An analysis of the proposed national strategy for smallpox vaccination of health care workers☆

The eradication of smallpox 

In the 1800s, smallpox killed approximately 50,000-60,000 Americans per year. President Abraham Lincoln, for example, was suffering from the early effects of smallpox during the Gettysburg Address. While never considered good-looking, his craggy face at the end of the war was as much a result of smallpox as stress. The latter 1800s and early 1900s saw the advent of public health departments that significantly reduced the infectious disease risk in America.

Quarantine, the medical treatment of persons ill with communicable disease, and isolation, the observation and contact prevention of those exposed but not yet ill, were aggressively used to contain communicable disease patients, and compulsory vaccination was required of the population. As an example, during 1901-02, Boston created “vaccination teams” composed of a doctor, a nurse, and a police officer who were instructed to enforce compliance—by force if necessary. By developing “herd immunity” and controlling potential disease carriers, the last case of smallpox in the United States occurred in 1946 in Hidalgo, Texas.

The last great repository of smallpox resided in the Indian subcontinent. During the 1960s, the WHO undertook an eradication project by deploying 55,000 workers who went door-to-door in India to identify and then quarantine or isolate suspected cases. Quarantine and isolation were enforced by the local constabulary, and no medical care was provided to those identified, only food and water. By aggressively controlling contacts, the last case of smallpox occurred in 1972. Smallpox was declared officially eradicated in 1977.

An overlooked factor in this great victory was that it occurred through the suspension of civil rights. In all cases, the medical workers who managed the vaccination, quarantine, isolation, and search for smallpox cases were vaccinated before their deployment.

A troubling occurrence 

In 1971, a smallpox outbreak occurred in Aralsk, Kazakhstan, a port city on the Aral Sea, the fourth largest body of inland water in the world at the time. This outbreak was not large (10 victims), but it occurred in an unusual fashion. A worker on the Soviet ship Lev Berg became ill after being deployed approximately 15 km south of Vozrozhdeniye Island. No one else on the ship developed the disease. Vozrozhdeniye Island at that time was a Soviet biologic test site. The smallpox outbreak that ensued was unusual in several respects. First, natural smallpox is not known to have a significant “downwind” spread. Second, the outbreak seemed to be as aggressive with vaccinated individuals as nonvaccinated. Lastly, the disease outbreak took an unusual hemorrhagic form of the disease. What does this mean?

The Aralsk outbreak is troubling because it seems to indicate a Variola virus that has characteristics that enhance its spread and virulence. No others on Lev Berg became ill, and the worker had been at sea for several weeks before her illness, indicating a probable downwind exposure from Vozrozhdeniye Island. The others who became infected were her family, associates, and neighbors, even though they were largely immunized. Lastly, the Aralsk outbreak was concealed by the Soviet government until the fall of the USSR. Other previous outbreaks were not concealed by the Soviets.

It seems unwise to ignore the suspicion that the Soviet Union was experimenting with Variola. Numerous reports from defectors and émigrés have confirmed the USSR's biologic weapons program in general and the smallpox program specifically. The fall of the Soviet Union and the subsequent “brain drain” from their military science institutes have escalated the risk of inadvertent or intentional release of Variola as many of those scientists emigrated to Iran, Iraq, North Korea, Libya, India, and Pakistan. Of great concern, there have been unconfirmed reports of a smallpox vaccination program in Iraq.

The issue of intent 

The Soviet Union developed the smallpox weapon to ensure the destruction of the United States in a postnuclear holocaust. Smallpox was to be dropped on America after cities and health care systems had been destroyed to “mop up” the population. Because of its lethality and communicability, the outbreak likely would go worldwide, thereby reducing civilization to a “stone-age” model.

This horrendous plan for unrestricted warfare on the human race was not in the best interests of the USSR. Simply stated, it did not make sense to use this weapon offensively. The intent of the Soviet Union smallpox weapon was to defend their empire and further ensure the Mutual Assured Destruction principle of the Cold War. Smallpox was not used to expand communism throughout the world. A noncommunicable disease like anthrax or tularemia, for example, is more useful in the military sense. To expose your enemy and remain safe from the disease is the goal. The problem with all aerosol-delivered weapons is that, once released, their dissemination is unpredictable, limiting their use as an offensive.

Terrorist groups have a wide range of potential intent. Although the number of potential scenarios is great, not many include a worldwide plague. In fact, most “hate groups” are not benefited by an indiscriminate disease outbreak because their followers also could be infected. The sort of groups that would be interested in smallpox would likely be apocalyptic cults and nationalist groups like the old USSR facing extinction. As the narrowly targeted anthrax events of 2001 revealed, bioterrorism may be large or small, and the targeting and dissemination is closely related to the terrorist's intent. With regard to smallpox, it is entirely possible that groups would possess the agent in a defensive rather than offensive posture.

Smallpox overview 

Smallpox is an untreatable condition in which 30% of those exposed will develop the disease, and 30% of those will succumb. Smallpox takes 4 primary forms. Variola Minor is a mild form of the disease in which almost all exposed are expected to survive. Variola Major refers to the characteristic large pustular rash in which a 30% mortality rate is expected in native smallpox. Malignant smallpox or “sledgehammer” smallpox refers to the disease in immunocompromised individuals in which pustules do not occur and death is quick by viral sepsis. Hemorrhagic smallpox refers to the concomitant vasculitis and coagulopathy that is the most feared form of the disease. Malignant and hemorrhagic smallpox each occur in 1% of cases historically.

Smallpox management 

The medical management of smallpox has not changed much since the advent of public health. The historical bedrock of smallpox management is containment and ring vaccination. Containment (the application of quarantine and isolation) is essential, but American medical systems do not practice in this method. Because enforcement is not an option without military rule, any quarantine or isolation order must rely on a cooperative population. Our populace has not faced a potentially lethal airborne disease in modern memory and therefore, if one should occur, we initially may not comply with orders. In addition, isolation means that individuals may be asked to stay with others suspected of smallpox, putting them at significant risk of developing the disease.

One of the interesting phenomena that has occurred in the modern management of infectious disease is that hospitalization increases the spread of disease; the current ventilation systems not present in the 1800s are quite capable of spreading the virus from place to place. Where then should we quarantine exposed victims? Who should care for them? These legitimate albeit difficult questions must be asked of the medical authorities.

Vaccination concerns 

Vaccination against smallpox has not changed much since the 1800s. The “vaccine” is actually a less virulent infection than smallpox. The virus Vaccinia is closely related to cowpox. In fact, the term “vaccine” comes from “vacca,” the Latin word for cow. This Vaccinia infection causes immunity to both diseases after the recovery of the vaccinated individual. In most cases, that process takes 3 weeks to commute full immunity. In a minority of cases, the Vaccinia infection produces complications, the most severe of which is encephalitis. Vaccinia encephalitis has a 33% mortality rate and will occur in 10 cases per million vaccinations. It is also possible to develop a number of other complications, including the inadvertent transfer of the Vaccinia virus to other sites or other individuals. Vaccinia infection also can be aggressive in some individuals, causing an untreatable local or systemic infection requiring excision of the infected flesh. These complications were acceptable in a time when smallpox was a great killer in our nation, but without the presence of the disease, smallpox vaccination represents a predictable cause of mortality and morbidity.

Vaccination strategies 

Given the probable development and deployment of smallpox weapons, it might be wise to vaccinate our population against this dread disease. However, the process of vaccination definitely will kill some recipients. The nature of the American legal system assigns fault and financial responsibility for poor outcomes of medical therapies, regardless of the reasoning or intent. The mitigating factor in the liability question is the assessment of risk. A potentially harmful treatment is deemed “reasonable” if the disease is lethal. In the case of smallpox, vaccination made great sense when the disease was killing large numbers of Americans. Therefore, the key estimation in the smallpox vaccination question is whether or not an attack is likely and whether that likelihood justifies the risk.

The 2 “postexposure” strategies that have emerged are ring or traced vaccination and mass vaccination. Postexposure vaccination will mitigate the progression of disease by decreasing the likelihood of disease development in “exposed” but not yet symptomatic victims. Ring vaccination is the historical method of vaccinating the contacts and those who are exposed or are associates of the index case. The risks of vaccination are mitigated by the probability of exposure. The strategy works well in communities where contact between individuals is limited.

Mass vaccination, however, refers to vaccinating all individuals within a given population to create herd immunity. This strategy is indicated in a large outbreak or if contact association between individuals is high. Prevaccination is a derivation of the mass vaccination policy. To justify prevaccination, the risk of smallpox must be clear and present.

To choose the correct strategy, one also must understand the process and impact of vaccination on health care workers. First, full immunity requires 21 days after vaccination to develop. This means that if vaccination is started after an outbreak occurs, health care workers will not be adequately protected. This fact places the health care worker in a choice of conscience. Does he work with the chance of contracting a lethal communicable disease that could spread to his family, or does he opt to avoid the risk? Without prevaccination, the choice between one's profession and one's life and the lives of one's family is likely to degrade the workforce.

In addition, the vaccination causes the Vaccinia virus to shed from the site. This virus can infect other patients and cause significant morbidity in pregnant women and immunocompromised and critically ill patients. Thus, the vaccinated health care workers become risks to their patients. Lastly, should a health care worker contract smallpox, his or her high contact among ill individuals can be expected to accelerate the transmission of this disease. For these reasons, there is really no alternative to vaccinate against smallpox if the threat of terrorist use of smallpox is large.

A suggestion for health care policy 

Although the threat of smallpox use by terrorists is real, the day-to-day likelihood of occurrence depends on world events and how those events affect terrorist groups. Going to war in the Middle East, for example, particularly deposing an Islamic nation's government, will increase terrorist activity here in the United States. The nature of Islamic fundamentalism is such that apocalyptic war is among the stated goals of these groups. Furthermore, Islamic fundamentalist terrorists have martyred themselves quite frequently in past years. These characteristics increase the threshold that smallpox or other apocalyptic weapons would be seen as attractive.

Should a large number of cases simultaneously occur in several U.S. cities, ring vaccination would not be viable, and our national strategy must focus on quarantine and mass vaccination. Quarantine and isolation would be difficult decisions to make and more difficult to enforce. Because mass vaccination after the outbreak would occur in a potentially terrified population, screening would likely be degraded, inadvertent viral transmission from viral shedding would occur, and no one would be fully protected for 3 weeks. If a single case occurred, perhaps postoutbreak vaccination would be useful, but because of the malicious nature of terrorism, the worst case would be the most likely case.

For these reasons, there is really no alternative to pre-event screening and orderly vaccination of the health care workforce in significant numbers. If done over time, vaccination can be handled with good screening procedures and a minimum of inadvertent exposures. Any complications can be recognized by a health care system not preoccupied with the containment and management of smallpox.