A deadly disease known as African sleeping sickness has puzzled doctors for decades. It would disappear from villages without a trace, only to re-emerge weeks or months later with no known cause. Frustrated health officials wondered how sleeping sickness could persist when not a single villager or animal—the disease’s only carriers—tested positive for the insect-borne parasite that causes it. Now, scientists may have an answer at last: They’ve discovered the disease was hiding in plain sight this whole time, living in and even transmitting via human skin.
African sleeping sickness, also known as African trypanosomiasis, is caused by a microscopic wormlike parasite spread exclusively by the tsetse fly. As such, it’s limited by the fly’s range to sub-Saharan Africa. Locals avoid places where the flies are numerous, but political unrest can displace residents and force them into the path of the disease. Once infected, people have anywhere from weeks to years before the parasite crashes into the brain, causing headaches, tremors, confusion, and paralysis. Those infected also suffer from a disrupted sleep cycle, bouts of random sleepiness and wakefulness that gives the disease its name. Without treatment—toxic drugs that keep patients bedridden for weeks—those infected nearly always slip into a coma and die.
In the 1950s and 1960s, health officials got the number of reported cases down to a few thousand per year and were on track to eradicate it, says parasitologist Annette MacLeod of the University of Glasgow in the United Kingdom, who led the new discovery. But despite their best efforts, they could never get rid of the last few thousand cases. Today, the World Health Organization estimates that between 7000 and 10,000 people are infected every year, and as many as 65 million people live in at-risk areas. In 2010, about 9000 people died from the disease.
MacLeod has been traveling to sub-Saharan Africa, primarily Guinea, for the past 20 years to study sleeping sickness. Like everyone else, she was boggled by the disease’s mysterious reappearing act. A few years ago, when she was studying the parasite in mice, she noticed that under a microscope she could see it burrowing in a mouse’s skin. Unlike mosquitoes that tap directly into the bloodstream, tsetse flies bite through flesh, giving potential skin-based parasites the opportunity to infect the flies while they’re eating.
MacLeod wanted to travel to Guinea to look for similar evidence in humans, but the recent Ebola outbreak prevented her from going. So she turned to colleagues in the Democratic Republic of the Congo, who provided her with skin biopsies and medical histories from more than a thousand people who had fallen ill in the early 1990s during an outbreak of another insect-borne disease, river blindness.
She examined the samples for the sleeping sickness parasites and found them in a handful of people, even though they showed no symptoms of the disease at the time. Further testing revealed that mice with parasites in their skin, but undetectable levels of the parasite in their blood, can easily transmit the disease to tsetse flies. Taken together, these results indicate that human skin is likely an “unappreciated reservoir of infection,” MacLeod and colleagues report this week in eLife. People who display no symptoms and have virtually no parasites in their bloodstream can still carry the disease and transmit it to others if they’re bitten by tsetse flies, she says. Skin-to-skin transmission between humans is technically possible, she adds, but is likely rare because it would have to get into broken skin.
The upshot is that if health agencies only test people’s blood for African sleeping sickness—the most common practice—they’re going to miss remnants of the disease that prevent it from being completely eradicated. “These asymptomatic people are the secret reservoirs that keep the disease going,” MacLeod says.
James Morris, a pathogen geneticist at Clemson University in South Carolina, wrote in an email that if further tests bear out these preliminary results, they could prove important to disease eradication efforts. “If the data stands the test of time, I think this study provides an important update to how we think about African trypanosome infections, particularly with regard to diagnostic approaches,” he wrote. “Is it ‘the hidden reservoir’? Maybe.”
Morris suggests that parasites might also hide in fat tissue. Mostly, the study highlights the fact that “current diagnostics may be missing many reservoirs of infection,” he adds.
For now, skin biopsies can reveal the parasite, and MacLeod says they should be added to regular screening regimens for the disease. But she hopes a noninvasive method for detecting the parasite on skin can be developed. It’s also not clear whether current drugs are effective at treating skin-based parasites. But if health officials and researchers can account for the heretofore unknown disease hiding in skin, she believes eradication will finally be within reach.
“Now that we’ve got the parasite on the run, we need to increase our efforts,” she says.