The Polio Vaccine: An Example of Evolving Risks and Benefits

In the last few years we have seen two major milestones towards polio eradication.

1. In 2015, one of the three types of poliovirus was declared eradicated.
2. In 2016, the oral polio vaccine (OPV) that included all three types of poliovirus was replaced with an OPV that only includes the two active polioviruses.

These milestones create an opportunity to discuss polio and how vaccine recommendations are adapted based on the changing risks of a disease vs. the risk and benefits of the vaccine. When we hear about changes to the CDC vaccine schedule, usually we only think about more vaccines being added; however, vaccines in the schedule can also be removed or altered. Currently, the only vaccine that has been completely withdrawn from the vaccine schedule is smallpox, which occurred after smallpox was eradicated. While polio has neither been eradicated nor the vaccine removed from the schedule, there have been many changes to the polio vaccine recommendations, including changes in the type of polio vaccine used.

This article will discuss polio disease, the risks and benefits of the different types of vaccines, how vaccine recommendations have changed, and the plans for polio eradication.

 

What is polio?

Polio (or poliomyelitis) is caused by the poliovirus. There are three different types of poliovirus, called, serotypes 1, 2, and 3. Each serotype can cause a polio infection. Polio does not cause symptoms in most people. The symptoms that do occur include^1,2:

• Flu-like symptoms – 1 out of 4 people
• Meningitis – 1 out of 25 people
• Paralysis – 1-2 out of 200 people

Paralysis could affect the small or large parts of the body. You have probably seen the old pictures of children in iron lungs. The iron lungs were used to help children breathe when the muscles around their lungs were paralyzed from polio. Polio used to be a leading cause of disability worldwide. Polio mostly affects children under the age of 5 years³.

People who have survived a polio infection are still at risk of developing post-polio syndrome 15-40 years after the original infection¹. Post-polio syndrome causes pain, weakness, or paralysis.

 

How is polio spread?

Polio can spread through saliva and feces. The most common way for polio to spread is through fecal-oral transmission. Objects contaminated with feces, such as water, food, or even children’s toys, can spread polio.

The polio virus replicates in mucosal tissue, which lines the nose, mouth, and intestines. The virus sheds through a person’s stool or saliva and can be spread to another person.

 

What are the different polio vaccines?

There are two types of polio vaccine. The oral polio vaccine (OPV) and the inactivated polio vaccine (IPV).

Oral Polio Vaccine (OPV)

The OPV uses live, weakened polioviruses. Patients swallow a few drops of the vaccine for protection. No shots are needed.  The weakened virus in the vaccine replicates in the intestines. The vaccine-virus stimulates the immune system to make antibodies against the polioviruses without causing an infection. The vaccine-virus replicates and is excreted from the intestines like the non-vaccine (also called “wildtype”) version would. Like the wildtype poliovirus, the vaccine-virus can spread to other people. When it spreads to other people, their immune systems also develop antibodies to the poliovirus, so in this way, the OPV gives passive immunity in those people⁴.

Inactivated Polio Vaccine (IPV)

The IPV uses killed polioviruses. Unlike the OPV, it is administered as an injection. It stimulates a strong antibody response to protect against getting symptoms of polio. It does not stimulate a strong mucosal response in the intestines, where polio replicates, so it does not prevent the spread of polioviruses and it does not give passive immunity to others. With the IPV someone can be protected from paralysis, but they can still spread the wildtype virus to others⁵.

 

What are the risks of the polio vaccines?

The OPV has a very rare, but very serious side effect: vaccine-associated paralytic poliomyelitis (VAPP).  VAPP occurs because the OPV uses a live, weakened virus. The weakened virus replicates in the intestines. Normally, the weakened virus will not cause an infection, but it will be enough viral exposure in the intestines to create a strong antibody response. In rare cases, however, the virus can mutate during replication, become virulent, and cause VAPP⁶.

In countries that use OPV, there are about 2-4 cases of VAPP per million births³. VAPP rates decrease when children receive at least one dose of the IPV before they receive the OPV³. Poliovirus serotype 2, was the most common cause of VAPP³. Serotype 2 has been eradicated and all OPV doses only contain type 1 and 3 polioviruses now, so it is likely that we will see a decrease in VAPP cases.

The other risks of the polio vaccines are minor, such as pain or swelling at the injection site, mild fever, and fatigue.

 

Table 1. Summary of Polio Vaccines

	Oral Polio Vaccine      (OPV)	Inactivated Polio Vaccine (IPV)
Also known as	Sabin Vaccine	Salk Vaccine
Benefits	Prevents polio in the person that receives the vaccine   Stops person-to-person spread of polio	Prevents polio in the person that receives the vaccine   Does not cause vaccine-associate paralytic poliomyelitis
Risks and Disadvantages	Vaccine-associated paralytic poliomyelitis (2-4 cases per 1 million births)4	Pain at the injection site, mild fever, fatigue   Does not stop person-to-person spread
Best for	Countries with high risk of polio infection   Prevention of epidemics	Countries with low risk of polio infection   Preventing polio in the individual only
Locations used	Endemic countries (e.g., Afghanistan, Pakistan)   High risk areas	Low risk areas (e.g., North America, Europe)

 

If OPV can cause vaccine-derived polio infection, why is it used at all when the IPV is available?

The OPV and IPV both give an individual protection from the poliovirus, but in different ways. The poliovirus replicates in a person’s digestive tract and is spread by either a fecal-oral or an oral-oral route. Both vaccines give the individual receiving the vaccine a similar level of protection. That is, a person who has received either vaccine will be protected from getting symptoms of polio. The IPV does not activate the immune system in the digestive tract where the virus replicates; so, it is possible for a person to be protected from symptoms of polio with the IPV, but they may still spread the wild-type virus⁵. The OPV is better at activating immunity in the digestive tract; therefore, it is better at stopping the spread of the poliovirus. The IPV can still prevent the transmission of polio from one person to another, but not as well as the OPV. The OPV is also easier to give people because it is only a couple of drops in the mouth that are swallowed. The IPV is an injection, which requires more medical equipment and medical personnel. In regions with less medical infrastructure, the OPV is easier to administer than the IPV.

 

Did polio rates go down because of vaccines or better sanitation?

Polio spreads by oral-to-oral and fecal-to-oral routes. It is true that areas with poorer sanitation can have a faster fecal-oral spread of polio. Improved sanitation does have some role in decreasing the risk of exposure to infected feces, but vaccines are largely responsible for the global decline of polio. Before the introduction of the polio vaccine, in certain populations the trends of polio cases and deaths were increasing rather than decreasing with sanitation⁷. The vaccine was introduced in the US in 1955, so sanitation was not an issue at that time, but outbreaks were still occurring. Annual polio rates would go up and down from year to year, but after vaccines were introduced, the total number of cases were consistently low (see figure 1).

 

Figure 1 Polio rates by year with inactivated polio vaccine (IPV) and (oral polio vaccine) OPV introduction. From CDC²

 

Did polio rates go down because of reclassification or diagnosis changes?

In short, no. Polio cases are diagnosed based on clinical laboratory tests. Other criteria beyond whether poliovirus was detected in someone, just serve to further subtype polio cases.

Several websites purport that administrative reclassification or diagnostic changes actually decreased the number of polio cases and not because of vaccinations. These claims are incorrect interpretations of how polio cases are counted and are centrally focused on paralytic polio.

As discussed above, not all patients with polio have paralysis or even have clinical symptoms. Total polio cases are counted based on whether a person tests positive on a diagnostic test for polio. Therefore, even if the paralytic polio classification changes the number of paralytic cases, it does not change the number of total polio cases.

The CDC currently defines “paralytic polio” as: onset of acute flaccid paralysis of 1 or more limbs; no other apparent cause; no sensory or cognitive loss; neurological deficit 60 days after onset of initial symptoms or death or unknown follow-up status; and then further classified based on epidemiological and laboratory data⁸.

The current definition of “non-paralytic polio” is any person without symptoms of paralytic poliomyelitis with confirmed poliovirus laboratory data⁹.

The further sub-classifications of polio developed in response to epidemiological data and improved diagnostic testing. The most recent sub-classifications based on epidemiology were updated in 1989 and are based on whether the person received a vaccine, whether the case was imported, etc¹⁰.  At the height of the polio epidemics in the US in the 1950’s, polio was primarily diagnosed by stool cultures¹¹. Today, we use PCR tests, which look at the DNA of the virus. By looking at the DNA, clinical investigators can determine the serotype, and whether the virus is derived from the OPV.

There’s another misconception that polio was reclassified into other diagnosis, such as, acute flaccid paralysis (AFP) or meningitis. Both AFP and meningitis have multiple potential causes. For example, poliovirus, other viruses or bacteria, autoimmune disorders, and neuro-muscular disorders can all cause AFP. When a patient has AFP a full work-up with blood tests, stool cultures, and possibly MRIs or other imaging to figure out what caused the paralysis. If the patient tests positive for polio, then they are counted as a polio cases. If they do not have a positive polio test, there is likely another cause for the AFP and they are not counted as a polio case.

As discussed, there have been changes to the definitions and classifications of different subtypes of polio disease, but these changes do not impact the total number of polio cases.

 

If polio cases are so rare, do we still need to vaccinate?

In the western world, the risk of polio is very low. The last case of paralytic polio in the United States was in 2009. Before 2009, there were no infections since 2005². It is reasonable to wonder if it is worth taking on any risk from a vaccine to protect against a disease that is not even active in your country. The reasons that polio vaccines are still recommended are that:

1)     Polio infections still occur. With global travel, polio infections have been imported to countries that do not have polio infections. Unvaccinated people are especially at risk for contracting polio.

For example, in Minnesota, polio was detected in an immunocompromised, unvaccinated infant¹². Doctors tested the infant when she was hospitalized for fever, diarrhea, and recurrent infections.  For two months, the poliovirus spread to 35% of the children tested in the community. Luckily, no one else had major symptoms. Genetic tests of the virus indicated that the virus likely came from an international traveler because the virus was derived from an OPV strain. Since OPV has not been used in the US for many years, the original infection would have come from outside of the US. This community was undervaccinated. Low vaccination rates create more potential for the virus to spread.

2)     Polio is a severe disease. Polio was a leading cause of disability before vaccination programs existed. Globally, it is estimated that 16 million people do not have a disability today because of polio vaccination programs³. The paralysis caused by polio can be temporary or permanent. It can affect small or large parts of the body.

Polio has been perceived as less severe because most people do not have symptoms. About 1% of patients will have paralysis². One percent is a low number, but when an outbreak occurs among a large number of people, then 1% still impacts a large number of people. The worse recorded polio epidemic in the US was in 1952, with 57,879 cases. Most of these cases were people with symptoms, such as paralysis, because people with symptoms are more likely to be tested and counted. This means that the number of people infected and spreading the virus is likely much higher than the reported number.

3)     Polio is very contagious. Polio is one of the most contagious diseases. In an unvaccinated household with one person infected, 100% of all children will become infected and 50% of all adults will become infected². It is difficult to avoid people who are infected because most do not have symptoms, but they can still pass the virus onto other people. This is one of the reasons polio is so dangerous and difficult to prevent without the use of vaccines.

4)     The IPV is very safe. The IPV cannot cause VAPP like the OPV. There are minor side effects of pain, low grade fever, redness and swelling at the injection site, but no major side-effects have been documented for the IPV¹³.

 

How have the changes in risks and benefits of the vaccine changed recommendations?

When polio rates are high, the OPV is a better vaccine to control epidemics. As noted above, it is easier to administer quickly to large groups of people and it activates immunity in the intestines where the virus replicates and spreads. However, OPV causes the rare risk of VAPP. When making vaccine recommendations, public health officials consider all the risks of using and not using vaccines including: VAPP risk, wildtype polio risk, current outbreaks and epidemics, other vaccine side effects, consequences of polio infection, etc.

When polio rates declined in the US, it was no longer worth the risk of VAPP, so the US switched all vaccination programs to include only the IPV. IPV is one of the safest vaccines: it cannot cause VAPP because it uses a killed virus, it has mild side-effects, and it is effective at protecting the individual against polio.

Globally, there have also been changes in polio vaccination programs because of changing risks and benefits.

Last year, there were more cases of polio from circulating viruses from the OPV than wildtype viruses¹⁴. The benefits of the original OPV schedule are no longer worth the risks. Some things have been done to further decrease this risk and there is a plan to remove OPV from all vaccination programs.

Since the eradication of the type 2 poliovirus, the OPV vaccines have removed that strain of virus. OPVs are now only manufactured with type 1 and type 3 polioviruses. This decreases the risk of VAPP.

Evidence shows that the risk of VAPP is decreased with a dose of IPV. So, in countries where endemic polio is still a risk, people now receive one dose of IPV, followed by the OPV. They are then protected from VAPP and still have the community benefits of OPV. Introducing the IPV in these regions also ensures that individuals are protected from the type 2 poliovirus. While serotype 2 was eradicated, the virus could still exist in regions with less robust testing to screen for the virus and it may remain undetected. Therefore, it is still important that the IPV provides protection for all three serotypes.

The Global Polio Eradication Initiative has a stepwise plan to further decrease risks of the vaccines, while maintaining robust protection for everyone.

 

What is the Global Polio Eradication Initiative?

The Global Polio Eradication Initiative is a partnership between the World Health Organization (WHO), Rotary International, the US Centers for Disease Control and Prevention (CDC), the United Nations Children’s Fund (UNICEF), the Bill and Melinda Gates Foundation and other partners. They provide tools and resources global in order to eradicate polio. They also provide information on current outbreaks. For more information, visit their website: http://polioeradication.org/

 

Is polio eradication possible?

Yes. The poliovirus can only survive in human hosts; therefore, if we can prevent all people from being infected, polio can be eradicated. Other bacteria and viruses can live in other hosts. For example, the flu virus can live in humans, chickens, and pigs, so even if all humans are immunized, the flu virus can still survive in other hosts. The polio virus would not survive in other hosts.

 

What are the plans for polio eradication?

Polio eradication cannot occur without global vaccine compliance. It is difficult to fully eradicate an infectious disease because it depends on global coordination and compliance, even in areas without active infections. People become less motivated to vaccinate when the number of cases of a disease go down. Because of this, the final stages before eradication take a long time¹⁵. This has been seen in other diseases. Measles and whooping cough have both been close to eradication, but due to low vaccination rates the number of cases increased up from a couple hundred to several hundred thousand cases within a few years of low vaccination coverage.

There were 114 cases of polio in 2017¹⁴. However, if polio vaccinations decrease to critically low numbers, polio cases could increase to over 200,000 within 10 years³. Between 2011 and 2014, areas with political conflicts and population displacement have seen increases in polio cases, including Cameroon, Equatorial Guinea, Ethiopia, Iraq, Kenya, Nigeria, Pakistan, Somalia, and Syria¹⁶. As conflicts continue, it may take longer than hoped to completely eradicate polio.

Complete eradication in the next decade is possible, but vaccination programs have to continue.

Eradication cannot happen until OPV is withdrawn. Even though the risks of VAPP are small, they can still occur as long as OPV is around. Global efforts have centered on using the OPV for its best use, to prevent and stop outbreaks, while withdrawing it from routine use.

To help combat VAPP cases and decrease total cases of polio, the Global Eradication Initiative has planned for a complete withdrawal of the OPV in 2019¹⁷. To start, the OPV containing all 3 polio serotypes was withdrawn and replaced with the version containing only the 2 serotypes still causing wild-type infections.

To decrease the risk of VAPP while still using the OPV to stop outbreaks in endemic countries, at least one dose of the IPV is recommended. Then, in 2019, the goal is to only have IPV programs globally. OPV stockpiles will still be maintained in case an outbreak occurs. Until OPV is completely withdrawn, production of the IPV will increase to meet the new demand. The medical infrastructure and coordination in key areas will be improved to make the IPV accessible for everyone.

Removing OPV globally will eliminate vaccine-derived polioviruses. The IPV will protect people from wild-type and vaccine-derived polioviruses.

 

If polio reaches global eradication, will we still have to vaccinate?

If global eradication occurs, polio vaccination programs would not need to continue. We will likely need to continue vaccination programs for some number of years after the last confirmed case of polio because it is not possible to test every single person in the world to make sure no one is infected, so there could be cases we cannot detect. If after several years, there are still no reported polio cases, vaccination programs would be withdrawn.

 

Final thoughts

Polio was once a major cause of childhood infection and disability. With vaccination programs, rates of polio have been consistently declining. Different polio vaccines have different risks and benefits. With the changing risks of epidemics and as new research is produced, the recommendations for polio vaccines have changed. One of the three serotypes of polio has been eradicated. Through a globally coordinated effort, plans have been underway to make sure the last two serotypes of polio are also eradicated. Hopefully, very soon, polio will be completely eradicated and fade into history.

 

References

1. Global Health [Internet]. Atlanta, GA: Center for Disease Control and Prevention; What is Polio?. 2017 July 25 [cited 2018 February 7]; [about 2 screens]. Available from: https://www.cdc.gov/polio/about/index.htm
2. Centers for Disease Control and Prevention. Epidemiology and Prevention of Vaccine-Preventable Diseases. Hamborsky J, Kroger A, Wolfe S, eds. 13th ed. Washington D.C. Public Health Foundation, 2015. https://www.cdc.gov/vaccines/pubs/pinkbook/polio.html
3. World Health Organization [Internet]. Geneva, Switzerland: World Health Organization. Poliomyelitis; 2017 April; [cited 2018 February 7]; [about 3 screens]. Available from: http://www.who.int/mediacentre/factsheets/fs114/en/
4. Global Polio Eradication Initiative [Internet]. Geneva, Switzerland: World Health Organization. OPV; [cited 2018 Feb 7]; [about 3 screens]. Available from: http://polioeradication.org/polio-today/polio-prevention/the-vaccines/opv/
5. Global Polio Eradication Initiative [Internet]. Geneva, Switzerland: World Health Organization. IPV; [cited 2018 Feb 7]; [about 2 screens]. Available from http://polioeradication.org/polio-today/polio-prevention/the-vaccines/ipv/
6. Global Polio Eradication Initiative [Internet]. Geneva, Switzerland: World Health Organization. Vaccine-derived Polioviruses: Managing the Risks; [cited 2018 Feb 7]; [about 3 screens]. Available from http://polioeradication.org/tools-and-library/research-innovation/vaccine-derived-polioviruses/
7. Nathanson N, Kew OM. From Emergence to Eradication: The Epidemiology of Poliomyelitis Deconstructed. Am J Epidemiol. 2010 Dec 1; 172(11): 1213–1229.
8. National Notifiable Diseases Surveillance System [Internet]. Atlanta, GA: Centers for Disease Control and Prevention. Poliomyelitis, Paralytic 2010 Case Definition; [cited 2018 February 7]; [about 1 screen]. Available from: https://wwwn.cdc.gov/nndss/conditions/poliomyelitis-paralytic/case-definition/2010/
9. National Notifiable Diseases Surveillance System [Internet]. Atlanta, GA: Centers for Disease Control and Prevention. Poliovirus Infection, Nonparalytic 2010 Case Definition; [cited 2018 February 7]; [1 screen]. Available from: https://wwwn.cdc.gov/nndss/conditions/poliovirus-infection-nonparalytic/case-definition/2010/
10. SutterRW, Brink EW, Cochi SL, Kew OM, Orenstein WA, Biellik RJ, Hinman AR. A new epidemiologic and laboratory classification system for paralytic poliomyelitis cases. Am J Public Health. 1989 Apr;79(4):495-8.
11. Laboratory Diagnosis of Poliomyelitis. Can Med Assoc J. 1956 Jul 15; 75(2): 148.
12. Alexander JP, Ehresmann K, Seward J, Wax G, Harriman K, Fuller S, Cebelinski EA, Chen Q, Jorba J, Kew OM, Pallansch MA, Oberste MS, Schleiss M, Davis JP, Warshawsky B, Squires S, Hull HF; Vaccine-Derived Poliovirus Investigations Group. Transmission of imported vaccine-derived poliovirus in an under vaccinated community in Minnesota. J Infect Dis. 2009 Feb 1;199(3):391-7.
13. Update: Vaccine Side Effects, Adverse Reactions, Contraindications, and Precautions: Recommendations of the Advisory Committee on Immunization Practices (ACIP). Morbidity and Mortality Weekly Report. 1996 Sep 6;45:1–35.
14. Global Polio Eradication Initiative [Internet]. Geneva, Switzerland: World Health Organization. This Week; 2018 January 31; [cited 2018 February 7]; [about 2 screens]. Available from: http://polioeradication.org/polio-today/polio-now/this-week/ -now/
15. Saint-Victor DS, Omer SB. Vaccine refusal and the endgame: walking the last mile first. Philos Trans R Soc Lond B Biol Sci. 2013 Jun 24;368(1623):20120148.
16. Akil L, Ahmad HA. The recent outbreaks and reemergence of poliovirus in war and conflict-affected areas. Int J Infect Dis. 2016 May 26;49:40-46.
17. Global Polio Eradication Initiative [Internet]. Geneva, Switzerland: World Health Organization. OPV Cessation; [cited 2018 Feb 7]; [about 2 screens]. Available from: http://www.polioeradication.org/Posteradication/OPVcessation.aspx