Three years ago, the leaders of the international campaign to eradicate polio pulled off a landmark feat, phasing out a problematic component of the vaccine used in developing countries, and introducing a newer version that they hoped would put the world on a better footing to finally eliminate a global scourge.
Now, some organizers are weighing whether “the switch,” as the process was known, needs to be reversed.
If it’s not, some fear, the world could face a heightened risk of spread of the disease, currently confined to its last redoubt, Pakistan and Afghanistan.
“We’re having those conversations, but we haven’t concluded anything,” said Michel Zaffran, director of polio eradication at the World Health Organization, when asked about the possibility the polio program may have to resume routine vaccination of children against type 2 polioviruses.
The decision to reverse the switch would be a devastating blow to the Global Polio Eradication Initiative, which is already nearly 20 years past its original deadline. The campaign and other polio experts stress that no decision has been made, but acknowledge that the vaccine could be returned to routine use again for a period, at least in some countries or regions.
“At this point I think I’m hesitant to switch [back],” said Dr. Walter Orenstein, a consultant for the Global Polio Eradication Initiative. “But I think that’s certainly in discussion and is a potential.”
The goal of the switch was to remove from circulation the part of the vaccine that protected against type 2 polioviruses, which were declared eradicated in 2015. The oral vaccine contains live but weakened polioviruses, which can on occasion paralyze children. If type 2 viruses no longer existed, the thinking went, it was unethical to expose children to the risk the vaccine viruses posed.
It was known it would be risky to stop vaccinating children against type 2, because vaccine viruses remaining in the environment could begin to circulate and infect children with no immunity to those viruses.
Thorough planning on how to do it safely was undertaken and, in most of the world, the switch was a success. But not so in parts of Africa, where three years later, type 2 vaccine viruses are being found over a widening swath of territory.
Many experts are banking on a new oral vaccine that all hope may solve the growing problem. If all goes well, the polio program may be able to start using it in mid-2020. In the meantime, however, experts are wrestling with how to address the unsettling reality amid other signs of trouble in the eradication campaign.
So far this year there have been 78 cases of polio caused by wild polioviruses recorded in Pakistan and Afghanistan, more than double the number — 33 — seen in 2018.
Some experts are strongly opposed to the idea of a reversal. Even those who think it may be inevitable speak of it with dread in their voices.
“We definitely do not want to do that. It’s a really big deal if we have to go down that path,” said Kimberly Thompson, a mathematical modeler whose calculations have helped the polio eradication campaign chart strategy for nearly two decades.
Thompson said she and her group have been warning that when it comes to the polio program’s ability to successfully cope with transmission chains of type 2 vaccine viruses, things weren’t going in the right direction.
“We’ve been saying … for I think the past year that things didn’t look good on the type 2 and that they needed a plan,” she said. The response to that advice has been slower than Thompson thinks is advisable. “It’s hard to watch,” she said.
“The longer we wait, the higher that risk goes,” said Thompson, who is president of the nonprofit Kid Risk, which conducts research on infectious diseases including polio, measles, and rubella. “It’s just growing with time.”
To understand the problem, you need to know some basics about polio vaccines — and, specifically, the oral vaccine, known as OPV.
OPV contains the live but weakened viruses that Albert Sabin engineered in the late 1950s. This is the vaccine that is used in most of the developing world, unlike the United States, which uses IPV, or inactivated polio vaccine.
The strengths of Sabin’s vaccine are many. They include: its pennies-a-dose price; its ease of administration; and the fact that the vaccine viruses spread from vaccinated children to others around them, which means vaccination campaigns protect many more children than just those the vaccination teams find. Back in the day in the developing world, if you vaccinated some kids in a neighborhood, you pretty much vaccinated the neighborhood.
But that last benefit, which was helpful when there were hundreds of thousands of polio cases a year, is a decidedly mixed blessing now. The Sabin vaccine viruses, once released in a community, continue to spread if they encounter children who are not immune to polio. In places where sanitation and hygiene are poor, viruses find their way into water sources, and onto contaminated hands or foods, and are then ingested by other children.
As they cycle from child to child, the vaccine viruses can regain the virulence traits that Sabin engineered out of them. If the vaccine viruses circulate long enough, they regain the power to paralyze.
The part of the oral vaccine that protected against type 2 viruses was removed in spring 2016 in a move synchronized around the world.
Since then, the number of children with zero immunity to type 2 polio (and type 2 vaccine viruses) has grown daily. This cohort numbers in the tens of millions.
In parts of the world where type 2 vaccine viruses aren’t spreading, that lack of immunity doesn’t matter. But in countries in Central Africa, where the vaccine viruses are spreading over greater and greater territory, those unprotected children are at risk.
Children without any type 2 polio protection give the vaccine viruses the chance to circulate enough to regain paralytic powers. Even children who have received IPV — countries were urged to give all children one dose each before the switch, but a global shortage of IPV hindered that effort — can be infected by and transmit the vaccine viruses. (The inactivated vaccine prevents paralysis, but it doesn’t prevent infection.)
In the year of the switch, there were only two children paralyzed — one in Pakistan, one in Nigeria — by type 2 vaccine-derived polio viruses. But the next year, the number rose to 96, in two countries. Last year there were 71 in five countries. To date in 2019, there have been 68, in 10 countries.
All but one of those countries — China — are in Africa. Most if not all had low vaccination rates even before the type 2 component was removed from OPV. In Ghana, it’s estimated that only 55% of children have immunity to type 2 polio.
Each time these vaccine viruses are discovered to be circulating, the polio eradication campaign responds in a way that might seem paradoxical: by sending health workers to affected areas and giving all the children they can find a special oral vaccine that targets only type 2 viruses.
The idea is to go in quickly and vaccinate as broadly as possible to deprive the vaccine viruses of children to cycle through. In other words, fight fire with fire.
“You don’t mess around,” Thompson said. “You go in big — big enough that you can really shut it down and you do it as fast as possible.”
That’s the protocol, but execution has sometimes been imperfect. In some cases, people have been afraid of fighting fire with fire. “There was just a lot of hesitancy about using the type 2 OPV,” Thompson explained.
Inadequate responses to the outbreaks have left embers that smoldered and then started new blazes. The numbers of outbreaks involving the type 2 vaccine viruses are rising and those viruses are spreading — over vast terrains. The Democratic Republic of the Congo, the Central African Republic, Angola, and Somalia have reported finding type 2 vaccine viruses this year, either isolating them from paralyzed children or finding them in sewage surveillance conducted to look for polio.
A vaccine virus transmission chain discovered in Nigeria in 2018 illustrates the alarming potential of these vaccine viruses. First identified in Jigawa state in the north of the country, the viruses have spread to more than a dozen Nigeria states as well as to Niger, where they have paralyzed at least six children, Cameroon, Benin, and most recently Ghana.
In mid-August it was confirmed a toddler in northeastern Ghana, near its border with Togo, had been paralyzed by vaccine viruses from the Jigawa transmission chain. Days earlier, type 2 vaccine viruses from this chain were found in sewage in Ghana’s capital, Accra, nearly 400 miles away.
Multiple rounds of vaccination with the type 2 OPV will be conducted to try to stop the vaccine viruses from spreading in Ghana, with more than 2 million children targeted for vaccination. That work began this week.
The problem, though, for the containment effort is the children on the margins of these mop-up campaigns.
Using type 2 oral vaccine to snuff out the spread of the type 2 vaccine viruses appears to work where the vaccine is given. But across a state line or national border, unprotected children who aren’t targeted by the emergency response, but who have no immunity to type 2 polio, are tinder for new brush fires as the vaccine viruses spread. Children with no immunity to type 2 polio in Togo, for instance, may encounter vaccine viruses disseminated in the Ghana campaign.
“We are getting to that point where not only do you have to go in aggressively to a much larger population because you’ve got cohorts [of kids] that are much bigger as you get further out in time, but you also have this increased risk that OPV itself could move to another place … to start new chains of transmission,” Thompson said.
“It is polio. It behaves the same way,” she said of the vaccine viruses. “And if you just keep trickling in with a little bit of vaccine every time you think you have a problem all you’re doing is reseeding [more transmission chains]. That’s not the way to do it.”
When the type 2 component was taken out of the oral vaccine, a stockpile of the special type 2 OPV was created to deal with vaccine virus outbreaks, which were expected. (They were also expected to have died down by now, Thompson noted.)
That stockpile has been drawn down to a far greater degree than was expected, leaving the polio program with some tough decisions to make.
Several OPV manufacturers, some of whom have indicated they will exit the market in anticipation of the eventual cessation of all OPV use — which must happen as part of eradication — have type 2 vaccine in bulk. There are about 1 billion doses, said WHO’s Zaffran, and the manufacturers, which include Sanofi (SNY) Pasteur and Indonesia’s Bio Farma, have been asked to begin the work of converting some of that bulk vaccine into vials that can be purchased and shipped.
In another move aimed at ensuring the polio program has enough vaccine to respond to the type 2 vaccine problem, the WHO’s vaccine advisory committee, know as the SAGE — short for Strategic Advisory Group of Experts on Immunization — will be asked at its next meeting, in October, if it would be all right to vaccinate children with one drop of OPV2 vaccine, instead of two. Halving the dose would stretch out supplies.
Improving the quality of vaccination efforts — making sure all eligible children get IPV through routine immunization and that emergency responses using type 2 OPV to stamp out vaccine virus outbreaks are run effectively — is also high on the list of steps that can be taken to lessen the risk while the polio program waits for the new vaccine, experts say.
Dr. Stephen Cochi, senior advisor to CDC’s global immunization program, said it would also help if the WHO agreed to treat each discovery of type 2 vaccine viruses as what’s known as Level 3 emergency, the way a discovery of wild poliovirus would be. Currently they are deemed a Level 2 event.
“They are given a lower designation and countries — not uncommonly — are just sitting on these. And they’re slow to respond,” Cochi said.
All of these are patches, though. The real fix, everyone hopes, will be the new oral vaccine.
The Gates Foundation has spearheaded the drive to develop an oral vaccine that doesn’t have the Achilles’ heel of the Sabin vaccine. The goal — and early testing looks promising — is that the vaccine viruses will be more stable, that they won’t be able or at least will be less likely to regain the power to paralyze.
Two candidates are being tested and the best one will be developed. The plan is to use the vaccine under the WHO’s emergency use protocol, even before it is licensed. It currently looks like that could happen midway through next year, at which point 100 million doses of the vaccine should be available. Bio Farma, which will produce the vaccine, will have the capacity to make 35 million doses a month, Cochi said.
If the new oral vaccine is safer than Sabin’s vaccine, it would be used to respond to type 2 vaccine virus outbreaks, Zaffran said. And if a decision is eventually taken to reintroduce type 2 oral vaccine in a region to deal with the vaccine virus transmission problem, the new vaccine would also be the choice for that task, he said.
Dr. Jay Wenger, director of the polio program at the Gates Foundation, said it looks like the risk that the new oral vaccine might seed transmission chains is a lot lower — though the only way to know for sure will be to use the vaccine. The foundation is pushing hard to get the vaccine into the field as soon as possible.
“We recognized that the sooner we get this new tool out, the new OPV, the better we’ll be,” Wenger said. “So we are pushing very hard to make that happen as quickly as possible.”