These new insights might lead to a new line of clinical laboratory testing, particularly if the results could guide the patient to microbiome-based repellents that would remain effective for months once applied
Researchers are beginning to identify what compounds make individuals more attractive to mosquitos. That is a first step in the development of a biomarker that could be developed into a clinical laboratory test. Question is: would there be enough consumers wanting to do a lab test to determine if they were highly attractive to mosquitos, thus making this a revenue-generating test for labs?
The SA article reported on their study published in the journal Cell titled, “Differential Mosquito Attraction to Humans Is Associated with Skin-Derived Carboxylic Acid Levels.” The researchers, according to SA, found that individual humans have “a unique scent profile made up of different chemical compounds” and that “mosquitoes were most drawn to people whose skin produces high levels of carboxylic acids.” The researchers also found that “attractiveness to mosquitoes remained steady over time, regardless of changes in diet or grooming habits.”
At a minimum, there would be widespread consumer interest to at least understand why some individuals get more mosquito bites than others. What may be of particular interest to microbiologists is the statement by molecular biologist Omar Akbari, PhD, of the University of California, San Diego, who told Scientific American that by “taking human-colonizing skin bacteria … and engineering them in such a way that they can either express a repellent compound or be able to degrade something that’s attractive,” a mosquito repellant could be developed that would last for months once applied.
“This study clearly shows that these acids are important,” neurogeneticist Matthew DeGennaro, PhD (above), told CNN. “… how the mosquitoes perceive these carboxylic acids is interesting because these particular chemicals … are hard to smell at a distance. It could be that these chemicals are being altered by … the skin microbiome … if we understand why mosquitoes find a host, we can design new repellents that will block the mosquitoes from sensing those chemicals, and this could be used to improve our current repellents.” Clinical laboratory testing will be needed to produce biomarkers for developing such improved repellents. (Photo copyright: Laboratory of Tropical Genetics.)
Clinical Laboratory Testing Needed to Identify Levels of Carboxylic Acids
To complete their study, the researchers had 64 participants wear nylon stockings for six hours on their arms to get their unique scent into the fabric. The scent on the stockings was not discernible to the human nose, but it was to the mosquitos.
Two pieces of the nylon were then placed in a closed container with Aedes aegypti mosquitoes. The researchers found that certain samples were more popular with the mosquitos than others. Upon further analysis the researchers found that the most popular samples came from subjects with higher levels of carboxylic acids, and the least popular had the lowest levels. The scientists ran the test with the same participants several times over three years and the results remained largely the same.
Carboxylic acid is an organic compound found in humans in sebum, the oily layer protecting our skin. The level at which humans release carboxylic acid varies from person to person. And there is no discernible way the human nose can determine whether a person has the level of carboxylic acid on the skin that mosquitos find desirable. The answer would need to be determined by a diagnostic test performed in a clinical laboratory.
Although the development of a test to determine someone’s susceptibility to mosquitos may be far away, there could be significant consumer interest in developing such a test.
“The question of why some people are more attractive to mosquitoes than others—that’s the question that everybody asks,” Leslie B. Vosshall, PhD, Chief Scientific Officer, Howard Hughes Medical Institute, who led the research team to find out why some people are more attractive to mosquitos than others, told Scientific American. “My mother, my sister, people in the street, my colleagues—everybody wants to know.” She credits their interest as the inspiration for embarking on the study.
“Understanding what makes someone a ‘mosquito magnet’ will suggest ways to rationally design interventions such as skin microbiota manipulation to make people less attractive to mosquitoes. We propose that the ability to predict which individuals in a community are high attractors would allow for more effective deployment of resources to combat the spread of mosquito-borne pathogens,” the researchers wrote in their Cell paper.
Preventing Spread of Deadly Diseases
Although mosquitos are an annoyance, they also can be dangerous vectors of disease.
“Every bite of these mosquitoes puts people into public health danger. Aedes aegypti mosquitoes are vectors for dengue, yellow fever, and Zika,” Vosshall told CNN. “Those people who are magnets are going to be much more likely to be infected with viruses.”
Further research into these early findings may help develop diagnostic tests to protect against the spread of these diseases and identify individuals who are more attractive to the mosquitos, and therefore, more likely to contract and spread disease.
Being able to identify which individuals are mosquito magnets could help keep individuals safe from dangerous diseases, and development of a better repellent could also make outdoor summer events more bearable for the (unfortunately) popular among the pests. Medical laboratory tests associated with determining an individual’s susceptibility to mosquito bites could give clinical laboratories a new way to add value to consumers and patients.
An assay using mass spectrometry could go to clinical trial within two years
Dark Daily has regularly observed that humans generate a variety of volatile substances—particularly in breath—which can be used for diagnostic purposes. But what if people, like certain trained animals, could smell the presence of disease before the onset of symptoms? What types of clinical laboratory testing biomarkers could be developed based on human-generated volatile organic compounds?
Researchers at the University of Manchester (UM) in the United Kingdom (UK) say their “breakthrough” test to diagnose Parkinson’s disease “can diagnose disease from skin swabs in three minutes,” according to a university press release.
Perdita Barran, PhD (right), head of the University of Manchester research team that developed the mass spectrometry Parkinson’s test, is shown above with Joy Milne (left), the retired nurse from Scotland who inspired Barran’s team to develop a new Parkinson’s biomarker and method for identifying it. “We are tremendously excited by these results which take us closer to making a diagnostic test for Parkinson’s Disease that could be used in clinic,” she said in a press release. A viable clinical laboratory test for Parkinson’s disease is greatly needed, as more than 10 million people worldwide currently live with the neurodegenerative disorder. (Photo copyright: University of Manchester.)
Using Mass Spectrometry to Analyze Sebum
The UM scientists hypothesized that the smell could be due to sebum, a light oily substance on skin that was going through a chemical change due to the Parkinson’s disease, Hull Daily Mail explained.
Increased sebum, which is produced by the sebaceous glands, is a hallmark of Parkinson’s, the researchers noted.
Their new method involves analysis of sebum using mass spectrometry, according to the JACS AU paper. The method, the researchers claim, makes it possible to diagnose Parkinson’s disease from skin swabs in three minutes.
“There are no cures for Parkinson’s, but a confirmatory diagnosis would allow [Parkinson’s patients] to get the right treatment and get the drugs that will help to alleviate their symptoms,” Perdita Barran, PhD, told the Hull Daily Mail. Barran is Chair of Mass Spectrometry in the Department of Chemistry and Director of the Michael Barber Centre for Collaborative Mass Spectrometry at UM’s Manchester Institute of Biotechnology. “What we are now doing is seeing if (hospital laboratories) can do what we’ve done in a research lab in a hospital lab,” she added.
Sebum Analyzed with Mass Spectrometry
Parkinson’s disease—the world’s fastest growing neurodegenerative disorder—needs “robust biomarkers” that could advance detection and head off onset of motor symptoms such as tremor, rigidity, and postural instability, the researchers note in their paper.
Their recent study builds on earlier 2019 findings they published in ACS Central Science about volatile compounds in sebum possibly being used as Parkinson’s biomarkers.
“Sebum is an underexplored biofluid, which is readily obtained from non-invasive skin swabs, which primarily consists of a mixture of triglycerides, cholesterol, free fatty acids, waxy esters, and squalene,” the researchers explained in their JACS AU paper.
The scientists sought, “to develop a method to analyze sebum in its native state to facilitate rapid assessment of the Parkinson’s disease status. Paper spray ionization mass spectrometry, which allows the direct analysis of compounds from paper, has previously been demonstrated to detect small molecules from unprocessed biofluids, such as blood and urine, but not to date with sebum,” they wrote.
The UM researchers used mass spectrometry to analyze sebum collected on cotton swabs from the backs of 79 people with Parkinson’s and 71 healthy individuals, BBC Scotland News reported.
Depanjan Sarkar, PhD, Research Associate, University of Manchester, further explained the technique in the UM news release:
Sebum is taken from the swab to filter paper cut in a triangle.
Using a solvent and voltage, sebum compounds transfer into the mass spectrometer.
“When we did this, we found more than 4,000 unique compounds of which 500 are different between people with Parkinson’s compared to the control participants,” Sarkar said.
Fatty Acids Make Assay Possible
Could fatty acids pave the way to an assay? The UM researchers believe so.
“We have identified two classes of lipids, namely [triglycerides] and diglycerides, as components of human sebum that are significantly differentially expressed in PD,” the researchers wrote in JACS AU. “Non-invasive sampling followed by PS-IM-MS [paper spray-ion mobility–mass spectrometry] analysis targeting these compounds could provide an inexpensive assay to support clinical phenotyping for the confirmatory diagnosis of Parkinson’s disease.”
A clinical trial for their test, which costs about $20, may be done within two years in Manchester area, the Daily Mail reported.
When Dark Daily reported in 2020 on Joy Milne’s unique ability to smell her husband’s Parkinson’s disease before it was formally diagnosed, we predicted a diagnostic test for Parkinson’s may be years away. And here it is, albeit with regulatory clearance needed following clinical trials.
It may in fact be possible to leverage sebum analysis to detect other diseases, the UM researchers noted.
For diagnostics developers, this story of Joy Milne and her husband Les Milne is a useful example of how, in tracking the life of a specific patient with a specific disease and close family members, researchers were able to identify a new class of biomarkers that could be used in a diagnostic assay.
It will be interesting to follow the University of Manchester researchers in their quest for a diagnostic mass spectrometry clinical laboratory test for Parkinson’s disease. According to Parkinson’s Foundation statistics, about 10 million people worldwide live with the neurodegenerative disorder. Such a new diagnostic test could be vitally important to medical laboratory care, and to patients and their families.
