A year ago, when former president Jimmy Carter told the world that he had been diagnosed with cancer, he announced a dying wish: He wanted the last Guinea worm to die before he did. Carter was referring to a parasite that plagued 3.5 million people across 21 African countries as recently as 1986.
Today, Carter's cancer is in remission, and Guinea worm infections have never been more rare. Last year, there were 22 cases in four countries. This year, so far, there have been only seven human cases. If the global eradication program, led by the Carter Center, succeeds, Guinea worm will be only the second human disease in history to be eradicated, after smallpox.
But the final stage of an eradication program can be the most difficult. The biggest obstacle is that Guinea worm is infecting not just people, but also dogs. Ending the disease in both humans and dogs may be necessary before Carter, now 91, can see his wish fulfilled.
Guinea worm infections are rarely fatal, but they are devastating. The parasites are transmitted to people who drink water infested with water fleas that have eaten Guinea worm larvae. The larvae burrow through the person’s intestine and into the layer of tissue beneath the skin, where male and female worms mate.
The male Guinea worm dies, but the female worm incubates in a person’s body for a year, where it grows three to five feet long. It forms a horribly painful and itchy blister until it erupts through the flesh of the legs, arms or even chest. To alleviate the pain and itching, an infected person seeks out water — where the worm releases her larvae to start the whole cycle over again.
People suffering from Guinea worm are exhausted and in agony. It can take weeks to slowly extract the worm. Among the Yoruba people in southwest Nigeria, there is an expression: “The guinea worm has knocked him down.” In southeastern Nigeria, a local word for Guinea worm also means “silent magistrate,” because of the parasite’s power to remove students from schools and prevent farmers from planting their crops.
The Centers for Disease Control and Prevention started an initiative to combat guinea worm in 1980. In 1986, the Carter Center began leading the program along with the CDC, and the World Health Assembly formally targeted Guinea worm for global eradication.
There is no vaccine for Guinea worm, because the parasite induces no immune response. Someone who caught Guinea worm from contaminated water one year could get infected again the next year. And one worm doesn’t stop a simultaneous infection, or three, or 10, said Don Hopkins, who led the CDC’s Guinea worm effort and then joined the Carter Center to become director of health programs. He’d heard of a man infected with 84 worms at one time.
The program combines surveillance in remote and often war-torn areas with seemingly simple measures like water filtration, water treatment, rewards for notifying health workers of infection, and education programs. The results are stunning: There were fewer than 10,000 cases in 2007, 542 in 2012. And the cases kept dropping until they reached seven reported this year.
But the parasite is more elusive than experts first realized.
In 2010, Chad reported a human case of Guinea worm, even though the country had been free of reported human infections for 10 years. Members of the Guinea worm eradication programs were very concerned.
“We knew from past experience, if we missed any cases in a year, the potential is that a single case could walk into a village and contaminate a pond and give rise to 80 or more cases the next year,” Hopkins said. “That was the fear.”
But the numbers didn’t take off. Since 2010, the number of people infected per year has ranged from nine to 14. And instead of clustering around a single village, the cases were scattered over 150 miles. In 2011, when all 11 of the reported cases for that year were in separate villages, it became clear to Mark Eberhard, a parasitologist and researcher at the CDC, that something very unusual was taking place.
“Each year it was different people in different villages, in villages that didn’t have Guinea worm the year before,” Eberhard said. “Honestly, we couldn’t really explain it.”
Two years after the mysterious human infection, dogs were found with Guinea worm in Chad. Canine infections had been reported in the past, but never in large numbers. Now dog infections are rising in Chad, with more than 600 this year. Eberhard thinks dogs are somehow spreading Guinea worm to people.
The exact method of transmission is unclear. When dogs lap water, water fleas skitter away, so it’s unlikely dogs are ingesting larvae-infested water fleas directly.
Eberhard suspects there's a biological middleman. Dog infections, like the human cases, cluster around the Chari River. Eberhard guessed that fish were eating guinea worm larvae and dogs were eating the fish. People eating undercooked fish could similarly ingest worms. But in the lab, Eberhard hasn't been able to transmit the worms through fish.
During a trip to Chad this summer, Eberhard collected samples of various animals a dog might eat and will test infected dogs for traces of those animals. If the dogs with Guinea worm were eating the same food, it could provide clues to how the worms are spreading.
The studies are part of an extensive effort to make sense of the dog infections.
Dog behaviorists at the University of Exeter will attach collars with GPS units to dogs to see where they go and will test dog whiskers to find out what they’ve eaten.
The Wellcome Trust Sanger Institute is sequencing the DNA of Guinea worms. One goal is to "reconstruct the pedigree, the family tree, of all the worms," said the institute's James Cotton. "This would let us show that, for example, a worm extracted from a dog in one year is the mother of a worm from a human case in the next year."
Eberhard and his colleagues are testing whether drugs like Heart Guard and Advantage Plus, used for other canine parasites, could treat Guinea worm. If so, such treatment might be the key to killing every last worm.
Without the dog infections, Carter’s wish to outlive Guinea worms might well have been achievable.
David Molyneux of the Liverpool School of Tropical Medicine and a member of the eradication commission, said “with eradication programs, make sure you are ready for surprises. I’m not suggesting for a minute that this hasn’t been a fantastically successful public health program. It certainly has. And it’s a model, but it shows you how difficult actual eradication is.”
Hopkins turns 75 this year. He said that in 1980, when he started the program, he had no idea that it would be going for this long. He has a preserved Guinea worm named Henrietta in a jar on his bookshelf. “I keep it there as a reminder of what we’re up against, and how awful this disease is,” he said.
Joel Breman, another longtime member of the eradication effort, was in West Africa working on smallpox eradication in the 1970s when he first encountered Guinea worm. He knew he was entering an afflicted village when he saw that fraying roofs hadn’t been re-thatched, water hadn’t been fetched, and people were lying around listlessly.
“It’s rare that someone would die,” said Breman, the current vice chair of the commission to certify Guinea worm eradication, and an emeritus scientist at the National Institutes of Health. “But I saw some villages decimated by Guinea worm, and I was really stunned.”
Breman, who will be 80 this year, said he’s learned to never pair the completion of an eradication program and an end date in the same sentence.
“We’re getting really, really close,” Breman said. “And that’s exciting. But with eradication programs, it’s perfection we’re seeking. Down to the last inch, whatever time it takes.”
