Smallpox pathophysiology

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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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