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Smallpox: Threat, Vaccine, and US Policy
Part V 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 continued guidance, editing, and support during the writing of this series.]

V. The Supplemental Strategy

Based on the criteria discussed in the earlier parts of this series for implementing the CDC's Supplemental Strategy, it appears that phase five of the vaccination plan will be set in motion only if a large-scale release of the smallpox virus somehow overwhelms preparedness measures and phase four vaccination. Based on the challenges outlined in Part III of this series, such an action and outcome are highly unlikely. Further, even if the virus were somehow acquired, produced, and effectively disseminated among a large and unsuspecting population, the nature of smallpox suggests that the "extended ring" surveillance-containment strategy would effectively contain the disease. This addresses the concept of contagiousness. In Part I, it was emphasized that based on CDC estimates of historical data, on the average one active smallpox case infects fewer than 2 otherwise well persons. However, it was also noted that infectious individuals can transmit the virus to as many as 10 to 20 persons, and that "hyper-spreaders" of the disease have occasionally appeared in the past (the example offered was that of an isolated patient who managed to infect individuals on three floors of a German hospital). The question then becomes: just how contagious is the smallpox virus?

Eradication data from the Indian subcontinent showed that when one member of a household became sick with smallpox, 36 to 88 percent of other unvaccinated household contacts would contract the disease.[1] However, because individuals suffering from the symptoms of smallpox were usually bedridden by the time the rash formed (essentially signaling contagiousness), such household contacts were often the only ones exposed to the virus. Thus, each smallpox case passed on the disease to only 0 to 3 healthy persons on the average, the majority of whom were household contacts.[2] In the 49 documented outbreaks of smallpox in Europe between 1950 and 1971, the average case in the general public led to 1.6 second-generation cases (the average case identified in a hospital setting led to 2.4 second-generation cases, again reflecting the propensity for transmission of the virus within a given medical establishment).[3] Upon diagnosis, 34 of these 49 outbreaks did not continue beyond the second generation of cases,[4] and 13 demonstrated no transmission of the virus whatsoever beyond the index case.[5]

This information is provided as a reminder that in the unlikely event of an outbreak, historical data suggest that the virus will not spread uncontrollably and ravage the US population. That being said, given the fact that we are an immunologically naive population and conceding the point that other variables may favor such spread (for example, if the virus were simultaneously released in multiple locations nationwide), the Supplemental Strategy has been developed as a contingency plan to prevent such an eventuality.

Proper planning for phase five begins with the designation by public health officials in each city or county of four unique clinic types (this is in addition to a central facility (or facilities) tasked with the care of confirmed smallpox cases): (1) "vaccination clinics" (VCs) for large-scale vaccination of non-exposed, non-contraindicated individuals (contraindicated persons may also receive the vaccine upon counseling and if informed consent is given, as described below); (2) "contact clinics" for the vaccination, counseling, and care of known smallpox contacts, in which vaccine is given whether or not the contact is contraindicated (again, in the event of face-to-face contact with a confirmed smallpox case, the risk of the disease outweighs the risk of the vaccine); (3) "treatment clinics" for vaccine recipients suffering from ill effects of vaccination; and (4) "evaluation clinics" for symptomatic individuals who must be "ruled-out" for smallpox (i.e., for whom smallpox must be eliminated from the differential diagnosis, a list of possible causes of illness). This segment, Part V of the series, will focus on VCs specifically, with the goal of providing some insight into the complex capabilities and demands of the Supplemental Strategy.

Vaccination Clinics (VCs): A Brief Overview

While preparedness is the key to phase four (and certainly plays a major role in phase five as well), the key to phase five is speed. Should the Supplemental Strategy have to be implemented, healthcare workers will be racing against the clock, and presumably the spread of the disease, in an attempt to establish a level of herd immunity in the threatened population that is adequate to limit further spread. VCs represent the major front for this action. Thus, according to Center for Disease Control (CDC) guidelines, VCs are to be established such that 1 million persons can be vaccinated in 10 days or less. To accomplish this goal, each VC must be located appropriately (relevant to each other and the target population), and personnel tasking and performance must be optimal within each clinic. It should also be noted that accessibility is crucial.[6] Each VC must be proximal to public transportation (e.g., bus or metro) or at the very least offer plentiful free parking, either at the site itself or at offsite collection areas (CAs) with adequate transportation services in place. The clinic building must also offer accessibility for disabled persons.

It is estimated that 20 VCs will be required for every one million persons in need of vaccination. The target rate of vaccination for each VC is 5,900 persons per day. In order to achieve this target rate, at any given VC, 8 vaccinators must vaccinate 30 to 60 individuals per hour for a minimum of 16 hours per day.[7] With 20 VCs assigned in a given area, this translates to approximately 100,000 persons vaccinated per day, and 1 million persons vaccinated in 9 to 10 days.[8] A larger area such as Los Angeles County, with its population of approximately 10 million persons, will therefore require 200 VCs in order to vaccinate this population using the above estimates.

Vaccinators are of course not the only personnel involved in this process. The CDC has estimated that as many as 4,600 persons might be required in order to vaccinate 1 million people in such a demanding timeframe.[9] This level of manpower is necessary to meet the many needs of each VC, from securing vaccine supplies, to screening potential recipients, to obtaining informed consent, and so on. These and other needs are highlighted in the following scenario in which an outbreak exceeds the containment ability of phase four and the Supplemental Strategy is initiated.

Vaccine Distribution, Preparation, and Maintenance

The Supplemental Strategy can only be set in motion by the Director of the CDC and with the approval of the Secretary of Health and Human Services (HHS).[10] Assuming such approval is given, an initial shipment of supplies from the National Pharmaceutical Stockpile (NPS) will be authorized. This shipment will contain vaccine, diluent (used to reconstitute the vaccine into a deliverable form), bifurcated needles, and vial holders (to prevent accidental spillage during needle preparation), as well as bilingual (English and Spanish) supporting materials such as screening and consent forms, descriptive passages on the smallpox virus and vaccinia vaccine, vaccination site care instructions, and vaccination take recognition cards.

The first shipment of vaccine will be delivered in a specialized container, called a Vaxicool unit, which can be connected directly to a power source and used for vaccine storage (this power requirement presents a security issue, as discussed below). Each Vaxicool unit contains approximately 300 vials of vaccine. One vial contains 100 individual doses unless the vaccine in question is DryVax (different vaccines are delineated in Part II of this series). These 100 doses are prepared by adding 0.25 ml of diluent to a given vial and then drawing from the resulting solution. Because doses will need to be maximized in the event of phase five implementation and given the aforementioned five-fold dilutional potential for DryVax, each vial of DryVax will be combined with 1.25 ml of diluent, and thus a given vial contains 500 individual doses of the vaccine.

The primary concern when diluting the vaccine is the potential for wastage.[11] The fact that vaccine types must be differentiated in order to ensure proper dilution suggests another potential stumbling block to effective vaccine preparation. A third concern is storage temperature: while the Aventis-Pasteur vaccine requires a temperature of 0 degrees Celsius or below, all other vaccines must be maintained at 2 to 8 degrees C.[12] In any case, the vaccine must be brought to room temperature before the diluent is added.[13]

The NPS has the ability to ship up to 500 Vaxicool units on the first day of Supplemental Strategy activation. Assuming that DryVax will--as is currently expected--constitute the initial shipments (until supplies run out), the capacity exists to deliver up to 75 million doses on day one alone to sites within the continental United States. After shipment of the Vaxicool units, subsequent shipments will contain 1,000 to 1,500 vials of vaccine packaged in large Styrofoam containers that are not self-cooling and thus require cold storage for their contents upon receipt.[14] The NPS is capable of shipping 615 of these containers each day for the next five days, making distribution of enough vaccine for the entire US population feasible within a week's time.

VC Walkthrough

As the vaccine is being delivered and prepared, public service announcements (PSAs) will be used to provide the community with general information about the outbreak as well as more specific local information such as where citizens should go to be vaccinated, wait times at each VC, and so on. Importantly, these announcements must remind citizens that identification is required for clinic entry and that loose clothing should be worn to allow for easier vaccination.[15] PSAs should include messages in languages other than English and transmitted via alternative language media outlets.[16]

What happens when an individual arrives at a given VC? Upon entering the clinic, the individual encounters a triage station,[17] the personnel of which have two primary tasks: (1) to identify and redirect suspected contacts of confirmed smallpox cases or potential smallpox cases themselves, suggested by the presence of fever and/or rash; and (2) to distribute the above-described forms and information sheets relating to smallpox and the vaccine. This first point addresses the concern of patient crossover among the four types of clinics. Such crossover must be anticipated among these clinics, particularly between VCs and contact clinics, due to confusion among those seeking vaccination.

Once through triage, the individual views an orientation video containing information about informed consent, such as data on the risks of the vaccine and possibilities for alternative treatments.[18] The script of the video, written in both English and Spanish, will also be provided. However, communities with other language requirements potentially present a problem in that additional translations of the orientation video will have to be made available. Thus, foresight on the part of such communities is necessary in order to ensure that these translations are prepared well in advance.

Next, the individual moves on to the screening area, where careful measures are employed to identify individuals contraindicated for the vaccine. Strategies must be in place so that at this point, should a potential vaccine recipient be identified as at-risk for HIV or pregnancy, rapid referral to the local public health authority for confidential testing is available. Persons identified during this process may still elect to receive the vaccine as long as they are "counseled" on its risks and are willing to sign a "witness consent form" (i.e., an informed consent agreement, which is essentially a witnessed authorization acknowledging inherent risks of as well as alternatives to a given treatment).[19]

Assuming no contraindications are identified and no further testing is requested or deemed necessary, the individual proceeds to a vaccination station (VS). Three things happen here: (1) a witness consent form must be signed; (2) the vaccine is administered; and (3) a vaccination card stating that the individual has received the smallpox vaccine is provided to the recipient. The first point is important because despite the crisis situation inherent to phase five implementation, at the time of this writing the vaccine is an Investigational New Drug (IND) pending final approval by the FDA, and informed consent must therefore be obtained prior to its administration.

After vaccination, the individual passes through an exit review area where any additional questions may be addressed. Personnel at this area are also tasked with ensuring that each vaccinated individual departs with all information sheets and instructions.[20]

Specialized Personnel

Specialized personnel are required to address specific concerns throughout this process. Security is a primary consideration. Security personnel must be in place for crowd control purposes and to ensure proper patient flow both inside and outside the VC (including traffic flow). These security personnel are also required to protect other clinic workers as well as vaccine supplies, as noted above.[21] Thus, security personnel will make up the highest proportion of clinic personnel in any given VC.[22] Further, any off-site vaccine supplies must be actively guarded, along with vehicles used for the vaccine's transportation and backup power generators necessary for maintaining the vaccine at its required temperature in the event of primary source failure.[23]

Because language barriers must be overcome in the event of phase five activation (and throughout the entire vaccination process from phase one forward), each VC should be staffed with one translator "for each major language spoken in [the] community per shift."[24] The CDC further recommends that consideration be given to "identifying specific clinics for referral of populations who need translators."[25] Individuals dependent on sign language must also be accommodated. And finally, at least one emergency medical technician (EMT) should be on location at all times to respond to medical emergencies, fainting patients, and the like.

Summary

The establishment of well-placed and efficient VCs is only one step toward successful phase five implementation. Yet the above scenario illustrates the many complex interactions necessary to meet this need alone. CDC guidelines adequately outline the Supplemental Strategy and address the majority of the author's concerns with respect to its proper execution. It should be noted, however, that only after a substantial amount of research was conducted did the author discover a door-to-door description of tasking within a VC similar to that provided above (the description is buried in the middle of a 50-page annex to the main vaccination guidelines). This serves to re-emphasize the need for succinct and accessible information provided by the CDC in order to allow for optimal preparedness on the part of each and every community in the United States. Only with a clear understanding of the CDC's recommendations can such universal preparedness be ensured.

[1] US Army Medical Research Institute of Infectious Diseases (USAMRIID), "Smallpox: Recognition and Response," satellite broadcast, November 6, 2002.
[2] Ibid.
[3] Ibid.
[4] Ibid.
[5] Ibid. Further, 12 of the 49 outbreaks demonstrated transmission to only 1 to 4 individuals.
[6] "Mobile VCs"--consisting of vaccination teams, security personnel, and so on--may be deployed to pockets within a given community that have limited access to vaccination clinics, for example nursing homes, hospitals, and prisons. Such mobile teams may also be utilized in remote, rural areas where a widespread population is considered too far removed from the nearest vaccination clinic. "Annex 3--Smallpox Vaccination Clinic Guide," Smallpox Response Plan and Guidelines (Version 3.0), CDC website, http://www.bt.cdc.gov/agent/smallpox/response-plan/index.asp, pg. 12.
[7] Ibid., pg. 8. Whether such demanding physical and psychological requirements can be met is of course debatable, suggesting a potential pitfall in the very foundation of the strategy.
[8] Ibid.
[9] Ibid., pg. 34.
[10] "Guide B--Vaccination Guidelines for State and Local Health Agencies," pg. B-4; "Annex 3--Smallpox Vaccination Clinic Guide," pg. 3.
[11] Russell, "Smallpox Vaccine Stockpile for the United States," 2002.
[12] These important differences demand that "storage and handling instructions for the specific vaccine being used...be reviewed with all staff before they begin their shift." See "Annex 3--Smallpox Vaccination Clinic Guide," pg. 5.
[13] "Guide B--Vaccination Guidelines for State and Local Health Agencies," pg. B-8.
[14] The assumption is that these Styrofoam containers will be cooled during delivery, but the mechanism for doing so is not delineated in the CDC guidelines.
[15] "Annex 3--Smallpox Vaccination Clinic Guide," pg. 17.
[16] Ibid., pg. 13.
[17] Ibid., pg. 15.
[18] Ibid., pg. 18.
[19] Ibid., pg. 15.
[20] Ibid., pg. 19.
[21] Ibid., pg. 6.
[22] Ibid., pg. 9.
[23] Ibid., pg. 6.
[24] Ibid., pg. 11.
[25] Ibid.

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