Smallpox pathophysiology: Difference between revisions

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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-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-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-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| Right eye of the same 80 year-old female patient who's been accidentally infected by her grandchild, who’d been vaccinated not long before. Note the severe distortion of the palpebral margins due to the typical vaccinial lesion of the outer canthus.<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| Right eye of a 6 year-old child, who'd been accidentally inoculated with the vaccinia virus, and subsequently developed these severe conjunctival vaccinial lesions. The child had received a primary vaccination, and inadvertently transferred the vaccinial virus to his/her own eye.<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| 6 year-old boy, who'd been accidentally inoculated with the vaccinia virus, and subsequently developed these vaccinial lesions upon his face. This boy's lesions healed with no residual scarring.
<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| Right lower lip and chin region of a 25 year old woman, who had been accidentally infected on her face after her daughter was vaccinated against smallpox. Here we see the residual scarring left behind,<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| Right lower lip and chin region of a 25 year old woman, who had been accidentally infected on her face after her daughter was vaccinated against smallpox. Here we see the residual scarring left behind,<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>

Revision as of 23:10, 12 July 2014

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 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.

Transmission

Smallpox virus is transmitted by:[1]

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.

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.[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, conjunctivae as well as through the placenta.[4] Although the viral scabs may contain life viruses, they are commonly contained within thickened material, which limits transmissibility.

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 scabs. 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
  • Memory T cells, remaining for 50 years

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

Gross Pathology

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

Ordinary Smallpox

Characterized by the following progression of lesions:[8]

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

Flat-type Smallpox

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

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 to 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

Image 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 14.7 "Public Health Image Library (PHIL), Centers for Disease Control and Prevention".

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