A health worker administers polio vaccine drops to a child at a school during a door-to-door polio vaccination campaign in Lahore, Pakistan on August 22, 2022.
AFP via Getty Images
August 31, 2022 2:12 PM EDT

The recent return of polio has hit like something of an epidemiological thunderclap. It was in 1979 that polio was officially declared eradicated in the U.S.—an early step in a multi-generational effort to wipe out the disease around the world. On July 21, however, the New York State Department of Health announced a case of polio in an unvaccinated man in Rockland County, and since then, circulating poliovirus has been found in wastewater there and in neighboring Orange County, as well as in New York City. In London, the virus was also found in wastewater in February, and in Jerusalem, a case of the disease turned up that same month.

The three cases, though seemingly isolated, point to a troubling trend—one that goes against more than three decades of progress in eradicating the disease. In 1988, polio was endemic in 125 countries and led to the death or paralysis of 350,000 people—mostly children—each year, according to the World Health Organization (WHO). But thanks to a massive vaccination push by the WHO, Rotary International, UNICEF, the U.S. Centers for Disease Control and Prevention (CDC), and more, polio is now endemic in just two countries—Afghanistan and Pakistan—which have seen only 18 cases between them so far this year.

Polio, however, is creeping back, and health officials are now on the alert for what Raul Andino-Pavlovsky, a professor of microbiology and immunology at the University of California, San Francisco, calls a “silent epidemic” of the disease around the world. “This is just the tip of the iceberg,” he warns.

Adds Yvonne Maldonado, a professor of global health and infectious disease at Stanford University School of Medicine, “The case we saw [in New York] was unusual but a red flag that we need to be on the lookout for potential outbreaks. We do run the risk of developing more cases of paralytic disease.”

The bad news is that polio is stalking us anew. The good news is that just in the past year, a new vaccine has been added to the arsenal of existing polio vaccines—one that, properly deployed, could halt a new global outbreak of polio before it can get started. No matter what, the reappearance of the disease has raised a host of challenges—all of which need to be met if we’re to keep polio contained.

What’s behind the current outbreak?

Multiple factors have played a role in the return of polio—not the least of which is complacency, especially in the U.S. and other developed countries. When a majority of people alive have never encountered a case of a given disease, it’s easy to put it out of mind. “People don’t remember polio, they don’t see it,” says Ian Lipkin, professor of epidemiology at Columbia University’s Mailman School of Public Health. “There’s something about our species that just allows us to forget about the importance of these things.”

That can lead to a slow erosion in vaccine compliance—something that the numbers bear out in the U.S. Nationwide, 92.6% of children are fully vaccinated against polio by age 2, according to the CDC. Broadly speaking, that’s an encouraging figure, but vaccination rates vary state to state and even county to county. In Oklahoma, for example, polio vaccination rates are just 79.5%, and in South Carolina, the figure is 80.3%. In the Rockland County zip code where the case of polio turned up in June, the vaccination rate stands at an alarmingly low 37.3%.

The COVID-19 pandemic has also played a role in the return of the disease. “During the COVID era, families didn’t see their doctors or pediatricians as frequently as they normally would,” says Dr. William Schaffner, professor of infectious diseases at Vanderbilt University School of Medicine in Nashville, Tenn. “That has resulted in children falling behind in their routine vaccination schedules.”

According to Maldonado, the fall-off has been minimal, with just a 1% decline in polio vaccination rates among children since the pandemic began. But when it comes to infectious diseases, even a single percent can matter a lot. “It translates to tens of thousands of kids who aren’t completely vaccinated,” Maldonado says, “and those children are at risk for diseases that really shouldn’t exist in well-resourced countries.”

Read More: Polio Is Back. Here’s How to Keep Yourself Safe

The vaccine paradox

The irony of polio’s comeback is that the very vaccination campaign the CDC estimates has prevented 16 million cases of paralysis and 1.5 million deaths since 1988 is also partly responsible for the new resurgence. There are two kinds of polio vaccines. The first, known as the inactivated polio vaccine (IPV)—administered by injection—uses a killed virus to familiarize the body with the disease and prime it to recognize and attack a live virus if it ever encounters it. The other, known as the oral polio vaccine (OPV)—administered by mouth—uses an attenuated, or weakened, virus that can do the same job of priming the immune system, without actually causing the disease. The advantage of the OPV is that it’s easier and cheaper to administer, which is why it’s used in global eradication campaigns. The big disadvantage is that on rare occasions, the weakened vaccine can revert to its virulent strain. That can potentially lead to the disease in the person who received the vaccine, and even if it doesn’t, the reinvigorated virus is shed in feces, entering wastewater and potentially infecting other people. For that reason, the U.S. switched to the IPV exclusively in 2000—even though cases of viral reversion were exceedingly rare.

“The crude estimate was one in 3 million doses of oral vaccine administered would lead to a case of polio in the U.S. before 2000,” Schaffner says. “It’s rare, but it’s not inconsequential.”

Indeed it’s not. Genetic sequencing revealed that the virus that caused the recent cases in New York and Jerusalem and was found in wastewater in London was so-called circulating vaccine-derived poliovirus (cVDPV). So far this year, cVDPV has led to 535 other cases of polio in 18 other countries, according to the Global Polio Eradication Initiative (GPEI).

But the IPV has its problems too—in addition to its comparative difficulty of administration. The OPV, since it’s taken orally, establishes what’s known as gut immunity. Assuming the person who receives the vaccine is not among the unlucky few in whom the virus reverts to its virulent form, there is no viral replication in the intestinal system and thus no virus shed in the feces. The IPV protects the recipient from ever contracting polio, but does not prevent intestinal replication and spread if that person ever picks up a cVDPV.

Andino-Pavlovsky believes that sampling wastewater in any part of the world where the IPV is used would likely turn up some circulating vaccine-derived poliovirus that IPV recipients contracted, replicated, and shed, endangering unvaccinated people. “In Europe, in America, in Australia—every place where people are using the inactivated vaccine—it is likely,” he says.

A new vaccine

Even with the drawbacks to both vaccines, getting vaccinated is obviously better than not getting vaccinated, since all vaccine recipients are protected against contracting symptomatic polio. But the OPV and IPV do exist in a state of tension, with one producing vaccine-derived virus and the other contributing to its spread. For that reason, the WHO and other global health organizations call for an eventual switchover to the IPV exclusively—a move that would mean there would be no vaccine-derived virus to be picked up and shed at all.

“We need to stop giving the live virus so it stops circulating,” says Maldonado.

That, however, is not practical at the moment—not while there are still millions of babies and children who need vaccines in the developing world, where the IPV remains too pricey and skilled vaccinators who can administer injections are in far shorter supply than field workers who require little special training to administer drops to the mouth. As a stopgap, the WHO, the Bill and Melinda Gates Foundation, and the U.K.’s National Institute for Biological Standards and Control have come together to develop a new oral vaccine that is far more stable than previous versions, reducing the likelihood of the attenuated virus used in the drops ever reverting to its virulent state.

Andino-Pavlovsky, who was part of the team that designed the vaccine, explains that it works by targeting the spot on the viral genome that is responsible for reversion to virulence. In existing OPVs, that part of the genome needs to go through just a single mutation to go from being harmless to dangerous.

“What we basically did was modify this sequence,” he says, “so a single point mutation cannot cause reversion; a virus now has to go through four or five different changes before acquiring a more virulent phenotype. Basically, it’s a numbers game.” As Andino-Pavlovsky earlier described it to the journal Nature, “It’s like putting the virus in an evolutionary cage.”

The vaccine that contains that caged virus went into use in March 2021 and so far, 450 million doses have been administered in 22 countries. “The new vaccine is as effective as the previous one in generating immunity,” says Andino-Pavlovsky, “[and is] able to stop the silent epidemic.”

The goal, ultimately, is to drive polio over the cliff to extinction—as smallpox was in 1980—with a slow phase-out of all OPV, universal use of IPV, and the eradication of any form of poliovirus circulating anywhere in the world. The current return of the disease is a reminder that that job is not nearly done. Until it is, an old scourge will haunt us anew.

Correction: The original version of this story misstated the introduction date and distribution of the new polio vaccine. Rollout of the vaccine began in March 2021, not the end of 2021; and 450 million doses have been administered in 22 countries, not 180 million doses in 13 countries.

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Write to Jeffrey Kluger at jeffrey.kluger@time.com.

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