Smallpox comes with a legendary paternity. It was one of the most prevalent of all diseases; it was a massive killer, and created wretched disfigurement. Its very name could petrify an entire community.
But smallpox, as opposed to the "great pox," syphilis, is no more. With the arrival of vaccinia virus vaccination and subsequent widespread immunization, along with the vigorous efforts of the World Health Organization, smallpox was declared eradicated from the world in 1979, the only microbial disease to achieve such destinction.
How could that happen? Eradication was possible because smallpox is so obvious. Thick with pox pustules and scabs, the body is like no other; it can't be missed by searchers, no one would hide a pustule displaying individual, and there are no asymptomatic carriers or animal reservoirs. We humans are the only ones to get smallpox, and it has a short period of infectivity. Because we are the only hosts, its spread was prevented until no new cases developed. Smallpox is gone. Well, almost. The virus is kept frozen under liquid nitrogen in two safe locations: at the CDC in Atlanta and at the Research Institute for Viral Preparations, in Moscow. This maintenance has been the subject of much debate—whether the stocks in both repositories should be incinerated—totally destroyed. One side says destroy, the other says, save, because its genome needs mapping, so the controversy continues. But there is little controversy in microbiology textbooks, as those published since 1990 have little if anything on smallpox. For textbooks and the classroom, smallpox is no more.
If the case on smallpox is closed, and seemingly tightly, why is it on the short list of elite bioweapons? How could would-be terrorists obtain it, let alone use it? Actually—and this is an assumption, a bit of a stretch, but not out of the realm of possibility—as eradication approached, all countries that held smallpox cultures were requested to destroy them or turn them over to WHO. Does that provide a clue? As I say, its only an assumption, but did everyone turn their cultures in, or destroy them? So, do cultures still exist, in viable condition? If so, it is also within the realm of possibility that smallpox is obtainable. The idea is heinous, but in our tormented world, we would be remiss not to prepare our defenses, not to know about this vicious virus. The threat is low, but not zero.
For Europe and the American colonies, the earliest hint of possible control of smallpox arrived with Lady Mary Whortley Montague, wife of the British Ambassador to Turkey. Lady Montague had seen Turkish women inoculating their children, who had mild cases and became immune. On her return to England around 1710, she tried to educate the public about the procedure, but had little success  '
The year was 1777, and George Washington, Commander of the Continental Army, was in possession of a report indicating that the British planned to infect his troops with smallpox. Taking a bold step, against what was widely decried as ungodly, he ordered his troops inoculated with smallpox-infected material . Edward Jenner had yet to be heard from.
Edward Jenner, a young apprentice to a country doctor, overheard a young girl say that she could not get smallpox because she already had cowpox.
With smallpox, a person would develop a rash of malodorus pus-filled blisters over the body, which would become crusty scabs. If the person lived, the scabs would fall off, leaving deep pocked scars. It could also lead to blindness. Cowpox infected the teats of cows and the hands of milkers, usually young girls. It produced sores and fever but was rapidly transient, with subsequent immunity to smallpox.
Jenner became a physician in Berkeley, England. In May 1796, well after the Revolutionary War, Jenner vaccinated James Phipps, his gardener's 8-year-old son. (Jenner got the term vaccination, from the Latin vacca, for cow.)
Young James contracted cowpox, but recovered in a few days. Eight weeks later, allowing time for the boy's body to build immunity, Jenner exposed the boy to smallpox. James remained healthy. Today, that kind of experimentation would be considered totally unacceptable, unethical, and immoral. Over the next year Jenner vaccinated another 23 people with similar success. Good thing for all of us that he did this. The results of his work were published in 1798 in "An inquiry into the causes and effects of the variolae vaccinea a disease discovered in some of the western countries of England particularly Gloucestershire and known by the name cowpox." The medical community would have none of it—not until another experiment with cowpox and smallpox in London proved him right .
The outcome of his work was seen in reduced numbers of smallpox cases. But the pustular fluid was difficult to obtain and preserve, and the methods of vaccination used by other physicians varied from Jenner's permitting smallpox to continue, but the threat declined.
The preservation of pustular fluid for later use seemed insurmountable until Dr. Xavier de Balmis, a Spanish military physician, ventured yet another ingenious scheme. The Spanish colonies in the new world were being devastated by smallpox. King Charles II ordered Dr. Balmis to bring Jenner's vaccine to the Spanish colonies. But the voyage to South America would take at least a month. How to preserve the cowpox vaccine? De Balmis brought aboard 22 orphan children. He infected one child and waited for about 10 days as pustules formed. He then took the fluid from the lesions and inoculated it into a second child, continuing the cycle with successive immunizations. In this way fresh vaccine reached Mexico, Venezuela, and Puerto Rico. De Balmis continued on to Spain' s colonies in Asia, picking up new children along the way and finding homes for those now vaccinated, while an assistant reached Columbia, Peru, and Chile. It is estimated that 100,000-500,000 people could have been vaccinated, marking an end to the epidemic .
The variola virus is a double-stranded DNA (dsDNA) member of the genus Orthopoxvirus and the Poxviridae family, which includes cowpox, camelpox, and monkeypox. Smallpox is the largest of all viruses and its double-stranded DNA is reported to code for some 200 different proteins, one of the largest viral genomes known, which makes it almost impossible to create a synthetic copy. No effective treatment has ever been devised. Perhaps this is reason enough to maintain the virus—mapping out its genome and seeking to discover both an appropriate preventive and a cure.
When WHO launched its eradication program in 1967, the "ancient scourage" still threatened 60% of the world's population, killed every fourth victim, scarred or blinded most survivors, and eluded any form of treatment. It had to go.
Smallpox had two forms: variola major and variola minor. Both produced similar lesions, but the minor form followed a milder course, and had almost
a negligible fatality rate. Smallpox has an inoculation period of 12-14 days, during which time there is no shedding of virus, and the infected person looks and feels well and is not infectious—the lull before the storm. Suddenly a cascade of symptoms occurs: fever, headache, depression, fatigue, severe back and abdominal pain, and vomiting. Two or three days later, the fever abates and the person feels somewhat better, but now a rash appears on the face, hands, and forearms, progressing to the trunk. Lesions develop in the nose and mouth and ulcerate, releasing huge amounts of virus into the month and throat. This is the time when coughing, sneezing, and talking expel virus particles into the air, and when others are at great risk of breathing in virust containing droplets or aerosols. Now the lesions are changing from macules (flat spots) to papules (raised spots) to vesicles to pustules and onto scabs, which, when dry, fall off, leaving disfiguring scars on healing; this repulsive affliction is seen in Figure 3.2. In the absence of immunity, recall that the virus has not been circulating in the United States for more than 50 years, so that few people age 50 and under have any natural or acquired immunity. Those over 50 may or may not have antibodies. It' s a real concern today, and it is widely accepted that there is universal susceptibility—an excellent reason for smallpox to be on the short list. Contaminated clothes and bedding are also sources of infection, but much less of a risk.
Figure 3.3. Multiple puncture vaccination for smallpox by bifurcated needle. (Figure copyright WHO, Geneva.)
Figure 3.3. Multiple puncture vaccination for smallpox by bifurcated needle. (Figure copyright WHO, Geneva.)
Epidemics appear to develop relatively slowly; weeks between new cases. Experience gained during the eradication campaign indicates that given the presence of a strong surveillance system, rapid containment can break the drain of infectivity and halt an outbreak in a short time. Containment includes efficient detection, isolation (this is essential—but difficult to ensure in an open society), and vaccination of all known contacts. The public would be told, in the strongest terms, to avoid crowded places and to follow precautions for personal protection. This will, of course, have a chilling effect on business, education, and entertainment or sporting events, movies, theater, and schools. The stock exchanges could be curtailed for months until surveillance indicates a peak and certain decline in new cases. Smallpox surveillance is easier than for any other disease given the distintive rash on face, hands, and feet. Terrorists know all this, and that's their target—to disrupt the economy and society generally, which must not be allowed to happen. Emphasis must be placed on preventing epidemic spread. Bear in mind that immunity develops rapidly after vaccination. Figure 3.3 depicts the vaccination process. It ' s quick and painless, and postvaccination complications are rare. The best estimates of number and type derive from a 1968 study involving 14 million people. Progressive vaccinia, in which the local lesion failed to heal, occurred only in those with immune deficiency. It occurred in 11 people, resulting in four deaths. Generalized vaccinia, occurring 6-9 days postvaccination, produces a rash that disappears over weeks. That occurred in 143 of the 14 million vaccinated. Eczema vaccinatum occurred in 74 people who had a history of eczema. In these cases an eruption occurred at sites on the body that were affected by eczema. Symptoms were severe. Encephalitis, the most serious complication, occurred 16 times with 4 deaths .
From this study we see that approximately one death per million resulted from complications following primary vaccination, and one death per 4 million following revaccination. Whether one death per million is too high a price to pay for a protective smallpox vaccination is a personal decision. But one that must be weighed against the well-known ravages of the disease. Dr. Jenner believed that a successful vaccination produced lifetime immunity to smallpox. That may have been true in the eighteenth and nineteenth centuries, when average life expectancy was under 50, but in the twenty-first century, with life expectancy approaching 80, that is no longer the case. Revaccination will be required for protection in the event smallpox should return.
Consideration of smallpox would not be complete without noting its furious passage among the Indians of the high plains in the 1830s, which was "completely devastating." In fact, it was one of the most catastrophic epidemics recorded on the North American continent.
Smallpox had swept up from Mexico and across the plains in the eighteenth century, decimating the Mandans, Ojibway, and Pawnees, but by the 1830s the acquired immunity of their elders had waned, and none of their younger people had any immunity to smallpox. When the steamboat St. Peters from St. Louis arrived at Fort Clark with the first thaw of spring, there was great jubilation, until it was learned that several passengers had contracted variola major. Three weeks after the ship departed, Indians began dying. Many committed suicide by leaping off cliffs and stabbing themselves with knives and arrows, the pain of the pox was so excruciating. Along the upper reaches of the Missouri River, traders bungled an attempt to inoculate Indian women with scabs taken from smallpox cases. Dozens died. Seven months after the first Mandans died, the tribe had been reduced from 1600 to 31, and many other tribes approached annihilation. The Great Plains had been converted into a graveyard. As many as 2000 plains Indians had died of the hideous pocking disease . Today, all manner of Americans have arrived at the same dilemma—wholly susceptible, few vaccinated. All unsuspecting.
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