Resistance – Vet Med and One Health

This week I was given a rather interesting thought experiment: to take something that we spend most of our day in or around, and design it in some way that addresses a specific one health problem. So I chose clothing; we think about it all the time, but also don’t think about it. Obviously, we wear it all the time, so we could use it to help in multiple ways. Since several of my previous blogs discussed diseases caused or spread by ticks, fleas or mites, I will specifically focus on that.

Many dog owners use topical flea and tick preventative. It’s very convenient: just put a few drops of a liquid on the pet’s back, comb it through, and for 30 days you don’t have to worry about a flea infestation or any nasty diseases from a tick. Has anyone ever considered applying it to people, especially people in areas where neglected tropical diseases run rampant? If clothing could be laced with products to repel or kill pests, many infestations could be prevented or reduced in severity.

https://columbiamosquitosquad.files.wordpress.com/2013/04/dog-getting-application-of-dermal-flea-and-tick-control.jpg

The main ingredient for the topical flea and tick preventative Frontline is methoprene, a chemical that mimics the juvenile insect hormone. This hormone is present before insects molt to the adult stage, and they cannot finish their development so long as it is around. With Frontline, it is used to prevent fleas from being able to complete their life cycle and establish an infestation on a dog. Humans and dogs have no receptors for the compound, so it has little to no effects on us even if we drink or inhale it.[1] It has a faint, fruity smell and no taste, and so is not repulsive to people. As such, this chemical has been added to drinking water to control mosquitos that carry malaria, and used in the production of many food products to prevent spoilage due to insects.[2]

An ingredient for another popular preventative—Advantage Multi—is moxidectin, a drug that kills parasites by disrupting nerve transmission and causing paralysis. It was found safe enough to be used en masse in Africa to prevent infection by a parasitic worm that causes blindness in people.[3] Combined on clothing with a similar chemical called imidacloprid, it could also control mite infestations.

There are, of course several obstacles to utilizing such a method of control. The first and biggest is the long-term development of resistance, a subject I have previously spoken of.[4] Allowing parasites to constantly come into contact with these chemicals will naturally select for some few who can survive, and allow them to rapidly spread their resistance among the population.

Next is the practical problem of manufacturing clothing with these compounds mixed in. Everyone who uses topical flea and tick preventative on their pet knows it must be reapplied regularly. And if the pet gets bathed too often, or takes too many trips into the swimming pool or pond, there is a risk of washing the protection off. Having to reapply the compound to clothing every month or two defeats the purpose of such a measure.

But even allowing for solutions to these difficulties, clothing is not incredibly cheap to manufacture even on its own, and adding insecticide compounds would likely increase the cost. It would be difficult to develop a cost-effective method to be able to produce and distribute clothing to areas of need, and then would require help from anthropologists to make sure the people knew why they had to wear the clothes.

Perhaps an easier medium would be an ankle bracelet similar to the Seresto flea collars used for dogs and cats. If a bracelet would slowly release the insecticide and last for 8 months like the pet product does, it could be a more viable option for distribution. However, it could pose a risk for waste build-up and environmental effects if the bracelets were simply discarded in a trash heap once they no longer provided enough protection for the wearer.

More study and development would have to go into this idea to be able to solve its other problems, most notably the risk of resistance. But if used as part of a multimodal one health approach, it could be one useful piece of the control plan.

[1] https://nepis.epa.gov/Exe/ZyNET.exe/P100MT2M.txt?ZyActionD=ZyDocument&Client=EPA&Index=1991%20Thru%201994&Docs=&Query=&Time=&EndTime=&SearchMethod=1&TocRestrict=n&Toc=&TocEntry=&QField=&QFieldYear=&QFieldMonth=&QFieldDay=&UseQField=&IntQFieldOp=0&ExtQFieldOp=0&XmlQuery=&File=D%3A%5CZYFILES%5CINDEX%20DATA%5C91THRU94%5CTXT%5C00000031%5CP100MT2M.txt&User=ANONYMOUS&Password=anonymous&SortMethod=h%7C-&MaximumDocuments=1&FuzzyDegree=0&ImageQuality=r75g8/r75g8/x150y150g16/i425&Display=hpfr&DefSeekPage=x&SearchBack=ZyActionL&Back=ZyActionS&BackDesc=Results%20page&MaximumPages=1&ZyEntry=2

[2] https://nepis.epa.gov/Exe/ZyNET.exe/P100MT2M.TXT?ZyActionD=ZyDocument&Client=EPA&Index=1991+Thru+1994&Docs=&Query=&Time=&EndTime=&SearchMethod=1&TocRestrict=n&Toc=&TocEntry=&QField=&QFieldYear=&QFieldMonth=&QFieldDay=&IntQFieldOp=0&ExtQFieldOp=0&XmlQuery=&File=D%3A%5Czyfiles%5CIndex%20Data%5C91thru94%5CTxt%5C00000031%5CP100MT2M.txt&User=ANONYMOUS&Password=anonymous&SortMethod=h%7C-&MaximumDocuments=1&FuzzyDegree=0&ImageQuality=r75g8/r75g8/x150y150g16/i425&Display=hpfr&DefSeekPage=x&SearchBack=ZyActionL&Back=ZyActionS&BackDesc=Results%20page&MaximumPages=1&ZyEntry=1&SeekPage=x&ZyPURL

[3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4072596/

[4] https://vetmedone.health.blog/2019/02/11/its-the-resistance/

Antimicrobial resistance is a hot topic today. Studies have shown that it is spreading and starting to involve more microorganisms and antibiotics. But what is it, exactly?

Antimicrobials are any medicine designed and used to kill microscopic organisms that cause disease. The term is usually used to refer to bacteria, but it also technically includes fungi, protozoa, viruses, and parasites. However, when a microorganism survives the treatment designed to kill it, it continues to grow and pass on its resistance to its progeny. This is exacerbated by the fact that the other microorganisms that are susceptible to the drug, and die off, used to limit the growth of the resistant organisms by competition for resources. With them gone, the resistant microbe is free to spread throughout the host, unable to be controlled by modern medicines.[1]

https://www.cdc.gov/drugresistance/pdf/5-2013-508.pdf

How widespread is this problem? A Review on Antimicrobial Resistance, completed in May 2016, estimated that 700,000 people die each year from diseases that were resistant to available antibiotics. They also postulate that, by 2050, the number of deaths will increase to 10 million annually.[2]

A commonly held belief is that antibiotic use in animals is the main cause of most antimicrobial resistance. While it is true that antibiotics used to be used as growth promotants—thus exposing bacteria to low levels of antimicrobials, which they could survive and then develop resistance to—the FDA recently instituted the Veterinary Feed Directive (VFD), a program that regulates and limits the use of medically important antimicrobials.[3] What do we mean by “medically important”? Only some of the antibiotics used in food animals are the same as those used in human medicine. Because of the risk of resistance cross-over into humans, producers must consult with a veterinarian and obtain a specific prescription before they are able to use them in their herds.[4] This helps to reduce the development of resistance to antimicrobials used in humans.

Unfortunately, resistance to antimicrobials is a natural result of mutation, rapid growth and gene transfer. The same thing happens even in insecticides, and the consequences can be severe. For example, insecticides are important in the control of mosquitoes that spread malaria. However, 61 countries have reported resistance to at least one of the four classes of insecticide. Resistance is probably more widespread than this, because many countries do not perform adequate monitoring for insecticide resistance.[5]

Resistance to antimicrobials and insecticides are difficult to control, and impossible to prevent. All that can be done is to monitor for resistance, accurately gather data, learn more about the mechanisms of resistance, and develop new methods of control and prevention.[6] It’s a steadily regressing battle, as few breakthroughs have been made in antimicrobials in the past 20 years.[7]

It’s a very difficult subject to talk about considering the likelihood of such a grim outcome. But if awareness of this problem is increased, some solutions may be researched and brought to light.

[1] https://amr-review.org/sites/default/files/160525_Final%20paper_with%20cover.pdf

[2] Ibid.

[3] https://www.fda.gov/AnimalVeterinary/DevelopmentApprovalProcess/ucm449019.htm

[4]https://www.fda.gov/downloads/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/UCM299624.pdf

[5] https://www.who.int/malaria/areas/vector_control/insecticide_resistance/en/

[6] Ibid.

[7] https://amr-review.org/sites/default/files/160525_Final%20paper_with%20cover.pdf