Jeroen Spitzen quickly snaps on a glove. He takes a deep breath, as he rolls up his sleeve to expose his arm. Before him is a cage that is literally, buzzing with excitement. The colony within it is starved for human company.

He stoically eases his bare arm into the cage, sealing it shut so that none of its members escape. Almost immediately, he feels the first skin-prick—he is now delivering an invigorating blood meal for a female Anopheles mosquito. It is only a matter of seconds before others sense his presence and settle down to feed. In the next ten minutes, from four hundred to a thousand female mosquitoes will engorge themselves on his bare arm.

“It hurts more when they feed on fingers,” he states matter-of-factly.

That explains the glove.

“Volunteers could never start with this many mosquitoes in a cage.  You have to test first how sensitive you are, gradually building up immunity,” he continues.  “It took me about three months before I became immune to the bites.  Now, I still feel it during feeding but the itch will disappear within 30 minutes.”

“Hardly any swellings”

With that, he dismisses my many concerns.

***************

Anopheles gambiae, by James D. Gathany via Wikimedia Commons

Jeroen Spitzen and his colleagues are interested in how anthropophilic (human-loving) mosquitoes forage. How do they know there is a host nearby?  Is it our piquant odour?  Or perhaps the warmth emanating from our bodies?

CDC records indicate that over three billion people live in areas at risk of malaria transmission. In 2010 alone, the World Health Organisation estimates that malaria caused 219 million clinical visits, and 660,000 deaths.

aasdasd
Figure 1. Parasite life cycle in the human host and mosquito vector. Image from Derbyshire et al. (2011)

Malaria is a formidable adversary, and to answer these and other questions, the Laboratory of Entomology at Wageningen University has studied the ecology and behaviour of malaria mosquitoes for more than twenty years.

They have discovered the biological reason behind the exaggerated attractiveness of some humans to mosquitoes over others: Mosquitoes prefer humans with low diversities, but high abundances, of specific bacteria on their skin. The laboratory has also used olfactometers to identify synthetic compounds that either attract mosquitoes to traps or can serve as repellents. Intriguingly, just as Toxoplasmosis gondii can influence mice to run towards cats (the host for the next stage in their life-cycle), the Entomology lab has demonstrated that female Anopheles gambiae infected with Plasmodium falciparum are more attracted to their human hosts than those without the malaria parasite.

Although mosquitoes—specifically, those that are vectors of malaria—have been studied intensively, some fundamental questions regarding their behaviour still remain unanswered. We know that human kairomones—volatiles of one species that attract other species—serve as cues for anthropophilic mosquitoes such as Anopheles gambiae. These odours can be effective even in the dark. Other cues, such as heat, carbon dioxide, and visibility of prey, are less successful, but we are still trying to understand why this is so.

Once they sense a host nearby, how do mosquitoes respond?

***************

A team of researchers at Wageningen University have created a fascinating system to automatically track the flight of a single mosquito in three dimensions.

jhgjhg
Figure 1. Schematic diagram of wind tunnel. Air inlet (A1), lamination screen (LS), glass funnel containing heat element (F), mesh screen (S), release cup (RC), cameras (C1, 2), and IR lights (IR1, 2). Image adopted from Spitzen et al. (2013)

Within the wind tunnel, each mosquito was exposed to either heat, or a combination of odour and heat.  Researchers filmed the reflection of infra-red light off the mosquito’s wings to obtain three-dimensional flight tracks.

asdasdasd
Figure 3. Examples of flight tracks of Anopheles gambiae s.s. for each treatment viewed from different angles. Each treatment represents a single female. A-C clean acclimatized air only (9 s), D-F heat (21 s), G-I human odour (112 s), and J-L human odour+heat (231 s). Red tracks indicate flight paths outside the odour plume, and green tracks are within the plume. Image from Spitzen et al. (2013).

The source of the human odour? Just a worn sock!

***************

Approximately three-quarters of the 200 mosquitoes tested in this study, behaved such that clear tracks were able to be recorded. When exposed to wind alone, these mosquitoes flew directly into the wind, generally in a straight line. They performed similarly when a heat source was provided to them, flying directly toward it. However, flight patterns remained anything but simple when they sensed a human scent.

Mosquitoes displayed “prolonged and highly convoluted flight patterns” when within the odour plume from the dirty human sock.  When both heat and odour were used in combination, their flight became even more erratic, extended, and rapid.

These results are puzzling, as one could easily imagine that they could  be quite successful if they exhibited exactly the opposite behaviours to cues—in the presence of a warm, inviting host, a mosquito that identifies its prey, hones in on its target, and flies directly to it, should be highly effective. Instead, it appears as if these insects expend excessive energy on rapid, darting flight patterns in the vicinity of their host.

One explanation is that they are likely scanning their environment intensely, before alighting on the host for a meal. Of the female mosquito, Jeroen is emphatic that “taking a blood meal may be the most risk full event in her lifetime. She could be killed if she makes a mistake!”

I wonder if a direct flight path would result in far too many mosquitoes attempting to feed on a host at the same time? This would increase the chance that a host moves away, out of reach of the insects in the area. Convoluted flight paths, in conjunction with odour and heat cues, could have thus evolved as an optimised feeding strategy, to not only avoid flooding the host, but also to locate the ideal feeding area on the host.

Each mosquito is driven to reproduce as many times as she can during her life. The present study utilised only newborn mosquitoes that had not received a single blood-meal, since there is some indication from other studies that mosquitoes can adapt to cues over their short lifespans. The authors of this study suggest that their work could increase the efficacy of mosquito capture systems in areas with malaria:  They could optimize the location of odours released in relation to the entrance of the trap, and use a heat source to increase the landing frequency of wild mosquitoes.

***************

Mercifully, the mosquito colonies at Wageningen are too large to subsist entirely on human volunteers today. Instead, the laboratory has developed a system of membranes that, in conjunction with worn socks and carbon dioxide, are used to feed the mosquitoes (all mosquitoes within the lab are, of course, free of the malaria parasite, Plasmodium).

Those individuals that originally participated in the feedings—including Jeroen Spitzen and key personnel, Leo Koopman, André Gidding and Frans van Aggelen—have felicitously developed an immunity to the saliva of the mosquitoes.

“You understand that no employee can ever be forced to feed [the] mosquitoes.  Some people are more sensitive to bites than others, some just don’t like the idea,” states Jeroen, ever the pragmatist.

Frans van Aggelen claims that these unique experiences have improved his holidays: Where others routinely suffer, myself notwithstanding, he has the advantage of not feeling mosquito bites at all!

Sources:

Spitzen J., Spoor C.W., Grieco F., ter Braak C., Beeuwkes J., van Brugge S.P., Kranenbarg S., Noldus L.P.J.J., van Leeuwen J.L. & Takken W. & (2013). A 3D Analysis of Flight Behavior of Anopheles gambiae sensu stricto Malaria Mosquitoes in Response to Human Odor and Heat, PLoS ONE, 8 (5) e62995. DOI:

Verhulst N.O., Qiu Y.T., Beijleveld H., Maliepaard C., Knights D., Schulz S., Berg-Lyons D., Lauber C.L., Verduijn W. & Haasnoot G.W. & (2011). Composition of Human Skin Microbiota Affects Attractiveness to Malaria Mosquitoes, PLoS ONE, 6 (12) e28991. DOI:

Verhulst N.O., Mbadi P.A., Kiss G., Mukabana W.R., van Loon J.J., Takken W. & Smallegange R.C. (2011). Improvement of a synthetic lure for Anopheles gambiae using compounds produced by human skin microbiota, Malaria Journal, 10 (1) 28. DOI:

Smallegange R.C., van Gemert G.J., van de Vegte-Bolmer M., Gezan S., Takken W., Sauerwein R.W., Logan J.G. & Dimopoulos G. (2013). Malaria Infected Mosquitoes Express Enhanced Attraction to Human Odor, PLoS ONE, 8 (5) e63602. DOI:

Thumbnail imagery by Stacabom via Deviantart

More on Malaria:

Watch a video of mosquitoes tracked by the Wageningen team for this study.

The CDC provides an interactive feature that maps malaria endemicity across the globe.

Mosquitoes are glittering and beautiful up close.

Finally, beer consumption increases attractiveness to malaria mosquitoes; so watch out!

Advertisements