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Vaccinia (Smallpox) Vaccine
What PAs need to know about smallpox
Last update: January 15, 2003
Herman L, Toth S, Blanchard E, Larson L, Quigley T, Leger M, and McNellis R
This document was prepared by AAPA's Clinical and Scientific Affairs Council for PAs to help maintain their knowledge base on smallpox and the vaccinia vaccine, provide resources for further education, and encourage them to take an active role in preparing their community for vaccination. The material has been approved for 1 hour of clinical Category I CME for AAPA members. (See CME Approval Information.)
(Suggested Citation: Vaccinia (smallpox) vaccine: What PAs need to know about smallpox. CSAC monograph. January 2003. American Academy of Physician Assistants, Alexandria, VA. http://www.aapa.org/clinissues/Smallpoxtext.htm.)
See companion article in the January 2003 issue of The Journal of the American Academy of Physician Assistants
Table of Contents
Download a .pdf version of the document. (750k)
Learning Objectives
After reading this article, the physician assistant will be able to:
- identify the key public health organizations responsible for preparing for a smallpox outbreak
- describe the clinical manifestations and epidemiology of smallpox
- identify the relative contraindications to the vaccinia vaccine
- describe the strategies of case isolation and ring vaccination
Introduction
Smallpox represents an extremely serious threat to populations as a biological weapon because its case-fatality rate is approximately 30% among unvaccinated persons and no specific therapies are available.(1) The potential for devastation is higher today than at any point in recent history. Smallpox is highly infectious, routine vaccination ceased more than 25 years ago, initial signs and symptoms are nonspecific, and ease of travel enables the disease to spread rapidly throughout this country and the rest of the world.
Although the risk of a smallpox attack is uncertain, smallpox vaccination has known risks, including severe disabilities and death. PAs need to know who should be vaccinated, when, and how.
Smallpox, then and now
Smallpox (variola) has been known for centuries and as recently as 1968 killed 2 million persons annually. The last known naturally occurring outbreak was in Somalia in October 1977. (2) The last case of naturally occurring smallpox in the United States was in Texas in 1949. (3) This country discontinued routine smallpox vaccination of children in 1972, of health care workers in 1976, and of Army recruits in 1990. (4) Approximately 120 million Americans were born after routine vaccination ended, and most of those who received the vaccination did so more than 30 years ago.
Recently, concern over the use of smallpox as an agent of bioterrorism has heightened. Despite the provisions of the 1972 Biological Weapons Convention, the Soviet Union is known to have maintained a large-scale bioweapons program well into the 1990s. (5,6) Concerns are growing that Russia's bioweapon expertise and equipment might move - or might have already moved - to other countries.
The smallpox virus is less readily available than other potential biological weapons, such as anthrax or plague, which can be found in many laboratories. Special skill is required to grow the smallpox virus in large enough quantities to be dispersed over a large area, but infection of a small number of persons as intentional vectors may have equally catastrophic results.
Epidemiology and appearance
Before the age of vaccinations, smallpox was a disease of worldwide proportions. The virus spreads from person to person by inhalation of air droplets or aerosols. The two principle forms of the disease are variola major and the much milder variola minor. The case-fatality rate for variola major is 30% or higher; for variola minor, it is 1% or less. (7)
Fever is typically the initial symptom, appearing 12 to 14 days after infection and often accompanied by severe myalgia and exhaustion. A papular rash appears over the face and mouth 2 to 3 days later and then spreads to the extremities. The rash soon becomes vesicular and later pustular. The patient remains febrile throughout the evolution of the rash and generally experiences considerable pain as the pustules grow and expand. Scabs form gradually, eventually separate, and leave pitted scars. In variola major, death due to internal hemorrhage or overwhelming sepsis usually occurs during the second week. (8)
Variola is a DNA virus and a member of the genus Orthopoxvirus, among the largest and most complex known viruses. Smallpox virions are characteristically brick-shaped with a diameter of 200 nanometers. The variola virus is extremely stable in aerosolized form under conditions of cool temperatures, low humidity, and protection from ultraviolet light. (9) Although the infectious dose of aerosolized variola is not known, a 1970 outbreak in Germany demonstrated that significant transmission can occur from a single case through a hospital ventilation system. (10)
Whether previously vaccinated persons retain immunity is not known. A monograph by Hanna published in 1913 examined 1,163 cases from the 1902-1903 smallpox outbreak in Liverpool, England. The study demonstrated that immunity waned over time, yet protection remained significant even after decades. (11)
A 1972 study by Mack of 680 cases occurring between 1950 and 1971 provides the most substantive data regarding mortality and waning immunities. The study revealed mortality rates of 1.4% in persons vaccinated 1 to 10 years before exposure, 7% in persons vaccinated 11 to 20 years before exposure, 11% in persons those vaccinated more than 20 years before exposure, and 52% among those who were unvaccinated. (12) A very small recent study at the University of North Carolina, however, revealed different results: Of 13 persons vaccinated as many at 35 years ago, all showed a "robust" immune response. (13)
Experts estimate that at least 90% of the US population are fully susceptible to smallpox, although as many as 20% of adults have some degree of protective immunity. The degree to which these data reflect real-world circumstances is questionable, but even a small outbreak could trigger widespread demand for vaccine. (14)
Vaccine risks and benefits
Vaccinia, a related orthopoxvirus, is used for immunization and provides protection against all orthopoxviruses. Although never measured in controlled trials for obvious reasons, the efficacy of the vaccine is estimated to be 80% to 90%. (4) In addition to conferring primary immunity, administration of the vaccine within 4 days after exposure to the smallpox virus can minimize the severity of disease or prevent it from developing. (15)
Reactions and side effects from vaccination are wide-ranging and can vary among persons. Fever occurs in approximately 70% of children 4 to 14 days postvaccination, and approximately 15% to 20% will have fever 102 degrees F. or higher. Fever is less common in adults. Autoinnoculation, the appearance of lesions distant from the inoculation site, occurs in 529 cases per 1,000,000 vaccinations and accounts for nearly half of all complications related to primary vaccination. (16) Mild erythematous or urticarial rashes, more serious bullous erythema multiforme, and even fulminant Stevens-Johnson syndrome have been reported.
In life-threatening reactions, moderate or severe rash occurs in 39 cases per 1,000,000 vaccinations, generalized vaccinia infection occurs in 212 cases per 1,000,000 vaccinations, and postvaccinial encephalitis occurs in 3 to 12 cases per 1,000,000 vaccinations. These reactions are more common after primary vaccination in infants. Fatal complications occur in 1 per 1,000,000 primary vaccinations and in 0.25 per 1,000,000 secondary vaccinations. (17) Death is most frequently caused by encephalitis.
Vaccinia immune globulin (VIG) can be used to treat severe cutaneous reactions. By conservative estimates, VIG stockpiles are adequate for reactions resulting from only 4 to 6 million vaccinations, one tenth the amount needed for a smallpox outbreak. Stockpiles would be rapidly exhausted, leaving clinicians unable to treat severe reactions. (18)
Those at greater risk for serious side effects from the vaccinia (smallpox) vaccine include pregnant women, immunocompromised patients, and persons who have atopic dermatitis or eczema. Transmission of vaccinia virus to immunocompromised persons could result in serious infection and death. During a smallpox outbreak, however, the protection against smallpox outweighs the risk associated with the vaccine.
Vaccine availability
Optimistic estimates are that at least 40 million doses of vaccine are needed to respond effectively to a smallpox outbreak in the United States. (17) Currently, there is no commercially available vaccinia vaccine. Vaccinia vaccines produced by Wyeth and Aventis Pasteur are available under Investigational New Drug protocols held by the Centers for Disease Control and Prevention (CDC). In October 2001, the federal government contracted with Acambis and Acambis-Baxter Pharmaceuticals to produce at least 209 million doses of smallpox vaccinia vaccine. This new vaccine, expected to be available near the end of 2002 or shortly thereafter, will be produced in cell cultures by new techniques that may result in a small reduction in some adverse events. These live vaccines will be administered with bifurcated needles creating a localized vaccine "pock" (see Figures below).
Federal guidelines
In light of the limited supply of the vaccine and VIG, the CDC currently does not recommend vaccination of any group other than persons who work with orthopoxviruses (variola, vaccinia, monkey pox, and cowpox) in a laboratory and others who have potential exposure to orthopoxviruses. The CDC Advisory Committee on Immunization Practices (ACIP) issued draft supplemental guidelines recommending against mass vaccination of the general public but supporting pre-outbreak vaccination of selected personnel in public health facilities and at designated smallpox care facilities. (18) How and when this will happen is yet to be determined. President Bush was expected to announce the details of the federal government's vaccination plan after this article went to press.
The CDC's primary strategies to control an outbreak include isolation of possible cases beginning at the onset of fever and implementation of a "ring vaccination" strategy, in which the vaccine is given first to persons presumed infected, then to persons who had been or could have been exposed to an infected person, and then to those who may have had contact with contacts of an infected person. This approach creates a "ring" of vaccinated people around those who were initially infected and is a strategy credited with eradication of the disease. The size of the outbreak and availability of the vaccine guide decisions for supplemental voluntary vaccination.
The CDC has protocols for rapid and simultaneous delivery of vaccinia vaccine to every state within the United States within 12 to 24 hours, with priority given to states with confirmed cases. State and local bioterrorism and public health agencies are charged with developing and implementing response plans for the rapid distribution and appropriate administration within their own geographic jurisdiction.
Conclusion
The United States is not currently in an ideal position to respond to an intentional smallpox release, but it is rapidly moving in the right direction. The risk for deliberate release of smallpox as a bioterrorism weapon remains low. Persons previously vaccinated may be better protected than originally assumed. The CDC continues to raise appropriate levels of awareness in law enforcement, customs and immigration, first responders, health care providers, and the general public and has recently released to state agencies a detailed primer on setting up clinics for mass vaccinations.
At this time, doses or resources to vaccinate the entire population, and, therefore, resource allocations must be made. Current stocks of vaccine and VIG should be utilized for highly selected groups of essential first-responder teams and the balance held in reserve and utilized only in the unlikely event of an intentional release of smallpox. Efforts should concentrate on the strengthening of federal, state, and local surveillance and response capacities and capabilities.
Under current circumstances, vaccination of the general public is not suggested because the potential benefits of use of the vaccine are outweighed by both vaccination complications and by this country's larger public health mandates. This conclusion should be considered fluid and should be scrutinized regularly, especially after larger stocks of safer vaccine become available.
Resources
References (underlined references will link you to PubMed or source article)
1. Kortepeter M, Eitzen E, McKee K, editors. USAMRIID's Medical Management of Biological Casualties Handbook. 4th ed. Fort Detrick, Frederick, MD: U.S. Army Medical Research Institute of Infectious Diseases; 2001.
2. Henderson, DA, Moss B. Smallpox and vaccinia. In: Plotkin SA, Orenstein WA, editors. Vaccines. 3rd ed. Philadelphia: WB Saunders; 1999. p. 74-97.
3. Albert MR, Ostheimer KG, Breman JG. The last smallpox epidemic in Boston and the vaccination controversy, 1901-1903. N Engl J Med. 2001;344:375-379. (Or try this alternate reference)
4. Centers for Disease Control and Prevention. Vaccinia (smallpox) vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR. 2001;5(RR-10):1-25.
5. Institute of Medicine. Assessment of future scientific needs for live variola virus. Washington DC: National Academy Press; 1999.
6. Leitenberg M. The biological weapons program of the former Soviet Union. Biologicals. 1993;21:187-191.
7. Fenner F, Henderson DA, Arita I, Jezek Z, Ladnyi ID. Smallpox and its eradication. Geneva, Switzerland: World Health Organization; 1988: p. 1460.
8. Henderson DA. Smallpox: clinical and epidemiologic features. Emerg Infect Dis. 1999;5:537-539.
9. Harper GJ. Airborne micro-organisms: survival test with four viruses. J Hyg. (Lond) 1961;59:479-486.
10. Wehrle PF, Posch J, Richter KH, Henderson DA. An airborne outbreak of smallpox in a German hospital and its significance with respect to other recent outbreaks in Europe. Bull World Health Org. 1970;43;669-679.
11. Hanna W, Baxby D. Studies in smallpox and vaccination. 1913 [classical article]. Rev Med Virol. 2002;12:201-209.
12. Mack TM. Smallpox in Europe, 1950-1971. J Infect Dis. 1972;125:161-169.
13. Frelinger JA, Garba L. Response to smallpox [letter]. N Engl J Med. 2002;347:689-690.
14. Henderson DA. Risk of a deliberate release of smallpox virus; its impact on virus destruction. Working paper - WHO ad hoc Committee on Orthopoxvirus Infections. January 1999.
15. Krugman S, Ward RW, editors. Smallpox and vaccinia. In: Infectious Diseases of Children. 2nd edition. St Louis: CV Mosby Company; 1960: p. 275-293.
16. Lane JM, Ruben FL, Neff JM, Millar JD. Complications of smallpox vaccination, 1968. N Engl J Med.1969;27:1201-1208.
17. Meltzer MI, Damon I, LeDuc JW, Millar JD. Modeling potential responses to smallpox as a bioterrorist weapon. Emerg Infect Dis. 2001;7:959-969.
18. Centers for Disease Control and Prevention. Draft supplemental recommendations of the ACIP: Use of smallpox (vaccinia) vaccine, June 2002. Available from: URL: http://www.bt.cdc.gov/agent/smallpox/vaccination/acip-guidelines.asp.
CME Approval Information
This program has been reviewed and is approved for a maximum of one hour of clinical Category I (Preapproved) CME credit by the American Academy of Physician Assistants. Physician assistants should claim only those hours actually spent participating in the CME activity.
This program was planned in accordance with AAPA's CME Standards for Lecture-Learner Programs and for Commercial support of Lecture-Learner Programs.
Approval is valid for one year from the issue date of January 15, 2003. Participants may submit the self-assessment at any time during that period.
Successful completion of the post-test (minimum score: 70%) is required to earn Category I (Preapproved) CME credit. The post-test must be completed on-line and is available at no charge to members.
Link to Post-test
