In a previous post on July 16, 2013, ‘All in the mind… the placebo effect’ I described the concept and origins of placebos and the placebo effect. This post shifts focus to the changing perception of placebos within the field of scientific research and clinical practice using published articles framed by counter arguments. The literature largely signals a growing interest in the use of placebos – not because researchers believe placebos have the power to trick the mind into healing the body but because there is an increasing body of research providing evidence linking chemical reactions in the brain to development of our expectations which moderate and influence our behaviour and perceptions. (Scott et al 2007)
[I have included a couple of short videos which entertainingly explore the placebo effect…. and so if you aren’t in the mood for reading, or short of time scroll straight down to the visual aids. Alternatively if you are in the mood for some interactive experience watch the video at the end and follow the accompanying link to test one person’s idea of the placebo effect through an app. I am by no means recommending the app as I have not tested it myself being still rather old fashioned when it comes to phones but it could be fun – and by all means let me know. ]
And now back to the topic at hand….
Placebos have been critical in the running of randomized clinical trials as a comparison marker. As Kaptchuk writes in The Lancet (1998), ‘Until the RCT, medical therapy became legitimate because of beneficial outcomes; after the RCT, a medical intervention was only scientifically acceptable if it was superior to placebo… method became more important than outcome’, (p. 1724). Critics also recommend that a third ‘no treatment’ control group is used to gauge the placebo effect.
In some cases, it has also been shown that well-established prescribed medical interventions are no more effective than a placebo (or perhaps I should say the placebo is no less effective) suggesting that the effectiveness of the branded product is probably only due to the placebo effect. This seems quite profound when considering our increasing consumption of drugs and ballooning expenditure in the over-burdened health system. To read of widely prescribed anti-depressants such as Prozac testing no better than a placebo seems shocking. And this is not to suggest the anti-depressants in question are just ‘sugar pills’ – just their ingredients are not active for that specific illness. A survey of General Practitioners in the US revealed that 50% regularly prescribed ‘placebos’. This raises another concern regarding the possible side effects of non-active medical inventions (whether a drug or procedure) with other active ingredients upon people’s health which could be avoided.
So how can any non-active treatment seemingly be so effective?
‘The scientific study of the placebo and nocebo effect is part of the exciting advances in modern neuroscience on the way in which the brain normally controls many bodily functions. We do know that this is mostly done by operating below conscious awareness’, writes Marcello Costa, Professor of Neurophysiology, Department of Physiology at Flinders University.
Animation: ‘The Strange Powers of the Placebo Effect’ from The Professor Funk.
The body of current research points to several factors underlying the placebo effect which are only now being unravelled through more extensive research and the use of such tools as magnetic resonance imaging (MRI) scans to understand how the brain reacts to medical intervention. Between accumulated research findings and new MRI brain scans taken during testing as proof, it appears the ‘effectiveness’ of placebos which induce a sense of increasing wellbeing and also alleviate specific types of symptoms is linked to the opioid system. Researchers have found that placebo effects can stimulate real physiological responses, from changes in heart rate and blood pressure to chemical activity in the brain, in cases involving pain, depression, anxiety, fatigue, and even some symptoms of Parkinson’s disease. From research in the late 1970s we have known the placebo effect is linked to the release of endorphins which are the brain’s ‘natural pain relievers’ when it was shown that blocking the release of endorphins removed the placebo effect (Feinberg 2013). We can be conditioned to release such chemical substances as endorphins, catecholamines, cortisol, and adrenaline. Telling research participants they will likely experience adverse effects from the placebo treatment also reliably leads to them reporting those same symptoms – this is called the nocebo effect.
Challengers to alternative medicine practitioners and those who believe it is purely a case of ‘positive thinking’ propose the placebo effect can be largely attributed to a mix of the following mechanisms;
- Natural history where illnesses naturally peak and then taper off with recovery – patients usually seek medical treatment at the peak and so recovery correlates with treatment;
- Regression to the mean (natural fluctuations in illnesses);
- Standard medical and nursing care;
- Impact of modified rest, diet, exercise and relaxation;
- Reduction of anxiety by receiving a diagnosis and prescribed treatment;
- Influence of the doctor-patient relationship (including the desire by trial participants to ‘give the right answer’);
- Expectation of recovery; and
- Classic conditioning (which on a very basic level refers to our learned belief associating medical intervention with recovery but can also be more complex).
It is, however, difficult to unravel and measure these often inter-dependent mechanisms, especially when their significance will naturally vary from patient to patient. (McCann et al 1992)
Studies have also found the placebo effect is influenced by the manner of the placebo delivery and these variables needs to be accounted for in trial results. It has been shown in the last decade that variables such as the form of placebo delivery (pill versus injection, or pill colour or size); demeanour of the placebo provider (level of verbal interaction, body language, perceived level of ‘care’,etc); framing of the procedure; aims and expectations to participants; physical environment (hospital versus standard room); and there are now even claims that individuals will be variously disposed towards the placebo effect dependent upon their genetic make-up (Furmark 2008). There is also a recognised predisposition of participants to try to please with their responses which may skew results. Hence the push for a double-blind testing approach in trials to measure these influences.
Dean Leyson’s : The Placebo Effect (BTW if you can’t pick his accent, it’s Belgian)
Here is a list of placebo influencing factors:
- trusted brand-name drugs work better than others;
- expensive treatments work better than cheaper ones;
- green pills may be better for phobias and anxiety;
- red and yellow pills may work better for depression;
- sham devices may work better for pain than pills;
- treatments work better if administered by a practitioner perceived as being kind, warm and caring; and
- in general, invasive treatments (eg. surgery, injections, procedures) seem to work better than less invasive ones.
The sense of recovery and healing people credit to alternative therapies is also attributed by sceptics to a placebo effect. For example a study undertaken by Harvard Medical School researchers demonstrated that of the participants suffering from Irritable Bowel Syndrome those who experienced the greatest alleviation of discomfort had who received the most attention and care in the form of pretend acupuncture and non-active medication. All participants received fake treatment but were either given a minimal or high level of attention and interaction from those administering the treatments.
Numerous studies have demonstrated the placebo effect can be a significant factor in people’s sense of recovery – even if this is subjective on the part of the patient rather than an objective reduction in illness. This is why a growing number of researchers and medical practitioners believe placebos should no longer be wholly defined by their inert content/ attribute. Focus should be shifted to what the, ‘placebo intervention – consisting of a simulated treatment and the surrounding clinical context – is actually doing to the patient. Accumulated evidence suggests that the placebo effect is a genuine psychobiological event attributable to the overall therapeutic context,’ (Finniss et al 2010, p. 686). Thinking about this and the evidence of the placebo effect for pain relief, I wondered whether there was a role for the placebo in palliative care where it would perhaps raise less ethical issues. Something I will discuss in my final post on the placebo effect… to come.
In a US study involving asthma sufferers, it was shown the placebo had little effect on the measurable physical outcome of lung function (equal to the ‘no treatment’ control group) measured through lung capacity testing; versus the administration of a standard albuterol bronchodilator. However, the participants themselves reported improvements in terms of relieving discomfort and self-described asthma symptoms equal to albuterol. This supports the theory a ‘subjective’ placebo effect exists and that a placebo treatment may be just as effective as active medication in improving patient-centred outcomes. ‘It’s clear that for the patient, the ritual of treatment can be very powerful,’ notes Kaptchuk. ‘This study suggests that in addition to active therapies for fixing diseases, the idea of receiving care is a critical component of what patients value in health care. In a climate of patient dissatisfaction, this may be an important lesson.‘
Here’s how to administer your own placebo effect…. but at your own risk…
[NB having read the webpage and various blog posts of the app’s creator I have to say I don’t endorse much of what is written… a little too much ‘feel good’ content which in my opinion doesn’t accurately reflect scientific research despite using it to support their advocacy of the placebo effect… and business idea]
And here’s your very last little pill … There is also a published study (Furmark 2008) which claims to have found a certain variation of a gene linked to the release of dopamine which makes the individual far more susceptible to the sham treatment and therefore also the placebo effect. The ability to screen prospective trial participants based upon a lower susceptibility to the placebo effect is argued for on the basis of creating more efficient medical trials, reducing the time and costs of testing and therefore getting effective treatments onto the market faster and more cheaply to benefit patients.
Some recommended further reading:
A third and final post will discuss contrary views and ethical considerations attached to the administration of placebos. Did you know placebos are still regularly ‘prescribed’ by GPs here and overseas?
Until next time,
the domestic scientist.
As a Thursday night post I’ve decided to share my mini class presentation with you. How lucky are you?! (But ‘lady luck’ could be a whole other blog post topic…)’
As part of the assessment for our ‘Communicating with Science’ course we were required to mentally digest and communicate the contents of a peer-reviewed scientific journal article in a 2 minute timeslot followed by a brief Q & A with our classmates and a couple of obliging ring-ins. It was a very useful and practical exercise pin-pointing what the most significant and interesting aspects of the paper were with a view to being able to then communicate the information clearly and accurately… and of course, engagingly. With another assignment due the previous night preparation time was limited…
I opted for a 2013 paper I had already read for my blog post, ‘Why might stinky feet be so important in the fight against malaria?’ but had only briefly referenced. This is a tale of fatal attraction and I hoped its quirkiness might appeal to the audience comprised of my classmates (and assessors) as it had to me.
The paper detailed experiments focussing upon fungus as an active ingredient in a biopesticide control of malaria mosquitoes. I love it when the natural world has the answers, and especially when those solutions can trump our own ‘inventions’ and their associated adverse side effects. And so the concept of biopesticides (with a likelihood of less harmful side effects) seems really cool to me.
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.
A mounting problem with preventative measures for controlling malaria is that mosquitoes are becoming resistant to some chemical insecticides and so some researchers are looking at alternative biopesticides (‘a form of pesticide based on micro-organisms or natural products’).
(Click on slide for enlarged image)
In this case the active ingredient under research is a fungus called Beauveria bassiana which infects insects and kills them slowly (in relative terms for insects… 1-2 weeks for mosquitoes).
(Click on slide for enlarged image)
Previous research has shown insects may be deterred from landing upon pesticides which are harmful to them. If the fungus proved a deterrant to its target than it would not be an effective active ingredient in a biopesticide. Hence, the researchers wanted to see if mosquitoes would be repelled by the Beauveria bassiana. They did this by giving a ‘cage’ of mosquitoes a choice between two fungi using a y-tube olfactometer (I like to call it a ‘smellometer’). And to the researchers’ collective delight, the mosquitoes chose Beauvaria (despite its fatal effects) over the less harmful and obviously less sweeter smelling Penicillium. This suggested the Beauveria bassiana smells almost irresistible to female mosquitoes. That would seem to suggest the researchers had been successful in reaching the objective of their experiments… but they wanted to go further. They knew mosquitoes would almost definitely become infected by landing upon a surface to which dry fungi spores had been applied (tests showed a 95% likelihood) but this would likely prove a very onerous, time intensive and expensive task – especially when considering the extent of land where malaria is present. And so the researchers also looked to prove that Beauveria bassiana is irresistible to female mosquitoes through ‘natural’ transfer.
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In this case, the fungus takes advantage of the mosquitoes somewhat gruesome predilection for feeding upon insect larvae, dead or alive. And mosquitoes are particularly partial to the squishy, tender bodies of caterpillars…
(Click on slide for enlarged image)
… which may already be infected by Beauveria bassiana and dying a slow death. The researchers tested a hypothesis that female mosquitoes would be drawn to infected caterpillars over infection free caterpillars. (Click on slide for enlarged image)
The earlier test was repeated but with cadavers of caterpillars infected with Beauvaria bassiana against caterpillar cadavers which weren’t infected. Similar results were achieved.
(Click on slide for enlarged image)
While this proves that Beauveria bassiana could be a very useful active ingredient in bio-pesticides to prevent malaria, the researchers couldn’t fully explain the fatal attraction the fungus had for the female mosquitoes. These are also experiments at the early stage of developing a biopesticide. Conclusion: More research needs to be undertaken.
(Click on slide for enlarged image)
Interestingly, research has also shown, the slow death by biopesticides (in comparison to the rapid death caused by insecticides) also makes it harder for the mosquito population to build up a resistance. Isn’t that cool considering the ability of mosquitoes to build up resistance to traditional pesticides has been affecting the ability to control mosquito populations recently? Win-win, I say.
(Click on slide for enlarged image)
In case, you’re wondering – Yes it did run over the allocated two minutes…. do you know how fast two minute speeds by? Feedback suggested I could have left out slides 4, 5 & 6 and just covered the key investigation of the experiment.
Interesting questions I fielded from the audience included among others: whether application costs of biopesticides were affordable and would this affect its viability ergo was cost a factor between traditional pesticides and biopesticides; and could mosquitoes infect eachother… do they feed on eachother as they do on other insects? Do any readers know the answers?
Placebo – Drug of Champions?
Could infamous cycling champion, Lance Armstrong, have done so well if his ‘drug of choice’ had been a placebo? I pose the question because it may not be as ludicrous as it sounds according to research by Italian neuroscientist Dr Fabrizio Benedetti. Although with hindsight, believing Armstrong was so successful without assistance seems just as ludicrous.
Most people have probably heard of ‘the placebo effect’. This is a term I seem to be hearing with more regularity and recently I have begun to wonder if it has become just another fashionable, catchy saying; likely misunderstood and misapplied but used nevertheless because it sounds edgy and knowledgeable.
There also seems to have been a cultural change in attitude towards the framing of placebos. This may be due in large part to increasing distrust of prescription medications and the appeal of the idea of non-intrusive healing through ‘positive thinking’ or of ‘mind over matter’; especially when the terminally ill and their loved ones are desperately looking for a cure where conventional treatments no longer give any hope. Guess et al (2002) also note a shift in the bio-medical research field and among medical practitioners, describing the placebo as, ‘transformed in a few short years from a sham in medical practice and a control agent in clinical trials to a therapeutic ally’, (p.1).
To most lay people I think ‘the placebo effect’ is commonly understood in reference to patients taking a ‘pretend medication’ (placebo) but when believing it to be real attest to a physical response to the ‘medication’ – which may be either positive or adverse. This is how I would have explained the placebo effect if asked but I was by no means sure I understood the phrase properly either. Are people really misinformed when they think the placebo effect points to an ability of the mind to enhance the body’s ability to overcome physical ills? It is certainly an appealing concept and one which can seem more reasonable when we are forever being told how little we truly understand the workings (or unmapped potential) of the human brain.
And so sensing I was on shaky ground in my own understanding of the placebo effect I decided to make it the topic of a couple of blog-posts and I discovered there are a number of interesting perspectives to discuss.
So here goes…. a brief history on the origins of the placebo…. (and its effect).
The term ‘placebo’ comes from the Latin verb ‘placare’ which means ‘to please’ (as opposed to ‘nocebo’ which means ‘to harm’). Although ‘placebo’ started to be used in English during the 13th century, it wasn’t part of medical terminology until the late 18th century. A medical dictionary from 1811 defined the term as ‘any medicine adapted more to please than benefit the patient’ which reflects the practice of doctors of the time to give some patients placebos in the form of bread or starch pills because they had little confidence in the efficacy of their ‘real’ range of medications. Doctors would also prescribe ‘sub therapeutic doses’ of ‘pharmacologically active drugs’ (Edward 2005, p.1023) in order to satisfy those patients who were simply looking for the process of treatment and possibly to protect their authoritative standing.
Generally, a placebo is an inert substance with no inherent pharmacological activity, and looking, smelling and tasting like the real drug being used. An ‘active placebo’ may be used which is one possessing its own inherent effects but which don’t apply to the condition for which it is being prescribed. A placebo may also be a procedure rather than drugs or medication. This can be quite extreme extending to placebo surgery where a patient is anaesthetised and ‘superficial procedures’ including skin incision are performed without surgery being undertaken (Rajagopal 2006). I have been wondering if the previously mentioned ‘placebo surgery’ is a treatment or a component of clinical trials. Either use is somewhat hard to fathom and points to much of the current debate surrounding the ethics of using placebos through deception, although technically participants in clinical trials must be made aware that they may receive a placebo rather than the active drug or real procedure.
The phrase ‘the placebo effect’ has been attributed to American anaesthetist Henry K. Beecher in his work, ‘the powerful placebo’ (1955), when he reported that, on average, a third of his patients with a range of medical complaints improved when taking placebos. Rajagopal (2006) claims this then led to the use of placebos in the establishment of randomized control trials (RCT) where ‘active drugs’ are tested against placebos rather than no treatment which Edwards (2005) suggests, ‘implicitly assumes that the placebo itself exerts an effect’ although not of a pharmacological nature (p.1023).
In the next blog-post I will identify current opposing (as well as overlapping) views of researchers about the application of placebos, including a case study, and return to make sense of the question first posed by this post: Could Lance Armstrong have done so well if his ‘drug of choice’ had been a placebo?
Edwards, M 2005, ‘Placebo’, The Lancet, vol. 365, pp 1023.
Guess, HA, Kleinman, A, Kusek, JW, Engel, LW 2002, The Science of the Placebo, BMJ Books, London.
Rajagopal, S 2006, ‘The placebo effect’, The Psychiatrist, vol. 30, pp 185-188.
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.
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.
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.
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.