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 ubiquitous...as 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".

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.

Benzimidazoles

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).

Ivermectin
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.

Niclosamide

Niclosamide
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.

Piperazine
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.

Praziquantel
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.

Stem Cells in Schistosomes!

Good news everyone! A parasite-related paper was released on Wednesday in Nature that involved those monogamous little blood flukes we call the schistosomes! The paper was titled "Adult somatic stem cells in the human parasite Schistosoma mansoni" and it brought up some interesting new information regarding how these worms live so long.

These worms are well-known for their longevity. S. mansoni has been known to live for years, even decades within their hosts.  These worms live an average of 5-6 years, however there are reports of people becoming infected during childhood and not developing clinical symptoms until adolescence or adulthood. 

A composite image of a scanning electron micrograph
of a pair of male and female Schistosoma mansoni with
the outer tegument (skin) of the male worm "peeled back" (digitally)
to reveal the stem cells (orange) underneath. (Credit: Jim Collins,
Ana Vieira and Phillip Newmark, Howard Hughes Medical Institute
and University of Illinois at Urbana-Champaign)

This newly released study reveals that these worms may be able to achieve such long live spans through the use of stem cells. These findings aren't completely shocking.  These flukes are related to a type of non-parasitic flatworm known as Planaria.  These adorable little turbellarians are often used in zoology labs to demonstrate regeneration to students.  They have a remarkable ability to regenerate from longitutinal and transverse cuts because they house special stem cells known as neoblasts. Stem cells, by definition are able to develop into any type of cell the worm needs...blood cells, muscle cells, etc.  Neoblasts don't just help the Planaria regenerate damaged tissues, they also help to repair tissues that become damaged over time as the worm ages.

Lead researcher Phillip Newmark wondered if maybe schistosomes were living so long because they also had stem cells that repaired damaged tissues to keep the worms young. Following up on his suspicions, he and his team began searching for these cells in schistosomes.

They used fluorescent tagging techniques to find actively dividing cells within the blood flukes, then they isolated the cells and studied them.  Through their observations of these cells, they were able to determine that the cells divided to create two new cells: one that differentiated into another cell type (which varied) and one that was another stem cell.  This is characteristic about what is already known of stem cells.

Here's a quote from Newmark about the research:

The cells we found in the schistosome look remarkably like planarian neoblasts. They aren’t associated with any one organ, but can give rise to multiple cell types. People often wonder why we study the ‘lowly’ planarian, but this work provides an example of how basic biology can lead you, in unanticipated and exciting ways, to findings that are directly relevant to important public health problems.

 
This paper isn't insinuating that these neoblast-like stem cells are the only reason that schistosomes can live for so long, it is merely demonstrating that having these cells plays a role in their longevity. With continued research, it is believed that new treatments for curing people of schistosome infections will be created that target these stem cells for more efficient killing of the parasite.

Isn't biology fascinating?! There's always something new to learn about things that we have spent decades and probably millions...maybe even billions...of dollars researching! Yay for a field that is ever-changing and oh-so-exciting! :D

Zombie-Slave Spiders

I love spiders.  I'm also a big fan of zombie-lore, and of course of parasites.  This week, I decided to bring those three things together to tell you about a species of parasitic wasp that infects spiders.  This parasitic wasp (belonging to the genus Zatypota) hijacks the spider's body making it not only a zombie, but also a slave.  Infected spiders spin slightly abnormal webs to make better areas for the parasites' cocoons.

Zatypota specimen
mounted on a pin.

There are probably hundreds of species of parasitic wasps.  Most of theses belong in the family Ichneumonidae.  (In fact, they might all be in this family...but I can't remember, and I don't want to lie to you!) Within this family is a subgrouping that includes wasps that specifically parasitize spiders.  Members of this group are known as polysphinctine wasps. The female parasitic wasps use their ovipositors to insert eggs into the bodies of many different types of hosts...caterpillars, cockroaches, and as you will soon learn, spiders.  These wasps' eggs usually hatch within the host, using it as a food source, shelter, and in some cases as a vehicle to a more suitable emergence area.  Today, we will look specifically at a type of parasitic wasp that infects a spider that lives in the rainforests of Costa Rica.

Anelosimus octavius is a type of spider belonging in the trash-web family, Theridiidae.  This family is full of spiders with large abdomens that are carried in a distinctive way by members of this family.  I can't describe this very well...it's really something you just have to see to understand.  This family is also known as the family of  "comb-footed" spiders due to these neat little modifications they have on their back set of legs. Spiders in this family are also sometimes referred to as "cobweb" spiders because their webs take on a haphazard cotton-y appearance rather than the intricate patterns created by orbweavers or the distinctive sheets made by funnel-web spiders and their relatives.  Some of the more infamous members of this family include members of the genus Laterodectus...also known as black widows.

A typical web built by Anelosimus octavius.

Getting back to our little Zatypota, this wasp, like other polysphinctine wasps, modifies the behavior of their spiders hosts.  More specifically, these parasites modify the spiders' web-building behaviors. After a female wasp inserts its eggs into the spider hosts, the wasp larvae grow for about a week, feeding on the spiders' hemolymph for sustenance. Then, the larvae commands the spider to construct a modified "cocoon web".  Then the larvae emerge from their hosts, eat the hosts, then build a cocoon next to the cocoon web in which to pupate.  The idea is that these cocoon webs and other parts of modified web structures increases the likelihood of survival for the wasps by serving as additional protection during the pupal stage.

Central platform of web
showing top of wasp cocoon.

According to reports of observations of infected spiders, the hosts spend a great deal of time and effort preparing the cocoon webs for their parasites.  After tireless efforts, the exhausted spiders crawl back into the central part of the site only to become immobile  before being consumed by its parasite.  The following day, the parasite would began constructing its own cocoon right on top of the area where it ate its host.

It is interesting to think about how this could have evolved among these two species! However it happened, this is yet another awesome example of behavioral modification due to parasitism.  Hooray for making your hosts into zombies!

This is from a paper describing the odd behavioral changes induced by these parasitic wasps.
"Figure 2: Cocoon web of A. nr. studiosus (a) in which the wasp larva holds onto the densely-meshed central area just after having discarded the corpse of the spider. Lateral (b) and dorsal (c) views of wasp cocoons in cocoon webs of A. octavius, showing the radial pattern of lines around the upper end of the cocoon (c), and that the lines intersecting the cocoon (indicated by small “pimples”) are in the upper portion of the cocoon, with an open space below in which the cocoon hangs free (bar in (b)). The cocoon web spun from scratch in captivity (d) incorporated flat leaves (covered with white dust in the photo) as parts of the sheet."

Toxo on the Brain

Toxoplasma gondii is one of those parasites that, once you learn about what it's capable of, you can't get it out of your head.  In some cases, that could be taken literally.  To learn the basics about this parasite, see this previous post.  Did you read it? Good! Let's move on.

Since the early 90's, scientists have known that T. gondii causes drastic behavioral changes in rats and mice.  It represses the animals' innate fears by essentially screwing with their brain chemistry until they start to actually like the odor of cat urine rather than being afraid of the scent.  This behavioral change is believed to be instigated by the parasite in order to get it into the definitive host (a cat).

Those studies were vastly interesting, but in recent years scientists have begun to find correlations between  toxoplasmosis and changes in human behavior.  Therefore, we will focus on the research presented with regard to human manipulation as opposed to rodent manipulations for the purposes of this post.

The idea that Toxoplasma could actually affect human behavior was radical when first proposed by a Czech biologist named Jaroslav Flegr.  His work has been highly controversial among people within the scientific community, but his diligence has paid off.  In November of 2012, a group of Swedish researchers discovered that this parasite hijacks white blood cells in order to make its way to the brain. Back in 2009, U.K. scientists discovered that this parasite has two genes for making a precursor molecule for the production of dopamine (1-DOPA, in case you were wondering). Upon further testing, it was found that the parasite induces the upregulation of dopamine production once in the brain of rats, and later it was found that infected humans also have increased levels of this neurotransmitter.

A Pseudocyst of parasites that forms in the brain.

The significance of increased dopamine production is how dopamine affects our behaviors. It was noted in rats to affect male and female rats differently, something that is, again, reflected in infected humans. In men, the increase in dopamine leads to a decrease in the production of the stress-hormone known as cortisol. This causes a spike in testosterone levels, which can drastically change a man's personality. These changes include increased aggression, social difficulties, increased dominance, impulsiveness, and a disinterest in the feelings of others (often to the point of psychopathy).

The increased production of dopamine in females causes very different changes.  Women's bodies are more adapted to dealing with increases in dopamine levels.  To cope with this, a female's body releases an influx of the sex hormones oestrogen and progesterone into the dopamenergic systems.  Unlike in men, this causes an increase in cortisol production in females, which drops the already low levels of testosterone.  Infected women tend to be less impulsive, more sensitive to the needs of others, more motivated, more outgoing, and more relaxed.  However, they do seem to experience hair loss and lowered libido in response to infection.

The personality changes described above become more drastic over time. Regardless of gender, infected people have been shown by some of Flegr's studies to be almost twice as likely to be involved in a car accident.  This is because the parasite leads humans to having slower reaction times and increased fatigue.  Infected people have an increased risk of both suicide and of developing mental problems for which they will need to be institutionalized for their own safety.  There are also many links between toxoplasmosis and psycological disorders. Mood disorders such as bipolar disorder and clinical depression have been connected  with infection as has obsessive-compulsive disorder.

The disorder that has been most studied in connection with toxoplasmosis is schizophrenia.  Dopamine plays a big role in the development of schizophrenia.  Many people diagnosed with this disorder test positive for Toxoplasma gondii antibodies.  The link between schizophrenia and toxoplasmosis is still being studied, but it makes sense that an interplay could be present due to their connections with dopamine.

Toxoplasma gondii in green,
multipling inside a dendritic cell.

I mentioned earlier, it was recently discovered that the parasites hitch rides on white blood cells.  To be more specific, they grab hold of dendritic cells and use them to get into the host's brain. To get the dendritic cells to move, the parasites induce these cells to produce GABA (a neurotransmitter).  Like igniting a flame, the release of GABA by the dendritic cells excites GABA receptors outside the cell and sends it blasting through the body until it reaches the brain.  Another interesting thing about GABA? Changes in GABA levels are associated with psychiatric disorders such as...you guessed it...schizophrenia.

Now let's switch gears...we know that this tiny, single-celled protist may be the cause of some serious neurological disorders and that it induces some interesting changes in personality.  But this parasite isn't all bad, it has been reported that women infected with an asymptomatic form of toxoplasmosis (known as "latent toxoplasmosis") may benefit from the infection.  It seems that women infected with this prior to pregnancy are protected from contracting acute toxoplasmosis and their fetuses are protected from getting congenital toxoplasmosis! How cool is that?

It gets cooler!  Some scientists are doing cutting-edge research on using this parasite to TREAT neurological problems.  Yes, you read that right!  It seems that controlled infections can help people with problems relating to decreases in dopamine, such as ADD and ADHD.  It is also being used in researching treatments for both Parkinson's disease and Alzheimer's disease!

I guess that just goes to show you that there are two sides to every coin...or in this case, to every unicellular eukaryotic endoparasite! :p  With all of the advances being made in helminthic therapy, it will be great to see what medical science is able to do to utilize the manipulative capabilities of this parasite in the treatment of low-dopamine related disorders.

Who can resist posting rainbow pictures of parasites?!

New Insights on Old Worms

As we've seen with past work, it's not easy to find parasites in coprolites that date back to 270 million years ago.  However, a team of researchers has found such diamonds in the rough...if you think of tapeworm eggs as tiny diamonds, and fossilized shark poop as the rough.

Shark coprolite containing 270 million year old tapeworm eggs.

These researchers published their work in PLoS One in January of this year (2013). From a Brazilian coprolite dating back to the Paleozoic era, this team found a group of 93 tapeworm eggs.  Like modern fish tapeworm eggs, these possessed a single operculum, and one even looked to contain a developing larva.  The oval-shaped eggs were beautifully preserved inside the coprolite encased within what appears to have been a proglottid. 

#1, this is awesome because it is the first time that tapeworm eggs have been recovered from anything that is this old.  We are talking older by FAR...these eggs predate parasites found in the fossil record dating back to dinosaurs. In fact, these eggs predate known instances of any form of vertebrate parasites by about 140 million years.  This sets the evolutionary time stamp much further back for intestinal parasites than we ever thought they had existed. (This is why biology is awesome! What we think we know today, could be completely wrong with the discoveries of tomorrow!)

This discovery will hopefully spur the interest of other researchers into doing paleoparasitology work.  It is absolutely amazing to have the definitive proof of the existence of something as soft-bodied as a tapeworm preserved for 270 million years.  This discovery was made from just one of over 500 similar coprolites located in a single area where researchers believe fish may have been trapped due to a dry spell.

270-million-year-old tapeworm eggs from a section taken from a shark coprolite.  In "A" you can see the proglottid surrounding the eggs.  In "B" you can see the eggs up close...the arrows indicate the opercula.

The state of preservation was astounding.  There was quiet a bit of pyrite (fool's gold) found in the coprolites, which tells us that the environment must have been pretty well depleted of oxygen.  Even though these coprolites can tell us a lot about the environmental conditions at the time of deposition, the exact species that deposited the coprolite will remain a mystery since all shark poop looks the same.

The tapeworm species is yet to be determined, but is similar to extant species found within Tetraphyllidea (which contains 540 extant species that parasitize Elasmobranchs).

I can't wait to see just how much more we discover about these little dudes in the coming year! :)

Clearing the Bad Air: Let's Talk About Malaria!

It occurred to me today that I have yet to post about one of the most famous and infamous parasitic diseases: Malaria.  The name of this disease literally translates to "Bad Air" because early conquistadors believed you could get it from breathing in...well...bad air.  This misconception came along as the Spanish pushed into the tropical regions of the New World and lost many lives to this strange new (to them) tropical disease.  It's interesting to note that although the Spanish believed  the disease originated in the New World, it has been established in recent times that the disease was actually brought to the New World by the Spanish...who brought with them slaves from Africa that were likely already infected.  Today we understand far more about this devastating disease.  Because of its prevalence in tropical regions and its socio-economic impact, this disease has probably been THE most studied parasitic disease.  Billions of dollars have been spent battling the disease and the impacts that it has on countries around the world.  But let's not get too far ahead of ourselves....

Taxonomy

Plasmodium (in yellow) bursting RBCs

Malaria is caused by protozoan parasites belonging in the genus Plasmodium.  Like all protozoa, these parasites once belonged in kingdom protista, but some texts now break that kingdom into several others.  In such texts, these belong to kingdom Chromalveolata under the subgroup Alveolata, or in some cases kingdom Alveolata may be listed.  While phylogeneticists debate the true kingdom-level classification, we will move on to more solid taxonomic statuses.  There are no debates at all as to which phylum Plasmodium belongs.  Because of the collection of organelles that function in host-penetration processes known as the "apical complex", these parasites and their brethren are placed within phylum Apicomplexa.  Because they lack a conoid, they are placed in class Aconoidasida ("a" meaning "without").  They are within order Haemosporida along with other malaria-like organisms and piroplasms.  And, naturally, they belong to family...you guessed it...Plasmodiidae.  There are four species of Plasmodium that infect humans: P. falciparum, P. ovale, P. malariae, and P. vivax.

Life Cycle
Ask any undergraduate biology student with a few years of classes under their belt to draw you the life cycle of Plasmodium.  Go on...I'll wait....Did they do it?...Correctly?...Awesome!  The life cycle for this parasite is often one of the first life cycles encountered by students of biology.  Let's start with the vector.  This parasite is spread via bites from female mosquitoes belonging to the genus Anopheles.  

Anopheles Up Close and Personal

As the mosquito bites you, tiny sporozoites wiggle their way out of the salivary glands of this vector and into your blood stream.  It rides the tide of your briskly moving currents of blood until it reaches the liver, where it invades liver cells (a.k.a. hepatocytes).  Here, the sporozoites undergo a rapid form of multiple asexual divisions known as schizogony to produce merozoites.  The merozoites break out of the hepatocytes and seek out red blood cells (a.k.a. erythrocytes) to infect.  Once inside, the host erythrocytes become transformed into factories producing additional merozoites and bursting (a.k.a. "lysing") to release 8-24 new merozoites that seek out more erythrocytes.  While some merozoites are content to continue to reproduce in this manner, others will develop into gametocytes.  When an uninfected Anopheles female comes around to take a blood meal from a person housing Plasmodium, many of the gametocytes are ingested with the blood.  These cells mature in the gut of the mosquito. Eventually, male and female gametocytes will fuse to create  zygotes (a.k.a. "ookinetes" in this case), which will eventually become sporozoites.  After developing into this motile, infective form, the sporozoites move into the mosquito's salivary glands and the cycle is complete.

Outsmarting Our Immune Systems
Plasmodium is a devious little dude.  These parasites are largely protected from the treat of a host's immune system because they live within cells rather than outside of them.  This hides them from circulating immune police, such as macrophages.  However, erythrocytes are prone to aging because they work so hard for our bodies.  When these cells pass through the spleen, they are checked for signs of damage or aging, and are subsequently filtered out of regular circulation.  The parasites becomes the cutting edge of anti-aging technology for these little cells by using proteins to prop up the cells, making them seem young to the busy spleen, and saving the parasites' homes for another road trip through the circulatory system.  Some species, such as P. falciparum, will even go so far as to produce adhesive proteins that force cells to stick to walls of small vessels in order to save themselves from being processed via the spleen.

Symptoms of Malaria
The symptoms of malaria may not appear until 8-30 days post-infection.  As the parasites enter into the phase of their life cycle in which they invade erythrocytes and force them to burst, people tend to spike fevers.  In some instances, people infected by P. viviax won't display symptoms for several months or even years post-infection.  This is because this species produces hypnozoites, which allow for long incubation periods and late relapses of infections.

The most common symptoms are flu-like in nature: headache, fever, shivering, joint and muscle pain, vomiting...but some are more severe such as anemia, jaundice, and retinal damage.  The most defining symptom is paroxysm.  Paroxysm is a period of coldness followed by chills and then by high fevers and sweating.  The time frame of paroxysm states is dependent upon the type of malarial parasite with which one is infected.

The World Health Organization (WHO) splits malaria cases into two categories: "Severe" and "Uncomplicated".  To be classified as "severe", one must demonstrate any of the following: decreased consciousness, significant weakness (e.g. inability to walk), loss of ability to eat, convulsions, low blood pressure, breathing difficulties, circulatory shock, kidney failure, red (hemoglobin-rich) urine, uncontrollable bleeding, enlarged liver, enlarged spleen, pulmonary edema, low blood glucose, acidosis, high levels of lactate, or an extremely high parasite level present in the blood.  The disease can progress to an even more severe form (if infected with P. falciparum) known as cerebral malaria.  This form presents with neurological problems such as seizures and comas.
 
Diagnosis, Treatment, and Prevention
Malaria is diagnosed by finding the parasites in a blood sample.  This can be through microscopic examinations of blood smears, or through antigen-based diagnostics tests.  The later is more accurate, but also more costly, and these tests are not yet sophisticated enough to tell how many parasites are present within a sample.  Polymerase Chain Reaction (PCR) has been shown to diagnose malaria efficiently, but is not widely used due to its complexity.

People diagnosed with malaria are usually treated using chloroquine in areas where Plasmodium isn't already resistant. Because resistance is so prevalent, most patients are also given mefloquine, doxycycline, or Malarone.  To prevent resistance, many places are now instituting the use of artemisinin-combination therapys (ACTs), which involves treating with traditional anti-malarial medications in conjunction with artemisinin compounds.  ACT is about 90% effective if used to treat "uncomplicated" forms of malaria.  When treated correctly, patients can experience a complete recovery. 

Various Anti-Malarial Medications

"Severe" forms of malaria were once treated with quinine, but now artesunate is more widely used because of its efficiency.  Treatment also includes supporting patients by helping them manage high fevers and seizures as they come and go as well as monitoring respiratory rates, blood pressure, and blood glucose levels.  This form of malaria can progress so fast that it can cause death within days or in some cases hours.

To prevent malaria, most tropical regions take on a three-pronged approach:
1) They give out prophylactic medications (if they can afford to do so).
2) They work to eliminate Anopheles mosquitoes.
3) They devise ways to prevent people from getting bitten by mosquitoes.

Prophylactic medicines are often the same medicines used for treatment (mefloquine, chloroquine, Malarone, etc.).  Travelers heading to malaria-endemic regions begin taking prophylactics a few weeks before leaving and continue taking them for about a month after coming back home.  (I personally took Malarone when I traveled to Panama for two weeks, and I didn't have any problems, but many people have side effects of this and other such drugs.)  This form of prophylaxis is not typically practical for residents of malaria-endemic areas because drug resistance and partial immunity can come from prolonged use.  This is also a costly endeavor, and has had many historical roadblocks.

To prevent mosquito bites, people can use DEET-based repellents and insecticide-treated mosquito nets.  Treating the nets with insecticides reduces the chances of mosquitoes living long enough to find a way to breech the nets themselves.

A woman tucks a mosquito net into her child's mattress.

 Some places have instituted spraying for mosquitoes (both indoors and outdoors).  Indoor spraying is highly effective as the mosquitoes tend to land on wall surfaces after taking in blood meals.  The WHO advises the use of 12 insecticides for such purposes.  Like anti-malarial drugs, these insecticides should be used in combination to prevent resistance.

Community-aimed educational programs are also helpful in preventing the spread of malaria.  After all, knowledge is power!  Seriously!  Teaching people to cover areas with stagnant water that could become mosquito-breeding grounds, as well as helping people to recognize the signs and symptoms of malaria can greatly reduce the number of malaria cases reported in an area.

An old poster encouraging people to spray for mosquitoes.

Ultimately, the best approach would be to prevent malaria rather than to treat it. (More cost effective and less costly in terms of human life.)  However, the monetary costs of instituting a program for prevention are beyond the means of the countries where malaria posses the biggest threat to public health.  Luckily, there are some amazing researchers (namely Jay Keasling...go on...Google him!) working to produce an anti-malarial drug that can be mass-produced cheaply.  Thanks to this kind of research, and humanitarian efforts directed at distribution, the next few decades are sure to reduce the number of annual cases of malaria.  It will be interesting to see how things change from a socio-economical perspective in response to a decline in a disease with such wide-reaching impacts on global health and economies.

Moral of the Story 
Though I could go on and on and on about malaria, this post has already gotten rather lengthy, so we will call it quits for today.  Maybe a future post will discuss the amazing way some populations have developed genes that prevent them from contracting malaria...or we could delve deeper into the work of Jay Keasling.  Perhaps a future post could discuss the history of malaria, an exciting tale of man's ups and downs as he fights to erradicate a disease that just won't seem to die.  For now, at least you can proudly say that you know the basics about malaria.  So if you ever travel to malaria-endemic areas, be sure to take your antimalarials (before, during, and after), sleep with a special insecticide-drenched, netted canopy surrounding your bed, and be sure to invest in plenty of DEET!

P. falciparum...because I can't resist a rainbow-colored image!
(Even if it is artificially done! :p)