World Polio Day: "Vaccine-derived" polio, eradication, and surveillance

What does it mean that polio was found in wastewater in London and New York? What is “vaccine-derived” polio? What does eradication mean, and how will we achieve it? On this World Polio Day, Dr. Ananda Bandyopadhyay, deputy director of the polio team at the Bill & Melinda Gates Foundation, explains the most up-to-date information and maps out the future of tackling polio.

Read The Lancet's recent editorial on polio eradication:
Polio eradication: falling at the final hurdle?

Read the recent article on detecting polio in London:
Sustained detection of type 2 poliovirus in London sewage between February and July, 2022, by enhanced environmental surveillance

You can continue the conversation with Jessamy and Gavin on Twitter by following them at @JessamyBagenal and @GavinCleaver.

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Transcript

This transcript was automatically generated using speech recognition technology and may differ from the original audio. In citing or otherwise referring to the contents of this podcast, please ensure that you are quoting the recorded audio rather than this transcript.

Jessamy: Hello and welcome to the Lancet voice. It's October 2022 and I'm Jessamy Bagenal. I'm here with my co host Gavin Cleaver. Polio is an infectious disease caused by a virus that can spread from person to person, and in the worst cases, in about 1 out of 200 people to 1 out of 2, 000 people, depending on the virus type, it can cause irreversible paralysis.

You might have heard about polio being detected in sewage in the US and UK. Earlier this month, The Lancet published an environmental surveillance study from London demonstrating how early detection of poliovirus had permitted a rapid public health response, including enhanced surveillance and an inactivated polio vaccine campaign among children aged one to nine years old.

We speak to Ananda Bandiopadhyay, Deputy Director, for polio global development at the Bill and Melinda Gates Foundation to get a deeper understanding about what has been happening with polio over the last year and what it all means.

Ananda, thanks so much for joining us. There's lots of news about polio and it can be quite confusing so I thought that we could start sort of from the basics and if you could just briefly outline at the moment how we prevent polio. And what are the different types of immunizations, the routes that we use, and why we choose one over the other?

Ananda: Hi, Jessamy. Thanks for asking that. We prevent polio primarily by vaccinating. And we have excellent vaccines you know, to conduct such vaccination activities. Primarily, there are two types of polio vaccines. The inactivated poliovirus vaccine, or IPV, that is given through the injectable route. And this was developed by Jonas Salk.

You know, this was in fact, in fact, the first vaccine to be licensed against polio back in the 1950s. It's an excellent vaccine with a great safety profile and with adequate number of doses. The IPV, the inactivated polio vaccine prevents paralysis. There is the other type of polio vaccine which is called the oral polio vaccine or OPV developed by Dr.

Albert Sabin back in the 1960s. This is a live attenuated polio virus vaccine and again an excellent vaccine with a great safety profile. And, much like IPV with adequate number of doses, OPV also induces immunity that would prevent paralysis. What OPV also does, Jessamy, is to also induce what we call intestinal mucosal immunity.

In a way, and to an extent, that OPV can also interrupt transmission of polioviruses. So in other words, it's a great tool also for outbreak interruption. Obviously OPV can be given orally, so it's much easier to administer. Particularly if you think about remote and hard to access places, it's also a much more affordable vaccine.

So those are the primary tools to vaccinate against folio. We also have newer tools. So a prominent example is the novel oral folio vaccine type two or N. O. P. V. Two, which is You can call it a next generation OPV or, or an OPV 2.0 where the existing Sabin, OPV the genetic structure of it, we have modified.

You know, with a hope and aim to ensure the new vaccine will be much more genetically stable. So that's what NOPV2 is. And this idea of making it more genetically stable. Is with the understanding that for the completeness of eradication of polio, we will have to interrupt the transmission of poliovirus variants or the vaccine derived polioviruses, which to be clear is not really a vaccine issue, but essentially a vaccination issue.

In areas where there is persistently poor immunization coverage. That's where the Sabinopiv can circulate for a long time and essentially revert into poliovirus variant forms and can itself cause paralytic outbreaks. So again, if vaccination campaigns are adequately maintained and routine immunization is strengthened, the vaccine derived poliovirus issue can be mitigated.

But with the novel oral folio vaccine type 2, we have the promise of even more decisively interrupting and stopping the poliovirus variants. So just, just to me, those are the three primary tools of vaccination. There are, of course, subtypes of the vaccines that I just mentioned. But there are other ways of preventing folio as well, and that is to stay alert.

You know, that's why you do polio virus surveillance. There's an extensive network of global surveillance that exists for polio, and that enables the program and the country authorities to detect polio virus in a time frame that would be meaningful for a decisive an effective outbreak response. So in addition to vaccination, I think I would highlight that maintaining the surveillance mechanism and infrastructure is also very important.

to present polio. And finally, just to me also, we need to be aware. So staying aware is also part of preventing not only polio, but but essentially any infectious diseases where even if our own community, our own country or maybe our region is polio free, we still need to be aware of of the risks of the disease that still exists somewhere.

And we need to ensure that we are fully vaccinated and taking adequate precautions so that the, the disease cannot affect. 

Jessamy: Thanks, Ananda. That's really helpful. There's a lot of information there. So I just wanted to kind of go back slightly because we started talking about surveillance and the importance of sort of monitoring.

So if maybe you could just put that into context in what's been found in New York and UK. sewage surveillance, what that's showing and why it's concerning. 

Ananda: That's an excellent segue, Jessamy. I think, again, thanks to the existence of poliovirus surveillance, such detections could be made and could be made in time that a response could be mounted.

So I'll break it down a little bit just to me what polio virus surveillance really means in the real world. So there are two broad types of polio virus surveillance. One form is the sewage surveillance or surveillance based on the environmental collection of sewage samples from different strategically located environmental surveillance sites.

And those sewage samples are then processed in globally recognized laboratories. And there are more than 140 globally recognized laboratories. In more than 90 countries in the world where environmental surveillance exists. So these collection sites then pass it on to such recognized laboratories.

And then we search for the existence or absence of polio viruses there. So it's a continuous process, Jessamy, across the world and this helps us track trend of transmission of polio viruses in different areas, polio infected and polio non infected areas. Then there is a clinical syndromic surveillance.

We also call it the acute flaccid paralysis surveillance or AFP surveillance, where a sudden onset Paralysis of any part of the body you know, especially in under 15 age group is immediately investigated by a clinical expert an epidemiologist. And if there are sufficient criteria to satisfy the case as an acute placid paralysis, stool samples are collected.

And sent again to those recognized laboratories, accredited laboratories. And again the stool samples are checked for the presence or absence of polioviruses, all types of polioviruses. So, Jessamy, these are the primary fillers of surveillance. To go back to your question, this is exactly how London and New York picked up the existence of polioviruses in, in their area.

So, London or UK they have been conducting environmental surveillance for polio for several years now. And thanks to that system the, the London site picked up the presence of a vaccine derived polio virus variant. in the sewage sample over several months. And this was an extremely significant public health event to pick this virus up in an area that is polio virus free.

And then public health response was mounted. The New York example is is an again a shining example of the clinical syndromic surveillance being practiced where an unvaccinated adult presented with sudden onset paralysis, and that particular individual was investigated with stool samples being collected as I described.

And again, eventually poliovirus presence was confirmed again, a major public health event. In a country that has been polio free. So back to your point, just to me. These are the examples of surveillance in practice on how surveillance works, even in areas that are polio free. And this also reiterates just to me the importance of not only maintaining polio surveillance and remaining what I call polio alert in all the countries.

But strengthening the surveillance system so that we don't really, you know, be late in detecting polioviruses should they arrive through importations or other events. 

Jessamy: Why is this concerning then? If we've had, we've got the surveillance, which is reassuring, the surveillance is doing its job in picking up different polio cases in, you know, different areas around the world.

So why, why are people worried about it? 

Ananda: This is very concerning, Jessamy, because polio is a highly infectious disease. The virus can spread rapidly from one place to the other. And that is why polio essentially is a plane ride away, as long as it's there somewhere. And once it arrives, Jessamy, in polio free areas, it can spread.

But particularly in unvaccinated or under vaccinated communities, and that's why there is a significant risk of paralysis or paralytic outbreaks. if polio finds its way into such under vaccinated or unvaccinated communities. So that is why it is very worrying because we have perfect tools to prevent such paralysis, which, by the way, is typically lifelong.

And with those tools, if we can maintain the vaccination status In polio free countries are essentially everywhere. Then even if the importation happens, of course, it's still a worry because we need to track how the spread is going on. You know, if it is finding the vulnerable population, etcetera.

But at least if we could maintain high vaccination coverage, be it with I. P. V. Or with O. P. V. Then there is at least lower risk of paralysis from such importation events. So there are those risks, Jessamy, of paralysis and also spreading of a virus that's highly infectious and many a times difficult to control if not, if timely responses are not mounted.

Gavin: Can I ask an extremely broad follow up question that's probably quite basic? We've been talking about polio free areas, of course, in in the UK and the US, polio free countries. What's the kind of broad status of polio around the world? You know, which countries is it still present in, which areas is it still present in, and how long have the UK and the US been polio free, I suppose?

Ananda: Great questions, Gavin. So, you know, first of all, when it comes to polio you know, I would like to characterize the polio free countries are not polio risk free. And that goes to your second part of the question as to where does polio hide? Because there are polio endemic countries that still exist.

That is why no other country Thank you. Is essentially polio risk free because it's highly infectious virus. Pakistan and Afghanistan are the two countries remaining that are endemic to wild polio viruses. So that basically that means that these are the two countries where we have never quite stopped.

polio virus transmission, wild polio virus transmission. So, and that also gives you the glimpse of how dramatic the progress has been when it comes to the eradication campaign for polio. We started off back in 1988 when Rotary International, W. H. O. U. S. C. D. C. And UNICEF came together to essentially you know, form this commitment to eradicate polio.

We had 125 countries endemic for polio circulation with approximately 1000 cases of paralysis being reported globally every day. So that gives you a glimpse of the burden of disease that was there and, and the dramatic progress, as I just mentioned, you know, it's coming down to only two countries. Now, the countries like the U.

S. or U. K., they have stopped polio a long time ago. So just as an example, the United States had its last wild polio virus case, last indigenous wild polio virus case back in the 1979 and ever since the country has been polio free, there have been some reports of importations, etcetera. But that's how the trajectory has been.

So, you know, again, the point remains that We have the proof of concept that this virus can be eliminated from most part of the world and building on that eradication is also possible, which is a global target and most of the countries have done that. And the point to be noted here is not only most of the countries have been folio free.

They have remained polio free for a long time, other than some of these chance importations that have happened, and particularly in areas of poor vaccination. The last point I would make to your question, Gavin, is the problem of the vaccine derived polioviruses, the poliovirus variants. When it comes to those types of polioviruses, we have several countries, as we speak, that are infected.

with poliovirus variant type 2 or circulating vaccine derived poliovirus type 2, in short CVDPB2. There are several countries in the Afro region in particular where these types of viruses are being reported. And that is a matter of concern and that requires a very well coordinated response. With the promising new tool that we have, the novel OPV2, to interrupt those types of transmission as well.

Gavin: So how does a vaccine derived poliovirus come about? And what's the difference between it and the wild poliovirus that you were talking about there? 

Ananda: I'm glad you asked it. So again, as I started off by saying the vaccine derived polio virus is actually a function of poor vaccination. It's not really a vaccine issue.

It's a vaccination problem. So wherever we have persistently poor vaccination coverage with the oral polio vaccine. That's where the the strains of the oral polio virus vaccine can evolve into strains through essentially circulation from one person to the other who are under unvaccinated that they evolve into strains that are revertent.

Essentially meaning they lose certain attenuating mutations in the genetic structure of the vaccine, and they acquire neurovirulence, which means they can cause paralysis. if they find a susceptible individual. So it's a mix of these two issues, really. The fact that these strains can circulate in under immunized communities, and two, they can evolve into strains that can cause paralysis.

Those are the two elements that make such evolution of vaccine derived strains a public health concern. And The Sabin strains are excellent in terms of interrupting outbreaks. But as I said, in certain settings, it can evolve into into such vaccine variants. And that is why, Gavin, we have come up with this whole new vaccine, the novel OPV2, which by now has been administered in more than 20 countries across the world, wherever the type two outbreaks are happening, the type two circulating vaccine derived outbreaks are happening.

And as we speak today, it's been 500 million doses that have been administered. over a period of roughly 18 to 20 months because the first use of this novel vaccine started back in March 2021 under the emergency use listing process of WHO, which by the way the EUL process enables such tools, such newer tools to be used for a public health benefit.

You know, for public health emergencies of international concern, which polio is. So you know, it's, it's again, quite an example of a global health effort to roll out a new tool for a public health emergency. In a massive scale, as I said, 500 million doses administered as we speak today from the time the rollout of the vaccine started, but to your point, you know, this is a promising tool that could really sustainably eradicate polio, particularly focusing on the type two vaccine derived variant and hopefully this vaccine will maintain its genetic stability and complete the interruption of the type 2 CVDPVs.

Jessamy: Can I ask a couple of clarifications, Ananda? What does under vaccination mean or poor vaccination mean in this context and how do you? define it, understand it, and, and survey it. 

Ananda: To put it simply, Jessamy, it is not having the recommended number of vaccinations by the age group recommended. So essentially, if, if a, if a particular child had to receive Just as an example, four doses of OPV and the child did not receive it, then it's an under vaccination issue.

We also have to put this into context. So, you know, if there is an active outbreak happening in an area and in that area, there are mass vaccination campaigns happening, which are, you know, essentially outbreak response options to interrupt virus transmission. In those areas, the child should receive the campaign doses as well to boost immunity against the outbreak virus.

And so just to expand the definition a little bit, Jie under vaccination could also mean that the child did not receive the campaign vaccine doses that the child. was supposed to receive given the context, given the geographic setting that the child is living in. It's a complex issue. 

Jessamy: Very difficult to keep on top of really.

Ananda: Exactly. Yes. But we need to beat the virus. You know, we need to overcome the speed of transmission that the virus has with the speed and effectiveness. of vaccination campaigns. That's what it's all about, Jessamy. 

Jessamy: And what does eradication mean in this context? Because it often doesn't mean eradication, you know, it doesn't mean that it's completely removed.

What does it mean in this context? 

Ananda: I'm so glad you asked that question because this is one of my favorite topics that I keep clarifying. So eradication, to put it simply, means this. It is the permanent reduction of a disease incidence to zero. And that permanent reduction of incidence to zero has to be worldwide, has to be global.

So those three components are essential for our understanding. of eradication, Jessamy. And so that's why the need to distinguish elimination and eradication is so important because most of the world has actually already eliminated polio. It doesn't exist in most part of the world in terms of indigenous transmission.

However, As I said, the two endemic countries remain and a few reinfected countries are there. So the, the target, Jessamy, is to wipe polio out of those reservoirs, the endemic countries and the reinfected countries or areas. That's when we'll reach eradication. So again, keep in mind, no matter how much of progress 99.

9 percent of the world does in eliminating or stopping folio, it's still not quite eradication. We need to reach that last child in the last community in that last country to eradicate this virus. 

Jessamy: Smallpox is the virus that we have eradicated and that took an enormous amount of answer, leadership, a final sort of plug of, of money to, to get that done and wasn't an easy task by any shape or, or form.

I understand there's just been more pledging for the polio in the form of 2. 6 billion. Is that, is that right? What does that mean now? Is that enough? without maybe a particular country or a particular push on leadership or how do you see the next steps playing out? 

Ananda: Again, a very important and timely point, Jessamy.

So you are absolutely right. You know, as of October 18th the 2. 6 billion dollars were committed thanks to the donor communities and, and participating agencies. And, and it's an extremely positive step, Jessamy, towards. Enabling the 2022 2026 eradication strategy that has been developed. And this strategy is quite unique and you know, adaptive in a way where several new components have been added, Jessamy towards an approach to eradication.

And that includes being more integrative in the approach where other health services and the delivery of other health services and immunization would be included in the overall polio vaccination as far as and there is an ongoing attempt to do that. Gender equality and informed empowerment of the frontline health workers who are mostly woman is also a primary focus off of this new strategy.

And then finally, just made the focus to ensure that the vaccination campaigns the tools to interrupt outbreaks are of highest quality and reach you know, and that happens in the hardest to reach areas. You know, that's the the target that we have. So several new components are components that are building on the existing ones.

Are there in the strategy, but to your point, you know, obviously, the 2. 6 billion being committed is a very positive step, but it's the first step. It needs to be pushed forward to ensure we reach the overall requirement, not only financial. but political and social as well. We need to come together as a global community, Jessamy both in terms of the funding commitments that are, you know, extremely important.

But also in terms of our political commitment to ensure polio is there on our radar, including in the polio free countries, knowing that they're not polio risk free. And then finally, socially also, we need to be inclusive and adapt the health delivery and the immunization delivery activities. In a way that is acceptable to the communities, the underserved communities that are in need of such life saving tools.

So that's where we are, Jessamy. You know, it's a, you know, we, we have seen a lot of from promise this week, particularly from the Berlin event. But as I said, you know, it's it's a long journey that we'll have to really, you know, come together for and ensure not only we get to eradication, but we sustain eradication.

And that's where, you know, all these scientific tools like the novel vaccine options, the delivery options, empowering the frontline health workers. The woman community, particularly who participate in the vaccine delivery activities. All of these will be critically important, Jessamy, to ensure we have not only smallpox as that one example of a human disease to be eradicated, but polio very soon.

In fact, to be honest Jessemy, two third of polio is already gone. Wild type 2 and wild type 3 are certified eradicated. So we need to finish the job for wild type 1, the one third of all wild types that we ever had. And also complete the interruption of the vaccine derived polio forms with likely with the novel oral polio vaccine type 2, and most importantly with good quality and timely vaccination campaigns.

Jessamy: Is there a big price difference between the novel oral polio virus, this, this more genetically stable one that, you know, might be able to be more effective against vaccine derived variants? strains. What's the cost difference? 

Ananda: There is no meaningful cost difference at all. So it's very comparable to the per dose cost of oral polio vaccine, which is under 20 cents.

So overall, there is not much of a cost difference at all. The only difference is the fact that this vaccine is significantly more genetically stable. The other difference, of course, is the use case, Jessamy, where the novel oral polio vaccine type two is being used under the emergency use listing authorization pathway only for type two outbreak response.

and not for routine immunization. So those are the differences, but not much in terms of the cost. 

Jessamy: So interesting and such a complex challenge to be able to really get to those hard to reach areas. I mean, are you hopeful? 

Ananda: I'm strongly hopeful, Jessamy. If I go back into my journey for polio eradication, I started off as a medical doctor, a young medical doctor in India.

When India was intensely endemic, it would report the highest number of paralytic cases in the world. At, at one point of time when I was working in India you know, as a shoe leather epidemiologist in several parts of the country. And just to me, I saw on one hand many paralytic cases, which was heartbreaking, but on the other hand, I also saw how vaccination campaigns.

And also how surveillance activities came together to kick polio out of the country. And it's been more than 11 years now that a diverse country like India you know, with a lot of complexities in terms of vaccine delivery and, and healthcare services it has remained polio free. You know, take Nigeria, for example, again, a big country with a lot of challenges, but it has stopped wild polio virus transmission successfully.

And then there are many other examples, but I cited the ones that I'm very close to, and that gives me strong hope, and I think I'm not only hopeful, I'm essentially confident that if we come together if we sustain the interest from the donor organizations to the national program managers and the authorities, to the global communities that have been engaged for polio.

And then finally, probably most importantly, if we keep the encouragement alive, keep empowering and enabling the frontline health workers, I call them frontline health warriors, essentially. And again, mostly women from the local communities, we will get to eradication of polio. We have to. There is an ethical obligation to do so.

And there is scientific principles giving us confidence that it can be done. And then there are human stories, you know, many of those I had experience with in my work in India. off, you know, overcoming challenges that were known to be impossible to overcome. I think all of that gives me a lot of confidence just to me that this can be done.

It remains an audacious task. It remains a challenging task. But we can get there.

Gavin: That's it for this episode of The Lancet Voice. If you want to carry on the conversation, you can find Jessamy and I on Twitter, on our handles, at Gavin Cleaver, and at Jessamy Barginal. You can subscribe to The Lancet Voice, if you're not already, wherever you usually get your podcasts. And if you're a specialist in a particular field, Why not check out our In Conversation With series of podcasts, tied to each of the Lancet specialty journals, where we look in depth at one new article per month.

Thanks so much for listening, and we'll see you again next

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