Robert Fortner

{Polio Eradication, Part 2}

By Robert Fortner & Alex Park

Authors’ note: 

In late 2017/early 2018, Alex Park and I co-authored a three-part series on polio for De Correspondent, originally appearing in Dutch:

Na 30 jaar en 15 miljard dollar is polio bijna helemaal uitgeroeid. Hoe?

Als je een ziekte bijna uitroeit. En daarmee een nieuwe variant de wereld in helpt

Waarom de miljarden van Bill en Melinda Gates malaria niet uit zullen roeien

De Correspondent initially planned to publish English versions of the articles but, during the course of our series, announced plans for an English-only web publication, The Correspondent. That publication has been struggling to get off the ground ever since. 

Fortunately, we were able to find a home for the third piece in the series, at Undark under the title “The Enduring Appeal (and Folly) of Disease Eradication”. But parts one and two never found an English-language publisher.

Back in 2017 when we were writing, eradication of wild poliovirus was quite close but, to our astonishment, modeling showed a disconcerting 1 in 20 chance of huge outbreaks of 50,000 cases or more in the decades after eradication. These theoretical epidemics didn’t spell the return of wild polio-- the dreaded, crippling virus which has been the constant target of the largest medical campaign in history, but of vaccine-derived poliovirus (VDPV)-- another disease with virtually the same symptoms, and one whose sole cause is the oral vaccine meant to end polio in the first place. 

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As a global alliance built to eradicate wild polio approaches the finish line, one of its biggest legacies may also be the greatest threat to its progress: vaccine-derived poliovirus, or VDPV. By some estimates, post-eradication VDPV outbreaks could be larger than any polio outbreaks to date. But how will the world celebrate the achievement when VDPV outbreaks are almost certain to occur into the future? 

At the Bill & Melinda Gates foundation in Seattle, this year’s World Polio Day event followed what has become a standardized ritual. Before an audience of hundreds, a series of speakers praised the work of volunteers and donors, reiterating the point that the end of polio was near. “We are this close to ending polio,” Dean Rohrs, Vice President of Rotary International, told the crowd of several hundred people, holding up a thumb and finger mere centimeters apart. As several speakers emphasized, only 12 cases of wild polio had been reported so far that year, anywhere in the world. 

But wild polio is not the only polio left.

When the World Health Assembly adopted global polio eradication in 1988, the disease was limited to three naturally occurring virus types. That changed in 2000, when scientists realized the weakened virus in the Sabin oral polio vaccine (OPV) used in most developing countries could revert to a pathological state, creating a new virus which can spread and paralyze just like polio: vaccine-derived poliovirus, or VDPV. 

Reversion in the body of a vaccine recipient is surprisingly common, but transmission to another person is extraordinarily rare: There have been relatively few outbreaks of VDPV this century, although billions of doses of oral vaccine have been delivered over the course of the campaign. When VDPV does manage to catch hold, however, the “attack rate” is about the same as it is for wild polio: one case of paralysis for roughly every 200 people infected. 

VDPV only spreads in areas where immunity rates are low, often due to war, such as eastern Syria and the Democratic Republic of the Congo. But as the global polio eradication campaign winds down, susceptibility to VDPV is rising, leaving literally millions of children unprotected against paralysis from VDPV.

At the Seattle event, none of the speakers even mentioned VDPV. However, global health experts generally believe that VDPV will outlast wild polio, meaning the anticipated “end of polio” will be nothing of the sort. At the moment the world celebrates the end, the talk around VDPV “will be a complicated communication exercise,” according to Michel Zaffran, director of the polio program at the World Health Organization. “We know that we actually might continue to get outbreaks after the certification of the wild poliovirus eradication.” And those outbreaks could be massive, perhaps larger than any polio outbreak in history.

{Getting ready for a party}

With the end of wild polio in sight, some of the eradication campaign’s key stakeholders are eager to declare victory and withdraw. 

By some projections, the last case could be detected as early as next year. If no cases are detected for another three years, WHO will officially certify the end of wild polio. Although the Global Polio Eradication Initiative (GPEI) targets both wild polio and VDPV, after certification, much of the apparatus it commands to vaccinate the world’s people against any form of polio will shut down practically the day after wild polio is declared vanquished. In April 2017, the Polio Oversight Board formally decided to “sunset” GPEI at certification instead of waiting some period of time after certification.

What would an outbreak of VDPV a few years from now look like? Let’s assume for a moment that the last case of wild polio is detected in 2019, and that VDPV lingers on in a few corners of the world. Based on current risk assessments and mathematical models, it is possible to imagine a future not long after when a VDPV outbreak catches the world off guard. 

{The outbreak of the future}

The following scenario begins in January 2018, in Syria.

As the Syrian war civil war draws to a close healthcare workers are continuing to fight an outbreak of VDPV which began almost a year ago. In Aleppo, a fourteen-year-old named Mohammed is one of countless people trying to put his life back together. 

Mohammed comes from a large family which was divided during the war. The most recent split occurred last May, shortly after his sister gave birth to a child, Asif. From the beginning, Asif was a sickly child, and with healthcare broken in Aleppo, the family chose to send him to live with grandparents in Damascus. Now that his sister and nephew are settled in the capital, Mohammed decides to visit them.

Before leaving, Mohammed receives a dose of oral polio vaccine, one of hundreds of thousands healthcare workers distribute around Syria in response to the VDPV outbreak. Mohammed thinks nothing of it. But the vaccine’s virus mutates and turns to VDPV. Showing no symptoms of the disease, and completely unaware that he has it, Mohammed heads west.

In Damascus, Mohammed holds Asif nephew, and accidentally coughs on him, infecting him with VDPV. But Asif’s constant sickness is due to Primary Immunodeficiency, a rare condition, although one more common in the Middle East and North Africa. Asif’s immune system never clears the infection. 

Five years later, Syria is a changed country. With the war now ended, healthcare is slowly rebuilding in Aleppo. In June 2023, Asif and his mother travel back to the city to live in the family home. There he distributes VDPV into the open sewers around his family’s house every time he defecates. 

Among Syrians, VDPV is low on a long list of issues facing the country. But the mood is optimistic as the flow of refugees has reversed, with more Syrians now entering the country than leaving it for the first time in years. The work of rebuilding is also attracting an international group of contractors. 

One of those people is a 26-year-old electrician from Romania named Vasile. Vasile grew up in a small village in northern Romania, where it was common for children not to receive all WHO’s recommended vaccinations. (In 2016, Romanian authorities estimated 89 percent of the population had received the recommended third dose of polio vaccine, though some areas had a much lower vaccine rate.) When he was a child, Vasile received one dose of polio vaccine, but not the recommended second or third, and he never developed immunity.

Last year, Vasile’s company was hired to rebuild a municipal building in Aleppo, Syria’s most devastated city and now the site of an international reconstruction effort. In January, he flies from Bucharest to Aleppo to observe some work on the site. Since the war destroyed the city’s water pumps, drinking water is scarce. Six kilometers away, a group of returnees have launched a makeshift bottling plant in a bombed out hotel. Unfortunately, unbeknownst to them, sewage, some of which was laced with VDPV, has contaminated the water supply.

In late February, Vasile buys water from the vendors and drinks it. He’s quickly infected with VDPV, but, like most people who catch the disease, he doesn’t show any symptoms. 

Weeks later, Vasile returns to his hometown in northern Romania. Vasile’s arrival after months abroad is an occasion, and family members from other parts of the country come to visit. Vasile kisses his wife, and coughs on his neighbor’s children, spreading the disease to each of them. In a matter of weeks, the VDPV Vasile brought into Romania infects more than twenty other people, but the outbreak remains undetected. (According to one analysis, VDPV could spread undetected in Europe for up to a year.)

In May, a person infected with VDPV in Bucharest travels to Italy. Another, infected in Cluj-Napoca, travels to Ukraine, where polio vaccination rates have been inconsistent but generally low for more than a decade. By August, Italian authorities announce a handful of paralysis cases, the first sign that the disease has entered Europe. In Ukraine, VDPV is spreading much faster, undetected. From this huge pool of infected people, small clusters of paralysis begin popping up, eventually turning into thousands of cases across Europe while international travelers have spread VDPV across the world. WHO declares an emergency and announces plans to re-introduce the oral polio vaccine--the only way to halt the outbreak. What had been a thirty-year eradication campaign starts over again.

{How great is the risk?}

This scenario is not far-fetched: In recent years, scientists have attempted to quantify the risk of a VDPV outbreak after wild polio is declared eradicated. One such effort, by the Orlando, Florida research group Kid Risk, put the risk of an outbreak of 50,000 or more cases of paralysis at around 5.7 percent. The same paper said there could be as many as 800,000 cases of paralysis. Kid Risk’s research on polio has been funded by both the US Centers for Disease Control and Prevention (CDC) and the Bill & Melinda Gates Foundation. 

Experts disagree on what factors could contribute to an outbreak and their likelihood. The most likely trigger, according to Kid Risk, comes from individuals with immune deficiencies, like Asif in our story. One patient in the UK has been excreting VDPV for 28 years, although in countries with weak health systems, immune deficiency usually leads to death at a young age. 

After eradication of wild poliovirus, use of the oral vaccine will stop. Many newborn children will no longer be protected from polio. Years after the global celebration of polio eradication, an immunodeficient carrier of VDPV could infect one of the many millions of non-immune people, starting an outbreak.

The Gates Foundation said that predicted outbreaks of over 50,000 cases “were based on a few assumptions in the study that illustrate potential risks, but do not represent the current plans for polio eradication and global immunization.”

However, the 5.7 percent chance of a massive outbreak might be a low estimate. According to Tapani Hovi, “there are other excreters,” who are relatively healthy. Hovi, an infectious disease expert at Finland’s National Institute for Health, and other researchers have found VDPV-positive sewage samples in Finland and Slovakia over extended periods. But records of nearby hospitals found no patients with an immune deficiency. Genetic sequencing of the Finnish samples suggested one person might have been excreting VDPV for ten years. Said Hovi: “How healthy they are and how frequent they are, I have no idea. But they exist and should be taken in account in risk assessment.”

Research continues on whether immunodeficiency caused by HIV/AIDS could result in a chronic VDPV infection. A recent study found that "mildly symptomatic” HIV-infected children are able to clear the oral polio vaccine virus. Scientists cautioned that the group studied was small (just 57 children) and received life-saving antiretroviral therapy. But there are some two million children in the world living with HIV and, in some regions, as few as 20 percent receive treatment that keeps the immune system functioning. The possibility that untreated children suffering from AIDS could develop a chronic VDPV infection cannot be ruled out. As one group of researchers put it: “At present, no evidence exists whether secondary immunodeficient groups, such as HIV infected patients, could act as a long-term reservoir of poliovirus, but it is possible."

A smaller threat than chronic VDPV infection, according to Kid Risk, is polio escaping a laboratory. But lab breaches are not unheard of. In an incident this year in the Netherlands, two lab workers were exposed. One developed an infection and, confined at home, excreted virus-contaminated faeces into the local sewer system. WHO later complained that the environment around the breach was not monitored long enough.

Risk modeling for disease outbreaks is an imperfect science, and not everyone agrees on the exact range of probabilities. Stephen Cochi, a senior polio researcher at the CDC, said “We cannot take 5.7 percent as any kind of a precise number,” because it’s based on a model and numerous assumptions. Some model inputs, like the number of immunodeficient people infected with VDPV in the world, are uncertain estimates but are assumed to be 100 percent accurate. 

But with the health of millions of people at stake, even highly improbable events have to be taken seriously. Researchers believed there was only a 9 percent chance that wild polio had not been eliminated from Nigeria in 2016. At the time, it hadn’t been seen for three years. Yet as the paper with that estimate went to press, new cases were found from transmission that had gone undetected for five years. “[T]his may call into question the presented results,” the scientists wrote. They stood by their model and pointed to “a probable surveillance failure.” 

{The end of polio eradication}

Even with the current polio eradication alliance intact, fighting a large-scale outbreak would be difficult. But as the campaign closes in on wild polio, it’s also preparing to close up shop. 

Three years after the last case of wild polio is detected, the Global Certification Commission (GCC) tasked with certifying its eradication will cease to exist. GPEI will also dissolve upon certification of wild polio eradication.

“I worry about the ongoing commitment that will be necessary to surveillance after the interruption of wild poliovirus,” said David Salisbury, who heads the GCC. “We still will have to have surveillance to ensure any vaccine-derived viruses are being detected.”

Whether there will be any certification process for VDPV eradication has not yet been decided. There might be an informal certification process, or none at all, according to CDC’s Cochi. “It’s too early to tell exactly what form the monitoring of vaccine-derived polioviruses… will take and how formalized any certification process will be,” he said.

The campaign’s rush to close down comes in part from the donors’ fatigue, says Jon Abramson, chair of WHO’s Strategic Advisory Group of Experts (SAGE). Now that the campaign has missed three deadlines, he says, and donors are “already losing interest in polio eradication.”

“There is exhaustion in a lot of the donor community,” he says, including at Rotary, the donor that started it all.

“Our commitment is the certification of the eradication of the wild poliovirus,” Rotary’s Pandak said. Though she recognizes that VDPV spreads and causes paralysis just like wild polio, rather than committing to its eradication, she only said Rotary is “open to conversations and discussions” about the campaign’s future.

{“Every last child”?}

Compounding the risk of a major epidemic is the fact that so many people are vulnerable to the most common form of VDPV. 

Last year, the type 2 component was dropped from the oral vaccine. Type 2 wild polio had not been reported since 2015, and the vaccine component was also the most common source of VDPV. 

But, type 2 VDPV still exists in the world. And without type 2 in the vaccine, millions of children born since the change aren’t protected. Exactly how many, WHO doesn’t know for sure. Roland Sutter, Coordinator of WHO’s Polio Research, Policy and Containment team, guesses that “probably less than 10 percent of the global birth cohort,” or “less than 13 million” children are vulnerable. 

For decades, the polio eradication campaign slogan has been to immunize and protect “every last child.” But the millions of these type 2-vulnerable children are a stunning betrayal of the program’s own values. 

Asked about the eradication program allowing such a large population of kids to be susceptible to type 2 paralysis, Rotary’s Carol Pandak replied: “That is a tough question. I don’t really have an answer for that, to be honest.”

Asked by email if citizens in donor nations would accept such a risk to their children if so many were left unvaccinated, the Gates Foundation sent us a lengthy comment on why the campaign used OPV in developing countries. A favorite slogan of the foundation is: “All lives have equal value.” 

But parents in wealthy countries would never tolerate gambling with the health of their children. The parents of unprotected children in poor countries likely don’t even know their children have been hazarded in the quest to achieve eradication.

When type 2 VDPV outbreaks do occur, absent a new vaccine, healthcare workers will have to rely on the existing type 2 oral vaccine. But using large amounts of type 2 vaccine, as health care workers are currently doing to fight the real VDPV outbreak in Syria in our (otherwise) fictional scenario, may have as much as a 50 percent risk of seeding future outbreaks, according to researchers at the Institute for Disease Modeling. 

{A new vaccine? Now?}

One way to ameliorate the VDPV risk would be to use a vaccine that could immunize people without the risk of it becoming pathological. 

After the first known VDPV outbreak, on the Caribbean island of Hispaniola in 2000, a few scientists proposed doing exactly this, but it was ten years and several outbreaks before development began in earnest, with support from the Gates Foundation. Asked why it waited so long, foundation spokesperson, Rachel Lonsdale said “the field’s understanding of end-game realities evolved.”

If it works, the vaccine would function like the current oral vaccine, but the virus inside would be unable to mutate. Trials are taking place now in Belgium, but researchers are still waiting to see whether taking away the virus’ ability to mutate will also reduce the strength of the immune response it elicits. 

{The noble lie}

Through its investments in new vaccine development and support for researchers like Kid Risk attempting to model the risk of future outbreaks, the Gates Foundation appears to be preparing for a future with VDPV. But the assumptions they convey suggest an expectation that outbreaks will be modest in size and easy to control. “We would treat vaccine-derived polio in small, localised campaigns,” the head of the Gates Foundation’s polio program, Jay Wenger told The Independent earlier this year. “It’s obviously a complication, but we see it as a doable." 

It’s commendable that the Gates Foundation intends to sustain its efforts against VDPV after wild polio is gone. If VDPV outbreaks are limited to small outbreaks, the world may be able to fight them without the billion dollar per-year campaign. But based on current models, there’s no reason to assume small epidemics are the only scenario the world should plan for. Much of the planning is being undertaken by the Transition Independent Monitoring Board headed by Liam Donaldson. A spokesperson for Donaldson said he was too busy for an interview. According to his office, he was too busy to answer questions we emailed over a month ago.

There appear to be too many constraints for a clean solution, either to stop VDPV now or to deal with it in the future. And it all comes back to the question: How do you celebrate polio eradication if polio isn’t gone? If VDPV is swept under the carpet, why would donors pay for a quiet campaign to clean up and truly eradicate polio when the eradication moment has already passed and the world’s attention has moved on? 

If the campaign acknowledges VDPV-- a disease whose eradication is far from certain-- then the eradication moment the world has been waiting thirty years for will lose its special quality, and the idea of eradication itself as a tool of public health will lose its lustre. Instead of a huge achievement for humanity, it will be yet another missed deadline as the finish line recedes beyond the horizon. 

Consequently, what is likely to happen is that the campaign will have its eradication moment. Although the public danger of massive polio outbreaks will be higher after the celebration, VDPV will be relegated to the fine print, a critical difference, missed by the public until, perhaps, an outbreak of the disease makes international news. 

The risk may be dumped on the very countries polio eradication was supposed to help, where already millions of kids could be paralyzed by polio.