Why We Can’t Eradicate Poliovirus

by Gertrud U. Rey

Child in Papua New Guinea receiving OPV. Credit: WHO

In 1988 the World Health Organization, Rotary International, UNICEF, and the U.S. Centers for Disease Control and Prevention passed the initiative to eradicate polio globally by the year 2000. We are now 23 years past this deadline, and it is increasingly clear that this goal will likely never be achieved.

Smallpox remains the only major infectious disease of humans that has been eradicated so far. According to the epidemiologist Donald Henderson, who played a key role in the process, three essential criteria need to be met to eradicate a pathogen: 1) it may only replicate in one host (e.g., humans only), 2) vaccination must induce lifelong immunity; and 3) asymptomatic infections should not contribute to the spread of the pathogen. The causative agent of smallpox – variola virus – fit all three of these criteria. An additional feature that simplified the eradication of smallpox was the fact that there is only one serotype of variola virus. In contrast, there are three serotypes of poliovirus, and immunity induced by infection or immunization with one serotype does not protect against the other two.

Poliovirus is transmitted through contact with stool or respiratory droplets from an infected person. A prime opportunity for transmission occurs during the consumption of food prepared by someone who did not wash their hands properly after using the toilet. After the viral particles are ingested, they replicate in the intestines and new viral particles are shed in the feces, leading to a possible new cycle of transmission. Although most infected people never develop symptoms, about 1% of infections lead to paralysis, which can affect mobility and is fatal if it progresses to the respiratory muscles.

There are two types of polio vaccines currently in use across the globe, both of which historically protected against all three serotypes. Inactivated polio vaccine (IPV), developed by Jonas Salk in 1953, is an inactivated virus that is injected into the muscle. This vaccine induces only systemic immunity but no gut immunity because it never reaches the intestines. This means that despite being well-protected against disease and paralysis, an IPV recipient who is naturally infected with “wild-type” poliovirus may replicate the virus in the intestines and pass it in their feces. This phenomenon is well documented in countries that use IPV and monitor their wastewater for poliovirus; and because IPV is the only polio vaccine currently used in the U.S., it is very likely that our sewers and environment are also teeming with poliovirus.

Oral polio vaccine (OPV), developed by Albert Sabin in 1961, is an attenuated virus that is administered by ingestion. Once the vaccine particles reach the intestines, they replicate and induce production of local antibodies that ultimately eliminate the virus. However, OPV also concurrently enters the bloodstream, so the vaccine induces production of antibodies in the blood as well, and thus leads to both gut and systemic immunity. OPV is used primarily in developing countries because it is cost-effective, easy to administer, and does not require cold storage.

Although OPV appears to be the better vaccine based on this information, its ability to replicate leads to some major complications. After OPV viruses have undergone a few cycles of replication, the attenuating mutations in the viral genome that prevent disease revert to their original wild-type sequence and the viruses re-attain the ability to cause paralysis. The presence of these “vaccine-derived viruses” in the environment is particularly problematic in under-immunized populations, where the viruses circulate and cause outbreaks identical to those caused by wild-type poliovirus. In rare cases, the attenuated vaccine virus itself may even cause paralysis in the vaccine recipient. Because most vaccine-derived outbreaks have been caused by OPV serotype 2 and because the wild-type version of this virus was eradicated in 2015, serotype 2 was removed from all OPV formulations in 2016. Despite this intervention, vaccine-derived type 2 polioviruses have continued to circulate extensively and have caused numerous cases of paralytic polio. One such incident happened right here in the U.S. when, in July 2022, an unvaccinated, previously healthy young adult developed poliovirus-induced paralysis.

In an effort to address the reversion problem, the Bill and Melinda Gates Foundation recently funded a new type 2 OPV (nOPV2) that contains three modifications, which presumably reduce its ability to revert in the intestine. Data collected after administration of 600 million doses of nOPV2 over the course of two years suggest that although this vaccine reverts substantially less often than Sabin’s original vaccine, nOPV2 is not perfect, and it has led to several revertants that caused paralysis. 

There appears to be no practical way to eradicate poliovirus completely. In fact, poliovirus only meets one of Henderson’s three criteria – that is, to our knowledge the three serotypes only infect humans. In all likelihood, not meeting the other two criteria will interfere with eradication. Although many people assume that the immunity induced by poliovirus infection and/or vaccination is lifelong, it’s actually not clear whether that is the case. And most importantly, the vast majority of poliovirus infections do not produce symptoms, leading to extensive undetected spread.

The most logical way forward is to continue routine childhood vaccinations against poliovirus indefinitely – and preferably with IPV.  

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