Sunday, March 10, 2013

Battles for Our Bodies: New World vs. Old World Parasitism

So I've been busying myself with learning more and more about archaeoparasitology...since that's the field I am working in as I pursue my PhD.  I recently learned that people and medieval Western Europe had LOTS of parasites.  These high parasite loads can be attributed to an array of sanitation issues and societally acceptable behaviors and practices.  The numbers of whipworm, maw worm, and other types of parasites found from latrines from this time period are absolutely staggering. 

The New World, on the other hand, had a much better control of their parasites.  Though there were still sanitation issues and odd behavioral practices that increase changes of parasitism, such as the intentional ingestion of arthropods that may have carried parasitic disease, Native Americans had far less severe cases of parasitism. 

The most recent hypotheses for this stark contrast in New World and Old World parasitism involve the differences in medical technologies of these two groups that are...let's be honest....worlds apart.  It seems that religion had a HUGE influence on how people in both regions viewed medical "science".  The medical practices that spawned from these beliefs were very, very different.

Let us first look at the New World.  Many Native American cultured relied on the use of medicinal plant to cure ailments, including those induced by parasites.  Though not all folk medicine has been shown to have true biological capability to cure diseases, many (if not most) of these treatment methods have been scientifically proven to actually work for controlling parasites.  There are a variety of plants that have antihelminthic properties, a fact that medicine men where aware of long before the creation of microscopes and ivermectin.

Religion was important to these people, but much of the religious beliefs were centered around observations and interpretations of the natural world.  Medicine was therefore developed from the things provided naturally by the gods.  This notion helped them to control parasites effectively using natural botanical treatments.  Many of these people were also nomadic, and those that did establish permenant homes did not live in densely overpopulated regions (at least not relative to Western Europe).  This helped to control crowd parasites.  Don't let this mislead you, there are many types of parasites that have been found from these people...pinworms were especially prevalent in many areas and hookworms are often found in North American coprolites.  That being said, the extent of parasitism in these areas was no where near what is found in the Old World.

Now let's shift our focus to the Old World...specifically to Medieval Western Europe.  This region of the world at this time was vastly overpopulated.  Crowd diseases were you might imagine when discussing outbreaks such as boubonic plague.  These people had TONS of whipworms and maw worm infections.  Not only were these parasites more prevalent than those found in the New World, they were also much more devastating.  These sorts of infections can cause much more serious health problems...especially if they are not properly treated.

Speaking of treatment, let's talk about Medieval medicine.  As opposed to the Native American use of natural botanicals which had antihelmenthic properties, Medieval European physicians used treatments that rarely actually treated parasitic diseases.  In fact, many of the practices of these doctors exacerbated the problems their patients were dealing with.  Scienfic studies of medicine were non-existant.  Medicine during this period was regulated by spiritual influences and religious beliefs.  As Christianity began to push out paganism, so did prayers begin to push out the use of herbal remedies.  The idea in those days was that people became ill when they angered God and were in need of punishment or when they were being targeted by demons.  Repentance of sins and exocism were the most important vehicles to medical recovery.  Much of society actually saw medicine as a profession unsuitable for Christian people since disease was mandated by God.  Despite this notion, some monastic orders, such as the Benedictines, were known for their involvement in caring for the sick and dying.

By the time of the 12th century Renaissance, medicine had greatly improved as medical texts became available following translation from Greek and Arabic.  Prior to these texts, classical medicine was largely influcenced by the works of Hippocrates and Galen.  The writings of Galen were based on animal dissections...which gave false assumptions about human anatomy.  His work also discouraged physiological research by incorrectly describing the process of circulation.

The major medical theories were typically fusions of classicaly held ideas, pre-Christian beliefs, and Christian beliefs. Techniques for diagnosis and treatments are reflective of such fusions.  The most underlying principle of medicine was the belief of the humours.  This was the belief that the body has four humours (fluids) made by the body that must maintain a balance to keep a person healthy.  If any of these humours became unbalanced, a person became sick.  Treatments were aimed at restoring balance to blood, phlegm, black bile, and yellow bile.  Treatments involved changes in diets, administering medicines, and using leeches for blood-letting.  The humours were also associated with the seasons (blood-spring; phlegm-winter; black bile-autumn; yellow bile-summer).  This brought astrology into medical practices, assigning patients to particular seasons describing their "nature" and their elements (Fire, Water, Earth, and Air).
The use of herbal remedies were influcenced by pre-Christian religious beliefs, but the success of such remedies were judged by their ability to rebalance the humours.  Such remedies were also influenced by the Doctrine of Signatures...a book connecting medically important plants to disease treatment not by their ability to cure diseases, but by their morphological likeness to various body organs.  For example, liverworts were thought to be useful for treating liver problems since they had morphological similaries to the shape of the liver. These beliefs stemmed from the idea that God left signatures or mark on these plants as clues to how he intended for people to use them.  Much like the writings of Galen, this text slowed the progress of true medical science.

Although medicine did eventually become more relient on observations than on long-standing religious beliefs, it was a long, drawn out process that I won't got into for this blog.  Suffice it to say that the majority of conventional medical practices did not actually treat people infected with parasitic diseases.  Also keep in mind that some of these practices, such as blood-letting, were actually causing more harm to patients with parasitic diseases than they were helping them.  It doesn't take a genius born in today's world to understand that blood-letting probably isn't the best way to treat a person with parasite-induced anemia or malnutrition/malabsorption.  But in those days, that was the best way to restore balance to the humours of a person caring so many whipworms that her intestines were losing their elasticity.

Moral of the Story
It is easy to look back now and see the flaws of medical history, but can we apply the lessons learned from those mistakes to our culture today?  Is spirituality important?  Absolutely!  But given a choice between praying for a migrane to go away and taking an asprin...I'd take the asprin (and probably pray too because it couldn't hurt...but I wouldn't rely solely on the prayer...that's just silly!).  I doubt God wants any of us to get sick or die, but the world around us is full of infectious agents and eventually we will do both.  If you believe that God gave us the free will and the intellegence to develop medical technologies that prolong our life, then you have to agree that using those technologies is not somthing that goes against God's will.  Most Christians aren't this stupid (I hope), but there are certainly those who feel that they shouldn't trust medical science and that leaving it all up to chance is a superior option.

That little rant aside, we have archeological evidence to prove that people in the New World had more efficent ways of controling their parasite burdens.  Everything from the way these people lived, to the way they treated their sick was superior for keeping parasitic infections at bay.  The people of the Old World were much less effective because of overcrowding and flawed medical practices influenced by religion.  It is amazing to think of these parasite-ridden Europeans as the very people who would later see the Native Americans as "savages".

Sunday, March 3, 2013

Keeping the Worms at Bay: Mechanisms Behind Antihelminthic Agents

Lately I've been reading a lot about immunity and drug-parasite interactions.  So, I thought it was time to share some of that knowledge with all of you!  Today, we will talk about a few antihelminthic drugs (a.k.a. "de-wormers") and how these drugs work to rid parasite hosts of their wormy burdens.

First of all, antihelmenthics typically work by either stunning worms (vermiguges) or by killing them altogether (vermicides).  There are a number of natural remedies for riding oneself of parasitic worms.  Most involve plants that are able to affect the worms when ingested directly, when made into a teas, or when inhaled.  The validity of most of these remedies are questionable, but there are some that have been scientifically proven to be effective antihelminthic agents (such as creosote, tobacco, and wormwood).  In fact, some of these natural compounds for the basis for pharmaceuticals.  Then again, others are products of folk medicines which have yet to be tested in scientific laboratories.  These include treatments with cloves, garlic, chive juice, black walnut, pineapples, honey mixed with vinegar, plumeria, and even diatomaceous earth (which originates from diatoms rather than plants).

For this post, we will focus more specifically on the pharmaceutical antihelminthics.  These drugs have been developed to treat flatworms, such as flukes and tapeworms, as well as roundworms, such as hookworms, threadworms, and maw worms.  Flukes are often treated using antimonials, metrifonate, oxamnaquine, praziquantel, or closantel.  Tapeworms are treated using niclosamide, benzimidazoles, or praziquantel.  Roundworms  that infect the intestine may be treated using piperazine, benzimidazoles, morantel, pyrantel, levamisole, avermectins, closantel, or emodepside.  Tissue-invading roundworms tend to be treated using diethylcarbmazine, surmin, or ivermectin.

Now that I've scared some of you with all these big, difficult to pronounce words, let's try to simplify things by looking at the most commonly used drugs and how they work to cleanse hosts of their parasites.

These drugs include a variety of broad spectrum antihelminthics.  The first drug of this class was discovered in 1961 and was called "thiabendazole".  The drugs belonging to this class all work by compromising functionality of the worms' cytoskeletons.  This makes it difficult for the worms to move and to reproduce.  Although these compounds are highly effective for most types of roundworms and some tapeworms, there are some species which have developed a resistance to these drugs.  The resistance has been attributed to the replacement of a single amino acid with a different amino acid within the alleles controlling β-tubulin within the cytoskeletons of these worms that renders the drugs useless.  Drugs in this class include Albendazole (treats threadworms, whipworms, other roundworms, and tapeworms), Mebendazole (treats pinworms, hookworms, and other roundworms), Thiabendazole (treats hookworms and other roundworms), and Triclabendazole (treats liver flukes).

This drug was first introduced as an antihelminthic in the 1980s.  It is a derivative of avermectin, which comes from Streptomyces avermitilis, a  type of bacterium.  (Members of the genus Streptomyces have also been used to create antifungal, antibacterial, and even anticancer drugs.)  This drug interacts with a variety of ion-gated channels, but is specifically good at interfering with glutamate-gated chloride channels within the bodies of nematodes.  The drug utilizes these channels via overactivation to cause paralysis of musculature in both the body wall and in the pharynx (not all species of worms are subjected to pharyengeal paralysis).  Mutations in glutamate-gated chloride channels can lead to resistance, but requires multiple mutations rather than singular mutations.  This makes resistance much more complicated and as a result, less frequently found in nature.


This drug is especially good for killing tapeworms.  In fact, it's often classified as a teniacide (from the word "tenia" which refers to tapeworms).  It isn't really effective against roundworms even to a small degree, but tapeworms exposed to this drug are killed on contact.  This happens because the drug has the ability to "uncouple oxidative phosphorylation"...which translates to, the drug stops all energy production (ATP synthesis) within the worm's cells.  Essentially, it starves the worms on a cellular level.

Nicotinic Receptor Antagonists
This drug class includes drugs like levamisole, pyrantel, and morantel.  All of them act as antagonists at nicotinic receptors within muscles.  They cause continual muscle spasms that eventually lead to paralysis.  This happens because nicotinic acetylcholine receptors will shut down communication when they have been excited for too long.

This drug was first used in the 1950s to treat threadworm infections in children.  It is still used for many over the counter types of medicines.  It works by causing a paralysis within the muscles lining the body wall of these worms.  This is achieved by mimicking the neurotransmitter GABA to induce the relaxation of these muscles.  Diethylcarbmazine is a synthetic derivative of piperazine that is helpful for the treatment of tissue-dwelling roundworms in humans and for the prevention of heartworms in dogs.

Created in German laboratories in the 1970s, this drug has become an important means for controlling flatworm infections.  It works, and it works really well.  Unfortunately, no one is really sure exactly how it works.  Through experimentation with blood flukes, it seems that the drug increases permeability of cell membranes and induces an influx of calcium ions leading to sustained contractions.  This leads to paralysis of the parasites, which causes them to become dislodged from their hosts and leaves them floating in bodily fluids where they are either destroyed by immune reactions or filtered out into waste materials.  Other studies hypothesize that this drug stops the worms' ability to synthesize purines, such as adenosine, making them vulnerable to host digestion.

Moral of the Story
There is certainly more than one way to kill a parasitic worm...sustained contractions, cellular starvation, deprivation of vital nucleotides...but in the end, we are just happy that these antihelminthics work.  As with all drugs, we have to be weary of over-prescription to prevent drug resistance, but it is still comforting to know not just that these drugs work, but how they work, and why they work so well.  Antihelminthics, we salute you and all of your devastatingly intricate modes of action leading to what are probably pretty painful deaths for our parasites!

A person dispensing ivermectin tablets to a young girl during a central point distribution in her village.