Dracunculus scriptum:

My explorations in the fascinating world of parasites

"Parasites don't just make hosts sick; they are an important part of life on earth."

Did people really swallow tapeworms to lose weight? This wouldn't have worked very well. c. 1900 USFDA
April 6, 2017

Amber Reveals Prehistoric Parasites Preserved in Blood

Perhaps 20 million years ago, a pair of monkeys in what is today the Dominican Republic sat grooming each other. Somewhere nearby, possibly in the tree where they sat, there was a sticky and probably aromatic collection of plant resin. This wasn’t an unusual jungle scene at the time, but what happened next was. 

One of the monkeys discovered a tick feeding and already bloated with its blood meal. The monkey pulled it free. Something punctured the body of the tick – claws perhaps, or teeth - and monkey blood leaked out. Discarded, or dropped by accident (would the monkey not have preferred to eat this tasty morsel?), the tick fell into the resin and stuck there, still oozing blood.

The tick wasn’t the only organism to die in the resin that day. Within the tiny monkey red blood cells, there were piroplasms – parasites that multiply asexually inside blood cells, burst out, and invade new blood cells. Eventually, the process produces male and female forms that can reproduce only after being ingested by a tick, in a blood meal.*























Fossil Red Blood Cells

The piroplasms ingested by the tick in this story never reproduced. Instead, they became fossilized in amber, along with the blood cells and the tick. All are still identifiable millions of years later. This piece of amber holds the only fossilized red blood cells from a mammal yet found; the parasites within them are an added fascinating treasure.

Infection with Piroplasms: Babesia, Theileria, Cytauxzoon

Was the monkey sick? Possibly. The destruction of red blood cells caused by the multiplication of the parasites can lead to severe anemia and even death. Babesia bigemina is a notorious killer of cattle in the United States.  Theileria parva causes East Coast fever and death in African cattle. Cytauxzoon felis kills domestic cats in the United States. Some infections go unnoticed, however, and animals can develop immunity. It’s possible the monkey wasn’t all that bothered by its infection.

Throughout the ensuing millennia, ticks continued to bite mammals and infect them with piroplasms, and no one even knew it was happening until the early 1880s when Theobald Smith and Frank Kilbourne proved that a tick transmitted Babesia bigemina to cattle. Not only did they solve the mystery of what was causing Texas cattle fever, it was the first proof that creatures such as insects and arachnids (spiders, ticks, mites etc.) could spread diseases with their bites. 

It took about another 75 years before anyone documented a case of piroplasms infecting humans, and then only in humans who lacked a spleen. Caused by Babesia divergens, there were very few such cases, and the disease remained a medical rarity until recently. In 1969, Babesia microti began turning up in the United States in the same places where Lyme disease is emerging. Today, it’s a spreading infection in the United States and Canada, striking thousands of people every year, and killing some.

Evolution of Babesia

Lots of people still haven’t heard of Babesia, much less piroplasms, and for the rest of us, they still seem quite new. So the discovery of organisms resembling Babesia sp. fossilized in amber that might well be more than 20 million years old is delightful. For all of that time, they’ve been evolving and adapting to their hosts until we finally became aware of them. We might never have known Babesia has been around that long if those two monkeys hadn’t stopped to pick off a few ectoparasites in the jungle so long ago.

Photographs published in the report of this finding are tantalizing, though not as clear as a modern-day blood film. What they mostly do is make me want to sit down at a microscope and look at that magnificent piece of amber myself!

*Researcher George Poinar Jr. can’t be absolutely certain that the animal the tick was feeding on was a monkey, or that the parasites in the blood are piroplasms; however, after considering other evidence – red blood cell and parasite characteristics, the fossil record, knowledge of primates, piroplasms, and other organisms alive today etc. – this is most likely the correct interpretation.

Read the paper in the Journal of Medical Entomology:

 Poinar, George, Jr. (2017) “Fossilized Mammalian Erythrocytes Associated with a Tick Reveal Ancient Piroplasms.” J Med Entomol tjw247. 
doi: 10.1093/jme/tjw247

Further Reading About Babesia and Other Piroplasms

Schmidt, Gerald D. and Larry S. Roberts. Foundations of Parasitology 8th Ed. New York: McGraw Hill, 2009.

CDC. Surveillance for Babesiosis - United States, 2014: Annual Summary



Life cycle diagram for Babesia microti. CDC
Amber is fossilized tree resin. It has unique properties for preserving organisms that become embedded in it. Image by Wibowo Djatmiko CC BY-SA 3.0
Like the tick in this article, this mosquito was discovered in amber in the Dominican Republic. Image by Didier Desouens CC BY-SA 4.0 (not licensed for upload to Facebook)
April 25, 2017

Historical and Traditional Treatments for Guinea Worm Disease

The female Guinea worm, Dracunculus medinensis, causes a burning, itching, excruciatingly painful blister on the skin of her human host. She pushes part of her body out through the lesion and waits to release her young into fresh water.

She can be nearly a yard long and the only way to get rid of her is to physically remove her: there is no drug to treat dracunculiasis, and no vaccine to prevent it. Dracunculus medinensis has been with us for thousands, perhaps millions, of years.

Guinea Worm Treatment in Antiquity

Scholars believe that one of the earliest written prescriptions for treatment of this parasite is found in the Papyrus Ebers, an ancient Egyptian medical document dated to about 1500 BCE. In Parasites and Parasitic Infections in Early Medicine and Science, Hoeppli provides a translation by B. Ebbell: “Thou shalt perform an operation for it, the same being split with a... knife and seized with a... -instrument (forceps); that which is in its interior is seized with a forceps, and then thou shalt remove it... That which is like the head is seized...”

This describes surgical removal: an incision to expose the worm, then extraction with forceps. Without pain medication, this would be exquisite torture, but the approach is still sometimes used. A variation, described by A. Hooton in 1927 (Hoeppli), removed the worm from the incision with suction, using the mouth and a funnel.

A third quasi-surgical approach sounds horrific and seems unlikely to have worked: cauterization of the inflammation in several places with a hot iron. The worm was said to emerge through one of the wounds thus created.

More common than surgery, and probably older, is the technique of slowly pulling the worm out through the original lesion. There are several variations of this approach as well.

Removing the Guinea Worm Without Surgery

To remove Dracunculus medinensis, you can tie a thread around the end of the worm so that it cannot withdraw back into the skin, and then attach a lead weight to create a steady pull to draw it out. The weight of the lead is presumably critical because, in the words of Hoeppli, “The symptoms of Guinea worm infection were described by numerous authors all of whom agreed that in no circumstances should the worm be broken, as, generally speaking, a severe reaction would follow.”

One can imagine that a Guinea worm nearly a yard long would be increasingly cumbersome as more and more was extracted. A second method addresses this problem: fasten the end of the worm to a small stick, like a matchstick, and slowly draw the worm out – over a period of days or weeks - by turning the stick, thus winding the worm around it like a spool.

Slow and careful extraction of the worm remains the typical method for treating Guinea worm disease to this day.

Herbal Remedies for Guinea Worm

Hoeppli found a handful of herbal remedies for Guinea worm infection, recorded by R. G. Anderson in 1908. These would have been used when the emergence of the worm was already in progress: typically one would not know of its presence before this point.

Castor bean:

"Powder 1 oz. dried castor oil leaves, add water until a daughy mass is obtained. Place this as a poultice on the wound... night and morning."

Ricinus communis, native to Africa, is perhaps best known for castor oil and the poison ricin, both made from the beans. Today, the plant is grown all over the world.

Siqqiqui and colleagues mention the use of leaf poultices for boils and swellings, and for removing the Guinea worm. They also describe the use of various parts of the plant to treat chest diseases such as asthma and bronchitis, to relieve gas, rheumatism, back problems, and digestive issues, and to make hair grow.

While much research into the antihelminthic (anti-worm) properties of R. communis has investigated its usefulness only in animals, there is evidence that it is toxic to filarial worms of humans. Thus, it may be somewhat effective against D. medinensis as well.

Tundub tree:

 "A pulp made from the freshly cut ends of branches... may be applied to the inflamed area."

The tundub tree (Capparis aphylla, also known as C. decidua or desert broom) is an evergreen but mostly leafless shrub, growing in the same places that Guinea worm has flourished over the centuries - deserts and places where water sources are rare and sometimes seasonal.

Applying a paste made from the cut ends of tundub tree stems might ease your Guinea worm lesion. It might also fend off infection.

Historically, the people in these regions have used the plant to treat a variety of medical problems including jaundice, heart disease, stomach problems, constipation, skin diseases, and infectious diseases including worms.

This ancient remedy may have had some effect. Research has shown that the pulp has antihelminthic, as well as antibacterial and antifungal properties.

It may be helpful in avoiding the secondary infections that so often accompany Guinea worm infection. Recently, scientists found that an extract of C. aphylla causes infertility in male rats, suggesting contraceptive properties.

Asafoetida:

 "Three drachms [3/8 oz] of powdered [asafoetida] should be mixed in... milk and drunk every morning..."

Asafoetida (Ferula asafoetida) is a gum resin prepared from the root and rhizome of a flowering herbaceous plant. It is commonly used as a spice in Middle Eastern and Southern Asian cuisine, and has been used as an herbal medicine for various ailments for centuries. It is reputed to be an antispasmodic, expectorant, diuretic, and even an aphrodisiac. A number of cultures have used it to expel worms. Interestingly, Mahendra and Bisht write that the people of India also eat the gum to prevent guinea worm infection, a rare preventative approach.

Although research suggests the plant may have antihelminthic, as well as antibacterial and antiviral properties, we don't know whether ingesting it with milk would have any effect on D. medinensis.

No Drugs for Guinea Worm

The fact that no drug has been found to vanquish the Guinea worm in the human host might be surprising, but such a cure might be worse than the disease anyway. Writing in the Bulletin of the World Health Organization Supplement, R. Muller wonders “whether direct antiparasitic activity against such a large amount of foreign protein is desirable.”
“...metrifonate has some action against many helminths..." Muller explains, "and was the only substance shown to be effective against guinea worms in infected rhesus monkeys. ...unfortunately, the monkey also died with symptoms indicative of anaphylactic shock” ("Guinea Worm Disease: Epidemiology, Control and Treatment," 1979). Having a large worm decomposing in the tissues could lead to serious secondary problems in people as well.

Fortunately, it's likely this will soon be of only academic interest. The Guinea Worm Disease Eradication program spearheaded by the Carter Center in the United States looks set to succeed. There were only twenty-five cases reported, worldwide, in 2016. For comparison, in 1986 there were an estimated 3.5 million cases.

Related

The Rise and Fall of the Guinea Worm

Guinea Worm Eradication

Resources

Atlas of Pediatrics in the Tropics and Resource-Limited Settings. "Dracunculiasis." (n.d.) Accessed May 28, 2013.

Hoeppli, R. Parasites and Parasitic Infections in Early Medicine and Science. (1959). University of Malaya Press.

Iranshahy, Milad, and Iranshahi, Mehrdad. "Traditional Uses, Phytochemistry, and Pharmacology of Asafoetida (Ferula assa-foetida oleo-gum-resin) – A Review." (2011). Journal of Ethnopharmacology. 134:1.

Nisha, Mathew, Kalyanasundaram, M et al. "In Vitro Screening of Medicinal Plant Extracts for Macrofilaricidal Activity." (2007). Parasitology Research. 100:3.

Mahendra, Poonam, and Bisht, Shradha. "Ferula asafoetida: Traditional Uses and Pharmacological Activity." (2012). Pharmacognosy Review. 6:12.

Mishra, S. N., Tomar, P. C. et al. "Medicinal and Food Value of Capparis – a Harsh Terrain Plant." (2007). Indian Journal of Traditional Knowledge. 6:1.

Muller, R. "Guinea Worm Disease: Epidemiology, Control and Treatment." (1979). Bulletin of the World Health Organization Supplement. 57:5.

Siddiqui, Munawar., Bayer, Marc J. et al. "Ricin." (July 1997). Mithridata. 8:2.

Revathi, P., Vani, B. et al. Reproductive Toxicity of Capparis aphylla (Roth.) in Male Albino Rats. (2010). International Journal of Pharmaceutical and Biomedical Research. 1:3. 

The Carter Center. "Guinea Worm Disease Eradication." Accessed April 25, 2017.

An ancient remedy for Guinea worm involved making a paste from the leaves of the castor bean plant. Castor oil and ricin are made from the beans of the same plant.
Image by Rickjpelleg; CC BY-SA 2.5
Applying a paste made from the cut ends of tundub tree stems might ease your Guinea worm lesion. It might also fend off infection. D. Brandis, Illustrations of the Forest Flora of North-West and Central India PD-1996
Asafoetida is commonly known as a spice in Southern Asian cooking, but it's been used medicinally for generations. Those afflicted with Guinea worm have consumed it to avoid the worm, and to treat infection.
 Image by Iustinus CC BY-SA 3.0
May 25, 2017

Does Toxoplasma gondii Cause Prostate Cancer?

Cats are making headlines again, courtesy of Toxoplasma gondii, that tiny protozoan that infects warm blooded vertebrates far and wide, but especially, most especially, cats. The latest news flash is that T. gondii may cause prostate cancer. Of course some headlines go one step farther and blame the cats. More on that later.

Toxoplasma gondii Causes Prostatic Inflammation

A study reported in the journal Prostate found that mice inoculated with T. gondii in the lab developed prostatic inflammation that persisted and progressed (Colinot et al). Two weeks after the mice were infected, cysts of T. gondii could be found in the prostatic tissue. The aim of the study, however, was not to determine whether mice infected with T. gondii develop prostate cancer, but to determine whether T. gondii causes inflammation and hyperplasia (enlargement of the prostate) in mice. Inflammation and hyperplasia are both benign.

Inflammation in the prostate is associated with development of prostate cancer, though the relationship is not well understood. The authors remark that their work has provided “a powerful new mouse model for the study of chronic prostatic inflammation and microglandular hyperplasia” (my emphasis). They don’t claim to have found a cause for prostate cancer.














Further work reported in the Journal of Urology found that men with antibodies to T. gondii (indicating infection) are about five times more likely to have an elevated PSA (prostate specific antigen) level than men who have not been infected. High PSA results also correlate with prostate cancer; however, the test has a high false positive rate, and also correlates with benign prostate conditions.

Prostate Cancer Causation vs Correlation

I’ve noticed that when I pull a dandelion out of my lawn, there’s usually an earthworm entangled in the roots. Does that mean earthworms come from dandelions? No.

A number of articles reporting on the study in question have used the faulty logic that prostate cancer is associated with inflammation and hyperplasia, and T. gondii causes inflammation and hyperplasia, therefore T. gondii causes prostate cancer. Some have gone farther: T. gondii is a parasite of cats, therefore cats cause prostate cancer.

It may turn out that T. gondii plays a role in the development of some prostate cancers (or it may not), however getting rid of the family kitty as a preventative measure would be not only premature, but also pointless. Many people acquire toxoplasmosis from other sources: undercooked meat, contaminated soil or water, from an infected mother prior to birth.

Do We Find Toxoplasma gondii in Human Prostate Tissue?

Since the 1960s, hematoxylin and eosin (H&E) staining of prostate tissue has been used for diagnosis of prostate cancer. Toxoplasma gondii is also quite recognizable in tissues stained with H&E. One would think that if T. gondii is a common cause of prostate cancer, we would have noticed the relationship a long time ago. Instead, Colinot et al (Prostate) write that “this is the first report that T. gondii chronically encysts and induces chronic inflammation within the prostate of any species.”

Finally, if T. gondii is a common cause of prostate cancer, one would expect to see a correlation between the incidence of prostate cancer and the incidence of T. gondii infection in various countries around the world. This one’s tricky because most data for prostate cancer comes from older men, while most data on T. gondii infection comes from pregnant women. It would be an interesting thing to look at however.

Meanwhile, let’s wait for research to give us more answers, and give the cats a break.

Further Reading

Colinot DL, Garbuz T, Bosland MC, Wang L, Rice SE, Sullivan WJ Jr, Arrizabalaga G, Jerde TJ. 2017 “The common parasite Toxoplasma gondii induces prostatic inflammation and microglandular hyperplasia in a mouse model.” Prostate. May 12. doi: 10.1002/pros.23362 

Colinot DL, Garbuz T, Bosland MC, Sullivan WJ Jr, Arrizabalaga G, Jerde TJ. 2017 “Toxoplasma gondii Infects the Prostate and Induces Microglandular Hyperplasia in a Mouse Model of Prostatic Hyperplasia.” Journal of Urology 197, No. 4S Supplement, May 12.


Toxoplasma gondii forms cysts in mouse prostate tissue and causes imflammation. Image by Rama CC BY-SA 2.0
H&E stain of normal prostate tissue. Image by Alex brollo CC BY-SA 4.0
H&E stain of prostate cancer. Image by Otis Brawley, US National Cancer Institute
Toxoplasma gondii cyst in mouse brain. Image by Jitinder P. Dubey, US Dept of Agriculture