Smallpox pathophysiology: Difference between revisions

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Revision as of 20:42, 9 July 2014

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Transmission

Smallpox virus is transmitted by:^[1]

Physical contact
Contact with infected body fluids
Contact with infected objects
Air through aerosolized particles

Genetics

Pathogenesis

The smallpox virus commonly enters the body through the upper respiratory tract, invading the oropharyngeal and respiratory mucosa.^[2] Other possible ports of entry include: skin, conjunctivae as well as through the placenta.^[3] 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:^[4]^[3]^[5]

Asymptomatic respiratory mucosa infection
Viral replication within respiratory epithelium
Transient primary asymptomatic viraemia
Virus enters macrophages and spreads to lymph nodes and reticuloendothelial system, where it replicates during 4 - 14 days
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:^[5]

Spleen

Liver

Bone marrow

Kidneys

Associated Conditions

Gross Pathology

Microscopic Pathology

References

↑ "Smallpox disease overview".
↑ Cecil, Russell (2012). Goldman's Cecil medicine. Philadelphia: Elsevier/Saunders. ISBN 1437716040.
↑ ^3.0 ^3.1 "Smallpox and its Eradication" (PDF).
↑ 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.
↑ ^5.0 ^5.1 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.

Template:WH Template:WS

[CDC-1] "Smallpox disease overview".

[2] Cecil, Russell (2012). Goldman's Cecil medicine. Philadelphia: Elsevier/Saunders. ISBN 1437716040.

[WHO-3] 3.0 ^3.1 "Smallpox and its Eradication" (PDF).

[MooreSeward2006-4] 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.

[BremanHenderson2002-5] 5.0 ^5.1 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.

[1]

[2]

[3]

[4]

[5]

@@ Line 15: / Line 15: @@
 ==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, 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.
 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>
@@ Line 40: / Line 40: @@
 ==Microscopic Pathology==
-==Pathophysiology==
-===Infection===
-[[image:4728_lores-1.jpg|thumb|200px|left|Child showing rash due to smallpox variola major virus]]
-Smallpox is not notably infectious in the [[prodrome|prodromal]] period—viral shedding is usually delayed until the appearance of the rash. Smallpox is transmitted primarily through prolonged social contact or direct contact with infected body fluids or contaminated objects (fomites) such as bedding or clothes. Infection in the natural disease will be via the [[lung]]s. The fact that there has been no recurrence of wild smallpox since its elimination thirty years ago makes the assumptions made at the start of the elimination campaign - that human smallpox carriers do not exist, and that the virus does not exist outside humans - some of the most certain facts in medical science.
-Smallpox is a member of the family [[poxviridae]], subfamily chordopoxvirinae. The lifecycle of poxviruses is complicated by having multiple infectious forms, with differing mechanisms of cell entry. It is a large virus, with a double stranded DNA genome of about 200 [[base pair|kilobases]], making it more complicated than many [[bacteria]].
-The incubation period between contraction and the first obvious symptoms of the disease is around 12 days. In the initial growth phase the virus seems to move from cell to cell, but around the 12th day, [[lysis]] of many infected cells occurs and the virus is found in the [[blood]]stream in large numbers. The initial or prodromal symptoms are similar to other viral diseases such as [[influenza]] and the [[common cold]]: [[fever]]s, [[muscle]] pain, [[stomach]] aches, etc. The digestive tract is commonly involved, leading to [[vomit]]ing. Most people become prostrated at this stage.
-Smallpox virus preferentially attacks skin cells, and by days 12–15, smallpox infection becomes obvious. The attack on skin cells causes the characteristic [[pimple]]s associated with the disease. The pimples tend to erupt first in the mouth, then on the arms and the hands, and later on the rest of the body. At this point the pimples, called macules, are usually still fairly small. This is the stage at which the victim is most contagious.
-By days 15–16 the condition worsens, and at this point the disease can take two very different courses, depending on whether it is ordinary or hemorrhagic smallpox. The most common type is classic ordinary smallpox, in which the pimples grow into vesicles and then fill up with pus, turning them into pustules. Ordinary smallpox generally takes one of two basic courses. In ''discrete'' ordinary smallpox, the pustules stand out on the skin separately. There is a greater chance of surviving this form. In ''confluent'' ordinary smallpox, the blisters merge together into sheets which begin to detach the outer layers of skin from the underlying flesh. This form is usually fatal. If the patient survives the course of the disease, the pustules deflate in time (the duration is variable), and start to dry up, usually beginning on day 28. Eventually the pustules completely dry and start to flake off. Once all of the pustules flake off, the patient is considered cured, and is no longer contagious.
-[[Chickenpox]] and smallpox can be distinguished in the field via several methods.  An examination of the patient's [[Hand|palm]]s and [[sole]]s is necessary: unlike smallpox, chickenpox does not usually affect the palms and soles. Additionally, chickenpox pustules are of varying size due to variations in the timing of pustule eruption: smallpox pustules are all very nearly the same size since the viral effect progresses more uniformly.
-===Hemorrhagic Smallpox===
-In the other form of ''Variola major'' smallpox, known as hemorrhagic smallpox, a mortality of 96
-percent has been reported. An entirely different set of symptoms starts to develop. The skin does not blister, but remains smooth. Instead, bleeding occurs under the skin, making the skin look charred and black (this is known as [[black pox]]). The eyes also hemorrhage, making the whites of the eyes turn deep red (and, if the victim lives long enough, black). At the same time, bleeding begins in the [[Organ (anatomy)|organs]]. Death may occur from bleeding (fatal loss of blood or by other causes such as brain hemorrhage), or from loss of fluid.  The entry of other infectious organisms, since the skin and intestine are no longer a barrier, can also lead to multi-organ failure. This form of smallpox occurs in anywhere from 3–25% of fatal cases (depending on the virulence of the smallpox strain).
-The historical modes of death are similar to those in burns, with catastrophic losses of fluid, protein and electrolytes beyond the capacity of the body to replace or assimilate, and fulminating [[sepsis]], both due to the removal of the barrier between the internal milieu and outside world.  Supportive treatments have improved since the last large smallpox epidemics, but it would be grossly optimistic to imagine that, even with a small number of patients, the most intensive modern treatment would ensure survival, even where the damage is predominantly only in the skin.  A reduction in the severity of the disease by raising immunity is likely to make a large difference in numbers reaching the threshold of death, and supportive treatment a small one in elevating that threshold.
 ==References==