Do OTC Head Louse Treatments Work? Part 1: Mechanisms

I think it’s safe to say that most folks have had experiences with lice. Every entomologist I’ve ever met (including myself… buy me a few beers and I’ll tell you) has at least one entertaining pubic louse story. Head lice are a childhood rite of passage, with most kids being infested at one point or another. They’re generally harmless with the occasional secondary infection, but infested kids are prone to teasing and other forms of exclusion by classmates. Distraction due to constant itching can also be a problem. Since schools don’t want children being infested for obvious reasons, kids are sent home because of infestation, resulting in parents missing work. Even though lice are mainly nuisance pests, they’re still a pretty big economic pest and account for billions of dollars per year in lost productivity.

When lice strike

"We all have lice" by Antonia Hayes via Flickr.

Head lice are something almost everyone has to deal with, and head lice treatments are something someone buys every once and awhile. These are big business in and of themselves. Because they’re big business, many firms have started popping up offering louse treatments with varying degrees of effectiveness.

A while back, I went through my own head louse ordeal with my daughter. Treatment was complicated by a family member who didn’t realize they were infested. We originally thought the lice were resistant to treatment, so I had to get a second treatment. Since then, I’ve become curious about what is for sale in stores for Over The Counter (OTC) head louse treatments and generally take a look at whatever treatments I can when I get the chance. Over the years, I’ve become surprised at how many dubious treatments are offered for sale (although perhaps I shouldn’t be) and how many of these use questionable advertising techniques mostly built upon fear rather than science. Many treatments offered for sale over the counter are either unproven, or have been proven not to work.

First, let’s discuss some headlouse biology. Then, let’s discuss how the treatments currently FDA approved work. In Do OTC Head Louse Treatments Work? Part 2: Questionable treatments, I’ll discuss the dubious treatments.

Disclaimer: I have worked in entry level positions at companies which sell these products. This, has not influenced my position. I should also mention that I’m not a medical professional and will not be discussing side-effects or risk-benefit analysis. I am an entomology graduate student who studies insect physiology and although I’ll mention the side effects of these products in passing I will not discuss them in detail. This post will discuss the science behind head louse therapies, how they work, and why some aren’t thought to work. I’ll also discuss the evidence that would be required to show that they work. This post deals with insect physiology and should not be mistaken for medical advice. Always consult a doctor if you think you may have health issues because blogs are notoriously bad places for medical advice*.

Lice biology

Male head louse, via Wikipedia.

Head lice are small hemimetabolous insects – basically booklice that have evolved to be parasitic. They start life as an egg or nit attached to hair, then go through a series of nymphal stages before maturing to an adult.  The adults and nymphs both feed, injecting saliva that causes small localized immune reactions which is why you itch. They’re very well adapted to hair and grasp it with clawlike legs. They can only grasp onto some kinds of hair which is why you don’t get pubic lice and head lice occurring on the same body parts. They spend all their lives on hair, even staying on the hair while they feed. Actually, off hair (or similar

fibrous material) human lice are nearly useless and have trouble getting around. They must feed every few hours, otherwise they quickly starve to death or die of dehydration off the host. Lice are transmitted mainly through direct hair to hair contact, with objects like combs and hats playing a potential minor role in transmission.

The nervous system of head lice is surprisingly similar to ours, with differences that are minor as far as we’re concerned. The nervous system is composed of several thousand cooperating neurons and is involved with every aspect of a louse’s life, movement, feeding and reproduction and many products target this system. When a nerve fires, sodium and potassium channels open which causes potassium to flow out of the cell and sodium to flow back in. Often, this process is touched off by the binding of another messenger such as acetylcholine which causes these channels to open. The charge changes from a negative charge to a positive charge, known as depolarization. The positive charge is very localized and moves down the nerve cell as a result of the sodium/potassium channels opening and closing in a very tightly regulated sequence that is essential to function. Other channels can prevent the nerves from firing such as GABA which binds to a receptor and causes the opening of chloride channels which prevent the nerve cell from firing by causing it to attain a very negative electrical charge. The pesticides used in headlouse treatments target all these systems, all of which can lead to a dysregulation of the nervous system and a collapse of nervous system function.

How do louse treatments work?

The safest products are sold over the counter and are used as commonly available first line treatments. Pyrethroids are generally considered to be the least toxic product, and are the most widely available. Lindane is a bit more toxic than either pyrethrum or malathion but most adverse reactions are still due to misuse. All three of these pesticides target different systems in the louse. Resistance has been documented in lindane and pyrethroid insecticides, but not malathion in the US. Pyrethroid based insecticides are used as a first line of attack with lindane and malathion being listed as a second and third route of attack respectively due to resistance of lindane and lack of resistance to malathion.

Pyrethroids are compounds similar to pyrethrum which is derived from the chrysanthemum plant.

Chemical structure of pyrethrum, the most commonly used pyrethroid derived from chrysanthemum plants.

Pyrethrum is a botanical product, while pyrethrins are artificial versions of this compound which have varying degrees of effectiveness on insects. In general, the artificial versions are more toxic to insects and less toxic to mammals based on LD50 values. Pyrethrum is the compound used in head lice treatments. Pyrethrum acts by propping open the sodium channels, allowing a sodium influx into the nerve cells. The nerve cells then become depolarized in unison, which results in the discoordination of the nervous system. The nervous system eventually shuts down, followed by the louse’s vital systems.

Resistance to this pesticide exists in two forms, knockdown resistance and cytochrome p450 degredation. Cytochrome p450s are enzymes which detoxify various compounds and catalyze a wide variety of breakdown reactions. These enzymes are present in humans as well, and also serve to detoxify the small amount of pyrethroids which are absorbed during treatment. In many resistant strains, the cytochrome p450s are upregulated, or overproduced. The overproduction of specific cytochrome p450 enzymes results in the increased breakdown of the pesticide. To combat this, a common additive called piperonyl butoxide is added as a cytp450 inhibitor. Knockdown resistance occurswith a change in the sodium channel that decreases the sensitivity to the pyrethrum, which is more difficult to combat. This is a wonderful example of evolution in action because it’s something which has evolved in direct response to usage of pyrethroids in headlouse treatment.

Chemical structure of lindane, courtesy of wikipedia commons. The molecule consists of a 6 membered ring decorated with chlorine atoms.

Lindane acts by binding to the GABA receptor and permanently inhibiting it. This results in the influx of chloride ions. With the GABA receptor stuck to the ‘on’ position, the nerves are unable to transmit any signals. This  mechanism is semi-complex mechanism but briefly the chloride ions reduce the charge in the cells, so much so that when the potassium flows out the nerve cell is still negatively charged and never fires. The nerves are unable to fire, and are in effect turned off. With the nervous system turned off, the louse becomes permanently paralyzed and dies as a result of not being able to feed. Resistance has been documented to lindane, but I’m not sure what the mechanism is. This product is one of the more toxic substances on the market for head louse treatment, and generally isn’t prescribed for children.

A third mechanism revolves around acetylcholinesterase, an enzyme not directly involved in the transmission of nerve signals. Acetylcholine Is used as a neurotransmitter, being sent between nerve cells to cause them to fire. When an action potential reaches the end of a nerve cell, the nerve cell releases acetylcholine which results in the nerve cell firing. Acetylcholine is degraded by an enzyme called acetylcholinesterase. Without acetylcholinesterase, the nerve remains permanently depolarized and the ion gradients collapse.

Chemical structure of malathion. The active portion of the molecule is the phosphate-like group on the far left which modifies the place in the enzyme responsible for catalyzing the reaction which shuts off nerve cells temporarily.

Even though acetylcholinesterase isn’t directly involved in the transmission of the signal, the enzyme is still important in ensuring the proper working of the nervous system. Organophosphates such as malathion knock the enzyme out, killing the insects. Malathion is an interesting molecule in and of itself. Toxicity requires degredation to another product, which happens better in insects than in mammals. Malathion is sold in a solution that contains isopropyl alcohol and tea tree oil which both synergize the effects of malathion by mechanisms which aren’t well understood. They work either by denaturing protiens in the lice as in isopropyl alcohol or by acting as a supplementary antiacetylcholinesterase as in tea tree oil.

Another method which has been used to cure head lice is what I refer to as the ‘nuclear option’ (or, to use a rare euphemism… landscaping for crab lice), and that’s simply removing the child’s hair. Without hair, the lice cannot hold onto their host and simply fall off. While side effects of the above treatments are relatively rare when the pesticide is used properly, this is by far the safest and most effective method of louse control. Unfortunately, this may not be acceptable for many people. When my daughter had head lice, she did not want to have her head shaved and this is the case for many little girls.

Are there treatment risks?

Although I’m keeping this post focused mainly on the mechanisms of these pesticides, remember that it’s the dose which makes the poison and any substance can be toxic when given in a high enough dose. Exposing yourself to a small amount of pesticide is OK so long as you allow it to break down and leave your system. Repeated exposure over a very long period isn’t a good thing because these products do inhibit neuronal function, leaving the door open for possible neurodevelopmental effects. Because of this, these products are not reccomended for long term use and treatment regimens are designed to last as short as possible. Head lice generally take about ten days to two weeks to mature into adults which is why retreatment is recommended within a week. Many products (except lindane) do not kill eggs, so any leftover eggs will hatch and eventually grow to reproductive adults if a followup treatment isn’t performed. The active ingredients have proven useful in a variety of contexts, including agriculture, but in this case the trick is to treat the patient with a dose high enough to kill most of the lice but low enough to not cause symptoms in the human.

Classifying these chemicals as pesticides sounds scary to many, and many companies have figured out how to take advantage of the unease many parents feel about treating their kids to sell products which have no evidence of efficacy. Next week, I’m going to expose many of these products and further explain the science behind clinical trials for these products.

* One of my favorite fellow entomobloggers, Bug Girl, even has a page titled ‘I will not diagnose you’ and this applies to me as well. Do not contact me asking for any diagnosis because any E-mails of this character will be sent directly to my junk E-mail folder as it is outside of my duties as an entomologist to perform this sort of work and would be completely irresponsible.

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Joe Ballenger is an entomologist who works in the biotech industry as a contractor. In his spare time, he helps answer questions about bugs at Ask an Entomologist. https://askentomologists.wordpress.com/