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The global endgame for polio has long been eradication, but recent events in the U.S. and around the world have raised questions about whether that lofty goal can be achieved, poliovirus experts say.

In 1988, the World Health Organization (WHO) for global eradication of poliomyelitis, the disease caused by both wild type and, in rare cases, vaccine-derived poliovirus (VDPV). The goal was to do so by 2000, and from the CDC suggested that public health workers were making quick progress. Globally, the number of reported cases of poliomyelitis dropped by 70% from 1988 through 1993 -- and the driving force of success was the oral poliovirus vaccine (OPV).

Yet, 22 years after that target date, poliovirus is still showing up in communities around the world. In July, a well-documented case of polio paralysis in an unvaccinated man in New York state. There have also been of VDPV in wastewater in New York and the U.K.

And wild poliovirus -- once thought to be isolated in Pakistan and Afghanistan -- was detected in Mozambique and Malawi earlier this year, two countries in a global region that was as recently as 2020.

This global resurgence has experts grappling with a new reality, one where countries all over the world must maintain high rates of vaccination and hope that VDPV does not result in the rare case of paralysis, according to Vincent Racaniello, PhD, a virologist at Columbia University in New York City.

"We can eradicate polio, the disease, as long as we keep immunizing, and achieve greater than 90% immunization rates," Racaniello told 麻豆传媒. "Note that the original goal of eradicating polio was linked to cessation of polio vaccination. However, as long as strains of poliovirus circulate in any country, it is not possible to stop immunizing."

Oral Polio Vaccine Paradox

Paradoxically, eradication has remained out of reach for the same reason that rates of poliomyelitis have decreased -- because of OPV.

"I doubt that poliovirus can be eradicated," Racaniello said. "As long as we keep using OPV in some countries, OPV-derived viruses will continue to circulate and pose a threat to any unvaccinated people."

While OPV was pivotal in the early efforts to eliminate poliomyelitis, it has now become one of the primary reasons experts like Racaniello say vaccination efforts against polio can't be eased. OPV contains a live, attenuated poliovirus that is designed to live harmlessly in a person's intestinal tract, but this strain can mutate and revert to a version of the virus (VDPV) that can cause poliomyelitis in individuals who are not vaccinated. While this mutation occurs as rarely as once in approximately 3 million cases, it presents enough of a risk that polio vaccination can never be eased while it is in use.

This is one reason that the U.S. has exclusively used the injectable poliovirus vaccine (IPV) since 2000, which only contains the inactivated poliovirus. Concern over the limitations of OPV have led many experts, including those at the WHO, to recommend a switch to IPV globally.

"The U.S. would certainly be able to help expand the use of IPV globally," Racaniello said. "It is not easy. Not only would production need to be ramped up, but sterile needles would need to be supplied as well as trained healthcare workers to use them. It is my understanding that WHO would like to globally switch to IPV after 2026."

The turn to IPV has not been a panacea for poliovirus in the U.S., though. IPV is made up of three poliovirus serotypes. It provides protection against paralysis in individuals, but it does not prevent infection in the intestines. While any infection would be harmless to someone who's been vaccinated with IPV, the vaccine doesn't prevent further transmission of the poliovirus, according to the CDC.

This means that even after a global switch to IPV, poliovirus will still be capable of circulating through the global population, which will pose a threat of paralysis to unvaccinated individuals.

This is one reason that the CDC also said that immunization efforts must remain the core tool in the push to limit and eradicate poliovirus despite several challenges to those efforts, including low rates of vaccine compliance, difficulty reaching certain communities, geopolitical instability, supply-chain issues, and more recently the COVID-19 pandemic.

"Although challenges remain, it is important to emphasize that the number of polio cases has been reduced by 99.9% in the last three decades thanks to the commitment of frontline staff, affected communities, governments, donors, and partners," a CDC spokesperson told 麻豆传媒.

Regardless of which vaccine is used, the primary dilemma is still the ability of poliovirus to continue circulating -- but there is a new potential weapon in the this fight to eliminate poliovirus.

A New Tool to Fight Poliovirus

The CDC spokesperson said global immunization campaigns are still "the most effective way to end outbreaks and prevent the emergence of new ones within a community or across borders. When high-quality immunization campaigns and surveillance are coupled with strong government, civil society, and community commitment, we can eradicate polio."

To that end, the agency has been monitoring a new tool that has the potential to untangle the OPV paradox -- , which was designed to be more genetically stable than previous versions of OPV and ideally resistant to reverting to the more transmissible and dangerous VDPV.

It's the latest version in a series of updates to the OPV vaccine that includes the type-2 version of OPV, which the CDC reported was responsible for "approximately 90% of all cVDPV [circulating vaccine-derived poliovirus] outbreaks."

In November 2020, the WHO granted nOPV2 to be used in response to outbreaks in 2021. According to the CDC, this novel vaccine demonstrated immunization efficacy without leading to mutations that might result in circulating VDPV.

"Based on promising results from clinical trials of nOPV2 and the initial use in the field, the vaccine should prove as immunogenic and more genetically stable than mOPV2 [type-2 monovalent OPV], and therefore be less likely to result in new emergence of variant type-2 polioviruses in under-immunized communities," the CDC spokesperson said.

According to the CDC, over 100 millions doses of nOPV2 have already been administered globally. The CDC also noted that early data suggest that nOPV2 is indeed genetically stable in real-world settings, and therefore might be the solution to limiting much of the VDPV transmission seen around the world.

"At this point, 6 years after the OPV switch to remove Sabin-strain poliovirus type 2, use of nOPV2 is essential to stopping all transmission of vaccine-derived poliovirus type 2 as well as strengthening the effectiveness of nOPV2 campaigns," the CDC spokesperson said.

But experts warn that production and manufacturing challenges have been a hindrance to global vaccination programs, even before the approval of a novel vaccine that can help limit the circulation of VDPV. (See this sidebar on supply-side challenges.)

Polio Endgame Interrupted

Given the nature of earlier vaccines and the evolution of VDPV, global eradication of poliovirus has been challenged from the start. Even the consistent use of IPV for 22 years has not protected the U.S. from poliomyelitis completely, Racaniello said.

"Currently, many people in the U.S. are likely infected with poliovirus, but they have no signs of disease," he said. "We can keep immunizing with IPV and as long as greater than 90% of the U.S. is immunized, we will not have polio the disease, but the virus will still be here."

The CDC maintains that ongoing immunization campaigns will continue to protect the U.S. from outbreaks, and the WHO has begun to push for use of IPV in more counties, according to Racaniello.

Still, he noted that even global adoption of IPV would not necessarily lead to the eradication of poliovirus because people immunized with IPV could still spread VDPV. Even with worldwide use of IPV, Racaniello said, "no one can predict whether these viruses would circulate indefinitely or not."

The inability of current vaccines to eradicate the virus has led the public health community to start considering a new endgame. A in The Lancet noted that the "recent surge of polio cases urgently calls for a reassessment of the programme's current strategy and a new design for the way forward."

The authors proposed a plan of "sustainable protection" that focuses on "maintaining high rates of population immunity indefinitely."

This article echoes the language that appears in a on the 2018 status of poliomyelitis and the poliovirus, which called for awareness of "the urgent need to accelerate globally activities to implement and certify containment of polioviruses" and to focus on the containment of all polioviruses to "ensure the long-term sustainability of the eradication of poliomyelitis."

Eradicating poliovirus is not the language used by global health leaders. The focus is on containing the poliovirus to prevent the occurrence of paralysis. As Racaniello noted, the reason for this change is the realization that past public health efforts overestimated the ability of both IPV and OPV to achieve eradication.

"Even if all three wild poliovirus serotypes are eradicated, we will still have circulation of vaccine-derived strains of poliovirus in humans," Racaniello said. "We will have simply replaced wild polioviruses with vaccine-derived polioviruses. Therefore, to protect the world's population against paralysis caused by vaccine-derived polioviruses, immunization must continue indefinitely."

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