Yale professor and author of tsetse fly study John Carlson: 'African sleeping sickness is a dreadful disease that’s hard to treat'

Scientists at Yale University recently announced a groundbreaking discovery of a volatile pheromone emitted by the tsetse fly, and the findings could lead to controlling their populations and, in turn, combat the spread of disease among humans and animals in sub-Sahara Africa. John Carlson, the Eugene Higgins Professor of Molecular, Cellular, and Developmental Biology in Yale's Faculty of Arts and Sciences and senior author of the study published in Science on Feb. 16, emphasized the urgency of finding effective solutions. 

"African sleeping sickness is a dreadful disease that's hard to treat," said John Carlson, who is the senior author of the study published in Science on February 16 and the Eugene Higgins Professor of Molecular, Cellular, and Developmental Biology in Yale's Faculty of Arts and Science. "Our immune systems have a hard time clearing trypanosomes, and most of the drugs we have to kill them are toxic. And nagana, which affects livestock, has had terrible economic impacts in the region."

According to a release by Yale, the team of Yale scientists achieved the discovery in what is a fight against tsetse fly-borne illnesses that plague sub-Sahara Africa. Hany Dweck and Brian Weiss, both from Yale, are among the other authors who contributed to this research. For the first time, the researchers have successfully identified a potent volatile pheromone emitted by these blood-sucking insects.

The discovery of the pheromone could help researchers better understand the communication of the flies and lead to new innovative efforts to curb populations combat diseases like African sleeping sickness and nagana. African sleeping sickness is a lethal disease with limited treatment options, while nagana poses significant economic threats to livestock and agricultural productivity. 

The findings shed light on the intricate communication mechanisms of tsetse flies and present potential solutions to mitigate the devastating impact of those diseases. Tsetse flies are notorious vectors of African trypanosomes, which are parasites responsible for diseases that affect both humans and animals across the region.

Adding to the challenges is the projected expansion of tsetse fly habitats due to climate change, which raises concerns about the increasing impact of these diseases on human and animal populations in the coming years. To address this critical issue, the researchers investigated using pheromones, particularly volatile ones that work over distances, to attract and trap tsetse flies as a strategy to control their spread. 

According to the release the Yale research team took tsetse flies of the species G. morsitans and collected any chemicals they might be emitting by placing them in a liquid. These extracts were then analyzed using a gas chromatograph-mass spectrometer. This is a device capable of identifying specific compounds in a mixed sample. 

The researchers were thrilled to discover several previously unreported chemicals, three of which elicited responses from the tsetse flies. Among them, methyl palmitoleate (MPO), emerged as the most promising candidate. 

Shimaa Ebrahim, a postdoctoral fellow in Carlson's lab and the first author of the study, led a series of experiments that revealed MPO's remarkable effects on male tsetse flies. 

"A drop of liquid containing MPO attracted male tsetse flies to knots in yarn that only resembled flies and to females of another tsetse fly species that they would not typically interact with," Ebrahim said in the release by Yale. "Additionally, MPO acted as an aphrodisiac, causing the flies to stop and remain in place for a significant amount of time." 

The researchers also identified a specific subpopulation of olfactory neurons on the antennae of the tsetse flies that increased their firing rates when exposed to MPO, providing insight into how the pheromone mediated the flies' behavior. The discovery of MPO as a potent tsetse fly attractant offers promising prospects for slowing the spread of diseases transmitted by these insects. 

Currently, the most effective method of controlling tsetse fly populations is through traps that use odors from the preferred animals the flies feed on. 

"Now we've found this pheromone that could be used in combination with the host odors," Carlson said. "Especially since MPO not only attracts the flies but causes them to freeze where they are."

While animal odors are effective in attracting tsetse flies over large distances, they quickly fade. However, MPO works at shorter distances but remains effective for more extended periods. This characteristic makes it a valuable tool in the fight against tsetse flies and the diseases they spread. 

According to the release, the researchers are now collaborating with partners in Kenya to test the efficacy of using MPO in real-world traps, moving beyond laboratory settings to determine its practical applications. Furthermore, the team aims to understand the reasons behind the tsetse flies infected with trypanosomes emitting an entirely different set of chemicals, another notable finding from the study, and its potential impact on fly communication. 

The potential to develop innovative approaches for tsetse fly control and disease prevention becomes increasingly promising due to this type of research. The newfound understanding of tsetse fly communication through pheromones offers hope for reducing the burden of African sleeping sickness and nagana and improving the lives of millions across sub-Saharan Africa.