Polio Primer

In 1988, the forty-first World Health Assembly adopted a resolution calling for the worldwide eradication of poliomyelitis (polio). The Global Polio Eradication Initiative (GPEI) was launched to carry out the task. It was spearheaded by the World Health Organization (WHO), Rotary International, the United States Centers for Disease Control and Prevention (CDC), and the United Nations Children's Fund (UNICEF), in partnership with governments around the world together with many local, regional, and global agencies.

At the time, polio was paralysing an estimated 350,000 children per year; by the end of 2015, that number had been reduced to 106, and polio is on the verge of being eradicated. This success has not come easily. It has taken a massive global public health effort which immunised over 2.5 billion children, mobilised 20 million volunteers, and cost 11 billion dollars (so far). In its wild form, polio now circulates in only two countries: Afghanistan and Pakistan (though a weaker vaccine-derived form has been circulating in Lao People's Democratic Republic, Madagascar, Myanmar, Nigeria, Ukraine, and Guinea).

In spite of the size and overall success of the GPEI, the virus is tenacious and continues to survive in areas of conflict, where poverty and poor access to basic health services leave too many children un- or under-immunised, malnourished, and/or without access to clean water or sanitation. The next few years are critical for the eradication programme as it enters what the GPEI hopes will be its endgame.

What follows provides a primer on polio eradication with a particular focus on the end game strategy. It presents a simple history, some basic facts on the virus and the vaccines, and an overview of the endgame strategy.

Where did polio come from and what does it do?
Polio is an incurable but vaccine-preventable disease that mainly affects children under 5 years of age and is transmitted from person to person largely through faecal-oral contact or, less frequently, by a common vehicle such as contaminated water or food. It multiplies in the intestine and, while most people never know they have been infected, a small number contract the disease. There are three types of wild polio virus (WPV) called Type 1, 2, and 3. As the graph on the left shows, Type 2 has been eradicated in its wild form and Type 3 has not been detected since November 2012.

As the table on the right shows, in the case of Type 1, approximately 72% of those infected have no symptoms, 24% suffer only a minor illness, and 1% to 4% get aseptic meningitis. Between 0.1% and 0.5% or upwards of 1 in 200 will have irreversible paralysis. On the other hand, Type 3 results in 1 paralytic case per 2,000. In the case of WPV1 this means that for every person paralysed, 199 others have no idea they are carriers of the virus and are shedding it back into the environment. For WPV3, there are 1,999 symptomless carriers for every person who is paralysed. Among those paralysed, 5% to 10% die when their breathing muscles become immobilised. There is also a rare type of polio virus which is derived from the oral polio vaccine itself – vaccine-derived polio virus (VDPV), which is explained in more detail below.

Polio has been around for thousands of years, as this well-known Egyptian hieroglyphic shows. It circulated at low levels for much of that time and is thought to be relatively uncommon until the early 1900s, when epidemics began in countries with high standards of living. This increase in polio infection has been paradoxically linked to improved sanitation and hygiene conditions that reduced exposure to the polio virus and the development of natural immunity at a very young age, when infant immune systems were still bolstered by maternal antibodies. This led to exposure to the virus being delayed until after maternal protection had waned (4 to 6 months after birth), and this later exposure increased vulnerability to more extreme forms of the disease. Polio epidemics became more frequent and severe and, by the early 1900s, polio grew to be one of the most feared diseases in the industrialised world.

Why was polio chosen for eradication?
No matter how devastating a disease may be or how many people it might impact, there are relatively few diseases that can be eradicated¹. To make it on this list, there are a number of essential criteria that must be met. Polio has several characteristics that make it vulnerable to eradication.

• A single host or reservoir: polio cannot survive for long outside of the human body and depends on its human host to replicate.
• A vaccine or antibiotic capable of interrupting transmission: there are two very effective vaccines capable of interrupting transmission.
• Understanding the lifecycle and transmission dynamics: these are well understood for polio.
• Having dependable diagnostic tools: polio has good and reliable diagnostic tests and surveillance tools that allow the virus to be detected.
• Understanding the social, cultural and cost feasibilities: success in controlling polio in North America and Europe provided a reasonably solid picture of the financial, social, and cultural feasibility of the effort.

All of this made polio a good candidate for eradication.

However, it has become clear over the course of the programme and the many missed deadlines for eradication that not enough was known about social and cultural issues, especially regarding minority and underserved groups, or the impact of conflicts and the geopolitical fallout they engender. These factors increased the complexity of the programme and its cost manifold. The lesson here may be to accept that any global programme of this size has to be prepared to run into unforeseen and potentially very large issues, and the longer a programme of this size takes, the more likely it is to confront an increasing array of complex issues. No one can predict the social and cultural nuances of every group - let alone how they may change over time in light of an evolving geopolitical environment. There is no question that polio was, and remains, a good candidate for eradication, and there is every reason to be optimistic the programme will be successful. But it is equally clear that any eradication programme will come with significant risks no matter how good the tools or how tantalisingly simple the transmission routes may be – polio is no exception.

What about the vaccines?
In 1938, the National Foundation for Infantile Paralysis (better known as the March of Dimes) began and over the following decades raised millions of dollars for research and patient aid. Highly visible and popular, the March of Dimes provided impetus and significant resources for the search for a vaccine. In the 1950s, two effective vaccines were developed - Oral Polio Vaccine (OPV) and Inactivated Polio Vaccine (IPV) by Albert Sabin and Jonas Salk, respectively. These vaccines have different strengths and weaknesses and both have been essential in the fight to eradicate polio.

OPV or the Sabin vaccine uses an attenuated or weakened form of the virus to produce an immune reaction with a very low risk of actually contracting polio. The oral vaccine follows the same route as the virus itself, passing into the digestive system via the mouth. It generates an immune response quickly within the mucosal membrane of the intestines, which reduces replication of the virus in the gut. These attributes make it particularly useful during an epidemic, as they help to quickly build immunity and reduce the amount of wild virus in the environment. The attenuated virus shed via an immunised child's stool has the secondary benefit of exposing others to a weakened form of polio and providing a secondary albeit weaker immunising effect to those who come into contact with it in the environment.

On the negative side, the attenuated virus can revert to more virulent strains in very rare cases (1 per 2.7 million doses) which can cause paralytic polio. This is the vaccine-derived polio virus (VDPV) mentioned above.

OPV comes in four forms:

• Monovalent OPV contains only one type of polio virus and is effective only on that type. mOPV1 stands for monovalent Type 1 vaccine and works only on Type 1 polio, and mOPV3 works only on Type 3 polio.
• Bivalent OPV contains two types of polio virus (1 and 3) is effective against those types - bOPV.
• Trivalent OPV contains all three types (1, 2, and 3) and is effective against all three - tOPV.

Trivalent would seem to be the best to use as it immunises against all three types of polio but has two major drawbacks. The first is that it is not as effective as the monovalent and bivalent vaccines at building immunity. The second is that its use means that, even though Type 2 virus has been eradicated in its wild form, it is continually being reintroduced into the environment in a weakened state and is the source of Type 2 VDPV.

IPV or the Salk vaccine uses killed polio viruses of all three types to give the individual immunity from polio. IPV is just as effective at protecting the individual from polio as OPV and has the significant benefit of not shedding weakened live virus back into the environment. However, IPV costs more per dose of vaccine and more to deliver, as it has to be given by a health worker trained in intermuscular injection (over than 6 times more expensive than OPV²). It also induces low immunity to the gut in contrast with OPV which means that it protects the individual immunised but does not stop that individual from being a carrier of polio virus and unwittingly a source of continued viral circulation.

As we noted, polio cases have decreased by over 99% since 1988 with just 106 cases in 2015. However, these cases were not all the same type. There were 74 cases of WPV Type1 (20 in Afghanistan and 54 in Pakistan) and 32 cases of circulating VDPV (2 in Pakistan, 7 in Guinea, 8 in Lao PDR, 10 in Madagascar, 2 in Myanmar, 1 in Nigeria, and 2 in Ukraine). Click here to access asearchable, regularly updated case count. The programme is adjusting to this new context of fewer wild cases in fewer places and of small pockets of circulating VDPV in countries or amongst peoples with low immunisation rates. With only 2 endemic countries remaining (Pakistan and Afghanistan), only 1 type of wild virus circulating³ and the genetic diversity of wild polio shrinking, there is every reason to be optimistic that we are indeed in the polio endgame. The video timeline above offers a good picture of the wins and losses and how the circulating space has shrunk between 2003 and 2015. Yet as long as a single child remains infected with poliovirus, children in all countries remain at risk of contracting the disease. That is why the endgame strategy has to involve different approaches.

The Polio Eradication and Endgame Strategic Plan 2013-2018 (for a summary, click here) represents a major milestone in polio eradication and describes specific actions that need to happen to successfully achieve eradication. It lays out a set of four main objectives as explained in the chart on the right. As was mentioned above, deadlines for interrupting wild polio transmission have been missed several times and, after missing the last 2015 deadline noted in Objective 1, the hope is now for the end of 2016. Equally, Objective 2 will prove difficult in some countries where immunisation systems are very weak. This means the programme will need to adapt on a country by country basis to ensure levels of immunisation are sufficient and the right vaccine is being used. In general, this will mean:

• Removing trivalent OPV from use starting in April 2016 (what's called the switch) and only using bivalent vaccine. This means identifying all stocks in all countries and turning them in to avoid accidental use or release into the environment. Done well, this removes the possibility of Type 2 being reintroduced and starting to circulate again.
• Where VDPV2 is circulating, IPV needs to be introduced as widely as possible as it provides immunity to all three types of polio without the risk of reintroducing the virus back into the environment. In countries where routine immunisation rates are low, and capacity for high rates of IPV coverage is limited, remaining stocks of trivalent OPV (held only in central and secure locations after the switch) may be used in some contexts to interrupt circulation of VDPV2.
• As circulation of both WPV and VDPV is interrupted, the use of OPV will be phased out entirely to remove the risk of any polio virus being shed into the environment and starting to circulate again. This is presently planned to happen in 2019-2020 but will depend on meeting other objectives such as the interruption of WPV transmission.
• Strengthening of routine immunisation services will remain an important element throughout the endgame, as a critical final defense against the return of polio is the maintenance of consistent and high global immunisation rates.

So that's the plan, and GPEI will be providing status updates on country planning for IPV introduction and OPV switch at this link. But it is clear that each remaining country presents its own set of challenges, and the road ahead will continue to be rocky.

1 There have been eight attempts to eradicate infectious disease in humans and animals. Of these: two have been successful - smallpox in humans and rinderpest in cattle; four are ongoing - poliomyelitis, yaws, dracunculiasis, and malaria; two programmes have been suspended - hookworm and yellow fever; and there are five further candidates for possible future eradication campaigns - measles, mumps, rubella, lymphatic filariasis, and cysticercosis.
2 CDC Morbidity and Mortality Weekly Report (MMWR) Combined Use of Inactivated and Oral Poliovirus Vaccines in Refugee Camps and Surrounding Communities - Kenya, December 2013 Weekly, March 21, 2014 / 63(11); 237-241.
3 CDC Morbidity and Mortality Weekly Report (MMWR) Possible Eradication of Wild Poliovirus Type 3 - Worldwide, 2012 Weekly November 14, 2014 / 63(45); 1031-1033. It is possible type 3 continues to circulate at a low level, but with the decreasing genetic diversity noted in this paper from 2014 and no cases seen since November 2012, it is looking more and more like it has been interrupted.