Polio pathophysiology: Difference between revisions

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==Overview==
==Overview==
The poliovirus is transmitted by the fecal-oral or oral route. Acute infection involves the [[oropharynx]], [[gastrointestinal tract]], and occasionally the [[central nervous system]].  Poliovirus divides within gastrointestinal cells for about one week before penetrating the intestinal lining. Once the virus enters the bloodstream it becomes a [[viremia]] and is widely-distributed throughout the body.  Rarely, the major viremia progresses and the virus invades the [[central nervous system]], causing a local inflammatory response.  
The word poliomyelitis is derived from the Greek, where polio means grey and the work myelin means the marrow referring to the spinal cord. Polio myelitis primarily affects the spinal cord in turn leading to the manifestations. Poliovirus is a member of the enterovirus subgroup, family Picornaviridae. Poliovirus is primarily spread from the stools of the infected person and enters the body orally through contaminated water or food (feco-oral transmission), infecting the cells of the gastrointestinal tract, from the mouth to the ileum and mesentrium.   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.
==Case Definitions of Polio==
CDC has given a case definition of paralytic poliomyelitis for surveillance purposes
*“Acute onset of flaccid paralysis of one or more limbs with decreased or absent tendon reflex in the affected limbs, without other apparent causes, and without sensory or cognitive loss.”.<ref name="urlPoliomyelitis, Paralytic | 2010 Case Definition">{{cite web |url=https://wwwn.cdc.gov/nndss/conditions/poliomyelitis-paralytic/case-definition/2010/#:~:text=Confirmed-,Acute%20onset%20of%20a%20flaccid%20paralysis%20of%20one%20or%20more,onset%20of%20initial%20symptoms%3B%20OR |title=Poliomyelitis, Paralytic &#124; 2010 Case Definition |format= |work= |accessdate=}}</ref>
*A confirmed case requires persistence of neurological deficit for 60 days after the onset of the initial symptoms, fatal illness, or unknown follow-up status.<ref name="urlPoliomyelitis, Paralytic | 2010 Case Definition">{{cite web |url=https://wwwn.cdc.gov/nndss/conditions/poliomyelitis-paralytic/case-definition/2010/#:~:text=Confirmed-,Acute%20onset%20of%20a%20flaccid%20paralysis%20of%20one%20or%20more,onset%20of%20initial%20symptoms%3B%20OR |title=Poliomyelitis, Paralytic &#124; 2010 Case Definition |format= |work= |accessdate=}}</ref>
WHO case definition for a suspected case of poliomyelitis is:
*A suspected case is defined as a child under 15 years of age presenting with acute flaccid paralysis (AFP), or as any person at any age with paralytic illness if poliomyelitis is suspected<ref name="urlwww.who.int">{{cite web |url=https://www.who.int/ihr/Case_Definitions.pdf |title=www.who.int |format= |work= |accessdate=}}</ref>


== Pathophysiology==


{| class = "prettytable" style = "float:right; font-size:90%; margin-left:15px"
==Pathophysiology==
|+'''Outcomes of poliovirus infection'''
===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>
! style="background:#efefef;" | Outcome
! style="background:#efefef" | Proportion of cases
|-
| Asymptomatic
| align="center" |90–95%
|-
| Minor illness
|align="center" |4–8%
|-
|Non-paralytic aseptic<br/> meningitis
| align="center" |1–2%
|-
|Paralytic poliomyelitis
| align="center" |0.1–0.5%
|-
|— Spinal polio
|align="center" |79% of paralytic cases
|-
|— Bulbospinal polio
|align="center" |19% of paralytic cases
|-
|— Bulbar polio
|align="center" |2% of paralytic cases
|}


Poliovirus enters the body orally and most often infects nearby [[cell]]s, such as those of the mouth, nose, and throat. 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]]
===Pathogenesis===
===Pathogenesis===
[[Image:Polio spine.png|thumb|left|A blockage of the [[lumbar]] anterior spinal cord [[artery]] due to polio (PV3)]]
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>. Viral particles have been seen in:
<!--
* [[tonsils|Tonsillar]] cells
The pathology of poliovirus is typical for enteroviruses: the three serotypes replicate very efficiently in the GI tract (up to 60 days post infection). Only at a rate of 10−2 (for serotype 1) to 10−3 (for serotypes 2 and 3) does poliovirus cause neurological disease. Thus, the infamous propensity of poliovirus to invade the central nervous system and specifically target motor neurons is rare and accidental and it is neither a prerequisite nor does it present a benefit for its normal life cycle in humans. Poliovirus is a neurotropic virus by mistake; its CNS invasion is mostly a chance event and largely independent of the age, gender, or socioeconomic position of the infected person.
* [[Peyer's patches]] of the [[ileum]]
* [[Lymph nodes]] of the [[mesenterium]]


-->
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>
Poliovirus enters the body through the mouth, infecting the first cells it comes into contact with—[[follicular dendritic cell]]s residing within the germinal centers of the tonsils and intestinal M cells-by binding to a immunoglobulin-like receptor known as the poliovirus receptor (CD155) on the cell surface. Once inside a human cell the virus hijacks the host cell's own machinery, and begins to replicate. Poliovirus divides within gastrointestinal cells for about one week before penetrating the intestinal lining. Following penetration, the virus is absorbed into the blood via the [[mesentery]], and into the lymphatic system via the [[Peyer's patches]].


Once the virus enters the bloodstream it becomes a viremia and is widely-distributed throughout the body. Poliovirus can survive and multiply within the blood and lymphatics for long periods of time, sometimes as long as 17 weeks. In a small percentage of cases the virus spreads and replicates in other sites such as brown fat, the reticuloendothelial tissues, and muscle. This sustained replication causes a secondary major viremia, and leads to the development of minor [[influenza]]-like symptoms.
[[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.


Rarely, the major viremia progresses and the virus invades the central nervous system (CNS), causing a local inflammatory response. In most cases this causes a self limiting inflammation of the meninges, the layers of tissue surrounding the brain, causing non-paralytic aseptic meningitis. Penetration of the CNS provides no known benefit to the virus, and is quite possibly an "accidental" deviation of a normal gastrointestinal infection. The mechanisms by which poliovirus spreads to the CNS are poorly understood, but it appears to be primarily a chance event—largely independent of the age, gender, or socioeconomic position of the individual.
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>
# [[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.
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>


====Paralytic Polio====
[[Image:Poliovirus Myotonic dystrophic.jpg|center|thumb|Denervation of skeletal muscle tissue secondary to poliovirus infection can lead to paralysis.]]
In approximately 1% of infections poliovirus spreads along certain nerve fiber pathways, preferentially replicating in and destroying motor neurons within the spinal cord, brain stem, or motor cortex, which leads to the development of paralytic poliomyelitis. The various forms of paralytic poliomyelitis (spinal, bulbar, and bulbospinal) vary only with the amount of neuronal damage and inflammation that occurs, and the region of the CNS that is affected.


The destruction of neuronal cells produces lesions within the [[spinal ganglia]]; lesions can also be found in the [[reticular formation]], [[vestibular nuclei]], [[cerebellar vermis]], and [[deep cerebellar nuclei]]. Inflammation associated with nerve cell destruction often alters the color and appearance of the gray matter in the spinal column, causing it to appear reddish and swollen. Other changes associated with paralytic disease occur in the [[hypothalamus]] and [[thalamus]]. The molecular mechanisms by which poliovirus causes paralytic disease are poorly understood.
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]].


Early symptoms of paralytic polio include a high fever, headache, stiffness in the back and neck, asymmetrical weakness of various muscles, sensitivity to touch, difficulty swallowing, muscle pain, loss of superficial and deep reflexes, [[paresthesia]], irritability, constipation, or difficulty urinating. Paralysis generally develops 1 to 10 days after early symptoms begin, and progresses for 2 to 3 days. Paralysis is usually complete when the fever breaks.
===Course of Disease===
''The pre- paralytic or non-paralytic course of the disease'' includes:-<ref name="pmidhttps://dx.doi.org/10.1136/pgmj.72.853.641">{{cite journal| author=Schmoldt A, Benthe HF, Haberland G| title=Digitoxin metabolism by rat liver microsomes. | journal=Biochem Pharmacol | year= 1975 | volume= 24 | issue= 17 | pages= 1639-41 | pmid=https://dx.doi.org/10.1136/pgmj.72.853.641 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10 }} </ref>
*Headache
*Pharyngitis
*Myalgia
*Anorexia
*Nausea
*Vomiting
In non- paralytic illness, the symptoms go away within one or two weeks.


The likelihood of developing paralytic polio and the extent of paralysis increase with age. In children non-paralytic meningitis is the most likely consequence of CNS involvement, and paralysis occurs in only 1 in 1000 cases. In adults paralysis occurs in 1 in 75 cases. In children under 5 years of age paralysis of one leg is most common, while in adults extensive paralysis in the trunk and muscles of the chest and abdomen and affecting all four limbs—[[quadriplegia]]—is more likely. Paralysis rates also vary depending on the serotype of the infecting poliovirus. The highest rates of paralysis (1 in 200) are associated with poliovirus type 1, the lowest rates (1 in 2,000) are associated with type 2.
''Paralytic Poliomyelitis'': <ref name="pmidhttps://dx.doi.org/10.1136/pgmj.72.853.641">{{cite journal| author=Schmoldt A, Benthe HF, Haberland G| title=Digitoxin metabolism by rat liver microsomes. | journal=Biochem Pharmacol | year= 1975 | volume= 24 | issue= 17 | pages= 1639-41 | pmid=https://dx.doi.org/10.1136/pgmj.72.853.641 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10  }} </ref>
After the meningitis phase, the spinal form of poliomyelitis occurs which consists of:
*Muscle pain
*Muscle spasms
*Fasciculations


=====Spinal Polio=====
Weakness is asymmetrical affecting the lower limbs more than the upper limbs. The weakness usually becomes maximum within 48hrs, especially in children. In some, the weakness may further increase after a period of stability but no further weakness occurs once the fever subsides. Muscle tone is flaccid and the reflexes are absent along with paraesthesia. Any cranial nerve may be involved but most frequently leads to dysphasia, dysphasia, and respiratory failure<ref name="pmid13636523">{{cite journal| author=PLUM F, SWANSON AG| title=Central neurogenic hyperventilation in man. | journal=AMA Arch Neurol Psychiatry | year= 1959 | volume= 81 | issue= 5 | pages= 535-49 | pmid=13636523 | doi=10.1001/archneurpsyc.1959.02340170001001 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=13636523  }} </ref>. Vasomotor involvement such as hypertension, hypotension, and circulatory collapse lead to mortality in patients.
[[Image:Polio spinal diagram.jpg|center|thumb|The location of motor neurons in the anterior horn cells of the spinal column.]]
Spinal polio is the most common form of paralytic poliomyelitis; it results from viral invasion of the motor neurons of the [[Anterior horn (spinal cord)|anterior horn cells]], or the [[anatomical terms of location#Dorsal and ventral|ventral]] (front) [[gray matter]] section in the [[spinal column]], which are responsible for movement of the muscles, including those of the [[torso|trunk]], [[limb (anatomy)|limb]]s and the [[intercostal muscle]]s.<ref name= Henry1>{{cite book | author = Frauenthal HWA, Manning JVV | title = Manual of infantile paralysis, with modern methods of treatment.| publisher = Philadelphia Davis | year = 1914| pages= 79–101 |url= http://books.google.com/books?vid=029ZCFMPZ0giNI1KiG6E&id=piyLQnuT-1YC&printsec=titlepage | oclc= 2078290}}</ref> Virus invasion causes inflammation of the nerve cells, leading to damage or destruction of motor neuron [[ganglion|ganglia]]. When spinal neurons die, [[Wallerian degeneration]] takes place, leading to weakness of those muscles formerly [[innervate]]d by the now dead neurons. With the destruction of nerve cells, the muscles no longer receive signals from the brain or spinal cord; without nerve stimulation, the muscles [[atrophy]], becoming weak, floppy and poorly controlled, and finally completely paralyzed.<ref name=Henry1 /> Progression to maximum paralysis is rapid (two to four days), and is usually associated with fever and muscle pain.<ref name= ConoJ>{{cite book | author = Cono J, Alexander LN | chapter = Chapter 10, Poliomyelitis. | title = Vaccine Preventable Disease Surveillance Manual | edition = 3rd ed. | pages = p. 10–1 | publisher = Centers for Disease Control and Prevention | year = 2002 | url = http://www.cdc.gov/vaccines/pubs/surv-manual/downloads/chpt10_polio.pdf | format = PDF}}</ref> Deep [[tendon reflex|tendon]] [[reflex]]es are also affected, and are usually absent or diminished; [[sensation]] (the ability to feel) in the paralyzed limbs, however, is not affected.


The extent of spinal paralysis depends on the region of the cord affected, which may be [[cervical]], [[thoracic]], or [[lumbar]].<ref name=Guide>{{cite book |author= |title=Professional Guide to Diseases (Professional Guide Series) |publisher=Lippincott Williams & Wilkins |location=Hagerstown, MD |year= 2005|pages=243–5 |isbn=1-58255-370-X |oclc= |doi=}}</ref> The virus may affect muscles on both sides of the body, but more often the paralysis is asymmetrical.<ref>Yin-Murphy M, Almond JW (1996). "Picornaviruses: The Enteroviruses: Polioviruses", Baron's Medical Microbiology (Baron S et al, eds.), 4th ed., Univ of Texas Medical Branch, e-text. ISBN 0-9631172-1-1</ref> Any [[Limb (anatomy)|limb]] or combination of limbs may be affected—one leg, one arm, or both legs and both arms.  Paralysis is often more severe [[proximal]]ly (where the limb joins the body) than [[distal]]ly (the [[fingertip]]s and [[toe]]s). <ref>Yin-Murphy M, Almond JW (1996). "Picornaviruses: The Enteroviruses: Polioviruses", Baron's Medical Microbiology (Baron S et al, eds.), 4th ed., Univ of Texas Medical Branch, e-text. ISBN 0-9631172-1-1</ref>


=====Bulbar Polio=====
''Bulbar form'':<ref name="pmid13174358">{{cite journal| author=ANDERSON GW, RONDEAU JL| title=Absence of tonsils as a factor in the development of bulbar poliomyelitis. | journal=J Am Med Assoc | year= 1954 | volume= 155 | issue= 13 | pages= 1123-30 | pmid=13174358 | doi=10.1001/jama.1954.03690310001001 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=13174358  }} </ref>
[[Image:Brain bulbar region.jpg|center|thumb|The location and anatomy of the bulbar region (in orange).]]
Seen more in children in which tonsils and adenoids have been removed.
Comprising about 2% of cases of paralytic polio, bulbar polio occurs when poliovirus invades and destroys nerves within the [[bulbar]] region of the [[brain stem]]. The bulbar region is a [[white matter]] pathway that connects the [[cerebral cortex]] to the brain stem. The destruction of these nerves weakens the muscles supplied by the [[cranial nerve]]s, producing symptoms of [[encephalitis]], and causes difficulty breathing, speaking and swallowing. Critical nerves affected are the [[glossopharyngeal nerve]], which partially controls swallowing and functions in the throat, tongue movement and taste; the [[vagus nerve]], which sends signals to the heart, intestines, and lungs; and the [[accessory nerve]], which controls upper neck movement. Due to the effect on swallowing, secretions of [[mucus]] may build up in the airway causing suffocation. <ref>Silverstein A, Silverstein V, Nunn LS (2001). Polio, Diseases and People. Berkeley Heights, NJ: Enslow Publishers, 12. ISBN 0-7660-1592-0.</ref> Other signs and symptoms include facial weakness, caused by destruction of the [[trigeminal nerve]] and [[facial nerve]], which innervate the cheeks, [[tear duct]]s, gums, and muscles of the face, among other structures; [[diplopia|double vision]]; difficulty in chewing; and abnormal respiratory rate, depth, and rhythm, which may lead to [[respiratory arrest]]. [[Pulmonary edema]] and [[Shock (medical)|shock]] are also possible, and may be fatal.


=====Bulbospinal Polio=====
==Vaccine mediated polio infection==
Approximately 19% of all paralytic polio cases have both bulbar and spinal symptoms; this subtype is called ''respiratory polio'' or ''bulbospinal polio''. Here the virus affects the upper part of the [[Cervical vertebrae|cervical spinal cord]] (C3 through C5), and paralysis of the [[Thoracic diaphragm|diaphragm]] occurs. The critical nerves affected are the [[phrenic nerve]], which drives the diaphragm to inflate the [[lungs]], and those that drive the muscles needed for swallowing. By destroying these nerves this form of polio affects breathing, making it difficult or impossible for the patient to breathe without the support of a [[medical ventilator|ventilator]]. It can lead to paralysis of the arms and legs and may also affect swallowing and heart functions.
[[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.


==Transmission==
===Vaccine associated paralytic polio===
Poliomyelitis is highly contagious and spreads easily from 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> It is seasonal in temperate climates, with peak transmission occurring in summer and autumn. These seasonal differences are far less pronounced in tropical areas. The time between first exposure and first symptoms, known as the [[incubation period]], is usually 6 to 20&nbsp;days, with a maximum range of 3 to 35&nbsp;days.<ref name=Racaniello>{{cite journal |author=Racaniello V |title=One hundred years of poliovirus pathogenesis |journal=[[Virology (journal)|Virology]] |volume=344 |issue=1 |pages=9–16 |year=2006 |pmid = 16364730}}</ref> Virus particles are excreted in the [[feces]] for several weeks following initial infection. The disease is [[Transmission (medicine)|transmitted]] primarily via the [[fecal-oral route]], by ingesting contaminated food or water. It is occasionally transmitted via the oral-oral route,<ref name= Ohri>{{cite journal |last= Ohri |first=Linda K. |coauthors= Jonathan G. Marquess |year=1999 |title= Polio: Will We Soon Vanquish an Old Enemy? |journal= Drug Benefit Trends |volume= 11 |issue= 6|pages=41–54 |id= |url=http://www.medscape.com/viewarticle/416890 |accessdate= 2007-11-06 }} (Available free on [[Medscape]]; registration required.)</ref> a mode especially visible in areas with good sanitation and hygiene. Polio is most infectious between 7–10 days before and 7–10 days after the appearance of symptoms, but transmission is possible as long as the virus remains in the saliva or feces.
*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.


Factors that increase the risk of polio infection or affect the severity of the disease include [[immune deficiency]],<ref>{{cite journal |author=Davis L, Bodian D, Price D, Butler I, Vickers J |title=Chronic progressive poliomyelitis secondary to vaccination of an immunodeficient child |journal=[[New England Journal of Medicine|N Engl J Med]] |volume=297 |issue=5 |pages=241–5 |year=1977 |pmid = 195206}}</ref> [[malnutrition]],<ref>{{cite journal |author=Chandra R |title=Reduced secretory antibody response to live attenuated measles and poliovirus vaccines in malnourished children| url= http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=1131622|journal=[[British Medical Journal|Br Med J]] |volume=2 |issue=5971 |pages=583–5 |year=1975 |pmid=1131622}}</ref> [[tonsillectomy]],<ref>{{cite journal |author=Miller A |title=Incidence of poliomyelitis; the effect of tonsillectomy and other operations on the nose and throat | url= http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=12978882 |journal=Calif Med |volume=77 |issue=1 |pages=19–21 |year=1952 |pmid=12978882}}</ref> physical activity immediately following the onset of paralysis,<ref>{{cite journal |author=Horstmann D |title=Acute poliomyelitis relation of physical activity at the time of onset to the course of the disease |journal=[[Journal of the American Medical Association|J Am Med Assoc]] |volume=142 |issue=4 |pages=236–41 |year=1950 |pmid=15400610}}</ref> skeletal muscle injury due to [[intramuscular injection|injection]] of vaccines or therapeutic agents,<ref>{{cite journal |author=Gromeier M, Wimmer E |title=Mechanism of injury-provoked poliomyelitis |url= http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=9573275| journal=J. Virol. |volume=72 |issue=6 |pages=5056–60 |year=1998 |pmid=9573275 |doi=}}</ref> and [[pregnancy]].<ref name= Evans_1960>{{cite journal |author=Evans C |title=Factors influencing the occurrence of illness during naturally acquired poliomyelitis virus infections | url=http://mmbr.asm.org/cgi/reprint/24/4/341.pdf | format = PDF | journal=Bacteriol Rev |volume=24 |issue=4 |pages=341–52 |year=1960 |pmid=13697553}}</ref> 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 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>
===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]].
 
==Microscopic Pathology Images==
<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==
==References==
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Latest revision as of 01:33, 16 October 2020

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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]Gurmandeep Singh Sandhu,M.B.B.S.[3]

Overview

The word poliomyelitis is derived from the Greek, where polio means grey and the work myelin means the marrow referring to the spinal cord. Polio myelitis primarily affects the spinal cord in turn leading to the manifestations. Poliovirus is a member of the enterovirus subgroup, family Picornaviridae. Poliovirus is primarily spread from the stools of the infected person and enters the body orally through contaminated water or food (feco-oral transmission), infecting the cells of the gastrointestinal tract, from the mouth to the ileum and mesentrium. 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.

Case Definitions of Polio

CDC has given a case definition of paralytic poliomyelitis for surveillance purposes

  • “Acute onset of flaccid paralysis of one or more limbs with decreased or absent tendon reflex in the affected limbs, without other apparent causes, and without sensory or cognitive loss.”.[1]
  • A confirmed case requires persistence of neurological deficit for 60 days after the onset of the initial symptoms, fatal illness, or unknown follow-up status.[1]

WHO case definition for a suspected case of poliomyelitis is:

  • A suspected case is defined as a child under 15 years of age presenting with acute flaccid paralysis (AFP), or as any person at any age with paralytic illness if poliomyelitis is suspected[2]


Pathophysiology

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. [3][4] Poliomyelitis is highly contagious and spreads easily through human-to-human contact.[5] In endemic areas, wild polioviruses can infect virtually the entire human population.[6] 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.[7] Maternal antibodies can also cross the placenta, providing passive immunity that protects the infant from polio infection during the first few months of life.[8]

Poliovirus enters the body orally and most often infects nearby cells, such as those of the mouth, nose, and throat. Poliovirus commonly targets specific tissues in the CNS such as:[9]

Pathogenesis

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:[9]. Viral particles have been seen in:

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.[9] 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.[9]

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:[9]

  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.

Several recent findings supporting the retrograde axonal transport hypothesis have been reported:[9].

    • 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.[10]
    • 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.[9]


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.[9]


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.

Course of Disease

The pre- paralytic or non-paralytic course of the disease includes:-[11]

  • Headache
  • Pharyngitis
  • Myalgia
  • Anorexia
  • Nausea
  • Vomiting

In non- paralytic illness, the symptoms go away within one or two weeks.

Paralytic Poliomyelitis: [11] After the meningitis phase, the spinal form of poliomyelitis occurs which consists of:

  • Muscle pain
  • Muscle spasms
  • Fasciculations

Weakness is asymmetrical affecting the lower limbs more than the upper limbs. The weakness usually becomes maximum within 48hrs, especially in children. In some, the weakness may further increase after a period of stability but no further weakness occurs once the fever subsides. Muscle tone is flaccid and the reflexes are absent along with paraesthesia. Any cranial nerve may be involved but most frequently leads to dysphasia, dysphasia, and respiratory failure[12]. Vasomotor involvement such as hypertension, hypotension, and circulatory collapse lead to mortality in patients.


Bulbar form:[13] Seen more in children in which tonsils and adenoids have been removed.

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.[2][14][15]
  • 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.[2][16]
  • 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.

Microscopic Pathology Images

References

  1. ↑ 1.0 1.1 "Poliomyelitis, Paralytic | 2010 Case Definition".
  2. ↑ 2.0 2.1 2.2 "www.who.int" (PDF).
  3. ↑ 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.
  4. ↑ "Poliomyelitis".
  5. ↑ 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.
  6. ↑ Parker SP (ed.) (1998). McGraw-Hill Concise Encyclopedia of Science & Technology. New York: McGraw-Hill. p. 67. ISBN 0-07-052659-1.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ 9.0 9.1 9.2 9.3 9.4 9.5 9.6 9.7 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.
  10. ↑ Gromeier M, Wimmer E (1998). "Mechanism of injury-provoked poliomyelitis". J Virol. 72 (6): 5056–60. PMC 110068. PMID 9573275.
  11. ↑ 11.0 11.1 Schmoldt A, Benthe HF, Haberland G (1975). "Digitoxin metabolism by rat liver microsomes". Biochem Pharmacol. 24 (17): 1639–41. PMID https://dx.doi.org/10.1136/pgmj.72.853.641 Check |pmid= value (help).
  12. ↑ PLUM F, SWANSON AG (1959). "Central neurogenic hyperventilation in man". AMA Arch Neurol Psychiatry. 81 (5): 535–49. doi:10.1001/archneurpsyc.1959.02340170001001. PMID 13636523.
  13. ↑ ANDERSON GW, RONDEAU JL (1954). "Absence of tonsils as a factor in the development of bulbar poliomyelitis". J Am Med Assoc. 155 (13): 1123–30. doi:10.1001/jama.1954.03690310001001. PMID 13174358.
  14. ↑ 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.
  15. ↑ Sullivan AA, Boyle RS, Whitby RM (1995). "Vaccine-associated paralytic poliomyelitis". Med. J. Aust. 163 (8): 423–4. PMID 7476613.
  16. ↑ 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.
  17. ↑ 17.00 17.01 17.02 17.03 17.04 17.05 17.06 17.07 17.08 17.09 17.10 "Public Health Image Library (PHIL), Centers for Disease Control and Prevention".

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