaccinia virus:
– Vero monkey kidney cells
– Human fibroblast cell line (MRC5)
• It is thought that these vaccines may cause less side effects than
the calf-lymph vaccine.
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Smallpox Vaccination Program
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On December 13, 2002 President Bush announced a plan to better protect the
American people against the threat of smallpox attack by hostile groups or
governments:
• Small Response Teams
– Under the plan, the Department of Health and Human Services (HHS) will
work with state and local governments to form volunteer Smallpox
Response Teams who can provide critical services in the event of a
smallpox attack.
– The federal government is not recommending vaccination for the general
public at this time.
• Department of Defense and State Department Personnel
– The Department of Defense (DOD) has vaccinated the army and certain
civilian personnel who may be deployed in high threat areas. Some
United States personnel assigned to certain overseas embassies will also
be offered vaccination.
Strengthening Homeland Security
• Immediately after the 9/11 attack, HHS began working, in cooperation with
state and local governments, to strengthen our preparedness for a bioterrorist
attack by expanding the national stockpile of small pox vaccine. According to
the CDC, the US currently has sufficient quantities of the vaccine to vaccinate
every single person in the country in an emergency.
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Statistics
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Vaccination Local
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Vaccination Local
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Vaccination Local
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Complications
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Smallpox 04.01.03 :: W4158 Microbiology
Complications
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Postvaccinial Encephalitis
•
Between 8 to 15 days after vaccination, individual develops
encephalitic symptoms,-fever, headache, vomiting, drowsiness, and
sometimes spastic paralysis, meningitic signs, coma, and
convulsions. Recovery is either complete or associated with
residual paralysis, and sometimes death.
Progressive Vaccinia (Vaccinia Gangrenosa)
•
It is a frequently fatal complication in which the vaccinial lesions
fails to heal and progresses to the adjacent skin with necrosis of
tissue, spreading to other parts of the skin, to bones, and to viscera.
Eczema Vaccinatum
•
Vaccinial skin lesions extended to cover all or most of the area
once, or currently afflicted with eczema.
Generalized Vaccinia
•
A secondary eruption, resulting from blood-borne dissemination of
virus. Lesions emerged between 6 to 9 days after vaccination and
were either few in number of generalized.
Inadvertent Inoculation
•
Transmission to close contacts or auto inoculation to sites such as
face, eyelid, mouth, and genitalia, sometimes occurs.
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VIG
Vaccinia immunoglobin (VIG) is a collection of antibodies prepared from the
blood of people who have been vaccinated against smallpox. Individuals that
are at high risk for adverse reactions to the vaccinia virus can be given VIG
along with the vaccine. It is also used to treat people who have had adverse
affects to the vaccine.
Individuals that are at high risk to side effects are those that have the following
conditions:
• Eczema or atopic dermatitis
• Skin conditions that result in a break of the skin such as burns, shingles,
impetigo, herpes, and psoriasis
• Weakened immune system such as someone who has received a transplant, is
HIV positive or receiving treatment for cancer
• Anyone taking immune suppressing medications like corticosteriods
• Pregnant women
• Women that are breastfeeding
• Children under 12 months
• Allergies to the vaccine or any of its components
• Heart disease
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Post exposure Infection Control
In the event of a smallpox outbreak:
• Patients suspected to have smallpox should be vaccinated to ensure
that those who are misdiagnosed are not placed at risk of getting
smallpox. Vaccination that is administered within the first few days
after exposure may prevent or significantly reduce subsequent illness.
• All health care workers at clinics or hospitals that might encounter
patients as well as other disaster response personal, such as police,
firefights, transit workers and mortuary staff who might have to handle
the bodies, should be vaccinated.
• Those individuals that have been in the same household with infected
individuals (face-to-face contact) should be vaccinated.
• Possible establishment of separate hospitals for smallpox patients.
• Areas of infection and those infected should be isolated and
quarantined.
• Patients who die of smallpox should be cremated.
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Decontamination
• In a contaminated area, standard precautions of using gloves,
gowns, and masks should be observed. All waste should be
placed in biohazard bags and incinerated.
• Contaminated bedding and clothing should be autoclaved or
laundered in hot water with bleach.
• Standard disinfectants, such as hypochlorite and quaternary
ammonia are effective for cleaning surface.
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Potential Probability vs. Impact
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BIOLOGICAL
AGENT
NUCLEAR
WEAPON
IMPROVISED
NUCLEAR
DEVICE
POTENTIAL
IMPACT
CHEMICAL AGENT
OR TOXIC
INDUSTRIAL
CHEMICAL
RADIOACTIVE
MATERIAL
PROBABILITY/LIKELIHOOD
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Limitations of Biological Agents
•
It was formerly thought that smallpox was not very suitable for biological warfare,
because it was too infectious.
•
An attack would entail a high risk of a worldwide epidemic, striking even the
population of the attackers.
•
Effective dissemination difficult.
•
Delayed effects can detract from impact.
•
Terrorists generally lack the means for vaccinating large groups of people and have
less opportunity to run large-scale virus cultures. It has thus been considered far
more probable that they would prefer bacterial infectious matter such as anthrax,
which entails less risk of uncontrollable epidemics.
•
Only available on the international WMD black market.
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Growing Danger?
• Several factors contribute to the growing danger of smallpox as a
biological weapon:
– A terrorist movement or the military command of a state could
arrive at the conclusion that an attack with variola in the USA
could allow the epidemic to remain local because of the vigorous
countermeasures expected. If the risk of a worldwide epidemic
seems small, an attack might be attempted.
– The attacks on September 11, 2001 demonstrated the great
ruthlessness and considerable resources of some terrorists. The
fundamentalist ill-will toward the USA is another driving force and
the attacks in the USA with weapons-grade anthrax disseminated
via the postal service have shown that terrorists can get access to
pathogens.
• It is now widely considered that the risks of variola being used as a
weapon have been underestimated in the past.
Smallpox 04.01.03 :: W4158 Microbiology
Bio-Weapons Chief
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•
•
•
Former Soviet colonel and doctor Kanatjan Alibekov,
now known as Ken Alibek was the 1st Deputy Chief
of the secret Soviet germ warfare program,
Biopreparat, from 1988 to 1992.
In 1992, Dr. Alibek defected to the US and has since
spent his time briefing U.S. Military, Intelligence and
medical officials about biological weapons and
defenses. Dr. Alibek holds both M.D. And PhD.
Degrees.
In a recent interview Alibek admitted:
– for years it (Soviet Union) was researching the
ways to genetically alter variola major by
inserting some new genes in this virus genome.
– Q: If you had to pick one (1) bio-weapon for an
terrorist attack on the USA, based on former
Soviet doctrine, which one would you chose?
A: Smallpox.
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Ebolapox
• This disease is a genetic recombination of smallpox and Ebola.
• It would seem likely that it is more hardy than Ebola, more like
smallpox, with much more resistance to sunlight, heat, cold, drying,
and humidity. Like smallpox, it could lie dormant for weeks in the air.
– Common symptoms beginning 2-3 days after exposure are: fever,
headache, confusion, muscle pain, and prostration.
– Physical examination may reveal only conjunctival redness, mild
hypotension, flushing, and small skin hemorrhages (petichiae).
– Full-blown VHF typically evolves to shock and generalized
mucous membrane hemorrhage, and often is accompanied by
evidence of lung, bone marrow, kidney, and neurologic
involvement.
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Biological Agent Sources
• Home production
• Laboratory / commercial
production
• Industrial facilities
• Foreign military sources
• Medical / university research
facilities
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Groups That Threaten
• Lone individual
• Identified local or nonaligned terrorist groups
• Internationally sponsored
• Doomsday cults
• Insurgents
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Potential Terrorist Targets
•
•
•
•
Enclosed spaces
Large crowds (high profile events)
Critical facilities and infrastructure
Accessible facilities with significant
hazard / damage potential (materials in transit)
• Facilities of interest to terrorists’ cause
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Why Bio Terrorism?
•
•
•
•
•
•
•
Agents are available & relatively easy to manufacture.
Large amount not needed in enclosed space.
NBC incident difficult to recognize.
Easily spread over large areas.
Psychological impact.
Can overwhelm existing resources.
Great value!
– According to the Stockholm international peace research institute,
the cost to inflict civilian casualties is $2000 per square kilometer
with conventional weapons, $800 with nuclear weapons, and $1
with biological weapons.
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Biological Warfare Agents Aerosol Particle Size
Maximum
respiratory infection
is caused by a
particle in the 1 to 5
micron size range.
Larger particles
(trapped in
upper airways)
This particle will
reach the alveoli
during normal
respiration.
1-5 micron particles
(enter alveoli)
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Breaking Devices
Point Source
• Common Items
• Moderate
downwind hazard
Light Bulb
Vacuum
Bottle
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Bursting and Exploding Devices
PointSource
Timer
•
•
•
•
Moderate downwind hazard
May destroy agent
Detectable
Multiple hazard potential
Agent
reservoir
Explosive
with
igniter
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Spraying Devices
Line Source
• Moving vehicles
• Significant downwind hazard
Pressure
vessel
Pressure
release
valve
Point Source
• Aerosol can
• Garden sprayer
• Moderate/significant
downwind hazard
Agent
release
valve
Agent
reservoir
Pressurize
d
agent
Disseminati
on
nozzle
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Impact of Dissemination Devices
Downwind Hazard
Most Likely Agent
Breaking
Moderate
Chemical
Bursting
Moderate
All
Explosive
Moderate
Device
Spray
Radiological (C/B Possible)
- Significant (Line Source)
- Moderate/Significant
Biological or Chemical
(Point Source)
Vector
Unpredictable
Biological or Chemical
Smallpox 04.01.03 :: W4158 Microbiology