Smallpox Vaccination

Keywords

Angina: chest pain caused by lack of blood flow to the heart

Bioterrorism: terrorism using biologic agents

Eczema: an inflammatory reaction of the skin in which there are typically tiny blister-like raised areas in the first stage followed by reddening, swelling, bumps, and crusting of the skin

Encephelitis: inflammation of the brain

Gangrene: the death of body tissue due to the loss of blood supply to that tissue, sometimes permitting bacteria to invade it and accelerate its decay

Myocarditis: heart inflammation

Myopericarditis: a combination of myocarditis and pericarditis

Pericarditis: inflammation of the membrane covering the heart

Smallpox vaccine: vaccine containing a live virus called vaccinia used to prevent smallpox

Vaccinia: a cutaneous or systemic reaction to vaccination with the smallpox vaccine

Variola Virus: medical term for smallpox; a highly contagious and frequently fatal viral disease characterized by a biphasic fever and a distinctive skin rash that causes pock marks

 

Purpose

On December 12, 2002 the Bush administration unveiled a National Smallpox Vaccination Program as the centerpiece of the administration’s effort to protect the nation against bioterrorism. The program’s principal goal “is the achievement of a preparedness capacity” to respond to a potential smallpox outbreak. [1] The initial phase called for voluntary vaccination of 450,000 health care workers who would form Smallpox Response Teams. These teams would be responsible for investigating outbreaks, caring for patients, and vaccinating members of the public who may have been exposed to the virus. After the first phase, a comprehensive evaluation of the program and its outcomes would be completed to assess the program’s safety and improve implementation practices. The second phase would then inoculate an additional 10 million health and emergency workers; and the final phase would inoculate the rest of the population, if a biological attack occurred. [2] The following table provides an outline of individuals to be vaccinated under each program phase.

Group to be vaccinatedApproximate
no. of persons
Status of
vaccination
Time of
vaccination
Program
phase
Selected members of the armed forces and personnel who serve in high-risk parts of the world500,000MandatoryInitiated 13 Dec 2002I
Selected personnel from the US State Department who serve overseasVoluntaryI
Public health response and health care teams450,000VoluntaryLate January 2003I
Other medical care providers and first responders10,000,000VoluntaryII
General publicNot recommended at present; would be administered under oversight of a clinical trialPossibly in late 2003 or 2004III

Source: Donald A. Henderson, etal, “Smallpox Vaccination in 2003: Key Information for Clinicians,” Clinical Infectious Diseases, Vol. 36: 883-902, (2003).

Now, four months after the campaign has commenced, impediments to participation have brought it to a virtual standstill. The program has proven to be less popular, medically riskier and more expensive than anticipated. Many health care professionals maintain the benefits of the program do not justify the risks and recommend it be delayed until there is clear evidence a smallpox attack is imminent.[3] Furthermore, more than a dozen states have suspended vaccination until more is learned about its recent link to myocarditis and heart attacks.[4]

What measures can be taken to bolster this policy’s waning success, and should they be taken? Initiating a large-scale vaccination effort against a disease that is no longer a natural threat presents many challenges for the medical community. A look at the history of smallpox in the U.S. and the ensuing smallpox vaccination program will provide a basis for addressing this question.

Background

Before 1971, smallpox immunization was routine in the U.S. Vaccination was required for school-aged children and adults often received a booster inoculation before traveling overseas. Studies dating back to the 1960’s indicate that for every one million people vaccinated there were 1 to 2 deaths and between 14 and 52 serious and potentially life-threatening adverse events.[5] At the time, these risks were deemed acceptable to control this contagious and often fatal disease.

By 1972 the risk of smallpox in the U.S. was sufficiently remote that vaccinations were discontinued. Eight years later, the World Health Organization (WHO) announced the disease had been eradicated worldwide. Presently, about one-third of the U.S. population has never been immunized, and it is unclear how much protection remains for people who were inoculated decades ago.[6]

Recent events, including the terrorist attack of September 11, 2001, followed by the dissemination of anthrax spores through the mail, and the second Gulf War, have catalyzed the U.S. government to prepare for a variety of threats. One perceived threat is the use of smallpox as a biological weapon. In a speech introducing the smallpox program, President Bush expressed the need to prepare for bioterrorism, “Our government has no information that a smallpox attack is imminent. Yet it is prudent to prepare for the possibility that terrorists… who kill indiscriminately would use diseases as a weapon.”[7] This marked the first time a U.S. vaccination campaign had been launched not simply for disease prevention, but to advance national security.[8]

On the spectrum of threats confronting the nation, officials and security analysts believe a smallpox attack is a low probability risk. Although only two countries, the U.S. and the former Soviet Union, are known to possess the variola virus, intelligence experts suspect that hostile nations or terrorist groups may have acquired stocks which could be spread in aerosolized form or through person-to person contact.[9]

In response to this threat, the vaccination campaign was launched on January 24, 2003. Officials had hoped to complete the first phase and consequently inoculate about 450,000 first response volunteers by February 24, 2003. But by then only 12,690 volunteers had come forward. To date, that number has risen slightly, to about 32,000, or 7 percent of the goal.[10] Despite plans to continue the program, a number of impediments to participation remain.[11]

National Smallpox Vaccination Program – Policy Formation & Implementation

Hesitancy of Medical Community. Implementation of the smallpox vaccination program is facing two major challenges. One is the program schedule, and the other is hesitancy of the two main groups involved in the program; those needed to implement it and those needed to volunteer to be vaccinated. The Institute of Medicine (IOM), many hospitals, and several large health care unions, including the American Nurses Association (ANA), have expressed concerns regarding the aggressive schedule, liability protection, safety, and workers compensation.[12]

A June 2002 poll by the Association of State and Territorial Health Officials (ASTHO) revealed that 91 percent of their members opposed any policy that would allow the general public to be vaccinated against smallpox before an attack. In October the Advisory Committee on Immunization Practices (ACIP), a body that serves as chief advisor to the government on vaccine matters, rejected the proposal to vaccinate 10 million people, backing only the plan to immunize 450,000 first response workers.[13] The IOM advisory panel warned “a hasty launch may mean insufficiently trained vaccinators and uninformed vaccines, leading perhaps to an increased likelihood of poor outcomes.”[14] Despite recommendations from these groups, including the government’s own vaccine advisory committee, to approach the campaign more cautiously, the administration was inclined to move forward without their support.[15]

Program Schedule. In collaboration with 62 states, local and territorial governments, CDC is responsible for implementing the vaccination program. The program plan is embodied in a complex set of federal guidance documents and individual CDC-approved plans from the 62 jurisdictions, from which CDC has defined a program schedule and targets.[16]

The schedule is challenging and has placed heavy demands on CDC and the jurisdictions, which were required to develop plans and targets for the first stage in less than three weeks. CDC provided some guidance about the types of workers to be vaccinated on each team; but provided no guidance for estimating the number of workers within a jurisdiction needed to achieve preparedness.[17]

The program’s goal of vaccinating 450,000 individuals within one month pressured jurisdictions to proceed with little guidance. CDC’s efforts to quickly produce and distribute guidance documents, such as implementation materials, education, and training materials has led to difficulties, confusion and safety concerns. For instance, in its haste, CDC provided conflicting information about the precise method for administering the vaccine. In many cases key materials, such as informed consent for vaccination documents, were not available until after the start of inoculation.[18] Materials used to educate and screen volunteers were not tested for comprehensibility to ensure that the screening process would function as intended. Moreover, CDC did not host training for adverse event monitoring until two days before the program began and did not issue detailed guidance about the adverse event monitoring system until two weeks after vaccination had begun.[19]

The program schedule has also pressured the advisory process that CDC set-up through IOM, to help ensure the program achieves its goals safely. IOM’s first report was released just eight days prior to beginning vaccination, providing little time for CDC to review and respond to their recommendations.[20]

Focus on Preparedness. The administration has been criticized for pushing to vaccinate as many people as possible, instead of focusing on preparedness as the program goal. Increasing the number of vaccinated people may contribute to that goal, but does not necessarily mean the nation will be more prepared to respond to an attack.[21]

To date, only about 32,000 of the 450,000 individuals targeted for the first phase have been vaccinated. In light of the weak response, the administration is considering a huge reduction in its targets. They believe a smaller number, perhaps as few as 50,000, could provide sufficient capacity to respond to an outbreak.[22] But as of late April, CDC had not set a new nationwide target, nor had it revealed how it calculated the lower figure. Although CDC announced it would provide guidance for revising targets, and subsequently request revised plans from the jurisdictions, it has not done so.[23]

Figures compiled by the government show about half of all people vaccinated to date are in eight states; California, Florida, Minnesota, Missouri, Nebraska, Ohio, Tennessee and Texas.[24] Until the revised targets are set, it is impossible to know if and where additional immunizations are needed to achieve preparedness.

Need for Evaluation. In an effort to rapidly increase the number of people vaccinated, the administration decided to merge the first two phases of the program.[25] On March 6, 2003 states were instructed to expand voluntary vaccination to all health care workers and first responders as a continuation of the first phase rather than a distinct second phase of vaccination. This deviated from the original plan, to complete and evaluate the first phase before moving on to inoculate millions of emergency responders. Many jurisdictions were baffled by the major policy change that was instituted with no formal announcement or written guidelines.[26] IOM criticized CDC for not “evaluating the effectiveness of implementation and the safe use of the vaccine” before moving ahead to the next phase.[27]

Presently, many health care workers and officials do not consider themselves at high risk of a smallpox attack and are confident that in the event of an outbreak ring vaccinations can take place quickly enough to protect them and the public.[30] Many health officials argue this intervention was not given due diligence before vaccination began.[31]

National Smallpox Vaccination Program – Policy Implications

Health Risks. The smallpox campaign is unique in the history of civilian immunization programs because it is not a public health program in the traditional sense, but rather a program of bioterrorism preparedness.[32] In past programs, the relatively small and known risks of adverse events associated with vaccines have been justified based on the need to reduce a known incidence of disease. For smallpox, such justification no longer exists.[33]

Historical studies indicate that inoculations will trigger a small but significant number of life-threatening reactions, including gangrene, encephalitis, and severe skin infections, and in some cases even death.[34] Today, immuno-suppressed patients, organ transplant recipients, and people infected with HIV and AIDS constitute new, vulnerable groups that pose unknown complications.[35] Therefore, mass vaccination of the U.S. population today will likely result in a higher occurrence of death than historical studies reveal.[36]

Most recently, the vaccine’s link to over thirty cases of heart complications has caused the program to be suspended completely in twelve states, further hampering the program’s progress.[37] According to CDC reports, careful monitoring of individuals who recently received the vaccination indicates the vaccine may cause myocarditis, pericarditis, myopericarditis, and angina.[38]

The program’s aggressive schedule has also presented some health risks. In its haste to stay on schedule, CDC has distributed contradictory screening materials for those considering vaccination. For example, some CDC materials specifically state that certain asthma patients taking immune-suppressing drugs should be excluded while others do not mention asthma patients at all.[39] The differences in these materials create confusion for individuals trying to determine if they should be excluded from vaccination. Furthermore, mistakes like this raise concerns about whether the costs to volunteers and their families will be covered should they experience an adverse event and require time off work.[40]

Compensation. When the program was first initiated, many health care workers were concerned about the lack of comprehensive, adverse event compensation and the implications of possible administrative leave or duty reassignment.[41] These concerns deterred many health care workers from participating in the program, and proved to be a barrier to the program’s success.

On April 11, 2003 after months of deliberation, Congress approved a measure to compensate individuals for adverse events. Despite disputes over the adequacy of the package, Congress, lead by Congressional Republicans, settled on a compensation plan in hopes that it would increase the medical community’s participation.[42]

Under the bill, people who are permanently disabled as a result of receiving the vaccine would be eligible for up to $50,000 annually in lost wages with no cap on the amount of damages they could collect during their lifetime. Partially disabled recipients would be eligible for the same compensation, up to a cap of $262,000.[43]

Nevertheless, many groups feel the compensation bill is inadequate. A spokesperson for ANA pointed out, the bill is “not the complete assurance we needed to really promote the smallpox vaccination program among our nurses.”[44] In sum, the compensation package is considered by many to be too little, too late.

Resource Waste. The program has also proven to be a drain on human, financial and medical resources. Since January 2003, CDC has shipped 284,000 doses of the vaccine to states. With an average shelf life of 60 days after the vial is opened, much of the distributed vaccine has lost its potency, and many doses are in danger of spoiling.[45] The program also risks wasting a huge quantity of medical resources that may be better used for the treatment and prevention of other existing diseases or to thwart a biological attackof another kind, such as anthrax.[46]

Mass vaccination could also have a devastating effect on the nation’s blood supply. Although not official, the deferral period for donating blood after receiving the inoculation could be up to four weeks after vaccination. Vital blood products, such as platelets, which have a five-day shelf life, would be quickly depleted during the deferral period.[47]

According to an analysis by ASTHO, immunization from screening through follow-up has cost an average of $265 per person, more than twice the $85 budgeted by federal officials.[48] CDC expects jurisdictions to redirected funds made available through bioterrorism cooperative agreements to pay for the program. However, state and local health officials report that as of March 2003 most of these funds were already committed to other bioterrorism activities; on average only 7 percent of these funds remain.[49] Thus in order to meet program demands, jurisdictions need to divert funds not only from other bioterrorism preparedness activities, but also from other public health services.

According to a recent study by the National Association of County and City Health Officials (NACCHO), of 539 health departments, 53 percent reported human resources for other public health services such as childhood immunization have been diverted to smallpox efforts.[50] The program could also leave the nation unprepared in the event of a different variety of biological warfare. According to Leslie Beitsch, Oklahoma’s health chief “the entire group of people we’ve employed to work on bioterrorism has been diverted to work exclusively on smallpox. If we started getting anthrax letters through the mail again, we would probably not be well-positioned to respond to those.”[51]

Discussion

The planning of public health interventions, particularly immunization programs, requires cautioned and deliberate consideration of the risks of the intervention compared to its benefits.[52] IOM reflected in their first report, “public health interventions are undertaken with recognition of some benefit to some individuals, no effect on others, and the possibility of some weighed risk to a small percentage of the population…with the expectation of overall benefit to the population receiving the intervention.”[53] The cost-benefit context of the vaccination program assumes the risks of the vaccine are significant, while the chance of an attack is very low; therefore the perceived benefit carries considerable risk.[54] This reality highlights the importance of both, (1) preparedness, to ensure optimal benefit to the public, and (2) evaluation to ensure the lowest risk from vaccine.[55]

1.To ensure preparedness, CDC should provide guidance and adjusted targets to jurisdictions to guarantee that smaller or fewer teams will be organized and distributed in a manner that will provide adequate response capacity.[56] Adjusting target numbers will also help mitigate jurisdiction’s financial and human resource concerns and allow them to better forecast spending and staffing. This may also be the incentive needed to engage the medical community and encourage them to take ownership of the program. The program’s feeble success to date has confirmed that their support is paramount to its success. Any policy without key stakeholder endorsement is destined for ruin.

2. The program should proceed cautiously, allowing continuous opportunity for adequate and thoughtful deliberation, analysis, and evaluation. CDC should conduct an evaluation at the national, state, and local level before expanding program activities; or an evaluation should at least occur simultaneously to ensure that lessons are learned as the program progresses. A comprehensive evaluation of the program and its outcomes will improve implementation and help protect vaccines and the public.[57] An evaluation may also help to assuage fears about adverse events and increase individual’s willingness to participate in the program.

3. Finally, the public should be reassured that efforts are in progress to protect them in the event of a smallpox attack. Because there has been a lot of ambiguity about the program’s timelines and evaluation of preparedness, it is possible to perceive the small number of individual’s vaccinated to date as a detriment to the first line of response. Such conclusions are not warranted. Every effort should be made to communicate clear, timely information to the public.[58]

Conclusion

The threat of a smallpox attack has not increased since the vaccination program was initiated four months ago. Given the unlikelihood of an attack, the program does not merit being pursued to the detriment of other public health programs and bioterrorism preparedness efforts. Instead, the program should be evaluated to assess if and how vaccinations to date have contributed to the goal of preparedness and also to determine exactly how many immunizations are needed in order to achieve preparedness. Every effort should be made to protect the vaccines and the public.


[1] LJ Anderson, “Smallpox Preparedness”, presented to the American College of Preventive Medicine Meeting on February 19-23, 2003.

[2] “Bush Announces Preventive Smallpox Vaccination Program,” U.S. Department of State International Information Programs Press Release, December 13, 2002.

[3] Ceci Connolly, “U.S. Smallpox Vaccine Program Lags,” The Washington Post, April 13, 2002, p. A3.

[4] Ceci Connolly, “U.S. Smallpox Vaccine Program Lags,” p. A3.

[5] General Accounting Office, Smallpox Vaccination: Implementation of National Program Faces Challenges: Report GAO-03-578, April (2003).

[6] Connolly, “Smallpox Vaccine Comes Full Circle,” The Washington Post, March 16, 2003, p. A28.

[7] White House Press Release: Smallpox Vaccination Program, December 14, 2002.

[8] David Brown, “In Vaccination Plan, A World of Unknowns,” The Washington Post, December 14, 2002, p. A01.

[9] Connolly, “Smallpox Vaccine Comes Full Circle,” p. A28.

[10] Connoly, “Smallpox Vaccine Comes Full Circle”, p. A28.

[11] Institute of Medicine, Review of the Centers for Disease Control and Prevention’s Smallpox Vaccination Program Implementation: Letter Report #2, (Washington, DC: The National Academies Press, 2003).

[12] Connolly, “U.S. Spurns Smallpox Vaccine Delays,” The Washington Post, January 18, 2003, p. A3.

[13] Brown, “In Vaccination Plan, A World of Unknowns,”p. A1.

[14] Connolly, “U.S. Spurns Smallpox Vaccine Delays,”p. A3.

[15] Ceci Connolly, “Second Vaccinated Health Worker Dies of Heart Attack,” The Washington Post, March 28, 2003, p. A09.

[16] General Accounting Office, Smallpox Vaccination: Implementation of National Program Faces Challenges: Report GAO-03-578, April (2003).

[17] General Accounting Office, Smallpox Vaccination,” (2003), p. 16.

[18] General Accounting Office, Smallpox Vaccination,” (2003), p. 14.

[19] General Accounting Office, Smallpox Vaccination,” (2003), p. 15.

[20] General Accounting Office, Smallpox Vaccination,” (2003), p.9.

[21] Institute of Medicine, Letter #2, (2003), p. 4.

[22] Robert Pear, “AFTEREFFECTS: Biological Defense: Report Faults Federal Officials for Problems in Smallpox Program,” The New York Times, April 30, 2003, p. A16.

[23] General Accounting Office, Smallpox Vaccination,” (2003), p.5.

[24] Pear, “AFTEREFFECTS: Biological Defense,” p. A16.

[25] Connolly, “Second Vaccinated Health Worker Dies of Heart Attack,” p. A09.

[26] Ceci Connolly, “U.S. Smallpox Vaccine Program Lags,” p. A3.

[27] Institute of Medicine, Letter #2, (2003), p. 3.

[28] Ben Harder, “The vaccinia dilemma: smallpox shot poses modest danger, uncertain benefit,” Science News, April 5, 2003, Vol 163: i14 (2003), pp. 218-221.

[29] William Foege, “Can Smallpox Be as Simple as 1-2-3?” The Washington Post, December 29, 2002, p. B05.

[30] Institute of Medicine, Letter #2, (2003), p. 2.

[31] Harder, “The vaccinia dilemma,” p. 219.

[32] General Accounting Office, Smallpox Vaccination, (2003), p. 6.

[33] General Accounting Office, Smallpox Vaccination, (2003), p.3.

[34] M.A.J. McKenna, “Grady’s workers won’t be given smallpox shot yet: Risk outweighs threat, hospital says,” The Atlanta Journal-Constitution, December 17, 2002.

[35] Anthony S. Fauci, M.D, United States Senate :Testimony Before the Committtee on Appropriations Subcommittee on Labor, HHS, Education and Related Agencies, (2003).

[36] Thomas Mack, M.D., M.P.H., “A Different View of Smallpox and Vaccination,” New England Journal of Medicine, Vol 348[5], (2003), pp.460-463.

[37] Harder, “The vaccinia dilemma” pp. 220.

[38] CDC, “Interim Smallpox Fact Sheet: Smallpox Vaccine and Heart Problems,” n.d. Available at www.cdc.gov.

[39] General Accounting Office, Smallpox Vaccination,” (2003), p. 17.

[40] General Accounting Office, Smallpox Vaccination,” (2003), p. 21.

[41] Institute of Medicine, Letter #2, (2003), p. 2.

[42] Ceci Connolly, “Aid for Those Hurt by Vaccine Argued,” The Washington Post, April 3, 2003, A08.

[43] American Health Line, “Politics & Policy: Smallpox: House, Senate Approve Compensation Program,” April 14, 2003.

[44] American Health Line, “Politics & Policy: Smallpox,” April 14, 2003.

[45] Connolly, “U.S. Smallpox Vaccine Program Lags,” 2002, p. A3.

[46] Richard Harling, “Further information in support of a selective smallpox vaccination policy,” Eurosurveillance Weekly, Vol 7[1], (2003). Online at www.eurosurveillance.org.

[47] Paul Raslavicus, M.D, CAP President Letter to HHS Secretary of Federal Smallpox Vaccination Policy, (Dec 12, 2002). Online at www.cdc.gov/ncidod/EID/vol7no6/meltzer.htm.

[48] Connolly, “U.S. Smallpox Vaccine Program Lags,” p. A3.

[49] General Accounting Office, Smallpox Vaccination,” (2003), p. 17.

[50] Connolly, “U.S. Smallpox Vaccine Program Lags,” p. A3.

[51] Ceci Connolly, “Smallpox Campaign Taxing Health Resources,” The Washington Post, March 10, 2003, A04.

[52] Institute of Medicine, Review of the Centers for Disease Control and Prevention’s Smallpox Vaccination Program Implementation: Letter #1, (Washington, DC: National Academies Press, 2003).

[53] Institute of Medicine, Letter #1, (2003), p.4.

[54] Institute of Medicine, Letter #1, (2003), p.4.

[55] Institute of Medicine, Letter #2, (2003), p. 3.

[56] General Accounting Office, Smallpox Vaccination,” (2003), p. 8.

[57] Institute of Medicine, Letter #2, (2003), p. 7.

[58] Institute of Medicine, Letter #2, (2003), p. 9.