"That some who are vaccinated later become susceptible to smallpox infection is a fact, but why these unfortunates are different from those protected by vaccination is unclear."

"Other serious concerns hinder smallpox vaccination. One is an issue of the vaccine’s side effects. Past experience in the United States and elsewhere when smallpox vaccine was routinely administered yielded records that one individual in every thousand vaccinated persons required related medical attention, and one death from complications occurred for every one million persons vaccinated. "

In 1969 newspapers and broadcasts described the murder trial of Robert Kennedy’s killer in the United States and the seizing of the American ship Pueblo by the North Koreans. The good news broadcast at that time noted amazing achievements in space, the docking of spacecrafts and walking in space. But even as the Concord supersonic jet took flight, Palestinian terrorists detonated bombs and a TWA jet was hijacked. Also in that year, a twenty-year-old traveler (name withheld for confidentiality) from Meschede, Westphalia, Germany, was returning from adventures in the Orient and Pakistan. Eleven days after his return, he fell ill, and two days later developed a fever that rapidly rose to 102◦ and then 103◦ along with a severe headache and delirium. TThe next day (day sixteen after returning to Germany), he was taken to a local hospital, St. Walburga Krankenhaus, because of high temperature, sickness, and mental confusion (48,49). The initial diagnosis was typhoid fever, so the patient was placed in an isolation ward and was visited by Father Kunibert, a Benedictine monk who offered communion. Two days later the patient’s fever rose, and a rash developed that later formed massive blisters over his body. When a clinical diagnosis of possible smallpox followed, one of the blisters was biopsied and the fluid removed was sent to the State Health Laboratory in Düsseldorf. The next day, the report came back stating that smallpox viruses were seen by electron microscopy (48,49). The morphologic picture of smallpox was easily recognizable, and The World Health Organization in Geneva, Switzerland, was notified.

Aware of the danger to hospital personnel, since smallpox roughly kills one of three people it infects, the hospital administration mobilized the local police. A few hospital personnel, as well as Father Kunibert, had been exposed to the patient, and several other patients and visitors in the hospital might be at risk. The police closed the hospital to prevent people from entering or leaving. The patient was placed in a biocontainment bag and transported by motor escort thirty miles away to Mary’s Heart Hospital in the town of Winbern because this hospital had a newly built isolation unit specifically designed to handle highly contagious patients. A chain-link fence was installed to surround the hospital, and sentinels were posted to keep people out or in.

Although the patient survived his infection, the story did not end there. What of Father Kunibert and the other patients and staff who were at St. Walburga’s hospital at the time of this episode? Potentially, all of them were exposed directly or indirectly to the smallpox virus. The same risk of exposure was true for visitors to other patients on the same and different floors for five to six days after the patient was first admitted to St. Walburga. To be sure and for public health safety, all these potential carriers of smallpox were placed in quarantine. Subsequently, German health authorities ordered a massive vaccination for smallpox in and around the hospital as well as throughout the Meschede area. This ringtype vaccine containment approach was modeled after the successful plan used by the World Health Organization that efficiently eliminated outbreaks of smallpox in Africa and Asia. As for St. Walburga’s Hospital, it was boarded up, surrounded by a fence and sequestered by police barricades. Then, eleven days after this smallpox-infected traveler entered isolation at Mary’s Heart Hospital, the Benedictine priest came down with smallpox, albeit a mild form. Next, a five-year-old girl in an isolation room diagonally across a hall from the patient’s quarters developed a severe case of smallpox but survived. Thereafter one nursing student who worked on the second floor above the patient developed smallpox, soon followed by yet another nursing student who came down with smallpox and subsequently died. Overall, nineteen people in the area fell prey to smallpox infections, seventeen associated with the initial patient exposure (48). Most of these individuals had never entered the patient’s room, and several were not on the same floor of the hospital. The smallpox evidently spread via air ducts or air currents. Another two persons caught smallpox secondarily while visiting other patients in the hospital. Of the nineteen infected persons, there were four deaths. The reason why four infected persons died while the remaining fifteen lived is not known. Their genes, the amount of exposure, a competent immune system, and a vigorous anti-smallpox immune response are all likely possibilities. Interestingly, except for Father Kunibert, the majority of those developing smallpox never came into direct contact with the patient. Of particular concern is that seventeen persons who contracted and became ill from smallpox had been vaccinated previously. That some who are vaccinated later become susceptible to smallpox infection is a fact, but why these unfortunates are different from those protected by vaccination is unclear.

In 2001, the Bush administration expanded manufacture of the vaccine and, following the recommendation of the Institute of Medicine of the National Academy of Sciences (50), began the program of revaccinating health-care and emergency workers, government officials, and the military (51). However, some of these designees resisted the revaccination plan, especially health-care providers, and far fewer received vaccinations than planned. The arguments against vaccination were vigorous and focused on five central issues. First, about 20 percent of the population cannot be vaccinated because their immune systems are compromised by disease or medications, by eczema and other skin lesions, or by pregnancy. This group also includes young children and a large segment of the population who take medication that suppresses the immune system. Second, general apathy has accompanied the decreased urgency to vaccinate, that is, the philosophy of “it is not likely to happen to me.” Third, conservative or libertarian opposition insists that vaccination should be a self-choice and not one of a general public health concern, in line with suspicion of governments’ dictums. Fourth, the unlikely possibility remains that vaccines may be contaminated or may expose recipients to secondary bacterial infections. Fifth, economics do not favor vaccine production. According to Glaxo-Smith-Kline, the world’s largest vaccine maker, worldwide sales of vaccines in the year 1999 were slightly over $4 billion, but sales of just one drug like the cholesterol-lowering drug, Lipitor, yield $6 billion per year. Tamas Bartfai, currently a professor at The Scripps Research Institute and Chair of the Molecular and Integrative Neurosciences Department and previously the Director of Research for Hoffman-LaRoche Pharmaceuticals, told me that because of the economic reality for pharmaceutical houses, coupled with the public health and natural interest, the United States and most western European countries guarantee a profit for the manufacture of vaccines. In addition, these countries limit medical malpractice lawsuits for the manufacturers, an event that does not occur with any other of their produced drugs. These five arguments all have their champions. Economics and political philosophy about individual rights oppose group or public safety rights.

Other serious concerns hinder smallpox vaccination. One is an issue of the vaccine’s side effects. Past experience in the United States and elsewhere when smallpox vaccine was routinely administered yielded records that one individual in every thousand vaccinated persons required related medical attention, and one death from complications occurred for every one million persons vaccinated. However, the most perplexing dilemma is that, from the time of the vaccine’s discontinuation in the United States in the 1960s and in the world in the 1980s to the present, a large segment of the population has engaged in medical therapies that suppress the immune system to control such ailments as arthritis, diabetes, multiple sclerosis, and skin conditions. These medications did not exist in the 1960s. Further, immunosuppressive diseases like human immunodeficiency virus infection and AIDS, which were not present until the 1980s, now afflict millions. Currently, physicians and public health officials are being retrained in the diagnosis and management of smallpox.

As stated previously, an immune system that is suppressed for any reason is sufficient cause for exclusion from smallpox vaccination. This includes persons with genetic immune deficiencies and pregnant women because pregnancy suppresses the immune system and fetuses (whose immune systems have not yet matured) are highly susceptible to infection. Also at high risk for complications from smallpox vaccination are those with chronic skin conditions like eczema or psoriasis and individuals undergoing or recently given medical treatments to weaken their immune system. The latter group consists of patients receiving steroid or other immunosuppressive therapy for autoimmune diseases like diabetes, multiple sclerosis, rheumatoid arthritis, lupus erythematosus, and collagen-vascular disease like scleroderma or dermamyositosis. Further, individuals who would be in close physical contact with someone who falls into these categories should not get the smallpox vaccine because of the risk to those contacts. Examples of close contacts would be persons in potential vaccinees’ household, school, or place of employment. Also to be excluded from smallpox vaccination are those individuals having illnesses that can weaken the immune system. Included in this group are persons with HIV/AIDS, cancer, leukemia, or lymphoma; recipients of bone marrow, kidney, or other transplants; patients given radiation therapy within three months before proposed vaccination; or those taking steroid or immunosuppressive medication. If the dose of steroids received has been given long enough to significantly suppress the immune response, then a waiting period of one to three months after treatment ends would be recommended before vaccination. However, the waiting time required after discontinuing steroid therapy is still controversial.

If approximately 15 to 20 percent of the population of the United States cannot be vaccinated for protection from smallpox infection because of diseases they have or medication they take, the unresolved issue is, what about the remaining 80 to 85 percent of the population? Consider this: if smallpox is reintroduced as a bioterror weapon, then everyone on earth who was not vaccinated within the seven preceding years is likely in danger of infection. One plan for a protective program is to vaccinate everyone never exposed (naïve) and revaccinate all previously vaccinated persons. Despite the risks, the benefit-to-risk ratio dramatically favors vaccination. The second strategy is to vaccinate or revaccinate only health-care workers, military, and selected government personnel, then stockpile vaccine in multiple storage areas in case of a smallpox attack. In the event of an attack, begin vaccinating the population in a wide ring surrounding the outbreak site. Implicit in this approach is acceptance of loss of life from smallpox outbreaks, surveillance and isolation of all contacts, the enforcement of quarantine regulations, and travel restrictions. Implicit in this argument are the low probability of a terrorist attack using smallpox and the development of antiviral drugs to treat smallpox infection.

The first strategy, or universal vaccination, would eliminate most episodes of disarray, confusion, and panic that could occur and would alleviate the need for massive quarantine. This was the initial strategy used to eradicate smallpox. It was successful in industrialized countries where good public health/medical services are present. It was not as successful in Third World countries where, in addition to poorer health care, the lack of refrigeration (for vaccine storage) and difficulties in travel were problems. In those instances, ring vaccination around outbreaks was successfully utilized.