1. As a Bioterrorism Agent Updated 12/31/02
Smallpox
As a Bioterrorism Agent
Updated 12/31/02

2. Smallpox History Last naturally-occurring case in 1977
High (30%) case fatality rate
Caused at least 500 million deaths in the 20th century
Routine vaccination in U.S. ceased in 1972
U.S.S.R. weaponized
Smallpox likely originated in India or Egypt approximately 3,000 years ago. The disease didn’t reach the Americas until brought by explorers in the early 1500s. By the late-1700s, the disease was worldwide. The disease caused the death of more than 500 million persons during the 20th century, despite being eradicated in 1977.
The global campaign to eradicate smallpox began in 1967 under the aegis of the World Health Organization (WHO). The last endemic case occurred in Somalia in 1977; eradication was declared in 1980.
Vaccination against smallpox has not been performed routinely in the U.S. since 1972 and in the rest of the world since Consequently, there is now a large population of non-immunized persons. The duration of immunity in those previously vaccinated is unclear.
Following global eradication of smallpox, stocks of variola virus, the causal agent, were consolidated and now officially exist in only two laboratories - the CDC in Atlanta and a research institute in Moscow.
Ken Alibek, former deputy director of the former Soviet Union’s bioweapons program, reported that in the early 1980s, the former U.S.S.R initiated a program to produce smallpox virus for use in bombs and missiles. Intelligence reports indicate that other nations may have obtained the virus as well.
Use of smallpox as a bioweapon is of concern since the disease has a high rate of mortality (30%) and morbidity, most of the population is considered non-immune, there is no specific therapy, and the vaccine isn’t yet available for general use.
References:
Henderson DA, Inglesby TV, Bartlett JG et al. Smallpox as a biological weapon. Medical and public health management. JAMA 1999;281:
WHO: Fact sheet on smallpox
CIDRAP: Smallpox: Current, comprehensive information on pathogenesis, microbiology, epidemiology, diagnosis, treatment and prophylaxis. June 26, 2002
www1.umn.edu/cidrap/content/bt/smallpox/biofacts/smllpx-summary.html

3. Smallpox Microbiology
Caused by variola virus
Family Poxviridae
Brick shaped, DNA virus
200 nm in diameter
Smallpox is caused by the variola virus which belongs in the family Poxviridae. This family includes vaccinia (smallpox vaccine), monkeypox, camelpox, mousepox and several other animal poxviruses that cross-react serologically.
Poxviruses contain single, linear, double-stranded DNA molecules and replicate in cell cytoplasm. They are shaped like bricks and measure about 300 by 250 by 200 nm.
Graphic:
Electron micrograph of a Vaccinia Virus. (1975)
Reference:
Breman JG, Henderson DA. Diagnosis and management of smallpox. NEJM 2002;346:

4. Variola Virus Occurs in 2 strains variola major
90% of cases are clinically characteristic
30% case fatality rate
variola minor
Less severe
1% case fatality rate
There are two strains of smallpox virus, variola major and variola minor.
Variola major is the most serious form of the disease with death occurring in approximately 30% of those infected. Most cases of variola major are clinically characteristic of the disease.
In cases of variola minor, the disease is mild, and causes death in less than 1% of patients.
In the past, with naturally occurring virus circulating, variola major and minor could not be distinguished from each other, except in outbreaks.
Infection with smallpox confers lifelong immunity.

5. Smallpox Pathogenesis
Incubation: days (range 7-17d)
Infection occurs after implantation of virus on the oropharyngeal or respiratory mucosa
Day 3-4: viral multiplication in lymph nodes; asymptomatic viremia
Viral spread to spleen, bone marrow, lymph nodes
Day 8: secondary viremia followed by fever and toxemia
The incubation period for smallpox ranges from 7 to 17 days, with a mean of 12 to 14 days. Infection occurs after the virus enters the respiratory tract, implanting on mucosa and passing into local lymph nodes.
Asymptomatic primary viremia occurs 3-4 days following exposure. The virus further disseminates to the spleen, bone marrow and other lymph nodes.
Secondary viremia occurs by the 8th to 12th day after initial infection.
References:
Henderson DA, Inglesby TV, Bartlett JG et al. Smallpox as a biological weapon. Medical and public health management. JAMA 1999;281:

6. Smallpox Clinical Presentation
After incubation period, onset of high fever (usually not infectious)
Malaise, prostration with headache and backache
Rash develops 1-2 days later (infectious)
First appears on tongue, mouth, oropharynx
Spreads to face, forearms 2-3 days later
Finally appears on trunk and legs
Rash becomes vesicular then pustular
Most infectious from rash onset to first 7-10 days of rash
Death from smallpox occurs in 2nd week of illness due to toxemia
The prodromal phase, lasting about 2-3, days begins approximately days after exposure and is characterized by abrupt onset of high fever, severe headache, backache, and malaise. Vomiting and severe abdominal pain may also occur. The patient is usually not infectious during this prodromal phase.
A day or so after fever onset, a maculopapular rash appears on the tongue, mouth and oropharynx first and then spreads to face and forearms and finally to the trunk and legs. The rash begins as small, reddish macules progressing to papules to vesicles to pustules. The lesions occur first on the face and extremities and ultimately cover the whole body.
The patient is most infectious at the onset of rash up to when the lesions have scabbed over and the scabs have fallen off.
Death from smallpox is due to toxemia and hypotension and occurs in the second week of illness.

7. Smallpox Rash Stages of rash: maculopapular → vesicular → pustular
Smallpox rash has centrifugal distribution (i.e., most dense on face, then extremities)
Synchronous lesions (appear during a 1-2 day period and evolve at the same rate)
Smallpox rash begins as small reddish macules, which become papules with a diameter of 2 to 3 mm over a period of 1-2 days. After an additional 1-2 days, the papules become vesicles with a diameter of 2 – 5 mm. Cardinal features of smallpox are that the rash has a centrifugal distribution, that is, it is most dense on the face and the extremities and less on the trunk, the lesions are all at the same stage of development, lesions occur on the soles of the feet and palms of the hands, and progress together from the maculopapular to vesicular and finally pustular forms.

8. Smallpox Rash and Lesion Development
FEVER
Days
– 4
– 3
– 2
– 1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 21
Pre-eruption
Papules-Vesicles
Pustules
Scabs
RASH
This slide shows a timeline for onset of smallpox rash and lesion development. High fever occurs 1-2 days before rash onset, decreases somewhat around rash onset, then increases about 1-2 days after rash starts. Around the 3rd day after the rash appears the fever drops before spiking at about the 6th day after rash onset. From that time onward the fever gradually diminishes.
The papular stage of the rash develops during the 1st to 4th day of rash, followed by the pustular stage (days 5-10). Scabs form around the 11th day of rash and are gone around the 21st day after rash onset.
Graphic: WHO
Onset of rash
Source: WHO

9. Smallpox Rash Progression3 4 5
This slide shows the progression of the smallpox rash. The numbers indicate the days after rash onset. Papules are seen on days 3 and 4; vesicles around day 5; pustules on days Scab formation is apparent on day 13.
Graphic:
WHO 7 13 9
Source: WHO

10. Smallpox Rash
3rd Day
On the first day of rash, papules appear usually on the face. By day 3, as shown on this slide, the rash has spread more on the face and the lesions become distinct and raised above the skin surface. Fluid accumulates in the papules to form vesicles.
The smallpox rash is most dense on the face, arms, hands, legs and feet and also is usually present on the palms of the hands and soles of the feet. The trunk has fewer papules than the extremities.
References:
World Health Organization slide set on the diagnosis of smallpox. October 24,

11. Smallpox Rash
3rd Day
The rash developing on the arms is less dense compared to that on the face of the child in the two previous slides.
On day 4, the vesicles are more distinct and feel very firm to the touch. When broken, they don’t collapse because the fluid is contained in many small compartments.
References:
World Health Organization slide set on the diagnosis of smallpox. October 24,

12. Smallpox Rash
5th Day
On the 5th day, the rash has become more dense on the face. The fluid in the vesicles is cloudy and looks purulent. The vesicles have become pustules. At this stage the patient usually experiences an increased fever and feels worse.
References:
World Health Organization slide set on the diagnosis of smallpox. October 24,

13. Smallpox Rash
5th Day
Note that the pustules on the arm of this child all resemble each other in appearance.

14. Smallpox Rash
7th Day
On the 7th day, there is no question the rash is definitely pustular. The pustules at this point increase somewhat in size and again remain more dense on the head compared to the trunk.

15. Smallpox Rash
7th Day
Compared to the previous slide, the pustules are less dense on the arms and legs than on the face. Again, the pocks vary somewhat in size but all resemble each other in appearance.
Reference:
WHO

16. Smallpox Rash
Note the large pustules present on the palms of the hands and the soles of the feet.
Graphic:
WHO

17. Smallpox Rash
Smallpox pustules have overwhelmed this child’s face; neither his eyes, which are swollen shut, nor his ears are spared. The papules are firm to the touch and deeply embedded in the skin. During days 8 – 9, the pustules increase somewhat in size.
Gradually the pustules dry up. Dark scabs form between days after rash onset. The scabs contain live smallpox virus and the patient remains infectious until all scabs have fallen off which occurs around day 20. Depigmented areas are visible on the skin. After many weeks, the skin slowly returns to normal. Permanent scarring may result from smallpox infection.
References:
World Health Organization slide set on the diagnosis of smallpox. October 24,

18. Smallpox Differential Diagnosis
Varicella (chickenpox)
Vaccinia
Monkeypox
Cowpox
Herpes zoster
Drug-induced rashes
Sulfonamide reaction
Morbilliform rash
Coxsackie virus
Secondary syphilis
Molluscum lesions
Many eruptive illnesses could be misdiagnosed as smallpox. Key differential diagnoses of smallpox are varicella (chickenpox), vaccinia, monkeypox, cowpox, and disseminated herpes zoster. Drug-induced rashes can also be confused with smallpox but can be diagnosed by a careful history taking and examination. Sulfonamides can cause severe vesicular and bullous rashes.
A morbilliform (resembling measles) rash on the face due to measles virus (rare in the U.S.) or coxsackievirus (hand, foot and mouth disease)* may be confused with early smallpox. Lesions associated with secondary syphilis vary in size and distribution and a differentiating feature is that the papules do not evolve. Patients with AIDS may have widespread molluscum (soft tumors or papular epidermal growths) lesions.
*Hand, foot and mouth disease in humans is a different disease than foot and mouth disease which is a disease primarily of cloven hooved animals.

19. Differentiating Smallpox from Chickenpox
FEVER ONSET
2 to 4 days before rash
At rash onset
RASH
Evolution
Lesions at same stage
Lesions appear in crops
Lesions evolve at same rate
Lesions in different stages
Distribution
Rash centrifugal
Rash centripetal
Rash on palms and soles
Never on palms or soles
Development
Slow
Rapid
Pox don’t burst when probed
Lesions burst when probed
MORTALITY
30%
Rare
Chickenpox is the disease most commonly confused with smallpox. During the first 2 to 3 days of rash, it may be nearly impossible to distinguish between the two diseases. Some key aspects of the clinical presentation of chickenpox and smallpox are opposite in nature, which aids in differentiating the two diseases in the clinical setting.
•In smallpox, fever is present 2 to 4 days BEFORE the rash begins, while with chickenpox, fever and rash develop at the same time.
•All the papules of the smallpox rash, no matter where they are on the body, develop slowly and evolve at the same rate. Chickenpox lesions, on the other hand, appear in crops and develop in different stages. With chickenpox, scabs, vesicles and pustules may be seen simultaneously on adjacent areas of skin, whereas with smallpox there is uniformity in the development and progression of lesions.
•Smallpox lesions are most densely distributed on the face and extremities while chickenpox lesions are denser on the trunk.
•Smallpox lesions appear on the palms and soles of feet in contrast to chickenpox where the lesions are almost never present.
•Chickenpox papules are much more superficial, develop rapidly, and are most densely distributed on the trunk instead of the face and extremities (the reverse of the distribution of smallpox lesions).
•Smallpox pustules will not burst if probed, those of chickenpox will.
Death from chickenpox is rare; the mortality of smallpox is 30%.
References:
World Health Organization slide set on the diagnosis of smallpox. October 24,

20. Rash Distribution
This slide depicts the difference in the distribution of rash in smallpox and chickenpox. Smallpox lesions are concentrated more on the face, arms and legs. Chickenpox lesions, on the other hand, are concentrated mainly on the trunk.

21. Chicken Pox
This child has chickenpox. Although about 75% of children in the U.S. are immunized against chickenpox, more than 1 million cases occur annually.
During the first day or two of rash it may be difficult, from the rash alone, to differentiate smallpox from chickenpox.
At day 4 to 5, the distinction between the two diseases becomes quite clear. The patient with chickenpox shows several different stages of lesion development. Most chickenpox lesions are small - between 1 and 5 mm, the size of the smallpox lesions is larger - between 5 and 10 mm.
This slide shows the central distribution of chickenpox lesions. Note the lesions on the trunk as well as the varying stages of lesion development.
References:
World Health Organization slide set on the diagnosis of smallpox. October 24,

22. Chicken Pox
This slide more clearly shows the varied developmental stages of chickenpox lesions.

23. Possible Case of Smallpox
Call MDH immediately (24/7) at
or if a
case of smallpox is suspected.
A possible case of smallpox is a public health emergency. If a case of smallpox is suspected, call MDH immediately, at any time, for consultation and specific directions regarding proper sample collection.

24. Smallpox Clinical Treatment
Vaccination up to 4 days post-exposure can prevent/attenuate clinical symptoms
Supportive care is the mainstay of smallpox therapy
Ensure adequate fluid intake
Alleviate pain, fever
Aggressive treatment of secondary infections
Antiviral therapy is experimental (Cidofovir)
Vaccination can attenuate or even prevent clinical manifestations of smallpox if administered very early in the incubation period, up to 4 days postexposure.
Since there is currently no FDA approved treatment for orthopoxviruses, treatment for smallpox is limited to supportive care.
Adequate hydration and nutrition must be maintained since substantial amounts of fluid and protein can be lost by febrile persons with weeping lesions.
Pencillinase-resistant antimicrobial agents should be used if smallpox lesions are secondarily infected, for bacterial infection of the eyes or if the eruption is quite dense and widespread. Daily eye-rinsing is necessary in severe cases. Topical idoxuridine (Dendrid, Herplex or Stoxil) should be considered for the treatment of corneal lesions, although its efficacy has not been proven for smallpox. Keeping the skin lesions clean will help prevent secondary infections.
Recent data suggest that cidofovir has promise for the treatment of cowpox, vaccinia and monkeypox. In the event of a smallpox outbreak, cidofovir could become available under an investigational-new-drug protocol for treatment of smallpox or to treat adverse effects of smallpox vaccination.
References:
CIDRAP: Smallpox: Current, comprehensive information on pathogenesis, microbiology, epidemiology, diagnosis, treatment and prophylaxis. June 26, 2002
www1.umn.edu/cidrap/content/bt/smallpox/biofacts/smllpx-summary.html

25. Preventing the spread of smallpox is a critical component of the infection control strategy. Historically, isolation and quarantine were used to contain smallpox outbreaks. Persons infected with smallpox were required to remain in their homes or other areas specifically designated as quarantine zones. Signs such as this were placed on the entrances to the patients’ homes to notify the well to stay away. The last reported case of smallpox in Minnesota occurred in 1947.

26. Smallpox Transmission
Smallpox spreads primarily through respiratory droplets
Direct contact and contaminated clothing, bedding can also spread infection
Transmission: rash onset → scabs fall off
Winter and early spring most favorable for spread
Virus inactivated within 1-2 days in event of aerosol release
Smallpox spreads primarily through respiratory-droplet nuclei, although a few outbreaks have been associated with airborne spread. Infection is also spread through direct contact and contact with contaminated clothing and bedding. The infectious period of smallpox starts at rash onset (sometimes during the prodomal stage [fever, headache, malaise, etc.) and lasts through convalescence and stops after scabs have fallen off. Cool, dry winter months offer the most favorable conditions for the spread of smallpox because variola survives longer at lower temperatures and low levels of humidity.
The smallpox virus is fragile so in the event of an aerosol release of smallpox, the virus will be inactivated or dissipated within 1-2 days. Buildings exposed to aerosol release of the smallpox virus do not need to be decontaminated.

27. Smallpox Infection Control
Strict adherence to airborne and contact precautions
Isolate suspected case in negative air pressure room
Healthcare providers should be immunized and use standard, airborne and contact precautions
Virus destroyed with standard disinfectants and heat
Strict adherence to airborne and contact precautions must be followed if a smallpox case is suspected or confirmed. A suspected or confirmed case of smallpox should be isolated and managed in a negative air pressure room. Since smallpox patients are infectious from the time of development of rash, isolation of a possible case at onset of fever (1-2 days prior to rash) is optimal.
Secondary cases are often limited to family members or health care providers; consequently, all health care providers should be vaccinated and demonstrate a vaccine take prior to caring for a smallpox case. Health care providers should be immunized prior to caring for a smallpox patient and should use standard, airborne and contact precautions, including using NIOSH respirators, protective clothing and shoe covers when in contact with smallpox patients to prevent inadvertent spread of the virus. A smallpox patient who is coughing can transmit large quantities of virus. A slide set detailing personal protective equipment for smallpox patient care is available on the MDH website.
Laundry staff should be vaccinated before handling potentially contaminated materials. Until laundry staff can be vaccinated, use of disposable bedding and clothing for the smallpox patient is necessary. All non-disposable bedding and clothing of smallpox patients should be placed in biohazard bags and autoclaved or laundered in hot water with bleach. Infectious waste should be placed in biohazard bags and autoclaved before incineration. Standard hospital disinfectants such as quaternary ammonia are effective for killing the virus on surfaces and should be used for disinfecting patients’ rooms or other contaminated surfaces. Hypochlorite (bleach) is an acceptable alternative. Standard sterilization methods should be used for medical equipment used on smallpox patients.
References:
Breman JG, Henderson DA. Diagnosis and management of smallpox. N Engl J Med 2002;36:
Henderson DA, Inglesby TV, Bartlett JG et al. Smallpox as a biological weapon. Medical and public health management. JAMA 1999;281:
CDC. FAQ’s about smallpox. …

28. Smallpox Laboratory Procedures
Specimens should be collected by recently vaccinated personnel
Vesicular or pustular fluid, scabs, scraping of skin lesions, blood samples, tonsillar swabs
Diagnosis confirmed by PCR and electron microscopy
Specimens should be collected by someone who has been recently vaccinated if possible, even vaccinated that day, and who wears appropriate personal protective equipment.
Laboratory confirmation of the diagnosis is important in a smallpox outbreak. Vesicular or pustular fluid, scabs or scraping of skin lesions, blood samples and tonsillar swabbings from a possible case must currently be sent to the CDC after MDH has been notified. MDH will facilitate rapid transport of specimens.
Confirmation of diagnosis is made by PCR and electron microscopy.
References:
Breman JG, Henderson DA. Diagnosis and management of smallpox. N Engl J Med 2002;36:
Henderson DA, Inglesby TV, Bartlett JG et al. Smallpox as a biological weapon. Medical and public health management. JAMA 1999;281:

29. Smallpox Vaccination
Routine vaccination of civilians stopped in the U.S. in 1972
Immune status of those previously vaccinated is unclear
Beginning January 2003 smallpox vaccination for certain military personnel and smallpox response teams starts
Current vaccine, Dryvax, is same vaccine used in 1970s and contains live virus (vaccinia)
Because the risk of adverse reactions to smallpox vaccination outweighed the threat of endemic smallpox, routine vaccination of civilians in the U.S. ceased in On December 13, 2002, President Bush announced that smallpox vaccinations for military persons and smallpox response teams comprised of public health staff and healthcare workers likely to be involved in the initial care of any patients with smallpox will begin in January, Vaccination of smallpox response team members will be voluntary.
Smallpox vaccination provides immunity for 3 to 5 years and decreasing immunity thereafter. In the past, the vaccine has been effective in preventing smallpox infection in 95% of those vaccinated. Most Americans older than 30 were inoculated for smallpox as children, however the immune status of persons previously vaccinated is unclear. Older persons most likely have little remaining residual immunity. It is assumed that the general U.S. population is susceptible to infection.
Smallpox vaccine contains live vaccinia virus, which is similar to smallpox virus. Vaccinia virus is normally confined to cattle but imparts immunity to the smallpox Variola virus through vaccination. Even when administered to healthy people, smallpox vaccine can, although infrequently, produce serious side effects.
References:
Henderson DA, Inglesby TV, Bartlett JG et al. Smallpox as a biological weapon. Medical and public health management. JAMA 1999;281:
CDC FAQ’s about smallpox.
Center for Infectious Disease Research and Policy.

30. Smallpox Vaccination Adverse Events
1/10,000 persons have serious side effects including:
lymphadenopathy
fever
encephalitis (1/300,000)
progressive vaccinia (1/2,000)
eczema vaccinatum (1/26,000)
death (1-2/1,000,000)
Historical data indicate that one person in 10,000 who receives the smallpox vaccine will experience serious side effects that require a doctor’s care, although the number could be much higher today. Serious complications occur more frequently in those receiving their first dose of vaccine (as opposed to revaccination), and among young children (< 5 years of age). Adverse reactions include lympadenopathy, fever, encephalitis (1 per 300,000), progressive vaccinia (virus transferred by hand from site of vaccination to other areas causing large, oozing lesions on sites such as face, eyes, mouth, nose, genitalia, rectum), eczema vaccinatum (occurs in vaccine recipients with active or healed eczema or persons with this condition who come into contact with someone recently vaccinated). If the vaccine were given to everyone in the U.S., it is estimated that people would die. That is about 1-2 deaths per 1 million primary vaccinations.
Research data from the 1960s indicate that children under the age of 5 years old had the highest rate of complications following primary vaccination.
Adverse reactions associated with smallpox vaccine were 10 times more common among primary vaccinees than in those receiving repeat vaccinations. Lethal outcomes from any vaccine complication were more frequent in those vaccinated before the age of 1 year. The adverse reactions that have been associated with a risk of mortality included postvaccinal encephalitis (approx. 25% fatal), progressive vaccinia (approx. 36% fatal), and eczema vaccinatum (rates vary from approx 1% to 6%). While postvaccinal encephalitis was an idosyncratic event, the latter 2 adverse events were associated with predisposing risk factors. Progressive vaccinia was seen in those with preexisting immune deficiences (genetic, acquired, or iatrogenic). EV was evidenced as the widespread dissemination of vaccinia occurring in the skin of those with active or quiescent “eczematous skin conditions”” who had been intentionally or accidentally exposed to vaccinia.
Because the risk of intentional release of variola virus is low and the risk for adverse reactions associated with smallpox vaccination, mass vaccination of the general public is currently not advised.
References:
Henderson DA, Inglesby TV, Bartlett JG et al. Smallpox as a biological weapon. Medical and public health management. JAMA 1999;281:
CDC FAQ’s about smallpox.
Engler RJM, Kenner J, Leung DYM. Smallpox vaccination: risk considerations for patients with atopic dermatitis. J Allergy Clin Immunol 2002;110(3):

31. Vaccine Contraindications (Pre-exposure) For Vaccinees and Potential Contacts
Immunodeficiency
e.g., HIV infection, AIDS, many cancers, lupus
Immunosuppressive therapy
Cancer, transplants, steroid therapy*, topical steroids for skin dz, inhaled steroids**
Eczema/Atopic Dermatitis
Hx or presence of eczema, including “healed” eczema, atopic dermatitis
Skin Disorders***
Disruptive or eruptive, e.g., acne, burns, impetigo, zoster, wounds, contact dermatitis, current surgical incision wounds
Pregnancy
Current or planning within 4 weeks of vaccination
Current nursing
Child age 1 yr or less in household
Eye disease of the conjunctiva or cornea (Vaccinee only)
Pruritic lesions, florid inflammation
Allergies to Dryvax vaccine components (Vaccinee only)
Polymyxin B sulfate
Streptomycin sulfate
Chlortetracycline hydrochloride
Neomycin sulfate
Tetracycline
Potential vaccinees must be carefully screened for contraindications to smallpox vaccination. Household contacts or others who may be in close contact with a vaccinee who have vaccine contraindications must be identified to avoid accidental transplantation to that individual by the vaccinee, and also to ensure that the vaccinee breaks contact with the individual until scar formation, generally in 2-3 weeks, indicating lack of infectivity.
The vaccinia vaccine should not be administered for nonemergency indications if any of these conditions are present of if the vaccinee will be in close contact with someone, in their household who has one of these conditions. In the event of a smallpox outbreak, these contraindications would not apply.
*steroid therapy (equivalent to 2 mgm/kg or greater of prednisone daily, or 20 mgm/day, particulary if given for more than 14 days
**consult allergist/immunologist or the CDC. Requires individualized decisions as the absorption varies both with the steroid used and the dosage and frequency of administration
*** the size and extent of the skin disorder may be sufficiently small that vaccination can be safely performed. However, all such patients must be counseled to take great care to avoid any transfer from the primary site to the affected skin. Even persons with healed eczema may manifest complications. They should not be vaccinated and should avoid contact with a vaccinee.
All women of childbearing age should be queried as to pregnancy and nursing status.
Eye diseases may predispose to itching and rubbing of the eye with concomitant transfer of virus from the vaccination site.
Source: CDC

32. Smallpox Vaccine Administration
Administered via scarification with bifurcated needle
Needle held at right angles to skin
15 rapid strokes in upper arm*
Trace amount of blood at site indicates successful vaccine delivery
In the past, vaccination was performed by the scratch or multiple insertion method. The recommended method in the U.S. now is the multiple puncture vaccination, performed with a bifurcated (forked) needle. Each bifurcated needle is sterile and wrapped and is for single usage only.
The deltoid area on the upper arm is the preferred site for vaccination. In the past other sites have been chosen, such as the back or buttock, for cosmetic concerns. It is strongly recommended that the deltoid site be used. Some experts cite the fact that there is differential skin sensitivity to vaccination and that most of the efficacy studies analyzed vaccinees who received deltoid vaccinations.
No skin preparation is needed; alcohol should never be applied to the skin prior to vaccination as it has been shown to inactivate the vaccine virus.
The needle, which holds a dose of vaccine (2.5 microliters), is dipped into the vaccine vial and withdrawn. A drop of vaccine of sufficient size and strength to ensure a take is held in the “fork.” Needles should never be dipped into the vaccine vial more than once, in order to avoid contamination of the vial. The needle is held perpendicular (90 degrees) to the skin. The wrist of the vaccinator should be maintained in a firm position by resting on the arm of the vaccinee or other firm support. Vigorous punctures are rapidly made up and down in an area of about 5 millimeters in diameter in the upper arm (see package insert). A small amount of blood should appear at the site after seconds. If trace of blood does not appear, the strokes have not been sufficiently vigorous and the vaccination must be repeated.
After vaccination, excess vaccine should be absorbed with sterile gauze. Discard the gauze in a safe manner (hazardous waste container) in order to not contaminate the site or infect others who may come in contact with it. It is important that the vaccination site be covered to prevent dissemination of virus. Ingestion and intramuscular injection of a dose of vaccine are not recommended routes of administration, however, no harm has been recorded from such events.
*At this time there is discussion about the number of strokes necessary. In a recent innoculation program of 187 military members, primary vaccinees received 3 jabs (97% take rate) and revaccinees received 15 jabs (99% take rate).
The photo shows the bifurcated needle positioned to begin scarification.
Photo: World Health Organization, Geneva, Switzerland.
References:
CDC Smallpox Vaccination Module

33. Preventing Contact Transmission
Until a scab has formed:
Vaccination site must be covered
No touching, scratching, or rubbing vaccination site
Avoid person-to-person contact with susceptible persons
Avoid touching, rubbing or otherwise performing any maneuvers that might transfer vaccinia virus to the eye or surrounding skin
Carefully discard vaccination site covering
After handling the vaccination site covering, thoroughly wash hands with soap and running water
The covering contains viable virus which can be spread to others. Cultures of the vaccination sites of primary vaccinees have yielded positive cultures from days 3 through 14 after vaccination, meaning that live vaccinia virus is present at the vaccination site.
To avoid transmission of the virus in the vaccinee to another part of the body, or from the vaccinee to another person, vaccinees and parents/guardians must be cautioned that no rubbing or scratching of the vaccination site is allowed. This is especially tricky, since the site is usually itchy. Also, thorough hand washing must occur anytime the site is touched or the dressing is changed.
The vaccination site covering must be carefully discarded. Enclose the covering in a plastic bag that can be sealed prior to placing it in a trash receptacle. Hands must be thoroughly washed after handling gauze.
References:
CDC
Rosenthal SR, Merchlinsky M, Kleppinger C, Goldenthal KL. Developing new smallpox vaccines. Emerging Infectious Diseases 2001;7(6).

34. Smallpox Vaccination Site Reaction
This slide shows the progression of a primary (person never before vaccinated) smallpox vaccination reaction. About 3-4 days after vaccination the inoculation site becomes reddened and pruritic. A vesicle surrounded by a red areola forms and then becomes pustular by the 7th-11th day post vaccination. The pustule begins to dry, redness subsides, and the lesion develops a crust by the 2nd – 3rd week.
Effective vaccination, classified as a “take,” is indicated by the presence of a pustular lesion in a previously unvaccinated person. A pustular lesion or an area of definite induration or congestion surrounding a central lesion 6-10 days after inoculation indicates a take in a previously vaccinated person. The vaccine take rate of lesion formation for the currently stockpiled vaccine, Dryvax, is greater than 90%. Persons not exhibiting the pustular reaction at the vaccination site on day 7 should be revaccinated. The reaction of a person previously vaccinated will be somewhat less than pictured.
Expected vaccination side effects, particularly in those receiving their primary vaccination, include itching, tenderness, redness, swelling, and a lesion at the vaccination site. The vaccination may also cause fever for a few days and tenderness and enlargement of localized lymph nodes. These symptoms are more common in those being vaccinated for the first time (15-20%) than in those being revaccinated (5-10%) and among older children and adults than in infants.
Photo source:
CDC.
References:
Rosenthal SR, Merchlinsky M, Kleppinger C, Goldenthal K. Developing new smallpox vaccines. Emerging Infectious Diseases 200l;7(6)

35. Vaccinia Immune Globulin
Vaccinia immune globulin (VIG) is used to treat persons with adverse reactions to smallpox vaccine
Sufficient stock of VIG must be on hand before smallpox vaccinations can be administered
5,000 doses available at end of 2002
Additional VIG is being supplied from the plasma of recently inoculated persons
Vaccinia immune globulin (VIG) is the only antidote to treat adverse reactions to the smallpox vaccine and must be on hand before smallpox vaccinations may be administered. VIG is obtained from antibodies in the blood of people vaccinated in the past two months. As the federal government started negotiations to procure enough smallpox vaccine to inoculate every American, a separate effort began to obtain large quantities of vaccinia immune globulin (VIG). Antibodies from persons currently enrolled in smallpox vaccine clinical trials are being collected. By the end of 2002, the government should have about 5,000 doses of VIG, which would in theory be enough to allow at least 40 million people to be vaccinated. Making enough VIG in order to vaccinate all 280 million Americans safely could take 2 years, based on pessimistic estimates of need. No one knows exactly how much VIG would be needed because no one know how many bad reactions will occur or how effective efforts to screen out people will be.
VIG is not considered to be effective in treating postvaccine encephalitis and is contraindicated for the treatment of vaccinal keratitis.
The recommended therapeutic dosage of VIG is 0.6 mL/kg intramuscularly, or 4 for a 70-kg adult; this dosage may be repeated as often as weekly. Such high intramuscular volume can be associated with trauma and possible nerve damage.
In 1968, two separate studies found one life-threatening reaction per 67,000 vaccinations and one per 20,000. Of course in 1968, far fewer Americans had weakened immune systems.
One adverse reaction to the vaccine can deplete limited vaccinia reserves. For example, in the mid-1980s Army doctors administered a routine smallpox vaccine to a soldier in basic training. The soldier appeared to be healthy but was actually developing AIDS at the time of the inoculation. His body became covered with large sores and he nearly died. Saving him required all of the vaccinia present in a large Army medical depot.
Reference:
Search begun for medicine to treat adverse reactions. Keith Bradsher. New York Times

36. Ring Vaccination for Smallpox
Index Case
Jerry
Close Contact
Should a case of smallpox emerge, current U.S. policy calls for isolating the case and tracking down and vaccinating everyone who may have been in contact with the person and potentially exposed to the disease, therefore forming a ring of immunized persons around the virus, preventing it from spreading. The vaccine is effective is given up to four days following exposure to smallpox.
The ring vaccination strategy can be best explained by an example. Jerry Seinfeld has smallpox and is the index case. The first persons to be vaccinated against smallpox are those he has been in contact within the past 2 weeks prior to rash onset, Elaine, George and Cosmo. The next level of vaccination includes persons who have been in contact with Elaine, George and Kramer within the past two weeks, such as Elaine’s boss, Mr. Pederman, George’s fiancée Susan, and Kramer’s neighbor, Newman. All of these persons would be traced and offered smallpox vaccination. There may be other contacts of contacts that need to be considered such as persons dining at the same coffee shop as Elaine and George. These persons would be evaluated by MDH and local health departments.
Reference:
Mon, Jul. 08, 2002 Smallpox vaccine plan readied. CECI CONNOLLY. Washington Post.
Elaine
George
Kramer
Contacts of Contacts
J. Pederman
Susan
Newman

37. Current Smallpox Vaccine Supply
U.S. government has 15.4 million doses of Dryvax vaccine
Additional 85 million doses (Aventis Pasteur) held for emergency use
Clinical studies underway to determine safety and efficacy of other potential vaccines; Acambis vaccine in production
Currently there are 15.4 million doses of smallpox vaccine (Dryvax) available in the U.S. Recent data (2002) indicate that the vaccine may be diluted as much as 5 times without loss of potency. An additional 85 million doses of frozen smallpox vaccine have been located by Aventis and donated to the U.S. government. Clinical trials are underway to determine the safety and efficacy of this and other news vaccines under development.
In addition, the vaccine was proven to prevent or substantially lessen infection when given within a few days of exposure. It is important to note, however, that at the time when the smallpox vaccine was used to eradicate the disease, testing was not as advanced or precise as it is today, so there may still be things to learn about the vaccine and its effectiveness and length of protection.
References:
CIDRAP