Malaria kills hundreds of thousands of people every year, but the parasite itself, Plasmodium falciparum, infects many more people than it makes sick. The majority of people with malaria at any time are perfectly healthy walking parasite factories, and without knowing they are infected, these healthy carriers can easily spread the disease to new regions and new people who might not be so fortunate.
Luckily, man’s best friend is here to lend doctors a helping paw.
New research from the London School of Hygiene & Tropical Medicine suggests that dogs can identify the odor of malaria. In a small, proof-of-concept study, two trained dogs were able to distinguish between socks worn by children who had malaria and socks from the feet of those who did not. Researchers presented their preliminary findings today at the American Society of Tropical Medicine and Hygiene Annual Meeting.
Malaria is known to make people more attractive to mosquitoes. A team led by James Logan, head of the Department of Disease Control at the London tropical medicine school, previously demonstrated that socks worn by infected children were more alluring to the little bloodsuckers, likely because the garments' odors contained more chemicals called aldehydes. With tiny wires attached to the mosquitos’ antennae, the researchers puffed chemicals at them to see which odors produced a reaction. Compounds called heptanal, octanal and nonanal were the most exciting to the mosquitoes and were found in higher levels in the infected children's socks.
“So, if mosquitoes can [smell differences in people], then why not dogs?” says Steve Lindsay, a public health entomologist at Durham University in the U.K. and lead investigator of the new study.
Lindsay and colleagues asked apparently healthy children in The Gambia to wear a pair of new socks for one night. In the morning, they collected the socks—about 175 pairs—and tested the children for malaria. (About 30 kids tested positive, though they had no symptoms.) The researchers froze the socks to preserve the odors, packed them up and mailed them back to the U.K.
The nonprofit Medical Detection Dogs then spent six months training two dogs, named Sally and Lexi, to differentiate between the socks worn by children with malaria and socks worn by kids free of the disease. The pooches—a Labrador retriever and a Labrador mixed breed—would sniff each sample and freeze if they detected malaria, or move on if not. After training with one sock from each pair, the dogs were able to correctly identify 70 percent of the children with malaria and 90 percent of the healthy children by sniffing the socks from the other foot. The dogs even picked out infected children with very low parasite loads—10 to 20 parasites per microliter of blood. (The World Health Organization says a malaria diagnostic tool should be 75 percent accurate at 200 parasites per microliter—but then again, they never specifically mentioned dogs.)
"I think it's really exciting," says Audrey Odom John, a pediatrics physician scientist at Washington University School of Medicine in St. Louis. Odom John, who was not involved in the new study, is developing a breath test to detect malaria odors in infected children. "It's certainly a great start," she says of the dogs’ success.
There are some limitations to the work, however. The sample size of 175 pairs of socks is smaller than Medical Detection Dogs would have liked, says Claire Guest, cofounder and chief executive officer of the nonprofit. A better sample would have been 100 malaria-positive socks and 300 negative socks, she says.
Because of the small sample size, the dogs had to be trained on the same sock pairs they tested (the training was done with one sock from each pair, and the test was conducted with the other). The experiment is not ideal, because the dogs could have simply learned to recognize individuals rather than detecting the malaria odor.
However, Guest and her team don’t believe the dogs were memorizing individuals. When the dogs failed to identify a malaria-positive child, it was often a child infected with the sexual stage of the malaria parasite, which Lindsay says may have changed the odor. If the dogs were simply picking up on individuals' scents, matching one sock to the other, then they shouldn't have consistently made this mistake.
Overall, the team believes that the dogs did quite well, considering they were using "small pieces of socks that were worn [once] by one child and then frozen for a while," Logan says. "That gives us greater hope that if they were able to smell an actual person, they'd do much better because the signal should be much stronger."
Smelling a person, rather than a sock, could also eliminate possible confounding factors. Many of the children shared a bed with other relatives, for example, and the socks could have picked up odors from bed linens or other people. And "what small boys do with their socks, no one can tell," Lindsay says. “We had one boy turn up wearing one sock. What happened to the other sock?"
Lindsay says the sniffer dogs could be helpful in ports of entry to countries that have eradicated malaria, but where Anopheles mosquitoes, which spread the parasite, are still present. You could screen healthy-looking people who may be carrying the malaria parasite to prevent them from reintroducing the disease to an otherwise "clean" country. Since some estimates say up to 19 in 20 people can carry the malaria parasite without getting sick, a quick, non-invasive way to identify the carriers would be a major boon to those working to prevent the spread of the disease.
Current diagnostic methods aren’t practical to screen hundreds or thousands of people passing through an airport. To diagnose malaria, doctors can draw blood and use a microscope to identify the parasites, but this requires training and "things that seem straightforward but aren't," like clean glass slides, a functioning microscope and reliable electricity, says Heidi Hopkins, an associate professor in malaria and diagnostics at the London School of Hygiene & Tropical Medicine.
Alternatively, health workers can use any number of "rapid diagnostic tests," which involve dropping a pinprick of blood on a small device. Fifteen minutes later, a colored bar appears if an antigen produced by the malaria parasite is in the patient's blood. Such tests are easy to use by non-professionals in any setting. The downside is that you can't force every international traveler to submit to a blood test. A dog, in contrast, "could go down a line of people and be done in seconds," Logan says.
And if not sniffer dogs, then maybe an electronic "nose" could be used. A device could be designed to detect the same compounds that the dogs and mosquitoes smell—but to do that, more research on the specific molecules is needed.
One unknown piece of the puzzle is why, exactly, malaria-infected people smell differently. It's unclear whether the parasites produce odors directly, if they change a person’s microbiome, or if our bodies produce the odors in response to the parasites. However, Odom John says, the malaria parasite has a similar organelle to one found on plants that produces odorous compounds—"the thing that makes pine trees smell like pine trees or lemons smell like lemons." It’s possible that the malaria parasite manufactures odorous compounds directly with its weird, plantlike organelle.
Another avenue of research that needs to be explored is whether the smell is consistent across populations, so Lindsay plans to test people from all over Africa to see if the dogs can recognize malaria among their scents, too.
A final complicating factor is that there is more than one type of malaria. P. falciparum is the most common and deadly, but other species of the parasite can cause debilitating relapses months after the initial infection.
Malaria is a complex disease that won’t be eradicated easily, even with the help of our four-legged friends. But these puppers—and their human trainers—will be working with all their canine might, in the lab and in the field, to turn this underdog story into a success.