The global endgame for polio has long been eradication, but recent events worldwide have raised questions about whether that goal can be achieved, experts say, warning that to protect the international population from paralysis caused by vaccine-derived polioviruses, immunisation must continue indefinitely.
In 1988, the World Health Organisation (WHO) adopted a resolution for global eradication of poliomyelitis, the disease caused by both wild type and, rarely, vaccine-derived poliovirus (VDPV). The goal was to do so by 2000, and early reports from the US Centres for Disease Control & Prevention (CDC) suggested that public health workers were making progress. Globally, the number of reported cases of poliomyelitis dropped by 70% from 1988 to 1993. Driving the success was the oral poliovirus vaccine (OPV).
Yet, 22 years after that target date, poliovirus is still appearing in global communities. In July, the CDC confirmed a case of polio paralysis in an unvaccinated man in New York. There have also been several instances of detection of VDPV in wastewater in New York and Britain.
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 certified as polio-free in 2020.
This global resurgence has experts grappling with a new reality, one where countries worldwide must maintain high vaccination rates and hope that VDPV does not result in the rare case of paralysis, says Vincent Racaniello, PhD, a virologist at Columbia University, New York City.
“We can eradicate polio as long as we keep immunising, and achieve greater than 90% immunisation rates," he told MedPage Today.
“The original goal of eradication was linked to cessation of polio vaccination. However, while strains of the virus circulate in any country, it is not possible to stop immunising.”
Oral polio vaccine paradox
Paradoxically, eradication has remained out of reach for the same reason poliomyelitis rates have decreased – because of OPV.
“I doubt 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 unvaccinated people.”
While OPV was pivotal in the early efforts to eliminate poliomyelitis, it has now become one of the primary reasons why experts like Racaniello say vaccination efforts against polio can’t be eased. OPV contains a live, attenuated poliovirus designed to live harmlessly in the intestinal tract, but this strain can mutate and revert to a version of the virus (VDPV) that can cause poliomyelitis in unvaccinated individuals.
While this mutation occurs as rarely as once in 3m cases, it presents enough of a risk that vaccination can never be eased while it is in use.
This OPV paradox is one reason America has exclusively used the injectable poliovirus vaccine (IPV) since 2000, which only contains the inactivated poliovirus. Concern over the limitations of OPV has led many experts, including those at the WHO, to recommend a switch to IPV globally.
“The US 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 increased, but sterile needles would need to be supplied as well as trained healthcare workers to use them. I believe WHO would like to globally switch to IPV after 2026.”
The turn to IPV has not been a panacea for poliovirus in the US, though. IPV consists 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 vaccinated with IPV, the vaccine doesn’t prevent further transmission of the poliovirus, says the CDC.
This means even after a global switch to IPV, poliovirus will still be capable of circulating through the global population, posing a threat of paralysis to unvaccinated people.
This is one reason the CDC also said that immunisation efforts must remain core in efforts to eradicate poliovirus despite several challenges, including low rates of vaccine compliance, difficulty reaching certain communities, geopolitical instability, supply-chain issues, and more recently the COVID-19 pandemic.
“It important to note the number of polio cases has been reduced by 99.9% in the past three decades,” a CDC spokesperson said.
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 this fight.
New tool to fight poliovirus
The CDC spokesperson said global immunisation campaigns are still "the most effective way to end outbreaks and prevent the emergence of new ones”.
The agency has been monitoring a new tool with the potential to untangle the OPV paradox – the novel OPV2 vaccine (nOPV2), designed as more genetically stable than previous versions of OPV and ideally resistant to reverting to the more transmissible, dangerous VDPV.
This latest version in a series of updates to the OPV vaccine 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 an emergency use listing in response to outbreaks in 2021. This novel vaccine demonstrated immunisation efficacy without leading to mutations that might result in circulating VDPV.
“Based on promising results from clinical trials of nOPV2 and initial use, it 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-immunised communities,” the CDC spokesperson said.
More than 100m doses of nOPV2 have already been administered globally, with early data suggesting it is genetically stable in real-world settings, and therefore might be the solution to limiting much of the global VDPV transmission.
“Now, six 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.
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 US from poliomyelitis completely, Racaniello said. “Currently, many people in America are probably infected with poliovirus, but they have no signs of disease. We can keep immunising with IPV and as long as more than than 90% of the country is immunised, we will not have polio the disease, but the virus will still be here.”
The CDC maintains ongoing immunisation campaigns will continue, and the WHO has begun to push for use of IPV in more counties, but still, he says, even global adoption of IPV would not necessarily lead to the eradication of poliovirus because people immunised with IPV could still spread VDPV. Even with worldwide use of IPV, “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, and a reassessment of the programme’s current strategy, with a new design.
Eradicating poliovirus is not the language used by global health leaders. The focus is on containing the poliovirus to prevent the occurrence of paralysis. Racaniello said the reason for this change is the realisation 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. We will have simply replaced wild polioviruses with vaccine-derived polioviruses. To protect the world’s population against paralysis caused by vaccine-derived polioviruses, immunisation must continue indefinitely.”
MedPage Today – Experts grapple with new reality: polio may never be eradicated (Open access)
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Malawi declares outbreak following Africa’s first wild polio case in five years