Mosquitoes and the diseases they carry have killed more people than all the wars in human history combined.
Statistics indicate that the mosquito is by far the deadliest creature in the world to humans. In 2018 alone, the insect was responsible for around 725,000 deaths.
In that same year, the second deadliest animal was precisely humans, causing the death of 437,000 similar animals. And we were followed (with a long distance) by the combined aggressions of snakes, dogs, poisonous snails, crocodiles, hippos, elephants, lions, wolves and sharks.
This situation is naturally worrying and led the World Health Assembly — the annual decision-making event of the World Health Organization (WHO) — to approve, in 2017, the Global Response to Vector Control (GVCR). 2017-2030. This is an action aimed at strategically orienting countries to urgently strengthen vector control, among which mosquitoes stand out.
This insight is critical to preventing disease and responding to emerging infectious outbreaks. After all, mosquitoes can transmit numerous diseases, such as West Nile fever, Zika, dengue, yellow fever, chikungunya, St. valley fever, Semliki forest virus infection, Sindbis fever, Japanese encephalitis, Ross river fever, Barmah forest fever or malaria—the latter, responsible for 627,000 deaths in 2020 alone.
Carbon dioxide and body odors
Mosquitoes, male and female, could live without biting other animals. But females need blood to complete their reproductive cycle.
Almost a century ago, carbon dioxide (CO2) was identified as being attractive to mosquitoes. And that gas was used to capture the female mosquitoes, which look for the blood needed to acquire nutrients for oogenesis — the generation of eggs.
But there is no evidence available to indicate that CO2 acts as a gauge of the attraction differential. Also, carbon dioxide emission levels do not explain why mosquitoes systematically prefer one person over another. What is the reason then?
There are other physical-chemical signs that affect the mosquito’s attraction to certain people, particularly heat, water vapor, humidity, visual signs and, most importantly, the odors exhaled through the skin.
It is not yet known for sure which scents attract mosquitoes the most, but several studies indicate molecules such as indole, nonanol, octenol and lactic acid as main suspects.
A team of researchers led by Matthew DeGennaro of Florida International University in the United States has identified a unique odor receptor, known as ionotropic receptor 8a (IR8a), which allows the mosquito to Aedes aegypti identify lactic acid. As is known, this mosquito is the transmitter of dengue, chikungunya and zika.
When scientists mutated the IR8a receptor, found on insect antennae, they found that mosquitoes were unable to detect lactic acid and other acidic odors exhaled by humans.
Acetophenone: the ‘perfume’ that attracts mosquitoes
Recent research has indicated that dengue and zika viruses alter the odor of infected mice and humans to make them more attractive to mosquitoes. It is an interesting strategy, as it helps the insects to bite the host, withdraw their infected blood and transport the virus to another individual.
Viruses can do this by modifying the emission of an aromatic ketone – acetophenone – which is especially attractive to mosquitoes.
Normally, the skin of humans and rodents produces an antimicrobial peptide that limits bacterial populations. But it has been shown that, in mice infected with dengue or zika, the concentration of this peptide is reduced, and bacteria of the genus proliferate. Bacilluswhich activate the production of acetophenone.
In humans, a similar fact occurs: odors collected from the armpits of dengue patients contained more acetophenone than those of healthy people.
The interesting thing is that this can be fixed. Some of the rats infected with dengue were treated with isotretinoin, which reduced acetophenone emissions. As a result, the mice became less attractive to insects.
Microbes that alter odor
This is not the only case in which a microorganism manipulates the physiology of mosquitoes and their human hosts to favor their transmission.
People infected with the parasite that causes malaria, Plasmodium falciparumfor example, are more attractive than healthy individuals to Anopheles gambiae mosquitoes, vectors of the disease.
The reason is still unknown, but it may be related to the fact that Plasmodium falciparum produces an isoprenoid precursor called (E)-4-hydroxy-3-methylbut-2-enyl pyrophosphate (HMBPP). This precursor affects the mosquito’s blood-seeking and feeding behaviors as well as its susceptibility to infection.
Concretely, HMBPP activates human red blood cells to increase the release of CO2, aldehydes and monoterpenes, which together more strongly attract the mosquito and invite it to “suck our blood”.
And the addition of HMBPP to blood samples significantly increases the attraction aroused in other mosquito species, such as anopheles coluzzii, anopheles arabiensis, Aedes aegypti and species of the complex Culex peeps/Culex torrentium.
Understanding what are the factors involved in the preference expressed by mosquitoes to bite this or that person will help to determine and reduce the risk of spreading infectious diseases transmitted by vectors.
* Raúl Rivas González is Professor of Microbiology at the University of Salamanca, Spain.
This text was originally published here.