Who Ate the Dinosaurs? Part I: Ectoparasites

An artist's rendition of a Jurassic flea.

        At the recommendation of a well-known parasitologist, I began reading about the parasites that plagued everyone’s favorite prehistoric animals: the dinosaurs. I found lots of information on various forms of dino-parasites…everything from protists, to helminths, to insects. I’ve decided to break up this topic into a series of posts over the next few weeks. Today, let’s talk about things living on the outside of our beloved reptiles. In doing so, we will also mention a little about how these creatures probably feasted on the blood of ancient birds and mammals as well. You will also have the pleasure of reading a bit about ectoparasite evolution, and how studying these little guys helps us to paint a more accurate picture of life over a 100 million years ago.

Dino-Lice

            Lice are thought to have evolved over 65 million years ago according to a new study using modern lice DNA. That time frame places their ancestors in the same place as dinosaurs. One study is even showing that lice began diversifying on mammals and birds before the dinosaurs went extinct! (Which means that mammals and birds may have been diversifying at this time as well?!) How interesting is it that these little guys could be proxy indicators of bird and mammal radiations preceding what has been conventionally accepted as post-dinosaurian diversification of these types of creatures!!?!?!!  Here’s an awesome quote from Dr. Vincent Smith, a researcher who has been working on dino-lice at the Natural History Museum in London:

Fossilized lice remains from 44 million years ago (left) next to
a modern-day louse from an aquatic bird (right).

“Lice are like living fossils. The record of our past is written in these parasites, and by reconstructing their evolutionary history we can use lice as markers to investigate the evolutionary history of their hosts. …  It was thought that after the dinosaurs went extinct that's when these birds or mammals diversified into these different niches, but based on the evidence from lice, the radiation of birds and mammals was already under way before the dinosaurs went extinct.”

            

           Pretty cool huh? Some researchers believe that louse-lineages may even go back as far at 115-130 million years ago! It’s thought that these ancient lice may have fed on feathered dinosaurs such as China’s Sinornithosaurus. The most recent numbers I could find in the literature regarding lice stated that the first instances of parasitic lice occurred between 100 million and 125 million years ago. The same study suggested that these little guys didn’t become parasites until animals began to develop fur or feathers. It seems that modern birds may have gotten their modern louse-burdens from feathered versions of their dino-brethren. 

Dino-Fleas

Fossilized flea from the Jurassic period.

            Okay, so maybe some dinosaurs had lice…but what about another exciting group of ectoparasites…fleas? There are fossils of fleas that date back to the Jurassic, some 100 million years ago. They were anywhere from twice to ten times the size of modern fleas and lack the jumping potential that our familiar forms possess. They also donned elongated sucking mouthparts that were serrated…presumably for piercing hides that were much thicker than the hosts’ hides that contemporary fleas must penetrate. They were dorso-ventrally flattened rather than laterally compressed. (For those who aren’t biologists, this means that the bodies are flattened from front to back rather than from the sides. Fish, for example, are laterally compressed.) They also had spiny bodies and claws that helped them to cling to prehistoric feathers and fur. It is most likely that these guys fed on pterosaurs and early rodent-like mammals. 

Jurassic flea fossils from China.
(Note size compared to the human hand.)

A recent examination for fossilized fleas from China found that some fleas existed 165 million years ago! Two species have been named from these Chinese fossils. They were given the names Pseudopulex jurassicus and Pseudopulex magnus based on compression fossils, which provide much more detail of the fossil’s anatomy as opposed to impression fossils. P. jurassicus is smaller in size than P. magnus. It is believed that these fleas fed on feathered dinosaurs, such as Epidexipteryx hui and Pedopenna daohugouenis, during the mid-Jurassic period. I read a few articles that mentioned other types of dinosaur fleas, but I have yet to uncover the scientific names of those fleas.

Moral of the Story

            When a conversation turns to dinosaurs, we don’t often think about how these massive creatures may have played host to ectoparasites in the same way that animals like corgis do today. We think of the astounding size of these animals and about how they ruled the planet so long ago. As interesting as they are, I think it’s even more fascinating to know that they were not exempt from the most efficient form of symbiosis found in any ecosystem. In my head, I can’t help but picture a pissed off velociraptor rubbing up against a tree to sooth the itch of a group of 2cm long fleas feasting on his back. (For the record, that’s purely a figment of my imagination, there’s no evidence to support that fleas actually fed on velociraptors.) Anyway, the next time you are at a party, you should throw around the name Pseudopulex jurrassicus. If this attracts a woman, she’s a keeper. If it doesn’t, then no woman at that party is worth your time anyway! :p

On the Tip of Everyone's Tongue!

It has recently come to my attention that there are lots of new ways to talk about parasites and connect with others interested in parasites. Yay technology! So, as an almost-Halloween treat I have put together some of these sources I've just discovered for you to peruse at your leisure. You can also check out the "Links" tab for more parasitophiliac websites. Anyway, the following is a list of my new favorite parasite-related thing-a-mo-bobs!

1) First and foremost, if you haven't heard this, do it! Now! Okay, maybe not right now, but as soon as you have an hour to kill. This podcast was recommended to me by a friend and I just heard the parasite episode for the first time last night. Can I just say....AWESOME! This actually has an interview with THE Carl Zimmer! (See "Must-Read" tab.) He gave them three parasites as examples for why we should be in awe and have admiration for parasites rather than be disgusted by them. It went on to interview other important parasitophiliacs and gave you a chance to hear about hookworms from a historical perspective as well as from a medical perspective. They ended up talking about using hookworms for therapeutic purposes. If you haven't heard of this, you should check out my last blog post, and of course listen to this amazing podcast. Enough rambling...check it out already!!!

http://www.radiolab.org/popup_player/#

If the popup isn't working, try this link: http://www.radiolab.org/2009/sep/07/

2) While you are getting into podcasts, head over to Dr. Vincent Raciniello's site and check out This Week in Parasitism (TWiP). This virologist from Columbia University also has an awesome podcast known as This Week in Virology (TWiV). I learned about his podcast at a Virology Symposium that I attended for funzies a few weeks ago. I got to sit in on a recording of a TWiV podcast at that symposium and I was delighted to learn that he also had a podcast about parasites! (He also have TWiM for all you microbiology-lovers out there!) This podcast doesn't have all the fun sound effects and flair of radiolab, but it does get into more in-depth issues regarding parasitology. You should definitely check it out! This week he and his co-host Dr. Dickson Despommier interviewed a few post-docs who are working with the dreaded Plasmodium falciparum (a very virulent little protist that causes malaria...the worst strain of malaria, in fact). The great thing about this is that it is an on-going show, not just a single episode as the above link. I've been trying to download these to my iPod to listen to as a ride my bike to school, but I've been having technical difficulties. But enough about me, let's talk about you! And about how you should be listening to this:

http://www.microbeworld.org/index.php?option=com_content&view=category&layout=blog&id=99&Itemid=259

3) Here's a fun talk given by Carl Zimmer that I ran across. :) Enjoy!

http://magazine.storycollider.org/2012/features/interview-carl-zimmer-stories-from-the-parasite-hole/

4) While we are talking about Carl Zimmer....here's another great podcast called "Meet the Scientist". It's not specific to parasites, but I thought it was really cool, so I'm posting it anyway. :)

http://www.microbeworld.org/index.php?option=com_content&view=category&layout=blog&id=37&Itemid=155

Here's an episode about malaria from the same podcast:

http://www.microbeworld.org/index.php?option=com_content&view=article&id=640:mts49-irwin-sherman-the-quest-for-a-malaria-vaccine&catid=37:meet-the-scientist&Itemid=155

5) Even the CDC is jumping on the podcast bandwagon...worthy of a mention here.

http://www.cdc.gov/parasites/podcasts.html

I hope I have helped you all to kill some time learning about these wondrous creatures that we know as parasites! I'd love to hear any comments about parasite podcasting or any other topic related to parasites!

 

Helminthic Therapy

For this week’s post, I decided to cover a subject rather than a particular parasite. This is the subject of Helminthic Therapy.  So what is helminthic therapy you ask? Great question! Let’s delve in and explore this somewhat counter-intuitive idea.  Perhaps in the end you won’t think it’s quite so counter-intuitive after all!

The word “helminth” comes from the Greek word “hélmins”, which is a kind of worm.  For parasitologists, this term refers to any type of parasitic worm, be it a flat worm, roundworm, hairworm, etc.  The study of parasitic worms and how they effect their hosts is called “helminthology”.  Helminthic therapy is a type of treatment that utilizes helminthes or their eggs (a.k.a. “ova”) to heal patients with immune disorders or autoimmune diseases. This is a form of “immunotherapy”, a type of treatment that involves inducing, suppressing, or even enhancing an immune response in order to treat a disease. In this case, parasitic worms or their ova are introduced intentionally into a patient.

So, why would anyone think this was a good idea? 

Research has shown that people in well-developed, industrialized countries are at greater risk for autoimmune diseases and allergies than people living in less developed countries. Over time, epidemiologists (people who study the spread of diseases) have begun to link parasitic infestations to lower instances of autoimmune diseases.  Sure, you might be genetically predisposed to certain types of autoimmune diseases, but the rate of increased numbers of people afflicted with autoimmune diseases is not a result of genetic changes.  If this were the case, the emergence of autoimmune diseases would be able to be traced back much further. Since these diseases have a relatively recent emergence, environmental changes (rather than genetic changes) seem to be far more likely explanations.

Environmental factors that could induce such an emergence may include exposure to different medicines, foods (or food preparations), industrial chemicals, etc.  These factors are great for subduing particular diseases such as those associated with infection by bacteria, viruses, and yes, parasites.  However, because there is a lack of exposure to these diseases, human bodies may be likely to develop the antibodies needed to fight off a major infection by the aforementioned disease-causing agents. Therefore, by not ever being exposed to naturally occurring pathogens/parasites, you may be at a greater risk for developing autoimmune diseases and allergies.

This idea is consistent with what epidemiologists call “the hygiene hypothesis”. This hypothesis states that by not exposing people to infectious agents during childhood, the development of the immune system is naturally suppressed. This leads to increased susceptibility to allergic diseases.  Immunologists (people who study the immune system in all of its mind-boggling complexity) have shown that many types of bacteria and viruses elicit an immune response that is mediated by T_h1 cells. These cells cause a down-regulation of responses by T_h2 cells. If a human is not exposed to pathogens that induce a response mediated by the T_h1 cells, then that human’s body does not have a way of initiating the down-regulation of response by T_h2 cells.  The result is that the T_h2 cells respond excessively. When these cells respond to a harmless antigen inappropriately, you have an allergic reaction. When it comes to more complex issues, such as full-blown autoimmune diseases, it is hypothesized that immune systems that were never exposed to stimuli from infectious agents or parasites do not develop regulatory T cells adequately. Since these regulatory T cells don’t develop properly, they are not sufficient at repressing T_h1 or T_h2 immune responses, and therefore the immune system is more susceptible to autoimmune diseases. This second hypothesis regarding more complex issues is endearingly called the “old friends hypothesis”. The hypothesis is aptly named as such because it relies on the idea that exposure to microorganisms and parasites at low levels of pathogenicity instigate the development of regulatory T cells. It further implies that these organisms have evolved alongside humans throughout our own evolutionary history.

I rarely take quotes directly from sources, but this was much better than the way that I put it. So, for your reading pleasure I present a quote about the hygiene hypothesis from a paper titled “Helminths and Harmony” that was published by Gut in January of 2004 (authored by JV Weinstock, R Summers, and DE Elliott….53(1): 7-9):

“The development of vaccines, hygienic practices, and effective medical care have diminished or eliminated the prevalence and impact of many parasitic organisms, as well as bacterial and viral infections. This has been of obvious benefit with the effective eradication of many diseases that have plagued human beings. However, while many severe diseases have been eradicated, humans' exposure to benign and apparently beneficial parasites has also been reduced commensurately. The central thrust of the theory is, therefore, that correct development of T regulator cells in individuals may depend on exposure to organisms such as lactobacilli, various mycobacteria, and helminths.”

I have to muse at the fact that I’ve also heard the “old friends hypothesis” referred to as the “lost friends theory” or the “depleted biome theory” in various papers. This is just such a novel and interesting way of thinking about human evolution with regard to parasitism! But, I digress…back to helminthic therapy!

Researchers have established a link between parasitic infections and how these infections play a protective role against the development of autoimmune diseases! Geneticists have found that helminths have helped to shape part of the evolution of the human immune system based on a subset of interleukin (IL) genes. The immune system is highly dependent upon these particular genes. In fact, deficiencies in some of the IL genes seem to be the cause for autoimmune diseases. A lack of helminth exposure can be associated with deficiencies in the IL genes associated with Crohn’s disease, celiac disease, and ulcerative colitis. 

What types of diseases might helminthic therapy be useful for treating?

I’ve already mentioned a few here, but just to reiterate and to add in a few others:
-Asthma
-Celiac Disease 
-Crohn’s Disease                             
-Eczema
-Dermatitis        
-Hayfever
-Inflammatory Bowel Disease
-Multiple Sclerosis
-Ulcerative Colitis

Whipworm Ova

-Various Food Allergies 

So what types of helminths are used for this therapy? 

I’m glad you asked! As of now, the only organisms used have been hookworms (Necator americanus) and both pig and human whipworms (Trichuris suis and Trichuris trichiura respectively). From what little I know about the subject, adult hookworms are used while it is the ova of whipworms that are used.

How effective is helminthic therapy?

From some of the papers and forums I have run across researching this topic, I have found that this has a great success rate. Use of Trichuris suis ova have Crohn’s disease and ulcerative colitis remission rates of 55%. Use of Necator americanus has Crohn’s disease remission rates of 85%! Use of Trichuris trichiura has Crohn’s disease and ulcerative colitis remission rates of 85%. Remission rates for a combined use of hookworms and whipworms (while taking vitamin D supplements) are over 90%!!!

How do you introduce the parasites into a patient’s body? 

Vial containing 15 adult hookworms.
Photo from http://coloncomrades.wordpress.com/

Most people are a little creeped out by the idea of parasites living within their bodies. (Though some of us parasitophiliacs may like the thought of contracting a parasite just long enough to remove it and save it as a testament to our strengths as a biologist…) The medical world takes this fear into consideration. Apparently, the whipworm eggs come in a liquid suspension (eggs are in a buffer solution). The patient is to drink half a cup or so of this suspension, which, from forum posts, should taste no different than drinking a glass of water.  Administration of the hookworms is a little more involved. Patients pour a small vial of hookworms in a liquid medium onto a piece of gauze and apply the gauze to the inside of the arm. They secure the gauze with either medical tape or a band-aid for a little bit. The only symptoms associated were some minor itching and little red dots from where the worms burrowed into the patients. The hookworms don’t have to be reapplied for 3-5 years when the parasites will start to die off.

Application of Adult Hookworms
Photo from http://coloncomrades.wordpress.com/

So a treatment regime that can have anywhere from 55%-90% remission rates MUST be expensive, right? 

WRONG! True, some of the companies that sell the pig whipworms charge a pretty penny, but from what I understand, purchasing the hookworms or human whipworms is extremely inexpensive. (And those species have better remission rates anyway!) Some estimates show that you can be treated for less than $3 a day using hookworms!  The lump sum is fairly high, but when you take into account that you only have to dose once every 3-5 years and that most people are relieved of allergies to foods and to allergic reactions such as hay-fever, you are actually saving money in the long run. (No more medications like Zyrtec or Claritin and you can often eat foods you love once more without going into anaphylactic shock! Talk about a bonus!!!) 

Keep in mind that helminthic therapy is NOT FDA approved. From what I understand, you cannot patent a biological organism (though some companies patent the production of media for administration of these parasites). If it did become FDA approved, it would be something that anyone could produce for very little money. On average, it takes about 10 years and millions of dollars to get a drug approved, so most companies wouldn’t be able to recoup their costs from hookworm media production due to how cheaply it can be produced, and theoretically sold. Thus, big pharmaceutical companies don’t have an interest in funding drugs that can’t be patented and won’t have a big return on their investment. While we are on the subject, you should check out this link to a DIY for growing hookworms and whipworms at home. Just keep in mind that this is a “at your own risk” sort of thing. You don’t want to infect anyone too heavily as these ARE parasites we are working with here, and heavy infestations can have some nasty clinical manifestations. As you might have guessed, you are really better off having a doctor monitor your intentional infections.

Demodex folliculorum

           This little dude is tiny…microscopic…you wouldn’t even know it if he was right in front of your face. Or on it, for that matter.  These guys can live on the face of humans…in hair follicles, on eyelids, in eyebrows, on the nose or cheeks, and even in ear wax.  Some literature has reported finding these parasites in odd places such as on the scalp, penis, nipples, arms, chest, and even breasts.    Demodex folliculorum was first described by Dr. Jacob Henle, a famous anatomist, in 1841. It is generally accepted that under normal conditions, these mites aren’t harmful, in fact, they are sometimes regarded as commensals rather than parasites.  However, some people speculate that it may be responsible for various skin diseases based on the fact that increased numbers of these mites have been found on people who have conditions such as rosacea, perioral dermatitis, and blepharitis.  Causality has not been established (to my limited knowledge of the subject) for any of these diseases.

Taxonomy

        This mite is an animal belonging in the phylum arthropoda, which includes invertebrates such as insects, spiders, shrimp, millipedes, and lobsters.  Members of this phylum have jointed appendages and chitinous exoskeletons.  (Chitin is a long-chain polymer derived from glucose that is found in the cell walls of fungi as well as in the bodies of animals like mollusks and arthropods.)  Demodex belongs to subphylum chelicerata because it possesses chelicerae rather than mandibles for mouthparts.  It is in class arachnida which contains all mites, as well as other animals such as ticks and spiders. It can be further categorized into the subclass acari, which contains all living ticks and mites.  It used to belong to the large order trombidiformes which has over 22,000 species representing 125 families of mites.  Many mites in this order were medically important or agriculturally important.  However, that order has been split into two orders in recent times and these mites are now found in the order Prostigmata. (This taxonomic rank is what is accepted in the current literature, so I thought I would put it here.)  Demodex is in the family demodicidae, or the “pore mites” family. There are many species of Demodex, but the two found in humans are D. brevis and D. folliculorum.  The first one lives in sebaceous glands connected to hair follicles, but we won’t be talking much about him today. Today, we are looking exclusively at D. folliculorum, which lives in hair follicles.

Life Cycle

When a boy mite and a girl mite love each other very much…and their instinctive drives to reproduce overtake them, they make babies.  The males actually do have a penis that exists between the first and second pairs of legs, and the female has a vulva anus opening on her ventral side. After mating, female mites travel to the base of hairs and lay their eggs inside of the hair follicles. A female will lay anywhere from 20 to 24 eggs in a single follicle. The larvae emerge from the eggs and have only six legs.  The larvae feed on subcutaneous secretions until they reach adulthood, which takes about 7 days. These larvae may have a role to play in the formation of black-heads. When mature, the mites reproduce sexually and the cycle completes itself.  This life cycle takes about 18-24 days to complete.

Who’s Got Mites on Their Faces?

Virtually everyone has Demodex folliculorum living on them as part of their normal skin fauna.  The distribution of these mites varies from person to person, and can have variable impacts on individual health.  Children under 5 are almost never infected, but between 5 and 10 there is a 50% infection rate.  After the age of 10, the infection rate spikes to a whopping 80%.  This is typically attributed to the onset of puberty, a time in which sebaceous glands are producing oils in full swing.  These oily secretions are food for these mites, so since more food becomes available means that more mites can live in one place. Thus an increase in infection. These infections can last throughout life, with infection rates changing with age. About 25% of people in their twenties are infected, and at age 50, that percentage jumps up a little to about 30%.  Finally, in our twilight years, people age 80 to 100 have between 50%-100% infection rates. (The higher rates are among populations of people in nursing homes.) There tends to be more men who are infected than women in every age group…probably because men have more sebaceous glands.

Diagnosis, Prevention, and Treatment

                Demodex can be found by taking a skin scraping from the face and making a slide mount using mineral oil.  Sometimes KOH is used to digest some of the skin cells making it easier to find the little arthropods.  Apparently, in extreme cases, a skin biopsy may be taken for microscopic examination.

                 As the guy doesn’t usually cause any problems, you don’t really have to prevent it so much as try to keep the numbers of them in check.  To do this, one should cleanse the face twice a day with a non-soap cleanser, exfoliate from time to time to remove dead skin cells, and avoid oil-based facial products and greasy makeup.

                If your doctor thinks that you have a skin condition related to this parasite, he or she may recommend topical treatments such as crotamiton cream, permethrin cream, metronidazole gel, or even oral ivermectin (severe cases). 

Moral of the Story

                Don’t freak out about the fact that little mites are living on your face. After all, they are there on other peoples’ faces too! It’s perfectly normal. But don’t let that be an excuse to stop washing your face or wearing tons of makeup.  You should still use common hygiene practices to keep these guys from getting out of control whilst feasting on your facial sebum. :P

An adorable little Demodex folliculorum
here to give you an 8-appendaged hug,
a smile, and a big thank you for all of the
food you've provided over the years...
especially when you were a teenager! Awwww!!!