Poliomyelitis

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Dr Jonas Salk, who created the first polio vaccine in 1955.

Contents

Introduction

Until a generation or two ago, polio was a very common and serious disease. Poliomyelitis infection is caused by an enterovirus, which causes muscular paralysis. In some cases respiratory muscles are affected; in others limb muscles. The paralysis was not always reversible, leading to contractures and permanent damage. The disease has the potential for total eradication.

Vaccines have been very successful in preventing this disease, which has been eliminated from most parts of the world. While the virus causing it is still circulating in the world, however, the risk remains that it will recur. Indeed while in early 2014 the world was declared by WHO to be 80% free, during the year it became apparent that Pakistan, Cameroon, and the Syria posed the greatest risk of further wild poliovirus exportations with Afghanistan, Equatorial Guinea, Ethiopia, Iraq, Israel, Somalia and Nigeria being at most risk of new epidemics. By 2018 wild type poliovirus was confined to Afghanistan and Pakistan, with vaccine associated polio only reported from the Democratic Republic of the Congo and Nigeria. It appears to have been eliminated now from Syria. Some politicians have actively impeded eradication and only their removal from power (for other reasons !) has allowed progress. Until the world is free of the vaccine, we need to continue to vaccinate against it, so will have isolated cases of polio.

Until there's more information on ganfyd, try the HPA information on polio here or the information at the WHO site here.

Post-Polio syndrome

More of a problem in Western countries now than Polio.

This is a syndrome of weakness often occurring years after the primary infection. The exact mechanism is not entirely understood, but hypotheses include degeneration of neuromuscular junctions (which have had to innervate more muscle fibres than normal due to destruction of some NMJs at the time of infection).

Aetiology

Polio virus surface representation (It's also this website's logo !)

The poliomyelitis virus (Enterovirus C) that causes polio is a small, spherical, RNA, enterovirus. The genome is single-stranded positive-sense RNA about 7500 nucleotides long, typical for a picornavirus. The last 700 odd 5' end nucleotides are essential for viral RNA replication by its specific RNA polymerase. The translated peptide of the whole genome is processed by a well understood process[1]:

  1. The polyprotein is myristoylated at its N terminus
  2. The viral 2A protease undertakes an early cotranslational cleavage of the polyprotein releasing a precursor protein myristoyl-P1 from the N terminus
  3. This P1 protein contains all the capsid protein sequences
  4. The viral 3CD protease produces from P1 the capsid proteins VP1 and VP3 and the immature capsid protein myristoyl-VP0.
  5. These capsule proteins are assembled into a pentameric assembly intermediate, which spontaneously assembles into empty capsid containing 60 copies each of VP0, VP3, and VP1.
  6. Encapsidation leads to the formation of a precursor, called the provirion, that contains the RNA and 60 copies each of VP0, VP3, and VP1.
  7. Processing of myristoyl-VP0 produces myristoyl-VP4 and VP2 (possibly autocatalytic) increases markedly stability of the viron. The mechanism of release of the virus from the cell is unclear.

The other coded proteins are:

  • 3Dpol, an RNA dependent RNA polymerase whose function is to copy and multiply the viral RNA genome.
  • 2Apro protease which cleave the viral polypeptid
  • 3Cpro/3CDpro, proteases which cleave the viral polypeptide.
  • VPg (3B), a small protein that binds viral RNA and is permissive to the synthesis of viral positive and negative strand RNA.
  • 2BC part of protein complex needed for virus replication
  • 2B part of protein complex needed for virus replication
  • 2C part of protein complex needed for virus replication
  • 3AB part of protein complex needed for virus replication
  • 3A part of protein complex needed for virus replication
  • 3B part of protein complex needed for virus replication

The viral particle is about 30 nanometres in diameter with icosahedral symmetry. The endocytic mechanism of viral entry into the human cell is still not understood fully as of 2014.


The wild type virus is known as WPV, and of the three wild strains, type 1 (WPV1) caused 85% of the paralysis in polio. Wild types 2 and 3 are no longer associated with human disease. However vaccine-derived poliovirus (cVDPV) is now becoming a major cause of paralysis, with in 2013 63 cases of type 2 and type 3 infection[2] with 417 Wild cases[3]

Epidemiology

Three serotypes.

  1. Type 1 (WPV) as of 2018 is still circulating in Afghanistan and Pakistan and causing polio.
  2. Type 2 was formally declared as eliminated in the wild in 2009, although in fact the last case was in 1999. During 2017 96 vaccine derived polio cases were identified in outbreaks in Democratic Republic of the Congo and Syria and in April 2018 one case occurred in Nigeria. In vivo mutation of the vaccine strain has been described[4] with 9 cases of poliomyelitis identified worldwide in 2015. Given the eradication of the serotype 2 virus, most countries have now moved to a bivalent, rather than trivalent vaccine.
  3. The last reported case of Type 3 was in 2012.

Back in 2014 the virus was endemic for indigenous transmission in Nigeria, Pakistan and Afghanistan. An outbreak also occurred in the Horn of Africa (Kenya and Somalia) in 2013 and the virus is sporadically found in sewage monitoring in countries such as Israel where high rates of immunisation make major outbreaks unlikely[5]. In May 2014, Pakistan, Cameroon, and Syria provided the major foci of concern.

Clinical

  • Transmission faeco-oral
  • Virus has high infectivity
  • Initial infection in oropharynx for 1-3 weeks.
  • Excretion 3-6 weeks after infection, briefly in saliva and the in faeces
  • Clinical course:
    1. Asymptomatic
    2. Mild flu-like illness
    3. 4% Flu-like symptoms plus aseptic meningitis
    4. 1% paralysis or death
      • Physical activity is a risk factor for paralysis
        • Mortality up to 5% in children and 30% in adults
      • Tonsillectomy and adenoidectomy risk factor for bulbar form
        • Bulbar form may have autonomic features:
          • Extremes of blood pressure
          • Respiratory failure
          • Dysphagia
          • Dysphonia
    5. Rarely acute encephalitis

Investigations

PCR

On throat, stool or CSF samples the polymerase chain reaction can be diagnostic

Blood tests

  • Acute and convalescent serum
  • Bloods as indicated by differential diagnosis

Imaging

  • Rarely necessary in endemic areas but obviously necessary where condition is a rare differential diagnosis to exclude spinal lesions.

Treatment

Medical

  • Supportive
  • Ventilation

Prevention

Info bulb.pngThree doses of oral polio vaccine (OPV) were required because, as a result of competitive inhibition, only one strain will replicate reliably;


when the second dose is given, the immune system will prevent the strain that replicated the first time from doing so, leaving the field clear for one of the others;


and the third dose ensures that there is cover against the third strain.

Polio can be safely and effectively prevented by vaccination. Until 2004 the vaccine used in the UK was oral polio vaccine (OPV), which contained attenuated live viruses from the three significant strains of polio.

OPV very rarely (fewer than one recipient and one contact case in England and Wales for every two million doses[6]) causes a form of poliomyelitis disease known as vaccine associated paralytic polio (VAPP). When polio was widespread in the community the number of cases of disease caused by the vaccine were small compared to the number of extra cases of disease the vaccine prevented by immunising people who had not been administered it. Now that the disease has been eradicated from many parts of the world this advantage no longer applies and the overall risk of wild disease, and hence acceptable risk from measures against it, have decreased greatly, hence the move to inactivated polio vaccine. So in 2004 the UK policy changed with the introduction of routine vaccination with combined vaccines containing inactivated polio vaccine (IPV) - see CMO letter 2004(3) or the Green Book for details.

There remains a risk in those with immunosuppression that the live virus used in the vaccine could persist in the gut, mutate or recombine with other enteroviruses to become pathogenic, and cause a resurgence of polio disease, unless vaccination is maintained. Carriage with such pathological mutation has lasted over 28 years and so for complete elimination of polio cases might only be detected and traced by monitoring sewage, which is impractical in much of the world [4].

Notification

Polio should be notified urgently, on suspicion.

Historical

  • 1000 BCE~ Egyptian stele (stone engraving) consistent with disease
  • 1789 Michael Underwood describes disease.[7]
  • 1840 Jacob Heine describes diseases involvement of the spinal cord.
  • 1894 Vermont U.S.A. epidemic.
  • 1908 Karl Landsteiner and Erwin Popper transmit a virus to a monkey causing polio.
  • 1916 U.S.A. epidemic of 27,000 cases and 6,000 deaths.
  • 1921 Franklin Delano Roosevelt (FDR) contracts polio and so ultimately changes public perception of issue
  • 1927 Warm Springs Foundation founded for polio rehabilitation.
  • 1929 Iron lung invented by Philip Drinker and Louis Shaw.
  • 1934 First Birthday Ball to raise funds for the Warm Springs Foundation held on FDR's birthday January 30.
  • 1935 Disastrous first test of a polio vaccine by Maurice Brodie and John Kolmer.[8]
  • 1937 Sister Elizabeth Kenny (Australian army nurse) publishes on her active treatments developed since 1929.
  • 1938 U.S.A. National Foundation for Infantile Paralysis founded by FDR.
  • 1949 Poliovirus tissue culture by John Franklin Enders, Thomas Huckle Weller and Frederick Chapman Robbins for which they get 1954 Nobel prize[9]
  • 1953 Jonas Salk at University of Pittsburgh and his associates develop an inactivated (killed), injected polio vaccine(IPV).
  • 1953 Danish epidemic results in Björn Ibsen establishing first intensive care unit in December.
  • 1954 Dr. Thomas Francis Jr. at the University of Michigan implements first mass polio vaccine trial[10]
  • 1955 The results of the two million US children field trials of IPV announced.
  • 1959 Completion of Albert Sabin's (University of Cincinnati) live, attenuated vaccine trials in Russia and Congo
  • 1974 Donald Mulder first describes post polio syndrome
  • 1981 Poliovirus genome sequence published.
  • 1988 WHO estimates 350000 cases worldwide
  • 1993 Polio eradication in Western Hemisphere
  • 1999 Last case of paralytic poliomyelitis caused by serotype 2 wild poliovirus.
  • 2006 Four countries — Nigeria, India, Pakistan, and Afghanistan — account for 93% of the world's less than 2000 cases of poliomyelitis.
  • 2009 Serotype 2 wild poliovirus no loner detected
  • 2010 Imported cases in Angola, Chad and Congo re-establish transmission
  • 2012 Last case of wild poliovirus type 3 in April 2012 from Pakistan
  • 2013 406 reported cases in year
  • 2014 The civil war in Syria causes cases, although disruption of vaccination for political/cultural reasons in Pakistan is the major issue
  • 2015 Mutation of vaccine strain to pathogenic strain reported in vivo [4]

External links

References

  1. Hogle JM. Poliovirus cell entry: common structural themes in viral cell entry pathways. Annual review of microbiology. 2002; 56:677-702.(Link to article – subscription may be required.)
  2. WHO circulating vaccine derived poliovirus data
  3. WHO weekly poliovirus data
  4. a b c Dunn G, Klapsa D, Wilton T, Stone L, Minor PD, Martin J. Twenty-Eight Years of Poliovirus Replication in an Immunodeficient Individual: Impact on the Global Polio Eradication Initiative. PLoS pathogens. 2015 Aug; 11(8):e1005114.(Epub) (Link to article – subscription may be required.)
  5. WHO Bulletin 6 June 2013
  6. Green Book 1996 edition
  7. Underwood M. A treatise on the diseases of children; with directions for the management of infants from birth. London: J Mathews, 1784.
  8. Paul JR. A history of poliomyelitis. New Haven, Conn.: Yale University Press, 1971:252-62
  9. Enders JF, Weller TH, Robbins FC. Cultivation of the Lansing strain of poliomyelitis virus in cultures of various human embryonic tissues. Science 1949;109:85-87
  10. Francis T Jr. Evaluation of the 1954 field trial of poliomyelitis vaccine. Ann Arbor, Mich.: Edwards Brothers/National Foundation for Infantile Paralysis, 1957.
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