Monday, August 24, 2009

This Week's Sci-Fi Worthy Parasite: Leishmania spp.

Ah, the joys of a tropical getaway. There's warm, clear waters, soft, sandy beaches, and of course, a whole ton of amazing parasites waiting to gorge on your delicious flesh.

Anyone who has traveled out of the US has been told horror stories of the disgusting creatures that await them. Take a nice trip to Brazil for some sightseeing, for example, and you might find yourself at the mercy of a small, intracellular protozoan parasite of the genus Leishmania.

There are many species of Leishmania living all over the world, from Saudi Arabia to Texas. No one's entirely sure how the parasites ended up in such diverse locations, or where they originated, but wherever there are sand flies, there is Leishmania. Like many parasites, it has a fairly complicated life, full of developmental stages and alternate hosts. Here's a good explanatory figure:

Leishmania is a fascinating parasite because it actively lives in our immune cells. First it must be injested by a sand fly, which feeds on human blood like a mosquito. Once inside the fly, it changes form and creates a very strange substance called "promastigote secretory gel." The gel serves a very important purpose - it blockades the gut of the sand fly. For the fly to feed during its next meal, it must throw up this gel, which, conveniently, carries the parasites into the human host. There, the parasites wriggle their way inside our macrophages and reproduce. In short, they takes our best anti-parasite weaponry and turn them into comfy homes. How it does this has been a question of scientists for years.

What we have found is that first, the parasite does a fantastic job of playing dead. It tends to live inside apoptitic immune cells and use the fact that the immune system doesn't eat them right away to grow and reproduce in peace. But how do they get into cells in the first place?

The most up to date research might just have some clues as to the amazing slight of hand pulled by the protozoans to get inside our immune cells. In a new paper published in PLoS Pathogens, researchers found that the strange gel used to transport the parasites into the human host does more than just aid transmission between fly and blood. Firstly, it attracts far more immune activity than the bite does, and in doing so, gives the parasite a wide variety of cell targets. But the gel does even more - it changes the immune cells' behavior. Instead of creating death-inducing nitrous oxide, the macrophages produce other compounds that the parasites can feed on.

Once in our cells, Leishmania is hard to get rid of. The parasite causes a disease referred to as Leishmaniasis. There are three different types of leishmaniasis: cutaneous, visceral and mucocutaneous. In all cases, the parasite causes tissue damage, often in the form of ulcers or sores. In cutaneous or mucocutaneous forms, these sores are on the surface, and though disgusting, tend to clear up without too much danger to the person. Mucocutaneous is the worse of the two, though, as it leads to infections on the face and terrible disfigurement.

But the disfigurement is nothing compared to the dangers of visceral leishmaniasis. It is the second-largest parasitic killer in the world (only topped by another protozoan parasite: malaria), responsible for about 500,000 cases each year worldwide, with around 10% proving fatal. What happens is that the parasite doesn't stay in the skin. It travels to the internal organs - the liver, spleen and bone marrow - and lives in the cells there.

Infection can seem like many other illnesses at first; fever, weight loss, fatigue, anemia and enlargement of the liver and spleen are all signs of visceral leishmaniasis. The parasite itself rarely kills its host, but in living in immune cells, it opens the person up to secondary infections like pneumonia, tuberculosis, or bacterial infections. In a way, it is very similar to AIDS, depressing the immune system enough that even a common cold can be fatal. And if that's not enough to worry about, treatment can have an unfortunate side effect - pushing the parasite to the surface, causing disfiguring ulcers that are more pervasive than the cutaneous form of infection.

Like so many other parasites, we have yet to find a way to vaccinate or prevent infection with Leishmania except for avoiding the bites of sand flies. As anyone who has tried to avoid mosquitoes knows, this is a hard thing to do, if not impossible, for people living where flies do.

As for science fiction-worthiness, how's this: some suggest that Leishmania might have did in the dinosaurs. Researchers have successfully found ancient parasites in amber-preserved insects. There are even books on dino parasites.

How could these little creatures have wreaked so much havoc? Well, some argue, they were new and invasive back then, and the reptiles didn't have the opportunity to evolve immune defenses. Massive outbreaks causing devastating population decreases and even localized extinctions could have seriously hindered dinosaur species. So it's possible that parasitic overrun might just have contributed to the fall of the great reptiles. Of course, other factors were also in play, but perhaps the parasites gave the final blow which kept dinosaurs from adapting to changing environments.

Rogers, M., Kropf, P., Choi, B., Dillon, R., Podinovskaia, M., Bates, P., & Müller, I. (2009). Proteophosophoglycans Regurgitated by Leishmania-Infected Sand Flies Target the L-Arginine Metabolism of Host Macrophages to Promote Parasite Survival PLoS Pathogens, 5 (8) DOI: 10.1371/journal.ppat.1000555

Poinar Jr, G. (2007). Early Cretaceous trypanosomatids associated with fossil sand fly larvae in Burmese amber Memórias do Instituto Oswaldo Cruz, 102 (5) DOI: 10.1590/S0074-02762007005000070