A few years ago, it looked like humanity was about to wipe a debilitating parasitic disease off the face of the Earth. But the long road to eradicating Guinea worm just got a whole lot longer. Faced with evidence of previously unknown routes of transmission, the World Health Organization (WHO) has quietly pushed back the target date for stamping out the disease from 2020 to 2030.

“We are being realistic and down to earth,” says Dieudonné Sankara, who heads the WHO’s eradication effort.

So far, humanity has eradicated just one human pathogen: smallpox. The decision on Guinea worm ( Dracunculus medinensis ) is a major blow to the scientists and health workers who have been fighting the parasite since the 1980s. An international partnership — led by the Carter Center in Atlanta, Georgia — has reduced the number of new infections from 3.5 million per year in 1986 to just 28 in 2018. And the disease, once prevalent across Africa and Asia, has been limited to a handful of nations in Central Africa.

But a series of puzzling discoveries has made it impossible to meet the 2020 target. The most urgent issue is the soaring, and as yet unexplained, rate of infections among dogs in Chad — which has helped to keep Guinea worm circulating in the environment. Then there are the emergence of the first known cases among people in Angola, perplexing infections in baboons in Ethiopia, and conflicts that have hampered eradication efforts in parts of Mali, Sudan and South Sudan. Some public-health experts wonder whether wiping out the parasite is even possible.

“The question has been put on the table and has been on some of our minds. It is an evolving thought process,” says Mark Eberhard, a retired parasitologist and member of a WHO advisory group, the International Commission for the Certification of Dracunculiasis Eradication, whose job is to determine when Guinea worm is finally gone. He says that the rise of infections in dogs suggests that eradication will be extremely difficult — if not impossible.

But Donald Hopkins, the tropical-medicine specialist who has led the Guinea-worm eradication effort from its outset, is unwavering. “I am confident we will be able to wrap it up,” says Hopkins, a veteran of the campaign that in 1980 eradicated smallpox. Now a special adviser to the Carter Center, Hopkins hopes to repeat the feat with Guinea worm while his 94-year-old boss, former president Jimmy Carter, is alive to see it happen.

A simple plan

Once called the “disease of empty granaries” because its victims were too incapacitated to farm, work or attend school, Guinea worm afflicts the poorest of the poor. There is no drug to treat it, and no vaccine to prevent it.

People contract the parasite by drinking water that contains microscopic water fleas, known as copepods, that carry Guinea-worm larvae. A year or so later, a stringy worm that is 60 to 90 centimetres erupts through the skin on the leg or foot. Its excruciatingly painful journey out of the body can take weeks. To relieve the burning sensation, many people wade into the nearest body of water — often the same pond from which they drink. When an adult worm enters the water, it releases larvae, and the cycle starts anew.

For decades, parasitologists thought that this was the only route of transmission, and that Guinea worm infected only people. Researchers devised a plan to eradicate the disease by teaching people at risk to filter their drinking water and — if infected — to stay out of ponds until the worm exited their bodies. These simple measures were complemented by the strategic use of larvicides.

The World Health Assembly endorsed the plan in 1986, making Guinea worm only the second human disease after smallpox to be officially targeted for extinction. (Two years later, the assembly added polio to the list.) Public-health experts were confident that they could wipe out Guinea-worm disease because the parasite was not known to circulate in animals, which could help it to survive and spread.

Canine conundrum

Those long-standing assumptions began to falter in 2010, when Guinea-worm disease popped up in people living along the Chari River in Chad after a ten-year absence. Scientists were puzzled because the cases were sporadic and dispersed over a wide area, rather than clustered around contaminated water sources. Stranger still, field staff from the eradication programme spotted stringy worms hanging from the legs of domestic dogs. Genetic analysis confirmed that these parasites were D. medinensis , which had evaded surveillance in Chad for about a decade.

These developments suggested the existence of a previously unknown route of transmission related to the thriving fishing industry along the Chari River. But after eight years of investigation, researchers still haven’t pinned it down. The latest idea — that dogs and some people become infected by eating very small fish that harbour the parasite — is just “one step up from a hypothesis”, says Eberhard, who worked on Guinea-worm eradication for decades at the US Centers for Disease Control and Prevention in Atlanta. “We keep asking, what are we missing?”

The number of new Guinea-worm infections in people has remained relatively constant in Chad, at about a dozen per year since 2010. (This year is an exception, with 24 cases — half of which came from a village where people drank from a contaminated pond.) Yet the number of new cases in dogs has climbed from hundreds in the early 2010s to more than 1,500 so far this year. “In Chad, it is clear that dogs are driving transmission and humans are ancillary,” Eberhard says. “If we control it in dogs, human cases might go away.”

Cases of Guinea-worm disease in dogs had been reported before, in other countries. But there was no evidence that infections in dogs could sustain transmission. “Once it disappeared in humans, it disappeared in dogs,” says Sarah Cleaveland, a veterinarian and epidemiologist at the University of Glasgow, UK.

The eradication programme is offering a US$20 reward to anyone in Chad who reports a case of Guinea-worm disease in dogs. Field workers are also teaching people to tether infected dogs while the worms are emerging, and to bury fish entrails. The programme tried giving deworming medicine to dogs, to no effect. Now, it is scaling up the use of larvicides to kill the copepods that carry Guinea-worm larvae. Meanwhile, laboratory and field studies are under way to pinpoint the source of infection and to find ways to stop it.

Puzzling parasite

Infected dogs, and a few cats, have also been reported in Ethiopia and Mali, but the cases number in the tens and twenties, not the thousands seen in Chad. Researchers aren’t sure why Chad has been hit so hard. “It is important that we understand more about the epidemiology of the disease — learn the really key source of infections in dogs,” says Cleaveland. She leads a WHO working group that is developing criteria to verify when animals are free of Guinea worm.

The discovery in 2013 of infected baboons — a first — in a small forested area in southern Ethiopia also has researchers scratching their heads. So far, scientists have found 15 baboons with Guinea-worm disease. The eradication programme has hired hunters to find and map water sources deep in the forest, which are then treated with larvicide. Individual baboons have been collared and are being tracked to find out where they eat, drink and sleep. A key question, Cleaveland says, is whether baboons, like dogs, can sustain transmission independently.

Then there is the emergence of Guinea-worm disease in Angola. The country’s first known case of the disease, in an 8-year-old-girl, was detected in April 2018. A second person was found to be infected in early 2019, as was a dog.

“How long it has been there and where it came from is anyone’s guess,” Hopkins says. The parasite might have been lurking in Angola all along, or it could have hitched a ride in a person or a dog from another country. Scientists are looking for clues by sequencing DNA from Guinea-worm samples taken in Angola. The Carter Center is setting up surveillance in the country, and the WHO is working with the government of Namibia to scour its border with Angola for signs of the disease.

Tempering expectations

The WHO’s new 2030 target date for eradication is intended to allow time not only to stop the transmission of Guinea worm, but also for the certification commission to verify that the disease is gone. Doing so requires three or more years without an infection in a person or animal — in the face of intense surveillance.

David Molyneux, a parasitologist at the Liverpool School of Tropical Medicine in the United Kingdom and a member of the certification commission, wonders how its members will ever be sure that Guinea worm has been vanquished. “Our job is to work out how you might certify a country the size of Chad free of Dracunculiasis in humans and dogs. Can we ever envisage that level of surveillance?” he says, noting that there are 60,000 dogs roaming the Chari River basin alone.

Then there are the conflict zones in Mali, Sudan and South Sudan, where it is too dangerous to do eradication work. “How do you prove a negative in those settings?” Molyneux asks.

He is pushing for a plan B in case wiping out Guinea-worm disease proves to be impossible — and says that the world should celebrate what the eradication effort has already accomplished. “It has stopped millions of people from becoming disabled,” he says. And the number of people who are infected each year is small. If control measure continue, “it will never be a public-health problem again”.

But Hopkins won’t settle for control. “The daunting thing about eradication is there is no wiggle room,” he says. “Zero is zero.” And that remains the goal.