Why might stinky feet be so important in the fight against malaria?

Not so long ago while flicking channels as is my usual bad habit I caught part of Tony Jones’ interview with Bill Gates on a special feature episode of ABC television’s Q and A during Gates’ fly-in-fly-out visit to Australia promoting the Bill and Melinda Gates Foundation. I was curious for as founder of Microsoft he doesn’t have a particularly positive image among more liberal (note the small ‘l’) thinkers. And apart from the negative press I knew little about him or the foundation. Well, I may be gullible but I was quickly impressed by his quiet manner and the way he spoke in a fairly self-deprecating style.  Furthermore, my long-held sympathies towards developing nations struggling with diseases which we are hardly aware of in Australia were touched by the sincere and intelligent response from Bill Gates to a question from a Papua New Guinean Health worker.  I am including a clip below if you are interested in hearing what he had to say.

 

Since then I have been doing a little reading about malaria and the latest reported research (across disciplines). From a simple web search one quickly sees there are a great many groups working towards reducing the incidence of malaria around the world through preventative measures such as supplying mosquito nets, removing mosquito ‘habitat’ or implementing vaccination programs, research, community development, health education, and there are also a great many people supporting through donations and fundraising. Recently, two young university students from Burkina Faso and Burundi won the Global Social Venture Competition (GSVC) for inventing a mosquito deterring soap which they named Fasoap. Quoted in an online article they said, “In our country the majority of the population lives below the poverty line… most people can’t afford to regularly buy medicines and products such as anti-mosquito creams, sprays or protective nets,” but Fasoap will be cheap enough for most households to afford to use and can replace the standard soap in the house.

Soap Creators, Moctar Dembele from Burkina Faso and Gerard Niyondiko from Burundi

Soap Creators, Moctar Dembele from Burkina Faso and Gerard Niyondiko from Burundi

Malaria is a mosquito-borne infectious disease. It begins with a bite from an infected female mosquito, which introduces the microorganisms through saliva into the circulatory system from where they travel to the liver to mature and reproduce. Symptoms of malaria may include headache and fever and can lead to coma and/or death. Unfortunately there is no vaccine yet. Resistance has already developed to several anti-malarial drugs and increasing resistance to others is becoming a problem. (Thanks to Wikipedia for some of that info). Malaria is a huge problem affecting thousands of people through ill-health as well as the loss of loved ones. The loss of economic productivity for families, communities and developing nations is also immense and an obstacle to poverty alleviation and sustainable development in many affected nations.

A novel area of research is looking at the use of insect-killing fungus such as Beauveria bassiana as an active ingredient in biopesticides (‘a form of pesticide based on micro-organisms or natural products’[i]) against mosquitoes which transmit malaria. This has become necessary as mosquitoes become increasingly resistant to existing to conventional chemical insecticides. Interestingly, research has also shown, that the slow death by biopesticides makes it harder for the mosquito to build up a resistance.

Malaria kills more than 600,000 children each year and although this seems amazingly high there is only a mortality rate of 0.3% reflecting the high number of reported cases of over 200 million. Early diagnosis and treatment significantly control the mortality rates but it has also been proven that some people (particularly from regions in Africa) are naturally able to resist greater severity of the disease suggesting genetic factors play an important role.

Current research is looking to identify the genes affecting an individual’s immunity to malaria and from this potentially understand the molecular basis of protective immunity against the disease – and be able to apply this to the development of an effective malaria vaccine. For example researchers from MalariaGEN (Malaria Genomic Epidemiology Network)[ii] are conducting four key areas of research addressing different aspects of the problem:

  • Genetic determinants of resistance to malaria
  • Genetic determinants of the immune response to malaria
  • Human genome variation in malaria-endemic regions
  • Genetic linkage studies of resistance to malaria

The following animation from the Wellcome Trust Centre for Human Genetics (Oxford, UK) which is ‘home’ to MalariaGEN cleverly explains the purpose of the research. It also has a good percussion soundtrack so turn on your audio.

This is all interesting reading for some but all of you (whoever you are) may also be wondering where smelly feet come into it or if that was just a ruse to lure you into reading my post. Well you are half right – it was designed to lure you in but it isn’t a ruse.  I was inspired by the recently published research (peer-reviewed), ‘Malaria Infected Mosquitoes Express Enhanced Attraction to Human Odor’[iii], and some associated reporting[iv].

There is existing evidence some pathogens (such as malaria) can manipulate their hosts or the vector (the mosquito) to better aid in their spread from their mosquito host to assist transmission. The researchers, Smallegange et al (2013), have found mosquitoes are more likely to be attracted to human odour than others and malaria-carrying female mosquitoes (Anopheles gambiae sensu strict) are even more attracted to the human odour than those that are not infected. This is better illustrated by the useful little graph below sourced from the published paper.

Attraction of malaria infected mosquitoes to human odor. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0063602

Attraction of malaria infected mosquitoes to human odor. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0063602

To cut a long story short Smallegange et al discovered this by using a nylon matrix which had been treated with human odour and a clean control nylon matrix placed in a cage olfactometer with 20 infected mosquitoes and proceeded to count how many times and beneath which nylon matrix the mosquitoes landed (including ‘probing attempts’) in a 3 minute period. The same test was separately undertaken with uninfected mosquitoes.

[As an aside, I can imagine you wondering what a ‘nylon matrix’ is – some wondrous piece of technologically advanced lab equipment? Perhaps some sort of synthetic (nylon) net (matrix)? As it turns out what they used was simply a ‘panty-sock’ – which I take to mean some version of pantyhose. And they acquired the human odour by availing a man to wear the said panty-sock for twenty hours prior to the experiment. For those who may have any concerns for the man providing foot odour, the lead researcher/author also ‘performed odour collection on herself by wearing nylon stockings’. (!?!?)]

The results show infected female mosquitoes are more attracted to human odour than non-infected mosquitoes, indicating the pathogen effects the mosquito host’s behaviour and most likely in within their olfactory system. There is further research to be done to determine what impact the lifecycle stage has on the host’s attraction to human odour, as well as odour from multiple human subjects.

Why is this important in the fight against malaria? The researchers point out, ‘Further studies on the identification of new attractants for improved mosquito surveillance or trapping programs specifically targeting P. falciparum infected An. gambiae s.s. [malaria carrying mosquitoes] females may provide powerful tools for the global agenda of malaria eradication’(p.3).  Furthermore, “Every time we identify a new part of how the malaria mosquito interacts with us, we’re one step closer to controlling it better.” Dr James Logan, who headed part of the research at the London School of Hygiene and Tropical Medicine was quoted as saying in the news.com.au online article.

So in summary, we need more people to people to start using Fasoap on their smelly feet …  while also spreading insect-killing fungi about. Interestingly while the fungal infection from the biopesticide can take up to two weeks to kill the host mosquito, during that time it significantly impairs the hosts ability to respond to host-related odour cues by flying up wind as well as a ‘suppression of olfactory receptor neurons tuned to 1-octen-3-ol, a mammalian odorant known to attract biting flies, including mosquitoes’[v]. It all comes back to the smell doesn’t it? And there was I believing the malaria mosquitoes were the kamikaze-esque villains but really they’re more akin to mindless zombies driven by their ‘noses’ ….. hmmm, now why didn’t I use that for a title?

So, malaria is and will continue to be fought on many fronts. While I have looked at some of the more scientific approaches, it is also clear from the extra reading I have done that an interdisciplinary approach is still required with collaboration with government and aid agencies. There is more to write in follow-up but I am now at the end of my word limit.

Take care,

the Domestic Scientist.


[i] <http://ec.europa.eu/environment/integration/research/newsalert/pdf/134na5.pdf> European Commission (2008) Encouraging innovation in biopesticide development.

[ii]community of researchers in more than 20 countries who are working together to understand how genome variation in human, Plasmodium and Anopheles populations affects the biology and epidemiology of malaria, and to use this knowledge to develop improved tools for controlling malaria’ http://www.malariagen.net/about

[iii] Smallegange R, van Gemert G-J, van de Vegte-Bolmer M, Gezan S, Takken W, Sauerwein RW & Logan, JG 2013,  ‘Malaria Infected Mosquitoes Express Enhanced Attraction to Human Odor’, PLoS ONE, vol.8, no.5.

[iv] ‘Stinky feet may lead to better malaria traps, help fight the mosquito-borne disease’ June 04, 2013.
Read more: http://www.news.com.au/technology/sci-tech/stinky-feet-may-lead-to-better-malaria-traps-help-fight-the-mosquito-borne-disease/story-fn5fsgyc-1226657371727#ixzz2Z1lnnpW5

[v] George J, Jenkins NE, Blanford S, Thomas MB, Baker TC, 2013, ‘Malaria Mosquitoes Attracted by Fatal Fungus’, PLoS ONE vol. 8, no.5, p.1.

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