Polio pathophysiology: Difference between revisions

Jump to navigation Jump to search
Line 8: Line 8:
Poliovirus enters the body through the mouth and infects nearby [[cell]]s, such as those of the mouth, nose, and throat.  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: [[tonsils|tonsillar]] cells; [[Peyer's patches]] of the [[ileum]], and [[lymph nodes]] of the [[mesenterium]].<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 and infects nearby [[cell]]s, such as those of the mouth, nose, and throat.  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: [[tonsils|tonsillar]] cells; [[Peyer's patches]] of the [[ileum]], and [[lymph nodes]] of the [[mesenterium]].<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>


The virus enters the [[bloodstream]], and migrates to [[reticuloendothelial]] cells across the body.  In a fraction of the patients who develop [[symptoms]], [[poliovirus]] is able to reach the [[central nervous system]].<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>  Poliomyelitis develops in 1% of patientients infected with the virus, of tens being referred to as an "accident of enteric infection".  Not only isn't the disease a phase of the replication cycle of the virus, as it does not benefit poliovirus in any way.  The molecular mechanisms behind the disease are not understood.<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>
The virus enters the [[bloodstream]], and migrates to [[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>  Poliomyelitis develops in 1% of patientients infected with the virus, of tens being referred to as an "accident of enteric infection".  Not only isn't the disease a phase of the replication cycle of the virus, as it does not benefit poliovirus in any way.  The molecular mechanisms behind the disease are not understood.<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]] replicates inside primary [[monocytes]], which allows it to spread from the initially infected cells to the [[bloodstream]].  The [[pathogenesis]] behind the clinical manifestations of [[CNS infection]] by the [[poliovirus|virus]] results from the selective destruction of [[motor neurons]].  [[Motor neuron]] attack, may lead to symptoms such as [[paralysis]], [[respiratory arrest]] and death.  Although the mechanism of viral spread to the [[CNS]] is not fully understood, two theories persist:<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]] replicates inside primary [[monocytes]], which allows it to spread from the initially infected cells to the [[bloodstream]].  The [[pathogenesis]] behind the clinical manifestations of [[CNS infection]] by the [[poliovirus|virus]] results from the selective destruction of [[motor neurons]].  [[Motor neuron]] attack, may lead to symptoms such as [[paralysis]], [[respiratory arrest]] and death.  Although the mechanism of viral spread to the [[CNS]] is not fully understood, two theories persist:<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>

Revision as of 20:47, 31 August 2014

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

Polio pathophysiology On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Polio pathophysiology

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Polio pathophysiology

CDC on Polio pathophysiology

Polio pathophysiology in the news

Blogs on Polio pathophysiology

Directions to Hospitals Treating Polio

Risk calculators and risk factors for Polio pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2]

Overview

Pathogenesis

Poliovirus enters the body through the mouth and infects nearby cells, such as those of the mouth, nose, and throat. 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: tonsillar cells; Peyer's patches of the ileum, and lymph nodes of the mesenterium.[1]

The virus enters the bloodstream, and migrates to reticuloendothelial cells across the body. Poliovirus is able to reach the central nervous system in a small fraction of the symptomatic patients.[1] Poliomyelitis develops in 1% of patientients infected with the virus, of tens being referred to as an "accident of enteric infection". Not only isn't the disease a phase of the replication cycle of the virus, as it does not benefit poliovirus in any way. The molecular mechanisms behind the disease are not understood.[1]

Poliovirus replicates inside primary monocytes, which allows it to spread from the initially infected cells to the bloodstream. The pathogenesis behind the clinical manifestations of CNS infection by the virus results from the selective destruction of motor neurons. Motor neuron attack, may lead to symptoms such as paralysis, respiratory arrest and death. Although the mechanism of viral spread to the CNS is not fully understood, two theories persist:[1]

  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 muscle to the brain and spinal cord, through retrograde axonal transport. This hypothesis has been experimentally proven in mice, after CD155 transformation.

Retrograde Axonal Transport Hypothesis

Recent discoveries supporting the second hypothesis have been reported:[1]

  • Axonal presence of poliovirus, in patients with poliomyelitis, has been reported - This explains the "provocation poliomyelitis" phenomenon, in which muscle trauma, while viremia is present, was associated with higher risk of developing poliomyelitis.
  • In genetically transformed mice to express CD155, after injecting poliovirus in the left limb, viral replication was noted only in the left anterior horn of the spinal cord, 33h after injection, before commencement of paralysis. If the sciatic nerve was promptly sectioned after injection of the virus, the predisposition of the implicated leg to be paralyzed was eliminated.
  • In the same mice, if poliovirus was injected intravenously, poliomyelitis manifested initially in the limb injured by multiple empty needle injections. This leads to the idea that injured muscle opens a way for the virus to penetrate the terminal of the presynaptic motor neuron.
  • Bulbar poliomyelitis following tonsillectomy may possibly be explained by the previous mechanisms.
  • There is over expression of CD155 on the muscle fibers of patients with paralytic poliomyelitis.
  • CD155, through Tctex-1, directly interacts with the dynein retrograde complex.

In a synapse, the rate of endocytosis is related to the level of neuron activity. For the motor neuron, the level of neuron activity at the neuromuscular junction is associated with muscle contraction, therefore, increased muscle activity is related to increased rate of endocytosis. This explains the connection between extreme exercise activity and development of poliomyelitis in patients with viremia, since there is greater probability of viral uptake. Also, since most of CD155 receptors are transported back to the cell body, the virus is carried along, supporting the retrograde transport hypothesis.[1]

Once at the cell body of the neuron, the change from axoplasm to cytoplasm is thought to interfere with the viral coat stability, leading to the exposure of the viral RNA. Viral replication interferes with neuron stability, killing the motor neuron. Death of the motor neuron paralyzes the respective muscle fiber. Spread of the virus to the nearby neurons will then be responsible for their death.

In the CNS, poliovirus shows tropism for certain pathways and tissues:[1]

Lesion distribution in paralytic and non-paralytic cases is the same. Additionally, inflammation can be detected in any affected area of the CNS, supporting the idea that in order to produce clinical manifestations, severe neuron damage must occur. 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.[1]

Transmission

Poliovirus is transmitted through the fecal-oral route and through pharyngeal secretions.[2]

Poliomyelitis is highly contagious and spreads easily from human-to-human contact.[3] In endemic areas, wild polioviruses can infect virtually the entire human population.[4] 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 days, with a maximum range of 3 to 35 days.[5] Virus particles are excreted in the feces for several weeks following initial infection. The disease is transmitted primarily via the fecal-oral route, by ingesting contaminated food or water. It is occasionally transmitted via the oral-oral route,[6] 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.

Factors that increase the risk of polio infection or affect the severity of the disease include immune deficiency,[7] malnutrition,[8] tonsillectomy,[9] physical activity immediately following the onset of paralysis,[10] skeletal muscle injury due to injection of vaccines or therapeutic agents,[11] and pregnancy.[12] Although the virus can cross the placenta during pregnancy, the fetus does not appear to be affected by either maternal infection or polio vaccination.[13] Maternal antibodies also cross the placenta, providing passive immunity that protects the infant from polio infection during the first few months of life.[14]

Gallery

References

  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 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.
  2. 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.
  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. Racaniello V (2006). "One hundred years of poliovirus pathogenesis". Virology. 344 (1): 9–16. PMID 16364730.
  6. Ohri, Linda K. (1999). "Polio: Will We Soon Vanquish an Old Enemy?". Drug Benefit Trends. 11 (6): 41–54. Retrieved 2007-11-06. Unknown parameter |coauthors= ignored (help) (Available free on Medscape; registration required.)
  7. Davis L, Bodian D, Price D, Butler I, Vickers J (1977). "Chronic progressive poliomyelitis secondary to vaccination of an immunodeficient child". N Engl J Med. 297 (5): 241–5. PMID 195206.
  8. Chandra R (1975). "Reduced secretory antibody response to live attenuated measles and poliovirus vaccines in malnourished children". Br Med J. 2 (5971): 583–5. PMID 1131622.
  9. Miller A (1952). "Incidence of poliomyelitis; the effect of tonsillectomy and other operations on the nose and throat". Calif Med. 77 (1): 19–21. PMID 12978882.
  10. Horstmann D (1950). "Acute poliomyelitis relation of physical activity at the time of onset to the course of the disease". J Am Med Assoc. 142 (4): 236–41. PMID 15400610.
  11. Gromeier M, Wimmer E (1998). "Mechanism of injury-provoked poliomyelitis". J. Virol. 72 (6): 5056–60. PMID 9573275.
  12. Evans C (1960). "Factors influencing the occurrence of illness during naturally acquired poliomyelitis virus infections" (PDF). Bacteriol Rev. 24 (4): 341–52. PMID 13697553.
  13. 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.
  14. 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.
  15. 15.00 15.01 15.02 15.03 15.04 15.05 15.06 15.07 15.08 15.09 15.10 "Public Health Image Library (PHIL), Centers for Disease Control and Prevention".

Template:WH Template:WS