Mosquitoes always seem drawn to certain people, and theories have circulated over the years as to why—it's your soap, blood type, diet—but in the WHO African Region, which bears a disproportionately high share of the global malaria burden, the question demands an answer.
Using an ice-rink-sized outdoor testing arena in Zambia called a flight cage, researchers tested mosquito behavior under naturalistic conditions and gleaned critical insights into the chemistry of mosquito attraction to humans.
We asked McMeniman, a professor in the Department of Molecular Microbiology and Immunology at the Bloomberg School of Public Health, to discuss his findings and what they mean for the future of malaria prevention.
How does conducting research in this structure differ from conducting studies in smaller indoor settings?
In the laboratory, the majority of studies used to test mosquito smell preferences are performed on very small scales, in small boxes with volumes of around 0.5 cubic meters or less. For the study in Zambia we used a structure called a semi-field flight cage—a screened structure with a volume of around 1,000 cubic meters, about 2,000 times the volume used for regular laboratory assays.
In the flight cage, we can compare up to six humans' scents at a time. That increases the comparative power of the system—the number of comparisons that you can make between humans—by fifteenfold relative to two-choice experiments in the lab, in which you can only make one comparison between two humans.
Another powerful part of this system: We can test mosquito behavior under naturalistic conditions. Anopheles gambiae, the African malaria mosquito, likes to hunt at night when humans are sleeping. Using this structure, we can pipe the scent of humans sleeping in nearby tents into the cage to perform assays of mosquito landing behavior on targets heated to human skin temperature.
The most interesting part of this study was that mosquitoes consistently, night after night, would choose the same human scent and not prefer some humans.
Why is the role of human scent so important in understanding malaria transmission?
The most dangerous mosquito species for public health are those that have evolved a strong innate drive to seek out humans in their sensory environments. Anopheles gambiae feeds preferentially and frequently on humans, using their sense of smell to pick up on trails of scent emissions. Understanding what chemicals in human scent drive differential attraction to certain humans is important, because if we can identify these chemicals, we can help to inform personal bite risk.
Secondly, if we can understand what those chemicals are and how they blend together to provide an alluring fragrance for malaria mosquitoes, we could utilize that information to develop blends of molecules that are attractive to Anopheles gambiae and related malaria vectors to create human scent mimics that can be used as baits or lures in mass trapping efforts to control malaria.
How do these studies set the stage for advancing malaria research?
Using this system, we were able to discern through a small screen of six individuals that the most attractive human had a scent signature that was dominated by a class of molecules called airborne carboxylic acids. These are compounds produced by microbial metabolism on human skin. Interestingly, two of those carboxylic acids are also found in the headspace of cheeses, like Limburger cheese.
On the flipside, we found that one participant had a scent signature that was dramatically different from the others. It was depleted of airborne carboxylic acids and enriched for a compound known as eucalyptol, which was likely derived from the individual's plant-based diet.
This information could be used to create novel interventions to control malaria. For instance, by identifying microbes living on our skin that make us less attractive to mosquitoes, we could create new repellents that might ward mosquitoes away.
What's next for this research?
We're planning to build upon this semi-field system to conduct a large-scale screen of 100 to 120 humans in the next few years in Zambia. This work is being coupled in my laboratory with a higher-detail understanding of what we call the human volatilome, which is all of the chemical emissions emitted by the human body. We hope that by characterizing variability in the scent signature between humans, we can gain a high-resolution understanding of how we smell as humans and why we're so attractive to various bloodsucking insects.
We also genome-engineer mosquitoes to try to understand what neurons in their smell systems are responding to these chemicals and how this alluring blend emitted by humans is detected and processed in the mosquito nervous system to produce attraction to humans.
How can these findings translate into mosquito interventions in the U.S. and around the world?
We have plans to develop a similar system for mosquitoes found within the U.S. that pose risks to public health, including Culex mosquitoes, which transmit West Nile virus, and Aedes aegypti and Aedes albopictus, which are competent vectors for dengue and Zika.