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Smallpox: Threat, Vaccine, and US Policy
Part IV of a Six-Part Series

View: Parts I & II | Part III | Part IV | Part V | Part VI

View the entire series as a single PDF file. PDF format, 36 pages, 539 kb.

Illustration showing vaccination for smallpox. [Source: World Health Organization] View the entire series as a single PDF file. PDF format, 36 pages, 539 kb.

By Richard Pilch, M.D.

[The author would like to thank Dr. Raymond A. Zilinskas for his review of this segment.]

IV. The Current US Vaccination Strategy

As outlined in the Introduction to this series, the current US vaccination plan essentially consists of five phases. Phases one through three, outlined by President Bush on December 13, 2002, are pre-event measures meant to minimize the impact of a smallpox outbreak should one occur (in view of the disease's eradication, the word "outbreak" here refers to the appearance of one or more confirmed cases of smallpox). Phases four and five, based on the vaccination guidelines of the CDC, outline measures to be implemented in the event of just such an outbreak anywhere in the United States. The five phases of the vaccination plan are addressed below, with particular attention paid to the rationale behind and the concerns surrounding each phase's inclusion in the overall strategy.

Phase One

The first phase of President Bush's plan calls for (1) the voluntary vaccination (begun January 2003)[1] of approximately 500,000 front-line health workers and first responders serving on specialized "Smallpox Response Teams;" and (2) the mandatory vaccination by the Department of Defense (DOD) of some 500,000 military and civilian personnel who are or may be deployed in "high threat" locations, as well as the voluntary vaccination of a limited number of additional personnel stationed at certain overseas embassies. Because the goal of this report is to discuss the civilian vaccination plan, the DOD component of phase one will not be considered. However, it bears noting in brief that deployment of personnel in certain overseas areas, particularly the Middle East, carries what many analysts believe to be a higher risk for exposure to the virus and thus a need for preventive vaccination. The counterargument here is that the risk of a boomerang effect on the perpetrator's own population makes such use questionable, whereas remote delivery in the United States or United Kingdom carries no such risk in the short term.

The Smallpox Response Teams of phase one are meant to consist of any individuals who might be involved in the identification and management of a smallpox outbreak. For example, the Advisory Committee on Immunization Practices (ACIP) has recommended the inclusion of "emergency room physicians and nurses, intensive care unit staff, infectious disease specialists, medical personnel with smallpox experience, and other medical specialties, including dermatologists, pediatricians, ophthalmologists, pathologists and surgeons. In addition...radiology technicians, respiratory therapists, and proactive security and housekeeping personnel [should be included]."[2] The ACIP has further recommended that every hospital in America establish not one but two Smallpox Response Teams in order to maximize preparedness.

These teams are, as stated, in place to initiate response efforts should they be required. However, this is not their only purpose. In fact, ensuring an adequate response may well be only a secondary consideration at this stage. There is a much graver concern that is being addressed in the civilian component of phase one: the need to protect those individuals most likely to be the first ones exposed in the event of an outbreak. Illustrating this concern is the fact that in the 49 documented outbreaks of Variola major in Europe between 1950 and 1971, more than half of the cases occurred within a medical setting and greater than 50 percent of those cases involved medical personnel and hospital staff such as physicians and nurses.[3]

In the event of an outbreak, the highest likelihood is that an infectious smallpox patient (or patients) will present to either his or her family practitioner or a hospital emergency room complaining of such prodromal symptoms as fever, headache, and backache. The rash may or may not be present upon initial presentation. Because respiratory transmission of the virus is only possible after the lesions of the rash have formed and broken open in the oropharynx, the appearance of the external rash generally signifies contagiousness. However, the internal rash ("enanthem") precedes the external rash, such that a patient may already be exhaling viral particles in respiratory droplets up to 24 hours before a visible rash forms on the skin.[4] Thus, anyone who has had face-to-face contact with an infected patient any time after the onset of fever is considered at risk for infection.[5] A physician may therefore be unaware of being at risk when he or she first sees the patient. Further, at the earliest phase of the outbreak, before awareness has developed, smallpox may not even be considered in the physician's initial differential diagnosis (a list of possible diagnoses to be systematically ruled out). Without such awareness or a high index of suspicion on the part of the treating physician, identification, management, and isolation of the infected individual may be delayed, increasing the likelihood of transmission to the patient's direct caretakers and other personal, occupational, and incidental contacts in the area.

Pre-event vaccination in the above scenario would not only serve to protect these at-risk caretakers from the disease; it would also allow for both immediate management of the infected individual and rapid treatment of any contacts. At this stage of the disease, management of the infected individual is limited to supportive care (IV fluids and pain control, for example), with the lethality rate essentially fixed at approximately 30 percent. Vaccination is of no value once symptoms appear. But supportive care is of inestimable value to an ailing patient and his or her loved ones, and thus the capacity to provide it is an absolute necessity.

Contacts are a different story. Upon making the diagnosis, the public health authority of the city or county where the first case is diagnosed has a narrow window of opportunity in which to identify and vaccinate all of the infected individual's household and close-proximity (less than 2 meters) contacts, as well as additional response personnel at risk of exposure to the virus, in order to limit further spread of the disease. These additional response personnel include healthcare workers responsible for the care or transportation of suspected or confirmed cases; laboratory personnel responsible for collecting or processing clinical specimens of such cases; and laundry or medical waste handlers at the facility where the diagnosis has been made.[6] In such a case, i.e., the presentation in a hospital setting of a patient infected with smallpox, the CDC also recommends that "consideration...be given to vaccination of all individuals present in the hospital setting during the time a case was present and not isolated in the appropriate manner in a room with ventilation separate from other areas of the hospital."[7]

The rapid administration of the vaccine to these high risk groups could mean the difference between life and death: data has indicated that vaccination of a contact within four days of exposure reduces the likelihood of that person becoming sick with smallpox or, should sickness occur, significantly reduces mortality.[8] This process is discussed in phase four below, but its implications are critical here. While suspicion of a smallpox case demands notification of the Center for Disease Control (CDC), an action which would lead to the rapid mobilization of teams of specialized CDC personnel, these personnel are only meant to assist and coordinate activities on the local front.[9] Local healthcare workers must therefore be prepared to act immediately after the initial diagnosis is made in order to save lives, and pre-event vaccination allows them to do so.

What happens if these individuals are not preemptively vaccinated? In the event of an outbreak, they would immediately receive the vaccine. A waiting period of approximately seven days is then necessary to ensure that the inoculation is successful (called a "take") and to allow for the development of protective immunological factors in the vaccinated individual.[10] Additionally, the vaccine, which has been known to cause fever in up to 70 percent of recipients 4 to 14 days after inoculation, may temporarily incapacitate these workers and thus hinder response measures that might otherwise allow for disease containment and the saving of lives.

On an individual level, the major disadvantage of phase one relates to the drawbacks of the vaccine itself, namely the potential for a significant number of serious adverse reactions and possibly even one or two deaths in the initial pool of recipients (including the DOD component of phase one). Being aware of this risk and knowing that the threat has not been established to any degree of certainty by the US (or any other) government, physicians and healthcare personnel across the country have been resisting vaccination, and entire hospitals have declined to participate.[11] More general drawbacks include the potential for (1) temporary paralysis of some hospital emergency rooms due to compounding side effects of the vaccine, and (2) widespread negative impact on public health as a result of the redirection of resources normally allocated toward other highly beneficial preventative and therapeutic healthcare modalities (discussed in Part VI of this series).

There is also a small but real possibility of inadvertent transmission of the vaccinia virus through normal work-related exposure from healthcare workers to unvaccinated patients, including patients contraindicated for the vaccine. This concern reflects the vaccine's recognized dangers (described in Part II), namely (1) the potential for spread of the live vaccine virus to individuals who come into contact with the inoculation site, and (2) the increased incidence of pathology in contraindicated populations (for example, those with a history of eczema, pregnant or breastfeeding mothers, or most notably immunocompromised persons, for whom a lethal outcome is a distinct possibility should such transmission occur).[12]

Despite these worrisome drawbacks, the potentially devastating impact of a smallpox outbreak in a population lacking "firewalls" suggests the need for some level of pre-event vaccination. Thus, the author supports President Bush's decision to implement phase one of the vaccination plan, an action that allows for (1) protection of those most likely to be initially exposed to the virus in the event of an outbreak; (2) immediate care of the first cases of the disease; and (3) rapid implementation of phase four vaccination, thus minimizing the number and severity of ensuing infections among exposed and at-risk individuals, reducing overall mortality, and significantly increasing the likelihood of disease containment.

Phase Two

In phase two, voluntary vaccinations will be extended to up to 10 million additional members of the healthcare and first responder communities. Presumably, this represents a large proportion of these individuals nationwide. Because the threat is not quantifiable to any appreciable extent, it is very difficult to assess the need for such widespread vaccination. However, based on historical data, it can be estimated that if all 10 million of these individuals were to accept vaccinations, over 10,000 might suffer serious complications and 10 otherwise healthy individuals might die. Of course, not everyone is expected to volunteer unless the threat is clarified by sources in the know. Regardless, these numbers illustrate yet again the very real risks of the current smallpox vaccine.

While the forces behind establishing phase two of the vaccination plan likely did so for a good reason, they have not shared such reason with the American public (and perhaps rightly so, which is a debate for another time). Therefore, a course of action with the potential for such adverse consequences does not seem justified when the threat remains so undefined, especially when the allocation of limited budgetary and human resources is taken into consideration (discussed in Part VI of this series).

Phase Three

In phase three, the vaccine will be offered on a voluntary basis to adult members of the general public, with careful screening provided in order to prevent vaccination of contraindicated individuals. Initially, this was presented to the American public as what essentially amounted to a rights issue: in an interview with Barbara Walters, President Bush stated, "I think it ought to be a voluntary plan. In other words, I don't think people ought to be compelled to make the decision which they [don't] think is best for their family."[13] Regardless, the driving logic behind phase three seems to be that its implementation will raise "herd immunity" such that in the event of introduction of the virus into our population, subsequent spread will be limited. Theoretically, this makes sense, but two questions persist: (1) how effective will the aforementioned screening measures be in identifying contraindicated persons; and (2) what approach can be taken to guarantee an informed decision on the part of those persons electing to receive the vaccine?

In general, the first step to identifying an individual as contraindicated for the vaccine is the thorough review of his or her medical history. The questions begin immediately. What of patients with a questionable history? What about the significant number of US citizens who have no primary care provider and thus lack a thoroughly documented medical history? How do we identify the individuals who have undiagnosed conditions such as eczema or atopic dermatitis, or may be immunocompromised in some fashion (for example, the CDC has estimated that 300,000 Americans are unknowingly infected with HIV)?[14] Further, because individuals living with contraindicated persons are also contraindicated for the vaccine, the web of uncertainty expands rapidly.

The vaccination of contraindicated individuals might be limited by the judicious implementation of certain laboratory tests, for example pregnancy or HIV testing for at-risk individuals. Such blanket screening measures are not recommended by the ACIP, however, and have not been approved at this time. The current guidelines read: "[b]efore vaccination, women of child-bearing age should be asked if they are pregnant or intend to become pregnant in the next four weeks. Women who respond positively should not be vaccinated. In addition, women who are vaccinated should be counseled not to become pregnant during the four weeks after vaccination. However, routine pregnancy testing of women of child-bearing age was not recommended. With respect to screening for HIV infection...[b]efore vaccination, potential vaccinees should be educated about the risks of severe complications from smallpox vaccine among persons with HIV infection or other immunosuppressive conditions. Persons who think they may have one of these conditions should not be vaccinated. The ACIP does not recommend mandatory HIV testing prior to smallpox vaccination, but recommends that 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."[15]

Even if blanket screening measures were employed, nagging problems would surely remain. For example, what is the recommended course of action in the event that a woman becomes pregnant after receiving the vaccine? The limitations of the ACIP's solution, education to avoid such an end, appear self-evident: given that noncompliance is a fact of life (as is failed contraception, etc.), what happens after conception, when "what's done is done?" Or what of the individual who cannot be relied upon to declare his or her own at-risk status for HIV and thus slips through the screening process without being tested? Sifting through such unreliable histories, like managing the sequelae of noncompliance, is part of life as a healthcare practitioner.

To address the issue of how best to provide citizens with adequate knowledge to make an informed decision on whether or not to receive the vaccine, one must consider the various approaches to educating the public. The Internet currently has excellent information resources, but certainly exposure to these resources is not universal. Television and radio broadcasts are a possibility, as is printed information in newspapers, mailers, and the like. But because the government is asking civilians to make what amounts to a life or death decision for themselves and their families, clearly the responsibility is on the government to ensure that an informed decision is made. Interestingly, responsibility may be exactly what the government was trying to avoid when electing to offer voluntary vaccinations.

Offering voluntary vaccinations only makes sense if the action is directed toward meeting one of three possible objectives. One: additional vaccinations contribute to the establishment of an appropriate level of preparedness, indicating that the threat for release of the virus is in fact much greater than has been appreciated in the public domain. This is the herd immunity factor noted above, which if increased enough might effectively remove the smallpox virus from an "enemy's" arsenal of potential weapons. Two: the immunizations are being offered simply to reinforce to Americans that every possible measure in being taken to ensure their protection after the terrorist attacks of September 11, 2001. Three: these vaccinations are an effort by the government to reduce its own liability.

To elaborate on the last point, it seems clear that with a voluntary plan the government's bases are covered. If side effects of the vaccine occur, a public backlash can be quelled with the reminder that vaccinations were voluntary, and every vaccine recipient was after all warned of such effects. If an outbreak occurs and the public charges the government with withholding vital intelligence, it can be brought to the nation's attention that the administration did in fact do everything it could to alert the people to the likelihood of such an event through the diligent pursuit of a nationwide vaccination strategy, and further that the vaccine was offered to the American public with exactly the threat of deliberate release in mind. And again, US citizens can in the meantime feel secure with the notion that the government is doing everything it can to limit the biological weapons or bioterrorist threat.

In making this argument, I wish to stress the need for education on these issues.[16] President Bush has made evident that he feels the same way: "[W]hat's going to be very important is for us to make sure that there's ample information for people to make a wise decision."[17] But such has not been the case as yet. Therefore, only after the establishment and implementation of a thorough, comprehensive, and universal education campaign can voluntary vaccinations be justifiably offered to the American public.

Phase Four

Phase four is an enhanced version of the surveillance-containment strategy that was successfully employed by the World Health Organization (WHO) to eradicate smallpox worldwide in the sixties and seventies. It is only to be implemented in the event of a confirmed smallpox outbreak, with the primary goal being to contain the disease and treat exposed individuals as quickly as possible. The first and foremost concern to this end is the rapid identification and isolation of the initial smallpox case(s) to limit further transmission of the virus. Once this is accomplished, phase four calls for the vaccination of three groups of individuals.

First, all face-to-face and household contacts must be identified and vaccinated, regardless of whether a given contact is contraindicated for the vaccine, to create a ring of vaccinated individuals around each infected person. The vital consideration here is that should a confirmed outbreak occur, the risk of the disease outweighs the risk of the vaccine for any exposed individual, regardless of contraindications.

Second, all non-contraindicated individuals likely to come into contact with the individuals of the first ring (i.e., household members of these individuals) must be vaccinated. This amounts to what might be considered an "extended ring" approach, offering a second ring of protection around each exposed individual in order to contain the disease should that individual later develop smallpox. To minimize the potential for contact vaccinia and subsequent illness in contraindicated individuals (as well as to reduce the likelihood of further spread of the disease), the CDC recommends that "household members of contacts who cannot be vaccinated because of contraindications...avoid contact with the contact until the incubation period for the disease has passed (18 days) or 14 days following successful vaccination of the contact."[18] Given this recommendation, "[h]ousehold members with contraindications should consider housing themselves separately from vaccinated household members until the vaccination site has healed...."[19]

Third, as described in the discussion of phase one above, vaccination of additional individuals deemed to be at high risk for exposure to the virus must be vaccinated at this point. Again, these individuals include healthcare and public health workers directly involved in the evaluation, treatment, and transportation of potential smallpox cases. In addition, all individuals present in a given hospital or clinic at the same time as a confirmed, non-isolated smallpox case should be "considered" for vaccination. It is not made clear in the CDC guidelines whether this includes individuals contraindicated for the vaccine, a point that must be clarified given that contraindications would be expected in a substantial proportion of people in these medical settings.

The key to phase four is preparedness. In the event of a documented smallpox outbreak, members of the general public are likely to panic. Individuals will flood hospitals and emergency rooms demanding vaccination, and in doing so will essentially increase their risk for exposure. Misinformation will likely be widespread, as was the case with the early "anthrax letter" reports. The healthcare community must be prepared to deal with these and any number of other unforeseeable problems, while still mobilizing resources to initiate and sustain the necessary outbreak control measures. Given this need, I am of the opinion that there should be absolutely no questions left unanswered in the response plan itself.

What of the scenario mentioned above in which an individual later diagnosed with smallpox presents to a hospital and is not immediately isolated? Should everyone in the setting be vaccinated? Including contraindicated individuals? What is the course of action if an individual refuses vaccination? Should the hospital be temporarily quarantined until these vaccinations are carried out in order to ensure the highest likelihood of disease containment? Has a script been developed for use in such a situation, emphasizing to quarantined and sure-to-be panicking individuals that the measures are in place for their own protection? What about on a broader level: has a script been expertly developed to explain response plans to the American public should such an explanation be necessary?

Essentially, hundreds of pages of guidelines must be sifted through in order to locate discussions of these and other crucial issues, yet once located these discussions offer no definitive answers as to how such issues are to be resolved in practice.[20] Thus, while the response plan is a very good one in theory, certain practical issues must be worked through and succinctly clarified in order to ensure that its implementation is effective.

Phase Five

Phase five involves a broader "mass" vaccination strategy in order to contain the spread of smallpox in the event that phase four is deemed ineffective in its ability to contain the disease. Phase five is only to be initiated under one of three circumstances: (1) the size of the first wave of smallpox cases is too great to be effectively managed by contact identification and vaccination alone; (2) no decline is seen in the number of new cases after two or more generations from the index case(s); or (3) no decline is seen in the number of new cases after approximately 30 percent of current vaccine stores have been utilized. Part V of this series will focus on local planning and preparation for the implementation of phase five.

[1] McNeil, D., "Smallpox Inoculations Begin With 4 Connecticut Doctors," New York Times, January 25, 2003.
[2] CDC telebriefing transcript of ACIP Smallpox Vaccine Meeting Briefing, October 17, 2002, http://www.cdc.gov/od/oc/media/transcripts/t021017.htm.
[3] US Army Medical Research Institute of Infectious Diseases (USAMRIID), "Smallpox: Recognition and Response," satellite broadcast, November 6, 2002.
[4] Ibid.
[5] Henderson et al., "Smallpox as a Biological Weapon," 1999, pg. 8.
[6] "Guide B--Vaccination Guidelines for State and Local Health Agencies," pg. B-5, http://www.bt.cdc.gov/agent/smallpox/response-plan/index.asp.
[7] "Guide B--Vaccination Guidelines for State and Local Health Agencies," pgs. B-5 to B-6, http://www.bt.cdc.gov/agent/smallpox/response-plan/index.asp.
[8] Dixon, C., Smallpox (London: J&A Churchill Ltd., 1962), pg. 1460, as cited in Henderson et al., "Smallpox as a Biological Weapon," 1999.
[9] "Executive Summary," Smallpox Response Plan and Guidelines (Version 3.0), CDC website, pgs. 9-10, http://www.bt.cdc.gov/agent/smallpox/response-plan/index.asp.
[10] The appearance of the inoculation site will indicate a "take" in 3 to 4 days and offer a high level of certainty by day 7 to 11. "Guide B--Vaccination Guidelines for State and Local Health Agencies," pg. B-10, http://www.bt.cdc.gov/agent/smallpox/response-plan/index.asp.
[11] See, for example, Marcotty, J., and Lerner, M., "Smallpox vaccine signup less than expected," Star Tribune, January 18, 2003; "Hospitals refuse smallpox shots," Washington Post Service, December 19, 2002.
[12] In order to minimize this possibility, the ACIP recommends that healthcare workers involved in direct patient care keep their vaccination sites covered with gauze or similar absorbent material. The ACIP does not recommend that healthcare workers be placed on leave after vaccination unless (1) they are physically unable to work due to systemic signs and symptoms of illness, or (2) they fail to adhere to recommended infection control precautions. ACIP Smallpox Vaccine Meeting Briefing, October 17, 2002, http://www.cdc.gov/od/oc/media/transcripts/t021017.htm.
[13] Stevenson, R., and Altman, L., "Smallpox Shots Will Start Soon Under Bush Plan," New York Times, December 12, 2002.
[14] Grady, D., and Altman, L., "Smallpox Data Show Small but Serious Risk of Infecting Others," New York Times, October 16, 2002.
[15] ACIP Smallpox Vaccine Meeting Briefing, October 17, 2002, http://www.cdc.gov/od/oc/media/transcripts/t021017.htm. Emphasis added.
[16] For a fascinating and frankly alarming survey illustrating the need for public education about smallpox, see Blendon, R., et al., "The Public and the Smallpox Threat," New England Journal of Medecine 348:5 (January 30, 2003).
[17] Stevenson and Altman, "Smallpox Shots Will Start Soon Under Bush Plan," December 12, 2002.
[18] "Guide B--Vaccination Guidelines for State and Local Health Agencies," pg. B-3, http://www.bt.cdc.gov/agent/smallpox/response-plan/index.asp.
[19] "Guide B--Vaccination Guidelines for State and Local Health Agencies," pg. B-6, http://www.bt.cdc.gov/agent/smallpox/response-plan/index.asp.
[20] See, for example, "Guide C--Isolation and Quarantine Guidelines," "Guide E--Communication Plans and Activities," and "Annex 5--Suggested Pre-Event Activities for State and Local Health Authorities," Smallpox Response Plan and Guidelines (Version 3.0), CDC website, http://www.bt.cdc.gov/agent/smallpox/response-plan/index.asp.

CNS Experts on the Smallpox Threat, Vaccine, and U.S. Policy:

• Richard Pilch, M.D. | Bio
  Scientist-in-Residence, Chemical and Biological Weapons Nonproliferation Program (CBWNP)
  richard.pilch@miis.edu

• Raymond A. Zilinskas | Bio
  Director CBWNP
  rzilinkskas@miis.edu