Smallpox pathophysiology: Difference between revisions

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==Overview==
==Overview==
[[Smallpox virus]] may be transmitted through contaminated surfaces or aerosolized particles. It is able to induce 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]].
[[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 propensity to cause characteristic pock like lesions on the [[skin]].


==Transmission==
==Transmission==
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==Genetics==
==Genetics==
[[Smallpox]] [[virulence]] is due to its ability to evade the host's [[immune system]]. Most [[proteins]] responsible for the [[pathogenesis]] of the [[virus]] are located at the terminal [[DNA]] regions of the [[virus]].
[[Smallpox]] [[pathogenicity]] is due to its ability to evade the host's [[immune system]]. Most [[proteins]] responsible for the [[pathogenesis]] of the [[virus]] are located at the terminal [[DNA]] regions of the [[virus]].


[[Genetic]] comparisons of the [[smallpox virus]] with the [[vaccinia virus]] allowed to observe certain [[genetic]] changes that may be responsible for the [[virulence]] of the [[smallpox virus]]. However, without studying the [[gene]]'s transcripts, it is not possible to draw objective conclusions.<ref name="pmid8184534">{{cite journal| author=Massung RF, Liu LI, Qi J, Knight JC, Yuran TE, Kerlavage AR et al.| title=Analysis of the complete genome of smallpox variola major virus strain Bangladesh-1975. | journal=Virology | year= 1994 | volume= 201 | issue= 2 | pages= 215-40 | pmid=8184534 | doi=10.1006/viro.1994.1288 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8184534  }} </ref>
[[Genetic]] comparisons of the [[smallpox virus]] with the [[vaccinia virus]] allowed to observe certain [[genetic]] changes that may be responsible for the [[virulence]] of the [[smallpox virus]]. However, without studying the [[gene]] transcripts, it is not possible to draw objective conclusions.<ref name="pmid8184534">{{cite journal| author=Massung RF, Liu LI, Qi J, Knight JC, Yuran TE, Kerlavage AR et al.| title=Analysis of the complete genome of smallpox variola major virus strain Bangladesh-1975. | journal=Virology | year= 1994 | volume= 201 | issue= 2 | pages= 215-40 | pmid=8184534 | doi=10.1006/viro.1994.1288 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8184534  }} </ref>


==Pathogenesis==
==Pathogenesis==
The smallpox virus commonly enters the body through the [[upper respiratory tract]], invading the [[oropharyngeal]] and [[respiratory]] [[mucosa]].<ref>{{cite book | last = Cecil | first = Russell | title = Goldman's Cecil medicine | publisher = Elsevier/Saunders | location = Philadelphia | year = 2012 | isbn = 1437716040 }}</ref> Other possible ports of entry include: skin, conjunctivae as well as through the placenta.<ref name=WHO>{{cite web | title = Smallpox and its Eradication | url = http://apps.who.int/iris/bitstream/10665/39485/1/9241561106.pdf?ua=1 }}</ref> Although the viral scabs may contain life viruses, they are commonly contained within thickened material, which limits transmissibility.
The [[smallpox virus]] commonly enters the body through the [[upper respiratory tract]], invading the [[oropharyngeal]] and [[respiratory]] [[mucosa]].<ref>{{cite book | last = Cecil | first = Russell | title = Goldman's Cecil medicine | publisher = Elsevier/Saunders | location = Philadelphia | year = 2012 | isbn = 1437716040 }}</ref> Other possible ports of entry include: [[skin]], [[conjunctiva]] as well as through the [[placenta]].<ref name=WHO>{{cite web | title = Smallpox and its Eradication | url = http://apps.who.int/iris/bitstream/10665/39485/1/9241561106.pdf?ua=1 }}</ref> Although the [[viral]] scabs may contain life [[virus]]es, they are commonly contained within thickened material, which limits [[transmission]].


Once in the [[respiratory]] [[mucosa]], the [[infection]] commonly progresses as:<ref name="MooreSeward2006">{{cite journal|last1=Moore|first1=Zack S|last2=Seward|first2=Jane F|last3=Lane|first3=J Michael|title=Smallpox|journal=The Lancet|volume=367|issue=9508|year=2006|pages=425–435|issn=01406736|doi=10.1016/S0140-6736(06)68143-9}}</ref><ref name=WHO>{{cite web | title = Smallpox and its Eradication | url = http://apps.who.int/iris/bitstream/10665/39485/1/9241561106.pdf?ua=1 }}</ref><ref name="BremanHenderson2002">{{cite journal|last1=Breman|first1=Joel G.|last2=Henderson|first2=D.A.|title=Diagnosis and Management of Smallpox|journal=New England Journal of Medicine|volume=346|issue=17|year=2002|pages=1300–1308|issn=0028-4793|doi=10.1056/NEJMra020025}}</ref>
Once in the [[respiratory]] [[mucosa]], the [[infection]] commonly progresses as:<ref name="MooreSeward2006">{{cite journal|last1=Moore|first1=Zack S|last2=Seward|first2=Jane F|last3=Lane|first3=J Michael|title=Smallpox|journal=The Lancet|volume=367|issue=9508|year=2006|pages=425–435|issn=01406736|doi=10.1016/S0140-6736(06)68143-9}}</ref><ref name=WHO>{{cite web | title = Smallpox and its Eradication | url = http://apps.who.int/iris/bitstream/10665/39485/1/9241561106.pdf?ua=1 }}</ref><ref name="BremanHenderson2002">{{cite journal|last1=Breman|first1=Joel G.|last2=Henderson|first2=D.A.|title=Diagnosis and Management of Smallpox|journal=New England Journal of Medicine|volume=346|issue=17|year=2002|pages=1300–1308|issn=0028-4793|doi=10.1056/NEJMra020025}}</ref>
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* Exuberant secondary [[viraemia]], leading to [[symptom]] onset
* Exuberant secondary [[viraemia]], leading to [[symptom]] onset


During secondary [[viraemia]] the [[virus]] infects mucous cells of the [[pharynx]] and [[mouth]], and [[endothelium]] of the [[capillaries]] of the [[dermis]], causing skin scabs. Other [[organs]] with high [[viral]] loads include:<ref name="BremanHenderson2002">{{cite journal|last1=Breman|first1=Joel G.|last2=Henderson|first2=D.A.|title=Diagnosis and Management of Smallpox|journal=New England Journal of Medicine|volume=346|issue=17|year=2002|pages=1300–1308|issn=0028-4793|doi=10.1056/NEJMra020025}}</ref>
During secondary [[viraemia]] the [[virus]] [[infection|infects]] mucous cells of the [[pharynx]] and [[mouth]], and [[endothelium]] of the [[capillaries]] of the [[dermis]], causing [[skin]] lesions. Other [[organs]] with high [[viral]] loads include:<ref name="BremanHenderson2002">{{cite journal|last1=Breman|first1=Joel G.|last2=Henderson|first2=D.A.|title=Diagnosis and Management of Smallpox|journal=New England Journal of Medicine|volume=346|issue=17|year=2002|pages=1300–1308|issn=0028-4793|doi=10.1056/NEJMra020025}}</ref>


* [[Spleen]]
* [[Spleen]]
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* Neutralizing [[antibodies]], during first week of disease, remaining for many years
* Neutralizing [[antibodies]], during first week of disease, remaining for many years
* Hemagglutination-inhibition [[antibodies]], by the 16th day of [[infection]], beginning to decrease after 1 year
* Hemagglutination-inhibition [[antibodies]], by the 16th day of [[infection]], beginning to decrease after 1 year
* Complement-fixation [[antibodies]], by the 18th day of [[infection]], beginning to decrease after 1 year
* Complement-fixation [[antibodies]], by the 18th day of [[infection]], beginning to decrease after 1 year
* [[Memory T cell]]s, remaining for 50 years
* [[Memory T cell]]s, remaining for 50 years


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==Gross Pathology==
==Gross Pathology==
Depending on the status of the patient's [[immune system]], there may be identified 3 forms of [[smallpox]]:<ref>{{cite book | last = Mandell | first = Gerald | title = Mandell, Douglas, and Bennett's principles and practice of infectious diseases | publisher = Churchill Livingstone/Elsevier | location = Philadelphia, PA | year = 2010 | isbn = 0443068399 }}</ref>
Depending on the status of the patient's [[immune system]], there are 3 forms of [[smallpox]]:<ref>{{cite book | last = Mandell | first = Gerald | title = Mandell, Douglas, and Bennett's principles and practice of infectious diseases | publisher = Churchill Livingstone/Elsevier | location = Philadelphia, PA | year = 2010 | isbn = 0443068399 }}</ref>


===Ordinary Smallpox===
===Ordinary Smallpox===
Characterized by the following progression of lesions:<ref>{{cite book | last = Mandell | first = Gerald | title = Mandell, Douglas, and Bennett's principles and practice of infectious diseases | publisher = Churchill Livingstone/Elsevier | location = Philadelphia, PA | year = 2010 | isbn = 0443068399 }}</ref>
Ordinary smallpox is characterized by the following progression of lesions:<ref>{{cite book | last = Mandell | first = Gerald | title = Mandell, Douglas, and Bennett's principles and practice of infectious diseases | publisher = Churchill Livingstone/Elsevier | location = Philadelphia, PA | year = 2010 | isbn = 0443068399 }}</ref>
* Initial [[Hypopigmentation|hypopigmented]] [[macules]], initially in the mouth
* Initial [[Hypopigmentation|hypopigmented]] [[macules]], which appear first in the [[mouth]]
* [[Macules]] progress into [[papules]] and subsequently to [[vesicles]]
* [[Macules]] progress into [[papules]] and subsequently to [[vesicles]]
* [[Vesicles]] become [[pustules]]  
* [[Vesicles]] become [[pustules]]  
* At the 14th day [[pustules]] loose liquid content and become crusted
* At the 14th day, [[pustules]] loose liquid content and become crusted
* At the 3rd week, most crusts will separate (palms and soles last)
* At the 3rd week, most crusts will separate (palms and soles last)
This form of [[smallpox]] is typical of an [[immunocompetent]] patient, whose [[immune system]] is able to inhibit [[viral replication]].
This form of [[smallpox]] is typical of an [[immunocompetent]] patient, in whom the [[immune system]] is able to inhibit [[viral replication]].


===Flat-type Smallpox===
===Flat-type Smallpox===
Characterized by the following progression of lesions:<ref>{{cite book | last = Mandell | first = Gerald | title = Mandell, Douglas, and Bennett's principles and practice of infectious diseases | publisher = Churchill Livingstone/Elsevier | location = Philadelphia, PA | year = 2010 | isbn = 0443068399 }}</ref>
Flat-type smallpox is characterized by the following progression of lesions:<ref>{{cite book | last = Mandell | first = Gerald | title = Mandell, Douglas, and Bennett's principles and practice of infectious diseases | publisher = Churchill Livingstone/Elsevier | location = Philadelphia, PA | year = 2010 | isbn = 0443068399 }}</ref>
* Delayed appearance of [[macules]]
* Delayed appearance of [[macules]]
* Slow progression of the lesions, usually with flat and soft appearance
* Slow progression of the lesions, usually with flat and soft appearance
* Possible slough of [[skin]] sections
* Possible slough of [[skin]] sections
Most cases are fatal with presence of severe [[toxemia]]. This form of [[smallpox]] is typical of patients with weak cellular [[immune response]] to the [[virus]].
Most cases are fatal with presence of severe [[toxemia]]. This form of [[smallpox]] is typical of patients with weak [[Cell-mediated immunity|cellular immune response]] to the [[virus]].


===Hemorrhagic-type smallpox===
===Hemorrhagic-type smallpox===
Characterized by the following progression of lesions:<ref>{{cite book | last = Mandell | first = Gerald | title = Mandell, Douglas, and Bennett's principles and practice of infectious diseases | publisher = Churchill Livingstone/Elsevier | location = Philadelphia, PA | year = 2010 | isbn = 0443068399 }}</ref>
Hemorrhagic-type smallpox is characterized by the following progression of lesions:<ref>{{cite book | last = Mandell | first = Gerald | title = Mandell, Douglas, and Bennett's principles and practice of infectious diseases | publisher = Churchill Livingstone/Elsevier | location = Philadelphia, PA | year = 2010 | isbn = 0443068399 }}</ref>
* [[Skin]] [[petechiae]]
* [[Skin]] [[petechiae]]
* [[Mucous membrane]] and [[conjunctival]] [[bleeding]]
* [[Mucous membrane]] and [[conjunctival]] [[bleeding]]
* Subcutaneous hemorrhage gives skin and conjunctivae deep red appearance
* [[Subcutaneous]] [[hemorrhage]] gives [[skin]] and [[conjunctiva|conjunctivae]] deep red appearance
* Organ bleeding
* Organ bleeding
* Early death by multi organ failure, usually before appearance of [[macula|maculae]].
* Early death by multi organ failure, usually before appearance of [[macula|maculae]].
This rare form of [[smallpox]] is typical of patients with severely compromised [[immune response]], in which there is intense [[viral replication]] in the [[bone marrow]] and [[spleen]] It is also associated with intense [[toxemia]].
This rare form of [[smallpox]] is typical of patients with severely compromised [[immune response]], in which there is intense [[viral replication]] in the [[bone marrow]] and [[spleen]]. It is also associated with intense [[toxemia]].


==Microscopic Pathology==
==Microscopic Pathology==
The typical [[skin]] [[vesicles]] observed in [[smallpox]] occur following:<ref>{{cite book | last = Cecil | first = Russell | title = Goldman's Cecil medicine | publisher = Elsevier/Saunders | location = Philadelphia | year = 2012 | isbn = 1437716040 }}</ref>
The typical [[skin]] [[vesicles]] observed in [[smallpox]] occur following:<ref>{{cite book | last = Cecil | first = Russell | title = Goldman's Cecil medicine | publisher = Elsevier/Saunders | location = Philadelphia | year = 2012 | isbn = 1437716040 }}</ref>
* [[Viral infection]] of the [[epidermal]] [[cell]]
* [[Viral infection]] of the [[epidermal]] [[cell]]
* [[Cells]] in [[malpighian layer]] enter balloon degeneration due to formation of [[vacuoles]]
* [[Cells]] in [[malpighian layer]] entering balloon degeneration, from formation of [[vacuoles]]
* [[Cytoplasmic]] enlargement leads to loss of [[nuclear]] material
* [[Cytoplasmic]] enlargement leading to loss of [[nuclear]] material
* Destruction of upper and middle layers of [[stratum spinosum]]
* Destruction of upper and middle layers of [[stratum spinosum]]
* Formation of [[vesicle]], with high [[viral]] index
* Formation of [[vesicles]], with high [[viral]] index


On the other hand, in the [[infected]] [[mucous]] surfaces, the [[viral]] proliferation and absence of the [[stratum corneum]] lead to the formation of [[ulcers]]. These ultimately lead to the release of greater loads of [[virus]] to the [[oropharynx]].<ref>{{cite book | last = Cecil | first = Russell | title = Goldman's Cecil medicine | publisher = Elsevier/Saunders | location = Philadelphia | year = 2012 | isbn = 1437716040 }}</ref>
On the other hand, in the [[infected]] [[mucous]] surfaces, the [[viral]] proliferation and absence of the [[stratum corneum]], lead to the formation of [[ulcers]]. These ultimately lead to the release of greater loads of [[virus]] into the [[oropharynx]].<ref>{{cite book | last = Cecil | first = Russell | title = Goldman's Cecil medicine | publisher = Elsevier/Saunders | location = Philadelphia | year = 2012 | isbn = 1437716040 }}</ref>


===Histopathology===
===Histopathology===
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====B-type, or Guarnieri bodies====
====B-type, or Guarnieri bodies====
* Areas of active [[viral replication]]
* In areas of active [[viral replication]]
* Present in [[infections]] by all poxviruses
* Present in [[infections]] by all poxviruses
* Appear as [[basophilic]] bodies near the [[nucleus]] on hematoxylin and eosin-stained samples
* Appear as [[basophilic]] bodies near the [[nucleus]] on hematoxylin and eosin-stained samples
* Evident at [[epithelial cells]] underlying [[vesicles]] and [[pustules]]
* Evident at [[epithelial cells]] underlying [[vesicles]] and [[pustules]]


===Image Gallery===
==Gallery==
 
<gallery>
<gallery>
Image:Smallpox-1.jpg|Hematoxylin and eosin (H&E)-stained tissue sample, reveals some of the histopathologic changes found in a human skin tissue sample from the site of a smallpox lesion. <SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
Image:Smallpox-1.jpg|Hematoxylin and eosin (H&E)-stained tissue sample, reveals some of the histopathologic changes found in a human skin tissue sample from the site of a smallpox lesion. <SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>


Image:Smallpox-2.jpg|hematoxylin and eosin (H&E)-stained tissue sample, reveals some of the histopathologic changes found in a human skin tissue sample from the site of a smallpox lesion. <SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
Image:Smallpox-2.jpg|hematoxylin and eosin (H&E)-stained tissue sample, reveals some of the histopathologic changes found in a human skin tissue sample from the site of a smallpox lesion. <SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
Image:Smallpox-3.jpg| Upper arm revealing the site of a newly-administered smallpox vaccination, which had been performed using a “Ped-O-Jet®” jet injector.  Notice the wheal type morphology of the vaccination site.<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
Image:Smallpox-4.jpg| This was a vaccinial lesion that had manifested itself on the face of a mother who had acquired the virus after her daughter’s smallpox vaccination.<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>


Image:Smallpox-5.jpg| This is a chickenpox scab (left), and smallpox scab (right) viewed in profile as a demonstration in comparative morphology. <SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
Image:Smallpox-5.jpg| This is a chickenpox scab (left), and smallpox scab (right) viewed in profile as a demonstration in comparative morphology. <SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
Image:Smallpox-6.jpg| This image depicts the smallpox vaccination site, which in the case of this recipient, displayed a reaction after a period of seven days.<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>


Image:Smallpox-7.jpg| This image depicts three mounted chickenpox scabs seen from the side revealing the superficiality of these scabs when morphologically compared to a smallpox scab.<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
Image:Smallpox-7.jpg| This image depicts three mounted chickenpox scabs seen from the side revealing the superficiality of these scabs when morphologically compared to a smallpox scab.<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
Image:Smallpox-8.jpg| This image depicts the right shoulder region of a male patient from a lateral perspective, who’d received a smallpox vaccination, while ill with chickenpox. Note the intense reaction at the vaccination site.<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>


Image:Smallpox-9.jpg| Viewed from above, this image depicts a smallpox scab (left), and chickenpox scab (right) as a demonstration in comparative morphology. <SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
Image:Smallpox-9.jpg| Viewed from above, this image depicts a smallpox scab (left), and chickenpox scab (right) as a demonstration in comparative morphology. <SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>


Image:Smallpox-10.jpg| Classic maculopapular rash due to an ordinary, or “discrete” smallpox infection. Note distribution of the rash included his chest, left arm and hand, and left thigh and leg, affecting the contralateral side in the same manner.<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
Image:Smallpox-74.jpg| Cytoarchitectural pathologic changes found in a sample of skin tissue from a eczema vaccinatum lesion, which had manifested itself after this patient had received a smallpox vaccination.<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>


Image:Smallpox-11.jpg| African Cameroonian boy in the process of receiving his vaccinations during the African Smallpox Eradication and Measles Control Program.<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
Image:Smallpox-12.jpg| Male from Sierra Leone. Case of “modified” smallpox, in which the patient had received a smallpox vaccination some months before. Note the sparse amount of maculopapular skin lesions dispersed over his face. <SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
Image:Smallpox-13.jpg| Girl who received a smallpox vaccination in the left upper arm displayed a local complication at the vaccination site, where a chronic superinfection resulted in a granulation tissue reaction. <SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
Image:Smallpox-14.jpg| Child’s arm after having received a smallpox vaccination in the country of Sierra Leone. Note intradermal wheal, which is a raised area at the site where the Ped-o-jet® delivered the smallpox vaccine. <SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
Image:Smallpox-15.jpg| Newborn infant delivered during its 28th week of gestation, to a mother who’d received a primary smallpox vaccination during the 23rd week of her pregnancy. Upon delivery, this infant displayed typical vaccinial skin lesions, and died at 8 days of age. Vaccinia virus was isolated from the placenta.  <SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
Image:Smallpox-16.jpg|  <SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
Image:Smallpox-17.jpg|  <SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
Image:Smallpox-18.jpg|  <SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
Image:Smallpox-19.jpg|  <SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
Image:Smallpox-20.jpg|  <SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
Image:Smallpox-21.jpg|  <SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>


Image:Smallpox-76.jpg| Cytoarchitectural pathologic changes found in a sample of skin tissue from a eczema vaccinatum lesion, which had manifested itself after this patient had received a smallpox vaccination.<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
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[[Category:Needs overview]]
[[Category:Needs overview]]
[[Category:Disease]]
[[Category:Disease]]
[[Category:Infectious disease]]
 
[[Category:Pediatrics]]
[[Category:Pediatrics]]
[[Category:Smallpox]]
[[Category:Smallpox]]

Latest revision as of 19:04, 18 September 2017

Smallpox Microchapters

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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 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 propensity to cause characteristic pock like lesions on the skin.

Transmission

Smallpox virus is transmitted by:[1]

Genetics

Smallpox pathogenicity is due to its ability to evade the host's immune system. Most proteins responsible for the pathogenesis of the virus are located at the terminal DNA regions of the virus.

Genetic comparisons of the smallpox virus with the vaccinia virus allowed to observe certain genetic changes that may be responsible for the virulence of the smallpox virus. However, without studying the gene transcripts, it is not possible to draw objective conclusions.[2]

Pathogenesis

The smallpox virus commonly enters the body through the upper respiratory tract, invading the oropharyngeal and respiratory mucosa.[3] Other possible ports of entry include: skin, conjunctiva as well as through the placenta.[4] Although the viral scabs may contain life viruses, they are commonly contained within thickened material, which limits transmission.

Once in the respiratory mucosa, the infection commonly progresses as:[5][4][6]

During secondary viraemia the virus infects mucous cells of the pharynx and mouth, and endothelium of the capillaries of the dermis, causing skin lesions. Other organs with high viral loads include:[6]

Before development of the rash, the first lesions appear on the oropharyngeal mucosa, at which time the virus is released through the mucosal secretions, making that patient infectious.

Skin lesions develop due to migration of macrophages to the infected areas of the dermis, leading to edema and necrosis. With the influx of more polymorphonuclear cells, skin pustules will develop.[5]

The immune system responds to the viremia with activation of lymphocytes T and B and concomitant production of:[6]

  • Neutralizing antibodies, during first week of disease, remaining for many years
  • Hemagglutination-inhibition antibodies, by the 16th day of infection, beginning to decrease after 1 year
  • Complement-fixation antibodies, by the 18th day of infection, beginning to decrease after 1 year

Death by smallpox was commonly due to toxemia, following:[5]

Gross Pathology

Depending on the status of the patient's immune system, there are 3 forms of smallpox:[7]

Ordinary Smallpox

Ordinary smallpox is characterized by the following progression of lesions:[8]

This form of smallpox is typical of an immunocompetent patient, in whom the immune system is able to inhibit viral replication.

Flat-type Smallpox

Flat-type smallpox is characterized by the following progression of lesions:[9]

  • Delayed appearance of macules
  • Slow progression of the lesions, usually with flat and soft appearance
  • Possible slough of skin sections

Most cases are fatal with presence of severe toxemia. This form of smallpox is typical of patients with weak cellular immune response to the virus.

Hemorrhagic-type smallpox

Hemorrhagic-type smallpox is characterized by the following progression of lesions:[10]

This rare form of smallpox is typical of patients with severely compromised immune response, in which there is intense viral replication in the bone marrow and spleen. It is also associated with intense toxemia.

Microscopic Pathology

The typical skin vesicles observed in smallpox occur following:[11]

On the other hand, in the infected mucous surfaces, the viral proliferation and absence of the stratum corneum, lead to the formation of ulcers. These ultimately lead to the release of greater loads of virus into the oropharynx.[12]

Histopathology

Poxviruses are characterized by cytoplasmic inclusions, however, these do not identify specifically the smallpox virus on a biopsy. There are 2 types of inclusion bodies:[13]

A-type

Typical of some viruses of the:

  • Genus Orthopoxvirus:
  • Cowpox virus
  • Ectromelia virus
  • Genus Avipoxvirus

B-type, or Guarnieri bodies

Gallery

References

  1. "Smallpox disease overview".
  2. Massung RF, Liu LI, Qi J, Knight JC, Yuran TE, Kerlavage AR; et al. (1994). "Analysis of the complete genome of smallpox variola major virus strain Bangladesh-1975". Virology. 201 (2): 215–40. doi:10.1006/viro.1994.1288. PMID 8184534.
  3. Cecil, Russell (2012). Goldman's Cecil medicine. Philadelphia: Elsevier/Saunders. ISBN 1437716040.
  4. 4.0 4.1 "Smallpox and its Eradication" (PDF).
  5. 5.0 5.1 5.2 Moore, Zack S; Seward, Jane F; Lane, J Michael (2006). "Smallpox". The Lancet. 367 (9508): 425–435. doi:10.1016/S0140-6736(06)68143-9. ISSN 0140-6736.
  6. 6.0 6.1 6.2 Breman, Joel G.; Henderson, D.A. (2002). "Diagnosis and Management of Smallpox". New England Journal of Medicine. 346 (17): 1300–1308. doi:10.1056/NEJMra020025. ISSN 0028-4793.
  7. Mandell, Gerald (2010). Mandell, Douglas, and Bennett's principles and practice of infectious diseases. Philadelphia, PA: Churchill Livingstone/Elsevier. ISBN 0443068399.
  8. Mandell, Gerald (2010). Mandell, Douglas, and Bennett's principles and practice of infectious diseases. Philadelphia, PA: Churchill Livingstone/Elsevier. ISBN 0443068399.
  9. Mandell, Gerald (2010). Mandell, Douglas, and Bennett's principles and practice of infectious diseases. Philadelphia, PA: Churchill Livingstone/Elsevier. ISBN 0443068399.
  10. Mandell, Gerald (2010). Mandell, Douglas, and Bennett's principles and practice of infectious diseases. Philadelphia, PA: Churchill Livingstone/Elsevier. ISBN 0443068399.
  11. Cecil, Russell (2012). Goldman's Cecil medicine. Philadelphia: Elsevier/Saunders. ISBN 1437716040.
  12. Cecil, Russell (2012). Goldman's Cecil medicine. Philadelphia: Elsevier/Saunders. ISBN 1437716040.
  13. Mandell, Gerald (2010). Mandell, Douglas, and Bennett's principles and practice of infectious diseases. Philadelphia, PA: Churchill Livingstone/Elsevier. ISBN 0443068399.
  14. 14.0 14.1 14.2 14.3 14.4 14.5 14.6 "Public Health Image Library (PHIL), Centers for Disease Control and Prevention".

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