A new study led by Johns Hopkins researchers reveals the dynamics of a mosquito bite on human skin as never before. The work was supported by the Johns Hopkins Malaria Research Institute at the Johns Hopkins Bloomberg School of Public Health and the National Institutes of Health.
Mosquitoes are the deadliest creatures on the planet. Two groups of mosquitoes are responsible for most mosquito-related deaths: the malaria-parasite-carrying Anopheles—responsible for nearly 90%, or an estimated 610,000 deaths in 2024, according to the World Health Organization—and dengue-transmitting Aedes—an estimated 6% or 40,000 deaths. A subset of those who survive mosquito-borne illnesses can have lifelong aftereffects.
The researchers used advanced recording methods to capture the biting and feeding process of female mosquitoes that can carry pathogens that cause malaria, dengue, and other diseases, above and below the skin surface on a human host in real time. The researchers employed deep learning and other advanced computational techniques to analyze and synchronize the data to reveal the fine-scale female mosquito biting dynamics.
The team’s analysis of more than 550 mosquito bites on a human volunteer revealed well-defined actions, including probing for blood vessels beneath the skin surface, with notable differences between Anopheles and Aedes mosquitoes.
The researchers expect the experimental setup that includes custom-made devices and workflow they developed will be useful for scientists to research ways to disrupt disease transmission and to study the biology of mosquito biting.
The study was published October 21 in Science Advances.
To avoid confounding the results by using different human subjects, the study used just one volunteer—the study’s co-first author, Joanna Konopka, PhD, a research associate in the laboratory of study senior author Christopher Potter, PhD, professor of neuroscience at the Johns Hopkins University School of Medicine and faculty at the Bloomberg School’s Johns Hopkins Malaria Research Institute.
“We were struck by the ultra-fast synchronization of mouthpart and leg movements and observed five distinct sub-stages of mosquito bite under the skin: skin piercing, blood-vessel searching, blood ingestion, mouthpart retraction, and mouthpart withdrawal,” says Konopka. “The first two stages of the bite are most important for disease transmission, because this is when the pathogen is most likely to be introduced via mosquito saliva.”
Konopka’s co-first author was biomedical physicist Danny Poinapen, PhD, in the Department of Neuroscience at the Johns Hopkins University School of Medicine.
The authors think this work will be of significant interest to researchers across multiple fields, including researchers seeking new strategies to block transmission of mosquito-borne diseases.
Camera Ready
In order to produce their eggs, female mosquitoes take blood from animal hosts. They pierce skin using a highly flexible needle-like appendage called a stylet. Their saliva contains anticoagulants that stop blood clotting. This gives mosquitoes more time to find and drink from a blood vessel. Before they feed, they inject saliva into each bite. If female mosquitoes carry pathogens in their saliva, they can transmit those pathogens to the host during blood-feeding. An infected host can become a source of infection for mosquitoes that bite it, depending on the pathogen.
“Despite the fact that mosquitoes have been biting humans and transmitting disease for thousands of years, what happens during a bite has not been well understood, in part because so much of it takes place out of sight beneath the skin,” Potter says.
To meet this technical challenge, the team used electropenetrography—a method that detects tiny voltage changes—to record mosquito mouthpart actions below the skin surface—such as contact with a blood vessel. To capture mosquitoes’ rapid actions above the skin, the team used high-speed videography.
The study’s first recordings captured female Anopheles coluzzii, a common malaria transmitter in Africa. The researchers recorded with high resolution for what is believed to be the first time on human skin the complex orchestration of the insect’s mouthparts and other appendages as it searched for a suitable bite site, penetrated the skin, probed for and discovered blood vessels, drank its fill, and finally withdrew.
The data revealed previously unseen and unknown details of this sequence of events and confirmed the partial reliance of the process on sensory cues: The insect’s sensory appendages—including a pair of appendages called the maxillary palps—moved in close coordination with probing and biting actions, which were altered when key chemical-sensing genes in the insect were disrupted. Mutation of the IR76b gene—which is necessary for detection of compounds such as salts and acids—led to severe defects in initiating biting and finding a blood vessel. This suggests that mosquitoes rely heavily on their ability to flavor hosts—including humans—during the biting process.
The team used their experimental setup to perform a similar study of female Aedes aegypti mosquitoes, which can transmit dengue, yellow fever, Zika, and chikungunya virus infections. The scientists’ comparative analysis revealed significant differences between Anopheles and Aedes in their precise biting/feeding processes. Anopheles displayed a faster, more targeted blood vessel search while Aedes demonstrated a more exploratory blood-vessel search. Anopheles find a blood vessel about 17 seconds faster than Aedes mosquitoes.
Konopka says that while the mosquito biting data from the study represents a significant new resource for understanding mosquito behavior and disease transmission, the experimental platform she and her colleagues developed is itself an important asset that can be used for further mosquito-related science and translational efforts.
The authors note that capturing the mosquitoes’ biting dynamics in real time involved a team of collaborators from biomedical physics, neuroscience, and engineering at Hopkins and the HHMI Janelia Research Campus.
“We hope to use this platform to investigate how biting behavior is influenced by changes to mosquito factors such as sensory functions, age, and infection status, and of course by host factors such as age and diet, and the wearing of perfumes and insect repellents,” Konopka says.
“Coordinated Mosquito Biting Dynamics at the Human Skin Interface” was co-authored by Joanna Konopka, Danny Poinapen, Shivam Chitnis, Carmen Morrow, Gwyneth Card, and Christopher Potter.
The research was supported by grants from the National Institutes of Health (NIAID R01Al137078), Johns Hopkins Malaria Research Institute, and Natural Sciences and Engineering Research Council of Canada (NSERC-PDF). The Johns Hopkins Malaria Research Institute is supported by Bloomberg Philanthropies.
Mosquitoes are the deadliest creatures on the planet. Two groups of mosquitoes are responsible for most mosquito-related deaths: the malaria-parasite-carrying Anopheles—responsible for nearly 90%, or an estimated 610,000 deaths in 2024, according to the World Health Organization—and dengue-transmitting Aedes—an estimated 6% or 40,000 deaths. A subset of those who survive mosquito-borne illnesses can have lifelong aftereffects.
The researchers used advanced recording methods to capture the biting and feeding process of female mosquitoes that can carry pathogens that cause malaria, dengue, and other diseases, above and below the skin surface on a human host in real time. The researchers employed deep learning and other advanced computational techniques to analyze and synchronize the data to reveal the fine-scale female mosquito biting dynamics.
The team’s analysis of more than 550 mosquito bites on a human volunteer revealed well-defined actions, including probing for blood vessels beneath the skin surface, with notable differences between Anopheles and Aedes mosquitoes.
The researchers expect the experimental setup that includes custom-made devices and workflow they developed will be useful for scientists to research ways to disrupt disease transmission and to study the biology of mosquito biting.
The study was published October 21 in Science Advances.
To avoid confounding the results by using different human subjects, the study used just one volunteer—the study’s co-first author, Joanna Konopka, PhD, a research associate in the laboratory of study senior author Christopher Potter, PhD, professor of neuroscience at the Johns Hopkins University School of Medicine and faculty at the Bloomberg School’s Johns Hopkins Malaria Research Institute.
“We were struck by the ultra-fast synchronization of mouthpart and leg movements and observed five distinct sub-stages of mosquito bite under the skin: skin piercing, blood-vessel searching, blood ingestion, mouthpart retraction, and mouthpart withdrawal,” says Konopka. “The first two stages of the bite are most important for disease transmission, because this is when the pathogen is most likely to be introduced via mosquito saliva.”
Konopka’s co-first author was biomedical physicist Danny Poinapen, PhD, in the Department of Neuroscience at the Johns Hopkins University School of Medicine.
The authors think this work will be of significant interest to researchers across multiple fields, including researchers seeking new strategies to block transmission of mosquito-borne diseases.
Camera Ready
In order to produce their eggs, female mosquitoes take blood from animal hosts. They pierce skin using a highly flexible needle-like appendage called a stylet. Their saliva contains anticoagulants that stop blood clotting. This gives mosquitoes more time to find and drink from a blood vessel. Before they feed, they inject saliva into each bite. If female mosquitoes carry pathogens in their saliva, they can transmit those pathogens to the host during blood-feeding. An infected host can become a source of infection for mosquitoes that bite it, depending on the pathogen.
“Despite the fact that mosquitoes have been biting humans and transmitting disease for thousands of years, what happens during a bite has not been well understood, in part because so much of it takes place out of sight beneath the skin,” Potter says.
To meet this technical challenge, the team used electropenetrography—a method that detects tiny voltage changes—to record mosquito mouthpart actions below the skin surface—such as contact with a blood vessel. To capture mosquitoes’ rapid actions above the skin, the team used high-speed videography.
The study’s first recordings captured female Anopheles coluzzii, a common malaria transmitter in Africa. The researchers recorded with high resolution for what is believed to be the first time on human skin the complex orchestration of the insect’s mouthparts and other appendages as it searched for a suitable bite site, penetrated the skin, probed for and discovered blood vessels, drank its fill, and finally withdrew.
The data revealed previously unseen and unknown details of this sequence of events and confirmed the partial reliance of the process on sensory cues: The insect’s sensory appendages—including a pair of appendages called the maxillary palps—moved in close coordination with probing and biting actions, which were altered when key chemical-sensing genes in the insect were disrupted. Mutation of the IR76b gene—which is necessary for detection of compounds such as salts and acids—led to severe defects in initiating biting and finding a blood vessel. This suggests that mosquitoes rely heavily on their ability to flavor hosts—including humans—during the biting process.
The team used their experimental setup to perform a similar study of female Aedes aegypti mosquitoes, which can transmit dengue, yellow fever, Zika, and chikungunya virus infections. The scientists’ comparative analysis revealed significant differences between Anopheles and Aedes in their precise biting/feeding processes. Anopheles displayed a faster, more targeted blood vessel search while Aedes demonstrated a more exploratory blood-vessel search. Anopheles find a blood vessel about 17 seconds faster than Aedes mosquitoes.
Konopka says that while the mosquito biting data from the study represents a significant new resource for understanding mosquito behavior and disease transmission, the experimental platform she and her colleagues developed is itself an important asset that can be used for further mosquito-related science and translational efforts.
The authors note that capturing the mosquitoes’ biting dynamics in real time involved a team of collaborators from biomedical physics, neuroscience, and engineering at Hopkins and the HHMI Janelia Research Campus.
“We hope to use this platform to investigate how biting behavior is influenced by changes to mosquito factors such as sensory functions, age, and infection status, and of course by host factors such as age and diet, and the wearing of perfumes and insect repellents,” Konopka says.
“Coordinated Mosquito Biting Dynamics at the Human Skin Interface” was co-authored by Joanna Konopka, Danny Poinapen, Shivam Chitnis, Carmen Morrow, Gwyneth Card, and Christopher Potter.
The research was supported by grants from the National Institutes of Health (NIAID R01Al137078), Johns Hopkins Malaria Research Institute, and Natural Sciences and Engineering Research Council of Canada (NSERC-PDF). The Johns Hopkins Malaria Research Institute is supported by Bloomberg Philanthropies.
