To stem a growing polio crisis, health officials are accelerating the development of a new oral vaccine with plans for emergency approval and deployment in regions with active polio transmission as early as June 2020. The new vaccine, called nOPV2, might conclusively end the outbreaks, caused by the live virus in the vaccine reverting to a virulent form. But expedited approval means skipping the real-world testing of large clinical trials...
Read the rest at The Scientist
{Polio Eradication, Part 2}
By Robert Fortner & Alex Park
Authors’ note:
Today, VDPV is expanding quickly in Africa, where it threatens to triggerbring potentially very large outbreaks of paralysis. One of us, Robert, is working on an article on the subject. But for now, there’s still too little discussion of this threat in popular media. So we are bringing the pieces forward in English for the first time. Part 2 is below, Part 1 is here.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.
______
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.
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 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.
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.”
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.
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.
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.
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.
{Polio Eradication, Part 1}
By Alex Park & Robert Fortner
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.
Today, VDPV is expanding quickly in Africa, where it threatens to triggerbring potentially very large outbreaks of paralysis. One of us, Robert, is working on an article on the subject. But for now, there’s still too little discussion of this threat in popular media. So we are bringing the pieces forward in English for the first time. Part 1 is below, Part 2 is here.
After nearly 30 years and $22 billion, a massive, dedicated campaign has nearly eradicated wild polio. But as the campaign prepares to celebrate the end of one terrible disease, cases of an equally terrible one of its own creation-- vaccine-derived poliovirus, or VDPV, are rising. VDPV outbreaks could be massive and require restarting the eradication campaign after it ends. So why do we hear almost nothing about it?
In 1980, at a gathering of some of the world’s leading scientists, the person most responsible for the world’s first ever successful campaign to eradicate a disease was trying to prevent the idea of eradication from going mainstream.
DA Henderson, an American epidemiologist, had led the first campaign to successfully eradicate a disease. Smallpox killed an estimated 300,000 people in the twentieth century alone, and its official eradication in 1980 is still hailed as one of the great achievements in human health. As Henderson told the group, smallpox eradication had been a unique opportunity. The world had lept at a chance to wipe out the disease because unique circumstances meant it was possible. But, he added, “we have not demonstrated feasibility … with any other disease.”
There was another problem.
Henderson pointed out that the world’s health ministries widely agreed that the world should throw the weight of its healthcare resources into improving basic health infrastructure, to cope flexibly with multiple health problems. In a 1978 meeting in the Soviet Union, delegates from 134 nations had endorsed exactly this position under the slogan “Health for All,” with a goal of extending primary healthcare to all people by the year 2000. “A single-disease eradication program runs against this tide,” he said.
Henderson’s warnings were largely ignored. At the end of the meeting, the assembled scientists nominated three diseases for eradication-- measles, yaws, and polio. Yaws is a common but rarely fatal disease in some tropical countries. WHO nearly eradicated it in the 1950s and 1960s. More recently, WHO has described yaws as a “forgotten disease.” By contrast, measles remains a major child killer, causing almost 90,000 deaths last year. Yet back in 1988, WHO declared a goal of eradicating polio worldwide, formally launching a campaign which, nearly thirty years later, remains one of the most ambitious, most controversial, and best-funded health campaigns in history.
…
For the last two months, we’ve spoken with some of the people leading the polio eradication campaign about the campaign’s end stage.
Our interest in this story came from different starting points. For the last several years, Robert, a former employee of Microsoft, has been writing a book about Bill Gates. In 2010, Robert wrote a story for Scientific American on how super-human efforts in India, where polio was worst, had turned the corner. At the time, it seemed like one of precious few, transcendently positive developments in the world. But polio eradication was never India’s idea; they have had many, much bigger public health problems. And, as global eradication drew closer, WHO declared polio an emergency-- even though the threat of spread was lower than ever in human history.
Then a real emergency broke: Ebola. In 2014, I was covering the West African Ebola epidemic from the Washington, DC office of the US news site Mother Jones. After I wrote a story about the funding problems at WHO, Robert shared some of his blog posts, and we started talking more, eventually publishing a story on WHO, the US government, and the Gates Foundation during the epidemic for HuffPost.
We found that while the Gates Foundation cared a great deal about polio eradication, in the early days of the outbreak, it had ignored and downplayed Ebola’s threat. But WHO had lacked the capacity to respond from the very beginning. In the middle of the crisis, WHO extended the polio emergency before finally declaring one for Ebola. The distorted priorities could be seen in the very make-up WHO. At the time, 38 percent of WHO staff in Africa were supported through polio funds. Polio eradication had become so big that WHO had been largely reorganized around it. How did that happen?
One indisputable fact is that polio is a terrible disease, and one the world would be better off without. Polio attacks cells in the spinal cord that control the muscles. Affected people, usually children, lose the ability to move muscles, limbs, even their entire bodies. In the worst cases, when the virus affects the muscles which control breathing, polio can kill.
In wealthy countries, where polio has been eliminated except for lab specimens, the virus has historically spread through saliva. But polio can also spread through human waste. This is especially a problem in poor countries, such as Pakistan and Afghanistan, where the virus still exists, and where sanitation is often poor and sewage water can blend with sources of drinking water.
Polio has no cure. Though most people who contract it never show symptoms, for the minority who do, polio’s ravages can be mitigated but not reversed.
But if the health benefits are one motivation for polio eradication, another, perhaps even greater one is the right to say “we did it.” Reading the many reports on polio eradication and talking to its proponents, the desire to reach the end seemed at times to outweigh the desire to end a cause of paralysis in children.
Carol Pandak, director of the PolioPlus program at Rotary International-- historically one of the leading funders of polio eradication-- told us, “We made a promise to the world’s children, and Rotary keeps its promises.”
“It’s a superhuman achievement of the globe uniting against a common enemy,” said Walter Orenstein, an early advocate of the cause.
Had the original goal of the eradication campaign been lost after thirty years? Or had polio eradication always been about inspiring people, as much-- or more-- than it was about improving the health of the world? Before charting out the future of the eradication campaign (which we’ll discuss in Part II of this series), we needed to look at the origins of the campaign.
In 1988, the year the global eradication campaign officially began, there were more than 350,000 cases of naturally occurring, or “wild” polio in 125 countries. So far this year, 15 cases of wild polio in two countries-- Pakistan and Afghanistan-- have been reported, a drop of 99.99 percent.
This massive reduction is the work of the eradication campaign. Today, what people typically call the eradication campaign is a formal entity called the Global Polio Eradication Initiative, or GPEI. Though its main office is housed at WHO headquarters in Geneva, WHO is, officially one partner among many. Others include the US government’s Centers for Disease Control and Prevention and nonprofit groups, such as the Bill and Melinda Gates Foundation and the volunteer group Rotary International. Though many governments support it, the Gates Foundation is currently the single largest contributor to the campaign.
In principle, the campaign’s job is simple: to inoculate the vast majority of the world’s children against polio, year after year, until the disease disappears. In most wealthy countries, like the Netherlands, health care workers use an injectable vaccine. In most poor countries, the available option is an oral vaccine. Dropped on a child’s tongue a few times over a period of months, the vaccine stimulates the immune system in the digestive tract, virtually guaranteeing the person will be immune to polio for life.
But while vaccines are common component of public health regimens, the polio eradication campaign is not like any other public health effort in the world today.
“Eradication is a very unforgiving goal,” says Orenstein. “If I told you that I have a public health campaign that reduced disease incidence by 99.99 percent plus, you’d say ‘wow, what a program.’ But with eradication, one infection is one infection too many.”
Even polio’s double-digit figures are a nagging reminder that the campaign’s work is not yet done. Until the last case of polio is reported and isolated, the only way to prevent a resurgence is to vaccinate the vast majority of children everywhere, from Amsterdam to Tokyo to Zurich, from Armenia to Zambia, in cities, towns, and bedouin camps, war zones and refugee settlements. If vaccine rates drop before polio is gone forever, the risk remains that it could surge again.
This means every year until polio is officially eradicated, the campaign must buy and ship hundreds of millions of doses of vaccine, particularly to poor countries which cannot afford it on their own. Since vaccine is perishable, the campaign pays for refrigerators, coolers, and generators to carry it from factories to the field, often in rural areas in remote villages. Since polio cannot be diagnosed in these hard to reach places, the campaign also maintains a network of labs in cities around the world which can test for it. And all over the world, in cities, towns, and villages, the campaign marshals an army of workers to carry vaccine to anywhere and everywhere there are children.
After thirty years, sustaining this level of commitment has proven enormously complex and expensive. To date, the campaign has cost an estimated $15 billion. The campaign has also set-- and missed-- three deadlines-- in 2000, 2005, and 2012-- and is fast approaching a fourth, in 2018. At a current cost of around $1.25 billion per year, it ranks with HIV/AIDS and malaria as one of the most costly disease-specific campaigns in history.
But was polio also one of the most destructive diseases? Not really. In 1990, two years after the campaign began but before it had substantially cut down infection rates in most of the poor countries where polio remained, the World Bank estimated polio constituted 0.24 percent of the burden of all diseases on the world economy. This is an imperfect measure, but it points to a fact that was widely understood at the time: polio was not one of the greatest disease threats in the world. By comparison, measles, often called the greatest killer of children in history, caused four million deaths in 1990, representing a more than ten-fold greater burden. Yet WHO had chosen to dedicate massive resources to its eradication anyway. Why?
When we spoke with campaign leaders about its history, one name that came up repeatedly was Albert Sabin, the Polish-American inventor of the oral polio vaccine.
The historical record reveals some interesting details about how he promoted polio eradication as a goal. Remember that, after the 1980 meeting in the United States, attending scientists largely agreed that eradication of some disease was a worthwhile goal, but they ended the conference with a list of three candidates, of which, polio was just one.
Sabin had a preference, however, and it was polio. A few months after attending that meeting, he traveled the country to address thousands of members of Rotary International, a volunteer organization known for a well-connected membership dedicated to public service. Rotary members volunteered their time in their communities to help alleviate poverty. But in his address, Sabin said that, before it could eliminate poverty, the world first had to address the health problems of poor children, like polio. And as he explained it, Rotary members could lead this effort.
Together, Rotary and Sabin came up with a number for global polio eradication: a mere $120 million.
In 1985, Rotary adopted global eradication as a goal. Soon after, the organization sponsored campaigns that used oral vaccine to either dramatically reduced or eliminated polio in the Philippines, Bolivia, and the Gambia. With these successes, healthcare leaders came to a realization: Polio was useful for attracting outside funders-- an attractive cause with a clear objective that could bring in money for the less easily defined mission of building healthcare.
“You can go to donors and say, ‘help us do this thing which will take a really long time,’ or you can go to them and say ‘help us eradicate this disease,’ and they like that other option more” says Svea Closser, an anthropologist at Middlebury College in the United States, who has studied polio eradication.
Latin America was the next target. There, Rotary and local healthcare leaders appealed to governments and private donors, using the donations to eliminate polio and increase vaccinations for a number of diseases, including tetanus, pertussis and measles. Infection rates for widespread diseases plummeted while polio disappeared.
Though early critics of polio eradication had worried that focusing on a single disease would take away support from everything else, the Latin American case suggested the opposite was true. Polio eradication was the rising tide that would lift the health of the entire region.
By the late 1980s, WHO could no longer avoid joining the campaign. In 1987, several eradication leaders published a paper in WHO’s in-house journal calling for a global campaign. Polio eradication would be “a banner” which other health projects could rally behind, the group wrote. But these benefits would be ancillary. The priority would be eradicating polio once and for all.
“Global poliomyelitis eradication eradication… is inevitable,” they wrote. “The only question is whether we will accomplish it or pass on the needed action to our successors.” One year later, in 1988, the World Health Assembly declared a goal of eradicating polio worldwide by the year 2000. As healthcare workers had done in the Americas, the new campaign would use the oral vaccine.
In the Americas, polio eradication had been a common cause for an array of people wanting to lift the health of millions of people. But in becoming a global cause, eradication separated itself from any cause but its own.
Speaking with some of the people involved in polio eradication today, it was clear that many of them were tired of fighting polio. It’s hardly surprising: Many of them have been waiting for the end for decades.
But fatigue is not a new condition for the people working in and paying for polio eradication. Closser, the anthropologist, who attended meetings with leaders of WHO and other campaign partners in Pakistan a few years later, said the desire to finish the job narrowed the focus to polio alone. “I went to a lot of meetings where people said, ‘routine immunization is good, but we have to eradicate polio now or it won’t get done,’” she told us. “To get polio eradicated [they believed], they had had to push forward with this single-minded focus, and if they got too involved in routine immunization, it would slow them down and they would never eradicate polio.”
The campaign might have died around this time if not for the intervention of the richest man in the world.
In fall 2007, Steve Landry, the vaccine program manager at the Bill and Melinda Gates Foundation, asked Linda Venczel, a foundation program officer, to give a presentation on polio eradication to Bill Gates. Gates, whose aunt had been a polio victim and whose father was a Rotary member, was in the process of leaving Microsoft, the company he had founded, to become more involved in his namesake foundation.
Venczel had made similar presentations before, having spent three years as the deputy director of the polio eradication branch of the US CDC. What was different this time was the amount of money she had to budget for.
“I wasn’t used to the kinds of budgets that we could throw at a problem as we could at the foundation,” Venczel said with a laugh. “When I asked, ‘how much money,’ I was told ‘you can start at $400 million.’ That was an incredible amount that could really be game changing.”
Over two hours, Venczel stood before the organization’s executive leadership, describing in detail the various options for eradicating polio within the allotted budget. Throughout the meeting, Gates, whose aunt had been crippled by polio when he was a child, peppered Venczel with technical questions. “One thing about Bill Gates is he’s very astute,” Venczel said. “He’s very quick to understand the science of everything, so he truly is a technical partner in thinking through things.”
Then Gates, once a math major at Harvard, asked a big question. If he funded it, what percent chance did polio eradication have of succeeding? It was impossible to know for sure, so Venczel offered two other numbers. About 30 percent of the factors that would determine success-- like war, natural disaster, or political turmoil in the remaining countries-- were outside anyone’s control, she said. The other 70 percent depended on the campaign itself, and the money available to support it. Up to a point, with more money, the chances of success would increase.
If he wasn’t already, Gates was persuaded. Before the meeting adjourned, he committed $700 million to polio eradication, nearly a third of a billion dollars over the original baseline.
We don’t know why, exactly, Gates chose to focus so much on polio. When we asked the Foundation, they directed us to several speeches Gates had made, where he made broad statements about uplifting humanity. But like some of the early proponents of polio eradication, Gates has promoted the idea of eradication itself as an idea. Even before he committed resources to polio, Gates had declared a desire to eradicate malaria. Since then, he has connected polio eradication to malaria more specifically. “Polio, we hope to get done by 2018,” he said in a 2014 interview. “The credibility, the energy from that will allow us to take the new tools we’ll have then and go after a malaria plan.”
Just as polio eradication was launched through the dedication of a very small group of people invested in the idea of eradication itself, under Gates’ leadership, that tradition continues.
With Bill Gates now serving as its de facto leader, polio eradication is closer to success than ever. But while the campaign’s leaders prepare to celebrate the end of wild polio, another problem is slowly threatening to undermine its progress.
The reason is that the oral vaccine, unlike the injectable vaccine used in wealthy countries, uses a weakened but still-living form of the poliovirus which retains a penchant for mutating back toward paralyzing virulence. The resulting infection is called vaccine-derived poliovirus, or VDPV.
Since 2000, scientists have known that VDPV can spread through saliva and drinking water, and cause paralysis in children, just like wild polio. Technically, these cases are called Circulating VDPV, or cVPDV And while wild polio appears to be in terminal decline, VDPV cases are rising: In 2016, there were three cases of VDPV in the world. So far this year, there have been eighty. Scientists largely agree that VDPV will continue to exist after wild polio is gone.
VDPV would not be a serious threat if vaccination rates remained high throughout the world. But with the eradication campaign ready to declare victory, many fear that VDPV infections could surge. By one estimate, cases of VDPV-associated paralysis could number in the thousands after wild polio is officially eradicated.
So why don’t we hear anything about this disease of the campaign’s own creation?
A spot of bother in Maiduguri district, Nigeria (Source: Wikimedia)
Worldwide, in all but three of 155 countries, the trivalent oral polio vaccine has been replaced with bivalent oral vaccine. The bivalent formulation includes only attenuated versions of type 1 and 3 of poliovirus. The type 2 component has been dropped because, far more than the other types, it sometimes mutates back into virulent form. Also, type 2 polio was eradicated in 1999.
But just as the world moved to the bivalent vaccine, Nigeria reported finding a type 2 vaccine-derived virus in a sewage sample. Consequently, right on the heels of the vaccine switch, the type 2 vaccine is being immediately pressed back into service, although it will be used by itself, in monovalent form, according to the Global Polio Eradication Initiative.
Sequencing indicates the Nigerian virus has been circulating undetected since May of 2014. The sample comes from Maidaguri district, an area contested by government forces and Boko Horam, making vaccination problematic.
Last September, WHO removed Nigeria from the list of polio-endemic countries. However, the CDC continued to advise that US travelers to Nigeria be immunized against polio.
Initially, the polio eradication project envisioned stamping out all type 2 vaccine-derived virus transmission before dropping the type 2 vaccine component. But plans to switch vaccines ultimately went ahead despite the likelihood of continued circulation of type 2 vaccine-derived virus somewhere in the world.
There are now multiple hotspots. Besides Nigeria, according to the CDC's Steve Wassilak, "We consider [the] Guinea and Myanmar outbreaks still active." In addition, Brazil reported what researchers described as a "highly evolved" type 2 vaccine-derived virus found in sea water off São Paulo. Found in January 2014, sequencing indicates the virus has been circulating undetected for eight years. Brazil has very high population immunity to polio, so this virus likely came from somewhere else, according to Wassilak.
Eight years of undetected circulation suggests a perhaps large and as yet undiscovered surveillance gap somewhere in the world. Asked whether eight years set the record for undetected circulation, Wassilak answered: "Nigeria had documented circulation for 10 years." However, in Nigeria, there were multiple transmission chains, and it is not clear from Wassilak's answer if any one chain circulated eight years. The Brazilian isolate also had mutations at antigenic sites, suggesting possible evolution of resistance. However, researchers reported that type 2 antibodies still killed the virus.
The process of switching to the bivalent formulation also risks creating new type 2 vaccine derived virus. The switch was synchronized globally because if use of the trivalent vaccine continues anywhere, it might potentially infect children who have only been immunized with the bivalent vaccine. According to WHO:
"The primary risk associated with the cessation of use of type 2 OPV [oral polio vaccine] is the re-introduction of disease-causing type 2 poliovirus into a population with increasing susceptibility to type 2 poliovirus. The switch from tOPV to bOPV must therefore be globally synchronized to minimize the risk of new cVDPV type 2 emergence."
The precision of the large and un-rehearsable switch remains to be seen. Globally, susceptibility to type 2 vaccine derived virus is now rising given the switch to bivalent vaccine and the slow (and arguably belated) introduction of the injected vaccine, which includes all three virus types in a form in which mutation is not possible. Also, while the injected vaccine protects against paralysis caused by poliovirus, it does not prevent infection nor halt transmission. Polio circulated in Israel without causing any cases of paralysis because coverage with the injected vaccine was so high. Eventually, however, circulation might find someone missed by vaccination or with a compromised immune system, resulting in polio's hallmark acute flaccid paralysis.
The success in beating back wild poliovirus bodes well for the eradication effort to also smash outbreaks from vaccine-derived virus. But, out of the gate in the post-trivalent world, the race is already on. And, in Nigeria at least, type 2 vaccine-derived virus circulation has gone uninterrupted for a decade.
Bill Gates administering oral polio vaccine in Chad (Photo: Gates Foundation)
Thanks to oral polio vaccine, the world has nearly extirpated a crippling disease from the planet. In rare instances, however, the same vaccine can cause polio. With progress in eradication, vaccine-associated cases of paralysis began to surpass cases caused by the disease in 2012. A switch in oral vaccines next year might increase vaccine-induced paralytic polio. An inactivated version of the vaccine is available that cannot cause polio and can prevent the polio that infrequently results from the oral vaccine. However, the inactivated formulation is only now being rolled out and not in a way that will stop the oral vaccine from sometimes causing paralytic polio.
Schedule and budget appear to be driving polio policy, not minimizing cases of paralysis from all sources, including the oral vaccines.
The last case of paralytic polio in the world might be caused by the live oral vaccine.
The risk of “vaccine-associated paralytic polio” (VAPP) is very low: 3-4 cases per million births, according researchers at the World Health Organization (WHO) and US Centers for Disease Control (CDC). But with so many children immunized with it, the oral vaccine caused an estimated 399 cases of paralysis in 2012 compared to just 223 caused by polio itself. This disparity will only worsen as eradication proceeds. Schedule slips will mean not only more money (perhaps $1 billion a year) but also hundreds more polio cases caused by the oral vaccine.
Mutations in the live vaccine virus can cause not only VAPP but lead to infection of others, just like the wild virus. Madagascar, for example, has recently seen multiple cases of polio from circulating vaccine-derived viruses. Pakistan and Nigeria have also been battling transmission of polio virus that came from the oral vaccine.
As a first step toward complete cessation of live vaccine use, current plans call for the trivalent oral polio vaccine (tOPV) to be withdrawn worldwide next April, replaced by a bivalent vaccine which immunizes against only types 1 and 3 of the poliovirus. (Type 2 appears to be long gone, last seen in India in 1999.) However, the bivalent vaccine could increase VAPP cases.
The data are scant but concerning. Experience in Hungary “suggest a higher rate of VAPP associated with the use of bivalent OPV compared to tOPV," according to researchers at the CDC and WHO, 20 times higher. However, the data are limited, seemingly to one year, 1961.
VAPP risk varies widely depending on context. According to the CDC, the “best data on VAPP” for the monovalent oral polio vaccines “comes from Hungary, where these strains have been used the longest.” In addition, Hungary featured excellent detection and investigation, requiring that every suspected case of poliomyelitis be admitted to a central hospital for clinical and laboratory evaluation. However, these practices only came into full effect in 1966, five years after the 1961 administration of the bivalent vaccine that generated so many cases of VAPP.
Not only Hungary, but Belarus and especially Romania reported unusually high rates of VAPP, as many as one case per 183,000 doses. However, research published in the high-profile New England Journal of Medicine put these concerns to rest, attributing VAPP in Romania largely to “provocation paralysis,” or multiple intramuscular injections administered shortly after oral polio vaccination. However, some of the same researchers subsequently found that in the United States, intramuscular injections did not cause VAPP, results published to less notice in the Pediatric Infectious Diseases Journal.
The dismissal of higher VAPP rates in parts of Eastern Europe, however, still stands. According to WHO and the CDC: “There is no evidence that the high risk of VAPP observed in these studies is representative of the risk of VAPP in the majority of OPV-using countries globally.”
Most cases of VAPP are caused by the type 3 vaccine virus. But the trivalent vaccine causes less VAPP than the type 3 monovalent vaccine. Analysis of US data from the 1960s and 70s found that the trivalent vaccine halved the risk for VAPP, perhaps suggesting that the trivalent formulation has a taming effect on type 3 VAPP.
The type 2 vaccine virus is actually alpha dog, outcompeting both the type 1 and type 3 viruses of the trivalent vaccine when it comes to infecting (usually benignly) the body. Global health authorities expect that dropping type 2 from the vaccine will greatly reduce VAPP: “removal of type 2 serotype from OPV provided globally in routine immunization and campaigns could decrease the overall risk of VAPP by at least 25%–30%.”
However, just subtracting out the percentage of VAPP cases attributable to the type 2 component of the vaccine might be overly simplistic. The presence or absence of type 2 clearly impacts the effects of type 3 in the body. Leave out type 2 and better protection for type 3 results, for example. The only available evidence—the limited data from Hungary—points to much higher VAPP from bivalent than trivalent vaccine.
Roland Sutter, a scientist at the World Health Organization
and co-author of numerous of papers on VAPP, dismissed out of hand that bivalent vaccine might increase VAPP, saying: “I don’t believe anything
that hasn’t been proven.” Sutter pointed out that four billion doses of the
bivalent vaccine have been administered since 2009 and "no safety signal
has been detected anywhere in the world.” He asked: “Wouldn't you see
something?"
However, WHO might see
no safety signal because WHO doesn’t track VAPP. “The countries are keeping
track,” according to Sutter. The bivalent vaccine “does cause VAPP as well," Sutter said, but identifying VAPP cases is technically
demanding. “It’s not so easy to go through the algorithms," he explained. And countries, perhaps like WHO, may have little incentive to track
and report how many children and adults are being paralyzed by a public health
program. Asked if WHO had a spreadsheet aggregating country-level VAPP data,
Sutter replied: “Not at all. No.”
In theory, VAPP could be avoided entirely by using the inactivated polio vaccine (IPV). The United States dropped the live oral vaccine in 2000 “to eliminate the risk of vaccine-associated paralytic poliomyelitis (VAPP),” according to the CDC. Most wealthy countries immunize with IPV. But IPV poses a number of problems for eradication.
IPV must be injected, whereas a deluge of oral vaccine drops can be unleashed by armies of untrained vaccinators. The high levels of vaccine coverage needed, over 90%, would be much, much harder to attain if polio eradication relied on national routine immunization programs which can handle injections. The eradication effort opted for oral vaccines and also for a separate, polio-only vaccination infrastructure that actually drew resources away from routine immunization programs.
IPV by itself also likely would not suffice to eradicate polio. The live and inactivated vaccines confer different kinds of immunity. IPV only protects against paralysis from polio, not infection. In 2013, Israel found widespread polio transmission in sewage samples. Because of the country’s high IPV coverage and a little luck, no cases of polio resulted. But polio still circulated. Israel resumed immunizing with OPV while continuing IPV. Because OPV prevents both disease and infection, transmission in Israel soon stopped, demonstrating not only sharp work by scientists and public health officials, but also that eradication with IPV alone may be impossible. On the other hand, the strongest individual and population immunity to polio results from vaccinating with both IPV and OPV.
Another obstacle to universal adoption of IPV has been cost. Until recently, IPV cost about $2 per dose versus $0.10 - 0.15 for the oral vaccine. However, in 2000 when the US switched to IPV, a generous gift from the Bill & Melinda Gates Foundation led to the founding of Gavi. Gavi sought, among other aims, to slash the time it took for a vaccine to get from the rich world to the poor. Thanks to Gavi, relatively expensive vaccines for hepatitis and rotavirus became more quickly available in the developing world—but not IPV. More recently, Gavi began rolling out its most expensive vaccine yet, for Human Papillomavirus (HPV), which can cost more than $100 in developed countries.
The cost of IPV rather than its safety benefits continue to be at the forefront in policymaking decisions. A recent paper from Gates Foundation and CDC researchers stated: “In the global polio eradication end game, the cost of IPV will need to be balanced with effectiveness.”
Gavi’s support for IPV only began in 2013 with the publication of the polio endgame strategy, according to Gavi spokesperson Rob Kelly. Vaccine safety was not the main driver. According to Kelly, "the primary purpose of an IPV dose in Gavi countries is to maintain immunity against type 2 poliovirus," after withdrawal of the trivalent vaccine.
Gavi’s recent support for IPV will have little or no impact on VAPP because the oral vaccine will be administered first. To prevent VAPP, IPV must come before OPV. Brazil moved away from an OPV-only schedule, putting two doses of IPV first with the goal of “preventing rare cases of vaccine-associated paralytic polio” and “ensuring equitable access to IPV,” i.e. not inflicting VAPP on the poor.
However, WHO recommends only a single dose of IPV after the oral vaccine. According to WHO, children will then be older and maternal antibodies less likely to interfere with developing immunity in response to the vaccine. However, the CDC found that coverage with one dose of IPV “is expected to be lowest” when given on WHO’s recommended schedule and highest if given the first time a child is immunized. About 12 million children won’t get IPV if WHO’s plan is followed, according to the CDC.
But nations supported by Gavi will be following WHO guidelines, according to Gavi’s Rob Kelly: “countries have overwhelmingly decided to introduce the IPV dose at 14 weeks of age,” after the oral vaccine. The Gates Foundation supports WHO’s guidelines: “There are valid scientific and economic reasons why most Gavi countries still give OPV before the dose of IPV (generally at 14 weeks),” said foundation spokesperson, Rachel Lonsdale.
The foundation has criticized lags in rolling out vaccines in low-income countries but sees the handling of polio vaccines as similar “to what happened in the US,” according to Lonsdale. “When the risk of OPV is outweighed by the benefit the global program is moving to IPV.” Lonsdale emphasized: “We would not be where we are today and so close to eradication without OPV.”
However, we would be much closer to eradication if there were a genetically stable oral vaccine. Such a vaccine would cause no VAPP and no circulating vaccine-derived virus. There would be no need to rollout the needle-based IPV.
Gates Foundation research into a vaccine with the safety of IPV and the infection-prevention of OPV began in 2011, according Lonsdale. She dates the foundation’s involvement with eradication to 2007 and a $100 million grant to Rotary International. The foundation became the largest financial backer of polio eradication in 2008. Scientists are also working on a genetically stable version of the oral vaccine but only more recently.
By contrast, in the early 2000s, the Gates Foundation pursued thermostable versions of many existing vaccines that required storage at low temperatures. The effort largely came to naught because breaking free of the vaccine cold chain required a thermostable version of every vaccine, with little or no benefit from converting just a few.
The foundation's Lonsdale asserted that the global polio program "has always been concerned about VAPP." However, action on that decades-long concern has only come recently: "Due to the progress against WPV [wild poliovirus], VAPP is one of the major drivers in the 2013-2018 Endgame Plan to stop all OPV use by 2019," according to Lonsdale. Although VAPP is a driving concern, use of the live vaccine for a year after eradication of the wild virus means the last case of polio paralysis is likely to be caused by the oral vaccine.
The Gates Foundation hints that others have responsibility for choosing the two-edged sword of a polio vaccine that can cause polio: “for a more historical look at the history of polio vaccine policy, best to contact CDC or WHO,” Lonsdale suggested.
Years ago, Bill and Melinda Gates showed their children a documentary about polio. The kids asked about a crippled boy in the film: "Did you help that kid? Do you know the name of that kid? Well, why not?" Melinda answered "We don't know that boy, but we're trying to help lots of kids like him." Bill reportedly added: "I'm in wholesale. I'm not in retail!"
VAPP is retail.
A confirmed case of vaccine-derived polio in
Nigeria greatly complicates global plans to retire the trivalent vaccine next
year and switch to the bivalent formulation. The polio eradication
program is now between rock and hard place, with logistical momentum building
for the switch but a possible public health emergency should the switch go
ahead as planned.
In rare instances, the live oral vaccine can mutate, circulate and paralyze like its former self. Most cases of circulating vaccine-derived poliovirus (cVDPV) are caused by the type 2 virus in the trivalent vaccine, scheduled for retirement in April 2016. But the type 2 component of the vaccine both causes and protects against cVDPVs. In a Catch-22, the trivalent vaccine can’t be withdrawn until it stops the problem it is causing. Pulling the vaccine before halting type 2 cVDPVs would lead to a growing immunity gap and create the conditions for potentially large outbreaks.
Prior to the Nigerian case of cVDPV reported last week, Pakistan had caused the greatest concern with recent sewage samples testing positive for cVDPV. Nonetheless, the World Health Organization confirmed in April the scheduled replacement of trivalent vaccine with bivalent set for April 2016. The bivalent vaccine immunizes against only types 1 and 3 of the poliovirus. Type 2 appears to be long gone, last seen in India in 1999.
The logistics of the switch are daunting: 156 countries currently using or stockpiling the trivalent vaccine need to stop and switch to bivalent at the same time. Every dose of trivalent vaccine administered afterwards creates the risk of type 2 vaccine-derived virus.
In addition to the heavy logistical burden in the field, the switch also requires coordination among manufacturers who must scale back and eventually stop making the trivalent formulation and ramp up bivalent production. Once on, the switch is difficult to turn off.
Until recently, extinguishing all circulating vaccine-derived viruses was an unambiguous precondition for the switch. The eradication endgame plan states that “validation of the elimination of persistent cVDPV type 2…” must precede withdrawal of the trivalent vaccine. The US Centers for Disease Control (CDC) concurred that “persistent cVDPV2s need to be eliminated before the withdrawal of tOPV [trivalent vaccine].” Earlier this year, Paul Rutter, spokesperson for polio eradication's Independent Monitoring Board, said: "My understanding is that the switch could not happen unless cVDPVs are stopped—it is an absolute prerequisite."
No longer.
WHO’s Strategic Advisory Group of Experts (SAGE) decides vaccine policy. SAGE will meet again in October. “The SAGE is not only going to look at whether there is circulation,” said WHO spokesperson, Sona Bari, in early June. According to Bari, SAGE will also consider "what steps have been taken to stop circulation, what immunity levels are like, etc.”
The Independent Monitoring Board (IMB) backed off from its earlier more absolute position after SAGE gave its go ahead for the switch. Said IMB spokesperson, Paul Rutter: “making a judgement about what constitutes a 'showstopper' would be to second-guess SAGE."
Earlier this year, a modelling study warned of a
worrying possibility that vaccine derived virus would still be circulating next
year when the switch is set to occur. A co-author of the study, Kimberly
Thompson, expressed concern back in February that "It's possible that
world leaders will decide to coordinate OPV2 cessation in April 2016 without
being 95% confident that cVDPV2 transmission has stopped in Nigeria or
Pakistan." At the time, Thompson believed “Pakistan may be more of a
threat to global cessation than Nigeria." And subsequently, immunization
efforts in Nigeria included measures to drive down cVDPV risk, particularly by vaccinating
with the trivalent vaccine. As recently as June 22, Thompson believed Nigeria
“can be OK in April 2016 at the time of the switch.”
After the Nigerian cVDPV case last week, however, Thompson stated that "if global health leaders want at least 95% confidence that cVDPV2 transmission has stopped in Nigeria prior to coordinated OPV2 cessation they will need to delay cessation beyond April 2016." Polio’s annual infection cycle is at its low ebb in the month of April. Consequently, a delay in the switch would likely push the date a full year to April 2017.
Pakistan too remains a risk for having cVPDV come next April, according to Thompson, although the risk in both Pakistan and Nigeria can be reduced by the number and quality of vaccination campaigns using the trivalent vaccine.
Thompson and co-authors at the CDC said in a recent paper that switching to bivalent vaccine while vaccine-derived virus circulated “would represent a public health emergency…” WHO already declared polio a Public Health Emergency of International Concern (PHEIC), back in May 2014. The CDC raised polio to a maximal, Level 1 crisis in 2011.
Regarding the schedule for the switch, the Gates Foundation deferred to SAGE. Said foundation spokesperson, Rachel Lonsdale, “The SAGE will review the plans for the switch this fall and make the decision if it is moving forward next year.”
A WHO spokesperson made no comment to an emailed request.
[Article updated at 11:33 am and 11:52 am 7/6/2015]
[Article updated at 3:33 am 7/7/2015]
During high season for polio this year, Nigeria has seen only one case of paralysis caused by the wild virus – an achievement which, if viewed in isolation, can be hailed as a great global health success.
But the single-minded focus on polio eradication appears to have left routine immunization behind. Measles deaths spiked last year not only in Nigeria but globally.
Now, ironically, Nigeria’s exceptionally poor immunization system is obstructing the goal of polio eradication.
It's high season for polio in Nigeria--and there have been no cases for seven weeks. The Gates Foundation arguably runs the polio eradication effort, and apparently to good effect.
The remarkably low numbers seen in Nigeria are probably not due to missed cases. The quality of surveillance can be measured in a number of ways. There usually is at least one case of non-polio paralysis a year for every 100,000 children. Below that ratio, surveillance is considered inadequate. To distinguish polio from non-polio paralysis, stool samples must be analyzed, with a goal of testing 80% of cases. Nigeria's scores on both these measure have been climbing since 2006. The stool sample rate now approaches 100%.
It is difficult to descry changes in these measures easily attributable to new and improved management. Regardless, in a kind of pincer movement, better surveillance and increasing quality of immunization campaigns are slowly crushing polio.
Nigeria might or might not make it to the end of 2014 with no cases. If it does, transmission in the country could be declared as halted, which might be important for meeting the global eradication deadline of 2018. However, Pakistan, which faces an intense although geographically circumscribed polio explosion, unquestionably will not halt transmission this year. If the eradication timeline is taken literally, Pakistan's situation will require adding one year to the schedule, i.e. missing yet another eradication deadline and likely adding roughly $1 billion to the budget.
The Independent Monitoring Board, de facto interpreter of the eradication plan and arbiter of progress, will have a report out soon.
The World Health Organization (WHO), technically responsible
for the world’s health and declaring emergencies, is actually in charge of neither.
In late July, before declaring Ebola to be a global public health crisis, WHO’s
Emergency Committee declared polio a
public health emergency of international concern. Ebola only graduated to the
same status a week later after American health care workers became infected. The
world then ignored WHO’s alarm for weeks as Ebola exploded. The other
“emergency”—polio—overshadowed an actual Ebola crisis, and makes visible WHO’s
decline to infantilized order taker and the primacy of the Gates Foundation.
When WHO declared polio to be a public health emergency on May 5th, 2013, the risk of polio spreading sat near its lowest level in human history.
Polio is more than 99% extinguished compared to 1988 when there were 350,000 cases in 125 countries. The polio “emergency” came not from risk to public health but risk of not making the eradication schedule. To make a 2018 deadline, polio transmission must be stopped by the end of this year. Similarly, in 2011, the CDC declared polio to be a maximal, Level 1 crisis to meet a now-passed 2012 deadline. Still today, the CDC Emergency Operations Center recognizes two emergencies: polio and Ebola.
Calls for WHO to make polio a global health emergency originated from the Independent Monitoring Board (IMB) of the polio eradication initiative. Set up in 2010, IMB says it was “convened at the request of the World Health Assembly.” However, there is no World Health Assembly resolution that mentions or requests an independent monitoring board. “I have just had a good look too,” said IMB spokesperson, Paul Rutter, “and can't find it either.”
Notwithstanding the unclear provenance of IMB’s authority, the WHO Director-General in effect reports to IMB. According to IMB’s charter, the Director-General must “immediately inform the relevant Ministry of Health and donor or partner agency” of IMB recommendations and establish corrective action plans “within 4 weeks of notification.”
In late 2013, the IMB expressed its desire that WHO declare polio to be a public health emergency. However, the International Health Regulations governing emergencies emphasize “public health risk,” not schedule risk. But the campaign for a polio emergency continued. At the end of January, the United States’ representative to the WHO Executive Board, Nils Daulaire, asked WHO to declare polio to be a public health emergency and set a deadline of mid-May, 2014.
Before being named US representative to WHO, Daulaire served for more than a decade as president and CEO of the Global Health Council. Among its function, the council selected the winner of the $1 million Gates Award for Global Health. Under Daulaire, from 2000 forward, the Global Health Council received $36 million from the Gates Foundation. In 2006, Daulaire’s wife went to work at the foundation, continuing there until the end of 2013.
Daulaire has said he "does not see the Gates Foundation or private entities as having a rightful role in establishing WHO’s priorities.” He dismissed suggestions that the foundation has an outsized role although he said: “There are member states who believe the Gates Foundation has more influence than it ought.” Daulaire said it is “entirely wrong” that the United States is increasing the foundation’s role.
Polio eradication has topped the Gates Foundation’s priorities for several years. In 2011, then foundation president, Tadataka Yamada, answered critics of the polio-centric agenda saying: “They are right. We are overemphasizing polio eradication.” Earlier this year, Bill Gates said “polio is the single thing I work on the most.”
The WHO Executive Board did not vote on Daulaire’s proposal for a polio emergency. The board, which rotates, did happen to include a number of countries impacted by polio: Pakistan, Nigeria, India and Syria. None of their representatives supported or mentioned the US call for a public health emergency. The United States itself has been polio-free for more than three decades. The CDC saw no increased threat to Americans.
On May 5, just ahead of Daulaire’s deadline, WHO declared
polio a public health emergency. On the same date, WHO reported a cumulative 239
cases of Ebola and 160 deaths in three countries.
Daulaire, according to Executive Board meeting minutes, also said “His Government attached high priority to strengthening the International Health Regulations and had established global health security as a key issue,” precisely where WHO would soon fail. However, according to a Reuters report, a 2011 proposal for a $100 million epidemics task force was shot down by member states. Also, budget cuts forced WHO’s Africa regional office to cut its epidemic team from 12 to four staff over the past two years. As Peter Piot, discoverer of Ebola noted, WHO budgets cuts were “approved by the USA and other member states.”
The polio emergency, sought and won by Daulaire, had been based on the worry that “Pakistan, Cameroon, and the Syrian Arab Republic pose the greatest risk of further wild poliovirus exportations in 2014,” according to WHO. Subsequently, neither Cameroon nor Syria exported polio and domestically experienced no onset of polio-induced paralysis since before the first declaration. Pakistan, where polio transmission has never been interrupted, continued to export polio—as it always has, although without having prompted a global emergency. Nonetheless, WHO concluded on July 31st that “the international spread of polio in 2014 continues to constitute an extraordinary event and a public health risk to other States.”
At the same time, WHO also reported a total of 1,323 Ebola cases, 729 deaths and even the export of the disease to a fourth country, Nigeria. However, Ebola apparently did not come up at the polio meeting, according to Vice Chair Robert Steffen: “with the targeted agendas I would not imagine that the polio [Emergency Committee] suggested there should be an Ebola [Emergency Committee].”
Unmentioned at the emergency meeting, Ebola had become uncontrolled more than a month earlier. On June 23rd. Médecins Sans Frontières (MSF) issued a press release declaring “We have reached our limits.” An MSF spokesperson said, “we are no longer able to send teams to the new outbreak sites,” which numbered more than 60 across Guinea, Sierra Leone, and Liberia. MSF, which described itself as the sole responder to the epidemic, said: “The epidemic is out of control.” The next day, WHO Ebola expert Pierre Formenty briefed top WHO officials in Geneva. Days later, the WHO Ebola situation report recognized “Currently, the coverage of effective outbreak containment measures is not comprehensive,” as Formenty’s presentation had shown. WHO updates began reporting cases and deaths not in sentences but using a grid. The rout was on.
The science of epidemiology should have been able to predict, albeit tentatively, when the efforts of MSF were doomed to fail. But just as with polio, epidemiology played no role in the timing of emergency declarations and international response. WHO’s emergency announcement came only on August 8th when there were 1,778 cases—including, for the first time, two Americans.
Declaring polio an emergency did not unleash vast new efforts to stamp out the disease. Most everything had already been done in the $1 billion a year effort —except consecrating eradication as the single most important public health issue in the world. The day after the polio declaration, the Gates Foundation blog explained that “The sounding of an emergency often is seen as a sign of distress, and news of this announcement certainly communicated that.” Indeed, the supposed emergency fueled headlines like “Polio, Spreading Abroad, Threatens US.” Not only was there no increased threat, the risk of spread was near historic lows. Instead “what this alarm really signals,” continued the foundation blog, was doing “what it takes to end this disease as quickly as possible,” that is, meeting the 2018 deadline.
When WHO declared an Ebola emergency, its declaration also did not unleash vast new efforts to stamp out the disease. WHO lacked resources to do anything itself while whatever heft the UN has was not applied. UN Secretary General Ban Ki Moon was not at Margaret Chan’s side as the WHO Director-General announced the Ebola emergency. Moon appears more frequently with Bill Gates. Gates partnered with Moon and the UN, not WHO, for the Gates Foundation vaccine summit that raised more than $4 billion for polio. And, as symbolized by an article co-written by the two on vaccination, Gates and Moon author the global health agenda, not WHO.
The world reacted to WHO’s Ebola emergency as if declared by a clerk. The CDC dispatched a small team to Liberia to areas that had not yet reported any cases. Its purpose was not to assist in containment but to assess preparedness which was found to be woeful. The CDC’s “surge” response dispatched 50 more disease control experts to be deployed within a month. Although issuing a travel warning to US citizens, the CDC was “not screening passengers traveling from the affected countries.” For the ongoing polio emergency, the CDC reported “an average of 60-70 people” working on eradication at its Emergency Operations Center.
For the Ebola crisis, the Gates Foundation pledged
$1 (one) million to “help address the immediate need on the ground,” according
to foundation CEO, Sue Desmond-Hellmann. But the next day, on its “Impatient
Optimists” blog, the foundation optimistically moved on. A piece
entitled “How to Prevent the Next Health Crisis,” explained how the next
threat, cerebro-spinal meningitis, “could end up being far more destructive than
the current Ebola epidemic.”
Three weeks later, on August 25, Desmond-Hellman tweeted about how “Nigeria is using what they’ve learned battling polio to contain the ebola outbreak.” The story was not about Nigeria as harbinger of inexorable spread but how polio eradication investments had saved the day. And indeed, the $1.5 billion being spent in Nigeria for polio might have contributed to extinguishing Ebola there.
Bill Gates weighed in on Ebola for the first time on September 10, more than two months after MSF said the outbreak had become uncontrolled. Gates tweeted about the foundation’s upcoming chat on Twitter:
The foundation now pledged $50 million; earlier in the year, it committed $1.8 billion to polio. The United States, now finally acting on Ebola, drew applause from Desmond-Hellmann: “The time to act on Ebola is now,” she said with the case count at 4,963. But just days and 2,507 cases later, Desmond-Hellman wrote of Ebola: “If the world doesn't learn from this outbreak, one day we’ll have a real pandemic on our hands.”
It was not the foundation’s job to detect and declare emergency outbreaks. But the foundation and Gates evaluated the Ebola threat and publically projected the conclusion that Ebola was no emergency.
Gates is influential. “If … I need to go to the Indian parliament and say, ‘Let’s get serious about vaccines,’ ” said Gates, “then yes – since I’m giving my own money [on a] large scale and spending my life on it and I’m a technocrat – yes, that can be quite valuable.” In 2011, Gates had gone to the World Health Assembly and said it needed to get serious about vaccines. He explained to the assembly “how you can provide the leadership to make this the Decade of Vaccines.” The WHA followed Gates’ leadership advice and approved his initiative. Memorably, Gates also told the WHA: "Our priorities are your priorities."
Not only did polio come to uniquely occupy the pinnacle position in international public health, the Gates Foundation has come to effectively run the eradication effort. The Director-General began answering to the Independent Monitoring Board in 2010. In 2011, a Polio Partners Group (PPG) replaced a meeting previously convened by WHO. WHO participates in the new group but is barred from serving as its chair by PPG bylaws. The PPG “was not summoned into existence per se” by act of the World Health Assembly, according to its current chair, John Lange. As with the IMB, there is no resolution requesting that the PPG be instantiated. Lange, now at the UN Foundation, previously worked at the Gates Foundation from March 2009 to June 2013. He was a foundation employee when elected PPG chair. Lange said the PPG was conceived at a meeting held not in Geneva at WHO but the CDC in Atlanta in December 2011, at or near the time when the CDC elevated polio to a maximum level threat.
Space for initiative-taking by WHO has been systemically closed off, as if child-proofing a room by blocking electrical power outlets. In 2013, a new entity, the Polio Oversight Board (POB), took over operational decision-making from WHO. According to Lange, the POB "effectively oversees and manages" the polio eradication effort, although “technically” the POB does not have authority over budgets, for example. Nonetheless, said Lange: "Its decisions are implemented." The first POB chairperson was Lange’s former boss, Chris Elias, president of global development at the Gates Foundation.
The Gates Foundation’s subjugation of WHO is not new. WHO lost its global leadership and capacity to set the world’s health agenda years before. At the 2007 Malaria Forum, for example, the convening power of the Gates Foundation, not WHO, brought together the world’s leading malaria researchers and policy makers. WHO Director-General Margaret Chan sat in the audience as Melinda Gates shocked her invitees by proposing to eradicate malaria. Malaria eradication had been tried and failed disastrously. However, Chan converted on the spot, jumped up and, taking the microphone, enthusiastically supported eradication. At the time of the Malaria Forum, the foundation had cumulatively invested $1 billion in malaria, starting with an early, $50 million grant in 1999. By contrast, the purchasing power of WHO’s budget in 2007 had fallen by almost 25 percent compared with 2000.
The foundation did not ask WHO, its Director-General or the researchers it invited to the conference for their opinion about malaria eradication. For polio, the World Health Assembly voted on and approved a resolution on eradication. But a Gates Foundation spokesperson, asked whether there would be a vote on malaria eradication, said: “Not as far as I know.” Arata Kochi, then the head of malaria at WHO, fought back against what he described as a foundation “cartel.” He was replaced after his memo leaked to the New York Times. In 2014, the president of the American Society of Tropical Medicine and Hygiene (ASTMH) is Alan Magill, the head of malaria at the Gates Foundation. The keynote speaker for this year's ASTMH conference is Bill Gates.
The Gates Foundation isn’t on the sidelines haphazardly supporting good causes but actively architecting global health policy. The “overemphasis” on polio comes from foundation plans for malaria eradication. As Bill Gates recently explained: “Polio we hope to get done by 2018. Then the credibility, the energy from that we will allow us to take the new tools we’ll have then and go after a malaria plan.” The current malaria plan was paid for by the Gates Foundation. A year after shifting malaria policy to eradication, in 2008, the foundation became and has remained the largest funder of polio eradication.
Absent this link to malaria eradication, the foundation’s overemphasis of polio makes little sense. Even Gates acknowledges that, among eradication efforts, polio is borderline. Smallpox he said, “was a good choice. Polio is a hard but reasonable choice." Much better is malaria, which he characterized as "a very reasonable choice.” At no time in the past or present has polio merited the world’s sole focus—unless for symbolic reasons. Other diseases, like diarrhea, are more prevalent and deadly. Polio, for all its awfulness, rarely causes death.
The Gates Foundation has also hived off childhood
immunization from WHO. The cleaving began in in 1998 with the introduction
of the Bill & Melinda Gates Children’s Vaccine Initiative. The creators of
this early initiative worried that WHO “might consider that we are trying to
pre-empt their responsibility,” and worked to “find a way to present ourselves
that avoids all presumption of a challenge to WHO." (Quoted in Muraskin, Crusade to Immunize the World's Children.) The program eventually
became what is known today as GAVI. The money for immunization goes to GAVI and
no longer directly to WHO and UNICEF. By
2008, any challenge to WHO was over. A GAVI governance change submerged WHO on
a board
with 28 other members, its vote counting as much as a representative from the
vaccine industry.
Institutions of civil society were inadequate. “We must be willing to look at the failure of collective action and see how we can change it,” Bill and Melinda Gates wrote in 2007. More recently, regarding democratic processes, Gates said: “The closer you get to it and see how the sausage is made, the more you go, oh my God!” He questioned whether in the United States, “can complex, technocratically deep things…can that get done?” It was unclear that democracy was equal to complicated modern problems. According to Gates: “The idea that all these people are going to vote and have an opinion about subjects that are increasingly complex – where what seems, you might think … the easy answer [is] not the real answer. It’s a very interesting problem. Do democracies faced with these current problems do these things well?”
How well has Gates done in the face of important global health problems? Prior to Ebola, AIDS represented the greatest global health crisis of the present era. Although AIDS is far from solved, the epidemic has been controlled by the free provision of anti-retroviral therapy (ART). Free ARTs saved lives and reduced transmission of the disease. The PEPFAR program, unexpectedly initiated and signed into law by George W. Bush, made ARTs free in the world’s hardest hit regions. Even Bono credited Bush and American taxpayers: “…10 million people owe their lives to the U.S…George Bush started it,” the U2 frontman said last year.
Bill Gates opposed free AIDS drugs, because of the “harsh mathematics of the epidemic,” as he wrote in The Independent. “[F]or each person who starts getting treatment today, 10 more people will need treatment tomorrow.” Gates cited cost estimates as high as $40 billion a year by 2020. Instead, prices were forced down, anti-retrovirals saved lives and turned the tide of the epidemic.
The Gates Foundation, shaped by Foege, is constitutionally averse to short term crises. When the foundation at last pledged a modest $50 million for Ebola, it made much of how it was its largest ever grant for a humanitarian emergency. The foundation might have viewed Ebola as an acute need potentially competing for resources needed for vaccination efforts or perhaps to rid the world of polio and malaria forever.
The foundation presumably made assessments of the Ebola threat, but it is not clear how and by whom. The foundation does not appear to have a section or person dedicated to outbreaks. The portfolio of the foundation's Lance Gordon, neglected tropical diseases, perhaps comes closest to Ebola. Gordon did not reply to an email asking how the foundation assessed the Ebola outbreak.
The foundation prioritized meningitis vaccination above
Ebola. Gates, perhaps uniquely, audaciously defended the slow response to
Ebola, saying “I think it is amazing how the United States has responded to this.” He warned “it’s
easy to forget just how much has been done” in response to what he called a
“short-term crisis,” although he would not forecast when it would end. The
unprecedented deployment of the military he attributed
not to the exponentially expanding scale of the disaster but “the president who
said let’s get the Department of Defense involved because they’re the ones who
can do logistics and get people in and out and get things built.” In contrast to Gates,
President Obama has emphasized
that "the world is not doing enough" to fight Ebola.
The US response, according to Gates wasn’t late. "Was there some other government who took decisive action before we did?” he asked. “Was there a CDC equivalent who flew in and personally toured [the affected countries]?” WHO did not figure in his world. However, looking to the CDC as global sentinel—waiting for Tom Frieden’s trip report—further delayed the international response several weeks. Frieden recently said "Speed is the most important variable here.” But for Gates, only Frieden’s trip revealed that: “even though the US and we had given money,” a reference to the foundation’s $1 million pledge, “that seeing the urban impact, that we really all needed to step up.” Frieden, unlike Gates, has said of the outbreak “this was preventable." But the trigger for Gates was anecdote from a top official, not epidemiology, reports from those on the ground, nor a WHO emergency.
It is not the CDC’s job to be the first-line monitor of international disease outbreaks, being neither not suited nor designed for it. Pointing out the obvious, a Lancet editorial noted “the US Government is not a multilateral health agency.” WHO, not the CDC, has an international surveillance network tied into national ministries of health in nearly every country. “The final responsibility to prevent the international spread of disease rests with WHO and IHR [the International Health Regulations],” the editorial concluded.
But whether one looks to the CDC or WHO, as the polio emergency demonstrates, both agencies toe the line set by the Gates Foundation. The foundation has downplayed Ebola, with Gates defending the timing and strength of the international response.
Gates’ “Big idea” on Ebola is to circumvent WHO to speed approval of experimental drugs: He asked: “Who decides that if there’s some slight increased risk of a side effect the benefits here outweigh that?” Legal authority and responsibility lie with WHO. A WHO panel of ethicists has already approved untested treatments. But according to Gates, “It’s very tricky because really the world is not very practiced at what resources should come in and how these decisions should be made.”
Gates’ consistent answer to the world’s health problem remains: take away the functions served by the World Health Organization. He has been successful. Today WHO is timorous, enfeebled, and incapacitated, playing a mostly ceremonial, subservient role. Gates is protagonist. Ebola is out of control.
The fake vaccination campaign to ensnare Osama Bin Laden unquestionably harmed polio vaccination efforts in Pakistan. But cases began rising beforehand, in 2008, and actually declined in 2012—after Bin Laden's assassination and the swift disclosure of the fake vaccination plot in mid-2011.
The Taliban's announcement opposing polio immunization came a year after the vaccine imbroglio and fingered drone attacks. A month after the anouncement, vaccinator shootings began. Nonetheless, the polio situation in 2013 was better than in 2008.
Polio is a political game piece. Religio-political beliefs once halted polio vaccination in Nigeria. The Bin Laden ruse harmed Pakistan's polio effort but by focusing already existing anti-Western, anti-polio sentiments. Kristofer Harrison's article in Foreign Policy, which blames Pakistan's polio regress on the leaking of the vaccine ruse, oversimplifies too dramatically the chain of causality.
May 2011 Bin Laden killed
July 2011 Vaccination ruse revealed
June 2012 Taliban announces anti-polio stance because of drones
July 2012 First vaccinators shot