Special Feature

CDC Update: Smallpox and Vaccinia Vaccine Redux

By Richard J. Hamilton, MD, FAAEM, ABMT

Introduction

The Centers for Disease Control and Prevention (CDC) currently is releasing a large number of doses of vaccinia to health departments across the United States to vaccinate health care workers and emergency responders against smallpox, a disease that in theory has been eradicated from the planet. Why? Concerns regarding stockpiles of smallpox virus and bioterrorism have prompted health officials in the United States to vaccinate as a preventive measure. Think a smallpox attack couldn’t happen because it’s been contained in high-level laboratories? Remember, the anthrax attacks of 2001 may have been perpetrated by someone with access to laboratory stocks of Bacillus anthracis.

In the waning years of the smallpox epidemic, only at-risk contacts of a patient with smallpox were vaccinated—so-called "ring vaccination." That strategy will be used now only if a recognized outbreak occurs. In a new strategy, U.S. government public health officials want hospitals to develop immunized smallpox health care teams that are capable of providing immediate care for a patient with the condition. Primary vaccination is needed for a great number of health care workers. For those who have been vaccinated previously, revaccination is required because immunity wanes after 10 years. Those who have been vaccinated twice may have some immunity for more than 30 years, but this may protect only against fatal forms of the disease.

Since you may be asked to volunteer to be a member of your hospital’s smallpox team, a thorough and informed understanding of vaccinia is important to all emergency physicians and those who staff emergency departments (EDs). The goal of this brief essay is to provide a quick overview of the Smallpox Pre-Event Vaccination Program that the CDC and Department of Health and Human Services currently are undertaking. It is not meant to substitute for the exhaustive training that is available online from these agencies.

Background

The vaccinia vaccine is a live virus that multiplies in the superficial layers of the skin. It is an extremely rare orthopox virus of unclear origins. When introduced into the epidermis, it causes a small local infection that renders cross-immunity to smallpox (variola). Remember, the vaccine does not contain the actual variola virus. This method of vaccination is, in essence, little changed from Jenner’s 1798 demonstration that cowpox conferred cross-immunity to smallpox. In fact, the word "vaccination" is derived from Jenner’s description of this process in his work—"an inquiry into the cause and effects of the Variolae Vaccinae, a disease known by the name of cowpox."

Response to Vaccination

A successful vaccination is referred to as a "take," which begins with the formation of a papule 3-4 days after immunization. Days 5-6 bring surrounding erythema and a depression of the papule. In addition, the patient begins to experience fever, malaise, myalgia, soreness at the vaccination site, and local lymphadenopathy. Gradually, the lesion forms a pustule, and by the second week has scabbed. The scab detaches at the end of third week.

Care of the vaccine site is extremely important for health care workers, in particular. The vaccination site must remain covered and should not be touched, scratched, or rubbed, despite the fact that it often becomes itchy. In addition, a policy should be developed to avoid person-to-person contact with individuals who have a contraindication to receiving vaccinia. (See Table 1.) This does not preclude working as a health care worker, but assumes fastidious attention to prevention of spread. The site should be covered with gauze and a semi-occlusive dressing, such as an adhesive bandage or paper tape. A long-sleeved shirt and work uniform (e.g., lab coat) must be worn at all times. All materials in contact with the vaccine site should be considered highly infectious.

Contagion and Spread after Vaccination

Perhaps the most common concern, especially for health care workers who continue to care for patients, is inadvertent inoculation. This takes the form of inoculation to other skin sites (autoinoculation) and to other persons (secondary inoculation). The primary mechanism s for preventing inadvertent inoculation are hygiene and appropriate care of the vaccine site. The urge to scratch, handle, or examine the site must be avoided, as surface virus is transferred easily to the hands and to fomites. This concern, and the implications of a health care worker accidentally transferring vaccinia to an at-risk patient, has severely limited the enthusiasm with which hospitals have accepted the CDC’s pre-event immunization strategy. For many hospitals, the risk/benefit ratio of participating is favorable only when there is evidence that smallpox is more than an intangible threat. Nonetheless, the issue must be resolved, as many military reservists who work in hospitals are being vaccinated regardless of the hospital’s policy. According to the Advisory Committee on Immunization Practice, administrative leave is not required routinely for newly vaccinated health care personnel unless they become ill, have extensive skin lesions, or are unable to comply with infection-control precautions. In general, prior experience demonstrates that secondary inoculation largely is a result of the close contact seen in household members, and is unlikely to occur in the health care setting.1

Fortunately, Section 304 of the Homeland Security Act, which was enacted on Jan. 24, 2003, protects manufacturers of smallpox vaccine and those health care entities that would administer the vaccine from potential liability for involvement in a federal smallpox vaccination campaign. Section 304 provides an exclusive remedy against the United States for injury or death attributable to "smallpox countermeasures" (e.g., smallpox vaccine, other substances used to treat or prevent smallpox, or vaccinia immune globulin [VIG]). This means that no claim for liability for injury or death attributable to a smallpox countermeasure could be brought against entities or individuals covered by Section 304’s protections. This includes institutions and individuals who participate in the smallpox immunization program. For individuals and institutions seeking further guidance, the CDC smallpox website at www.bt.cdc.gov/agent/smallpox/vaccination/section-304-qa.asp addresses these liability issues.

Adverse Reactions to the Vaccine

There are several adverse reactions to vaccinia. Some are considered variants of normal and others, though rare, are extremely serious. One extreme, but normal reaction is a large vaccination reaction known as a "robust take" (RT). This is defined as a reaction greater than 7.5 cm in diameter at the site of inoculation, and occurs in approximately 10% of first-time vaccines. An RT easily is confused with cellulitis and is best differentiated by noting the time of onset and clinical course. An RT occurs 8-10 days post- vaccination, improves within 72 hours of peak symptoms, and does not progress clinically. In contrast, secondary bacterial infections typically occur within five days of vaccination and progress if not treated. The presence of fever is not a helpful differentiating characteristic. When an RT is suspected, management includes daily observation, patient education, rest of the affected limb, use of oral non-aspirin analgesia, and antihistamines. Salves, creams, or ointments, including topical steroids or antibacterial medications, should not be applied to the vaccination site.2

There are other, less common reactions to the vaccine hat are within the range of normal and occur in 5% of recipients. These include lesions that are satellites of the main take area, lymphangitis from the site to regional nodes, regional lymphadenopathy, dramatic local edema at the site, and intense erythema. The last complication probably represents a viral cellulitis, and is difficult to distinguish from bacterial cellulitis. All these reactions require no specific treatment.2

Of greatest concern are the reactions that are more serious and potentially can be debilitating or fatal. These reactions are extremely rare and must be minimized by screening individuals for contraindications such as immunosuppression, eczema or atopic dermatitis (active or resolved), inflammatory eye diseases, pregnancy, or other contraindications (see Table 1); reconsideration of these should follow in the event of a smallpox emergency. (See Table 2.)

Serious Adverse Reactions

Some serious adverse reactions to the vaccination include:

Generalized vaccinia—Characterized by a disseminated rash and occurs 6-9 days after first-time vaccination. Treatment with VIG is reserved for severe cases and patients who are immunocompromised;

Eczema vaccinatum—Occurs among persons with a history of atopic dermatitis (eczema), regardless of disease severity or activity. It has a predilection for areas of previous atopic dermatitis lesions. These patients often are severely ill and require VIG;

Progressive vaccinia—an often fatal complication among persons with immunodeficiencies, it is characterized by painless progressive necrosis at the vaccination site with or without metastases to distant sites (e.g., skin, bones, and other viscera). Intensive care and VIG are required to improve the chance for survival;

Erythema multiforme—common 1-2 weeks after vaccination. These are benign lesions that do not progress. Full-blown Stevens-Johnson Syndrome is rare but serious. Diagnosis is by typical rash seen in temporal association with primary vaccination. When this reaction takes on a vesicular or pustular form it is necessary to distinguish these from generalized vaccinia or inoculation vaccinia by observing their progression over several days;

Central nervous system disease—includes post-vaccinial encephalopathy (PVE) and post-vaccinial encephalomyelitis (or encephalitis) (PVEM). These are not believed to be a result of replicating vaccinia virus and are diagnoses of exclusion. They may represent an autoimmune process. No specific therapy exists for PVE or PVEM; and

Fetal vaccinia—the result of transmission of vaccinia to the fetus; this generally results in spontaneous abortion.

The good news for those who have received the vaccine in the past is that the overall rate of complications, including the most serious ones, is reduced by an order of magnitude.3

Conclusions

While the pre-event immunization of health care workers currently is underway, participation has been hampered severely by the complex and intimidating chance for adverse outcomes. The decision to participate is still an individual one. A clear understanding of the contraindications and complications is critical to informed participation in this program. Smallpox currently is a finite but real threat. Preparing for it with deliberate caution is the prudent public health approach.

References

1. Centers for Disease Control and Prevention. Recommendations for using smallpox vaccine in a pre-event vaccination program—Supplemental recommendations of the Advisory Committee on Immunization Practices (ACIP) and the Healthcare Infection Control Practices Advisory Committee (HICPAC). MMWR Morb Mortal Wkly Rep 2003:52 (Dispatch);1-16.

2. Centers for Disease Control and Prevention. Smallpox vaccination and adverse reactions. Guidance for clinicians. MMWR Morb Mortal Wkly Rep Dispatch 2003:52 (RR-4):1-28.

3. Lane JM, et al. Complications of smallpox vaccination, 1968: Results of ten statewide surveys. J Infect Dis 1970;122:303-309.

4. Drazen JM. Perspective: Smallpox and bioterrorism. N Engl J Med 2002; 346:1263-1264.

Dr. Hamilton, Associate Professor of Emergency Medicine, Program Director, Emergency Medicine, MCP, Hahnemann University, Philadelphia, PA, is on the Editorial Board of Emergency Medicine Alert.