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Smallpox

Smallpox is a DNA virus that was once a cause of serious morbidity and mortality throughout the world. Due to coordinated vaccination efforts coupled with improved monitoring and sanitation, the World Health Organization was able to eliminate smallpox from the wild, and it now only remains in two Biosafety level 4 facilities located in the USA and in Russia. For centuries, smallpox plagues were responsible for killing a significant fraction of the world population. Indeed, smallpox is believed to be one of the key diseases introduced to Native American populations that lacked any immunity thereto, resulting in widespread death and devastation in these susceptible individuals. While smallpox may not longer be an immediate threat to public health, it is always something that will haunt the public imagination owing to the lethality of this legendary disease.

Disease

Smallpox virus causes a disease in humans which can take the form of two serovars: variola major (20-40% fatal) and variola minor (1% fatal). Variola major is a more widespread and rapid form of the disease and is often accompanied by devastating fevers and possible hemorrhage at the skin surface, whereas variola minor will generally only exhibit localized pox blisters. These blisteres will still be incredibly painful regardless of teh form the disease takes. Which form the disease takes in any given person likely depends on the ability of their immune system to rapidly respond to the disease before it can gain a robust foothold, however due to a lack of ongoing infections in teh human population it will be difficult to confirm what may be the cause of these smallpox serovars. The virus has a high secondary attack rate of 37-88%, making it readily and rapidly spread if not controlled. The disease causes blistering all over the skin and internal organs, leading to fluid leaking and subsequent blood loss and dehydration. Papule formation coincides with viremia of the blood. In addition, these blisters are said to be incredibly painful. The disease also tends to cause a very high fever and leaves its sufferers bedridden for the duration of their illness.

No treatment is available for those infected, and even if a person survives they will likely be scarred for life as a result of the disease. Symptomatic treatment relies on keeping the patient comfortable, reducing the fever, and avoiding rupturing the blisters. The infection will likely resolve over the course of a week or so for those who are lucky enough to survive, and their blisters will begin to harden and peel off from the skin leaving characteristic pock mark scars on the infected areas of the body.

Vaccination

The smallpox vaccine is based on a procedure originally developed in ancient China known as variolation. Variolation involved the intentional infecting of people with a small amount of material from someone infected with smallpox, and was in general far less lethal than contracting the full disease thereby allowing for improved survival. The process was later brought to the Western world where it helped to reduce the devastation of smallpox epidemics, although as variolation was still dangerous it remained a controversial procedure and it was not widely practiced among most of the population, instead primarily remaining restricted to more well off families that places a greater value on protecting the lives of their children and had the means to do so.

The scientist Edward Jenner noticed that milkmaids who had suffered from infections with the cowpox virus (aka. Vaccinia) did not get severe smallpox, leading Jenner to suspect that infection with cowpox was protective against smallpox. In order to test his hypothesis, Jenner found a young orphan boy on the streets and inoculated him with cowpox and then with smallpox. The boy was indeed protected against smallpox infection, and this Vaccinia treatment became known as vaccination and gave rise to modern vaccine theory.

While most modern vaccines against other disease use inactivated viruses or protein mixtures, the smallpox vaccine still makes use of live Vaccinia virus, as this is still the only known method of effectively preventing smallpox outbreaks. As a consequence, this vaccine has a much higher rate of side effects than other vaccines as the live virus has the potential to cause adverse reactions, localized scarring, and inflammation in vaccinated individuals. It is still superior to the risk of contracting smallpox, and as a result it remains approved for use as needed, particularly for military members.

Eradication

Smallpox is a relatively unique virus, in that humans are the only known species to be infected by the disease. This means that there is no natural reservoir species for smallpox in the wild, such that if it were to be eliminated from all humans it would be eliminated from the entire world. This, coupled with the effective vaccine and the fact that anyone who had previously contracted the disease was immune to further infection, allowed the World Health Organization to put together the largest public health campaign in the history of the world with a focus on eliminating smallpox.

The program relied on rapid response times to reports of smallpox outbreaks. Outbreaks were quarantined, and everyone who had come into contact with an infected individual was vaccinated in a process known as “ring vaccination”, which prevented the virus from easily spreading to new groups of people. Over time, cases of smallpox in the wild declined, and in the 1970's smallpox was declared to be eradicated in the wild to much celebration.

The final person to die from smallpox was an unfortunate medical photographer who was working on a microscope in a laboratory above another lab which was working on smallpox research. Evidently poor safety procedures caused smallpox to escape into the ventilation shafts of the building, allowing it to spread to the upper floor infecting the photographer with teh variola major strain and killing her. Following a subsequent investigation, the professor responsible for the lab that had release the smallpox killed himself, and all stocks of smallpox in the world were destroyed except for those at the CDC in Atlanta, Georgia, USA, and those at the Biostat facility in Russia.

Controversy

Despite having been eliminated in the wild, there has been significant resistance to the goal of destroying all remaining stocks of smallpox held in laboratories. As the vaccine does not rely on the smallpox virus, there is no need to maintain a virus stock to produce vaccines. Instead, the stocks are maintained due to concerns that there may be future outbreaks of this or similar diseases, and that only by studying the virus in detail will it be possible to combat these novel infections as they arise. There are additional concerns that the virus will be used for the purposed of Bioterrorism, prompting increasingly frequent calls for its immediate destruction. Despite these concerns, the virus remains frozen down in these research facilities, and at times it is thawed to conduct research studies. As mice cannot be infected with smallpox, researchers need to instead infect rhesus monkeys with huge doses of the disease in order to get an effect. These studies are conducted both the understand the disease itself and to test out new vaccines or drug treatments for the disease that might be useful in the case of an outbreak or bioterrorism incident. In order to further reduce the risk of the release of smallpox into the world, scientists have not released the DNA sequence of the virus even though the technology exists to decode and identify that sequence. They have not done so because of fears that someone would be able to recreate smallpox from its DNA template. Indeed, scientists have been able to create synthetic viruses and bacterial or yeast DNA genomes, so it is a reasonable concern. Going forward, it will be essential that scientists maintain smallpox research to the bare essentials and that they restrict it from interacting with human society in any way in order to preserve lives.

References

  • 1. Barquet, N. and P. Domingo, Smallpox: the triumph over the most terrible of the ministers of death. Annals of Internal Medicine, 1997. 127(8_Part_1): p. 635-642.
  • 2. Breman, J.G. and I. Arita, The confirmation and maintenance of smallpox eradication. The New England journal of medicine, 1980. 303(22): p. 1263-1273.
  • 3. Breman, J.G. and D. Henderson, Poxvirus dilemmas—monkeypox, smallpox, and biologic terrorism. New England Journal of Medicine, 1998. 339(8): p. 556-559.
  • 4. Breman, J.G. and D.A. Henderson, Diagnosis and management of smallpox. New England Journal of Medicine, 2002. 346(17): p. 1300-1308.
  • 5. Dixon, C.W., Smallpox. Smallpox., 1962.
  • 6. Edghill-Smith, Y., et al., Smallpox vaccine–induced antibodies are necessary and sufficient for protection against monkeypox virus. Nature medicine, 2005. 11(7): p. 740-747.
  • 7. Ferguson, N.M., et al., Planning for smallpox outbreaks. Nature, 2003. 425(6959): p. 681-685.
  • 8. Gani, R. and S. Leach, Transmission potential of smallpox in contemporary populations. Nature, 2001. 414(6865): p. 748-751.
  • 9. Hammarlund, E., et al., Duration of antiviral immunity after smallpox vaccination. Nature medicine, 2003. 9(9): p. 1131-1137.
  • 10. Henderson, D.A., The eradication of smallpox. Scientific American, 1976. 235(4): p. 25.
  • 11. Henderson, D.A., Smallpox: clinical and epidemiologic features. Emerging Infectious Diseases, 1999. 5(4): p. 537.
  • 12. Henderson, D.A., et al., Smallpox as a biological weapon: medical and public health management. Jama, 1999. 281(22): p. 2127-2137.
  • 13. Massung, R.F., et al., Analysis of the complete genome of smallpox variola major virus strain Bangladesh-1975. Virology, 1994. 201(2): p. 215-240.
  • 14. Stickl, H., et al., MVA vaccination against smallpox: clinical tests with an attenuated live vaccinia virus strain (MVA)(author's transl). Deutsche medizinische Wochenschrift (1946), 1974. 99(47): p. 2386.
  • 15. Wehrle, P., et al., An airborne outbreak of smallpox in a German hospital and its significance with respect to other recent outbreaks in Europe. Bulletin of the World Health Organization, 1970. 43(5): p. 669.

Biology


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