Smallpox Update for Clinicians and Health Professionals

A Clinical Guide

Module I

Houston Department of Health and Human Services

Houston Department of Health and Human Services

As the local health authority for the City of Houston, the Department of Health and Human Services (HDHHS) is the lead agency for the Houston Smallpox Vaccination Program. In that regard, we have planned the coordination and execution of the Houston Harris County Smallpox Vaccination Program (HHCSVP) in partnership with Harris County Public Health and Environmental Services to provide smallpox vaccinations under the guidance and direction of the Centers for Disease Control and Prevention.

The nation has embarked upon the smallpox vaccination of military, hospital health care teams and public health personnel. We recognize that for most medical personnel the post vaccination follow up of individuals will be a challenging task. In that regard, we have prepared this document to aid you in the management and treatment of individuals receiving this vaccine.

Smallpox Overview

Smallpox Disease

Incubation Period(Duration: 7 to 17 days)Not contagious. Exposure to the virus is followed by an incubation period during which people do not have any symptoms and may feel fine. This incubation period averages about 12 to 14 days but can range from 7 to 17 days. During this time, people are not contagious.

Initial Symptoms (Prodrome)(Duration: 2 to 4 days)Sometimes contagious*. The first symptoms of smallpox include fever, malaise, head and body aches, and sometimes vomiting. The fever is usually high, in the range of 101 to 104 degrees Fahrenheit. At this time, people are usually too sick to carry on their normal activities. This is called the prodrome phase and may last for 2 to 4 days.

Smallpox Overview

Early Rash(Duration: about 4 days)Most contagiousRash distribution: A rash emerges first as small red spots on the tongue and in the mouth.These spots develop into sores that break open and spread large amounts of the virus into the mouth and throat. At this time, the person becomes most contagious.Around the time the sores in the mouth break down, a rash appears on the skin, starting on the face and spreading to the arms and legs and then to the hands and feet. Usually the rash spreads to all parts of the body within 24 hours. As the rash appears, the fever usually falls and the person may start to feel better.By the third day of the rash, the rash becomes raised bumps.By the fourth day, the bumps fill with a thick, opaque fluid and often have a depression in the center that looks like a bellybutton. (This is a major distinguishing characteristic of smallpox.)Fever often will rise again at this time and remain high until scabs form over the bumps.

Smallpox Overview

Pustular Rash(Duration: about 5 days)ContagiousThe bumps become pustules—sharply raised, usually round and firm to the touch as if there’s a small round object under the skin. People often say the bumps feel like BB pellets embedded in the skin.

Pustules and Scabs(Duration: about 5 days)ContagiousThe pustules begin to form a crust and then scab. By the end of the second week after the rash appears, most of the sores have scabbed over.

Smallpox Overview

Resolving Scabs(Duration: about 6 days)ContagiousThe scabs begin to fall off, leaving marks on the skin that eventually become pitted scars. Most scabs will have fallen off three weeks after the rash appears.The person is contagious to others until all of the scabs have fallen off.

Scabs resolvedNot contagiousScabs have fallen off. Person is no longer contagious.* Smallpox may be contagious during the prodrome phase, but is most infectious during first 7 to 10 days following rash onset.

About the Vaccine

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, which includes smallpox (variola), cowpox, monkeypox, gerbilpox, camelpox and others. When inoculated in the superficial layers of the skin, the virus grows and induces an immune reaction that serves to protect against smallpox.

A successful vaccination is often referred to as a take.

Two vaccines will be used in the coming years:

Calf-Lymph Vaccine

Dryvax, a stored calf-lymph vaccine manufactured in the 1970’s by Wyeth Laboratories, is freeze dried (lyophilized) and must be reconstituted to a 1/5 dilution before use.

The vaccine will be distributed to strategic holding centers throughout the United States and may be used in 2002 to fulfill the recommendations of the national Advisory Committee on Immunization Practice (ACIP) for immunization of certain teams of investigators and health care workers.

Dryvax has been used in the recent past to immunize laboratory workers.

Note: Dryvax contains antibiotics and preservatives.

Tissue Culture Cell Vaccine

As of October 2002, tissue culture cell vaccines are in preparation by Acambis-Baxter Laboratories.

Two cell lines were selected for propagation of vaccinia virus:

• Vero monkey kidney cells

• Human fibroblast cell line (MRC5)

Several lots of both vaccines have been prepared and are undergoing testing. It is anticipated that one of these vaccines will supplant calf-lymph vaccine if a more extensive vaccination program is implemented.

ContraindicationsREMEMBER: There are no contraindications to the smallpox vaccine if someone has been exposed to the smallpox virus!

Potential vaccinees must be screened for contraindications to smallpox vaccination during this initial phase. For details refer to specific adverse events.

Anyone with whom the potential vaccinee has contact and who has a susceptibility to complications must be identified to:

• Avoid accidental innoculation of that individual by the vaccinee , and

• Ensure that the vaccinee breaks contact with the individual until scar formation, generally in 2-3 weeks, indicating lack of infectivity

Contraindications

Eczema or atopic dermatitis and other acute, chronic, or exfoliative skin conditions

Persons who have ever been diagnosed with eczema or atopic dermatitis should not be vaccinated, even if the condition is not currently active. These patients are at high risk of developing eczema vaccinatum, a potentially severe and sometimes fatal complication. Additionally, persons with household contacts that have a history of eczema or atopic dermatitis, irrespective of disease severity or activity, should not be vaccinated.

If the potential vaccinee or any of their household contacts have other acute, chronic, or exfoliative skin conditions (e.g., burns, impetigo, chicken pox, contact dermatitis, shingles, herpes, severe acne, or psoriasis), they are at risk for inadvertent autoinoculation of the affected skin with vaccinia virus and should not be vaccinated until the condition(s) resolves.

The literature also reports that persons with Darier’s disease can develop eczema vaccinatum and therefore should not be vaccinated.

Contraindications

Diseases or conditions which cause immunodeficiency or immunosuppression

If a potential vaccinee or any of their household contacts have conditions such as HIV/AIDS, solid organ or stem cell transplant, generalized malignancy, leukemia, lymphoma, agammaglobulinemia, or autoimmune disease, they should not be vaccinated. People with these conditions are at greater risk of developing a serious adverse reaction resulting from unchecked replication of the vaccine virus (progressive vaccinia).

HIV testing should be readily available to all persons considering smallpox vaccination. HIV testing is recommended for persons who have any history of a risk factor for HIV infection and who are not sure of their HIV infection status. Anyone who is concerned that they could have HIV infection also should be tested. HIV testing should be available in a confidential or, where permitted by law, anonymous setting with results communicated to the potential vaccinee before the planned date of vaccination. Persons with a positive test result should be told not to present to the vaccination site for immunization.

Contraindications

Treatments which cause immunodeficiency or immunosuppression

If a potential vaccinee or any of their household contacts are undergoing treatment with radiation, antimetabolites, alkylating agents, corticosteroids, chemotherapy agents, or organ transplant medications, they should not be vaccinated. People who are receiving these therapies are at greater risk of serious adverse reactions to the smallpox vaccine.

Pregnancy

Live virus vaccines are generally contraindicated during pregnancy. Pregnant women who receive the smallpox vaccine are at risk of fetal vaccinia. Although this is a very rare condition (fewer than 50 cases have ever been reported), it usually results in stillbirth or death of the infant shortly after delivery.

Before vaccination, people should be asked if they or any of their household contacts are pregnant or intend to become pregnant in the next 4 weeks; those who respond positively should not be vaccinated.

ContraindicationsIn addition, women who are vaccinated should be counseled not to become pregnant during the 4 weeks after vaccination.

Routine pregnancy testing of women of child-bearing age is not recommended.

Any woman who thinks she could be pregnant or who wants additional assurance that she is not pregnant should perform a urine pregnancy test using a “first morning” void urine on the day scheduled for vaccination.

If a pregnant woman is inadvertently vaccinated or if she becomes pregnant within 4 weeks after vaccinia vaccination, she should be counseled regarding the basis of concern for the fetus. However, vaccination during pregnancy should not ordinarily be a reason to terminate pregnancy.

The contraindications above apply to potential vaccinees and their household contacts.

Contraindications

The following additional contraindications apply only to potential vaccinees:

Previous allergic reaction to smallpox vaccine or any of the vaccine’s components

Vaccinia vaccine (Dryvax®) contains small amounts of polymyxin B sulfate, streptomycin sulfate, chlortetracycline hydrochloride, neomycin sulfate, and phenol. Anyone who has experienced an anaphylactic reaction to these components should not be vaccinated.

In addition, anyone who has experienced a previous allergic reaction to the smallpox vaccine should not be vaccinated.

Moderate or severe acute illness

Moderate or severe acute illness is generally a contraindication to vaccination.

Vaccination should be deferred until the acute illness has resolved.

Contraindications

Infants and children

Smallpox vaccine is contraindicated for children under 12 months of age.

The Advisory Committee on Immunization Practices (ACIP) advises against non-emergency use of smallpox vaccine in persons younger than 18 years of age.

Breastfeeding

Breastfeeding mothers should not receive the smallpox vaccine. The close physical contact that occurs during breastfeeding increases the chance of inadvertent inoculation.

Careful screening is essential to minimize complications from the smallpox vaccine. If you have any questions about whether or not someone should receive the smallpox vaccine, visit the CDC website at www.cdc.gov/smallpox.

Non-Emergency vs. Emergency

The vaccinia vaccine should not be administered for nonemergency indications if any of the conditions in the accompanying table are present or if the vaccinee will be in close contact with someone, either in their household, or in a hospital setting, who has one of these conditions.

Note, however, that in the event of a smallpox outbreak where there is a high risk of contact with a patient, these contraindications would not apply.

Normal ReactionsA normal primary vaccination appears as a papule in 3-4 days, and rapidly progresses to a vesicle with the surrounding erythema by the 5th-6th day. On the 7th day the vaccinee should return to the clinic or designated location for "The vesicle center becomes depressed and progresses to a well-formed pustule by the 8th-9th day. By the twelfth day, or soon thereafter, the pustule crusts over forming a brown scab, which progresses from the center of the pustule to the periphery. After 2.5 to 3 weeks, the scab detaches and a well formed scar remains.

Rarely, in some previously unvaccinated individuals, seemingly appropriate vaccination techniques may result in no reaction. One should assume that the individual is not immune and repeat attempts should be made to achieve a primary take. At least three attempts should be made, switching skin sites after a second unsuccessful attempt.

Normal Reaction Time

Day Description

0 Vaccination

3-4 Papule

5-6 Vesic le with surroundingerythema –vesic le with depressedcenter

8-9 Well-formed pustule

12+ Pustule crusts over –scab

17-21

Scab detaches revealingscar

Systemic Symptoms

Systemic symptoms are expected and usually occur about a week after vaccination. These include:

•Soreness at the vaccination site•Intense erythema ringing the vaccination site•Malaise•Lymphadenopathy (local)•Myalgia, headache, chills, nausea, fatigue•Fever

The occurrence of these normal reactions varies considerably from study to study. The following table lists the symptoms covered by the studies and provides an indication of the range:

•Lymphadenopathy 25.0 - 50.0 % •Myalgia, headache, chills,

nausea, fatigue 0.3 - 37.0 % •Fever > 37.7° C 2.0 - 16.0 %

Variations to Normal Reactions

Variations of normal reactions that are not considered adverse events can include:

•Local satellite lesions(*) (that are normal in appearance)

•Lymphangitis •Local edema •Viral cellulitis(†)

(intense inflammation surrounding the papule)

* The frequency of satellite lesions varies from study to study and ranges from 2.4 to 6.6 %.

† This normal consequence of vaccination is often confused with bacterial infection.

Normal Variants

Satellite Lesions

Normal Variants

Lymphangitis

Normal Variants

Edema

Normal Variants

Viral Cellulitis

Management

None of these expected variations of normal reactions require any treatment other than symptomatic relief.

Revaccination

The nature of the response to revaccination depends on the degree of residual immunity following previous vaccination. One of the following responses will occur:

Response DescriptionTypical primary reactionClear cut pustule 6-8 days after vaccination

Major reactionArea of definite induration or congestion surrounding a central lesion that may be a scab or ulcer 6-8 days after vaccination. The evolution of the lesion is more rapid than following a primary reaction.

Revaccination

Equivocal reactionAny other reaction or response including:

• “Allergic” reaction Erythema and a small, evanescent papule present within several days that resolves quickly. These are “sensitivity” reactions that can be evoked with vaccine virus that is no longer viable. Revaccination is indicated.

•No reaction In some individuals, no take is seen after revaccination, even at long intervals after a primary vaccination. Usually this is due to poor technique, low potency vaccine, or inactivation of the virus at the skin site (e.g. if alcohol is used to prepare the site). Revaccination is indicated using vaccine of assured potency.

Revaccination

In general, the shorter the interval between primary vaccination and revaccination, the more likely it is that there will be no take or a major reaction.

Among those for whom 25 years or more has elapsed since last vaccination, essentially all should experience a "major reaction".

If a patient has never had a successful take, the patient should be

informed that he/she is almost certainly not immune.

Additional Resources

For additional information on this and related topics visit:•National Centers for Disease Control and PreventionNational Centers for Disease Control and Prevention http://www.bt.cdc.gov/agent/smallpox/index.asp

•Texas Department of HealthTexas Department of Health http://www.tdh.state.tx.us/smallpox/default.htm

•Houston Department of Health and Human ServicesHouston Department of Health and Human Services http://www.ci.houston.tx.us/hlt/smallpox-index.html

•National Institute of Allergies and Infectious DiseasesNational Institute of Allergies and Infectious Diseases National Institutes of HealthNational Institutes of Health http://www.niaid.nih.gov/publications/bioterrorism.htm

How to Contact Us

Houston Department of Health and Human ServicesOffice of the Director/Office of Strategic Development

8000 N. Stadium Dr.Houston, TX 77054

Office: (713)794-9313Fax: (713)798-0862

If you have questions about the HHCSVP and are in the City of If you have questions about the HHCSVP and are in the City of Houston:Houston:Valda Jean Combs, JD

ManagerPublic Health PreparednessOffice of the Director/Strategic Development

If you have questions about the HHCSVP and are in Harris If you have questions about the HHCSVP and are in Harris County:County:Richard P. Gaston

Emergency Response CoordinatorHarris County Public Health and Environmental Services2223 West Loop South, Houston, Texas 77027713.439.6020713.439.6090 (facsimile)