Pathogenesis

Pathogenesis of the poliovirus

Firstly, the poliovirus enters the host cells by binding to its receptor that is identified to be CD155, a glycoprotein of the immunoglobin superfamily, Once multiple cirus particles bind to the V-type domains of the receptors, these particles would have a conformational change in which they externalizes proteins VP4 and VP1 that is found on the capsid of the virus.


Proteins are then inserted into the cell membrane and forms a pathway where viral particles are internalized. The RNA genome is quickly released into the cytoplasma through a pore. [0]

RECAP:
As a positive-sense ssRNA, its first step of viral replication is to make early proteins. An RNA-dependent RNA polymerase (RdRp) is a protein that uses the virus present RNA as a template to make more RNA.

The RdRp copies the positive-sense RNA strand to make a double-stranded RNA replicative complex and this complementary negative-sense RNA is used as a guide to make more positive-sense ssRNA.

These positive-sense ssRNA can then be used as mRNA to make structural proteins or packaged into final virions. The final step displays the structural proteins and the positive-sense ssRNA being packaged together to exit the cell as it lyses. [2]

Pathway in the body:
The virus enters through the mouth normally and multiplies in the throat and GIT before moving into the bloodstream and carried to the Central Nervous System where is replicates further and destroys the motor neuron cells. Motor neurons control the muscles for swallowing, circulation, respiration, and the trunk of arms and legs.

References:
[0]Poliomyelitis. (n.d.). Retrieved July 31, 2015, from https://microbewiki.kenyon.edu/index.php/
[2]Viral Replication Strategy in Positive-Sense Single-Stranded RNA Viruses - Library. (2010, August 11). Retrieved July 31, 2015, from http://www.microbelibrary.org/library/virus/2781-viral-replication-strategy-in-positive-sense-single-stranded-rna-viruses

Polio brief description and history case

Here is a video where Polio is explained with a brief introduction of the American Polio Epidemic that occurred back in 1900s, and continued till a vaccine was approved in 1955.

Below is a more descriptive and specific video on how vaccines, such as the Polio vaccine, changed the world.
Due to the American Polio Epidemic, with most of their victims being very young children, the Polio vaccine approved in 1955 had a great impact on the American society.

"If the results from the observed
study are employed, the vaccine
can be considered to be 80-90%
effective against paralytic poliomyelitis"
~broadcasted on 12 April 1955

Source:
https://www.youtube.com/watch?v=lDMoBcZG72E
https://www.youtube.com/watch?v=48sO778KOmQ

The Problems of Polio Today

How does Polio affect the world..? Is it still an issue today?
There are vaccinations that eradicate Polio which are recommended worldwide to young children and some adults. However, there are cases of Polio in some countries despite having vaccines available. Why is that..? The most likely case of such happening is due to wild polioviruses that occur naturally as well as vaccine-derived Polio(cVDPV).

What is Vaccine-Derived Polio (cVDPV)?

Vaccines for Polio such as the Oral Poliovirus Vaccine(OPV) contains weakened or attenuated vaccine-virus which activates the immune responses in the body. When such vaccines are given to a young child, the attenuated vaccine-virus replicates in the intestines and allows the child to develop an immunity against this virus by producing antibodies. During this period, the vaccine-virus will also be excreted. Excretion of this vaccine-virus may spread to the community and offer "passive" immunization to the community children before eventually "dying out".

On some extremely uncommon circumstances, should a community be severely under-immunized, the excretion of the vaccine-virus may continue to circulate for an extended time. The longer the vaccine-virus is allowed to circulate, the chances of a genetic change occurring for the virus increases. This may cause the virus to genetically modify itself to be able to paralyze despite being in a weakened form initially.

It takes an incredibly long period of time, around a year or so, for such an instance to occur and a highly under-immunized community as a background setting is required. Circulating cVDPV occur in areas where routine or supplementary immunization activities are poorly conducted and a population is left susceptible to the disease.

If a population is fully immunized and lives in a well sanitized environment, they will not experience both vaccination-derived polio and wild polioviruses, [3]

Reference:
[3]What is vaccine-derived polio? (2014, October ). Retrieved May 27, 2015, from http://www.who.int/features/qa/64/en/

Research

The Global Polio Eradication Initiative is stressing on the importance of research against Polio to create and guide the world into a lasting polio-free world. The Global Polio Eradication Initiative coordinates and backs up an extensive programme of research from various core scientific disciplines with the 2 broad objectives f identifying, developing and evaluating new tools and tailored approaches to maximize the impact of eradication efforts as well as to inform long-term policies for the post-eradication era.

They currently support research areas including: Optimizing oral polio vaccine efficacy, Optimizing oral polio vaccine delivery, Developing affordable inactivated polio vaccine, Managing risks associated with vaccine-derived polioviruses and vaccine-associated paralytic polio (including Oral Polio Vaccine (OPV) cessation), Antivirus, Polio diagnostics and Surveillance research.[4]

Their efforts were not wasted when it was reported that the "World is ready for OPV2 cessation" in 11 December 2014. At the October 2014 meeting, the Strategic Advisory Group of Experts on immunization (SAGE) - the independent body advising the World Health Organization(WHO) on immunization - concluded that preparations for the Oral Polio Vaccine type 2 (OPV2) withdrawal in early 2016 are on track. According to the article, this conclusion is of utmost importance in the success of Polio Eradication & Endgame Strategic Plan 2013-2018. The main aim was to remove the risk of cVDPV2 emerging by switching from trivalent OPV(containing type 1,2 and 3 serotypes) to bivalent OPV (containing only type 1 and 3 serotypes) in routine immunization programmes since   cVDPV2 had emerged in several countries in 2014 despite the wild poliovirus type 2 being eradicated since 1999. [5]
But what does this mean?                                                          

There are plans to introduce inactivated polio vaccines (IPV) into the routine systems of 119 countries globally by the end of the year 2015. This marks one of the largest globally coordinated vaccine introduction projects in history. In order for this ambitious feat to be accomplished, all those countries will need to switch vaccines in the immunization programs carried out in April 2016. In a 2 week switch period, countries will decide on a National Switch Day in order to minimize the risk of a country continuing to use the trivalent OPV and inadvertently re-infecting other neighboring countries no longer using that particular vaccine.

The Global Polio Eradication Initiative is working closely with countries, regions, partners and manufacturers to ensure the vaccine supply is properly managed so as to gradually reduce the stck of trivalent OPVs that will eventually no longer be in use in the near future. This is to ensure that the trivalent OPVs remains in stock until the last day , countries of course would need to be cautious and arrange for service points as well as the proper disposal of stock. A one week buffer supply will be calculated and maintained to ensure that no child remains unimmunized during the switch week. [5]

As of 21 July 2015, WHO had put up a notice seeking consultants for the OPV expanded project in preparation for switch day. To see the application form, click Here.

[4] [http://www.polioeradication.org/Research.aspx] Research. (n.d.). Retrieved July 30, 2015.

[5][http://www.polioeradication.org/mediaroom/newsstories/World-ready-for-OPV2-cessation-/tabid/526/news/1181/Default.aspx?popUp=true] World ready for OPV2 cessation. (2014, December 11). Retrieved July 30, 2015.

How relative is Polio today?

As shown in the video, Polio has mostly been eradicated with the exception of 3 main countries

-Afghanistan

-Nigeria

-Pakistan

This however does not mean that countries other than the above mentioned 3 cannot be affected by the poliovirus. WHO recommends all those travelling to previously affected countries to be properly immunized before proceeding to that region.

The up to date 14 January 2015 data sheet depicts that in the year 2014, there was a total of 350 documented cases globally. Of the 350 cases, 331 of those cases were in these 3 endemic countries. This shows that Polio is infectious, and that we should not be complacent in our vaccinations since Polio is also documented in non-endemic areas. 

*endemic: (disease or condition) associated in a particular area. 

The current issue in the 3 countries mentioned above is that the cases documented were mostly caused by wild poliovirus type 1. Documented cases show that Nigeria and Afghanistan have mostly contained the situation but Pakistan remains as the top location of which most Polio cases are documented.  Below is a statistic guide of the cases documented in the 3 countries. [6]

Reference:
[6]Wild Poliovirus (WPV) cases week Ending 14 January 2015. (2015, January 14). Retrieved May 26, 2015, from http://clubrunner.blob.core.windows.net/00000050024/en-ca/files/sitepage/polio-headlines/14-jan-2015/Polio-Headlines-Jan-14.pdf

Cameroon Case (Part I)

21 November 2013 - A wild poliovirus type 1 was confirmed in Cameroon. The first reported case of poliovirus was in the 2009.  The Wild poliovirus was isolated from 2 acute flaccid paralysis(AFP) cases from the west region with the onset of paralysis on 1 October and 19 October 2013. Genetic sequencing of the virus indicates a possible link between the Cameroon poliovirus and the wild poliovirus detected in Chad in 2011.

Measures for an emergency outbreak response was implemented with at least 3 national immunization days (NIDs) that was conducted on 25-27 October 2013. Subnational immunization days in December followed by 2 subsequent NIDs in January and Febuary 2014. Routine immunization rates were approximately 85.3% for Oral Polio Vaccine (OPV3). Response from neighboring countries Chad and Central African Republic was also drafted.

As the strain was last detected in 2011 in Chad, plans to develop and strengthen sub-national surveillance sensitivity and activities with detailed analysis across the region was drafted to more ascertain any gaps.

In 2013, the far north region of Cameroon also reported 4 cases of circulated Vaccince Derived Poliovirus type 2 (cVDPV2). Patients developed paralysis between 9 May and 12 August 2013. Again, from genetic sequencing, it was discovered that the viruses were linked to a circulation in Chad which was also detected in Nigeria and Niger. Several large-scale supplementary immunization activities were then conducted during the months of August and September followed by NIDs subsequently in October 2013.

This confirms the risk of ongoing international spread of pathogens due to globalization. Who had reflected and assessed the risk of further international spread across the region based on the history of international spread of polio from Northern Nigeria across the West and Central Africa and subnational surveillance gaps and labelled the risk as HIGH. [7]

Reference:
[7] Wild poliovirus in Cameroon. (2013, November 1). Retrieved June 20, 2015, from http://www.who.int/csr/don/2013_11_21/en/

Cameroon Case (Part II)

17 March 2014 - 3 additional cases of wild poliovirus type 1(cVDPV1) was reported with the onset of paralysis on 6, 25, and 31 Janurary 2014 from 3 new regions (North West, Adamaoua and Center) confirming continuous WPV transmission and geographic expansion of infected areas following the detection of the 4 cases in Cameroon in October 2013. Due to the continual spread of cVDPVs in Cameroon, gaps in surveillance, and influx of vulnerable refugee populations from Central African Republic, WHO had elevated the risk assessment of international spread of polio from Cameroon to VERY HIGH.

Following the confirmation of the outbreak in October 2013, Cameroon conducted 3 National Immunization Days (NIDs) followed by a fourth Nationwide Activity on the 9 March 2014. Despite independent monitoring suggesting some minor improvements in poliovirus activity, serious gaps in quality, both implementation and monitoring of cVDPVs, remained an urgent issue. Quality varies greatly by region and many houses were not visited for immunization of the children of the household. Analysis of the overall population immunity (non-polio acute flaccid paralysisdata 6-59 months) suggests an upwards of 40% of children that still remained under-immunized, with a shocking 30% of those children having not received any doses of Oral Polio Vaccine (OPV).

With the reports of new cases of poliovirus in the country, additional emergency outbreak responses were implemented, such as converting subnational immunization campaign to a full nationwide activity in April 2014. Ensuring the improvement in the campaigns that reach all children is critical in the success of the movement and measures implemented. Rapid improvements to the quality of surveillance so that the full extent of the outbreak can be determined and tracked is also crucial for the success in eradicating the threat of an international spread of polio in Cameroon. [8]

Reference:
[8] Poliovirus in Cameroon – update. (2014, March ). Retrieved June 23, 2015, from http://www.who.int/csr/don/2014_03_17_polio/en/