The polio endgame

Authors:
Javier Casellas, M.D., Ph.D.
Enrique Chacon-Cruz, M.D., MSc
Felicitas Colombo, MPA

The unequivocal global authority in polio, Dr. Ananda Sankar Bandyopadhyay has led disease control initiatives in diverse settings across the globe. He began his career as a surveillance medical officer with the World Health Organization’s National Polio Surveillance Project in India, where he played a key role in the country’s polio elimination and measles surveillance efforts. In a career spanning more than 15 years, he also served as a medical epidemiologist at the Rhode Island Department of Health in the United States, coordinating public health surveillance and response activities.

Ananda, as he is affectionately known by his colleagues, grew up in Kolkata, India, and earned his medical degree from Calcutta National Medical College and Hospital, graduating with a gold medal and numerous honors. He later earned a Master of Public Health (MPH) from the Harvard T.H. Chan School of Public Health and is currently a guest faculty in several prestigious global programs focused on public health and vaccinology.

Currently, as the Deputy Director of Technology, Research and Analytics of the Polio Team at the Bill & Melinda Gates Foundation, Dr. Bandyopadhyay leads global research efforts aimed at achieving and sustaining polio eradication. His work includes the development of novel polio vaccines, the generation of data to inform immunization policies, and the advancement of effective detection and surveillance tools.

His contributions to public health have reverberated across the globe as he continues to build a remarkable legacy along his ever evolving and prolific career.

Formative years

When Dr. Bandyopadhyay was in medical school, India was grappling with a heavy burden of diseases, many of which were vaccine preventable. In his quest to understand the science behind these diseases, his mission was not only to study their development but also to explore how they could be prevented and treated. Reflecting on his journey, he often says that he did not choose polio, rather, polio chose him.

“I was looking for something more challenging, something different from the clinical studies that I was already doing,” he recollects. “So, post the medical graduation, I got selected for the WHO polio surveillance project in India as a surveillance medical officer. And I thought this was a great opportunity to do applied epidemiology,” he recollects it was a post that took him away from his hometown and deployed him around many locations within the country doing polio outbreak investigations, while coordinating large-scale vaccination campaigns. 

What initially was supposed to be a year-long association, in an era when India was intensely endemic with polio, happened to be a career long effort. After his training at the Harvard T.H. Chan School of Public Health, Dr. Bandyopadhyay started to focus almost exclusively on polio research at a global scale.

The basics about polio

Dr. Bandyopadhyay explains that, broadly speaking, polio has three naturally occurring or ‘wild’ serotypes: types 1, 2 and 3. Depending on its origin, whether from a naturally occurring polio virus or derived from a vaccine strain, it can be further subdivided. Wild types 2 and 3 have already been certified as eradicated, meaning that two-thirds of wild polio disease has been effectively wiped out of the planet. What remains is wild type 1, which is only endemic in Pakistan and Afghanistan.

On the other hand, there is a burden of vaccine-derived polio viruses (VDPVs) or variant polio viruses. These viruses are essentially derived from the oral poliovirus vaccine (OPV), a live attenuated vaccine. In settings with persistently low immunization coverage, the population remains vulnerable to virus circulation, allowing the live attenuated strains of the vaccine virus to evolve into forms capable of causing paralytic outbreaks.

“So, if you ask me, it’s more poor vaccination derived polio viruses than really vaccine derived polio viruses, because if vaccination coverage is uniformly high and high over time, then the risk of such strains is essentially negligible,” asserts Dr. Bandyopadhyay.

This phenomenon occurs primarily in areas where immunization coverage remains low for extended periods. In such settings, the oral polio vaccine (OPV) strains can lose the attenuating mutations that were originally present in the vaccine virus. As a result, the vaccine virus can replicate in unvaccinated or inadequately vaccinated children. Through this replication process, the virus can spread from one susceptible child to another, regaining the ability to cause paralytic outbreaks.

Why vaccination coverage is not optimal?

Dr. Bandyopadhyay explains that there are three main factors that can disrupt or hinder optimal vaccination coverage. One major factor in today’s world is geopolitical unrest, which takes many forms. In extreme situations, such as active conflicts or wars, healthcare and immunization services are often severely disrupted. In other cases, civil unrest or political instability can also interfere with or halt vaccination efforts.

“And, unfortunately, that’s in a way growing in today’s world. And that is concerning because it eventually impacts vulnerable children who are not receiving the lifesaving vaccines or other lifesaving interventions,” he points out with clear concern.

Another factor affecting vaccination coverage is vaccine acceptance, which can be suboptimal in some communities. Dr. Bandyopadhyay suggests that improving health communication is key—this involves reaching out to these communities with accurate, science-based information about the safety and effectiveness of vaccines.

A third challenge is disruptions in vaccine supply, which became especially prominent during the COVID-19 pandemic. The interruption of global supply chains led to sporadic shortages of vaccines.

It is also important to note that the majority of cases of circulating vaccine-derived polioviruses (cVDPVs) stem from the oral polio vaccine (OPV) targeting serotype 2, rather than vaccines for other serotypes. In response, the Global Polio Eradication Initiative (GPEI), in collaboration with several partners, developed novel oral poliovirus vaccines (nOPVs). These vaccines are now being deployed worldwide. The partnership also worked together to clinically develop these new vaccines and navigate the World Health Organization’s unique regulatory pathway, known as the Emergency Use Listing (EUL) process.

“So, this overall journey has been quite fascinating in terms of developing the idea, then getting into pre-clinical studies, clinical studies, down selection between candidates, and then, as I said, the regulatory pathway that was applied,” commented Dr. Bandyopadhyay. 

This vaccine is reserved for outbreak response and is only used in areas where circulating vaccine-derived polioviruses of type 2 variants have been detected. To date, approximately about 1.3 billion doses of nOPV2 have been administered across about 240 mass vaccination campaigns in 41 countries.

Sewage surveillance 

Polio is a notoriously elusive virus and knows ‘how to hide’, which is why sewage surveillance was added to complement acute flaccid paralysis (AFP) surveillance. Dr. Bandyopadhyay explains that polio behaves in a way that makes it difficult to detect: of 100 infected individuals, only one may show the classic signs of paralytic disease. The others may have no symptoms or exhibit only mild, atypical ones.

“So that means, when we have to search for the virus, we really have to be smart. So, one component of that was the focus on not polio paralysis surveillance, but acute flaccid paralysis surveillance, where you are essentially broadening your net,” he says, noting that even a rare case could be caused by polio.

As they gained a deeper understanding of how polio circulates, sewage surveillance was introduced, not to replace AFP surveillance but to complement it. The goal is to collect wastewater samples from strategically selected locations to detect whether the polio virus is circulating. Because polio is often subclinical, even the best AFP surveillance may miss that one paralytic case.

“With sewage surveillance, you are not only focusing on the disease part of the spectrum, but you’re actually focusing on the existence of the virus itself. And that, actually, is the essence of the idea of eradication. Because with polio eradication, we are not only talking about stopping the disease. But we are talking about wiping the world out of the polio virus,” he asserts adding that there are around 140 specialized laboratories globally trained to detect polioviruses. 

Dr. Bandyopadhyay notes that over the past five years, sewage surveillance networks have expanded significantly. However, he emphasizes that there is still more to be done, particularly in strategically locating sewage surveillance sites to track polioviruses more effectively.

The future of polio

Dr. Bandyopadhyay outlines two primary goals for the near future in the fight against polio: to stop the wild poliovirus type 1 once and for all, and to halt the spread of circulating vaccine-derived poliovirus type 2 (cVDPV-2). Both are significant challenges, but they are not insurmountable.

To put it in perspective, it’s important to note that while there were initially more than 10 sub-lineages of wild type 1, this number has now dwindled to just two, primarily in the border areas between Pakistan and Afghanistan. Unfortunately, ongoing geopolitical unrest is complicating efforts to reach these areas. Despite this, the progress made so far offers strong evidence that wild type 1 can be eradicated decisively and permanently.

“So that is a definitive indication, if you ask me, that the virus is gasping in these last corridors. That’s exactly what you see from a molecular epidemiology perspective everywhere,” he asserts. “And we know this through genetic sequencing.”

The second major goal is to stop the circulation of cVDPV-2, which is primarily circulating in the WHO AFRO Region, but spread to several other countries in recent years, and was detected in the UK, Israel, the US, and Canada, underscoring how easily polio can travel. “Polio is just a plane ride away,” Dr. Bandyopadhyay points out, highlighting the global risk.

“So, there are huge challenges to stop the spread of the variant type 2 poliovirus or the circulating vaccine-derived poliovirus. But on the other hand, we just discussed there is also the promise of a tool like the novel OPV2, the nOPV2, which has significantly more genetic stability,” Dr. Bandyopadhyay notes.

He emphasizes that the introduction of nOPV2 in outbreak response has reduced the risk of new cVDPV-2 emergence by about 75% to 80%, providing a crucial opportunity to break the cycle of new outbreaks. Looking further into the future, Dr. Bandyopadhyay points out the ongoing need to develop policies for long-term polio vaccination.

“As of now, SAGE (Strategic Advisory Group of Experts) has recommended that post-certification of eradication, countries continue using polio vaccines. And in this case, post-eradication polio vaccine, we understand, will be the inactivated polio vaccine (IPV) given by injection. That’s going to be kind of the exclusive use era of IPV post-certification of eradication,” he confirms. “And the duration of such use is at least 10 years post-eradication,” he explains that, for countries with polio-essential facilities, places where polioviruses are still studied or used for vaccine production, the period of vaccination could be longer.

In short, while the immediate goals are to end wild poliovirus type 1 and halt cVDPV-2 circulation, the long-term success of polio eradication will depend on continuing to vaccinate and fine-tune strategies to keep the virus from resurfacing.

Eradication of polio

One key factor that makes poliovirus an eradicable disease is the absence of a known carrier state in immunocompetent individuals. In contrast, immunocompromised individuals, especially those with B-cell related immunodeficiencies, can be exposed to the live attenuated poliovirus strains in the OPV, allowing the virus to replicate and be shed for an extended period. This prolonged shedding poses a potential risk for the reintroduction of poliovirus into the community.

“Now, there are two issues to understand here,” Dr. Bandyopadhyay explains. “One, we have not really seen definitive evidence of such prolonged shedding from individuals with immunodeficiency disorders leading to community outbreaks,” he continues. “So, that’s one thing to note. But there is a theoretical risk for sure that the community around such individuals will be exposed. And for that, we are trying to develop polio antivirals.”

The development of polio antivirals is part of the global polio research agenda. These antivirals, if proven effective, could stop prolonged replication and shedding if administered in time. Several antiviral candidates are currently in clinical trials or at the preclinical stage and, if successful, they will eventually be introduced to the market.

“I also must note, as I just mentioned to your previous question, if the world moves to an all IPV schedule, eventually the continuous risk that comes in with OPV use for immunocompromised individuals being infected and then starting to shed for a long time, that trigger will also not be there once you move to all IPV. So, you’ll also have to consider that even without polio antivirals, probably the risk gradient will go down over time as more and more countries move to an exclusive IPV schedule,” he concludes.

Polio and migration

In countries with large immigrant populations, relying solely on IPV, which provides only direct protection and no indirect protection and limited mucosal immunity, can present a complex epidemiological challenge.

Dr. Bandyopadhyay explains that in developed settings like the United States, IPV is an effective tool. While it doesn’t induce strong mucosal intestinal immunity, it provides robust humoral immunity after an adequate number of doses, offering good protection against paralytic disease. However, IPV can also help reduce person-to-person transmission by impacting oropharyngeal mucosal immunity. In environments with good sanitation and hygiene, oropharyngeal immunity plays a role in preventing transmission.

But this is just one piece of the puzzle. In certain settings, even with only IPV, there could still be protection against transmission. However, in areas with high population density and suboptimal sanitation, the need for a live attenuated vaccine like OPV becomes critical. OPV protects the gut by inducing mucosal immunity, which is vital in settings with high force of infection. This is why the policy is to continue using OPV until wild poliovirus type 1 is eradicated globally.

“And also, there are other indicators to move eventually to IPV only if the OPV coverage in a particular country is maintained at a recommended threshold for a period of time. So, there are these checks and balances, which probably gets you to that optimum timeframe that you can consider getting to an all IPV schedule. It’s not an all or none policy where we just move, you know, not considering all these epidemiologic factors,” he adds.

Dr. Bandyopadhyay emphasizes that the true risk of polio transmission related to migration is not population movement itself, but rather the adequacy of vaccination coverage.

“If the people who are moving in and out are adequately covered with vaccines that they need, and also, you know, the places where the people are moving into, if those places have adequate coverage, then it’s not really an epidemiologic risk,” he explains.

Rather than focusing solely on population movement, Dr. Bandyopadhyay suggests the key is maintaining robust surveillance systems to detect any new outbreaks and improving vaccination coverage with the most appropriate vaccine for each setting—whether IPV, OPV, or a combination of both.

Bio https://www.gatesfoundation.org/about/leadership/ananda-bandyopadhyay