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TThree years ago, the leaders of the international campaign for polio eradication had achieved a historic feat by progressively eliminating a problematic component of the vaccine used in developing countries and introducing a new version which, hopefully, it would allow the world to better position itself eliminate a global scourge.
Now, some organizers are questioning the opportunity to reverse the "change" as the process was known.
If this is not the case, the world could face an increased risk of spreading the disease, currently confined to its last redoubt, Pakistan and Afghanistan.
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"We have these conversations, but we have not concluded anything," said Michel Zaffran, director of polio eradication at the World Health Organization, about the possibility that the polio program be forced to resume routine immunization of children against type 2 poliovirus.
The decision to reverse the change would be a devastating blow to the Global Polio Eradication Initiative, which is already almost 20 years past its original deadline. The campaign and other polio experts point out that no decision has been made, but acknowledge that the vaccine could be re-used in a systematic way for a while, at least in some countries or regions.
"At this point, I think I hesitated to change [back]Said Dr. Walter Orenstein, consultant for the Global Polio Eradication Initiative. "But I think it's certainly in the discussion and it's a potential."
The aim was to remove from circulation the part of the vaccine that protected against poliovirus type 2 declared eradicated in 2015. The oral vaccine contains live but weakened polioviruses that can sometimes paralyze children. If type 2 viruses no longer existed, he thought, it was unethical to expose children to the risk that vaccine viruses accounted for.
It was known that it would be risky to stop vaccinating children against type 2 because vaccine viruses remaining in the environment could begin to circulate and infect non-immune children against these viruses.
Careful planning on how to do it safely was undertaken and, in most countries, the change was successful. This is not the case in some parts of Africa, where three years later, type 2 viruses are found in a wider and wider strip of land.
Many experts are banking on a new oral vaccine that hopefully will solve the growing problem. If all goes well, the polio program may be able to start using it in the middle of 2020. In the meantime, however, experts are struggling to find a solution to the troubling reality, in addition to other signs of problems in the eradication campaign.
So far this year, there have been 78 cases of poliomyelitis caused by wild polioviruses in Pakistan and Afghanistan, more than double the number recorded – 33 – in 2018.
Some experts are strongly opposed to the idea of a reversal. Even those who think it may be inevitable speak frightfully.
"We certainly do not want to do that. This is really a big problem if we are to follow this path, "said Kimberly Thompson, a mathematical modeling whose calculations have helped the mapping strategy of the polio eradication campaign for nearly two decades.
Thompson and his group said that, in terms of the ability of the polio program to successfully cope with the transmission chains of type 2 vaccine viruses, things were not going in the right direction.
"We said … because I think that last year things did not go well for type 2 and that they needed a plan," she said. The response to this advice has been slower than Thompson thinks desirable. "It's hard to watch," she said.
"The longer we wait, the higher the risk," said Thompson, president of Kid Risk, a non-profit organization that conducts research on infectious diseases, including polio, measles and rubella. "It only grows with time."
TTo understand the problem, you need to know some basics about polio vaccines – especially the oral vaccine, called OPV.
OPV contains the live but debilitated viruses created by Albert Sabin in the late 1950s. It is the vaccine used in most developing countries, unlike the US, which uses IPV or inactivated polio vaccine .
The strengths of the Sabin vaccine are numerous. They include: its price of a few cents; its ease of administration; and the fact that vaccine viruses spread from vaccinated children to those around them, which means that vaccination campaigns protect far more children than those discovered by vaccination teams. Back in developing countries, if you vaccinate children in a neighborhood, you vaccinate the neighborhood pretty much.
But this last benefit, which was helpful when there were hundreds of thousands of polio cases a year, is now a mixed blessing. Once released into a community, Sabin vaccine viruses continue to spread if they encounter children who are not immune to polio. In places where sanitation and hygiene are poor, viruses enter water sources, contaminated hands or food and are then ingested by other children.
By switching from one cycle to the next, vaccination viruses can recover the virulence traits they have created by Sabin. If the vaccine viruses circulate long enough, they find the power to paralyze.
The part of the oral vaccine that protected against type 2 viruses was removed in the spring of 2016 during a synchronized movement around the world.
Since then, the number of children with no immunity against type 2 polio (and type 2 viruses) has increased every day. This cohort counts tens of millions.
In areas of the world where type 2 viruses do not spread, this lack of immunity does not matter. But in the countries of Central Africa, where the vaccine viruses spread over more and more vast territories, these unprotected children are exposed to a risk.
Children without any protection against type 2 poliomyelitis give the vaccine viruses the opportunity to circulate sufficiently to recover their paralytic power. Even children who have received IPV – countries have been urged to give one dose to each child before the change, but a worldwide shortage of IPV has prevented this effort – can be infected and spread the vaccination viruses. (The inactivated vaccine prevents paralysis but does not prevent infection.)
IIn the year of change, there were only two paralyzed children – one in Pakistan, one in Nigeria – with polio viruses derived from the type 2 vaccine. But the following year, their 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 of these countries except one – 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 is estimated that only 55% of children are immunized against type 2 poliomyelitis.
Whenever we discover that these vaccine viruses are circulating, the polio eradication campaign reacts in a way that may seem paradoxical: by sending health workers to the affected areas and giving to all children, they can find a specific oral vaccine that targets only type 2 viruses.
The idea is to quickly enter and vaccinate as widely as possible in order to deprive the virus of the virus of childhood vaccination. In other words, fight the fire with fire.
"You do not play," said Thompson. "You're going big enough so that you can really close it and do it as fast as you can."
This is the protocol, but the execution has sometimes been imperfect. In some cases, people were afraid to fight fire by fire. "There was a lot of reluctance to use type 2 OPV," explained Thompson.
Inadequate responses to epidemics left burning embers that then triggered new flames. The number of outbreaks involving type 2 vaccine viruses is increasing and these viruses are spreading – over vast areas. The Democratic Republic of Congo, the Central African Republic, Angola and Somalia reported having discovered a type 2 virus this year, either by isolating paralyzed children or by detecting it during the year. sewage monitoring for polio research.
A vaccine transmission chain discovered in Nigeria in 2018 illustrates the alarming potential of these vaccine viruses. Identified for the first time in the state of Jigawa, in the north of the country, viruses have spread to more than a dozen states of Nigeria as well as to Niger, where they have paralyzed at least six children, Cameroon, Benin and, more recently, Ghana.
In mid-August, it was confirmed that a young child from northeastern Ghana, near his border with Togo, had been paralyzed by vaccine viruses from the Jigawa chain of transmission. A few days earlier, type 2 viruses from this chain had been found in wastewater in Accra, the capital of Ghana, some 400 kilometers away.
Multiple vaccination campaigns with OPV type 2 will be organized to try to prevent the spread of the vaccine virus in Ghana, with over 2 million children being targeted by vaccination. This work started this week.
The problem, however, for the containment effort is children on the margins of these sweeps.
The use of oral vaccine type 2 to quell the spread of the virus type 2 vaccine seems to work where the vaccine is administered. But beyond a national or national border, unprotected children who are not included in the emergency response, but who are not immune to type 2 polio, reduce new wildfires as vaccination viruses spread. Children not immunized against type 2 polio in Togo, for example, may be exposed to the vaccine viruses disseminated during the Ghana campaign.
"We are getting to the point where you not only have to aggressively address a much larger population, because you have cohorts [of kids] which are much bigger as you go forward in time, but you also have this increased risk that the OPV itself can be transferred elsewhere … to start new chains of transmission, "said Thompson.
"It's polio. It behaves the same way, "she said of the vaccine viruses. "And if you keep supplying yourself with a little bit of vaccine every time you think you have a problem, you're just reseeding [more transmission chains]. This is not the way to do it.
WWhen the Type 2 component was removed from the oral vaccine, a special type 2 OPV stockpile was created to deal with the planned vaccine virus outbreaks. (They were also supposed to be extinct now, Thompson noted.)
This stock has been much less used than expected, leaving the polio program with difficult decisions to make.
Several OPV manufacturers, some of whom have indicated that they will exit the market in anticipation of the ultimate cessation of OPV use – which must be done in the context of eradication – consists of a bulk type 2 vaccine. . Zaffran, of WHO, has about a billion doses, and manufacturers, including Sanofi (SNY) Pasteur and Bio Farma, in Indonesia, have been invited to begin the process of converting part of this vaccine in bulk in vials can be bought and shipped.
As part of another initiative to ensure that the polio program contains enough vaccine to address the problem of type 2 vaccine, the WHO Advisory Committee on Vaccines, known as the name of SAGE – abbreviated Strategic Advisory Group on Immunization – will be invited to its next meeting in October, if it would be acceptable to vaccinate children with one drop of OPV2 vaccine instead of two. Halving the dose would dilute the reserves.
Improve the quality of immunization efforts – ensure that all eligible children are vaccinated against IPV through routine immunization and that emergency interventions with the help of OPV type 2 aimed at curbing vaccine virus outbreaks is effectively implemented – is also among the steps that can be taken for the experts say the risk of waiting while the polio program waits for the new vaccine
Dr. Stephen Cochi, Senior Advisor of the CDC's Global Immunization Program, said it would also help if WHO agreed to treat each type-2 virus discovery at the same level as Emergency Level 3, as would be the case. a discovery of wild poliovirus. Currently, they are considered a Level 2 event.
"They are given a lower designation and the countries – which is not unusual – sit on it. And they are slow to react, "said Cochi.
AAll are patches, however. Everyone hopes that the real cure will be the new oral vaccine.
The Gates Foundation spearheaded the development of an oral vaccine that does not have the Achilles heel of the Sabin vaccine. The goal – and the first tests look promising – is that the vaccine viruses are more stable, that they will not, or at least will not be less likely to regain the power to paralyze.
Two candidates are tested and the best will be developed. The plan is to use the vaccine in accordance with the WHO Emergency Use Protocol, even before it is authorized. It currently seems like it could happen in the middle of next year, by which time 100 million doses of the vaccine should be available. Bio Farma, which will produce the vaccine, will have the capacity to produce 35 million doses a month, said Cochi.
If the new oral vaccine is safer than Sabin's vaccine, it will be used to respond to outbreaks of type 2 virus, Zaffran said. And if a decision was finally made to reintroduce the oral vaccine type 2 in one region to address the problem of vaccine virus transmission, the new vaccine would also be the choice of this task, he said.
Dr. Jay Wenger, director of the Gates Foundation's polio program, said that it appeared that the new oral vaccine was likely to significantly reduce seed transmission chains – although the only way to know for sure will be to use the vaccine. The foundation strives to ensure that the vaccine enters the field as quickly as possible.
"We recognized that the sooner we have this new tool, the new OPV, the better we will be," said Wenger. "We are doing everything possible to make this happen as quickly as possible."
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