Transcript Smallpox Virus - Cal State LA

Smallpox Virus
Case 16
Nadine Rodriguez
Mary Uy
Diana Perez
Unreported Outbreak!
• Summer of 1971 in Aralsk (Soviet
republic of Kazakhstan
• July 15, 1971
– Biological research vessel called the Lev Berg
set sail from Aralsk on an extended voyage
– Ship strayed inadvertenly near the
Vozrozhdeniye Island
– Biological weapons field testing site by Soviet
Ministry of Defense
– Released 400 grams of weaponized
smallpox within 15 kilometers of the island
Patient 1
• After arriving home in Aralsk
on August 12
• Patient 1- Fever, headache, and muscle aches
(vaccinated)
• Local doctor visit:
–
–
–
–
Noted fever of 39°C and a cough.
Prescribed antibiotics and aspirin
No definitive diagnosis
Shortly thereafter, diffuse rash covered her entire body
and her fever broke
– Everyone in her family including herself has been
vaccinated against smallpox
http://www.nlm.nih.gov/medlineplus/smallpox.html
Patient 2, Brother of Patient 1
• August 27, 15 days later…
• Patient 2- Nine year old boy
(vaccinated)
– Fever and rash
• Pediatrician diagnosed
– Hives
– Treated with tetracycline
– Recovered over the next two weeks
Patient 2
• Classic for smallpox
– Very high temperature.
– Followed by a pustular rash
which covered his whole body
• Pustules about 2 – 3 mm in
diamter
– Rash lasted 2 weeks and then
crusted over
– Smallpox scars from the rash
disappeared over a 2 yr. time
period
www.zkea.com
More Patients!
• Next three weeks
– Physicians in Aralsk saw eight additional
patients
• Six adults and two children
– Two children unvaccinated against
smallpox
• Developed hemorrhagic complications
and died
– One adult died from hemorrhagic variant
of the disease
www.visualsunlimited.com
Classification
• Family: Poxviridae
• Sub family:
Chordopoxvirinae
(vertebrates)
• Two Species of Variola
Vera:
– Variola Minor
– Variola Major
• Double stranded linear DNA
genome
• Core plus 2 lateral bodies
and a lipoprotein coat and
an envelope
• Larger than other viruses
Smallpox Endemic Areas 1945
Endemic smallpox
http://www.bt.cdc.gov/agent/smallpox/training/overview/
Smallpox Endemic Areas 1967
Endemic
Importations
Transmission Interrupted
http://www.bt.cdc.gov/agent/smallpox/training/overview/
Smallpox Virus
• Only human infectious disease to have been completely
eradicated in nature.
• Eradication 1979: Why and How ?
– Devastating Outcomes:
• Longterm – skin scars from lesions
• Occasional – blindness due to corneal ulcerations, and infertility in
men.
• Possible Death
– A very contagious disease that is unique to humans, NO other
known carriers
http://en.wikipedia.org/wiki/Smallpox
http:www.globalsecurity.org/wmd/library/report/1997/cwbw
Smallpox Declared Eradicated!
• Only human infectious
disease to have been
completely eradicated in
nature.
• Has not been contracted
naturally since 1977.
• Declared eradicated by
W.H.O. 1979.
How it is spread
(Epidemiology)
• Two main routes of entry:
– Air droplets make contact with lungs (most
common)
• Face to face contact- especially sneezing/ coughing.
• Inhalation of Aerosolized virus or virus droplets, can
include circulation through ventilation system.
– Direct contact with virulent rash or bodily fluids
• Kissing, touching (without protective gear).
• Sexual intercourse/ other forms of exchanging blood
and body fluids
• Contact with Fomites (less effective)- Bedding,
blankets, clothing of infected persons.
http://www.rhodes.edu/biology/glindquester/viruses/pagespass/smallpox/smallpox.html
Diagnosis:
Smallpox vs. Chickenpox
•Despite some clinical
similarities Smallpox can be
easily distinguished from
Chickenpox.
•Chickenpox localizes on the
covered areas of the body.
•Smallpox localizes on
uncovered areas of the body.
•Chickenpox lesions are easy to
pop, while smallpox lesions are
harder to touch and more
difficult to pop.
•Chickenpox have varied growth
stage, and smallpox have same
growth stage
http://www.scq.ubc.ca/?p=426
Timeline
-Day 1-12 Incubation- no symptoms, feel fine, not contagious.
-Day 12-14 Pre-eruption/prodromal stage- sudden onset high fever,
malaise, headache, backache. Sometimes: respiratory distress, sneezing,
coughing, abdominal pain and vomiting.
-Day 14-17 Vesicular rash begins to form- 2-3” diameter vesicles. Also,
temperature decreases, and patient begins to feel a little better. blindness
due to corneal ulcerations and infertility in men. Patient now contagious!
-Day 20-32 Scabbing- Later scabs separate and fall off. Patients is
contagious until last scab separates, patient is left with depressed
depigmented scars.
1. http://www.zkea.com/archives/archive02001.html; 2. http://www.who.int/mediacentre/factsheets/smallpox/en/; 3. Donald Henderson et al. JAMA June 1999;
281:2127-37
Variola Minor vs. Variola Major
• Mortality rate depends on variant type, case type,
and vaccination status. Infection does not
discriminate (sex, age,or race).
– Higher probability of complications for pregnant women.
– Variola Minor - causes a milder, less virulent form
of the disease (alastrim) has a mortality rate of
~1%
– Variola Major- mortality rate varies (30%-96%+).
• Case types: Ordinary (Discrete/Confluent);
Malignant/Flat; Hemorrhagic (of particular concern for
use as Biological Weapon).
http:www.globalsecurity.org/wmd/library/report/1997/cwbw
http://www.bt.cdc.gov/agent/smallpox/training/overview/
Variola Major: Case Types
- Differences in strain virulence and host response are
responsible for varied clinical case types.
• Ordinary (75-90% of Cases):
1. Discrete (Most common type) - refers to
vesicles that have areas of normal skin
between them
2. Confluent and Semi Confluent- blisters
merge together into sheets.
• Modified- Common in vaccinated
individuals.
– Less severe, lesions more superficial, not
as infectious.
– Fatality rate ~3%
http://www.bt.cdc.gov/agent/smallpox/training/overview/
http:www.globalsecurity.org/wmd/library/report/1997/cwbw
Semi-confluent
Variola Major: Case Types
• Flat/Malignant (rare: ~2-5% of cases)- Rash/pustules
appear flattened more superficial, and evolve slower.
– Pustules ~4-5 mm diameter
– Course of disease is similar to a burn, probably due to huge loss of
skin by peeling.
– Intense skin edema, abdominal pain, vomiting, mucosal/submucosal
hemorrhage, tachycardia, infection/sepsis is a possible complication.
– Mortification and death (70% mortality)- from tissue destruction.
equivalent to third degree burns.
http://www.bt.cdc.gov/agent/smallpox/training/overview/
Variola Major: Case Types
• Hemorrhagic (rare: ~3% of cases)- Widespread
hemorrhage: under skin, eyes, organs.
–Inflammatory Shock- Patients with high levels of circulating virus develop
hemorrhagic complications as a result of host induced massive inflammatory
response (non-specific immune response causes cloud of inflammatory mediators).
– Can be confused for meningococcemia (severe blood infection caused by
aggressive bacteria). May develop superficial purpuric papules. Doesn’t look like
classic smallpox
–Cause of death: hemorrhaging/blood loss; sepsis/toxemia can occur before rash
even develops (Hyper-acute course).
1. http://www.bt.cdc.gov/agent/smallpox/training/overview/
2. http:www.globalsecurity.org/wmd/library/report/1997/cwbw
3. http://www.journals.uchicago.edu/cgi-bin/resolve?id=doi:10.1086/381976&erFrom=-7477654646648014944Guest
Mortality Rates
Case Type
Mortality Rate %
Hemorrhagic
~96+%
(Most likely to be used as bioweapon)
Flat/Malignant
~70%
Ordinary- discrete(10-30%),
~30-35% overall
confluent(50-75%), and
semi-confluent(25-50%)
(Most Common)
Vaccine-modified
http://en.wikipedia.org/wiki/Smallpox
http://www.bt.cdc.gov/agent/smallpox/training/overview/
~3%
Natural Smallpox : Effective
bioweapon
• Facilitated Spanish conquest of the Americas
(Carribean 1507, Mexico 1520, Peru 1524, and
Brazil 1555 )
• Used as a biological weapon during the French and
Indian Wars of 1754-1767 when British forces in
North America distributed blankets that had been
used by smallpox patients to Native Americans
collaborating with the French."
http://en.wikipedia.org/wiki/Smallpox
Potentially More Dangerous
Than Any Other Bioweapon!
• Has a history of being tested and probably manipulated for
bioweapons possibilities for at least a couple decades.
• Cheap and easy to make and administer to unsuspecting
populations.
• Highly contagious- need relatively small amount of virus to
cause a epidemic outbreak.
• 2 week incubation period makes it hard to track.
• No proven curative treatment
• Naturally high mortality rate, which would be augmented
by several present day factors. Including- history of virus
testing and manipulation, general population would have
probably lost vaccination induced immunity by now (lasts
up to ~20yrs), Increased levels of Immunodeficient
populations (HIV/AIDS).
Potentially More Dangerous
Than Any Other Bioweapon!
• 43% of the US population who are under 30
years old have never received vaccinations for
smallpox
• If a terrorist were to release a small amount of
the virus into the air, the virus could infect the
population within 6 to 24 hours.
• But because of recent increase on global
terrorist activity, the US has prepared enough
vaccine to administer to the public
Spread of Disease
Prevented In The Past
• Edward Jenner (1749-1823)
- In the eighteenth century, Jenner hypothesized that milkmaids who were
infected by cowpox were resistant to smallpox
- Experimental procedure
∙ Injected a boy with the fluid of cowpox blister
∙ Once the boy recovered from
cowpox, he was then injected
with smallpox
- Results
∙ Boy remained healthy despite
inoculation
http://www.vaclib.org/news/jenner.jpg
Preventative Measures
& Treatments
• Pre-exposure
– Vaccinations
• Made from another pox-type
virus, vaccinia
• 95% success rate
• Post-exposure
– Vaccinations
• Within three days, can completely prevent or lesson the
severity of symptoms
• Four to seven days, vaccine offers limited protection
modifying severity
http://www.aapa.org/clinissues/images/vaccinia_vaccine.jpg
Treatment
• Once lesions appear
– No known cure
– Isolation
• 3-4 weeks, or until all scabs have fallen off
– Supportive therapy and antibiotics
• Supportive care
– Treatment for complications:
• Flat/malignant- treat as burn. Fluid/electrolyte/nutritional
replacement. Debridement and topical antibiotic to
prevent infection.
• Hemorrhagic- treat as septic shock- Oxygen/ to relieve
respiratory distress (if present), fluids, treat low blood
pressure, support any poorly functioning organs.
• Vaccination- prevention is the best medicine
http://www.who.int/mediacentre/factsheets/smallpox/en/
Possible Treatments
Currently Being Researched
•
Cidofovir
–
A DNA antiviral medication normally used to treat an infection
known as cytomegalovirus (CMV). May work if giving within two
days of exposure.
• Blockage of viral protein E3L binding site from DNA
– Researchers from MIT and Arizona State University
– Viral protein E3L binds to the DNA causing the infect.
• Hybrid antibodies
– National Institute of Allergy and Infectious Disease
– Composed of chimpanzees and human antibodies that blocks B5
protein
Works Cited
•
•
•
Henderson, D. A., Inglesby, T. V., Bartlett, J. G., & et al. Smallpox as a biological weapon medical and public health management.
1999.The Journal of American Medical Association 281 (22) 2127-2137.
Infectious disease smallpox treatment. 2007. Mayo Foundation for Medical Education and Research.
<http://www.mayoclinic.com/health/smallpox/DS00424/DSECTION=6>.
Jenner, Edward. Advameg Inc. 2007.
<http://www.discoveriesinmedicine.com/General-Information-and-Biographies/Jenner-Edward.html>.
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http://www.who.int/mediacentre/factsheets/smallpox/en/
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http://www.aapa.org/clinissues/images/vaccinia_vaccine.jpg
http://www.vaclib.org/news/jenner.jpg
http://www.bt.cdc.gov/agent/smallpox/training/overview/
http://www.nlm.nih.gov/medlineplus/smallpox.html
http://www.bt.cdc.gov/agent/smallpox/training/overview/
http://en.wikipedia.org/wiki/Smallpox
http:www.globalsecurity.org/wmd/library/report/1997/cwbw
http://www.rhodes.edu/biology/glindquester/viruses/pagespass/smallpox/smallpox.html
http://www.scq.ubc.ca/?p=426
http://www.zkea.com/archives/archive02001.html
http://www.who.int/mediacentre/factsheets/smallpox/en/