In September 2022, Gov. Kathy Hochul of New York declared a state of emergency for poliomyelitis. This is just the tip of the iceberg of a significant public health emergency. Polio still represents a threat to us all. And it's not just the United States that's experiencing a resurgence. There are also cases in London and Jerusalem, as well as in many other countries around the world.
It's been 34 years since the World Health Organization (WHO) launched the Global Polio Eradication Initiative (GPEI) with the ambitious aim of eradicating polio by the year 2000. "The chosen strategy was to stop circulation of wild polioviruses, following the successful example of smallpox eradication. The task, however, turned out to be much more challenging than eradicating smallpox had been, since there are hundreds of asymptomatic poliovirus infections for each paralytic case that occurs, which substantially complicates critical surveillance," wrote researchers Konstantin Chumakov, PhD, DSci; Christian Brechot, MD, PhD; Robert C. Gallo, MD; and Stanley Plotkin, MD, in a fascinating perspective article recently published in The New England Journal of Medicine (NEJM).
Salk and Sabin
The search for vaccines to fight poliomyelitis started in the 1920s, but it wasn't until the 1950s that the search bore fruit with the introduction of two vaccines. The first was the Salk inactivated polio vaccine (IPV), which was developed in 1955. This vaccine, which is still in use today in Italy as part of the six-in-one vaccine, induces humoral immunity but doesn't induce sufficient immunity of the intestinal mucosa (the tissue that is usually infected by the poliovirus). This vaccine protects individuals from the most severe symptoms of the disease, such as paralysis, but doesn't confer immunity from contracting the virus, thus enabling its continued circulation.
The second vaccine was Sabin's live attenuated oral polio vaccine (OPV), which was developed in 1959. Unlike IPV, OPV induces both humoral and mucosal immunity, thus conferring protection against contracting the virus. OPV promotes herd immunity by stopping the virus from spreading.
"We're nearing the end of a long haul which has seen the involvement of the scientific community, a variety of world leaders and their citizens, all focused on achieving a single objective: eliminating the three strains of polio as much as is possible. Yet in current conditions, achieving eradication, especially in the short term, I would say is not a given," commented Agnese Collino, PhD, biologist, popularizer, and scientific supervisor at the Umberto Veronesi Foundation. Collino also wrote the book La malattia da 10 centesimi: Storia della polio e di come ha cambiato la nostra società (The 10-Cent Disease: The History of Polio and How It Changed Our Society).
"The OPV had significant advantages over the IPV, being both cheaper and easier to administer, as it doesn't require syringes or specialized staff," Collino continued. "It's the only vaccine capable of bringing us close to eradicating the virus. Therefore, initially, it replaced the IPV vaccine in nearly all countries. So, what's the issue with this vaccine? Being a live virus, it replicates in gut-associated tissues of the vaccinated person for a small period. If, unfortunately, in the few replications that this virus makes, it accumulates mutations that give it back its original aggressiveness, we could end up with a virus that is as aggressive as wild poliomyelitis. This is a very rare side effect — around one case in every 4 or 5 million doses administered — but it obviously requires a reassessment of the risk-benefit ratio in countries that have already eliminated the disease."
And this is indeed what is happening in most countries using the Salk vaccine, while the only countries to still have endemic polio — Afghanistan and Pakistan — continue to use the OPV vaccine to try to eliminate wild poliovirus. "The problem," said Collino, "is that obviously in the countries using OPV and not achieving sufficient immunization coverage, outbreaks of vaccine-derived poliovirus cases emerge, which can spread to other countries. So, we're in the paradoxical situation in which we need to eliminate a wild virus with a vaccine, which in turn may circulate a version of the same virus in that environment (circulating vaccine-derived poliovirus)."
Long-Term Immunization Policies
In the article published in the NEJM, the authors emphasized that the focus must switch from eradication of the polioviruses — which is proving to be hard to achieve — to the development of new long-term immunization policies that will not only protect patients from paralytic disease, but also minimize the silent circulation of polioviruses.
"The current plan is to withdraw bivalent OPV within 3 years after the circulation of wild type 1 poliovirus is stopped, and then continue immunizations with IPV only," they wrote. "The decision to withdraw OPV should be made not on the basis of the perceived absence of poliovirus circulation, but rather on the basis of availability of ample supply of IPV and the readiness of vaccine-delivery infrastructure." According to the recommendation of the WHO Strategic Advisory Group of Experts on Immunization, the IPV-only phase should continue for 10 years after the withdrawal of OPV, at which time the question of whether polio immunization may become optional can be discussed.
"I find that, lately, in medical and public debate, we're talking very little about one key aspect," said Collino, "and this is the fact that it's very difficult to be certain that we can achieve total eradication of polio, especially in the short term, if most of the world uses the IPV vaccine. Without scrupulous sampling of wastewater — sadly not done everywhere — we cannot know with absolute certainty in which countries polio is still circulating, untraced in asymptomatic people, also because of IPV's ability to prevent the only distinctive symptoms of the disease."
Which Way Forward?
According to the authors of the NEJM article, there are two big limitations in the current strategy of focusing on polio eradication. First, setting a time horizon for the elimination of polio vaccines discourages manufacturers from investing in research and development of better vaccines. Second, cessation of polio vaccination sends a wrong signal to the public that vaccination against polio is not needed if there is no detected virus circulation. This signal contributes to vaccine hesitancy and immunity gaps.
"I'm more optimistic regarding the goal of eradication," said Collino. "The same authors cite the development of a new version of the Sabin vaccine for the type 2 strain of the poliovirus, which has been modified to have more mutations. The presence of more mutations in this attenuated virus is what lowers the chances of the vaccine-derived virus from gaining ground (ie, managing to regain aggressiveness by replicating itself in the mucosa). In 2 or 3 years, we could have a novel OPV comprising all three strains. I think we need to collectively discuss the possibility that these new vaccines, which would have the advantages of the oral vaccine without the risk of serious events like vaccine-derived polio, could help end the fight against polio once and for all.
"I agree with the authors in their belief that our strategy should be reassessed against the initial objective of the GPEI," added Collino, "but the prospect of having to shelve eradication in favor of lifetime vaccinations against polio, after all of the efforts made over the past 70 years, seems, on the one hand, sad — although not far-fetched — and, on the other, not yet a necessity in light of new vaccine tools. Personally, I would assess what the global role of the novel OPV could be: no longer an emergency tool only to be used in at-risk regions where outbreaks of vaccine-derived polio cases emerge, but as a possible alternative vaccine to the IPV. Obviously, with a gradual switch from one vaccine to the other."
This article was translated from Univadis Italy.
Lead image: AHMAD AL-BASHA/AFP via Getty Images
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Cite this: Is Our Polio Vaccine Strategy Mistaken? - Medscape - Mar 14, 2023.