smallpox 04.01.03 :: w4158 microbiology 1 treatment there is no specific treatment for smallpox and...

Smallpox 04.01.03 :: W4158 Microbiology

1Treatment

• 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.


2Identification

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.


3Differential Diagnosis I


4Differential Diagnosis II


5Eradication

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


6Vaccination• 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.


7Calf-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.


8Tissue 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.


9Smallpox Vaccination Program

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.


10Statistics


11Vaccination Local


12Vaccination Local


13

Vaccination Local


14Complications


15ComplicationsPostvaccinial 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.


16VIGVaccinia 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


17Post 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.


18Decontamination

• 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.


19Potential Probability vs. Impact

POTENTIALIMPACT

PROBABILITY/LIKELIHOOD

NUCLEARWEAPON

IMPROVISEDNUCLEAR

DEVICE

RADIOACTIVEMATERIAL

CHEMICAL AGENTOR TOXIC

INDUSTRIALCHEMICAL

BIOLOGICALAGENT


20Limitations 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.


21Growing 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.


22Bio-Weapons Chief• 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.


23Ebolapox

• 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.


24Biological Agent Sources

• Home production• Laboratory / commercial

production• Industrial facilities• Foreign military sources• Medical / university research

facilities


25Groups That Threaten

• Lone individual• Identified local or non-

aligned terrorist groups• Internationally sponsored• Doomsday cults• Insurgents


26Potential 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


27Why 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.


28Biological Warfare Agents Aerosol Particle Size

1-5 micron particles(enter alveoli)

Larger particles(trapped in

upper airways)

Maximum

respiratory infection

is caused by a

particle in the 1 to 5

micron size range.

This particle will

reach the alveoli

during normal

respiration.


29Breaking Devices

Point Source• Common Items• Moderate

downwind hazard

Vacuum Bottle

Light Bulb


30Bursting and Exploding Devices

PointSource

• Moderate downwind hazard• May destroy agent• Detectable• Multiple hazard potential

Timer

Agentreservoir

Explosivewith

igniter


31Spraying Devices

Dissemination

nozzle

Line Source

• Moving vehicles• Significant downwind hazard

Point Source• Aerosol can• Garden sprayer• Moderate/significant downwind hazard

Pressurized

agentPressurevessel

Pressurereleasevalve

Agentreservoir

Agentreleasevalve


32Impact of Dissemination Devices

Device Downwind Hazard Most Likely Agent

Breaking

Bursting

Explosive

Spray

Vector

Moderate

Moderate

Moderate

- Significant (Line Source)

- Moderate/Significant (Point Source)

Unpredictable

Chemical

All

Radiological (C/B Possible)

Biological or Chemical

Biological or Chemical

smallpox 04.01.03 :: w4158 microbiology 1 treatment there is no specific treatment for smallpox and...

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