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==Overview==
==Overview==
'''Smallpox''' is a contagious [[disease]] unique to humans.<ref name=Sherris>{{cite book | author = Ryan KJ, Ray CG (editors) | title = Sherris Medical Microbiology | edition = 4th ed. | pages = 525–7 | publisher = McGraw Hill | year = 2004 | pages = 525&ndash;8 |isbn = 0838585299 }}</ref> Smallpox is caused by either of two [[virus (biology)|virus]] variants named ''Variola major'' and ''Variola minor''. The deadlier form, ''V. major'', has a mortality rate of 30–35%, while ''V. minor'' causes a milder form of disease called ''alastrim'' and kills ~1% of its victims.<ref name=Behbehani_1983>{{cite journal |author=Behbehani AM |title=The smallpox story: life and death of an old disease |journal=Microbiol Rev |volume=47 |issue=4 |pages=455-509 |year=1983 | url = http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=6319980 |pmid=6319980}}</ref><ref name=Sherris /> Long-term side-effects for survivors include the characteristic skin scars.  Occasional side effects include blindness due to corneal ulcerations and infertility in male survivors.
'''Smallpox''' is a contagious [[disease]] unique to humans.<ref name=Sherris>{{cite book | author = Ryan KJ, Ray CG (editors) | title = Sherris Medical Microbiology | edition = 4th ed. | pages = 525–7 | publisher = McGraw Hill | year = 2004 | pages = 525&ndash;8 |isbn = 0838585299 }}</ref> Smallpox is caused by either of two [[virus (biology)|virus]] variants named ''Variola major'' and ''Variola minor''. The deadlier form, ''V. major'', has a mortality rate of 30–35%, while ''V. minor'' causes a milder form of disease called ''alastrim'' and kills ~1% of its victims.<ref name=Behbehani_1983>{{cite journal |author=Behbehani AM |title=The smallpox story: life and death of an old disease |journal=Microbiol Rev |volume=47 |issue=4 |pages=455-509 |year=1983 | url = http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=6319980 |pmid=6319980}}</ref><ref name=Sherris /> Long-term side-effects for survivors include the characteristic [[skin]] scars.  Occasional side effects include [[blindness]] due to [[corneal]] ulcerations and [[infertility]] in male survivors.
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==Historical Perspective==
==Historical Perspective==
Up until 1977, [[smallpox]] has been a very prevalent part of human history. The [[disease]] is estimated to be at least 16,000 years old and played a major role in the history of Europe, Asia, North America, Africa, etc. The first clinical evidence of the diseases was found in an Egyptian mummy, Ramses V. Smallpox has also been used as a weapon throughout history. The most recent example was the weaponization of smallpox during World War II. After successful [[vaccination]] campaigns throughout the 19th and 20th centuries, the WHO certified the eradication of smallpox in 1979.<ref name=WHO_Factsheet />  To this day, smallpox is the only human infectious disease to have been completely eradicated from nature.<ref>{{cite journal | author = De Cock KM | title = (Book Review) The Eradication of Smallpox: Edward Jenner and The First and Only Eradication of a Human Infectious Disease | journal = Nature Medicine | year = 2001 | volume = 7 | pages = 15&ndash;6 | url = http://www.nature.com/nm/journal/v7/n1/full/nm0101_15b.html}}</ref>
Up until 1977, when it became the only human [[infectious disease]] to have been completely eradicated, [[smallpox]] had had great impact in human history. The [[disease]] is estimated to be at least 16,000 years old and played a major role in the history of Europe, Asia, North America, and Africa. The first clinical evidence of the disease was found in an Egyptian mummy, Ramses V. [[Smallpox]] has also been used as a weapon throughout history. The most recent example was the weaponization of [[smallpox]] during World War II. After successful [[vaccination]] campaigns in the 19th and 20th centuries, the [[WHO]] certified the eradication of [[smallpox]] in 1980.<ref>{{cite journal | author = De Cock KM | title = (Book Review) The Eradication of Smallpox: Edward Jenner and The First and Only Eradication of a Human Infectious Disease | journal = Nature Medicine | year = 2001 | volume = 7 | pages = 15&ndash;6 | url = http://www.nature.com/nm/journal/v7/n1/full/nm0101_15b.html}}</ref>


===Eradication===
===Eradication===
The eradication of smallpox required a global effort. Every country was susceptible to the devastating disease. Eradicating this [[infection]] would take many years a significant sum of money, but with a worldwide commitment, it would be possible. Success was achieved in the 1970s and smallpox was officially eradicated.
[[Smallpox]] was declared eradicated in 1980 by the [[WHO]]. The eradication of [[smallpox]] required a global effort. Since every country was susceptible of the devastating [[disease]], eradicating this [[infection]] was expensive and took many years.


===Post-Eradication===
===Post-Eradication===
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==Pathophysiology==
==Pathophysiology==
[[Smallpox virus]] may be transmitted from contaminated surfaces or aerosolized particles. It is capable of inducing harm by evading the host's [[immune system]] and replicating inside host's [[cells]]. The [[virus]] may cause 3 forms of the disease: 1) ''ordinary''; 2) ''flat-type''; or 3) ''hemorrhagic [[smallpox]]''. It [[infection|infects]] different [[cells]] of the body, being known by it's characteristic lesions on the [[skin]].
[[Smallpox virus]] may be transmitted from contaminated surfaces or aerosolized particles. It is capable of inducing harm by evading the host's [[immune system]] and replicating inside host's [[cells]]. The [[virus]] may cause 3 forms of the disease: 1) ''ordinary''; 2) ''flat-type''; or 3) ''hemorrhagic [[smallpox]]''. It [[infection|infects]] different [[cells]] of the body, being known by it's characteristic lesions on the [[skin]].
==Causes==
==Causes==
[[Smallpox]] is caused by the [[variola]] virus that emerged in human populations thousands of years ago. Except for laboratory stockpiles, the [[variola]] virus has been eliminated.
[[Smallpox]] is caused by the [[variola virus]], a dsDNA [[virus]] of the [[Poxviridae]] family. There are two forms of this [[virus]] with different [[virulence]]s, evidenced on the discrepancy in respective [[death rate]]s. The [[virus]] survives in the cold and [[aerosol]]ed environments, what explains its oral [[transmission]] among humans, which are it's only host [[species]]. Unlike other [[DNA viruses]], it replicates within the [[cytoplasm]], to which it shows [[tropism]].


==Differentiating Smallpox from other Diseases==
==Differentiating Smallpox from other Diseases==
In the past, [[chickenpox]] was regularly mistaken for smallpox. [[Pustular]] scarring that can be seen in the face is a common symptom of both [[infections]]. Many times [[herpes zoster]] and [[erythema multiforme]] produce a [[vesicular rash]] and [[fever]] that has been confused with smallpox.
Prior to its eradication, [[smallpox]] would need to be differentiated from other diseases that cause a [[vesicular]] [[rash]] and a [[fever]] including [[chickenpox]] (which was often mistaken for smallpox), [[herpes zoster]] and [[erythema multiforme]].<ref name=CDC>{{cite web | title = Smallpox disease overview | url = http://www.bt.cdc.gov/agent/smallpox/overview/disease-facts.asp }}</ref>


==Epidemiology and Demographics==
==Epidemiology and Demographics==
The true [[incidence]] of [[smallpox]], before declared eradicated in 1980 by the [[WHO]], wasn't possible to specify due to the lack of new case reports from countries, particularly endemic regions, in which the reported numbers are stipulated to be 1-2% of the reality. Children and young adults were the most affected, especially in regions with low level of [[immunity]]. There is no evidence of gender or race difference in the [[incidence]] of the disease. Developing countries had a higher [[incidence]] of the disease.<ref name=WHO>{{cite web|title=The epidemiology of smallpox|url = http://whqlibdoc.who.int/smallpox/9241561106_chp4.pdf}}</ref>
==Risk Factors==
People who work in laboratories with the [[smallpox virus|virus]], or live in areas which have been target of bioterrorism, are at risk of contracting [[smallpox]]. Before eradication, [[risk factors]] included: physical contact with a patient with the disease, contact with contaminated body fluids, and exposure to contaminated aerosolized particles.<ref name=CDC>{{cite web | title = Smallpox disease overview | url = http://www.bt.cdc.gov/agent/smallpox/overview/disease-facts.asp }}</ref>


Smallpox killed an estimated 60 million [[Europe]]ans, including five reigning European monarchs, in the 18th century alone. Up to 30% of those infected, including 80% of the children under 5 years of age, died from the disease, and one third of the survivors became blind.<ref>{{cite journal |author=Barquet N, Domingo P |title=Smallpox: the triumph over the most terrible of the ministers of death |journal=Ann. Intern. Med. |volume=127 |issue=8 Pt 1 |pages=635-42 |year=1997 |pmid=9341063 |doi=}}</ref><ref>[http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1200696 Edward Jenner and the history of smallpox and vaccination]</ref>
==Natural History, Complications and Prognosis==
The [[natural history]] and [[outcome]] of [[smallpox]] depend on the form of disease. The common progress will start with [[flu]]-like [[symptoms]] followed by a [[skin rash]] that generally progresses in a typical fashion, leading to the formation of scabs that will fall off, leaving a scar. The [[complications]] may include [[respiratory]] conditions, from [[bronchitis]] to [[pneumonia]], but may also involve the [[joints]], [[bones]] and/or [[eyes]]. The overall [[fatality rate]] for the ''variola major'' form was about 30%.


Smallpox was responsible for an estimated 300–500 million deaths in the 20th century. As recently as 1967, the [[World Health Organization]] ([[WHO]]) estimated that 15 million people contracted the disease and that two million died in that year.<ref name=WHO_Factsheet>{{cite web | title=Smallpox | work=WHO Factsheet | url=http://www.who.int/mediacentre/factsheets/smallpox/en/ | accessdate=2007-09-22}}</ref>
==Diagnosis==


==Risk Factors==
===Diagnostic Criteria===
Smallpox is a [[contagious]] [[disease]] and contact with an infected individual could cause smallpox infection. It is also possible to acquire the infection through an airborne release of the smallpox [[virus]].
The [[diagnosis]] of [[smallpox]] is guided by an algorithm, elaborated by the [[CDC]], that follows certain ''major'' and ''minor criteria''.
 
===History and Symptoms===
[[Symptoms]] of [[smallpox]] progress in a typical fashion and some of its common [[symptoms]] may include high [[fever]], [[rash]] (initially in the [[oral mucosa]], followed by the [[skin]]), [[malaise]], [[fatigue]], [[muscle pain]] and [[vomiting]].
 
===Physical Examination===
Depending on the stage of the disease, physical findings may include: high [[fever]], [[tachycardia]] secondary to the [[fever]], [[rash]] of the [[oral mucosa]], [[skin rash]] with typical progression, [[ophthalmological]] changes, [[abdominal pain]], and altered [[mental status]].
 
===Laboratory Findings===
The [[polymerase chain reaction]] test and the growth of the [[virus]] in specific [[cell culture]]s allow the identification of the [[smallpox virus]].


==Treatment==
==Treatment==


===Medical Therapy===
===Medical Therapy===
There is no proven treatment for [[smallpox]]. Scientists are currently researching new treatments. Patients with smallpox may be helped by [[intravenous fluid]]s, medicine to control [[fever]] or [[pain]], and [[antibiotics]] for any secondary [[bacterial infection]]s that may occur.
There is no [[antiviral]] treatment for [[smallpox]]. In case of disease, it is only possible to manage the wellbeing of the patient, [[hydrate]] and administer certain [[drugs]] to decrease the [[fever]] or [[pain]] and to treat concomitant [[bacterial]] and/or [[viral]] [[infections]].


===Primary Prevention===
===Primary Prevention===
The smallpox vaccine helps the body develop [[immunity]] to smallpox. The vaccine        is made from a virus called vaccinia which is a “pox”-type virus        related to smallpox. The smallpox vaccine contains the “live”        vaccinia virus—not dead [[virus]] like many other vaccines. For that reason,         the vaccination site must be cared for carefully to prevent the virus from        spreading. Also, the vaccine can have [[side effects]]. The vaccine does not contain        the smallpox virus and cannot give you smallpox.
[[Primary prevention]] of [[smallpox]] consists in the administration of the ''vaccinia [[vaccine]]'', which attenuates or suppresses the manifestations of the disease, if administrated soon after [[infection]] has occurred. In the absence of an [[outbreak]], the [[vaccine]] is only administered to clinical and/or laboratory workers dealing with the [[smallpox virus|virus]] in specialized laboratories. It has several adverse effects, particularly in [[immunosuppressed]] individuals, those with [[heart]] conditions or [[allergies]], for whom its administration must be guided by specific rules.
 
Currently, the United States has a big enough stockpile of smallpox vaccine to vaccinate everyone in the United States in the event of a smallpox emergency.


===Outbreak Prevention===
===Outbreak Prevention===
CDC has a detailed plan to protect Americans against the use of smallpox as a biological weapon. This plan includes the creation and use of special teams of health care and public health workers. If a smallpox case is found, these teams will take steps immediately to control the spread of the disease. Smallpox was wiped out through specific public health actions, including vaccination, and these actions will be used again.
The [[CDC]] has elaborated a series of measures to protect the citizens in case of a [[smallpox]] [[outbreak]].<ref name=CDC>{{cite web | title = Smallpox Emergency Preparedness and Response
| url = http://www.bt.cdc.gov/agent/smallpox/basics/outbreak.asp }}</ref>


===Cost-Effectiveness of Therapy===
===Cost-Effectiveness of Therapy===
Smallpox has been successfully eradicated since the 1970s , but there was a great deal of money spent in the eradication process. Through donor governments, as well as other sources, it has been estimated that there was $300 million spent on eliminating smallpox.
The efforts made for the eradication of [[smallpox]] were cost-effective, since the disease was successfully eradicated in 1980.
 
===Future or Investigational Therapies===
Even though it has been eradicated, there are undergoing studies to find an [[antiviral drug]] against [[smallpox virus]] due to the potential of an [[outbreak]], and/or use as use in [[bioterrorism]].


==References==
==References==
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[[Category:Disease]]
[[Category:Disease]]
[[Category:Infectious disease]]
 
[[Category:Pediatrics]]
[[Category:Pediatrics]]
[[Category:Smallpox]]
[[Category:Smallpox]]

Latest revision as of 19:04, 18 September 2017

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2]

Overview

Smallpox is a contagious disease unique to humans.[1] Smallpox is caused by either of two virus variants named Variola major and Variola minor. The deadlier form, V. major, has a mortality rate of 30–35%, while V. minor causes a milder form of disease called alastrim and kills ~1% of its victims.[2][1] Long-term side-effects for survivors include the characteristic skin scars. Occasional side effects include blindness due to corneal ulcerations and infertility in male survivors.

Historical Perspective

Up until 1977, when it became the only human infectious disease to have been completely eradicated, smallpox had had great impact in human history. The disease is estimated to be at least 16,000 years old and played a major role in the history of Europe, Asia, North America, and Africa. The first clinical evidence of the disease was found in an Egyptian mummy, Ramses V. Smallpox has also been used as a weapon throughout history. The most recent example was the weaponization of smallpox during World War II. After successful vaccination campaigns in the 19th and 20th centuries, the WHO certified the eradication of smallpox in 1980.[3]

Eradication

Smallpox was declared eradicated in 1980 by the WHO. The eradication of smallpox required a global effort. Since every country was susceptible of the devastating disease, eradicating this infection was expensive and took many years.

Post-Eradication

After the reported death by smallpox accident in 1978, all known stocks of the virus were destroyed. Today only the United States CDC and Russian State Research Center of Virology and Biotechnology VECTOR have the virus in their laboratories for research purposes.

Pathophysiology

Smallpox virus may be transmitted from contaminated surfaces or aerosolized particles. It is capable of inducing harm by evading the host's immune system and replicating inside host's cells. The virus may cause 3 forms of the disease: 1) ordinary; 2) flat-type; or 3) hemorrhagic smallpox. It infects different cells of the body, being known by it's characteristic lesions on the skin.

Causes

Smallpox is caused by the variola virus, a dsDNA virus of the Poxviridae family. There are two forms of this virus with different virulences, evidenced on the discrepancy in respective death rates. The virus survives in the cold and aerosoled environments, what explains its oral transmission among humans, which are it's only host species. Unlike other DNA viruses, it replicates within the cytoplasm, to which it shows tropism.

Differentiating Smallpox from other Diseases

Prior to its eradication, smallpox would need to be differentiated from other diseases that cause a vesicular rash and a fever including chickenpox (which was often mistaken for smallpox), herpes zoster and erythema multiforme.[4]

Epidemiology and Demographics

The true incidence of smallpox, before declared eradicated in 1980 by the WHO, wasn't possible to specify due to the lack of new case reports from countries, particularly endemic regions, in which the reported numbers are stipulated to be 1-2% of the reality. Children and young adults were the most affected, especially in regions with low level of immunity. There is no evidence of gender or race difference in the incidence of the disease. Developing countries had a higher incidence of the disease.[5]

Risk Factors

People who work in laboratories with the virus, or live in areas which have been target of bioterrorism, are at risk of contracting smallpox. Before eradication, risk factors included: physical contact with a patient with the disease, contact with contaminated body fluids, and exposure to contaminated aerosolized particles.[4]

Natural History, Complications and Prognosis

The natural history and outcome of smallpox depend on the form of disease. The common progress will start with flu-like symptoms followed by a skin rash that generally progresses in a typical fashion, leading to the formation of scabs that will fall off, leaving a scar. The complications may include respiratory conditions, from bronchitis to pneumonia, but may also involve the joints, bones and/or eyes. The overall fatality rate for the variola major form was about 30%.

Diagnosis

Diagnostic Criteria

The diagnosis of smallpox is guided by an algorithm, elaborated by the CDC, that follows certain major and minor criteria.

History and Symptoms

Symptoms of smallpox progress in a typical fashion and some of its common symptoms may include high fever, rash (initially in the oral mucosa, followed by the skin), malaise, fatigue, muscle pain and vomiting.

Physical Examination

Depending on the stage of the disease, physical findings may include: high fever, tachycardia secondary to the fever, rash of the oral mucosa, skin rash with typical progression, ophthalmological changes, abdominal pain, and altered mental status.

Laboratory Findings

The polymerase chain reaction test and the growth of the virus in specific cell cultures allow the identification of the smallpox virus.

Treatment

Medical Therapy

There is no antiviral treatment for smallpox. In case of disease, it is only possible to manage the wellbeing of the patient, hydrate and administer certain drugs to decrease the fever or pain and to treat concomitant bacterial and/or viral infections.

Primary Prevention

Primary prevention of smallpox consists in the administration of the vaccinia vaccine, which attenuates or suppresses the manifestations of the disease, if administrated soon after infection has occurred. In the absence of an outbreak, the vaccine is only administered to clinical and/or laboratory workers dealing with the virus in specialized laboratories. It has several adverse effects, particularly in immunosuppressed individuals, those with heart conditions or allergies, for whom its administration must be guided by specific rules.

Outbreak Prevention

The CDC has elaborated a series of measures to protect the citizens in case of a smallpox outbreak.[4]

Cost-Effectiveness of Therapy

The efforts made for the eradication of smallpox were cost-effective, since the disease was successfully eradicated in 1980.

Future or Investigational Therapies

Even though it has been eradicated, there are undergoing studies to find an antiviral drug against smallpox virus due to the potential of an outbreak, and/or use as use in bioterrorism.

References

  1. 1.0 1.1 Ryan KJ, Ray CG (editors) (2004). Sherris Medical Microbiology (4th ed. ed.). McGraw Hill. pp. 525&ndash, 8. ISBN 0838585299.
  2. Behbehani AM (1983). "The smallpox story: life and death of an old disease". Microbiol Rev. 47 (4): 455–509. PMID 6319980.
  3. De Cock KM (2001). "(Book Review) The Eradication of Smallpox: Edward Jenner and The First and Only Eradication of a Human Infectious Disease". Nature Medicine. 7: 15&ndash, 6.
  4. 4.0 4.1 4.2 "Smallpox disease overview".
  5. "The epidemiology of smallpox" (PDF).

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