Sandbox: GDS: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
No edit summary
No edit summary
Line 2: Line 2:
My Practice Page
My Practice Page
{{CMG}}; {{AE}} {{GDS}}
{{CMG}}; {{AE}} {{GDS}}
__NOTOC__
{{Polio}}
{{CMG}}; {{AE}} {{JS}}


==Overview==
==Overview==
Tuberous sclerosis is a rare multi system genetic disorder that leads to growth of tumors in various areas such as brain,skin,heart,lungs and kidneys. It commonly involves the CNS and causes various symptoms such as seizures,hypotonia,intellectual disability,developmental delay and behavioral disorders. Other associated symptoms of TS depend on the involvement of the organ system.
Poliovirus enters the body orally, and infects cells of the [[gastrointestinal]] tract, from the mouth to the [[ileum]] and [[mesenterium]]. After [[replication]], the virus may either be secreted in feces, contributing to the [[transmission]] of the disease, or reach the [[bloodstream]], and be transported to other cells of the body, such as those of the [[reticuloendothelial system]]. Although the precise mechanism of infection of [[CNS]] is not fully understood, the most supported hypothesis is the retrograde axonal transport, according to which the virus enters the [[axoplasm]] of a motor neuron, travels to its cell body, where it replicates, and leads to neuron death.  In the [[CNS]], [[poliovirus]] shows [[tropism]] for cells of the [[anterior horn]] of the [[spinal cord]], [[hypothalamus]], [[thalamus]], [[cerebellar vermis]], [[vestibular nuclei|vestibular]] and deep cerebral nuclei.  Death of the [[motor neuron]] is responsible for the [[paralysis]] often seen in poliomyelitis.  
==Causes==
TSC is caused by defects, or mutations, on two genes—TSC1 and TSC2. Only one of the genes needs to be affected for TSC to be present. The TSC1 gene is on chromosome 9 and produces a protein called hamartin. The TSC2 gene is on chromosome 16 and produces the protein tuberin. Scientists believe these proteins act as growth suppressors by inhibiting the activation of a protein called mTOR. Loss of regulation of mTOR occurs in cells lacking either hamartin or tuberin, and this leads to abnormal differentiation and development, and to the generation of enlarged cells, as are seen in TSC brain lesions.
==Inheritance==
Although some individuals inherit the disorder from a parent with TSC, most cases occur as sporadic cases due to new, spontaneous mutations in TSC1 or TSC2—meaning neither parent has the disorder or the faulty gene(s). Instead, a faulty gene first occurs in the affected individual.


In cases where TSC is inherited, only one parent needs to have the faulty gene in order to pass it on to a child (called autosomal dominant inheritance). If a parent has TSC, each child has a 50 percent chance of developing the disorder. Children who inherit TSC may not have the same symptoms as their parent and may have either a milder or a more severe form of the disorder.
==Transmission==
Poliovirus is mostly transmitted through the [[fecal-oral route]], by ingestion of contaminated food or water. In some instances, the oral-oral route may be relevant through [[pharyngeal]] secretions. <ref name="pmid20978089">{{cite journal| author=Nathanson N, Kew OM| title=From emergence to eradication: the epidemiology of poliomyelitis deconstructed. | journal=Am J Epidemiol | year= 2010 | volume= 172 | issue= 11 | pages= 1213-29 | pmid=20978089 | doi=10.1093/aje/kwq320 | pmc=PMC2991634 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20978089  }} </ref><ref name=CDC>{{cite web | title = Poliomyelitis | url = http://www.cdc.gov/vaccines/pubs/pinkbook/polio.html#epi }}</ref> Poliomyelitis is highly contagious and spreads easily through human-to-human contact.<ref name=Kew_2005>{{cite journal |author=Kew O, Sutter R, de Gourville E, Dowdle W, Pallansch M |title=Vaccine-derived polioviruses and the endgame strategy for global polio eradication |journal=Annu Rev Microbiol |volume=59 |issue= |pages=587–635 |year=2005 |pmid=16153180}}</ref> In [[endemic]] areas, wild polioviruses can infect virtually the entire human population.<ref name=McGraw>{{cite book |author = Parker SP (ed.) | title = McGraw-Hill Concise Encyclopedia of Science & Technology |publisher=McGraw-Hill |location=New York |year=1998 | isbn=0-07-052659-1| page= 67}}</ref>  Viral particles are excreted in the [[feces]] for several weeks, after initial infection. Although the virus can cross the [[placenta]] during pregnancy, the [[fetus]] does not appear to be affected by either maternal infection, or polio [[vaccination]].<ref name=UK>{{cite book |author=Joint Committee on Vaccination and Immunisation (Salisbury A, Ramsay M, Noakes K (eds.) |title = Chapter 26:Poliomyelitis. ''in:'' Immunisation Against Infectious Disease, 2006  | url=http://www.immunisation.nhs.uk/files/GB_26_polio.pdf  | format = PDF |publisher=Stationery Office |location=Edinburgh |year=2006 |pages = 313–29 |isbn = 0-11-322528-8}}</ref> Maternal [[antibodies]] can also cross the [[placenta]], providing [[passive immunity]] that protects the infant from polio infection during the first few months of life.<ref>{{cite journal |author=Sauerbrei A, Groh A, Bischoff A, Prager J, Wutzler P |title=Antibodies against vaccine-preventable diseases in pregnant women and their offspring in the eastern part of Germany |journal=Med Microbiol Immunol |volume=190 |issue=4 |pages=167–72 |year=2002 |pmid=12005329}}</ref>
==Pathogenesis==
Poliovirus enters the body orally and most often infects nearby [[cell]]s, such as those of the mouth, nose, and throat. It infects cells by binding to an immunoglobulin-like receptor known as CD155 on the cell surface.  The most common course of [[infection]] is the replication of [[poliovirus]] in cells of the [[gastrointestinal]] tract, followed by viral shedding in feces. The specific cells of the [[gastrointestinal]] tract, where poliovirus replicates, are not known, however, the virus was successfully isolated from [[lymphatic]] cells of the [[GI tract]], including:<ref name="pmid15885840">{{cite journal| author=Mueller S, Wimmer E, Cello J| title=Poliovirus and poliomyelitis: a tale of guts, brains, and an accidental event. | journal=Virus Res | year= 2005 | volume= 111 | issue= 2 | pages= 175-93 | pmid=15885840 | doi=10.1016/j.virusres.2005.04.008 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15885840  }} </ref>
* [[tonsils|Tonsillar]] cells
* [[Peyer's patches]] of the [[ileum]]
* [[Lymph nodes]] of the [[mesenterium]]


In rare instances, people acquire TSC through a process called gonadal mosaicism. These individuals have parents with no apparent defects in the two genes that cause the disorder. Yet these parents can have a child with TSC because a portion of one of the parent's reproductive cells (sperm or eggs) can contain the genetic mutation without the other cells of the body being involved. In cases of gonadal mosaicism, genetic testing of a blood sample might not reveal the potential for passing the disease to offspring.
The virus enters the [[bloodstream]] and migrates to the [[reticuloendothelial]] cells across the body.  [[Poliovirus]] is able to reach the [[central nervous system]] in a small fraction of the [[symptomatic]] patients.<ref name="pmid15885840">{{cite journal| author=Mueller S, Wimmer E, Cello J| title=Poliovirus and poliomyelitis: a tale of guts, brains, and an accidental event. | journal=Virus Res | year= 2005 | volume= 111 | issue= 2 | pages= 175-93 | pmid=15885840 | doi=10.1016/j.virusres.2005.04.008 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15885840  }} </ref>  Not only is the disease not a phase of the [[viral replication]] cycle, it also does not benefit the virus in any way.  The molecular mechanism behind this disease process is not known.<ref name="pmid15885840">{{cite journal| author=Mueller S, Wimmer E, Cello J| title=Poliovirus and poliomyelitis: a tale of guts, brains, and an accidental event. | journal=Virus Res | year= 2005 | volume= 111 | issue= 2 | pages= 175-93 | pmid=15885840 | doi=10.1016/j.virusres.2005.04.008 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15885840  }} </ref>


==Clinical Features==
[[Poliovirus]] replicates inside [[monocytes]], which allows for secondary hematogenous spread.  The pathological mechanism responsible for the clinical manifestations of CNS poliomyelitis is characterized by selective destruction of [[motor neurons]].  Depending of the involved site, motor neuron loss may lead to focal or generalized symptoms. Most commonly observed signs and symptoms include asymmetric limb paralysis in spinal polio and respiratory disturbance with cranial nerve defects in bulbar polio.
*Infantile spams
*Seizures
*Intellectual Disability
*Developmental Delay
*Behavioural Disorder
**Higher incidence of autism
*Lesions in the brain
**Tubers in the convolutions of the white matter.
**Sub Ependymal Giant Cell Astrocytoma
**Sub Ependymal Nodules
*Rhabdomyosarcoma
*Skin Lesion
**Ash Leaf spots
**Shagreen Patches
**Facial sebaceous adenomas
**Forehead plaques
*Hamartomas in nail beds
*Renal
**Cysts
**Angiomyolipomas
*Lungs
**Lymphangioleiomyomatosis (LAM)
**Multinodular multifocal pneumocyte hyperplasia (MMPH)


==Diagnosis==
Although the mechanism of viral spread to the [[CNS]] is not fully understood, two main hypotheses have been proposed:<ref name="pmid15885840">{{cite journal| author=Mueller S, Wimmer E, Cello J| title=Poliovirus and poliomyelitis: a tale of guts, brains, and an accidental event. | journal=Virus Res | year= 2005 | volume= 111 | issue= 2 | pages= 175-93 | pmid=15885840 | doi=10.1016/j.virusres.2005.04.008 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15885840 }} </ref>
Diagnosing TSC is based upon clinical criteria.  The first clue may be the presence of seizures or delayed development. In other cases, the first sign may be white patches on the skin (hypomelanotic macules) or the identification of cardiac tumor rhabdomyoma.
# [[Poliovirus]] diffuses directly through the [[blood brain barrier]] from the [[bloodstream]] to the [[CNS]], regardless of cellular receptors.
# [[Poliovirus]] is transported from the peripheral [[muscles]] to the [[brain]] and [[spinal cord]], through retrograde axonal transport.  This hypothesis has been experimentally proven in mice, after [[CD155]] transformation.


Diagnosis of the disorder is based on a careful clinical exam in combination with computed tomography (CT) or magnetic resonance imaging (MRI) of the brain—which may show tubers in the brain, and an ultrasound of the heart, liver, and kidneys, which may show tumors in those organs. Doctors should carefully examine the skin for the wide variety of skin features, the fingernails, and toenails for ungual fibromas; the teeth and gums for dental pits and/or gum fibromas; and the eyes for retinal lesions. A small hand-help lamp that uses black light, otherwise known as ultraviolet light, may show hypomelanotic macules which are sometimes hard to see on infants and individuals with pale or fair skin. A doctor experienced in the diagnosis of TSC should evaluate a potential patient.
Once at the [[cell body]] of the [[neuron]], the change from [[axoplasm]] to [[cytoplasm]] is thought to interfere with the stability of the viral coat, leading to the exposure of the viral [[RNA]].  [[Viral replication]] interferes with [[neuron]] stability, killing the [[motor neuron]]. Death of a [[motor neuron]] paralyzes the respective [[muscle fiber]].


In infants, TSC may be suspected if the child has cardiac rhabdomyomas at birth or seizures (especially the kind called infantile spasms) in the first six months of life. With a careful examination of the skin and brain, it may be possible to diagnose TSC in a very young infant. However, many children are not diagnosed until later in life when their seizures begin and other symptoms such as facial angiofibromas appear.
===Retrograde Axonal Transport Hypothesis===
McCune Albright Syndrome occurs due to mutation in the GNAS gene which leads to constant G- protein activation which leads to overproduction of pituitary hormones.<br>Thus in addition to precocious puberty ( GnRH independent increase in LH and FSH), <font color="red"> MAS can cause an increasein n TSH and GH and ACTH leading to [[Cushing's syndrome|Cushing syndrome.]]</font>.
Several recent findings supporting the retrograde axonal transport hypothesis have been reported:<ref name="pmid15885840">{{cite journal| author=Mueller S, Wimmer E, Cello J| title=Poliovirus and poliomyelitis: a tale of guts, brains, and an accidental event. | journal=Virus Res | year= 2005 | volume= 111 | issue= 2 | pages= 175-93 | pmid=15885840 | doi=10.1016/j.virusres.2005.04.008 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15885840  }} </ref>
* Detection of axonal poliovirus in patients with poliomyelitis.
* Interruption of a nerve connection between a site of multiple intramuscular injections and the spinal cord in mice with poliovirus viremia led to improved clinical course of infection. This supports the ''provocation poliomyelitis'' hypothesis which states that muscle injury in patients with poliovirus viremia triggers retrograde axonal transport of the virus. This phenomenon is seen in children receiving intramuscular vaccines in areas endemic for poliovirus.<ref name="pmid9573275">{{cite journal| author=Gromeier M, Wimmer E| title=Mechanism of injury-provoked poliomyelitis. | journal=J Virol | year= 1998 | volume= 72 | issue= 6 | pages= 5056-60 | pmid=9573275 | doi= | pmc=PMC110068 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9573275  }} </ref>
* In mice [[genetically]] transformed to express [[CD155]], injection of [[poliovirus]] in the left limb led to viral detection in the left anterior horn of the [[spinal cord]] only.  When the [[sciatic nerve]] was promptly sectioned after injection of the virus, the risk of paralysis in the injected limb was greatly reduced.
* [[Bulbar poliomyelitis]] following [[tonsillectomy]] may possibly be explained by the previously described mechanisms.
* Overexpression of [[CD155]] in the [[muscle fiber]]s of patients with paralytic poliomyelitis. To note, [[CD155]] directly interacts with the [[dynein]] retrograde complex through Tctex-1.<ref name="pmid15885840">{{cite journal| author=Mueller S, Wimmer E, Cello J| title=Poliovirus and poliomyelitis: a tale of guts, brains, and an accidental event. | journal=Virus Res | year= 2005 | volume= 111 | issue= 2 | pages= 175-93 | pmid=15885840 | doi=10.1016/j.virusres.2005.04.008 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15885840  }} </ref>
<br>
The main explanation for increased susceptibility to retrograde axonal transport of poliovirus in areas of injured muscle has been explained. In a neuronal [[synapse]], the rate of [[endocytosis]] is related to the level of [[neuron]] activity.  Correspondingly, for a [[motor neuron]], the level of [[neuron]] activity and rate of endocytosis at the [[neuromuscular junction]] is related to the extent of [[muscle]] contraction.  This explains the connection between extreme exercise or muscle injury and development of poliomyelitis in patients with [[viremia]].  Also, since most of [[CD155]] receptors are transported back to the [[cell body]], the virus is carried along, supporting the retrograde transport hypothesis.<ref name="pmid15885840">{{cite journal| author=Mueller S, Wimmer E, Cello J| title=Poliovirus and poliomyelitis: a tale of guts, brains, and an accidental event. | journal=Virus Res | year= 2005 | volume= 111 | issue= 2 | pages= 175-93 | pmid=15885840 | doi=10.1016/j.virusres.2005.04.008 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15885840  }} </ref>
 
===Affected Tissues===
Poliovirus commonly targets specific tissues in the CNS such as:<ref name="pmid15885840">{{cite journal| author=Mueller S, Wimmer E, Cello J| title=Poliovirus and poliomyelitis: a tale of guts, brains, and an accidental event. | journal=Virus Res | year= 2005 | volume= 111 | issue= 2 | pages= 175-93 | pmid=15885840 | doi=10.1016/j.virusres.2005.04.008 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15885840  }} </ref>
* [[Anterior horn]] cells of the [[spinal cord]] (in severe cases of the disease, the intermediate, intermediolateral and posterior gray columns may also be affected)
* [[Hypothalamus]]
* [[Thalamus]]
* [[Vestibular nuclei]]
* Deep cerebral nuclei
* [[Reticular formation]]
* [[Cerebellar vermis]]
 
The different clinical forms of [[poliomyelitis]] will depend on the most affected area of the [[CNS]].  Individual host factors and the neuropathogenicity of the [[virus]] influence the severity of the lesions.<ref name="pmid15885840">{{cite journal| author=Mueller S, Wimmer E, Cello J| title=Poliovirus and poliomyelitis: a tale of guts, brains, and an accidental event. | journal=Virus Res | year= 2005 | volume= 111 | issue= 2 | pages= 175-93 | pmid=15885840 | doi=10.1016/j.virusres.2005.04.008 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15885840  }} </ref>
 
==Vaccine mediated polio infection==
[[Polio vaccine|Oral polio vaccine (OPV)]] is one of the safest and most effective vaccination programs that prevented millions of cases of [[polio]]  not only through direct [[immunization]] but also through [[herd immunity]]. In rare occasions, the [[vaccine]] is associated with [[Polio|paralytic polio]].
There are two subtypes of paralytic polio related to [[Polio vaccine|OPV]] vaccine: vaccine associated paralytic polio and vaccine derived paralytic polio.
 
===Vaccine associated paralytic polio===
*Vaccine associated paralytic polio (VAPP) occurs when the [[Attenuated virus|attenuated strain]] used in the [[vaccine]] reverts inside the intestine into more [[virulent]] form.<ref name="urlwww.who.int">{{cite web |url=http://www.who.int/immunization/diseases/poliomyelitis/endgame_objective2/oral_polio_vaccine/VAPPandcVDPVFactSheet-Feb2015.pdf |title=www.who.int |format= |work= |accessdate=}}</ref><ref name="pmid3029445">{{cite journal |vauthors=Nkowane BM, Wassilak SG, Orenstein WA, Bart KJ, Schonberger LB, Hinman AR, Kew OM |title=Vaccine-associated paralytic poliomyelitis. United States: 1973 through 1984 |journal=JAMA |volume=257 |issue=10 |pages=1335–40 |year=1987 |pmid=3029445 |doi= |url=}}</ref><ref name="pmid7476613">{{cite journal |vauthors=Sullivan AA, Boyle RS, Whitby RM |title=Vaccine-associated paralytic poliomyelitis |journal=Med. J. Aust. |volume=163 |issue=8 |pages=423–4 |year=1995 |pmid=7476613 |doi= |url=}}</ref>
*The more virulent form is capable of causing the disease only in the vaccinated child or a close susceptible contact. Therfore, no outbreaks are associated with VAPP.
*The [[prevalence]] of (VAPP) is 1 in 2.7 million doses of the vaccine.
*In developed countries, the risk of VAPP is increased with the first dose of the vaccine while in developed countries, It’s increased with subsequent doses.
 
===Vaccine derived paralytic polio===
*Vaccine derived paralytic polio (VDPP) is caused by very rare [[mutation]] of the original strain of polio in the vaccine.<ref name="urlwww.who.int">{{cite web |url=http://www.who.int/immunization/diseases/poliomyelitis/endgame_objective2/oral_polio_vaccine/VAPPandcVDPVFactSheet-Feb2015.pdf |title=www.who.int |format= |work= |accessdate=}}</ref><ref name="pmid14673763">{{cite journal |vauthors=Khetsuriani N, Prevots DR, Quick L, Elder ME, Pallansch M, Kew O, Sutter RW |title=Persistence of vaccine-derived polioviruses among immunodeficient persons with vaccine-associated paralytic poliomyelitis |journal=J. Infect. Dis. |volume=188 |issue=12 |pages=1845–52 |year=2003 |pmid=14673763 |doi=10.1086/379791 |url=}}</ref>
*VDPP has the ability to cause the disease in any non immune person whether the vaccinated person or a contact, therefore it has the ability to cause [[Outbreak|outbreaks]] or even [[epidemics]] especially in communities that are not properly covered with the [[vaccination]] program.
*When it causes [[outbreaks]], VDPP is called circulating vaccine derived paralytic polio (cVDPP).
*In the last 10 years, 24 VDPP reported [[outbreaks]] happened in 21 countries causing 750 cases of [[Polio|paralytic polio.]]
*The management of VDPP is conducting extensive vaccination campaigns in the affected community aiming for vaccinating every child and thus preventing the spread of the [[infection]].
 
 
 
 
==Gallery==
<gallery>
Image:Poliomyelitis1.png|A photomicrograph of skeletal muscle tissue revealing myotonic dystrophic changes as a result of Polio Type III.<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:Poliomyelitis2.png|A photomicrograph of the lumbar spinal cord depicting an infarct due to Polio Type III surrounding the anterior spinal artery.<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:Polio3.jpg|A photomicrograph of the lumbar spinal cord depicting an infarct due to Polio Type III surrounding the anterior spinal artery.<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:Polio4.jpg|A photomicrograph of the lumbar spinal cord depicting degenerative changes due to an infarct caused by Polio Type III.<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:Polio5.jpg|A photomicrograph of the thoracic spinal cord depicting degenerative changes due to Polio Type III.<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:Polio6.jpg|A photomicrograph of the thoracic spinal cord depicting degenerative changes due to Polio Type III.<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:Polio7.jpg|A photomicrograph of the cervical spinal cord in the region of the anterior horn revealing Polio Type III degenerative changes.<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:Polio8.jpg|A photomicrograph of the cervical spinal cord in the region of the anterior horn revealing Polio Type III degenerative changes.<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:Polio9.jpg|A photomicrograph of the cervical spinal cord in the region of the anterior horn revealing Polio Type III degenerative changes.<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:Polio10.jpg|Under a low magnification, this photomicrograph of pontine tissue at the level of abducens nucleus reveals histopathologic changes in a poliomyelitis patient.<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:Polio11.jpg|Photomicrograph of the Cervical Spinal Cord Affected by Polio Type III Virus<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>
</gallery>
 
==References==
{{Reflist|2}}
[[Category:Primary care]]
[[Category:Disease]]
 
{{WH}}
{{WS}}

Revision as of 17:48, 9 June 2020

My Practice Page Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Gurmandeep Singh Sandhu,M.B.B.S.[2]

Polio Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Poliovirus

Differentiating Polio from other Diseases

Epidemiology and Demographics

Risk Factors

Natural History, Complications and Prognosis

Diagnosis

History and Symptoms

Physical Examination

Laboratory Findings

Treatment

Medical Therapy

Prevention

Future or Investigational Therapies

Case Studies

Case #1

Sandbox: GDS On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Sandbox: GDS

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Sandbox: GDS

CDC on Sandbox: GDS

Sandbox: GDS in the news

Blogs on Sandbox: GDS

Directions to Hospitals Treating Polio

Risk calculators and risk factors for Sandbox: GDS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [3]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [4]

Overview

Poliovirus enters the body orally, and infects cells of the gastrointestinal tract, from the mouth to the ileum and mesenterium. After replication, the virus may either be secreted in feces, contributing to the transmission of the disease, or reach the bloodstream, and be transported to other cells of the body, such as those of the reticuloendothelial system. Although the precise mechanism of infection of CNS is not fully understood, the most supported hypothesis is the retrograde axonal transport, according to which the virus enters the axoplasm of a motor neuron, travels to its cell body, where it replicates, and leads to neuron death. In the CNS, poliovirus shows tropism for cells of the anterior horn of the spinal cord, hypothalamus, thalamus, cerebellar vermis, vestibular and deep cerebral nuclei. Death of the motor neuron is responsible for the paralysis often seen in poliomyelitis.

Transmission

Poliovirus is mostly transmitted through the fecal-oral route, by ingestion of contaminated food or water. In some instances, the oral-oral route may be relevant through pharyngeal secretions. [1][2] Poliomyelitis is highly contagious and spreads easily through human-to-human contact.[3] In endemic areas, wild polioviruses can infect virtually the entire human population.[4] Viral particles are excreted in the feces for several weeks, after initial infection. Although the virus can cross the placenta during pregnancy, the fetus does not appear to be affected by either maternal infection, or polio vaccination.[5] Maternal antibodies can also cross the placenta, providing passive immunity that protects the infant from polio infection during the first few months of life.[6]

Pathogenesis

Poliovirus enters the body orally and most often infects nearby cells, such as those of the mouth, nose, and throat. It infects cells by binding to an immunoglobulin-like receptor known as CD155 on the cell surface. The most common course of infection is the replication of poliovirus in cells of the gastrointestinal tract, followed by viral shedding in feces. The specific cells of the gastrointestinal tract, where poliovirus replicates, are not known, however, the virus was successfully isolated from lymphatic cells of the GI tract, including:[7]

The virus enters the bloodstream and migrates to the reticuloendothelial cells across the body. Poliovirus is able to reach the central nervous system in a small fraction of the symptomatic patients.[7] Not only is the disease not a phase of the viral replication cycle, it also does not benefit the virus in any way. The molecular mechanism behind this disease process is not known.[7]

Poliovirus replicates inside monocytes, which allows for secondary hematogenous spread. The pathological mechanism responsible for the clinical manifestations of CNS poliomyelitis is characterized by selective destruction of motor neurons. Depending of the involved site, motor neuron loss may lead to focal or generalized symptoms. Most commonly observed signs and symptoms include asymmetric limb paralysis in spinal polio and respiratory disturbance with cranial nerve defects in bulbar polio.

Although the mechanism of viral spread to the CNS is not fully understood, two main hypotheses have been proposed:[7]

  1. Poliovirus diffuses directly through the blood brain barrier from the bloodstream to the CNS, regardless of cellular receptors.
  2. Poliovirus is transported from the peripheral muscles to the brain and spinal cord, through retrograde axonal transport. This hypothesis has been experimentally proven in mice, after CD155 transformation.

Once at the cell body of the neuron, the change from axoplasm to cytoplasm is thought to interfere with the stability of the viral coat, leading to the exposure of the viral RNA. Viral replication interferes with neuron stability, killing the motor neuron. Death of a motor neuron paralyzes the respective muscle fiber.

Retrograde Axonal Transport Hypothesis

Several recent findings supporting the retrograde axonal transport hypothesis have been reported:[7]

  • Detection of axonal poliovirus in patients with poliomyelitis.
  • Interruption of a nerve connection between a site of multiple intramuscular injections and the spinal cord in mice with poliovirus viremia led to improved clinical course of infection. This supports the provocation poliomyelitis hypothesis which states that muscle injury in patients with poliovirus viremia triggers retrograde axonal transport of the virus. This phenomenon is seen in children receiving intramuscular vaccines in areas endemic for poliovirus.[8]
  • In mice genetically transformed to express CD155, injection of poliovirus in the left limb led to viral detection in the left anterior horn of the spinal cord only. When the sciatic nerve was promptly sectioned after injection of the virus, the risk of paralysis in the injected limb was greatly reduced.
  • Bulbar poliomyelitis following tonsillectomy may possibly be explained by the previously described mechanisms.
  • Overexpression of CD155 in the muscle fibers of patients with paralytic poliomyelitis. To note, CD155 directly interacts with the dynein retrograde complex through Tctex-1.[7]


The main explanation for increased susceptibility to retrograde axonal transport of poliovirus in areas of injured muscle has been explained. In a neuronal synapse, the rate of endocytosis is related to the level of neuron activity. Correspondingly, for a motor neuron, the level of neuron activity and rate of endocytosis at the neuromuscular junction is related to the extent of muscle contraction. This explains the connection between extreme exercise or muscle injury and development of poliomyelitis in patients with viremia. Also, since most of CD155 receptors are transported back to the cell body, the virus is carried along, supporting the retrograde transport hypothesis.[7]

Affected Tissues

Poliovirus commonly targets specific tissues in the CNS such as:[7]

The different clinical forms of poliomyelitis will depend on the most affected area of the CNS. Individual host factors and the neuropathogenicity of the virus influence the severity of the lesions.[7]

Vaccine mediated polio infection

Oral polio vaccine (OPV) is one of the safest and most effective vaccination programs that prevented millions of cases of polio not only through direct immunization but also through herd immunity. In rare occasions, the vaccine is associated with paralytic polio. There are two subtypes of paralytic polio related to OPV vaccine: vaccine associated paralytic polio and vaccine derived paralytic polio.

Vaccine associated paralytic polio

  • Vaccine associated paralytic polio (VAPP) occurs when the attenuated strain used in the vaccine reverts inside the intestine into more virulent form.[9][10][11]
  • The more virulent form is capable of causing the disease only in the vaccinated child or a close susceptible contact. Therfore, no outbreaks are associated with VAPP.
  • The prevalence of (VAPP) is 1 in 2.7 million doses of the vaccine.
  • In developed countries, the risk of VAPP is increased with the first dose of the vaccine while in developed countries, It’s increased with subsequent doses.

Vaccine derived paralytic polio

  • Vaccine derived paralytic polio (VDPP) is caused by very rare mutation of the original strain of polio in the vaccine.[9][12]
  • VDPP has the ability to cause the disease in any non immune person whether the vaccinated person or a contact, therefore it has the ability to cause outbreaks or even epidemics especially in communities that are not properly covered with the vaccination program.
  • When it causes outbreaks, VDPP is called circulating vaccine derived paralytic polio (cVDPP).
  • In the last 10 years, 24 VDPP reported outbreaks happened in 21 countries causing 750 cases of paralytic polio.
  • The management of VDPP is conducting extensive vaccination campaigns in the affected community aiming for vaccinating every child and thus preventing the spread of the infection.



Gallery

References

  1. ↑ Nathanson N, Kew OM (2010). "From emergence to eradication: the epidemiology of poliomyelitis deconstructed". Am J Epidemiol. 172 (11): 1213–29. doi:10.1093/aje/kwq320. PMC 2991634. PMID 20978089.
  2. ↑ "Poliomyelitis".
  3. ↑ Kew O, Sutter R, de Gourville E, Dowdle W, Pallansch M (2005). "Vaccine-derived polioviruses and the endgame strategy for global polio eradication". Annu Rev Microbiol. 59: 587–635. PMID 16153180.
  4. ↑ Parker SP (ed.) (1998). McGraw-Hill Concise Encyclopedia of Science & Technology. New York: McGraw-Hill. p. 67. ISBN 0-07-052659-1.
  5. ↑ Joint Committee on Vaccination and Immunisation (Salisbury A, Ramsay M, Noakes K (eds.) (2006). Chapter 26:Poliomyelitis. in: Immunisation Against Infectious Disease, 2006 (PDF). Edinburgh: Stationery Office. pp. 313–29. ISBN 0-11-322528-8.
  6. ↑ Sauerbrei A, Groh A, Bischoff A, Prager J, Wutzler P (2002). "Antibodies against vaccine-preventable diseases in pregnant women and their offspring in the eastern part of Germany". Med Microbiol Immunol. 190 (4): 167–72. PMID 12005329.
  7. ↑ 7.0 7.1 7.2 7.3 7.4 7.5 7.6 7.7 7.8 Mueller S, Wimmer E, Cello J (2005). "Poliovirus and poliomyelitis: a tale of guts, brains, and an accidental event". Virus Res. 111 (2): 175–93. doi:10.1016/j.virusres.2005.04.008. PMID 15885840.
  8. ↑ Gromeier M, Wimmer E (1998). "Mechanism of injury-provoked poliomyelitis". J Virol. 72 (6): 5056–60. PMC 110068. PMID 9573275.
  9. ↑ 9.0 9.1 "www.who.int" (PDF).
  10. ↑ Nkowane BM, Wassilak SG, Orenstein WA, Bart KJ, Schonberger LB, Hinman AR, Kew OM (1987). "Vaccine-associated paralytic poliomyelitis. United States: 1973 through 1984". JAMA. 257 (10): 1335–40. PMID 3029445.
  11. ↑ Sullivan AA, Boyle RS, Whitby RM (1995). "Vaccine-associated paralytic poliomyelitis". Med. J. Aust. 163 (8): 423–4. PMID 7476613.
  12. ↑ Khetsuriani N, Prevots DR, Quick L, Elder ME, Pallansch M, Kew O, Sutter RW (2003). "Persistence of vaccine-derived polioviruses among immunodeficient persons with vaccine-associated paralytic poliomyelitis". J. Infect. Dis. 188 (12): 1845–52. doi:10.1086/379791. PMID 14673763.
  13. ↑ 13.00 13.01 13.02 13.03 13.04 13.05 13.06 13.07 13.08 13.09 13.10 "Public Health Image Library (PHIL), Centers for Disease Control and Prevention".

Template:WH Template:WS

Retrieved from "https://www.wikidoc.org/index.php?title=Sandbox:_GDS&oldid=1612071"