Choosing the Right Path toward Polio Eradication
List of authors.
- Konstantin Chumakov, Ph.D., D.Sci.,
- Christian Brechot, M.D., Ph.D.,
- Robert C. Gallo, M.D.,
- and Stanley Plotkin, M.D.
The recent declaration of a public health emergency in New York State after a case of paralytic poliomyelitis caused by a circulating vaccine-derived poliovirus (cVDPV), along with cVDPV detection in wastewater both in New York and in London, is a sobering reminder that polio still represents a threat even in countries that have not seen it for decades.1 Silent circulation of poliovirus was not unexpected: such circulation was previously observed in countries using inactivated polio vaccine (IPV). Unlike oral polio vaccine (OPV), IPV does not induce the robust mucosal immunity that is important for preventing circulation. The continued circulation of wild and attenuated polioviruses suggests that the approach used by the polio-eradication campaign needs reevaluation.
The Global Polio Eradication Initiative (GPEI), launched 34 years ago, aimed to eradicate poliomyelitis by 2000.2 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. Aside from challenges inherent in vaccine delivery in some countries, another reason for the failure to eradicate polio were outbreaks caused by cVDPV strains that emerged from viruses used in OPV.3 Thus, to actually eradicate poliovirus, the use of OPV must also be stopped.
The conundrum was how to withdraw OPV that was essential to eradication efforts without jeopardizing their success. Stopping all immunizations after the disease is eradicated, as was done with smallpox, is a nonstarter because it’s impossible to ensure that no live virus remains loose anywhere in the world, and polio can easily be synthesized in laboratories. The absence of virus circulation and paralytic cases cannot be sustained without universal and comprehensive population immunity. The lack of immunity would result in global vulnerability, and reintroduction of the virus could start a pandemic with potentially catastrophic consequences. A preview of this scenario was provided by the 2016 switch from trivalent to bivalent OPV that omitted the serotype 2 OPV (OPV2) component4; this move created immunity gaps that led to the dramatic proliferation of mutated type 2 viruses. In contrast to what modeling had predicted, the targeted use of monovalent OPV2 to control outbreaks only seeded additional ones, creating a Catch-22.
Fortunately, the visionary thinking of some scientists as well as public health experts at the Bill and Melinda Gates Foundation and the World Health Organization (WHO) resulted in concerted efforts to develop a more genetically stable strain of vaccine poliovirus. The resulting novel OPV2 was introduced for outbreak control in 2020 and was found to be more stable than the original serotype 2 Sabin strain.5 More than 500 million doses have been distributed, and the vaccine has seeded no cVDPV outbreaks. Similar genetically stable strains of serotypes 1 and 3 were created and are undergoing clinical evaluation.
This important development fostered hope that cVDPV outbreaks that occur primarily in Africa and south central Asia might soon be controlled. But the New York case and the discovery of the silent circulation of poliovirus in high-income countries that use IPV demand reassessment of our approach to polio eradication. Although IPV provides excellent protection against paralytic disease, it does not prevent silent circulation of the virus that can eventually infect unimmunized and immunocompromised people. We need to develop new long-term immunization policies that will not only protect vaccinees from paralytic disease but also minimize 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. Unlike the 2016 switch from trivalent to bivalent vaccine, 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. This plan may be the biggest flaw in the current strategy, because it is imperative to maintain the highest possible population immunity level indefinitely. Putting off the decision until the distant future sends a number of wrong messages.
First, setting a time horizon for the elimination of polio vaccines discourages manufacturers from investing in research and development of better vaccines. There are several options for such vaccines. Genetically stable novel OPV might be the best solution for countries with high poliovirus transmission. Inexpensive and easy to deliver, it would create comprehensive immunity that would protect people from paralysis and minimize virus circulation without triggering cVDPV outbreaks. Highly effective combination vaccines such as hexavalent vaccines containing IPV along with diphtheria–tetanus–pertussis, Hemophilus influenzae type b, and hepatitis B antigens could be most useful for high- and middle-income countries. In addition, there are several innovative polio vaccines in development — for example, some based on virus-like particles, mucosal vectored vaccines, and RNA vaccines. But unless a clear signal is sent to vaccine manufacturers, these innovative products will never reach the market.
Second, cessation of polio vaccination sends a wrong signal to the general public that vaccination against polio is not needed if there is no detected virus circulation, thereby contributing to vaccine hesitancy and immunity gaps.
There are serious scientific questions that must be addressed if we are to formulate future immunization policies tailored to different parts of the world. High-income countries will most likely continue using IPV-containing combination vaccines, but is there also a role for novel OPV to close the gaps in mucosal immunity and stop silent virus circulation? What is the best policy for middle- and low-income countries, and how can a sustainable scheme for supporting the vaccination programs in resource-limited countries be created?
All these policy decisions must be based on solid science. In the past, the GPEI’s strategic thinking was guided by a scientific advisory committee, but that committee was disbanded years ago, in part because of the perception that science was no longer needed because eradication was just around the corner. This wishful thinking has prevailed for the past 30 years and has proven counterproductive.
The original 1988 World Health Assembly declaration called for eradication of poliomyelitis, emphasizing that “eradication efforts should be pursued in ways which strengthen the development of the Expanded Programme on Immunization as a whole, fostering its contribution, in turn, to the development of the health infrastructure and of primary health care.”2 We believe the GPEI should revert to the declaration’s original intent of eradicating the disease by creating universal immunity to polio rather than continue pursuing viral eradication that has been unsuccessful. It is important to engage the entire scientific and public health communities in developing a rational and sustainable future polio-immunization strategy. We urge the WHO and all their partners, including Rotary International and the Bill and Melinda Gates Foundation, to initiate an open dialogue with scientists about the strategy for preventing polio.