Seated before a table covered in a knit blue cloth, a researcher hands a young girl a peculiar device. Attached to one end is a small cardboard tube; to the other, a large clear bag. The child grasps the rig with her left hand, places her lips around the cardboard, and lets out a long, slow exhale. “Good, good, good,” coos the researcher. “Can you do one more?” The girl leaves her lips around the mouthpiece, inhales through her nose, and lets another breath go. The bag, which someone has labeled “269” in Sharpie, crinkles as it swells with air. “Good! OK, all done,” says the researcher as she stoppers the collection device and sets it aside.

Inside the bag, hundreds of molecules are swirling around—some of which might just clue scientists into an infection. To find out, they’ll pass her expired air through a narrow metal cylinder packed with a compound-trapping molecular sieve, seal the vessel at both ends with a twist of a wrench, and ship it from the pediatric care center in Lilongwe, Malawi to a laboratory at Washington University in St. Louis, Missouri. There, analytical chemists are dissecting these samples in search of a breathprint—a distinctive set of compounds that could serve as the world's first breath-based test for malaria.

A Malawian child practices breathing into an early version of the breath-collection device used in the study. Later versions were attached to large, clear bags that were easier for children to inflate. Indi Trehan

Today, every malaria diagnosis begins with blood. In the gold standard test, doctors spread a drop on a glass slide, stain the sample, and inspect it beneath a microscope. If the parasite is present, it’ll show up purple against a pink backdrop of blood cells. These "blood smears" are relatively straightforward to perform, but tough to implement in rural, resource-starved parts of the world. So-called rapid diagnostic tests are an increasingly common solution. They're cheap, easy to use, and accurate. Trouble is, RDTs work by detecting a protein called HRP2, and a growing number of reports suggest Plasmodium falciparum (the deadliest malaria-causing species) is learning to not produce the molecule. "It's a very tricky parasite," says Washington University microbiologist Audrey Odom John, the infectious disease expert who led the Malawi study. "And now we're literally losing one of the most effective tests that we have."

Fortunately, nature may have provided a workaround. Malaria is not airborne—the sickness spreads by way of mosquitoes—but researchers have started to suspect that respired air may carry clues to its transmission. Various studies suggest malaria may actually alter the molecular content of human exhalations, enticing mosquitoes to feed on infected humans and accelerating the parasite’s spread.

But malaria’s capacity for mosquito mind-control could also make it a prime target for breath-based diagnosis.

Back in Odom John’s Washington University laboratory, she and her team compared the molecular compounds in the breath of two groups of kids: one with malaria, the other without. They found six compounds whose concentrations varied dramatically between the groups.

They were the diagnostic markers the researchers had been looking for. (Odom John declined to identify the compounds by name, as her team's study is currently under review for publication.) By summing the relative abundance of each compound, the researchers came up with a diagnosis for each child. They were right 83 percent of the time.