Smallpox is a devastating disease that has been successfully eradicated. As a result, routine smallpox vaccination of the general population was halted in the United States in 1 972.1,2 Unfortunately, because of recent world events, concern exists that an intentional release of smallpox (variola) virus could occur. Whether we will see the actual disease is unknown. However, because of the threat, some segments of the US population are being vaccinated. Health care workers, first responders, and US military members are currently eligible for this vaccine. Although children are not included in current vaccination strategies,3 vaccinia can be transmitted to others via contact, thus children can potentially become infected in this manner. Therefore, pediatricians and other health care providers who care for children need to be aware of the complications of. and contraindications to, smallpox vaccination. Education to prevent vaccine complications is effective and preferable to the limited treatment options.
Currently, available smallpox vaccine in the United States is derived from the New York City Board of Health strain of the vaccinia virus.4 It is a live virus vaccine and does not contain smallpox (variola) virus. One of the reasons this particular strain was chosen is because it causes fewer adverse effects than other effective formulations. Dryvax is the brand name of the New York City Board of Health vaccine currently used in the United States. This vaccine should be administered every 10 years to those with exposure to less virulent orthopox viruses and more frequently (every 3 years) to those who might be exposed to more virulent pox viruses.5 Once vaccinated, recipients shed vu-us from day 3 to day 4 until the scab falls from the vaccination site (about day 21 in a primary vaccine recipient), with maximal shedding on days 4 through 14.
Contraindications to vaccinia are relative to risk of smallpox exposure. According to the package insert for Dryvax, infants younger than 1 year should not be vaccinated with this vaccine.6 As specified by the Advisory Committee on Immunization Practices (of the Centers for Disease Control and Prevention [CDC]), children younger than 18 years should not be vaccinated in the pre-outbreak setting.-'4 Individuals allergic to any component of the vaccine, including polymyxin B sulfate, streptomycin, tetracycline, and neomycin sulfate, should not be vaccinated. Individuals who are immunosuppressed or receiving systemic corticosteroid treatment (S= 2 mg/kg/d) or prednisone (^ 20 mg/d) for 2 weeks or longer, immunosuppressive agents, or radiation therapy should not receive the vaccine. Atopic dermatitis and eczema are major contraindications to the vaccine. Household contacts of individuals with these conditions should not be vaccinated. Contraindications to vaccine are outlined in Table 1 (page 180).
In the unlikely event of a high-risk exposure to smallpox disease, there are no absolute contraindications for receiving the smallpox vaccine. This is because the risk of a fatal outcome (estimated to be as high as 30%) from contracting smallpox is much greater than the risk of fatal complications of the vaccine ( 1 per million primary vaccinations and 1 per 4 million revaccinations).5
Vacane Adverse Reactions
Fever is commonly associated with vaccinia vaccine, with up to 70% of children running a fever of 10O0F or higher for 1 day or longer after primary vaccination, and up to 20% with a fever of 1020F or higher. Adults have less fever than children after primary vaccination, with 5% to 9% reporting a fever of 10O0F or higher and 3% with a fever higher than 1020F. Approximately one half of recipients report mild discomfort at the inoculation site. Typical erythema and edema can become exaggerated and appear similar to cellulitis, although that caused by vaccine usually resolves within 48 hours. Severe pain at the site occurs in a small minority (2% to 3%). Lymphadenopathy occurs in approximately one third of recipients, and occasionally lymphangitis may be seen, but is not associated with significant sequelae. Revaccinations are associated with significantly less severe symptoms.
The primary defense against vaccine complications is to screen vaccine recipients carefully prior to vaccination. The secondary defense is to reduce the transmission of vaccine virus to those who are highly susceptible. However, there is a strong possibility that a number of children will be unintentionally infected with vaccinia; some may develop serious consequences (Table 2, page 180). Inadvertent inoculation of other sites is the most frequent complication and is responsible for approximately half of all vaccine complications.7 The most common sites of inoculation are areas frequently touched, such as the face, nose, eyes, mouth, anus, and genital areas. Previous studies indicate that inadvertent inoculations with vaccinia vaccine were recorded at a rate of 529 per million primary vaccinations.8
Of particular concern is inoculation to the eye, because significant visual loss can result if corneal scarring occurs. Rapid ophthalmologic consultation is advised. In other locations, the lesions generally resolve, with only supportive care required.
Generalized vaccinia is a complication that may occur in healthy individuals within 6 to 9 days following vaccination, at a recorded rate of 242 per million first-time vaccine recipients.8 The virus disseminates hematogenously and seeds normal skin, producing a characteristic vesicular rash throughout the body. This reaction is generally self-limited and requires only supportive care in most cases. Vaccinia immune globulin (VIG) may be indicated in immunocompromised or toxic patients. Erythema multiforme is usually a self-limited complication following vaccination, at a recorded rate of 165 per million primary vaccinations.8 It is recognized by its characteristic erythematous rash and associated target lesions. Vaccinia immune globulin is not indicated.
Smallpox Vaccine Contraindications
Eczema vaccinatum can be a serious complication of smallpox vaccine. Affected individuals can be primary vaccine recipients or close contacts of recently vaccinated individuals. It occurs in children with either active, or a history of, atopic dermatitis or eczema. The severity of the atopic dermatitis or eczema, present or past, is not necessarily predictive of the severity of eczema vaccinatum. Eczema vaccinatum can be mild, severe, or, rarely, a fatal complication of vaccinia. Vaccinia immune globulin is indicated and may be Hfe-saving. Studies in the late 1960s reported a rate of 10 to 39 cases per million primary vaccine recipients, when the prevalence of atopic dermatitis in US children was approximately 6%.7,8 The current rate of atopic dermatitis is approximately 15% to 20%.9
Smallpox Vaccine Adverse Event Rates
Although children are not the target of primary vaccination adult vaccine recipients may transmit vaccinia virus to this population unintentionally. Other inflammatory skin conditions that are seeded with vaccinia virus inadvertently can also result in serious sequelae. Severe acne, herpes zoster, Darier disease (keratosis follicularis), burns (including sunburn), impetigo, and psoriasis are some conditions that could provide a fertile ground for vaccinia to replicate. These conditions in children or their household contacts are contraindications to vaccination until the condition is controlled or resolves.
Post- vaccinal encephalitis/encephalomyelitis is a rare and often devastating complication. It usually occurs in a primary vaccine recipient 8 to 15 days following vaccination, at a recorded rate of J 2 per million primary vaccinations.8 This particular complication is more frequent in infants younger than 1 year.7 It is associated with a fatality rate of 25%; another 15% to 25% are left with permanent neurologic sequelae. Unfortunately, VIG is not effective, and only supportive care is recommended. There is no known effective treatment.
Progressive vaccinia (vaccinia necrosum) is a serious and often lethal complication associated with immunocompromised hosts, especially those with deficiencies of cell-mediated immunity, such as human immunodeficiency virus or lymphoma. In this condition, the vaccine virus continues to replicate unchecked at the immunization site, causing extensive tissue damage and occurring in approximately 1 per million primary vaccinations.7 Vaccinia immune globulin has been used to treat this condition with varying success. The population of children at risk from this condition today human immunodeficiency virus, immunosuppressive therapies, organ transplantation) is of larger magnitude than in 1968, the last year from which we have reliable estimates of risk.
Fetal vaccinia (congenital infection with vaccinia) is a rare event, reported less than 50 times in the world to date. The condition occurs in women vaccinated in all three trimesters and it has been associated with primary vaccination, revaccination, and contacts of vaccine recipients. Stillbirth or death in the postpartum period is the usual result. Pregnancy is a contraindication to vaccination of women or their household contacts.4
Prior studies demonstrated the rate of serious, life-threatening reactions to be 14 to 52 per million doses of vaccine.4·10 In one study, the major causes of death from smallpox vaccination were post-vaccinal encephalitis/ encephalomyelitis and progressive vaccinia (vaccinia necrosum) in primary vaccine recipients, and eczema vaccinatum in contacts.4 The rate of contact transmission from these complicated vaccinia infections to others is extremely low; nosocomial spread, while also infrequent, has been documented, sometimes with fatal results in the secondary cases.11
Treatment of Vaccine Complications
Vaccinia immune globulin is used to treat complications of smallpox vaccine; it is derived from the plasma of individuals previously vaccinated with smallpox vaccine (produced by Baxter Healthcare Corporation) and is currently available from the CDC and the US Department of Defense as an investigational new drug product. The dose of VIG is based on weight, with the normal dose 0.6 mL/kg body weight, administered intramuscularly. The location of choice is the buttock or anterolateral portion of the thigh. There are no antivirals proven to be effective against vacci nia- related complications. However, cidofovir is available for treatment as an investigational new drug product (CDC's Smallpox Vaccinée Adverse Events Clinician Information Line at 877-554-4625; physicians at military medical facilities may request VIG by calling the US Army Medical Research Institute of Infectious Diseases (USAMRIID) at 301-619-2257 or 888USA-RlID).
Effective screening and infection control practices are important measures to reduce vaccinia virus transmission to susceptible individuals and to reduce subsequent complications. Vaccine recipients should avoid touching the inoculation site and should wash their hands thoroughly if they touch it.12 Fomite transmission (eg, towels, dressings) is possible and should be avoided. Educational tools and other materials are available through various agencies via the Internet (http://www.bt.cdc.gov/agent/ smallpox/vaccination).
The US national policy does not include routine vaccination of the general public against smallpox;13 currently, only a select subset of the US population, including first-response teams and selected health care volunteers, is scheduled to receive this vaccine. This strategy relies on the effectiveness of vaccinia vaccination in the post-exposure setting. If given within 3 to 4 days of exposure, the vaccine may prevent or lessen disease in a vast majority of exposed people, with some efficacy even if given up to a week after smallpox exposure. This strategy relies heavily on the ability of the US health care system to identify a case of smallpox.
A single verified case of smallpox is a public health emergency. If such a case were to be identified, the local public health department, in conjunction with the state public health department and the CDC, would initiate a large-scale vaccination in the region or regions involved. Such a program favors the use of targeted or "ring vaccination" instead of mass vaccination, but the size of the "ring" could be hundreds or thousands of individuals, depending on the circumstances. There would be no absolute contraindications to vaccinia vaccination under those circumstances, and large numbers of children would receive the vaccine.
1 . Henderson DA, Inglesby TV, Bartiett JG, et al. Smallpox as a biological weapon: medical and public health management. Working Group on Civilian Biodefense. JAMA. 1999:281:2127-2137.
2. Smallpox vaccine. Pediaîrics. 2002:110: 841-845.
3. Rotz LD, Dämon IK, Becher JA. Vaccinia (smallpox) vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2001. MMWR Morb Mortal WkIy Rep. 200l;50(RR-10):l-25.
4. Cono J, Casey CG, Bell DM. Smallpox vaccination and adverse reactions: guidance for clinicians. MMWR Morb Mortal WkIy Rep. 2003:52:1-29.
5. Centers for Disease Control and Prevention. Smallpox. In: Epidemiology and Prevention of Vaccine-Preventable Diseases: The Pink Book. 7th ed. Betnesda, Md: Centers for Disease Control and Prevention and US Department of Health and Human Services; 2002.
6. Dryvax [Package Insert]. Marietta, Pa: Wyeth Laboratories; Aug 30, 2002.
7. Lane JM, Rubén FL, Neff JM, Millar JD. Complications of smallpox vaccination, 1968. N Engl J Med. 1 969;281:1201-1208.
8. Lane JM, Rubén FL, Neff JM, Millar JD. Complications of smallpox vaccination, 1968: results often statewide surveys. J Infect Dis. 1970;122:303-309.
9. Neff JM, Lane JM, Fulginiti VA, Henderson DA. Contact vaccinia - transmission of vaccinia from smallpox vaccination. JAMA. 2002;288:1901-1905.
10. Centers for Disease Control and Prevention. Smallpox Pre-vaccination Information Packet. Available at: http://www.bt.cdc.gov/ agent/smallpox/vaccination/infopacket.asp. . Accessed February 10, 2003.
11. Sepkowitz KA. How contagious is vaccinia? N Engl J Med. 2003;348:439-446.
12. Centers for Disease Control and Prevention. Public health emergency preparedness and response: smallpox vaccination. Available at: http://www.bt.cdc.gov/agent/smallpox/vaccination/site-care-pub.asp. Accessed February 10, 2003.
13. Centers for Disease Control and Prevention. Protecting Americans: smallpox vaccination program. Available at: http://www.bt.cdc.gov/ agent/smallpox/vaccination/vaccinationprogram-statement.asp. Accessed February 10, 2003.
Smallpox Vaccine Contraindications
Smallpox Vaccine Adverse Event Rates