It was not long before cracks of discord began to appear. As the pandemic coronavirus swept across continents, it also sowed division among the ranks of experts tasked with fighting it. At the heart of COVID-19 battle plans was a dilemma familiar to humanity’s age-old struggle with disease-causing organisms: should we get rid of the virus completely, or should we suppress and learn to manage with it?

Credit: Wenmei Zhou / Getty

Most scientists have by now conceded that SARS-CoV-2 is here to stay. But as China still hangs on to a ‘zero-COVID’ policy that others abandoned long ago, it is keeping the long-standing debate alive.

A boy receives the oral polio vaccine in Karachi, Pakistan. Credit: Akhtar Soomro / Reuters / Alamy Stock Photo.

“It is not possible to eliminate SARS-CoV-2,” insists Marcel Tanner, president of the Swiss Academy of Sciences and Director Emeritus of the Swiss Tropical and Public Health Institute, who led Switzerland’s now-dissolved COVID-19 Science Task Force. “It’s no longer the time to think of zero COVID, even if you sit on an island.”

Cases of paralytic polio and Guinea worm disease have steadily decreased in past decades, but malaria continues to cause hundreds of thousands of deaths annually. Source: Our World in Data.

Key to making this kind of judgment, says Tanner, is understanding what eliminating a virus means and when it truly has a chance of working.

Decisions about whether and how to wipe out an infectious disease can be controversial, weighed up on fine lines in terminology and risk–benefit calculations. A basic distinction between elimination and eradication often gets lost, which causes confusion. Most experts agree that to eradicate means to make sure no cases of an infection are seen anywhere in the world, a goal that hinges on interrupting transmission permanently; to eliminate is to do this in a specific geographic area, usually a country. Depending on your source, the terms might apply to pathogens rather than diseases. Gray areas in definitions hardly help when disputes flare up.

But the prospect of a triumph by humanity over disease holds a simple allure. Smallpox is the only human disease to have ever been eradicated, and dominance over a virus that killed 300 million people worldwide in the twentieth century continues to inspire campaigns to vanquish dangerous pathogens. Yet the world is a very different place in the twenty-first century.

Polio’s last mile

“Commitments have been made to deliver a polio-free world,” says Fiona Braka, team lead of emergency operations at the World Health Organization (WHO) Africa office, who spent nearly 20 years working in immunization and polio-eradication programs. “I do not think that anyone would like to drop the ball at the last mile.”

The world set its sights on wiping out the three serotypes of poliovirus nearly 35 years ago. Thanks to this ambitious target, 18 million children have been saved from paralysis since the start of the Global Polio Eradication Initiative (GPEI), and the number of poliomyelitis cases has plunged by 99%. But getting to zero — the so-called ‘last mile’ — is notoriously difficult, beset by setbacks.

In February 2022, Malawi reported its first case of wild poliovirus in three decades. The discovery came less than 2 years after the WHO declared Africa polio-free: no cases of infection with wild poliovirus had been picked up anywhere on the continent since 2016. Announced in August 2020, Africa’s triumph over polio was a welcome respite from a COVID-19 pandemic in full swing, and was a feat worth celebrating for a long global campaign tantalizingly close to the finish line. But victory was short-lived. The case of paralysis in a girl in Lilongwe, the capital of Malawi, was traced back to a wild poliovirus strain last seen in Pakistan in 2019, but no one knows how the virus traveled to southeastern Africa.

Then, 3 months later, a similar strain was linked to a case of wild polio in Mozambique — another country that has not seen a case in three decades. Malawi and neighboring countries, including Mozambique, moved swiftly to launch mass vaccination and boost surveillance, in a bid to keep their polio-free status.

“The Malawi outbreak shouldn't by itself throw the whole baby of eradication [out] with the bathwater,” says Muhammad Ali Paté, a medical doctor who leads health programs at the World Bank, a former health minister of Nigeria and a member of the GPEI’s independent monitoring board. But beyond polio, he believes an eradication push would now be a hard sell, even when it is biologically feasible. “You saw what happened with COVID-19 vaccines, where the global consensus was just not there even for a disease that was ravaging the world in the form of a pandemic,” says Paté. “Even the best idea would be difficult to have traction given the direction that the world is in.”

Mastering the endgame

The pandemic has undermined basic health services as much as it has global solidarity. Of the diseases considered to be eradicable, polio and Guinea worm are the only official targets of ongoing campaigns, and they have edged close to their goal. But programs that support eradication screeched to a halt as the world threw all its resources at COVID-19, rolling out lockdowns and suspending or delaying routine healthcare. These disruptions have had a major impact on the ‘endgame’ for eradication campaigns, where narrow margins separate success from failure.

Unlike polio, there is no vaccine against Guinea worm disease (also known as dracunculiasis), and there is no effective treatment. Its eradication relies on public health measures to stop transmission through contaminated water, and the campaign has made astonishing gains. Just 15 human cases of the disease were reported from four countries in 2021, a 99% drop from the mid-1980s, when 3.5 million cases were reported each year from 21 countries. But the discovery of Guinea worm infections in dogs, first reported in Chad in 2012, was a turning point in the wrong direction that pushed back the eradication target by a decade. There are now more animal infections than human infections, so eradicating every last Guinea worm means keeping dogs and other animals away from discarded, and potentially infected, fish, such as by encouraging people to bury fish entrails.

The challenges of eradicating polio are different from those for Guinea worm and instead revolve around vaccine-derived poliovirus. This happens when the live virus used in the oral vaccine mutates to recover its neurovirulence, which allows the virus to enter the central nervous system and cause paralysis. Outbreaks of vaccine-derived polio are helped by the immunization gaps that grew with pandemic disruptions. Confined to Africa until recently, vaccine-derived polio has now cropped up in Israel, with the country’s first case of the disease since 1989, as well as in London and New York. In Pakistan and Afghanistan, the only two countries in which the wild virus remains endemic, polio cases were decreasing until this year, when there were 12 cases in Pakistan (at the time of this writing), after 15 months without a single case. There remains some opposition to vaccines — eight campaign workers were killed in northern Afghanistan in February 2022.

A moving target

Mastering the endgame means grappling with conflict and political instability. Among the handful of countries still reporting cases of Guinea worm disease, eradication is toughest in countries such as Chad, Mali and South Sudan. In 2020, when Ethiopia plunged into civil war, it also reported its first human cases of Guinea worm in over 2 years. Although wild polio has now been eliminated from five of the six WHO regions, it remains endemic in Afghanistan and Pakistan, while sporadic cases continue to crop up in parts of northeastern Nigeria, in addition to recent reports elsewhere. To stop polio from resurfacing, health workers need to achieve 95% immunization coverage, and to do that, they need access. “It boils down to, can you get the vaccine into the mouths of the children you're targeting — that is really it,” says Braka.

In Pakistan, where as many as 20,000 babies are born each day, elimination is a race against a fast-moving virus with an ever-growing pool of potential targets. Muhammad Suleman Rana, a laboratory virologist at Pakistan’s National Institute of Health in Islamabad, works in the country’s only lab responsible for infectious disease surveillance. He says that Pakistan’s high birth rate makes the polio-eradication goal a huge challenge. Added to that are nutritional deficiencies, which make for weak immune defenses, and low immunization coverage. “Not only [is this] dangerous for a country like Pakistan and Afghanistan, but also responsible for the international spread of the virus like the case of Malawi,” says Rana. “Nobody is safe until everybody's safe.”

Polio campaigners cannot rest even when surveillance charts show that a particular country has zero cases year after year. Before Malawi and Mozambique, it happened in Syria: in 2014, the country was forced to restart vaccinations when 26 cases cropped up 5 years after wild polio was declared eliminated. Just when you think you have won the race, that is when it is most dangerous to drop your guard, says Rana. “This period is very crucial.”

Access to an effective intervention — usually a vaccine or treatment — is one of the basic scientific requirements for a disease to qualify for eradication or elimination. Also essential are practical diagnostics that pick up infections with high specificity and sensitivity. And there are other considerations: whether the disease has an animal reservoir, for example, or spreads easily in the environment — both factors that Tanner calls on to rule out the prospect of wiping out SARS-CoV-2, which has infected deer, mink, hamsters and domestic pets.

A lively debate

Although the pandemic experience has reinforced a singular focus on vaccines, a successful eradication or elimination strategy does not stop — or sometimes even start — there. Tanner runs through the details with urgent energy. It is important to name your target, he says, whether a pathogen or disease, and design a strategy around it. The key is to break up transmission through the use of a targeted approach. This involves looking at how ‘focal’ a disease is, and knowing where to intervene. “It must be the whole chain — identifying a case, and quickly acting,” he points out. “Surveillance becomes an intervention.”

These are some of the principles Tanner drew on as chair of the WHO Strategic Advisory Group on malaria eradication (SAGme), which in 2019 concluded that eradicating this disease by 2050 is unrealistic. The verdict contradicted findings by The Lancet Commission on Malaria Eradication, funded by the Bill & Melinda Gates Foundation, which judged the goal was achievable. The split in the malaria community is yet another incarnation of a divisive debate.

David Molyneux, Emeritus Professor of the University of Liverpool and the School of Tropical Medicine in the UK, has argued that the case for malaria is ill conceived. A vocal advocate of realism in the pursuit of eradication goals, he also led colleagues in calling for the Guinea worm campaign to drop its zero target in favor of a ‘plan B’ strategy, whereby a small risk of spillover cases from animals to humans each year would be acceptable. As a member of the Guinea worm certification commission, Molyneux believes the commission faces an uphill struggle to certify with 100% certainty that no cases exist in vast areas of Sub-Saharan Africa where incidents of conflict are rising. Meeting the 2030 eradication goal, which requires 3 years of zero cases in each country, would require that this be done by 2027 at the latest.

Disputes over the prospect of eradicating diseases might be cast as a battle between optimism and pragmatism, were it not for limited budgets. One criticism of eradication goals is that they drain resources from other health programs. The polio campaign cost an estimated US $16.5 billion in its first three decades. The GPEI’s new 5-year strategy, endorsed by the WHO in April 2022, comes with a price tag of US $4.8 billion.

Shooting for eradication gets more expensive as the finish line approaches, and ‘last mile’ challenges are stretching the budgets of both campaigns. Yet an economic analysis published in 2021 says the cost–benefit scale still tips in favor of eradication. And there are high-profile backers. In March, leaders from a handful of countries gathered at the presidential palace of the United Arab Emirates to reaffirm their commitment to Guinea worm eradication by 2030. The event was co-hosted by the Carter Center, the driving force behind the campaign, and Reaching the Last Mile, an initiative of the Crown Prince of Abu Dhabi.

But global budgets are falling under severe strain, as the pandemic and the war in Ukraine pile on worrying levels of debt in poorer countries. Although development aid for health has been rising overall, there are signs that such spending on programs other than COVID-19 is decreasing. Today’s eradication campaigns operate in a world different from the one that triumphed over smallpox. Climate change will probably change the epidemiology of some infectious diseases, potentially giving eradication a moving target. Conflict impedes access to disease hotspots. Vaccine skepticism is widespread. The conditions for wiping out smallpox seem favorable by comparison.

Multilateralism needed

The environmental and social-political barriers to eradication in the twenty-first century make this a testing time for campaigns. Making the scientific case for eradication is simply a starting point, says Paté. “You also need to demonstrate [that] not only the tools are available, but also the economic case is there, the political consensus — which means who’s going to pay for it, and how are they going to pay for it, and are they willing to pay for it?” he points out. “That's a function of multilateralism. But COVID-19 has showed us the poor state of multilateralism in the world.”

That does not mean giving up on eradication or moving the goalposts, says Paté, but neither does it mean the world should pursue the idea unwisely. “I think we should just be realistic about what we're facing and continue to work on tools, and elimination where it's feasible, so that we continue to build momentum towards that agenda.”

Tanner agrees that elimination at the country level should be the starting point for any disease that qualifies as a target. “Always, [and] also in the malaria [case] we formulated very clearly in our SAGme report, you first go for elimination, country by country,” he says. “You cannot just lift everything to the global level. The risk [is] that [it] doesn't help a national control program.”

Each government should make its own decision based on a risk–benefit evaluation, according to Tanner, and that should factor in the wider health and social system, not simply focus on a single pathogen. Success then relies on careful strategy. Much needs to come together to make it work.

Adjustments are sometimes necessary. Shifting away from the live polio vaccine to an inactivated vaccine was needed to limit vaccine-derived infections. Sometimes it takes unconventional methods to get through the last mile. Braka recounts how in 2016, when two cases cropped up in northeastern Nigeria after 2 years polio free, the WHO had to get inventive. Trying to reach people trapped in areas under the Boko Haram insurgency was simply too dangerous. “It was a sensitive operation,” she says, which meant working with the government and the military to provide security. The team hired ‘key informants’ — people embedded within communities that could be trusted to keep watch. The campaign also used satellite imagery to locate areas that could not be reached on the ground.

The WHO’s confidence in eradicating polio appears unshakable. “That it can be achieved is beyond question,” an officer from the agency’s polio-eradication department in Geneva told Nature Medicine in an email. “We can't afford to fail,” says Braka. “There's been too much investment already.”

Some experts say the whole concept of eradication might hinge on the polio campaign’s success. If a change in strategy were to become an option, it might see the WHO celebrate successes but drop zero targets. If there is a third way, it could be to keep high ambition in sight, with feet on the ground.

“I think it will be a remarkable achievement for public health to knock off a disease like malaria,” says Paté. “But we should not go in there naively. And polio has not yet been eradicated. So that's also something that we have to finish.”