Friday, 11 September 2015

Mysteries of Entamoeba histolytica and Amebic Dysentery

A beautiful Entamoeba histolytica
trohpozoite; Image by Stefan Walkowski,
CC BY-SA 3.0

Entamoeba histolytica has always had us guessing. It’s the only Entamoeba species that causes disease. Why? It causes amebic dysentery in some people and not in others. Why? How does it invade tissue? Fedor Lösch was the first to describe the organism (1875), which he found while looking for the cause of dysentery in a Russian patient. Lösch guessed that the organism he called Amoeba coli was not the cause of the illness, but he guessed wrong.

Prevalence of Entamoeba histolytica

For more than a hundred years after its discovery, we thought E. histolytica was much more common than it actually is. During that time, researchers gradually separated out the look-alikes: Entamoeba coli (1879), E. hartmanii (1912), E. polecki (1912), E. moshkovskii (1941), and finally E. dispar (1978). We now know that many organisms formerly identified as E. histolytica were actually the morphologically identical, but nonpathogenic E. dispar. Estimates that 10% of the population is infected with E. histolytica have been revised downward to 50 million symptomatic cases (although many infections are asymptomatic) (Medscape). In reality, nobody really knows.

How Did Entamoeba histolytica Become Pathogenic?

Entamoeba histolytica differs from the other Entamoeba species in that it can invade tissue. It can cause amebic dysentery, with ulcers and abscesses in the intestine, and it can travel further to set up abscesses in other places - usually the liver, sometimes the lung or the brain.

I can see that causing diarrhea might be to the amoeba's advantage: this would result in organisms being rapidly expelled from the body to contaminate the environment, with other potential hosts being exposed. But diarrhea usually means the release of the vulnerable trophozoite stage, not the hardier infectious cyst stage, and organisms in deeper abscesses would never reach the outside world. How does tissue invasion benefit the parasite?

Maybe it doesn’t. One theory suggests that the ability of E. histolytica to invade and feed on human tissue is coincidental: the same thing that enables it to feed on bacteria and other organisms, and compete for food in the intestine, just happens to enable it to feed on our cells as well. That would make abscesses in the liver and other organs simply bad luck for both parasite and host.

Another theory explores the possibility that virulence develops when hosts are crowded together. When diseases are easily passed from one host to another due to crowding, the organisms that quickly make people sick and contagious do better than the slower-moving ones. This could explain how E. histolytica might have evolved as a pathogen in the cooler climate of Europe.

Where Did Entamoeba histolytica Evolve?

The recent discovery of E. histolytica in a Jerusalem cesspit dating back to Medieval times (15th and 16th century) is suggested evidence that people were visiting the city from Europe. Interestingly, E. histolytica has been confirmed in a number of European coprolites dating back as far as 500 BCE. But very few coprolites from tropical locations have been tested for E. histolytica and the evidence might be gone after so long in a tropical climate.

Did E. histolytica spread around the world from Europe? Europeans certainly had it and spread it, but I find it difficult to believe that E. histolytica evolved in what is today Europe for a number of reasons:
  • It is an ancient and predominantly human parasite, and humans didn’t evolve in Europe.
  • It is vulnerable to cold, dying at temperatures below 5C. This is in contrast to other parasites such as Giardia and Cryptosporidium, which survive much colder temperatures and are more common in cooler climates, even today.
  • It is relatively uncommon in Europe and other temperate climates today, but very common in the tropics.
  • A number of early accounts from other parts of the world appear to describe amoebic dysentery. The earliest of these came from 1000 BCE in India, and Avicenna’s writings from the Middle East around 1000 CE have good descriptions of both amebic dysentery and liver abscess.

The mysteries remain unsolved. I’m interested to see whether further research can resolve them. Meanwhile, E. histolytica continues to cause an estimated 100,000 deaths annually.

Further Reading

Cox, F. E. G. 2002. "History of Human Parasitology." Clinical Microbiology Reviews 15(4) 595-612 doi: 10.1128/CMR.15.4.595-612.2002

Harrison, Alan. 2015 “500 Year Old Toilet in JerusalemReveals Clues About Long-distance Trade and Travel in the Medieval Period" Bugbitten

Roberts, Larry S., and John Janovy Jr. 2009. Gerald D. Schmidt & Larry S. Roberts’ Foundations of Parasitology. Boston, McGraw Hill.

Samie A, ElBakri A, and AbuOdeh R. 2012 "Amoebiasis in the Tropics: Epidemiology and Pathogenesis." Current Topics in Tropical Medicine, Dr. Alfonso Rodriguez-Morales (Ed.), ISBN: 978-953-51-0274-8, InTech

Sargeaunt PG, Williams JE, and Grene JD. 1978 “The Differentiation of Invasive and Non-invasive Entamoeba histolytica by Isoenzyme Electrophoresis.” Transactions of the Royal Society of Tropical Medicine and Hygiene 72 (5): 519-521 doi:10.1016/0035-9203(78)90174-8

Singh U, Huston CD. 2012 “Evolution of Entamoeba histolytica Virulence.” In Evolution of Virulence in Eukaryotic Microbes, L. David Sibley, Barbara J. Howlett, Joseph Heitman (Eds.) Chapter 22.

Friday, 10 July 2015

Dodging Mosquito-Borne Diseases

Malaria, dengue fever, Japanese encephalitis, yellow fever, chikungunya, West Nile and other unpleasant diseases are mosquito-borne. The WHO estimates that, each year, there are:
•    390 million cases of dengue (2015)
•    198 million cases of malaria (2013)
•    200 thousand cases of yellow fever (2014)
•    68 thousand cases of Japanese encephalitis (2014)

Those are big numbers. Travelers need to be alert to health risks from mosquito bites in some parts of the world, but mosquito borne diseases can be avoided.

Who Has the Most Dangerous Mosquitoes?

You might not know you've been bitten by a mosquito
until you become ill. User: Ngari.norway CC BY-SA 3.0

Mosquito bites in North America, Europe, northern Asia and most of Australia are unwelcome but usually not considered life threatening. They’re painful, itchy, and can become infected, and the sound of a bloodthirsty mosquito whining around your head can drive you mad. Mosquito-borne diseases, however, aren’t usually a big concern. In recent years, a slight risk of contracting West Nile virus has heightened the level of concern about mosquito bites in North America.

In the tropics, it’s different. Mosquito bites can be deadly. Day flying mosquitoes transmit dengue fever and yellow fever: the night flyers bring malaria and Japanese encephalitis. Some locations as well as some seasons mean higher risk. Be careful. The first line of defense is to know the enemy – travelers should take time, before they go, to find out what the risks are at their destination.

Preventing Mosquito-Bourne Diseases

Travelers can be immunized against yellow fever and Japanese encephalitis, and antimalarial drugs are advised to prevent malaria, but none of these work 100 percent of the time, and there’s no protection against dengue or chikungunya. The only way to be sure you don’t catch any of the mosquito borne diseases is to be sure you don’t get any mosquito bites. It’s not as easy as you might think.

A trip to Southeast Asia – my first trip to a destination where mosquitoes were a particular concern – taught me many useful things:

•    Even in the dry season, there are mosquitoes virtually everywhere you go; I saw my first Asian mosquito in the taxi from the Bangkok airport.

•    Many hotels and guest houses do not have intact window screens and tight doors – mosquitoes get in through grates, tears in screens, and under doors. Perhaps this shouldn’t have surprised me, but it did.

•    Mosquito bed netting often isn’t provided either. Mosquito bed netting is indispensable, preferably netting that has been soaked in mosquito repellent. Buy it at home and take it with you. Don’t assume there will be a hook available to hang bed netting – carry a hook that can be screwed into wood and a long piece of cord that you can stretch across a room, say from a curtain rod to a closet rod or some other fixture. You may have to get creative.

•    Don’t expect the local people to warn you about mosquitoes or help you take precautions. Their level of concern can be surprisingly low and they may deny the presence of mosquitoes even when you have just seen one checking out your ankles.

•    Bring lots of mosquito repellent with a minimum concentration of 30% DEET (check recommendations for children). This can be hard to find in Asian shops, though, surprisingly, we had better luck in the small markets used by local people than in the shops aimed at tourists. Remember that insect repellent is only effective for a certain number of hours and will be removed by swimming, sweating, and showering. Carry repellent with you and reapply it diligently – at a minimum, morning and evening.

•    Light colored clothing is recommended, as well as long sleeves and long pants or skirts. Don’t be too quick to rule out the more extensive clothing – long sleeved shirts and pants made of light cotton can be surprisingly cool and they’ll protect you from both insects and sunburn.

I got through my Southeast Asian vacation without any mosquito bites that I was aware of, though one black fly did sample my blood in northern Thailand. I say “that I was aware of” because I found the mosquitoes in Thailand, Cambodia and Laos to be both smaller and quieter than the ones I’m used to; if you don’t react to the bite you might never know you had a visitor.

Friday, 26 June 2015

Crazy – Cats, Toxoplasma, and Your Mental Health

Is your cat making you crazy? If you’ve been reading the many recent articles about a theoretical link between Toxoplasma gondii infection and schizophrenia (and other mental health issues) you may think that your cat is a significant threat to your mental health.

Infected rodents pass Toxoplasma gondii
to wild and domestic cats. Yintan, CC BY-SA 3.0

But to say that your cat could literally make you mentally ill is a bit disingenuous. It’s not the cat itself, it’s the parasite Toxoplasma gondii that’s linked to mental illness. And while it’s true that T. gondii is a parasite of cats, it’s equally true that it infects more than 300 other species of animals, and there are a number of ways to catch it without a cat being anywhere in sight. Don’t be too hard on your pampered kitty which, in all likelihood, is not capable of infecting you with T. gondii.

Cats and Toxoplasma gondii

 Cats typically catch T. gondii by eating infected rodents. In the cat, T. gondii multiplies in the intestine and millions of microscopic oocysts (you might think of them as eggs, or germs) are released into the outside world in the cat’s feces. But an infected cat will usually only shed these oocysts for one to two weeks of its entire life - about 0.2 percent of its life if it lives to be sixteen. Cats that don’t hunt, don’t eat raw meat, and particularly cats that don’t go outside, are unlikely to be infected, and extremely unlikely to infect you with T. gondii.

Toxoplasma gondii in the Environment

There’s a bigger picture of course. Domestic cats have been instrumental in spreading T. gondii around the world and contaminating the environment everywhere with oocysts. But this parasite can survive without cats for a very long time, if not indefinitely. This is because the parasite multiplies asexually (clonally) in the tissues of any warm blooded vertebrate (and even fish can be infected). It can multiply in human tissues, in chickens, sheep, dogs, rats, mice, horses, and 300+ other animals. If a pig eats an infected rat, the pig will catch toxoplasmosis. If a wild or feral dog eats the pig, the dog will catch toxoplasmosis. So blaming it all on the cats at this point is like closing the barn door after the horses have left.

How Do Humans Get Toxoplasma

The cat is the only animal in which Toxoplasma gondii
can reproduce sexually, but it is widespread in the
tissues of other species. CDC image.

Humans become infected with Toxoplasma gondii in various ways:
•    Eating undercooked meat
•    Consuming food or water contaminated with oocysts
•    Exposure to oocysts in soil (gardening etc.)
•    Congenitally, from mother to fetus
•    Through blood transfusion or organ donation
•    Direct contact with an acutely affected cat
•    Sexual transmission (theoretical)

In the end, it’s clear that while it is possible to catch T. gondii from contact with your beloved domestic cat, if the cat has an acute case of toxoplasmosis, this is an unlikely source of infection. And while cats certainly bear responsibility for spreading this parasite far and wide, it’s the parasite that’s linked to mental illness, not the cat.

Further reading

Centers for Disease Control and Prevention. “Toxoplasmosis (Toxoplasma infection).”

Flegr, Jaroslav (2015). “Schizophrenia and Toxoplasma gondii: an undervalued association?”
Expert Review of Anti-infective Therapy 13:7 , 817-820

Flegr, J., Klapilová, K., & Kaňková, Š. (2014). “Toxoplasmosis can be a sexually transmitted infection with serious clinical consequences. Not all routes of infection are created equal.” Medical Hypotheses, 83(3), 286-289.

McAuliffa, Kathleen. (2012). “How Your Cat is Making You Crazy.The Atlantic

Zhang, M., Yang, Z., Wang, S., Tao, L., Xu, L., Yan, R., ... & Li, X. (2014). “Detection of Toxoplasma gondii in shellfish and fish in parts of China.” Veterinary Parasitology, 200(1), 85-89.