Modern health care has made us secure in many ways, but we live in an era not so long removed from a time when disease could wipe out a family, a city or a civilization. What we know of epidemics now mostly comes from the history books, and even that is simply a table of numbers and dates. In reality, these tomes tell us nothing. The common thread of humanity within us wants to know how people not numbers lived, thought, felt and died. It's only in literature where we can get a true sense of what living in an era of rampant disease must have been like. I'm a fan of the Horatio Hornblower novels, and C.S. Forester's gut-wrenching description of how Hornblower's little boy dies from smallpox, crying out for his father, carries more weight for me than all the statistics in the world.
Early efforts to prevent smallpox carried significant risk. The process of inoculation, brought to England from the East in the early part of the century, involved intentionally infecting a healthy person with a small amount of smallpox pus. The method was effective, as in conferring a mild case of the disease it often provided immunity from further infection. But the procedure carried a high risk of severe disease or death to the inoculation recipient. It must have been the terrible emotional toll of smallpox that led Edward Jenner, an 18th Century British physician, to recall that he had once heard a milkmaid say, "I shall never have smallpox for I have had cowpox. I shall never have an ugly pockmarked face." Apparently, they used "shall" a lot back then.
(For the record, cowpox is a disease in which pustular blisters develop on the hands or face, ulcerate and scar. Its cause is a related but distinct virus in the same family as smallpox. In the days of hand milking of dairy cows, it was often contracted by contact with an infected udder. It is usually self-limiting and poses no real danger to the healthy person. Today, cowpox is extremely rare.)
Jenner, a pioneer in public health, did willing battle with the premier killer of his time. His brilliance was in finding the kernel of wisdom within the milkmaid's folklore to invent the process of vaccination. While performing inoculation in his country practice, he noted that some people failed to show any reaction to the procedure. Learning that these persons had in common a prior case of cowpox, he concluded that not only did a prior case of cowpox protect one from smallpox infection, but that cowpox pus used as an inoculant could protect against smallpox without risk of inducing the dread disease. The breakthrough came in 1796, when he took cowpox pus from the hand of one Sarah Nelmes and inoculated eight-year-old James Phipps. When James was later inoculated with smallpox, he showed no symptoms despite repeated inoculation (apparently, the Institutional Review Boards were looser at that time. To Jenner's credit, however, he later built a cottage for James and planted the rose garden himself).
He first published his results with cowpox inoculation in 1798, introducing the word "virus" to the world. Jenner took his procedure to London and when he learned that the pustular material could be dried and preserved, the practice spread rapidly throughout Europe and along the lines of the British Empire. The process he developed was formally termed "vaccination" by Louis Pasteur in honor of Jenner's work. While our current vaccine is based on a related vaccinia virus, the principles of immunization remain the same.
Despite the practice of vaccination against smallpox, there were still 300 million deaths (that's 300,000,000) from the disease in the past century alone. But with the development of technology to mass-produce the vaccine and a coordinated international effort, smallpox became the first infectious disease to be eradicated from the world (the last reported case was seen in Somalia in 1977). Since then, the smallpox virus has existed only in a few high-security laboratories. As the virus was out of circulation, the need for global vaccination ceased as well. Medicine rested easy and smallpox became a mere historical curiosity.
This was the state of affairs until Sept. 11, 2001. The acts of that day brought the possibility of bioterrorism to light, including the use of smallpox as a weapon against an unimmunized population. This is not a new idea; the British used blankets from the smallpox hospital as a weapon against unimmunized Native Americans in the Colonial French and Indian Wars. The events of 9/11 simply reminded us of what had gone before.
(There is very little that came out of the 9/11 tragedy that might be considered funny. But I have to share with you a comment I ran across in a comedy piece entitled "The Heaven vs. Hell Baseball Game" by Dan St. Paul. He notes that a group of fans had taken the long bus ride up from Hell to see the game: "It's 22 former members of Al-Qaida. And don't they look surprised!" Turns out that even God can tell the difference between rational belief and blind fanaticism.)
As part of our national response to the specter of bioterror, President Bush created a program to immunize a cadre of first responders who would be able to provide initial care to those exposed to the smallpox virus. The initiative was announced in December 2002 as a three-phase program. Phase I would involve immunization of specific "high-risk" military and civilian personnel and would encompass as many as one million people. An additional 10 million medical providers and first responders would be immunized in Phase II. The vaccine would be offered to the general public in the final portion of the operation.
Reality has not met these expectations. In Florida alone, Phase I was to have seen 35,000 public health personnel vaccinated against smallpox. In Phase II, between 200,000 and 400,000 first responders and health-care providers were to be immunized. But at the time of this writing, the CDC reports that only 4,000 Floridians have received the smallpox inoculation. Here in Volusia County, we had hoped to immunize more than 1,000 first responders. We have performed only a hundred vaccinations.
This is not due to any lack of effort on the part of the State of Florida or of our local immunization staff and is not an issue of access to the process. The reasons for non-acceptance of the vaccine appear to be much deeper, and a fascinating series of articles in a recent issue of Annals of Emergency Medicine have reviewed both some practical and perpetual reasons for lack of participation in this program.
Let's start our discussion by reviewing the clinical facts about smallpox. Smallpox is a viral disease caused by variola, a member of the Orthopoxvirus family. The only known carriers of this virus are human. Variola is a hardy virus and can be isolated from scab tissue after 13 years. It is highly contagious and spreads between persons in droplets, aerosols and by contact. Symptoms usually begin within one to two weeks after exposure. Initial symptoms are non-specific, with fever, headache, generalized weakness, headache and back pain. A rash follows, progressing to the characteristic small vesicles (blisters) by the fourth or fifth day. The lesions rupture, crust over and scab the by the end of the second week. The rash is seen initially in the mouth and the face and moves downwards to involve the entire body. As scabs fall off, scarring results. A patient is most infectious in the first week of the rash and becomes noninfectious once all the scabs have separated from the skin.
Overall mortality from smallpox approaches 30%, and death usually results from secondary infection and dehydration. There is no specific medical therapy, and treatment is supportive only. It's of interest to note that while classically a disease of children (while virtually all persons were exposed to the virus, those who survived it in childhood had usually developed some degree of immunity), smallpox would now most likely be seen in the entire population born after smallpox immunization was no longer routine. (For more information about smallpox and pictures of the classic lesions, I'd refer you to the CDC Smallpox Home Page at http://www.bt.cdc.gov/agent/smallpox/index.asp.)
We've mentioned the work of Edward Jenner as a seminal moment in the history of medicine. The current state smallpox vaccine still uses Jenner's basic idea. While not made of cowpox, it is constituted from the related vaccinia virus and is a "live virus" vaccine. (Nonetheless, it's crucial to note that you CANNOT get smallpox from the vaccine.) After vaccination, a small blister forms within 10 days. The lesion crusts over, with the scabs separating in two to three weeks. A permanent scar at the site of vaccination persists. But because the vaccine is a "live virus," certain patients are more likely to suffer from side effects and probably should not receive the inoculation.
These groups include the very young (younger than one year old) and the elderly (older than 65), those with known cardiac disease, pregnant women, people with skin conditions, such as eczema or atopic dermatitis, and those who are immunocompromised for any reason.
Like any medical procedure, there are certain risks associated with the use of the smallpox vaccine. Large-scale studies in the 1960s and 1970s revealed that mild reactions occur in up to 30% of recipients and include local pain, erythema, adenopathy, myalgias and fatigue. More serious reactions were fortunately rare. Generalized vaccinia (a diffuse infection) occurred in 24 cases per million vacinees, and inadvertent inoculation of virus material from the vaccination site to other body areas was noted in 25 patients per million.
More recent work with the first crop of post 9/11 vacinees paints a somewhat different picture. Non-serious side effects were not measured, but the rate of generalized vaccinia rose to 111 per million in military personnel and 338 per million in civilians. The rate of inadvertent inoculation rose as well, having been seen in 48 military and 30 civilian personnel (a rate of 148 and 1,269 per million, respectively). Critically, there were 27 probable or confirmed cases of myopericarditis in the military group, five cases of cardiac ischemic events in the civilian group and two civilian deaths from myocardial infarction associated with the smallpox vaccine. These cardiac effects were not noted in previous works (although a new review of some 1940's New York City data does begin to hint at the problem). While the increases are alarming, it's important to put the risks in perspective. Even the risk of inadvertent inoculation, the most prominent of the serious side effects, is only 0.1% or one in a thousand. Still, you wouldn't want to be the one.The thoughtful person might reasonably ask why these cardiac effects were not noted before. After all, if we've been giving millions of doses of smallpox vaccine to the extent that we eradicated the disease from the world, why didn't these things happen during the mass vaccination process? It's a fascinating question that deserves some reflection and one we will pursue in next week's column.