The continuing evolution of mosquito nets may spell the end of suffering from mosquito-borne diseasessteemCreated with Sketch.

in steemstem •  3 months ago


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How do you stop the world’s most effective killing machines?

Mosquitoes spread disease on a terrifying scale. Annually, mosquito-borne diseases are responsible for the loss of approximately 100 million years’ worth of healthy life (i.e. 100,000,000 DALYs per year, (see previous post for an explanation of this concept) and they are responsible for the vast majority of the transmission, suffering and deaths caused by the following diseases and many more:

[I was recently told that the image I had here was spectacularly wrong. So I have removed it before it become immortalised on this blog and becomes a constant source of embarrassment for me]

Image created for post. 1 DALY = 1 disability adjusted life years = Years dead before life expectancy + years living in suffering/disability (weighted by disability severity).
Data is from here, here and here.

With these little bastards causing more suffering in the world than any other insect or animal (yes that includes us humans, well sort of) I was excited to hear, this week, of a new intervention for their control that may very soon be brought into play.

Mosquitoes as a vector of transmission

In epidemiology, a vector is any agent that is responsible for transmitting a pathogen to another organism 1. For the above diseases their main vector for transmission is the mosquito. Mosquitos don’t contract the diseases themselves in this case, but instead carry diseases from one human to another as they go about their day to day business of sucking tasty blood out of unsuspecting, soon-to-be-pissed off and itchy mammals.

This presents an interesting opportunity for those of us who work in global health. Instead of treating the diseases when patients start to show symptoms, or vaccinating for the diseases one at a time, we can find a means of cutting the diseases off at their shared vector and as such reduce the prevalence of all mosquito-borne diseases at once.

With mosquito-borne diseases, there are a number of vector control methods available in our toolkit. Spraying houses with insecticides 2, removing standing water, genetically engineering mosquitoes to make them sterile 3, and even the use of Guppies 4 (this is one of my friends’ wonderfully strange, but effective, areas of research) all have their place in vector control. However, currently the most effective vector control method, by a long way, is bed nets.

Bed nets are perfect for this job, as the mosquitos that commonly carry the diseases in question mostly come out at night (mostly). As such, sleeping under a physical barrier such as a fine mesh mosquito net prevents the mosquitoes from getting anywhere near the individual underneath. If the net is well made, undamaged and used correctly, this intervention is 100% effective.

But that doesn't mean 100% is the most effective that this intervention can be. No, no, no, we can in fact do far better than this!

Long lasting insecticide treated bed nets

Long-lasting insecticide treated bed nets (LLINs or ITNs) are one of the most spectacular innovations to come out of evidence-based global health in a long time (they’re no PlayPumps, that's for sure).

Not only do these special nets offer a durable physical barrier against mosquitos, but they are coated with an insecticide designed to kill any mosquito that lands on it (when a mosquito is killed in this way it’s known as knock down, how lovely a phrase is that?). This not only means that us tasty humans under the nets are protected by a lightweight breathable barrier, but also, occasionally, that barrier takes a disease-carrying mosquito out of the sky for good, ensuring that they don’t infect anyone else. As such, the nets are able to provide a small community benefit as well 5, similar to that of herd immunity found with vaccines.

Since their development, the roll-out of these nets has been extensive. It is now estimated that 54% of African households at risk of malaria now sleep under LLINs. Since 2000, malaria cases and deaths have reduced by 60%, with the LLINs often being credited with an amazing 70% of this reduction. They are very good nets!


Image credit: Malaria Atlas Project and Our world in data

The effectiveness of the current LLINs all comes from the pyrethroid insecticides they are treated with. Harmless to humans, this insecticide kills some, but not all, of the mosquitoes that land on the nets. The ones that the insecticide doesn’t kill likely have a natural immunity to the insecticide. The killing of those that don’t have immunity, and the survival and reproduction of those that do, sadly causes resistance to the insecticide to be selected for.

This leaves us with a problem. The more we use the nets (and spray houses with the insecticide) the quicker the mosquitoes adapt to the insecticide and the less effective it becomes. Using these nets therefore may mean a reduction in disease in the short term but an inevitable bounce back as the mosquitoes evolve to be resistant to the insecticide. This had lead many who work in global health to be concerned about the future of malaria control programs 6.

Although now there is a promising development on the horizon.

Try our new and improved LLINs now with added Piperonyl Butoxide!

The chemical Piperonyl Butoxide (PBO) is what is known as a synergist; a chemical that makes insecticides more effective. PBO acts to inhibit crucial enzymes in the natural defense mechanisms of the mosquitoes, effectively removing their resistance to the insecticide coating the nets and rendering it deadly again.

A nifty solution, eh? The mosquito evolved a defense and we developed a way to turn off that defense.

So according to the science this could be a highly useful tool in our mosquito vector control toolkit. As for the field evidence, initial findings look promising, with a recent double-blinded (yes you can actually double-blind with this intervention) cluster RCT demonstrating a significantly lower malaria prevalence after 9 months of use in the PBO insecticide treated nets compared to the LLIN nets 7.

This was from a relatively small trial of N=7,184 so now it’s time to scale up and test the nets further. Over the last year or so The Against Malaria Foundation have funded the distribution of 6 million POB nets to areas with particularly high levels of insecticide-resistant mosquitoes in Uganda. They, again, intend to compare the health outcomes of these 6 million users to a control group using the standard LLINs.

In a statement released this week The Against Malaria Foundation say:

”By understanding to what extent PBO nets can play a role in combating insecticide resistance in mosquitoes, the ultimate value of this study is to help net funders, including health ministries, make informed decisions about the nets they purchase and distribute that will optimize malaria control.”

Results from this study will likely be published in the spring of 2019 and if the results warrant it this could see a substantial shift in how we control mosquitoes on a global scale.

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About me:

My name is Richard, I blog under the name of @nonzerosum. I’m a PhD student at the London School of Hygiene and Tropical Medicine. I write mostly on Global Health, Effective Altruism and The Psychology of Vaccine Hesitancy. If you’d like to read more on these topics in the future follow me here on steemit or on twitter @RichClarkePsy.

Also I’m in the process of building up my Steem basic income shares so I’ve decide to sponsor a share a week to someone that engages in the comments below. I’ve no real system for this but get stuck in and I'll likely sponsor you in at some point.

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References:

[1] The World Health Organisation: Vector borne diseases

[2] The World Health Organisation: Core vector control methods

[3] Harris AF, Nimmo D, McKemey AR, Kelly N, Scaife S, Donnelly CA, Beech C, Petrie WD, Alphey L. Field performance of engineered male mosquitoes. Nature biotechnology. 2011 Nov;29(11):1034.

[4] Hustedt J, Doum D, Keo V, Ly S, Sam B, Chan V, Alexander N, Bradley J, Prasetyo DB, Rachmat A, Muhammad S. Determining the efficacy of guppies and pyriproxyfen (Sumilarv® 2MR) combined with community engagement on dengue vectors in Cambodia: study protocol for a randomized controlled trial. Trials. 2017 Dec;18(1):367.

[5] Levitz L, Janko M, Mwandagalirwa K, Thwai KL, Likwela JL, Tshefu AK, Emch M, Meshnick SR. Effect of individual and community-level bed net usage on malaria prevalence among under-fives in the Democratic Republic of Congo. Malaria journal. 2018 Dec;17(1):39.

[6] Hemingway J, Ranson H, Magill A, Kolaczinski J, Fornadel C, Gimnig J, Coetzee M, Simard F, Roch DK, Hinzoumbe CK, Pickett J. Averting a malaria disaster: will insecticide resistance derail malaria control?. The Lancet. 2016 Apr 23;387(10029):1785-8.

[7] Protopopoff N, Mosha JF, Lukole E, Charlwood JD, Wright A, Mwalimu CD, Manjurano A, Mosha FW, Kisinza W, Kleinschmidt I, Rowland M. Effectiveness of a long-lasting piperonyl butoxide-treated insecticidal net and indoor residual spray interventions, separately and together, against malaria transmitted by pyrethroid-resistant mosquitoes: a cluster, randomised controlled, two-by-two factorial design trial. The Lancet. 2018 Apr 21;391(10130):1577-88.

Additional sources:

Alfaro-Murillo JA, Parpia AS, Fitzpatrick MC, Tamagnan JA, Medlock J, Ndeffo-Mbah ML, Fish D, Ávila-Agüero ML, Marín R, Ko AI, Galvani AP. A cost-effectiveness tool for informing policies on Zika virus control. PLoS neglected tropical diseases. 2016 May 20;10(5):e0004743.

Vox: No mosquitoes aren’t deadlier than humans

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I find this insightful and I love the fact that piperonyl butoxide does a good job augmenting the effect pyrethrin based drugs. It's a welcome development.
I come from a country where malaria is endemic and while measures are put in place for vector control, from first hand experience using a long lasting treated net, wasn't a totally pleasant experience.

Reasons:

It gives discomfort during sleep, as you'll almost start to feel hot immediately you use it. I guess you can say tropical again.
More importantly, during first week of use, majority of users come down with flu-like and inflammatory symptoms resulting from reacting to insecticide impregnated nets.

I hope the research puts into consideration these problems and PBO is not just effective but safe for use.

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Thanks for your thoughts. Richard asked me to chime in here. The WHO Pesticide Evaluation Scheme (WHOPES) does review all insecticide-treated nets before they are pre-qualified and allowed to be purchased by Global Fund and other big donors. This includes safety concerns as you mentioned here. I have also slept under the nets and can attest to the fact they can be very hot in the tropics. I would suggest you link to actual data reguarding your comments about flu-like symptoms, because I don't think that is the case. It may be they come down with flu, but the causal link to the nets is likely spurious (although I don't know all the literature on that). To see the related WHOPES publication on PBO's nets please follow this link

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Hi @getencored, thank you for your comment. Yes, this is something I think about a lot (often in regards to vaccines). There is risk and suffering from the disease but there is also discomfort (and sometimes risk) from the intervention. As the disease becomes less prevalent, people (rightfully so) are less willing to put up with the negatives of the intervention. If we really want to make a dent in these diseases then it’s essential that work be done to address the these reasons that you list here. Otherwise, in this case, people will stop using the nets and the rates will bounce back to their previous level.

This is why I’m excited about the prospect of an effective malaria vaccine hopefully this will make the process of protecting from malaria a whole lot more comfortable.

I have a feeling my office mate could talk more on this topic (he’s the guppy intervention researcher that I mention in the post), he has a steemit account I’ll try and bring him in here.

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Its good to know you understand the point in trying to make. Until a suitable vaccine goes live, we'll keep surviving with what science offers. Thanks for the info, I learnt something new.



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Thank you SteemSTEM! I love you so so much! xxx

Great invention and happy it is helping so many people who are affected by these killer mosquitos. I'm no science junkie, but unfamiliar with how fast the mosquitos will get used to the insecticide...unless you did some massive spray to kill the majority of mosquitos all at once.

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Hi Victoria, it can really depend on the type of insecticide being used. Usually the guidance is to change the insecticides you use every 5-10 years, so that as more of the population becomes resistant you change to another one. You can find out more about mechanisms of resistance here. In areas where they are going for malaria elimination (especially south-east asia) they may suggest having multiple insecticides used at one time to try and crash the population and together with improved case management get rid of all the malaria parasites in the area. The idea is that you won't have to worry about mosquitoes becoming resistant in those areas if they are not carying anything harmful.

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Sleeping in a net really blows but I suppose comfort and luxury aren't really factors to take into consideration when preventing disease.

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They weirdly are. I’ve mention why in a similar comment here from @getencored. If an intervention is going to be effective it really needs to be as easy and comfortable for people as possible otherwise we’re more likely to trade a good night’s sleep now for a chance of illness later. Thanks for you comment. Also congratulations on your steemSTEM upvote! I’ll have to go give your work a look a little later.

With a toddler around, I am always cautious of spraying insecticides. A mosquito net infected with high chemicals, if comes in contact with babies, wouldn't it be dangerous? You know how kids are like, they are curious about everything and would try to touch it and put their hands in mouth frequently.
Secondly, what do you think about moquito repellent lotions?

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Hi @event-horizon, so sorry, I must have missed your comment last week. I know that the WHO are extremely careful on this issue so I'm confident in there safety. This reference goes into more detail on the safety issue although if you are in a high malaria location I would highly encourage the use of the nets with your children. Malaria is a hideous disease to go through even when its not lethal.

Lotions are good but need to be re-applied frequently as they are easily rubbed or sweated off.

Good post brother

I am trying to add up the number of people who did not die from 2005 onward. Kinda looks like 1 million people at the very least.

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Looks to be around 6 million malaria deaths prevented since the year 2000. A big achievement I'd say!

I see you've had another 5 posts, of solid quality, out in the time its taken me to have one. How do you find the time? I'm really going to have to up my game I think.

Having 54% of affected households using a pesticide coated net is actually quite impressive considering the problems we still have with anti-vaxers in well educated populations.
I was wondering, do mosquitoes play a very useful ecological role? Would there be any major downsides if we did succeed in cutting their populations to a fraction of what they are now?

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This is a great point. It's hard to know what the effects on the environment would be. That is why many people are calling for introduction of wolbachia infected mosquitoes instead. You can learn more about that here

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Yeah, I doubt there’s much rejection based on wanting all-natural organic net instead. If you’re in an area where a mosquito net is recommended then you’ve likely seen what nature can do and will take anything to protect you from it.

There’s a lot of debate along those lines when it comes to the genetic engineering approaches. The disease carrying mosquitos are only a few species out of many so there is a likelihood another will fill their niche in the eco system if we get a little genocidey at some point in the future. I’m also somewhat in the camp of: why not wipe them all out? we’ve accidently done it to so many other species we might as well add one that causes an outsized proportion of our suffering to the list.

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Some mosquitoes are obligate members of some pitcher plant communities and are non-sanguinous.

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Yay! I really like what you're doing with your little corner of steemit, keep up the good work !