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[ Fair Use: For Educational / Research / Discussion Purposes Only ] http://www.nursingceu.com/NCEU/courses/smallpox/ Smallpox Diseases Associated with Biological Warfare
Introduction The willingness of terrorist groups to employ weapons against the United States was alarmingly demonstrated by the World Trade Center bombing, in which the stated goal of the terrorists was to maximize civilian casualties. But the use of conventional weapons to terrorize a civilian population is not the only cause for concern. Health professionals should be acquainted with diseases that lend themselves to bioterrorism. The possibility of a biological attack against one or more American cities is a major concern. Should such an attack occur, medical professionals are the nation's first line of defense. The quickness with which they diagnose and respond to a bioterrorist outbreak could decide whether or not the U.S. suffers a calamity.
The two most threatening diseases associated with bioterrorism are smallpox and anthrax. Despite widespread assurances that smallpox is not longer a threat, there is overwhelming evidence that contaband samples of the virus remain stored in several laboratories throughout the world. That so little attention has been devoted to the possible emergence of a deliberately induced smallpox epidemic is evidence of poor planning as well as governmental irresponsibility.
History of Smallpox The smallpox virus probably existed since the infancy of the human species, but required the population density that can be supported by agriculture to spread quickly. The first historical record of smallpox infection occurred about 3000 years ago in Egypt. Since then massive smallpox epidemics have swept across Asia and Europe killing and disfiguring hundreds of millions. Its contagiousness and explosive infection rate allows the virus to spread rapidly . Smallpox is unique to humans and is believed to have killed more people than any other disease in recorded history.(1)
Egypt. The oldest known case of smallpox was that of Pharaoh Ramses V of Egypt who died in the twelfth century BC. His mummy reveals that the young king's face and torso were covered with blisters characteristic of smallpox.(2)
Rome. In 165 A.D. the Roman empire was devastated by a smallpox epidemic that raged for fifteen years and killed tens of millions. Romans were completely vulnerable to smallpox, the disease having suddenly emerged from the Asian continent. The decline in population reduced the Roman army which replaced its losses with barbarians who had no particular loyalty to Rome. Rome was never able to recover its former military prowess, and was eventually over-run by barbarian armies.(3)
Europe and Asia. The middle-ages saw devastating outbreaks of smallpox that killed untold millions throughout Europe and Asia leaving many of the survivors immune. It was not uncommon for victims of smallpox or some other plague to be catapulted over the walls of a city under siege in an attempt to start an epidemic within it.
Mexico. Cortez and his conquistadors invaded Mexico in 1518. The Aztecs had no immunity to a host of European diseases, the worst being smallpox. By the time Cortez and a few hundred of his exhausted warriors attacked Mexico City with its huge population, the defenders had been decimated and demoralized by smallpox. The city fell, and Aztec civilization fell with it.(4)
North America. It is estimated that smallpox, along with a number of lesser diseases, killed 56 million native Americans during the Spanish conquest of Mexico. The death toll mounted as smallpox spread to other Indian nations, none of which had any resistance to infection. Infected blankets from smallpox victims were presented to native Americans as gifts during the westward expansion of the United States.
Smallpox eradication campaign. In 1952, after the disease had killed about 300 million people in the twentieth century (5), a campaign to eradicate smallpox was initiated by the World Health Organization. The Smallpox Eradication Unit was led by Dr. Donald A. Henderson, a particularly capable epidemiologist. The disease existed in thirty-three countries and was killing more than two-million people per year. A program of mass inoculation was instituted over a twenty year period. Eighty percent of the population was inoculated in regions harboring the disease, and the number of new smallpox cases approached zero.
Yugoslavia. Yugoslavia had one of the last serious epidemics in 1972. A Muslim pilgrim returned from Mecca to his home in Kosovo carrying the deadly virus. No case had occurred in Yugoslavia since 1930, and the entire population of Yugoslavia had been routinely vaccinated for the past 50 years. The pilgrim himself was inoculated just two months earlier. Yugoslavia had, at the time, eighteen million doses of vaccine available to serve 21 million people. The World Health Organization of the United Nations had millions more. Yugoslavia had an authoritarian government under Tito which was capable of acting swiftly, and if need be, ruthlessly. The pilgrim felt achy with flu-like symptoms shortly after his return from Mecca. For over a week he had been exposing his family to infection. His first serious symptom was hemorrhaging in the whites of his eyes, which darkened until they were almost black. The development of lesions on his body did not immediately alert anyone to the possibility of smallpox, since no case had occurred in Yugoslavia for over forty years. After the onset of severe hemorrhaging, the pilgrim was rushed to a local hospital where he infected a nurse and eight other patients. From the local hospital he was rushed to a hospital in Belgrade where he infected twenty-eight more people including eight doctors and nurses. They in turn in infected 150 more. The disease was moving rapidly throughout Yugoslavia. The army was mobilized and martial law was declared. The borders were sealed and unauthorized travel was forbidden. Hotels and apartment houses were requisitioned and used to quarantine over ten thousand people. Within two weeks everyone in Yugoslavia had been revaccinated. The number of newly infected individuals dropped with each wave soon reaching zero.(6)
Bangladesh. In early 1975 smallpox broke out in Bangladesh and swept through more than five-hundred villages. Dr. Henderson and his team vaccinated people in rings around each new outbreak, and tracked down everyone who had contact with infected individuals. By the end of the year there were no new cases.(7) The last known case in the world occurred in Somalia in 1977.(8)
Epidemiology of Smallpox Smallpox is among the least pleasant diseases known to man. It is an explosively contagious viral infection that is unique to humans. It is classified as a hot agent in Biosafety Level 4 category, which means that a single case, anywhere in the world, would be considered a global medical emergency.(1) If smallpox infection is suspected, the Centers for Disease Control (CDC) Emergency Response Office should be immediately notified.
The Bioterrorism Emergency Number is (770) 488-7100.
Outbreak. In the event of an outbreak of even a single case of smallpox, emergency powers are immediatelt assumed by local, state, and federal authorities according to a chain of command and division of responsibilities. CDC personnel will rush to the scene with protective gear, vaccine, and whatever equipment is needed to collect samples. Specimen packaging and transporting includes a documented chain of possession coordinated by the FBI. Biosafety Level 4 disease specimens are rushed to CDC or several select Department of Defense (DOD) laboratories.(9) Travel may be restricted and quarantines imposed. Civil liberties and constitutional rights tend to fare badly during national emergencies of this gravity.
Epidemic outbreak. Smallpox epidemics develop in waves, with peaks and troughs separated by two-week intervals that correspond to the average incubation period of the virus. The virulence of the epidemic is a function of non-immune population density. Immunized people stifle the epidemic by lowering the average number of transmissions per infected individual. In an unvaccinated population, one infected person can infect all non-immune people with whom he comes in contact. Immunized people in an epidemic are analogous to control rods in nuclear reactors - they slow down and stifle chain-reactions.
Precautions. The U.S. Navy's Bioterrorism Task force specifies the use of masks, gowns, gloves, with thorough washing after each exposure, and the isolation of smallpox patients, preferably in negative pressure rooms. Face masks must be worn when entering the patientŐs room. Airborne precautions should be followed. Smallpox is transmitted by particles of five microns or less. They can remain suspended near the patient, or move considerable distances in air currents.
Contact precautions include use of clean gloves on entry into a patient's room, removing gown before leaving room, washing hands and exposed surfaces with antimicrobial soap, and air exchange every 6 to 12 hours through monitored high-efficiency filters.(10) For prophylactic and post-exposure immunization, smallpox vaccine should be administered to everyone in contact with infected individuals. If more than three days have elapsed since exposure, smallpox vaccine should be administered in conjunction with vaccinia-immune globulin (VIG) ) (0.6l/kg 1M).(11) (this, of course, assumes that such supplies exist). Exposed individuals should be on the alert for flue-like symptoms and rashes for 7 to 17 days after exposure. Isolating smallpox patients, individually when possible or in groups when not possible, is essential.
The Smallpox Virus (Variola) Variola, the causative agent in smallpox, is a large virus with a complex structure that belongs to a class of pox viruses called Chordopoxviridae. It has a somewhat brick-like shape with rounded corners and a knobby surface looking much like the surface of a hand-grenade. (Figure 1) By dry weight variola contains 90% protein, 5% lipid, and 3.2% DNA. Its double-stranded DNA consists of over 190,000 nucleotide base pairs built from over 100 proteins. Its dimensions are about 250 x 250 x 200 nm, large enough to be seen with an optical microscope.(12)
Replication. Variola replicates in the cytoplasm of the host cell independent of the host cell enzymes. The virus rapidly multiplies until the cell bursts, releasing tens of thousands of variolas capable of attacking other host cells. The replication cycle is repeated every few hours and by the time the victim shows symptoms, he is awash in quadrillions of variolas.
Identification. Confirmation of the presence of the variola virus is carried out by examination of fluid from an active lesion. Active skin lesions are characterized by altered epidermal cells containing eosinophilic intracytoplasmic bodies (Guarneri bodies). Further confirmation is carried out using immunofluorescence and microscopy. The distinctive shape and size of variola (it is the largest known virus) should make a diagnosis definitive.
Mechanism of Infection Droplet infection. To sustain itself, the smallpox virus is passed from person to person in a continuing and expanding chain of infection. It is spread primarily by the inhalation of airborne droplets, and secondarily by physical contact. A single invisible droplet of exhalant travels in still air about ten feet from its human source, and contains far more viruses than is needed to infect a single individual.(13)
Variola major. There are two variants of the smallpox virus: variola major which is the more lethal variant, and variola minor which is a weak mutant. We will only deal wih variola major. There is enough variation in the disease progression that smallpox may not be recognized even by doctors familiar with the disease of whom there are virtually none. Onset. During a typical incubation period of ten to fifteen days the infected person will feel normal, but is already contagious. The first signs of the onset of the disease are severe flu-like symptoms, headache and fever. In another three or four days, tiny red dots appear over the entire body. The spots develop, in order of progression, from macules to papules to vesicles to pustules. An identifying characteristic of smallpox is its foul and distinctive odor arising from the victim's pustules, which once smelled is never forgotten.
Figure 2. These photographs show the development of smallpox in a child who survived. They were taken 5, 7, 10, and 15 days after the appearance of a rash.
Pustules. If the pustules merge to form a cont inuous surface encasing the entire body, the disease is said to have split the skin, and the person will usually die. The pustules can be so close together that the skin resembles a cobblestone street. If the person survives, the blisters will turn into highly contagious scabs which fall off the body, leaving the victim permanently scarred and in some cases blind. The mortality rate is usually between twenty-five and fifty percent. An epidemic in Canada in 1924 killed 50% of those stricken.(14)
There are two particularly deadly forms of smallpox - flat black pox and hemorrhagic black pox:
Flat black pox. In flat black pox the skin remains relatively smooth, but blackens in large areas. The victim's immune system, having been paralyzed, produces no pus. The blackened areas merge as hemorrhaging under the skin advances. The skin sometimes detaches from the body and falls off in large sheets.
Hemorrhagic black pox. In the presence of hemorrhagic black pox, highly contagious black, unclotted blood seeps from the victim's orifices. The virus will sometimes break down the internal membranes which line the body's organs. Pieces of membrane can be expelled through the victim's orifices accompanied by a profusion of blood. The victim almost never survives this development.
The disease most commonly confused with smallpox is chicken pox. During the first two or three days after the rash has appeared, it may be difficult to tell them apart. Chicken pox lesions are more superficial and variated than the smallpox pustules which are dense and almost identical. Smallpox pustules tend to be more numerous than chicken pox on the face and limbs. Chicken pox lesions, unlike smallpox lesions, are very rarely found on the palms and soles.(15)
The Smallpox Vaccine Because many of the proteins present in other pox viruses are similar to those found in smallpox, it is possible to develop effective vaccines based on non-human pox viruses (cow pox for instance). Other pox viruses that might grant immunity to humans are monkey pox, orf in sheep, and molluscum contagiosum, a relatively mild sexually transmitted disease in humans. Smallpox vaccine is effective for approximately ten years, after which it begins to lose potency. No one has been vaccinated in the United States for the past twenty-five years. We are almost as virgin a population as were the Aztecs when the conquistadors descended upon them.
The Centers for Disease Control owns a small supply of smallpox vaccine that is stored in four cardboard boxes in the walk-in freezer of a pharmaceutical company in Pennsylvania. The company, Wyet-Ayerst Laboratories, manufactured fifteen million doses of smallpox vaccine over a period of five years some twenty-five to thirty years ago.(16) The CDC owns six to seven million doses of this production, a ridiculously insufficient amount to protect a population the size of the US. But even this may be an inflated figure and it has been reported that the vaccine has seriously deteriorated. Some people on whom it was tested have had serious and even fatal reactions. The antidote to these reactions has also deteriorated.(17) Such is our state of readiness.
When the World Health Organization declared total victory over smallpox in 1979 it had ten-million doses of smallpox vaccine in storage in Geneva, Switzerland. The CDC then proceeded to deliberately destroy nine and one-half million of these doses.(18) The people making this decision had total confidence in the highly unlikely proposition that variola was completely and permanently eradicated from the face of the earth. (Why, in that case, did they not destroy all ten million doses of vaccine?) This leaves one-half million doses to deal with a global crisis, or one dose for every 12,000 people.
Smallpox vaccine is not difficult to produce. In the late eighteenth century it was noticed by an English country doctor named Edward Jenner that dairy maids who had contracted a mild disease called cowpox were never stricken with smallpox. Using a drop of liquid from a cowpox blister, Dr. Jenner scratched it into the arm of a young boy. Several months later he introduced deadly smallpox pus into the boy's arm. The boy did not come down with the disease.(19)
Smallpox vaccine is almost 100% effective. Only three in one-million doses produce adverse side-effects. The most frequent of these side-effects is a condition called progressive vaccinia which affects immune-compromised people. This condition, in which vaccinia grows at the vaccination cite, can be cured with vaccinia immune globulin.(20)
The United States does not manufacture smallpox vaccine in even limited quantities. This nation, which managed to manufacture and distribute smallpox vaccine during the administration of Thomas Jefferson, seems incapable of doing so today. Compared to other defense and/or health systems, the cost of inoculating our entire population would be trivial. If the U.S. began a crash program to manufacture the vaccine and inoculate every person in the nation, it is estimated that it would take about 36 months to complete the task.(21)
Government Readiness If we compare our readiness with that of Yugoslavia in 1972 we might as well be a stone-age civilization. Official indifference to the threat of smallpox could be rationalized if the virus was known to be extinct. Unfortunately, the opposite is known to be the case. Anti-terrorist experts are certain that the virus, though outlawed by the United Nations, exists in a number of clandestine biowarfare laboratories located in several countries.(22)
These include Russia, China, North Korea, Pakistan, Iraq and Iran. The United States keeps several vials of live virus at the Centers for Disease Control in Atlanta, hopefully under foolproof security. The viruses are used to experiment with drugs that might be effective against smallpox. So far none have been found.(23)
In 1995 the CIA gave a classified briefing to a number of public health officials and biologists during which the list of possible variola sources was extended to include Osama bin Ladden's Islamic terrorist organization, and Japan's Aum Shinrikyo sect that was responsible for attacking subway commuters in Tokyo with nerve gas.(24) Unlike nuclear weapons, the virus could be surreptitiously introduced into a population without revealing that a deliberate attack had occurred, or who had launched the attack.
In 1992 the leading Russian bioweapons expert and the inventor of the world's most powerful anthrax virus, Dr. K. Alibekov, defected to the U.S. He revealed that the Russian military has secretly stored at least twenty tons of the live smallpox virus on various military bases throughout Russia. The intelligence community has corroborated this information.(25)
The leading Russian institute of virology, known as Vector, is situated outside Novosibersk in Siberia. It is also a viral weapons development facility that contains living variolas in a freezer.(26) Vector is underfunded and is considered by the intelligence community to be a viral Chernobyl - an accident waiting to happen. Since the fall of the Soviet Union, unpaid weaponry scientists have been leaving rotting Soviet military facilities in droves, carrying their expertise with them to unknown paymasters. There is no reason to believe that some Vector scientists are not numbered among them. Nor do we have any assurance that living variolas were not stolen amidst post-Soviet chaos. Our principle biodefence laboratory is the United States Army Medical Institute of Infectious Diseases in Fort Detrick, Maryland. The head of the laboratory, Dr. Peter Jahring, recently said the following: "I don't think there is any higher biological threat to this nation than smallpox... . If we have a bioterror emergency with smallpox, there will be no time to start stroking our beards. We'd better have vaccine pre-positioned on pallets and ready to go." (27)
In 1995 the National Security Council declared defense against smallpox bioterrorism to be a top priority. The Department of Health and Human Services (HHS), headed by Donna Shalala, was given responsibility for building a stockpile of smallpox vaccine large enough to protect the United States. A controversial study estimated the cost of producing 300,00 doses at seventy-five dollars per dose and a delivery date in the year 2006.(28) It was decided that the cost was prohibitive. (For several generations a much poorer U.S. managed to inoculate everyone in the nation). The project was put on a back-burner, from where it has apparently fallen off the stove. Retired General P. K. Russell MD, who headed the biohazard team that stopped an ebola epidemic in 1989, blames our vulnerability to smallpox on "a lack of effective leadership on the part of the government." D. A. Henderson said "The effort at HHS still isn't organized."(29) The Department of Health and Human Services is highly politicized even by Washington D.C. standards, and has no history of assuming responsibility for any portion of national defense. This makes the failure to build a smallpox vaccine stockpile even more incomprehensible, since it does not entail the risk of handling live variolas.
Conclusion Our lack of preparedness is not limited to smallpox. We cannot hope to be completely protected from every possible mode of attack. There is always a period of vulnerability between the introduction of a new attack weapon, and a defense against it. However in the case of smallpox, vaccination predated the bioterrorist threat by more than two centuries. There is no reason why we should remain vulnerable to this terrible disease.
Addendum In August 1999 the new director of CDC in Atlanta, Jeffrey Koplan, decided to end the bureaucratic stalemate concerning the production of smallpox vaccine. He called a meeting of high officials in the relevant agencies (the Pentagon, the White House, the National Institutes of Health, and the Department of Health and Human Services) and announced that no one was allowed to leave the room untill a feasable plan for manufacturing an adequate supply of vaccine in the shortest possible time was instituted. Dr. Koplan is one of the few doctors in the world with experience in fighting smallpox. He had served on the medical team that successfully stopped the world's last epidemic in Bangladesh in 1973. The CDC was given the responsibility of creating the stockpile of smallpox vaccine with a target date set for 2002.(30)
Copyright © 2000-2001 Robert Trupin. Reprinted with permission. --------------------
-- Doreen (firstname.lastname@example.org), October 29, 2001
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