Brazil is home to some 52 million dogs, most of whom are well-loved pets, and many of whom are hosts to Leishmania infantum, a parasite that is incredibly harmful to humans. Hundreds of Brazilians die every year when they are bitten by sand flies that obtained the parasite from dogs. Visceral leishmaniasis, the disease the parasite causes, leads to cutaneous sores on the skin, infections of organs including the spleen and liver and sometimes death.

Now, research published today in PLOS Pathogens reports that dogs infected with the parasite may smell more attractive to female sand flies, suggesting L. infantum could be manipulating its hosts as it travels from one to the next. Experts say the results could have implications for controlling the often-deadly tropical disease.

Visceral leishmaniasis is thought to kill between 20,000 to 40,000 people a year, says Christine Petersen, the director of the Center for Emerging Infectious Diseases at the University of Iowa, who was not involved in the new study. At least 80 percent of South American cases occur in Brazil, where leishmaniasis has been spreading since the 1980s, most likely carried by people and their pets as they migrated from rural to urban areas. Brazil’s favelas—crowded, low-income urban settlements often neglected by authorities—as well as poor areas of India and East Africa are hotbeds for the disease. “The people who are at the most risk of this disease are really in the most impoverished parts of the world,” Petersen says.

Gordon Hamilton, a medical entomologist at Lancaster University who co-authored the study, published a study in Scientific Reports in 2017 showing that in laboratory settings, female sand flies were more attracted to hamsters infected with L. infantum. About half of the rodents developed an odor that was more attractive to female sand flies. But hamsters, which are a model organism widely used in laboratory experiments, are not a natural host of the parasite. “It’s more relevant to [study] dogs, which the parasite has evolved along with,” Hamilton says.

In the new study, the researchers collected hair and blood samples from 133 infected and healthy dogs in the Brazilian city of Governador Valadares, located in an industrialized area where visceral leishmaniasis is common. The scientists isolated volatile organic chemicals—the molecules that convey scent—from 30 of the hair samples, half of which were from infected dogs, which they then exposed to male and female sand flies in a laboratory. The flies were given a choice between approaching the scent molecules from infected or healthy dogs. While the male flies showed little preference between the odors, females chose the infected dogs’ odor almost twice as often as healthy dogs’. “Every single infected dog we tested was more attractive to females than the uninfected dogs,” Hamilton says.

The evidence that female sand flies are more attracted to infected dogs than male flies is important, says Hamilton, because females are the ones who feed on the blood of dogs and humans and transmit the parasite. Male flies do not.

“This is the first study to confirm that odor of infected dogs is significantly more attractive to female sand flies than to male sand flies,” says Filipe Dantas-Torres, a veterinary parasitologist at the Aggeu Magalhães Institute in Recife, Brazil, who was not involved in the study.

Dantas-Torres says that while dogs are the primary hosts for L. infantum, the parasite can infect a wide range of hosts, including livestock and cats, which could also serve as reservoirs for the disease. Parasites often have a life-cycle that involves multiple host organisms—such parasites cause most zoonotic and emerging infectious diseases—and some of these can manipulate their hosts to help ensure they are passed on to the next unfortunate victim. Such manipulation can affect host behavior in bizarre ways. For example, the lancet fluke hijacks the nervous system of ants to ensure the insects make themselves vulnerable to predators so they are eaten. And the Plasmodium parasites that cause malaria make their human hosts smell more attractive to biting insects, who pass them to the next host.

One limitation of the recent study is that the dogs included were mixed-breed. Dantas-Torres says that some dog breeds may attract different biting insects more than others, and the study’s reliance on mutts could have missed this. Petersen says it is also possible the parasite was not directly manipulating the dogs’ odor; infected dogs might smell more attractive to sand flies because as the disease progresses, the dogs can develop renal complications, which can be malodorous. But Hamilton says that regardless of parasite load or observed symptoms, infected dogs were significantly more attractive to the female sand flies than uninfected dogs. Even dogs that had low levels of parasite infection still had a change in their smell that attracted female sand flies.

Both dogs and L. infantum were brought to South America from the Mediterranean basin by European colonizers. In Europe, the parasite is carried by a species of sand fly that is not as effective of a vector as the one in Brazil, but scientists don’t know why, Hamilton says.

Dantas-Torres says that understanding such host-parasite-vector interactions is fundamental to designing more comprehensive approaches to control parasites such as Leishmania protozoa. Canine infections are largely controlled with topical repellents such as insecticide-laced collars, with vaccinations being a second choice. Petersen says that vaccinations could help prevent dogs from contracting the disease the parasites cause, but they wouldn’t prevent them from carrying L. infantum and potentially passing it on to humans via sand flies. In the highest-impacted areas in Brazil, infected dogs are sometimes culled to control the spread of disease.

Hamilton says the new study’s findings could present new avenues of infection control for L. infantum. He is currently involved in a project that uses pheromones to attract sand flies to areas where they can be killed. “If we can identify what the chemicals are that make infected dogs more attractive, we can potentially combine that with the synthetic pheromone to make it even better,” he says.