Sit. Stay. Fetch. Diagnose?
The typical list of doggie demands won’t cut it anymore: If a mutt intends to impress, she needs to nose out patients harboring deadly parasites in their blood.
Today, at the 2018 American Society of Tropical Medicine and Hygiene Annual Meeting, researchers report that nature’s most famous superstar sniffers can now be deployed in the fight against malaria. Their ultra-sensitive noses are capable of detecting the presence of microscopic parasites in children through the breezy whiff of a sock—upping the ante on tricks that truly warrant a treat.
A single prick from a mosquito can be enough to jumpstart a malaria epidemic. The disease, caused by Plasmodium parasites chauffeured in by female Anopheles mosquitoes (who, unlike males, bite for blood, in which the parasites eventually set up shop), is sometimes asymptomatic, but for others will ravage the body with fevers and sweats, and can be deadly when left untreated.
Malaria claims nearly half a million lives each year, most of whom are children. While rates of infection have fallen in the past couple decades, progress has stagnated, due in part to inconsistent funding and rising levels of resistance to anti-malarial drugs. Additionally, because malaria’s initial symptoms tend to be vague and flu-like, current diagnostic procedures require an invasive blood test to confirm infection—and the course of treatment can involve weeks of dosing and some nasty side effects.
A few years ago, however, containment efforts received a second wind. Malaria stinks—but it wasn’t until recently that researchers began to realize just how much. It turns out being infected with this parasite alters a person’s fragrance in a way that female mosquitoes crave. These bloodthirsty bugs go bonkers for eau de malaria (which, apparently, has a lemony zing), increasing the likelihood that they’ll ferry Plasmodium from person to person in their feeding frenzy.
But even ill winds can sometimes blow for the good. When Steve Lindsay, a public health entomologist at Durham University and senior researcher on the new report, encountered a troupe of sniffer dogs patrolling luggage carousels at Dulles airport in Washington, DC, his mind began to connect the dots. With a sense of smell 10,000 to 100,000 times as powerful as a human’s, dogs have proved themselves invaluable for tracking everything from illegal drugs to wildlife smuggling. If malarial musk is irresistible to mosquitoes, an odor this potent could also be the key to a new, non-invasive diagnostic technique involving a particularly perceptive pooch.
“Dogs are just extraordinary animals,” says Lindsay. “They live in a totally different world. When they smell, it’s like they’re reading a newspaper.”
With a $100,000 Grand Challenges Exploration grant from the Bill & Melinda Gates Foundation, Lindsay assembled a team of researchers from around the world, partnering the forces of Durham University with Medical Detection Dogs, the London School of Hygiene & Tropical Medicine, and the Medical Research Council Unit, The Gambia. For the past two years, the team has been hard at work on their first pilot study, which involved training two dogs named Lexi and Sally to correctly identify the malarial odors on the clothing of infected patients. The first target? Socks.
Few things are funkier than feet. And previous work from other research groups has already shown that mosquitoes are suckers for stockings worn by infected kids—even when they’ve been taken off.
“If mosquitoes can do it,” Lindsay reasoned, “why can’t dogs?”
To gather test subjects for their doggie detectives, Lindsay and his team traveled to The Gambia—one of the countries in West Africa where malaria is prevalent—and recruited 586 schoolchildren between the ages of five and 13. Children often have the highest parasite loads and suffer the most severe symptoms of disease. So, in a move Lindsay describes as “loading the dice,” the researchers focused the first wave of efforts on kids, the population both at highest risk and most likely to give off a strong malarial signal.
The researchers confirmed the infection status of the children through standard blood testing, then asked each child to don a pair of nylon socks overnight. After the children returned the unlaundered socks, the researchers whisked them away for testing.
Lindsay marvels at the scent’s staying power. “It’s extraordinary that you can give nylons socks to a child, pick them up the following day, wrap the socks in aluminum foil, pop it in a plastic bag, freeze them for 12 to 15 months, then start training the dogs.”
Lexi and Sally were first given a crash course in sniffing on a subset of the socks. For several months, the pair underwent six sessions of intensive schooling each week at the Medical Detection Dogs charity in the United Kingdom, gradually learning to recognize the scent of infection from parasitically perfumed nylons. By the end of their training, both eagerly gravitated towards the socks that smelled of disease.
Then came the real test. When faced with a full battery of 145 uninfected and 30 infected socks, the dogs correctly identified 90% of the malaria-negative and 70% of the malaria-positive samples. Lindsay is confident that the numbers will only improve as Lexi and Sally practice with different samples and populations. And in the days since the first trials, a third dog named Freya has been trained for the same set of tasks.
“This is a very interesting and original idea,” says Marije K. Bomers, an infectious disease specialist at the VU University Medical Center in Amsterdam who has studied dogs’ ability to detect C. difficile infections in human stool. “The results are far from perfect, but I think it’s a really good start. It’s hopeful and positive.”
For now, Lindsay and his team have set their sights on a couple specific targets. The dogs could operate at ports of entry—where there is often already infrastructure to support canine professionals—into countries where malaria prevalence is low or diminishing, preventing the reentry of parasites that might spark a new wave of infection. In the United States, for example, malaria remains uncommon in clinics but often manages to invade U.S. ports of entry. About 1,700 cases are diagnosed each year within U.S. borders, mostly in travelers returning from countries where the disease runs rampant.
Additionally, dogs could act as scouts in the field, nosing out the last infected members of communities where malaria has almost been eradicated. These cases have proven especially troubling to detect, especially when the infections are asymptomatic. But even in the absence of active illness, canines may be able to sniff out the telltale bouquet of infected blood.
Researchers aren’t completely sure why mosquitoes and mutts are so sensitive to malarial musk, or where the scent originates. It may be that the parasites themselves are particularly pungent. When it comes to mosquitoes, at least, such a strategy could be beneficial to Plasmodium: It ups the parasites’ chances of hailing a cab to their next victim—an olfactory version of a hitchhiker’s thumb. Alternatively, the distinctive odor could arise from the human body’s response to infection. Both explanations could be true—or the answer could be something else entirely.
There’s also no guarantee that the aroma that’s attracting mosquitoes is also what is piquing the pooch proboscis. “We don’t know what the dogs might be detecting,” Lindsay says, “but at this stage, we just want to know whether they’re detecting or not.”
If the team’s first trials are any indication, it seems the dogs are detecting. But the researchers have a long road ahead of them before this breed of diagnostic leaves the lab. A scene of smelly socks lined up in a research facility doesn’t necessarily translate to patients speeding through clinics or tourists navigating chaotic hubs of travel. Additionally, the months-long training regimen could pose some significant logistical hurdles to implementing this strategy on a grander scale, says Audrey Odom John, a parasitologist who is investigating the utility of malarial odors for medical devices at Washington University in St. Louis.
As the researchers try to implement canine-based detection systems, they’ll have cultural barriers to consider as well. In some countries, canines aren’t always seen as companions. As Lindsay and his team move their efforts forward, he explains they will prioritize introducing the dogs and their role in disease prevention to locals before proceeding with their work. But acceptance may not be universal.
Because of these drawbacks, Odom John explains, it’s unlikely dogs will be a hospital staple in the near future. But other technologies are beginning to surface in the meantime, leveraging the power of medical devices also sensitive to scent. Odom John’s lab is currently investigating the use of breath detection technology in malaria diagnostics. Others, such as James Covington, an engineer at the University of Warwick in the United Kingdom, are developing electronic noses, or e-noses, to pick up subtle changes in a person’s aroma in the presence of disease—and the tech is already showing promise for tuberculosis and cancer.
These little machines certainly have their perks. For one, unlike dogs, they’re mass-producible and require no training, Bomers says, making them a potential gold standard in the clinic. But they have their own set of pitfalls: To get results, researchers need to obtain a sample, insert it into the device, and wait. Dogs, on the other hand, are proactive and spontaneous. If they catch a whiff of something, they’ll make sure you know it. And, of course, there’s still no device that beats that canine sense of smell.
“The e-noses are pretty good—about as good as our noses—but not as good as dogs’ noses,” Lindsay explains. “And dogs don’t need to be plugged in.”
Luckily, Odom John thinks that if medical technology and sniffer dogs both continue to progress, they’ll likely serve complementary purposes—one in the clinic, perhaps, and one in the field—rather than vying for diagnostic space. With nearly half the world’s population at risk of contracting malaria, there’s certainly plenty of work to go around.
“There’s such an urgent need for new diagnostics,” Odom John says. “So we need a lot of shots on goal.”