by
Michael Catlin
Meghan Joyce
Michael Reckhow

1
For thousands of years, the smallpox disease has had a devastating impact upon the human race (Barquet & Domingo, 1997). Thanks to a vaccine, the disease has been eliminated from the natural world. However, this vaccine itself poses significant health risks to people, and with the disease gone, vaccination has not occurred in the United
States since 1972 (Henderson, 1999) But with a resurgence in terrorism and the potential that the virus will be deliberately released into the environment, many have begun to wonder whether Americans should once again be vaccinated (Guterl, 2002).
Smallpox epidemics have occurred for at least the last three thousand years.
When several well-preserved Egyptian mummies from 1570 to 1085 B.C. were exhumed, smallpox lesions were found on the mummies’ faces (Barquet & Domingo, 1997). An epidemic in the second century A.D. killed between 3.5 and 7 million people and was instrumental in the early decline of the Roman Empire. The disease was not present in the New World prior to European colonization, but with the arrival of Spanish conquistadors and European settlers, the Aztecs, Incas, and Indians of the American East
Coast were all devastated. In the first known example of biological warfare, a British commander, Sir Jeffrey Amherst, ordered smallpox scabs to be ground into blankets and the blankets issued to Indian tribes (Cowley, 2002). By the end of the 18 th century, smallpox killed 400,000 Europeans every year, and almost everyone eventually developed the virus.
Smallpox disease is caused by variola, a substantial and extremely intricate virus found only in nature (Guterl, 2002). It is transmitted only through bodily fluids and is thus only seldom spread through the air (CDC, 2003). Instead, transmission most frequently requires extended close contact with an infected person or with sheets,

2 clothing, or another object used by an infected person. Because of this, smallpox is not considered as contagious as other infections such as measles, chickenpox, or the flu, which may spread easily in communities such as schools or offices (Ulick, 2002).
Rather, smallpox poses the most danger to families and cohabitants.
Once the virus has been transmitted, it sends the untreated, unvaccinated body into a series of seven distinct stages that generally take 21 to 37 days to run their course
(CDC, 2003). The first phase, infection, lasts from one to five days, and begins with initial contact with the germ (Ulick, 2002). Usually, the virus is inhaled, and once it reaches the lungs it travels to the local lymph nodes, located in the neck region. Once the infection has begun, the incubation period begins. During this time, the individual suffers from no apparent symptoms of the disease, and he or she is not contagious (CDC, 2003).
Inside the body, however, the virus is hard at work spreading and reproducing. Microbes move from the lymph nodes to the liver and the spleen and quickly proliferate (Ulick,
2002). The average incubation period lasts 12 to 14 days, although it can vary between anywhere from six to 17 (CDC, 2003).
The first symptoms begin to appear during the prodrome phase, which lasts from two to four days. During this stage, the victim experiences possible headaches, muscle pain, malaise, high fever, often between 101 and 104 degrees Fahrenheit, and occasionally vomiting (CDC, 2003). Full contagiousness is not attained, however, until the next phase, early rash. At the beginning of this four day period, small red spots begin to appear in the mouth and on the tongue (CDC, 2003). Eventually, these spots become sores which rupture and release the virus into the mouth and throat. Meanwhile, the fever falls and a rash develops all over the body, beginning with the face, extending to the legs

3 and arms, and subsequently the outer extremities. After three days of this rash, the bumps become raised, and by the fourth day they fill with pus and develop a central dent that resembles a bellybutton (CDC, 2003).
The fifth stage is characterized by the transformation of these bumps into pustules, hard, defined lumps which later crust and scab during the sixth stage of the disease (CDC, 2003). Throughout these phases, which last a total of ten days, the individual is still contagious, and faces the greatest risk of death (Ulick, 2002). Nearly two weeks after contraction of the virus, the scabs fall off leaving scars in their wake.
Only when the last scab falls off is the individual no longer contagious.
The disease is fatal for about 30 percent of its victims (CDC, 2003), although this figure can reach as high as 80 percent among young children (Barquet and Domingo).
Because the rash often affects a victim’s eyes, corneal infections commonly develop, leading to blindness in about a third of the survivors. All survivors are left with extensive scars (Barquet & Domingo, 1997).
A similar, but milder, disease called cowpox causes pustules to develop on a cow’s udder. This disease can spread to humans but is very rarely fatal. Rural English farmers were aware that milkmaids who developed cowpox were subsequently immune to smallpox. A scientist named Edward Jenner heard of this belief, and in 1796 he inoculated a small boy against smallpox using a vaccine created from cowpox germs
(Barquet & Domingo, 1997). The vaccination was successful, and by 1806, Napoleon mandated the inoculation of all French citizens (Cowley, 2002).
The United States soon followed suit. Soon, such an overwhelming proportion of the country was immune against smallpox that it became impossible for the germ to

4 spread any further. Lillian Barber, who died in Texas in 1949, was the last known case of smallpox in the United States (Cowley, 2002). By 1972, the United States deemed smallpox such an unlikely risk that it stopped requiring the vaccination of its citizens.
But the country’s motivation to cease inoculation was not without an ulterior motive.
Although the elimination of the variola virus from nature did remove the need for the vaccine, officials were more than willing to wash their hands of the vaccine completely.
In reality, the vaccine was known to cause serious and all too often deadly side effects
(Cowley, 2002). At times of greatest risk of a smallpox outbreak, the vaccine prevented the infection and the spread of the virus, and thus saved more lives than it harmed. Yet once the virus posed such a low risk to the general public, the vaccine was actually killing more people than the virus itself.
Like all inoculations, the smallpox vaccine works by infecting the body with vaccinia, a “relatively harmless virus” in the same family as variola (Ulick, 2002).
Whenever the body encounters a virus, its immune system develops antibodies specific to that germ that attack and eliminate it. These antibodies remain in the system for years, and are able to kill the virus if it ever enters the body again. This creates a quick and natural immune response, such as a body’s inability to contract chickenpox again after it has had the disease once. The same response is simulated when the vaccinia virus is put into the body. Antibodies are developed, and the virus is killed. Because vaccinia is so similar to variola, the antibodies created to eliminate the former also work to eliminate the latter if it ever enters the system (Ulick, 2002). Therefore, the vaccinated individual becomes immune to the variola virus, and to smallpox.

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The danger in the vaccine comes when vaccinia actually infects the body. It is a living microbe, after all, and therefore can cause infection if the immune system fails to muster antibodies properly. Those with weakened immune systems face the greatest risk.
For example, pregnant women, those suffering from AIDS or the skin disease eczema, and those being treated with organ transplant or chemotherapy, were all prohibited from receiving the vaccine (Ulick, 2002). Even so, for every seven million people vaccinated per year prior to 1972, about seven thousand endured negative side effects from the vaccine (Cowley, 2002). These side effects ranged from toxic reactions at the site of injection (erythema multiforme) to the spread of the vaccinia virus throughout the body
(generalized vaccinia) (CDC, 2003). Of the thousands effected, between 14 and 52 individuals per million nearly lost their lives. Ultimately, one or two per million did
(CDC, 2003). As Dr. Donald Millar and Dr. Michael Lane published in The New
England Journal of Medicine in 1969, “The benefits of routine . . . vaccination no longer outweigh its risks, and consideration should be given to its discontinuance” (Cowley,
2002). Discontinue the use of the vaccine the government did, and the United States has been smallpox free ever since.
Following the events of September 11, 2001, however, the country has begun to give the smallpox vaccine a second look. This disease has long been considered a potential weapon of bioterrorism. Before the virus was completely eliminated from nature throughout the world in 1979, samples were taken and preserved for research purposes only at the Center for Disease Control in Atlanta, Georgia, and at the Vector laboratory in Russia (Guterl, 2002). In addition, the Soviets maintained a 20 ton supply of the smallpox vaccine for weapons purposes during the 1970s (Guterl, 2002). Ken

6
Alibek, a former deputy director of the Soviet Union’s biological weapons program, has charged that the government prepared bombs and intercontinental ballistic missiles to deliver the smallpox virus (Henderson, 1999). Clearly, the smallpox vaccine is far from dead.
According to Russian officals, this weapons program was dismantled by the mid
1990s, but United States authorities still fear that the existence of smallpox, especially in the context and realm of bioweapons, could have allowed more dangerous forces to obtain samples of it as well (Guterl, 2002). Since financial opportunities for the scientists who worked in the Soviet labs have largely disappeared, for example, some fear that rogue nations or terrorists could have purchased weaponized smallpox (Henderson,
1999). Now, as the United States is feeling pressure from Osama bin Laden, Al Quaeda, and Saddam Hussein, the fear of a smallpox outbreak instigated by a bioweapon has increased exponentially. Fred Guterl of Newsweek reports:
The notion of a black market in smallpox keeps the Bush administration up at night. Homeland Security czar Tom Ridge points to ‘credible information within the international community at large that some of our enemies have smallpox.’
Vice President Dick Cheney thinks so, too. When bioweapons inspectors visited
Iraq in the mid-1990s they found no smoking gun, but they did find a disturbing sliver of evidence. They saw the word ‘smallpox’ written in Arabic on a freezedryer that could have been used to weaponize the virus; Iraq claimed the dryer was used to make vaccines. (2002)

7
Thus, while no direct evidence exists that suggests that a smallpox attack is imminent, such incidences have increased the attention and anxiety surrounding smallpox in both officials and the public.
Such fear and suspicion that a smallpox bioterrorist attack is possible brings the issue of the smallpox vaccine back into the public focus. Israel has recently begun to immunize all vital healthcare workers, and Britain and Australia have been stockpiling vaccines as well (Guterl, 2002). Now, officials in the United States are being forced to consider whether the risks still outweigh the benefits or not. Issues to be considered include the political climate and circumstances in which the vaccination should be reinstituted, if any, and if it is reinstituted, then who should be vaccinated.
Since the elimination of the smallpox vaccine, officials have depended on the
“ring vaccination” plan for any possible outbreak. Upon the diagnosis of an individual with smallpox, he or she would be isolated, and all of his “primary contacts,” for example friends, family, and co-workers, as well as the primary contacts’ primary contacts
(“secondary contacts”), would be vaccinated (Cowley, 2002). If vaccinated within four days of exposure to the virus, after all, smallpox may in fact be preventable (Ulick,
2002). While this may be adequate to deal with natural outbreaks, one caused by the shrewd calculations of bioterrorists may call for a plan that places a greater emphasis on preventative measures and widespread immunization.
Thus, officials are now considering alternative options. Dr. Lane favors a “postattack strategy,” which would involve the immediate vaccination of appropriate recipients following an attack (Cowley, 2002). He maintains that, since no direct evidence that a smallpox attack will take place, there is no need to subject thousands to

8 side effects of the vaccine. Furthermore, there are numerous other viruses that may be used in bioterrorism, such as the Marburg virus and Ebola, none of which officials are currently considering vaccinating against ahead of time. This plan rests on the belief that is better to wait and see what happens, and if facilities are indeed prepared, a post-attack vaccination will be sufficient and effective. Such a plan has gained the support of communicable-disease officials in New York City, Los Angeles County, and Butler
County, Pennsylvania, where healthcare staff and facilities are already preparing for a widespread post-attack or post-outbreak immunization (Cowley, 2002).
Dr. Millar, on the other hand, favors “voluntary peacetime vaccination” in order to not only immunize citizens against the disease, but also to decrease the number of people who could transmit the disease upon an attack (Cowley, 2002). The advantage of this plan is that “during peacetime, clinics could be more rigorous about taking people’s risk factors such as allergies, pregnancy, or compromised immunity . . . . And people who did react badly to the vaccine would stand a better chance of getting adequate care and medication” (Cowley, 2002). In other words, by taking the time to implement the vaccine carefully and methodically, those in the medical community can make it safer and decrease the number who will inevitably suffer from side effects. Therefore, if at outbreak were to take place, not only would less people get and spread smallpox, but by that point, fewer would have died as a result of the vaccine than if they were all vaccinated after the attack.
The problem with creating an effective plan is the incredible uncertainty surrounding the circumstances. If officials had some idea where, when, or how a bioterrorist attack would take place, they could more easily gauge best way to prepare for

9 it. A recent analysis in The New England Journal of Medicine describes six bio-terrorism attack scenarios that we used as a basis for our analysis. These possibilities range from small-scale attacks to large impact events, giving us a variety of situations to test the vaccination plans (Bozette, 2003).
The first plan that they outline involves a hoax situation where a similar virus such as monkeypox is mailed to a place in the US (Bozette, 2003). In this situation, those immediately affected would be vaccinated as a precaution before the virus had been discovered to be a fake. Their second situation is also a small-scale impact where a laboratory is sabotaged and releases some of the smallpox virus in a metropolitan area.
The vaccine spreads to the families of the employees but is contained.
Next they move into large-scale scenarios involving complex plans to infect the most possible people. The human vector scenario imagines several people infecting themselves and using mass transit in a large US city to infect other travelers (Bozette,
2003). In the next situation, the building attack, the smallpox virus is dispersed into the ventilation system of a federal office building in a major city. Many of the employees are exposed and the possibility exists for it to spread around the city.
The large impact attacks that they describe involve terrorists infecting US citizens in domestic airports by going to the major terminals and using portable nebulizers to infect travelers (Bozette, 2003). They divide these attacks into low and high impact types, depending on how successful the plan is.
In order to deal with these threats, this analysis considers six commonly considered plans of action involving vaccination. The options include no pre-vaccination for any citizen of the United States, post-vaccination of health care workers only, post-

10 vaccination of both health care workers and affected people, pre-vaccination of health care workers only, pre-vaccination of health care workers and post vaccination of affected people, and pre-vaccination of the entire population (Bozette, 2003). In each case, the pool of health care workers includes those throughout the country who agree to be inoculated. The pool of affected people includes those in the immediate area of the attack as well as those who may have come in contact with the virus through primary or secondary contact, who agree to be inoculated. The pool of the entire public includes citizens throughout the public who agree to be inoculated. This analysis acknowledges that additional members of each pool will request inoculation after an attack takes place if they previously refused available pre-vaccination, and takes this into account in its calculations. We feel that these options generally cover all of the possible actions that could be taken in order to deal with a smallpox attack.
The only factor we considered in our evaluation of the best possible plan was the net gain or loss of life. We postulated that since the government already possesses enough vaccines to vaccinate everyone in the United States, the costs in both pre- and post-vaccination procedures would not be prohibitively high (CDC, 2003). For this reason, a vaccination policy would be desirable if
or
that is, if

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(Bozette, 2003). Based on this equation and on the charts showing the number of deaths in each scenario under each plan, Table 1 shows the lived saved under each attack scenario if the attack occurs and the number of lives lost if the attack does not occur.
Hoax
Prior vaccination of health care workers
(Lives saved in attack)
Prior vaccination of health care workers
(Lives lost if no attack)
Additional prior vaccination of public
(Lives saved in attack)
Additional prior vaccination of public
(Lives lost if no attack)
-25
25
-457
457
Laboratory
Release
-21
25
-456
457
Human
Vectors
-18
25
-447
457
Building
Attack
87
25
-235
457
Low-
Impact
Airport
Attack
517
1095
457
Table 1: Expected Gains and Losses in Lives Under
Various Attack Scenarios and Vaccination Plans
25
High-
Impact
Airport
Attack
10827
25
41386
457
Now using the formulae for whether a policy is advantageous based on the probability of each attack scenario, we can derive minimum probabilities for which health care workers should be vaccinated, and for which the entire public should be vaccinated (Bozette,
2003). These probabilities are given in Table 2.

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Minimum probability for health care worker vaccination desirability
Minimum probability for
Hoax none
Laboratory
Release none
Human
Vectors none
Building
Attack
22.3%
Low-Impact
Airport
Attack
4.6% desirability of vaccination of entire public none none none none
Table 2: Minimum Probabilities for Desirability of Vaccination Plans
29.4%
High-Impact
Airport
Attack
0.2%
1.1%
The first decision that we made while examining these options was that vaccinating the entire population prior to an attack is not a good idea because it would lead to over 400 deaths whether or not an attack occurs. The only time that this is helpful is in the case of a successful airport attack, which we feel carries a low probability.
However, we do not argue that nothing should be done, since some prior vaccination, namely that of health care workers, would be beneficial in most attack scenarios. This plan is consistent with the calculations, but it also makes sense that those capable of caring for infected individuals and those more likely to be exposed to the disease be vaccinated in case of an attack in which affected individuals would require health care treatment. In addition, health care workers enter their field with the understanding that it may present increased health risks. Thus, some may be more willing to take a chance on the vaccine, and accept it as part of their job.
A comparison of the two plans involving pre-attack inoculation of health care workers, pre-attack vaccination of health care workers only and pre-attack vaccination of health care workers plus post-attack vaccination of the entire public, shows that the former produces fewer deaths than the latter in every situation other than the large-scale

13 airport attack. We feel that this post-attack vaccination is only necessary for the people who came in contact with the virus.
Therefore, our recommendation is for vaccination to begin for health care workers immediately. In addition, supplies of the vaccine should be distributed around the country in order for the vaccine to be administered quickly in the event of an attack. This sort of preparation, though it may be funded on the federal or state level, should be administered on the local level in order to provide the best service and fastest access to the vaccine.

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Works Cited
Barquet, Nicolau and Pere Domingo. “Smallpox: The Triumph over the Most
Terrible of the Ministers of Death.” Annals of Internal Medicine, 127 (1997):
635-642.
Bozzette, Samuel A., et al. “A Model for a Smallpox-Vaccination Policy.” New
England Journal of Medicine, 348.5 (2003): pre-release (page numbers not yet available).
Centers for Disease Control and Prevention. “Smallpox.” Updated 11 March 2003.
<http://www.bt.cdc.gov/agent/smallpox/index.asp>. Cited 18 March 2003.
Cowley, Geoffrey. "The Plan to Fight Smallpox." Newsweek (14 October 2002): 44-52.
Guterl, Fred. "Assessing the Threat." Newsweek (14 October 2002): 52.
Henderson, Donald A., et al. for the Working Group on Civilian Biodefense.
“Smallpox as a Biological Weapon: Medical and Public Health Management.”
Journal of the American Medical Assocation, 281.22 (1999): 2127-2137.
Ulick, Josh. "How the Virus Works." Newsweek (14 October 2002): 48-49.